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  • 151.
    Morin, Lucas
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Beaussant, Yvan
    Aubry, Regis
    Fastbom, Johan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Johnell, Kristina
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Aggressiveness of End-of-Life Care for Hospitalized Individuals with Cancer with and without Dementia: A Nationwide Matched-Cohort Study in France2016Ingår i: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 64, nr 9, s. 1851-1857Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To compare the aggressiveness of end-of-life care in hospitalized individuals with cancer with and without dementia in France. DESIGN: Nationwide register-based matched-cohort study. SETTING: Hospital facilities in France. PARTICIPANTS: All individuals with cancer aged 65 and older with a diagnosis of dementia who died between January 1, 2010 and December 31, 2013, matched one-to-one with individuals with cancer without dementia (n = 26,782 matched pairs). RESULTS: Older individuals with cancer with dementia were less likely to receive aggressive treatment in their last month of life than those who were not diagnosed with dementia. Dementia was associated with a significant decrease in the receipt of chemotherapy (2.8% vs. 8.5%, P < 0.001, adjusted odds ratio [aOR] = 0.33, 95% confidence interval [CI] = 0.31-0.36) during the last month before death. Individuals with dementia were also less likely to receive radiation therapy (aOR = 0.49, 95% CI = 0.43-0.56), blood transfusions (aOR = 0.67, 95% CI = 0.64-0.70), artificial nutrition (aOR = 0.79, 95% CI = 0.73-0.85), and invasive ventilation (aOR = 0.62, 95% CI = 0.57-0.68), although they were more likely to remain hospitalized over their entire last month of life (aOR = 1.42, 95% CI = 1.37-1.48) and to have more than one emergency department visit (aOR = 1.22, 95% CI = 1.12-1.34). CONCLUSION: Older hospitalized adults with cancer with dementia are less likely to receive aggressive cancer treatment near the end of life than those without dementia. This discrepancy raises important ethical questions for clinicians and healthcare policy-makers.

  • 152.
    Morin, Lucas
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Calderon Larrañaga, Amaia
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Welmer, Anna-Karin
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden; Stockholm Gerontology Research Center, Sweden.
    Rizzuto, Debora
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Wastesson, Jonas W.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Johnell, Kristina
    Polypharmacy and injurious falls in older adults: a nationwide nested case-control study2019Ingår i: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 11, s. 483-493Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To determine whether or not the exposure to multiple drugs (polypharmacy) increases the risk of fall-related injury among older adults, beyond the effect of fall-risk increasing drugs and chronic multimorbidity.

    Methods: Nested case-control study using linked register data with national coverage in Sweden. We defined cases as older adults (>= 70 years) who had an incident non-elective admission due to a fall between 1 January and 31 December 2013. Cases were matched 1:1 on sex, age and index date to randomly selected controls from the general population. The number of prescription drugs during the 7 days preceding the index date was the main exposure.

    Results: A total of 49,609 cases were included and matched to an equal number of controls. The number of prescription drugs was higher among cases than among controls (mean difference 1.2, 95% CI 1.16-1.26). While adjusting for potential confounders, we found that the risk of injurious falls increased in a nearly linear fashion for each additional drug (OR, 1.02; 95% CI, 1.01-1.03). When using a cut-off value of >= 4 drugs to define polypharmacy, the population attributable fraction for injurious falls was 5.2% (95% CI 2.8-7.6).

    Conclusion: This study shows a monotonic dose-response relationship between the number of drugs and the risk of injurious falls. However, after comprehensive adjustment for known confounders (including fall-risk increasing drugs and chronic multimorbidity), this association is substantially weaker than previously reported. Moreover, even if the relationship between polypharmacy and injurious falls is really causal, the population attributable risk fraction is low.

  • 153.
    Morin, Lucas
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Fastbom, Johan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Laroche, Marie-Laure
    Johnell, Kristina
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Potentially inappropriate drug use in older people: a nationwide comparison of different explicit criteria for population-based estimates2015Ingår i: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 80, nr 2, s. 315-324Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: The aim was to investigate the prevalence of potentially inappropriate medication use among older people in Sweden according to five different published sets of explicit criteria from Europe and the US.

    Methods: This was a nationwide cross-sectional, register-based study across the whole of Sweden in 2008. All individuals aged 65 years and older were included (n = 1 346 709, both community-dwelling and institutionalized persons). We applied all drug-specific criteria included in the 2012 Beers Criteria, the Laroche's list, the PRISCUS list, the NORGEP criteria and the Swedish National Board of Health and Welfare criteria. The main outcome was the potentially inappropriate drug use according to each set of criteria, separately and combined. Multivariate logistic regression models were used to identify individual factors associated with the use of potentially inappropriate drugs.

    Results: The prevalence of potentially inappropriate medication use varied between the explicit criteria from 16% (NORGEP criteria) to 24% (2012 Beers criteria). Overall, 38% of the older people were exposed to potentially inappropriate drug use by at least one of the five sets of criteria. While controlling for other possible covariates, female gender, institutionalization and polypharmacy were systematically associated with inappropriate drug use, regardless of the set of explicit criteria we considered.

    Conclusion: Although explicit criteria for inappropriate drug use among older people have been reported to be quite different in their content, they provide similar measures of the prevalence of potentially inappropriate drug use at the population level.

  • 154.
    Morin, Lucas
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Johnell, Kristina
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Laroche, Marie-Laure
    Fastbom, Johan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Wastesson, Jonas W.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    The epidemiology of polypharmacy in older adults: register-based prospective cohort study2018Ingår i: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 10, s. 289-298Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Polypharmacy is the concomitant use of several drugs by a single person, and it increases the risk of adverse drug-related events in older adults. Little is known about the epidemiology of polypharmacy at the population level. We aimed to measure the prevalence and incidence of polypharmacy and to investigate the associated factors. Methods: A prospective cohort study was conducted using register data with national coverage in Sweden. A total of 1,742,336 individuals aged >= 65 years at baseline (November 1, 2010) were included and followed until death or the end of the study (December 20, 2013). Results: On average, individuals were exposed to 4.6 (SD =4.0) drugs at baseline. The prevalence of polypharmacy (5+ drugs) was 44.0%, and the prevalence of excessive polypharmacy (10+ drugs) was 11.7%. The incidence rate of polypharmacy among individuals without polypharmacy at baseline was 19.9 per 100 person-years, ranging from 16.8% in individuals aged 65-74 years to 33.2% in those aged >= 95 years (adjusted hazard ratio [HR] = 1.49, 95% confidence interval [CI] 1.42- 1.56). The incidence rate of excessive polypharmacy was 8.0 per 100 person-years. Older adults using multi-dose dispensing were at significantly higher risk of developing incident polypharmacy compared with those receiving ordinary prescriptions (HR =1.51, 95% CI 1.47-1.55). When adjusting for confounders, living in nursing home was found to be associated with lower risks of incident polypharmacy and incident excessive polypharmacy (HR =0.79 and HR =0.86, p<0.001, respectively). Conclusion: The prevalence and incidence of polypharmacy are high among older adults in Sweden. Interventions aimed at reducing the prevalence of polypharmacy should also target potential incident polypharmacy users as they are the ones who fuel future polypharmacy.

  • 155.
    Morin, Lucas
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). French National Observatory on End-of-Life Care, France.
    Johnell, Kristina
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Van den Block, Lieve
    Aubry, Regis
    Discussing end-of-life issues in nursing homes: a nationwide study in France2016Ingår i: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 45, nr 3, s. 395-402Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: discussing end-of-life issues with nursing home residents and their relatives is needed to ensure patient-centred care near the end of life. Objectives: this study aimed to estimate the frequency of nursing home physicians discussing end-of-life issues with residents and their relatives and to investigate how discussing end-of-life issues was associated with care outcomes in the last month of life. Methods: post-mortem cohort study in a nationwide, representative sample of 78 nursing home facilities in France. Residents who died from non-sudden causes between 1 October 2013 and 31 May 2014 in these facilities were included n = 674). Results: end-of-life issues were discussed with at most 21.7% of the residents who died during the study period. In one-third of the situations (32.8%), no discussion about end-of-life-related topics ever occurred, either with the resident or with the relatives. Older people with severe dementia were less likely to have discussed more than three of the six end-of-life topics we investigated, compared with residents without dementia (OR = 0.17, 95% CI = 0.08-0.22). In the last month of life, discussing more than three end-of-life issues with the residents or their relatives was significantly associated with reduced odds of dying in a hospital facility (adjusted OR = 0.51, 95% CI = 0.33-0.79) and with a higher likelihood of withdrawing potentially futile life-prolonging treatments (adjusted OR = 2.37, 95% CI = 1.72-3.29). Conclusion: during the last months of life, discussions about end-of-life issues occurred with only a minority of nursing home decedents, although these discussions may improve end-of-life care outcomes.

  • 156.
    Morin, Lucas
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Vetrano, Davide L.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Catholic University of Rome, Italy.
    Grande, Giulia
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). University of Milan, Italy.
    Fratiglioni, Laura
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Fastbom, Johan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Johnell, Kristina
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Use of Medications of Questionable Benefit During the Last Year of Life of Older Adults With Dementia2017Ingår i: Journal of the American Medical Directors Association, ISSN 1525-8610, E-ISSN 1538-9375, Vol. 18, nr 6, s. 551.e1-551.e7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To investigate the prevalence and factors associated with the use of medications of questionable benefit throughout the final year of life of older adults who died with dementia. Design: Register-based, longitudinal cohort study. Setting: Entire Sweden. Participants: All older adults (>= 75 years) who died with dementia between 2007 and 2013 (n = 120,067). Measurements: Exposure to medications of questionable benefit was calculated for each of the last 12 months before death, based on longitudinal data from the Swedish Prescribed Drug Register. Results: The proportion of older adults with dementia who received at least 1 medication of questionable benefit decreased from 38.6% 12 months before death to 34.7% during the final month before death (P < .001 for trend). Among older adults with dementia who used at least 1 medication of questionable benefit 12 months before death, 74.8% remained exposed until their last month of life. Living in an institution was independently associated with a 15% reduction of the likelihood to receive >= 1 medication of questionable benefit during the last month before death (odds ratio 0.85, 95% confidence interval 0.88-0.83). Antidementia drugs accounted for one-fifth of the total number of medications of questionable benefit. Lipid-lowering agents were used by 8.3% of individuals during their final month of life (10.2% of community-dwellers and 6.6% of institutionalized people, P < .001). Conclusion: Clinicians caring for older adults with advanced dementia should be provided with reliable tools to help them reduce the burden of medications of questionable benefit near the end of life.

  • 157.
    Morin, Lucas
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Karolinska Institutet, Sweden.
    Wastesson, Jonas W.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Karolinska Institutet, Sweden.
    Laroche, Marie-Laure
    Fastbom, Johan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Johnell, Kristina
    How many older adults receive drugs of questionable clinical benefit near the end of life? A cohort study2019Ingår i: Palliative Medicine: A Multiprofessional Journal, ISSN 0269-2163, E-ISSN 1477-030X, Vol. 33, nr 8, s. 1080-1090Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The high burden of disease-oriented drugs among older adults with limited life expectancy raises important questions about the potential futility of care.

    Aim: To describe the use of drugs of questionable clinical benefit during the last 3 months of life of older adults who died from life-limiting conditions.

    Design: Longitudinal, retrospective cohort study of decedents. Death certificate data were linked to administrative and healthcare registries with national coverage in Sweden.

    Setting: Older adults (>= 75 years) who died from conditions potentially amenable to palliative care between 1 January and 31 December 2015 in Sweden. We identified drugs of questionable clinical benefit from a set of consensus-based criteria.

    Results: A total of 58,415 decedents were included (mean age, 87.0 years). During their last 3 months of life, they received on average 8.9 different drugs. Overall, 32.0% of older adults continued and 14.0% initiated at least one drug of questionable clinical benefit (e.g. statins, calcium supplements, vitamin D, bisphosphonates, antidementia drugs). These proportions were highest among younger individuals (i.e. aged 75-84 years), among people who died from organ failure and among those with a large number of coexisting chronic conditions. Excluding people who died from acute and potentially unpredictable fatal events had little influence on the results.

    Conclusion: A substantial share of older persons with life-limiting diseases receive drugs of questionable clinical benefit during their last months of life. Adequate training, guidance and resources are needed to rationalize and deprescribe drug treatments for older adults near the end of life.

  • 158. Männikkö, Reija
    et al.
    Komulainen, Pirjo
    Schwab, Ursula
    Heikkilä, Harri M.
    Savonen, Kai
    Hassinen, Maija
    Hänninen, Tuomo
    Kivipelto, Miia
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). University of Eastern Finland, Finland.
    Rauramaa, Rainer
    The Nordic diet and cognition - The DR's EXTRA Study2015Ingår i: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 114, nr 2, s. 231-239Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The rapid increase in the prevalence of dementia associated with ageing populations has stimulated interest in identifying modifiable lifestyle factors that could prevent cognitive impairment. One such potential preventive lifestyle factor is the Nordic diet that has been shown to reduce the risk of CVD; however, its effect on cognition has not been studied. The aim of the present study was to estimate the cross-sectional and longitudinal associations of the baseline Nordic diet with cognitive function at baseline and after a 4-year follow-up in a population-based random sample (n 1140 women and men, age 57-78 years) as secondary analyses of the Finnish Dose-Responses to Exercise Training study. The Nordic diet score was created based on reported dietary components in 4-d food records. Cognition was assessed by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery and the Mini-mental State Examination (MMSE). The baseline Nordic diet score had been positively associated with Verbal Fluency (beta 0.08 (95% CI 0.00, 0.16), P=0.039) and Word List Learning (beta 0.06 (95% CI 0.01, 0.10), P=0.022) at 4 years but not with the Consortium to Establish a Registry for Alzheimer's Disease total score (CERAD-TS) or MMSE at 4 years, after adjustment for baseline cognitive scores, demographic factors and health-related factors. After excluding individuals with impaired cognition at baseline, the baseline Nordic diet score had also been positively associated with the CERAD-TS (beta 0.10 (95% CI 0.00, 0.20), P=0.042) and MMSE (beta 0.03 (95% CI 0.00, 0.06), P=0.039) at 4 years. These associations disappeared after further adjustment for energy intake. In conclusion, the Nordic diet might have a positive association with cognition in individuals with normal cognition.

  • 159. Nerius, Michael
    et al.
    Johnell, Kristina
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Garcia-Ptacek, Sara
    Eriksdotter, Maria
    Haenisch, Britta
    Doblhammer, Gabriele
    The Impact of Antipsychotic Drugs on Long-term Care, Nursing Home Admission, and Death in Dementia Patients2018Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 73, nr 10, s. 1396-1402Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Behavioral and psychological symptoms of dementia are commonly treated with antipsychotic drugs (APDs), which have been associated with adverse health effects. We examine the effect of APDs on long-term care (LTC), nursing home (NH) admission, and death of dementia patients. Methods: We used health claims data of the largest German health insurer from 2004 to 2010 and followed newly-diagnosed dementia patients aged 60 years and older into LTC, NH, and until death. Cox proportional hazards models were estimated to explore whether the risk of these outcomes differed between patients receiving haloperidol, melperone, risperidone, or quetiapine. Results: In a cohort of 6,930 dementia patients who were initially free of LTC dependency, APD users generally faced a two-fold increased risk of LTC relative to nonusers. Quetiapine was the exception, showing a comparatively lower risk (HR = 1.64; CI = 1.35-1.98). Among 9,950 dementia patients initially living in private homes, the risk of moving into a NH was generally increased by about 50% among APD users relative to nonusers. Risk of death (N = 10,921) was significantly higher for haloperidol-, melperone-, and risperidone- but not for quetiapine users (HR = 0.91; CI = 0.78-1.08). The excess mortality associated with haloperidol and melperone was greater among patients living in private households. Conclusions: In our study, APDs appeared to accelerate adverse health outcomes in German dementia patients. Differentiating between the effect of antipsychotic drug use among dementia patients residing in private households and in NHs, we found that excess mortality for haloperidol and melperone users was higher in private settings.

  • 160.
    Nilsen, Charlotta
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Agahi, Neda
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Kåreholt, Ingemar
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Jönköping University, Sweden.
    Work Stressors in Late Midlife and Physical Functioning in Old Age2017Ingår i: Journal of Aging and Health, ISSN 0898-2643, E-ISSN 1552-6887, Vol. 29, nr 5, s. 893-911Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The aim of this study was to explore the relationship between work stressors in late midlife and physical functioning in old age. Method: Two linked nationally representative Swedish surveys were used: the 1991 Level of Living Survey (age 57-65) and the 2011 Swedish Panel Study of Living Conditions of the Oldest Old. Work stressors were measured with the job demand-control model and physical functioning in old age with physical performance tests, lung function tests, and self-reported mobility. Ordered logistic and linear regressions were performed (n = 166-214). Results: High demands, low control, and high strain (i.e., high demands combined with low control) were associated with limited physical functioning in women. Low control and passive jobs were associated with limited physical functioning in men. Discussion: Work stressors in late midlife are important predictors of physical functioning in older adults. However, women and men seem to be vulnerable to different work stressors.

  • 161.
    Nilsen, Charlotta
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Agahi, Neda
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Shaw, Benjamin A.
    Does the association between leisure activities and survival in old age differ by living arrangement?2018Ingår i: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 72, nr 1, s. 1-6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Government policies to promote ageing in place have led to a growing frail population living at home in advanced old age, many of whom live alone. Living alone in old age is associated with adverse health outcomes, but we know little about whether it moderates the health impact of other risk and protective factors. Engagement in leisure activities is considered critical to successful ageing. We investigated whether the association between different types of leisure activities and survival in non-institutionalised older adults (aged 76 and above) differs by living arrangement and gender. Methods We used the Swedish Panel Study of Living Conditions of the Oldest Old study from 2011 and the Swedish Cause of Death Register (until 30 June 2014) to conduct Cox regression analyses (n=669). Incident mortality was 30.2% during the follow-up period. Results Overall level of leisure activity was not significantly associated with survival in either living arrangement, but some specific leisure activities, and associations, were different across gender and living arrangement. More specifically, certain social activities (participation in organisations and having relatives visit) were associated with longer survival, but only in men living alone. In women, most results were statistically non-significant, with the exception of solving crosswords being associated with longer survival in women living with someone. Conclusion In order to facilitate engagement with life, interventions focusing on leisure activities in the oldest age groups should take gender and living arrangement into consideration when determining the type of activity most needed.

  • 162.
    Nilsen, Charlotta
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Andel, Ross
    Darin-Mattsson, Alexander
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Kåreholt, Ingemar
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Jönköping University, Sweden.
    Psychosocial working conditions across working life may predict late-life physical function: a follow-up cohort study2019Ingår i: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, artikel-id 1125Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Increasing life expectancy has made understanding the mechanisms underlying late-life health and function more important. We set out to investigate whether trajectories of change in psychosocial working conditions are associated with late-life physical function. Methods Two Swedish surveys, linked at the individual level, were used (n = 803). A psychosocial job exposure matrix was used to measure psychosocial working conditions during people's first occupation, as well as their occupation every five years thereafter until baseline in 1991. Physical function was measured in 2014. Random effects growth curve models were used to calculate intraindividual trajectories of working conditions. Predictors of physical function were assessed with ordered logistic regression. Results A more active job at baseline was associated with increased odds of late-life physical function (OR 1.15, CI 1.01-1.32). Higher baseline job strain was associated with decreased odds of late-life physical function (OR 0.75, CI 0.59-0.96). A high initial level followed by an upward trajectory of job strain throughout working life was associated with decreased odds of late-life physical function (OR 0.32, CI 0.17-0.58). Conclusions Promoting a healthier workplace by reducing chronic stress and inducing intellectual stimulation, control, and personal growth may contribute to better late-life physical function.

  • 163.
    Nilsonne, Gustav
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Karolinska Institutet, Sweden.
    Tamm, Sandra
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Karolinska Institutet, Sweden.
    Månsson, Kristoffer N. T.
    Åkerstedt, Torbjörn
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Karolinska Institutet, Sweden.
    Lekander, Mats
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Karolinska Institutet, Sweden.
    Leukocyte telomere length and hippocampus volume: a meta-analysis [version 1; referees: 2 approved]2015Ingår i: F1000 Research, E-ISSN 2046-1402, Vol. 4, artikel-id 1073Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Leukocyte telomere length has been shown to correlate to hippocampus volume, but effect estimates differ in magnitude and are not uniformly positive. This study aimed primarily to investigate the relationship between leukocyte telomere length and hippocampus gray matter volume by meta-analysis and secondarily to investigate possible effect moderators. Five studies were included with a total of 2107 participants, of which 1960 were contributed by one single influential study. A random-effects meta-analysis estimated the effect to r = 0.12 [95% CI -0.13, 0.37] in the presence of heterogeneity and a subjectively estimated moderate to high risk of bias. There was no evidence that apolipoprotein E (APOE) genotype was an effect moderator, nor that the ratio of leukocyte telomerase activity to telomere length was a better predictor than leukocyte telomere length for hippocampus volume. This meta-analysis, while not proving a positive relationship, also is not able to disprove the earlier finding of a positive correlation in the one large study included in analyses. We propose that a relationship between leukocyte telomere length and hippocamus volume may be mediated by transmigrating monocytes which differentiate into microglia in the brain parenchyma.

  • 164.
    Nilsson, Jonna
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Lebedev, Alexander V.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Lövdén, Martin
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    No Significant Effect of Prefrontal tDCS on Working Memory Performance in Older Adults2015Ingår i: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 7, artikel-id 230Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Transcranial direct current stimulation (tDCS) has been put forward as a non pharmacological alternative for alleviating cognitive decline in old age. Although results have shown some promise, little is known about the optimal stimulation parameters for modulation in the cognitive domain. In this study, the effects of tDCS over the dorsolateral prefrontal cortex (dIPFC) on working memory performance were investigated in thirty older adults. An N-back task assessed working memory before, during and after anodal tDCS at a current strength of 1 mA and 2 mA, in addition to sham stimulation. The study used a single-blind, cross-over design. The results revealed no significant effect of tDCS on accuracy or response times during or after stimulation, for any of the current strengths. These results suggest that a single session of tDCS over the dIPFC is unlikely to improve working memory, as assessed by an N-back task, in old age.

  • 165. Niskanen, Eini
    et al.
    Könönen, Mervi
    Määttä, Sara
    Hallikainen, Merja
    Kivipelto, Miia
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Casarotto, Silvia
    Massimini, Marcello
    Vanninen, Ritva
    Mervaala, Esa
    Karhu, Jari
    Soininen, Hilkka
    New insights into Alzheimer's disease progression: a combined TMS and structural MRI study2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 10, s. 1-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Combination of structural and functional data of the human brain can provide detailed information of neurodegenerative diseases and the influence of the disease on various local cortical areas.

    METHODOLOGY AND PRINCIPAL FINDINGS: To examine the relationship between structure and function of the brain the cortical thickness based on structural magnetic resonance images and motor cortex excitability assessed with transcranial magnetic stimulation were correlated in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients as well as in age-matched healthy controls. Motor cortex excitability correlated negatively with cortical thickness on the sensorimotor cortex, the precuneus and the cuneus but the strength of the correlation varied between the study groups. On the sensorimotor cortex the correlation was significant only in MCI subjects. On the precuneus and cuneus the correlation was significant both in AD and MCI subjects. In healthy controls the motor cortex excitability did not correlate with the cortical thickness.

    CONCLUSIONS: In healthy subjects the motor cortex excitability is not dependent on the cortical thickness, whereas in neurodegenerative diseases the cortical thinning is related to weaker cortical excitability, especially on the precuneus and cuneus. However, in AD subjects there seems to be a protective mechanism of hyperexcitability on the sensorimotor cortex counteracting the prominent loss of cortical volume since the motor cortex excitability did not correlate with the cortical thickness. Such protective mechanism was not found on the precuneus or cuneus nor in the MCI subjects. Therefore, our results indicate that the progression of the disease proceeds with different dynamics in the structure and function of neuronal circuits from normal conditions via MCI to AD.

  • 166. Noack, Hannes
    et al.
    Lövden, Martin
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Schmiedek, Florian
    Lindenberger, Ulman
    Age-Related Differences in Temporal and Spatial Dimensions of Episodic Memory Performance Before and After Hundred Days of Practice2013Ingår i: Psychology and Aging, ISSN 0882-7974, E-ISSN 1939-1498, Vol. 28, nr 2, s. 467-480Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Normal aging impairs the representation and integration (binding) of spatial and temporal context in episodic memory. We directly compare age differences in episodic memory in relation to processing spatial and temporal context. As part of the COGITO study, 101 younger and 103 older participants trained an object-location serial recall task for 100 sessions. Training exacerbated the recall deficit of older relative to younger adults. Younger adults improved in recall performance on both spatial and temporal dimensions. In contrast, older adults improved on the spatial dimension only. Individual differences in pretest performance and change were positively correlated across dimensions among younger adults but negatively related among older adults. We conclude that older adults are impaired at simultaneously processing spatial and temporal context and preferentially process spatial at the expense of temporal context.

  • 167. Noack, Hannes
    et al.
    Lövdén, Martin
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Lindenberger, Ulman
    Normal aging increases discriminal dispersion in visuospatial short term memory2012Ingår i: Psychology and Aging, ISSN 0882-7974, E-ISSN 1939-1498, Vol. 27, nr 3, s. 627-637Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Computational models of cognitive aging propose that age-related decrements in cognitive performance, including short-term memory (STM), result from less distinct stimulus representations. When applied to visual STM, these models predict higher discriminal dispersion (L. L. Thurstone, 1927, Psychophysical analysis, The American Journal of Psychology, 38, 368-389.) in older adults than in younger adults. To test this prediction, we used a change-detection paradigm for visuospatial locations, with different levels of cognitive load (one, three, or five items) and retention interval (100 or 1,000 ms). Adult age differences were not reliable at Load 1, but were substantial at Loads 3 and 5. Effects of retention time did not differ across age groups, suggesting that age-related differences originated mainly from early processing stages. Applying a mixture model to the data revealed age-related increases in discriminal dispersion and decreases in asymptotic discrimination performance (indexing STM capacity). We concluded that age-related declines in discriminal dispersion, in addition to increasing capacity limitations, impair visual STM performance with advancing adult age.

  • 168.
    Nyberg, Anna
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Peristera, Paraskevi
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Hanson, Linda L. Magnusson
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Westerlund, Hugo
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Socio-economic predictors of depressive symptoms around old age retirement in Swedish women and men2019Ingår i: Aging & Mental Health, ISSN 1360-7863, E-ISSN 1364-6915, Vol. 23, nr 5, s. 558-565Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To estimate trajectories of depression around old age retirement in Swedish women and men and examine if socio-economic status predicted the trajectoriesMethods: The analytic sample comprised 907 women and 806 men from the Swedish Longitudinal Occupational Survey of Health. B-spline smoothers and group-based trajectory modelling were used to identify groups of individuals with similar trajectories of depressive symptoms around retirement. Multinomial regression analyses were conducted to investigate if socio-economic factors were associated with odds of belonging to trajectory groups with higher depression scores.Results: Four depressive symptoms trajectories were identified in both genders, all showing similar symptom levels across the retirement transition. Low levels of depressive symptoms were observed in the three largest groups. In the last trajectory group among women (2.5%) depression scores were moderate to severe and among men (3.3%) depression scores were persistent moderate. Higher educational level and lower subjectively rated social status were associated with higher odds of belonging to trajectory groups with higher levels of depressive symptoms in both genders. Conclusion: Retirement transition was not associated with symptoms of depression. Higher educational level and lower subjective social status may predict higher depressive symptom levels the years around old age retirement.

  • 169. Nyberg, Lars
    et al.
    Lövdén, Martin
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Riklund, Katrine
    Lindenberger, Ulman
    Bäckman, Lars
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Memory aging and brain maintenance2012Ingår i: Trends in cognitive sciences, ISSN 1364-6613, E-ISSN 1879-307X, Vol. 16, nr 5, s. 292-305Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Episodic memory and working memory decline with advancing age. Nevertheless, large-scale population-based studies document well-preserved memory functioning in some older individuals. The influential ‘reserve’ notion holds that individual differences in brain characteristics or in the manner people process tasks allow some individuals to cope better than others with brain pathology and hence show preserved memory performance. Here, we discuss a complementary concept, that of brain maintenance (or relative lack of brain pathology), and argue that it constitutes the primary determinant of successful memory aging. We discuss evidence for brain maintenance at different levels: cellular, neurochemical, gray- and white-matter integrity, and systems-level activation patterns. Various genetic and lifestyle factors support brain maintenance in aging and interventions may be designed to promote maintenance of brain structure and function in late life.

  • 170.
    Nyberg, Lars
    et al.
    Umeå universitet, Umeå, Sweden.
    Salami, Alireza
    Umeå universitet, Umeå, Sweden.
    Andersson, Mikael
    Umeå universitet, Umeå, Sweden.
    Eriksson, Johan
    Umeå universitet, Umeå, Sweden.
    Kalpouzos, Grégoria
    Umeå universitet, Umeå, Sweden.
    Kauppi, Karolina
    Umeå universitet, Umeå, Sweden.
    Lind, Johanna
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen. Stockholm Brain Institute, Stockholm, Sweden; University of Oslo, Oslo, Norway.
    Pudas, Sara
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen. Stockholm Brain Institute, Stockholm, Sweden; Umeå Center for Functional Brain Imaging, Umeå, Sweden.
    Persson, Jonas
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen. Stockholm Brain Institute, Stockholm, Sweden.
    Nilsson, Lars-Göran
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen. Stockholm Brain Institute, Stockholm, Sweden.
    Longitudinal evidence for diminished frontal-cortex function in aging2010Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, nr 52, s. 22682-22686Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cross-sectional estimates of age-related changes in brain structure and function were compared with 6-y longitudinal estimates. The results indicated increased sensitivity of the longitudinal approach as well as qualitative differences. Critically, the cross-sectional analyses were suggestive of age-related frontal overrecruitment, whereas the longitudinal analyses revealed frontal underrecruitment with advancing age. The cross-sectional observation of overrecruitment reflected a select elderly sample. However, when followed over time, this sample showed reduced frontal recruitment. These findings dispute inferences of true age changes on the basis of age differences, hence challenging some contemporary models of neurocognitive aging, and demonstrate age-related decline in frontal brain volume as well as functional response.

  • 171. Oksuzyan, Anna
    et al.
    Sauer, Torsten
    Gampe, Jutta
    Höhn, Andreas
    Wod, Mette
    Christensen, Kaare
    Wastesson, Jonas W.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Is Who you Ask Important? Concordance Between Survey and Registry Data on Medication Use Among Self- and Proxy-Respondents in the Longitudinal Study of Aging Danish Twins and the Danish 1905-Cohort Study2019Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 74, nr 5, s. 742-747Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: This study investigates the accuracy of the reporting of medication use by proxy-and self-respondents, and it compares the prognostic value of the number of medications from survey and registry data for predicting mortality across self-and proxy-respondents.

    Methods: The study is based on the linkage of the Longitudinal Study of Aging Danish Twins and the Danish 1905-Cohort Study with the Danish National Prescription Registry. We investigated the concordance between survey and registry data, and the prognostic value of medication use when assessed using survey and registry data, to predict mortality for self-and proxy-respondents at intake surveys.

    Results: Among self-respondents, the agreement was moderate (kappa = 0.52-0.58) for most therapeutic groups, whereas among proxy-respondents, the agreement was low to moderate (kappa = 0.36-0.60). The magnitude of the relative differences was, generally, greater among proxies than among self-respondents. Each additional increase in the total number of medications was associated with 7%-8% mortality increase among self- and 4%-6% mortality increase among proxy-respondents in both the survey and registry data. The predictive value of the total number of medications estimated from either data source was lower among proxies (c-statistic = 0.56-0.58) than among self-respondents (c-statistic = 0.74).

    Conclusions: The concordance between survey and registry data regarding medication use and the predictive value of the number of medications for mortality were lower among proxy-than among self-respondents.

  • 172. Olsson, Jonny
    et al.
    Bergman, Asa
    Carlsten, Anders
    Oké, Thimothy
    Bernsten, Cecilia
    Schmidt, Ingrid K
    Fastbom, Johan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Quality of drug prescribing in elderly people in nursing homes and special care units for dementia: a cross-sectional computerized pharmacy register analysis2010Ingår i: Clinical drug investigation, ISSN 1173-2563, E-ISSN 1179-1918, Vol. 30, nr 5, s. 289-300Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Drug prescribing to the elderly is extensive and often inappropriate. Furthermore, the number of drugs used is the most important risk factor for adverse drug reactions. Despite this, drug prescribing in the elderly in Sweden is high and increasing. In 2003 the Swedish National Board of Health and Welfare launched a set of indicators to evaluate the quality of drug therapy in the elderly. Use of this tool in combination with the Swedish computerized national register covering all persons receiving multi-dose drug dispensing (drugs dispensed in one dose unit bag for each dose occasion) would enable detection of inappropriate drug prescribing and could help reduce the risk of drug-related problems among the elderly.

    OBJECTIVES: To assess the extent and quality of drug prescribing in younger and older elderly residents receiving multi-dose drug dispensing in ordinary nursing homes (NHs) and special care units for dementia (NHDs), and to evaluate the relationship between the quality of prescribing and the number of prescribers per resident, in a Swedish county.

    METHODS: The computerized national pharmacy drug register provided the database and a cross-sectional design was used. Selected drug-specific quality indicators proposed by the Swedish National Board of Health and Welfare in 2003 were used to assess the quality of drug prescribing.

    RESULTS: This study included 3705 residents. Their mean age was 85 years and 72% were women. The mean number of prescribed drugs was 10.3 per resident. The proportion of residents with prescriptions for psychotropic drugs was 80% in NHs and 85% in NHDs. The prevalence of each drug-specific quality indicator was as follows: long-acting benzodiazepines 16.4% (NHs) versus 11.7% (NHDs), anticholinergic drugs 20.7% versus 18.5%, drug duplication 14.6% versus 13.6%, three or more psychotropic drugs 25.6% versus 35.3%, class C interactions (drug combinations that may require dose adjustment) 41.9% versus 38.7% and class D interactions (drug combinations that should be avoided) 8.1% versus 5.6%. Younger elderly residents (age 65-79 years) had a lower quality of drug prescribing. An increasing number of prescribers per resident was associated with a lower quality of drug therapy.

    CONCLUSIONS: We found a lower quality of drug prescribing, e.g. anticholinergic drugs prescribed to approximately 20% of residents of NHs and NHDs, and a higher rate of psychotropic drug use (>/=80%) compared with previous studies in NHs. Our results also demonstrated a negative correlation between quality of prescribing and number of prescribers per resident.

  • 173. Onder, Graziano
    et al.
    Vetrano, Davide L.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
    Villani, Emanuele R.
    Carfi, Angelo
    Lo Monaco, Maria Rita
    Cipriani, Maria Camilla
    Gravina, Ester Manes
    Denkinger, Michael
    Pagano, Francesco
    van der Roest, Henriette G.
    Bernabei, Roberto
    Deprescribing in Nursing Home Residents on Polypharmacy: Incidence and Associated Factors2019Ingår i: Journal of the American Medical Directors Association, ISSN 1525-8610, E-ISSN 1538-9375, Vol. 20, nr 9, s. 1116-1120Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To assess 1-year incidence and factors related to deprescribing in nursing home (NH) residents in Europe. Design: Longitudinal multicenter cohort study based on data from the Services and Health for Elderly in Long TERm care (SHELTER) study. Setting: NHs in Europe and Israel. Participants: 1843 NH residents on polypharmacy. Methods: Polypharmacy was defined as the concurrent use of 5 or more medications. Deprescribing was defined as a reduction in the number of medications used over the study period. Residents were followed for 12 months. Results: Residents in the study sample were using a mean number of 8.6 (standard deviation 2.9) medications at the baseline assessment. Deprescribing was observed in 658 residents (35.7%). Cognitive impairment (mild/moderate impairment vs intact, odds ratio [OR] 1.41, 95% confidence interval [CI] 1.11-1.79; severe impairment vs intact, OR 1.60, 95% CI 1.23-2.09), presence of the geriatrician within the facility staff (OR 1.41, 95% CI 1.15-1.72), and number of medications used at baseline (OR 1.10, 95% CI 1.06-1.14) were associated with higher probabilities of deprescribing. In contrast, female gender (OR 0.76, 95% CI 0.61-0.96), heart failure (OR 0.69, 95% CI 0.53-0.89), and cancer (OR 0.64, 95% CI 0.45-0.90) were associated with a lower probability of deprescribing. Conclusions and Implications: Deprescribing is common in NH residents on polypharmacy, and it is associated with individual and organizational factors. More evidence is needed on deprescribing, and clear strategies on how to withdraw medications should be defined in the future.

  • 174. Orešič, M
    et al.
    Hyötyläinen, T
    Herukka, SK
    Sysi-Aho, M
    Mattila, I
    Seppänan-Laakso, T
    Julkunen, V
    Gopalacharyulu, PV
    Hallikainen, M
    Koikkalainen, J
    Kivipelto, Miia
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Helisalmi, S
    Lötjönen, J
    Soininen, H
    Metabolome in progression to Alzheimer's disease2011Ingår i: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 1, s. e57-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mild cognitive impairment (MCI) is considered as a transition phase between normal aging and Alzheimer's disease (AD). MCI confers an increased risk of developing AD, although the state is heterogeneous with several possible outcomes, including even improvement back to normal cognition. We sought to determine the serum metabolomic profiles associated with progression to and diagnosis of AD in a prospective study. At the baseline assessment, the subjects enrolled in the study were classified into three diagnostic groups: healthy controls (n=46), MCI (n=143) and AD (n=47). Among the MCI subjects, 52 progressed to AD in the follow-up. Comprehensive metabolomics approach was applied to analyze baseline serum samples and to associate the metabolite profiles with the diagnosis at baseline and in the follow-up. At baseline, AD patients were characterized by diminished ether phospholipids, phosphatidylcholines, sphingomyelins and sterols. A molecular signature comprising three metabolites was identified, which was predictive of progression to AD in the follow-up. The major contributor to the predictive model was 2,4-dihydroxybutanoic acid, which was upregulated in AD progressors (P=0.0048), indicating potential involvement of hypoxia in the early AD pathogenesis. This was supported by the pathway analysis of metabolomics data, which identified upregulation of pentose phosphate pathway in patients who later progressed to AD. Together, our findings primarily implicate hypoxia, oxidative stress, as well as membrane lipid remodeling in progression to AD. Establishment of pathogenic relevance of predictive biomarkers such as ours may not only facilitate early diagnosis, but may also help identify new therapeutic avenues.

  • 175. Orrell, Alison
    et al.
    McKee, Kevin
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Dahlberg, Lena
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Gilhooly, Mary
    Parker, Stuart
    Improving continence services for older people from the service-providers’ perspective: a qualitative interview study2013Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 3, nr 7, s. e002926-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To examine in depth the views and experiences of continence service leads in England on key service and continence management characteristics in order to identify and to improve our understanding of barriers to a good-quality service and potential facilitators to develop and to improve services for older people with urinary incontinence (UI).

    Design: Qualitative semistructured interviews using a purposive sample recruited across 16 continence services.

    Setting: 3 acute and 13 primary care National Health Service Trusts in England.

    Participants: 16 continence service leads in England actively treating and managing older people with UI.

    Results: In terms of barriers to a good-quality service, participants highlighted a failure on the part of commissioners, managers and other health professionals in recognising the problem of UI and in acknowledging the importance of continence for older people and prevalent negative attitudes towards continence and older people. Patient assessment and continence promotion regardless of age, rather than pad provision, were identified as important steps for a good-quality service for older people with UI. More rapid and appropriate patient referral pathways, investment in service capacity, for example, more trained staff and strengthened interservice collaborations and a higher profile within medical and nurse training were specified as being important facilitators for delivering an equitable and high-quality continence service. There is a need, however, to consider the accounts given by our participants as perhaps serving the interests of their professional group within the context of interprofessional work.

    Conclusions: Our data point to important barriers and facilitators of a good-quality service for older people with UI, from the perspective of continence service leads. Further research should address the views of other stakeholders, and explore options for the empirical evaluation of the effectiveness of identified service facilitators.

  • 176.
    Osmanovic-Thunström, Almira
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Mossello, Enrico
    Åkerstedt, Torbjörn
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Fratiglioni, Laura
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Stockholm Gerontology Research Center, Sweden.
    Wang, Hui-Xin
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Do levels of perceived stress increase with increasing age after age 65? A population-based study2015Ingår i: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 44, nr 5, s. 828-834Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Methods: a dementia-free cohort of 1,656 adults aged 66-97 years living at home or in institutions, participating in the Swedish National Aging and Care study, Kungsholmen (SNAC-K) was assessed for levels of perceived stress using the 10-item perceived stress scale (PSS).

    Results: prevalence of high stress according to the top tertile of the population (PSS score 20+) was 7.8% in adults aged 81+ years, 7.5% in adults aged 72-78 and 6.2% in adults aged 66 years (P = 0.020). More women than men reported high stress, 8.3 versus 5.4% (P = 0.001). Levels of stress increased with increasing age (P = 0.001) in the linear regression model. This association remained after adjustment for demographic and psychosocial factors, but no longer was present after adjusting for health-related factors.

    Conclusion: health-related stress is highly prevalent in older adults and seems to play an important role in the association between levels of perceived stress and age in older adults.

  • 177.
    Paillard-Borg, Stéphanie
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Stockholm Gerontology Research Center, Sweden.
    Fratiglioni, Laura
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS). Stockholm Gerontology Research Center, Sweden.
    Xu, Weili
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Winblad, Bengt
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Wang, Hui-Xin
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    An active lifestyle postpones dementia onset by more than one year in very old adults2012Ingår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 31, nr 4, s. 835-842Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The purpose of this study was to test the hypothesis that an active lifestyle delays age at dementia onset. This study included 388 incident dementia cases (DSM-III-R criteria) that developed over a 9-year follow-up period among 1,375 baseline dementia-free community dwellers with good cognitive function (MMSE > 23) (mean age = 81.2) from the Kungsholmen Project. An active lifestyle was defined as participation in mental, physical, or social activity. We used linear regression models to estimate influence of baseline active lifestyle on age at onset of incident dementia and general linear models to estimate mean age at dementia onset. Age at onset of dementia was significantly older in persons who had higher levels of participation in mental, physical, or social activity (beta: 0.18, 0.29 and 0.23 respectively, p < 0.001 for all the activities) independent of education, medical condition, functional status, and other confounders including APOE. When the three types of activities were integrated into an index, we found that the broader the spectrum of participation in the activities, the later the onset of disease (beta = 0.93, p = 0.01 for participating in two activities, and beta = 1.42, p < 0.001 for three activities). There were 17 months difference in mean age at dementia onset between the inactive group and the most active group. An active lifestyle operates as a protective factor for dementia by delaying the clinical onset of the disease. These findings highlight the relevance of encouraging old adults to have active lifestyles, which could have a great impact on public health.

  • 178. Palmer, K.
    et al.
    Vetrano, Davide L.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Università Cattolica del Sacro Cuore, Italy.
    Marengoni, A.
    Tummolo, A. M.
    Villani, E. R.
    Acampora, N.
    Bernabei, R.
    Onder, G.
    THE RELATIONSHIP BETWEEN ANAEMIA AND FRAILTY: A SYSTEMATIC REVIEW AND META-ANALYSIS OF OBSERVATIONAL STUDIES2018Ingår i: The Journal of Nutrition, Health & Aging, ISSN 1279-7707, E-ISSN 1760-4788, Vol. 22, nr 8, s. 965-974Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Background: There is increasing evidence that frailty may play a role in chronic diseases, but the associations with specific chronic disorders are still unclear. Objectives: To conduct a systematic review and meta-analysis assessing the association of anaemia and frailty in observational studies. Methods: The review was performed according to PRISMA guidelines. We searched PubMed, Web of Science, and Embase from 01/01/2002-10/09/2017. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Homogeneity was assessed with the I2 statistic. Publication bias was assessed with Egger's and Begg's tests. Results: Nineteen studies were included; two longitudinal, seventeen cross-sectional. All studies except three reported an association between anaemia and frailty. The pooled prevalence of prefrailty in individuals with anaemia was 49% (95% CI=38-59%; I2=89.96%) and 24% (95% CI=17-31%; I2= 94.78%) for frailty. Persons with anaemia had more than a twofold odds of frailty (pooled OR=2.24 95% CI=1.53-3.30; I2=91.8%). Only two studies longitudinally examined the association between anaemia and frailty, producing conflicting results. Conclusions: Frailty and prefrailty are common in anaemic persons. Older persons with anaemia have more than a two-fold increased odds of frailty. These results may have clinical implications, as they identify the need to assess frailty in anaemic people and investigate any potential negative effects associated with the co-occurrence of both conditions. Longitudinal research that examines temporal changes in anaemia and effect of treatment are needed to further clarify the relationship between anaemia and frailty.

  • 179.
    Palmer, Katie
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen.
    Kabir, Zarina N.
    Ahmed, Tanvir
    Hamadani, Jena D.
    Cornelius, Christel
    Kivipelto, Miia
    Wahlin, Åke
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen. Karolinska Institutet, Sweden; University of Queensland, Australia; Jönkoping University, Sweden .
    Prevalence of dementia and factors associated with dementia in rural Bangladesh: data from a cross-sectional, population-based study2014Ingår i: International psychogeriatrics, ISSN 1041-6102, E-ISSN 1741-203X, Vol. 26, nr 11, s. 1905-1915Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There are currently no published reports of dementia prevalence or factors associated with dementia occurrence in Bangladesh. The aims are to report the prevalence of definite and questionable dementia in rural Bangladesh, and examine factors potentially associated with dementia occurrence, including sociodemographic, clinical, social, and nutritional factors. Methods: We used data from a population-based, cross-sectional study from Matlab, in rural Bangladesh, on 471 persons aged 60+ years. Participants underwent a clinical examination including diagnosis of somatic disorders, and a structured interview including questions about sociodemographic and social factors. Nutritional status was measured with the Mini Nutritional Assessment, and blood tests were conducted to assess a range of nutritional and clinical aspects. Age-and sex-specific dementia prevalence was calculated. Crude and adjusted logistic regression was used to examine associations between dementia and clinical, social, and nutritional factors. Dementia was diagnosed using a two-step procedure by physicians according to DSM-IV criteria. Results: The prevalence of questionable dementia was 11.5% and definite dementia was 3.6%. Dementia prevalence increased with increasing years of age (adjusted OR: 1.04; 95% CI = 1.002-1.1) and decreased with more years of education (adjusted OR: 0.8; 95% CI = 0.6-0.99). Being malnourished increased the odds of dementia almost six-fold (adjusted OR: 5.9; 95% CI = 1.3-26.3), while frequent participation in social activities was associated with a decreased odds (adjusted OR: 0.5; 95% CI = 0.2-0.9). Conclusions: The prevalence of dementia in rural Bangladesh is similar to other countries in the South Asia region, but lower than reports from other world regions. Malnutrition is strongly associated with dementia occurrence, and is a relevant area for future research within low-income countries.

  • 180.
    Pan, Kuan-Yu
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Xu, Weili
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Mangialasche, Francesca
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Dekhtyar, Serhiy
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Fratiglioni, Laura
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Stockholm Gerontology Research Center, Sweden.
    Wang, Hui-Xin
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Working Life Psychosocial Conditions in Relation to Late-Life Cognitive Decline: A Population-Based Cohort Study2019Ingår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 67, nr 1, s. 315-325Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    While the importance of working conditions on cognitive function has been tentatively suggested previously, few studies have considered cumulative effects of exposure throughout the working life. We examined the association between job demand-control status and late-life cognitive decline, taking into account exposure durations. In the population-based cohort study, Swedish National Study on Aging and Care-Kungsholmen, 2,873 dementia-free participants aged 60+ were followed up to nine years. Cognitive function was measured using the Mini-Mental State Examination. The entire working life was outlined through interview and occupations were graded with a psychosocial job-exposure matrix. Multivariate linear mixed-effects models were used. Slower cognitive decline was observed among people with high job control (beta: 0.10, 95% CI: 0.03, 0.19) and demands (beta: 0.15, 95% CI: 0.07, 0.22) in the longest-held job. Compared to active job, faster decline was shown in low strain (beta: -0.17, 95% CI: -0.26, -0.08), high strain (beta: -0.13, 95% CI: -0.24, -0.03), and passive job (beta: -0.22, 95% CI: -0.34, -0.11). Longer duration of active jobs was associated with slower cognitive decline (beta: 0.24, 95% CI: 0.16, 0.32), whereas faster decline was associated with longer durations of low strain (beta: -0.12, 95% CI: -0.19, -0.05), high strain (beta: -0.13, 95% CI: -0.21, -0.04), and passive jobs (beta: -0.12, 95% CI: -0.20, -0.04). In conclusion, not only psychologically stressful jobs, but also low-stimulating and passive jobs are associated with faster cognitive decline in later life. Duration of exposure may play a role in the psychosocial working condition-cognitive decline association.

  • 181.
    Pantzar, Alexandra
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Atti, Anna Rita
    Bäckman, Lars
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Stockholm Gerontology Research Center, Sweden.
    Laukka, Erika J.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Effects of psychiatric history on cognitive performance in old-age depression2015Ingår i: Frontiers in Psychology, ISSN 1664-1078, E-ISSN 1664-1078, Vol. 6, artikel-id 865Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cognitive deficits in old-age depression vary as a function of multiple factors; one rarely examined factor is long-term psychiatric history. We investigated effects of psychiatric history on cognitive performance in old-age depression and in remitted persons. In the population-based Swedish National Study on Aging and Care in Kungsholmen study, older persons (>= 60 years) without dementia were tested with a cognitive battery and matched to the Swedish National Inpatient Register (starting 1969). Participants were grouped according to current depression status and psychiatric history and compared to healthy controls (n = 96). Group differences were observed for processing speed, attention, executive functions, and verbal fluency. Persons with depression and psychiatric inpatient history (n = 20) and late-onset depression (n = 49) performed at the lowest levels, whereas cognitive performance in persons with self-reported recurrent unipolar depression (n = 52) was intermediate. Remitted persons with inpatient history of unipolar depression (n = 38) exhibited no cognitive deficits. Heart disease burden, physical inactivity, and cumulative inpatient days modulated the observed group differences in cognitive performance. Among currently depressed persons, those with inpatient history, and late onset performed at the lowest levels. Importantly, remitted persons showed no cognitive deficits, possibly reflecting the extended time since the last admission (m = 15.6 years). Thus, the present data suggest that cognitive deficits in unipolar depression may be more state- than trait-related. Information on profiles of cognitive performance, psychiatric history, and health behaviors may be useful in tailoring individualized treatment.

  • 182.
    Pantzar, Alexandra
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Laukka, Erika
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Atti, Anna-Rita
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Fastbom, Johan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Fratiglioni, Laura
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Bäckman, Lars
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Cognitive deficits in unipolar old-age depression: a population-based study2014Ingår i: Psychological Medicine, ISSN 0033-2917, E-ISSN 1469-8978, Vol. 44, nr 5, s. 937-947Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction

    Recognition of cognitive deficits in old-age depression is especially important since they contribute to poor function outcome, have strong implications for coping abilities and treatment compliance. However, substantial variability in cognitive deficits among older depressed persons has been reported. Clinical and demographic characteristics are likely to have contributed to inconsistencies in previous findings.

    Objective

    To assess effects of unipolar depression on cognitive performance in a population-based sample of elderly persons (60+ years).

    Methods

    An extensive cognitive test battery was administered. Eighty-nine persons fulfilled ICD-10 criteria for unipolar depression (mild, n=48; moderate; n=38, severe; n=3) after thorough screening for dementia (DSM-IV criteria), psychiatric comorbidities, antidepressant pharmacotherapy, and lastly preclinical dementia.

    Results

    Unipolar old-age depression was associated with deficits in processing speed, attention, executive function, verbal fluency, and episodic free recall. No depression-related deficits were observed in short-term memory, semantic memory, or spatial ability. Increasing age did not exacerbate the cognitive deficits in old-age depression. The cognitive deficits remained significant after exclusion of persons with preclinical dementia, except free recall, where performance differences were at trend level.

    Conclusions

    Cognitive deficits in unipolar old-age depression involve a number of cognitive domains, and are also present among persons with mild depression. Importantly, no statistically significant performance differences between mild and moderate/severe depression were observed. Given the prevalence of depression in older populations, the impact of this disorder on cognitive functioning may be relatively large at the population level.

  • 183.
    Papenberg, Goran
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Bäckman, Lars
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Fratiglioni, Laura
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Stockholm Gerontology Research Center, Sweden.
    Laukka, Erika J.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Fastbom, Johan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Johnell, Kristina
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Anticholinergic drug use is associated with episodic memory decline in older adults without dementia2017Ingår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 55, s. 27-32Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Anticholinergic drug use is common in older adults and has been related to increased dementia risk. This suggests that users of these drugs may experience accelerated cognitive decline. So far, however, longitudinal data on this topic are absent and the available evidence is inconclusive with respect to effects on specific cognitive domains due to suboptimal control of confounding variables. We investigated whether anticholinergic medication use is associated with cognitive decline over 6 years in a population-based study of older adults (aged 60-90; n = 1473) without dementia. We found that users (n = 29) declined more on episodic memory over 6 years compared to nonusers (n = 1418). These results were independent of age, sex, education, overall drug intake, physical activity, depression, cardiovascular risk burden, and cardiovascular disease. By contrast, anticholinergic drug use was unrelated to performance in processing speed, semantic memory, short-term memory, verbal fluency, and global cognition (the Mini-Mental-State Examination). Our results suggest that effects of anticholinergics may be particularly detrimental to episodic memory in older adults, which supports the assertion that the cholinergic system plays an important role in episodic memory formation.

  • 184.
    Papenberg, Goran
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Bäckman, Lars
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Nagel, Irene E.
    Nietfeld, Wilfried
    Schröder, Julia
    Bertram, Lars
    Heekeren, Hauke R.
    Lindenberger, Ulman
    Li, Shu-Chen
    Dopaminergic Gene Polymorphisms Affect Long-term Forgetting in Old Age: Further Support for the Magnification Hypothesis2013Ingår i: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 25, nr 4, s. 571-579Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Emerging evidence from animal studies suggests that suboptimal dopamine (DA) modulation may be associated with increased forgetting of episodic information. Extending these observations, we investigated the influence of DA-relevant genes on forgetting in samples of younger (n = 433, 20–31 years) and older (n = 690, 59–71 years) adults. The effects of single nucleotide polymorphisms of the DA D2 (DRD2) and D3 (DRD3) receptor genes as well as the DA transporter gene (DAT1; SLC6A3) were examined. Over the course of one week, older adults carrying two or three genotypes associated with higher DA signaling (i.e., higher availability of DA and DA receptors) forgot less pictorial information than older individuals carrying only one or no beneficial genotype. No such genetic effects were found in younger adults. The results are consistent with the view that genetic effects on cognition are magnified in old age. To the best of our knowledge, this is the first report to relate genotypes associated with suboptimal DA modulation to more long-term forgetting in humans. Independent replication studies in other populations are needed to confirm the observed association.

  • 185.
    Papenberg, Goran
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Max Planck Institute for Human Development, Germany.
    Li, Shu-Chen
    Nagel, Irene E.
    Nietfeld, Wilfried
    Schjeide, Brit-Maren
    Schröder, Julia
    Bertram, Lars
    Heekeren, Hauke R.
    Lindenberger, Ulman
    Bäckman, Lars
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Dopamine and glutamate receptor genes interactively influence episodic memory in old age2014Ingår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 35, nr 5, artikel-id 1213.e3Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Both the dopaminergic and glutamatergic systems modulate episodic memory consolidation. Evidence from animal studies suggests that these two neurotransmitters may interact in influencing memory performance. Given that individual differences in episodic memory are heritable, we investigated whether variations of the dopamine D2 receptor gene (rs6277, C957T) and the N-methyl-D-aspartate 3A (NR3A) gene, coding for the N-methyl-D-aspartate 3A subunit of the glutamate N-methyl-D-aspartate receptor (rs10989591, Val362Met), interactively modulate episodic memory in large samples of younger (20-31 years; n = 670) and older (59-71 years; n = 832) adults. We found a reliable gene-gene interaction, which was observed in older adults only: older individuals carrying genotypes associated with greater D2 and N-methyl-D-aspartate receptor efficacy showed better episodic performance. These results are in line with findings showing magnification of genetic effects on memory in old age, presumably as a consequence of reduced brain resources. Our findings underscore the need for investigating interactive effects of multiple genes to understand individual difference in episodic memory.

  • 186.
    Papenberg, Goran
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Max Planck Institute for Human Development, Germany.
    Lövdén, Martin
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Max Planck Institute for Human Development, Germany.
    Laukka, Erika J.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Kalpouzos, Gregoria
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Keller, Lina
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). KI-Alzheimer Disease Research Center, Department NVS, Karolinska Institutet, Sweden.
    Graff, Caroline
    Köhncke, Ylva
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Li, Tie-Qiang
    Fratiglioni, Laura
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Stockholm Gerontology Research Center, Sweden.
    Bäckman, Lars
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Stockholm Gerontology Research Center, Sweden.
    Magnified effects of the COMT gene on white-matter microstructure in very old age2015Ingår i: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 220, nr 5, s. 2927-2938Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genetic factors may partly account for between-person differences in brain integrity in old age. Evidence from human and animal studies suggests that the dopaminergic system is implicated in the modulation of white-matter integrity. We investigated whether a genetic variation in the Catechol-O-Methyltransferase (COMT) Val158Met polymorphism, which influences dopamine availability in prefrontal cortex, contributes to interindividual differences in white-matter microstructure, as measured with diffusion-tensor imaging. In a sample of older adults from a population-based study (60-87 years; n = 238), we found that the COMT polymorphism affects white-matter microstructure, indexed by fractional anisotropy and mean diffusivity, of several white-matter tracts in the oldest age group (81-87 years), although there were no reliable associations between COMT and white-matter microstructure in the two younger age groups (60-66 and 72-78 years). These findings extend previous observations of magnified genetic effects on cognition in old age to white-matter integrity.

  • 187.
    Papenberg, Göran
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Becker, Nina
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Max Planck Institute for Human Development, Germany.
    Ferencz, Beata
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Naveh-Benjamin, Moshe
    Laukka, Erika J.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Bäckman, Lars
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Brehmer, Yvonne
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Max Planck Institute for Human Development, Germany.
    Dopamine Receptor Genes Modulate Associative Memory in Old Age2017Ingår i: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 29, nr 2, s. 245-253Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous research shows that associative memory declines more than item memory in aging. Although the underlying mechanisms of this selective impairment remain poorly understood, animal and human data suggest that dopaminergic modulation may be particularly relevant for associative binding. We investigated the influence of dopamine (DA) receptor genes on item and associative memory in a population-based sample of older adults (n = 525, aged 60 years), assessed with a face-scene item associative memory task. The effects of single-nucleotide polymorphisms of DA D1 (DRD1; rs4532), D2 (DRD2/ANKK1/Taq1A; rs1800497), and D3 (DRD3/Ser9Gly; rs6280) receptor genes were examined and combined into a single genetic score. Individuals carrying more beneficial alleles, presumably associated with higher DA receptor efficacy (DRD1 C allele; DRD2 A2 allele; DRD3 T allele), performed better on associative memory than persons with less beneficial genotypes. There were no effects of these genes on item memory or other cognitive measures, such as working memory, executive functioning, fluency, and perceptual speed, indicating a selective association between DA genes and associative memory. By contrast, genetic risk for Alzheimer disease (AD) was associated with worse item and associative memory, indicating adverse effects of APOE epsilon 4 and a genetic risk score for AD (PICALM, BIN1, CLU) on episodic memory in general. Taken together, our results suggest that DA may be particularly important for associative memory, whereas AD-related genetic variations may influence overall episodic memory in older adults without dementia.

  • 188.
    Papenberg, Göran
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Max Planck Society, Germany.
    Bäckman, Lars
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Nagel, Irene
    Nietfeld, Wilfried
    Schröder, Julia
    Bertram, Lars
    Heekeren, Hauke R.
    Lindenberger, Ulman
    Li, Shu-Chen
    COMT polymorphism and memory dedifferentiation in old age2014Ingår i: Psychology and Aging, ISSN 0882-7974, E-ISSN 1939-1498, Vol. 29, nr 2, s. 374-383Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    According to a neurocomputational theory of cognitive aging, senescent changes in dopaminergic modulation lead to noisier and less differentiated processing. The authors tested a corollary hypothesis of this theory, according to which genetic predispositions of individual differences in prefrontal dopamine (DA) signaling may affect associations between memory functions, particularly in old age. Latent correlations between factors of verbal episodic memory and spatial working memory were compared between individuals carrying different allelic variants of the Catechol-O-Methyltransferase (COMT) Val158Met polymorphism, which influences DA availability in prefrontal cortex. In younger adults (n = 973), correlations between memory functions did not differ significantly among the 3 COMT genotypes (r = .35); in older adults (n = 1333), however, the correlation was significantly higher in Val homozygotes (r = .70), whose prefrontal DA availability is supposedly the lowest of all groups examined, than in heterozygotes and Met homozygotes (both rs = .29). Latent means of the episodic memory and working memory factors did not differ by COMT status within age groups. However, when restricting the analysis to the low-performing tertile of older adults (n = 443), we found that Val homozygotes showed lower levels of performance in both episodic memory and working memory than heterozygotes and Met homozygotes. In line with the neurocomputational theory, the observed dedifferentiation of memory functions in older Val homozygotes suggests that suboptimal dopaminergic modulation may underlie multiple facets of memory declines during aging. Future longitudinal work needs to test this conjecture more directly.

  • 189.
    Parker, Marti G.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Aging in a Gendered Society: Social and Biological Determinants of Health in the Elderly Population2012Ingår i: HANDBOOK OF CLINICAL GENDER MEDICINE / [ed] SchenckGustafsson, K; DeCola, PR; Pfaff, DW; Pisetsky, DS, Basel: Karger , 2012, s. 482-488Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    Gender and sex differences accumulate throughout the course of life, leading to continued health and mortality differentials between men and women in late life. Teasing apart social and biological factors becomes increasingly complex. Due to their longer life, women are more likely to provide informal care to others, and more likely to need institutional care.

  • 190.
    Parker, Marti G
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Agahi, Neda
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Cohort change in living conditions and lifestyle among middle aged Swedes: the effects on mortality and late-life disability2012Ingår i: Aging in European societies: healthy aging in Europe / [ed] Constantinos Phellas, New York: Springer-Verlag New York, 2012, s. 237-253Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 191.
    Parker, Vanessa
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Andel, Ross
    Nilsen, Charlotta
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Kareholt, Ingemar
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    The Association Between Mid-Life Socioeconomic Position and Health After RetirementExploring the Role of Working Conditions2013Ingår i: Journal of Aging and Health, ISSN 0898-2643, E-ISSN 1552-6887, Vol. 25, nr 5, s. 863-881Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To explore the role of working conditions in the association between socioeconomic position and health after retirement age using over 20 years follow-up. Method: Two Swedish nationally representative Level of Living Surveys (total N = 1,131) were used. Ordered logistic regression was used to assess the association between socioeconomic position and health (self-rated health, psychological distress, musculoskeletal pain, circulatory problems, physical and cognitive impairment). The role of physical and psychological working conditions was also assessed. Results: Lower socioeconomic position was associated with more adverse physical, but not psychological, working conditions. Physical working conditions partially explained the differences in physical impairment and musculoskeletal pain in old age attributed to socioeconomic position, but not differences in self-rated health, circulatory problems, psychological distress, and cognitive impairment. Socioeconomic position was a stronger correlate of health than psychological working conditions alone. Discussion: Improving physical working conditions may be important for reducing the influence of socioeconomic position on health after retirement.

  • 192. Pentikäinen, Heikki
    et al.
    Ngandu, Tiia
    Liu, Yawu
    Savonen, Kai
    Komulainen, Pirjo
    Hallikainen, Merja
    Kivipelto, Miia
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Karolinska Institutet, Sweden; National Institute for Health and Welfare, Finland; University of Eastern Finland, Finland.
    Rauramaa, Rainer
    Soininen, Hilkka
    Cardiorespiratory fitness and brain volumes in men and women in the FINGER study2017Ingår i: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 46, nr 2, s. 310-314Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: high cardiorespiratory fitness (CRF) is associated with larger brain volumes but data on sex differences in the association of CRF with brain volumes are scarce. We investigated whether the association of CRF with total grey matter (GM) and white matter volumes as well as medial temporal lobe and striatum volumes is different between men and women at increased risk for Alzheimer's disease (AD). Methods: we used baseline data from The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in which the inclusion criteria were set to select individuals with cognitive performance at the mean level or slightly lower than expected for age according to Finnish population norms. Our sub-study included 39 randomly selected men and 29 women aged 61-75 years. CRF was assessed as peak oxygen consumption (VO2peak) measured in a maximal exercise test on cycle ergometer. Brain structural imaging was performed using a 1.5-T scanner. Results: in men, VO2peak was associated with cortical GM volume (beta = 0.56, P = 0.001) and total GM volume (beta = 0.54, P = 0.001). In women, no associations were found between VO2peak and brain volumes. VO2peak accounted for 23% and 1% of total variance of cortical GM volume as well as 25% and 4% of total variance of total GM volume in men and women, respectively. Conclusion: CRF is associated with cortical GM and total GM volumes in elderly men at increased risk for AD, but not in women.

  • 193.
    Persson, Jonas
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen.
    Kalpouzos, Gregoria
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Nilsson, Lars-Göran
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen.
    Ryberg, Mats
    Nyberg, Lars
    Preserved Hippocampus Activation in Normal Aging as Revealed by fMRI2011Ingår i: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 21, nr 7, s. 753-766Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The hippocampus is deteriorated in various pathologies such as Alzheimer's disease (AD) and such deterioration has been linked to memory impairment. By contrast, the structural and functional effects of normal aging on the hippocampus is a matter of debate, with some findings suggesting deterioration and others providing evidence of preservation. This constitutes a crucial question since many investigations on AD are based on the assumption that the deterioration of the hippocampus is the breaking point between normal and pathological aging. A growing number of fMRI studies specifically aimed at investigating hippocampal engagement in various cognitive tasks, notably memory tasks, but the results have been inconclusive. Here, we optimized the episodic face-name paired-associates task in order to test the functioning of the hippocampus in normal aging. Critically, we found no difference in the activation of the hippocampus between the young and a group of older participants. Analysis of individual patterns of activation substantiated this impression. Collectively, these findings provide evidence of preserved hippocampal functioning in normal aging.

  • 194.
    Persson, Jonas
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen. Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Umeå center for Functional Brain Imaging (UFBI), Sweden.
    Pudas, Sara
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen. Umeå center for Functional Brain Imaging (UFBI), Sweden.
    Nilsson, Lars-Göran
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen. Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Nyberg, Lars
    Longitudinal assessment of default-mode brain function in aging2014Ingår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 35, nr 9, s. 2107-2117Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Age-related changes in the default-mode network (DMN) have been identified in prior cross-sectional functional magnetic resonance imaging studies. Here, we investigated longitudinal change in DMN activity and connectivity. Cognitively intact participants (aged 49-79 years at baseline) were scanned twice, with a 6-year interval, while performing an episodic memory task interleaved with a passive control condition. Longitudinal analyses showed that the DMN (control condition > memory task) could be reliably identified at both baseline and follow-up. Differences in the magnitude of task-induced deactivation in posterior DMN regions were observed between baseline and follow-up indicating reduced deactivation in these regions with increasing age. Although no overall longitudinal changes in within-network connectivity were found across the whole sample, individual differences in memory change correlated with change in connectivity. Thus, our results show stability of whole-brain DMN topology and functional connectivity over time in healthy older adults, whereas within-region DMN analyses show reduced deactivation between baseline and follow-up. The current findings provide novel insights into DMN functioning that may assist in identifying brain changes in patient populations, as well as characterizing factors that distinguish between normal and pathologic aging.

  • 195. Petersen, R. C.
    et al.
    Caracciolo, Barbara
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet. Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Brayne, C.
    Gauthier, S.
    Jelic, V.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Fratiglioni, L.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Mild cognitive impairment: a concept in evolution2014Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 275, nr 3, s. 214-228Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The construct of mild cognitive impairment (MCI) has evolved over the past 10years since the publication of the new MCI definition at the Key Symposium in 2003, but the core criteria have remained unchanged. The construct has been extensively used worldwide, both in clinical and in research settings, to define the grey area between intact cognitive functioning and clinical dementia. A rich set of data regarding occurrence, risk factors and progression of MCI has been generated. Discrepancies between studies can be mostly explained by differences in the operationalization of the criteria, differences in the setting where the criteria have been applied, selection of subjects and length of follow-up in longitudinal studies. Major controversial issues that remain to be further explored are algorithmic versus clinical classification, reliability of clinical judgment, temporal changes in cognitive performances and predictivity of putative biomarkers. Some suggestions to further develop the MCI construct include the tailoring of the clinical criteria to specific populations and to specific contexts. The addition of biomarkers to the clinical phenotypes is promising but requires deeper investigation. Translation of findings from the specialty clinic to the population setting, although challenging, will enhance uniformity of outcomes. More longitudinal population-based studies on cognitive ageing and MCI need to be performed to clarify all these issues.

  • 196.
    Pimouguet, Clement
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Rizzuto, Debora
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Lagergren, Mårten
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Stockholm Gerontology Research Center, Sweden.
    Fratiglioni, Laura
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Stockholm Gerontology Research Center, Sweden.
    Xu, Weili
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Living alone and unplanned hospitalizations among older adults: a population-based longitudinal study2017Ingår i: European Journal of Public Health, ISSN 1101-1262, E-ISSN 1464-360X, Vol. 27, nr 2, s. 251-256Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The association of living alone with hospitalization among the general elderly population has been rarely investigated, and the influence of common disorders on this association remains unknown. Methods: We used data on participants in the Swedish National study on Aging and Care in Kungsholmen (n = 3130). Risk and number of unplanned hospitalizations and length of hospital stays were studied over a period of 2 years. We used Cox proportional hazard models to estimate hazard ratios (HRs) of incident hospitalization and zero-inflated negative binomial regression models adjusted for potential confounders to estimate incident rate ratios (IRR) of the number of hospitalizations and total length of stay associated with living alone. Results: A total of 1768 participants (56.5%) lived alone. Five hundred and sixty-one (31.7%) of those who lived alone had at least one unplanned hospitalization. In the multivariate analyses, living alone was significantly associated with the risk of unplanned hospitalization (HR = 1.21, 95% confidence interval [CI] 1.01-1.45) and the number of hospitalizations (IRR = 1.35, 95% CI 1.04-1.76) but not with the length of hospital stays. In stratified analyses, the association between living alone and unplanned hospitalizations remained statistically significant only among men (HR = 1.52, 95% CI 1.17-1.99). Conclusions: Living alone is associated with higher risks of unplanned hospitalization in elderly, especially for men.

  • 197. Pivodic, Lara
    et al.
    Pardon, Koen
    Morin, Lucas
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). French National Observatory on End-of-Life Care, Paris, France.
    Addington-Hall, Julia
    Miccinesi, Guido
    Cardenas-Turanzas, Marylou
    Onwuteaka-Philipsen, Bregje
    Naylor, Wayne
    Ramos, Miguel Ruiz
    Van den Block, Lieve
    Wilson, Donna M.
    Loucka, Martin
    Csikos, Agnes
    Rhee, Yong Joo
    Teno, Joan
    Deliens, Luc
    Houttekier, Dirk
    Cohen, Joachim
    Place of death in the population dying from diseases indicative of palliative care need: a cross-national population-level study in 14 countries2016Ingår i: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 70, nr 1, s. 17-24Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Studying where people die across countries can serve as an evidence base for health policy on end-of-life care. This study describes the place of death of people who died from diseases indicative of palliative care need in 14 countries, the association of place of death with cause of death, sociodemographic and healthcare availability characteristics in each country and the extent to which these characteristics explain country differences in the place of death. Methods Death certificate data for all deaths in 2008 (age >= 1 year) in Belgium, Canada, the Czech Republic, England, France, Hungary, Italy, Mexico, the Netherlands, New Zealand, South Korea, Spain (Andalusia), the USA and Wales caused by cancer, heart/renal/liver failure, chronic obstructive pulmonary disease, diseases of the nervous system or HIV/AIDS were linked with national or regional healthcare statistics (N=2 220 997). Results 13% (Canada) to 53% (Mexico) of people died at home and 25% (the Netherlands) to 85% (South Korea) died in hospital. The strength and direction of associations between home death and cause of death, sociodemographic and healthcare availability factors differed between countries. Differences between countries in home versus hospital death were only partly explained by differences in these factors. Conclusions The large differences between countries in and beyond Europe in the place of death of people in potential need of palliative care are not entirely attributable to sociodemographic characteristics, cause of death or availability of healthcare resources, which suggests that countries' palliative and end-of-life care policies may influence where people die.

  • 198.
    Qiu, C
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Cotch, M F
    Sigurdsson, S
    Jonsson, P V
    Jonsdottir, M K
    Sveinbjornsdottir, S
    Eiriksdottir, G
    Klein, R
    Harris, T B
    van Buchem, M A
    Gudnason, V
    Launer, L J
    Cerebral microbleeds, retinopathy, and dementia: the AGES-Reykjavik Study2010Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 75, nr 24, s. 2221-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To determine whether microvascular damage, indicated by cerebral microbleeds (CMBs) and retinal microvascular signs, is associated with cognitive function and dementia in older persons.

    METHODS: This is a cross-sectional study of 3,906 participants (mean age 76 years; 58% women) in the AGES-Reykjavik Study (2002-2006). We assessed CMBs on MRI and retinal microvascular signs on digital retinal images. Composite Z scores of memory, processing speed, and executive function were derived from a battery of neurocognitive tests. Dementia and subtypes were diagnosed following international criteria. Regression models were used to relate cognitive Z scores and dementia to CMBs and retinal microvascular signs, adjusting for demographics, cardiovascular factors, and brain ischemic lesions.

    RESULTS: People with multiple (≥ 2) CMBs had lower Z scores on tests of processing speed (β-coefficient -0.16; 95% confidence interval -0.26 to -0.05) and executive function (-0.14; -0.24 to -0.04); results were strongest for having multiple CMBs located in the deep hemispheric or infratentorial areas. The odds ratio of vascular dementia was 2.32 (95% confidence interval 1.02 to 5.25) for multiple CMBs and 1.95 (1.04 to 3.62) for retinopathy. Having both CMBs and retinopathy, compared to having neither, was significantly associated with markedly slower processing speed (-0.25; -0.37 to -0.12), poorer executive function (-0.19; -0.31 to -0.07), and an increased odds ratio of vascular dementia (3.10; 1.11 to 8.62).

    CONCLUSION: Having multiple CMBs or concomitant CMBs and retinopathy is associated with a profile of vascular cognitive impairment. These findings suggest that microvascular damage, as indicated by CMBs and retinopathy lesions, has functional consequences in older men and women living in the community.

  • 199.
    Qiu, Chengxuan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Preventing Alzheimer's disease by targeting vascular risk factors: hope and gap2012Ingår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 32, nr 3, s. 721-731Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Alzheimer's disease (AD) is a major cause of functional dependence, poor quality of life, institutionalization, and mortality among elderly people. As a multifactorial disorder, AD has been frequently linked to vascular risk factors (e.g., smoking, hypertension, obesity, diabetes, hyperlipidemia, and inflammation) in numerous prospective cohort studies of the general population. Systematic reviews and meta-analyses of prospective studies have from the life-course perspective revealed an age-dependent association with the risk of AD for several vascular risk factors such as high blood pressure, obesity, and high total cholesterol, such that possessing these factors in mid-life, but not necessarily in late-life, is associated with an increased risk of AD. The biological plausibility for vascular risk factors to be involved in the pathogenesis and clinical manifestation of Alzheimer syndrome is partly supported by population-based neuroimaging and neuropathological studies. However, randomized controlled trials that target those major cardiovascular risk factors (e.g., antihypertensive, cholesterol-lowering, and anti-inflammatory therapies) have generally failed to prove as efficacious preventative approaches for AD. To bridge the gap, the multifactorial nature of AD and the proper time-window for intervention should be taken into account in the future when designing preventative interventions against this devastating disorder.

  • 200.
    Qiu, Chengxuan
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Cotch, Mary Frances
    Sigurdsson, Sigurdur
    Eiriksdottir, Gudny
    Jonasson, Fridbert
    Klein, Ronald
    Klein, Barbara E. K.
    Harris, Tamara B.
    van Buchem, Mark A.
    Gudnason, Vilmundur
    Launer, Lenore J.
    Cerebral microbleeds and age-related macular degeneration: the AGES-Reykjavik Study2012Ingår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 33, nr 12, s. 2935-2937Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We test the hypothesis that cerebral microbleeds (CMB) and age-related macular degeneration (AMD), both linked to amyloid-beta deposition, are correlated. This study includes 4205 participants (mean age 76.2; 57.8% women) in the Age, Gene/Environment Susceptibility (AGES)Reykjavik Study (2002-2006). CMB were assessed from magnetic resonance images, and AMD was assessed using digital retinal images. Data were analyzed with multinomial logistic models controlling for major confounders. Evidence of CMB was detected in 476 persons (272 with strict lobar CMB and 204 with nonlobar CMB). AMD was detected in 1098 persons (869 with early AMD, 140 with exudative AMD, and 89 with pure geographic atrophy). Early and exudative AMD were not associated with CMB. The adjusted odds ratio of pure geographic atrophy was 1.62 (95% confidence interval 0.93-2.82, p = 0.089) for having any CMB, 1.43 (0.66-3.06, p = 0.363) for strict lobar CMB, and 1.85 (0.89-3.87, p = 0.100) for nonlobar CMB. This study provides no evidence that amyloid deposits in the brain and AMD are correlated. However, the suggestive association of geographic atrophy with CMB warrants further investigation.

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