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  • 1. Andel, Ross
    et al.
    Silverstein, Merril
    Kåreholt, Ingemar
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Jönköping University, Sweden.
    The Role of Midlife Occupational Complexity and Leisure Activity in Late-Life Cognition2015In: The journals of gerontology. Series B, Psychological sciences and social sciences, ISSN 1079-5014, E-ISSN 1758-5368, Vol. 70, no 2, 314-321 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine whether occupational complexity of working with data or people, and cognitive or social leisure activity at midlife predicted cognition in advanced old age.

    METHODS: We used 810 eligible participants from Longitudinal Study of Living Conditions of the Oldest Old, a Swedish nationally representative study of individuals aged 77+ with cognitive assessments (an abridged version of the Mini-Mental State Exam) administered in 1992 and 2002 and linked to information about their midlife occupation and leisure activities collected in 1968 and 1981. A bootstrapping technique was applied to examine the direct and interactive associations of occupational complexity and leisure activity with late-life cognition.

    RESULTS: Controlling for demographic and health-related factors from childhood, midlife, and late life, we found that greater work complexity, both with people and with data, and greater participation in cognitive or social leisure activities independently related to better late-life cognitive scores. The complexity-cognition link was moderated by leisure activity such that the cognitive benefit related to the complexity of work-especially complexity of working with people-was rendered insignificant when participation in leisure activities-especially social activities-was above average.

    DISCUSSION: Results are discussed in terms of using work complexity to compensate for lack of leisure activity as well as in terms of promoting leisure engagement to compensate for long-term cognitive disadvantage imposed by working in less challenging occupations.

  • 2.
    Angleman, Sara B.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Santoni, Giola
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Von Strauss, Eva
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). The Swedish Red Cross University College, Sweden.
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). The Swedish Red Cross University College, Sweden.
    Temporal Trends of Functional Dependence and Survival Among Older Adults From 1991 to 2010 in Sweden: Toward a Healthier Aging2015In: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 70, no 6, 746-752 p.Article in journal (Refereed)
    Abstract [en]

    Background. Declines in functional dependence among older adults were observed before the 1990s, but there is uncertainty about subsequent trends. Our study aimed to verify the temporal trends in disability during 1991-2010 in an older Swedish population and to estimate the associated changes in survival. Methods. Functional status in octogenarians and nonagenarians was assessed at seven occasions with intervals of 2-3 years. Sample size varied at each assessment with an average of 646 (range 212-1096). Disability was defined as difficulty in one or more of personal activities of daily living. We compared prevalence and incidence, as well as mortality, and survival associated with disability over the 20-year period. Results. Sex-standardized prevalence of disability remained steady over time with a tendency toward a gradual decline, and a statistically significant decrease was present among nonagenarians. Sex-standardized cumulative incidence also remained steady. The proportion of people with prevalent disability who died <3 years remained stable, as did the survival time of people with incident disability. In contrast, among nondisabled persons, 3-year mortality decreased significantly, and for octogenarians median survival time was 1.3 years longer at the more recent assessment than a decade earlier. Conclusions. Both prevalence and incidence of disability remained stable over the last two decades in this urban Swedish population, with a trend toward a slow decline. Mortality remained steady among disabled persons but decreased among persons without disability, suggesting that increased life expectancy during the last two decades may be essentially driven by longer lives of functionally independent people.

  • 3. Anisimov, Vladimir N.
    et al.
    Egorov, Maxim V.
    Krasilshchikova, Marina S.
    Lyamzaev, Konstantin G.
    Manskikh, Vasily N.
    Moshkin, Mikhail P.
    Novikov, Evgeny A.
    Popovich, Irina G.
    Rogovin, Konstantin A.
    Shabalina, Irina G.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Physiology.
    Shekarova, Olga N.
    Skulachev, Maxim V.
    Titova, Tatiana V.
    Vygodin, Vladimir A.
    Vyssokikh, Mikhail Yu.
    Yurova, Maria N.
    Zabezhinsky, Mark A.
    Skulachev, Vladimir P.
    Effects of the mitochondria-targeted antioxidant SkQ1 on lifespan of rodents2011In: Aging, ISSN 1945-4589, E-ISSN 1945-4589, Vol. 3, no 11, 1110-1119 p.Article in journal (Refereed)
    Abstract [en]

    The effect of the mitochondria-targeted, plastoquinone-containing antioxidant SkQ1 on the lifespan of outbred mice and of three strains of inbred mice was studied. To this end, low pathogen (LP) or specific pathogen free (SPF) vivaria in St. Petersburg, Moscow, and Stockholm were used. For comparison, we also studied mole-voles and dwarf hamsters, two wild species of small rodents kept under simulated natural conditions. It was found that substitution of a LP vivarium for a conventional (non-LP) one doubled the lifespan of female outbred mice, just as SkQ1 did in a non-LP vivarium. SkQ1 prevented age-dependent disappearance of estrous cycles of outbred mice in both LP and non-LP vivaria. In the SPF vivarium in Moscow, male BALB/c mice had shorter lifespan than females, and SkQ1 increased their lifespan to the values of the females. In the females, SkQ1 retarded development of such trait of aging as heart mass increase. Male C57Bl/6 mice housed individually in the SPF vivarium in Stockholm lived as long as females. SkQ1 increased the male lifespan, the longevity of the females being unchanged. SkQ1 did not change food intake by these mice. Dwarf hamsters and mole-voles kept in outdoor cages or under simulated natural conditions lived longer if treated with SkQ1. The effect of SkQ1 on longevity of females is assumed to mainly be due to retardation of the age-linked decline of the immune system. For males under LP or SPF conditions, SkQ1 increased the lifespan, affecting also some other system(s) responsible for aging.

  • 4. Bell, J. Simon
    et al.
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wimmer, Barbara C.
    Wiese, Michael D.
    Multidose drug dispensing and optimising drug use in older people2013In: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 42, no 5, 556-558 p.Article in journal (Refereed)
  • 5. Berglund, Linnea Hergot
    et al.
    Prytz, Hanne Sandberg
    Perski, Aleksander
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Svartberg, Johan
    Testosterone levels and psychological health status in men from a general population: the Troms circle divide o study2011In: The Aging Male, ISSN 1368-5538, E-ISSN 1473-0790, Vol. 14, no 1, 37-41 p.Article in journal (Refereed)
    Abstract [en]

    Methods. aEuro integral Total testosterone and sex hormone-binding globulin levels were analysed and free testosterone levels was calculated in 3413 men participating in the fifth Troms circle divide o study in 2001. Self-administered questionnaires including information about education, marital status, smoking habits and the Hopkins Symptom Checklist-10 (SCL-10, a 10-item psychological health questionnaire) were completed. The cross-sectional data were analysed with partial association and analysis of variance and covariance. Results. aEuro integral The complete SCL-10 was not associated with total or free testosterone, but symptoms of anxiety were negatively associated with both total and free testosterone (p < 0.05). Men presumed to be testosterone deficient, with testosterone levels in the lowest 10th percentile, had increased SCL-10 score compared to men with higher testosterone levels (p == 0.021), before and after adjusting for age, waist circumference, marital status, education and smoking. There was an even stronger association between men presumed to be testosterone deficient and symptoms of anxiety (p < 0.001). However, men with more pronounced symptoms indicating mental disorder did not have lower testosterone levels. Conclusions. aEuro integral Men presumed being testosterone deficient had a higher symptom score, in particularly regarding anxiety, but they did not have pathological symptoms. Thus, lower testosterone levels was only associated with subthreshold symptoms of anxiety and depression.

  • 6.
    Berndt, Hanna
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Gothenburg University, Sweden.
    Fors, Stefan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Childhood living conditions, education and health among the oldest old in Sweden2016In: Ageing & Society, ISSN 0144-686X, E-ISSN 1469-1779, Vol. 36, no 3, 631-648 p.Article in journal (Refereed)
    Abstract [en]

    The objectives were to investigate the associations between social and financial living conditions in childhood, education and morbidity in old age. The study population (N = 591; 76+ years old) was assembled from two nationally representative Swedish surveys, in 1968 and 2011, that together made longitudinal analysis possible. Morbidity in old age comprised self-reported measures of musculoskeletal disorders, cardiovascular disease, self-rated health and impaired mobility. There were no independent associations between adverse childhood living conditions and morbidity. However, adverse childhood living conditions were associated with an increased likelihood of low education. Moreover, low education was associated with a higher probability of health problems in old age. The results did not show any associations between adverse childhood conditions and late-life morbidity. However, adverse childhood conditions were associated with lower levels of education which, in turn, was associated with health problems and attrition from the study. These results suggest that adverse childhood conditions may indeed be associated with health and survival in old age, but mainly through mechanisms acting earlier in the lifecourse.

  • 7. Berner, Jessica
    et al.
    Rennemark, Mikael
    Jogréus, Claes
    Anderberg, Peter
    Sköldunger, Anders
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wahlberg, Maria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Elmståhl, Sölve
    Berglund, Johan
    Factors influencing Internet usage in older adults (65 years and above) living in rural and urban Sweden2015In: Health Informatics Journal, ISSN 1460-4582, E-ISSN 1741-2811, Vol. 21, no 3, 237-249 p.Article in journal (Refereed)
    Abstract [en]

    Older adults living in rural and urban areas have shown to distinguish themselves in technology adoption; a clearer profile of their Internet use is important in order to provide better technological and health-care solutions. Older adults' Internet use was investigated across large to midsize cities and rural Sweden. The sample consisted of 7181 older adults ranging from 59 to 100 years old. Internet use was investigated with age, education, gender, household economy, cognition, living alone/or with someone and rural/urban living. Logistic regression was used. Those living in rural areas used the Internet less than their urban counterparts. Being younger and higher educated influenced Internet use; for older urban adults, these factors as well as living with someone and having good cognitive functioning were influential. Solutions are needed to avoid the exclusion of some older adults by a society that is today being shaped by the Internet.

  • 8. Brose, Annette
    et al.
    Lovden, Martin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Schmiedek, Florian
    Daily Fluctuations in Positive Affect Positively Co-Vary With Working Memory Performance2014In: Emotion, ISSN 1528-3542, E-ISSN 1931-1516, Vol. 14, no 1, 1-6 p.Article in journal (Refereed)
    Abstract [en]

    Positive affect is related to cognitive performance in multiple ways. It is associated with motivational aspects of performance, affective states capture attention, and information processing modes are a function of affect. In this study, we examined whether these links are relevant within individuals across time when they experience minor ups and downs of positive affect and work on cognitive tasks in the laboratory on a day-to-day basis. Using a microlongitudinal design, 101 younger adults (20-31 years of age) worked on 3 working memory tasks on about 100 occasions. Every day, they also reported on their momentary affect and their motivation to work on the tasks. In 2 of the 3 tasks, performance was enhanced on days when positive affect was above average. This performance enhancement was also associated with more motivation. Importantly, increases in task performance on days with above-average positive affect were mainly unrelated to variations in negative affect. This study's results are in line with between-person findings suggesting that high levels of well-being are associated with successful outcomes. They imply that success on cognitively demanding tasks is more likely on days when feeling happier.

  • 9.
    Caracciolo, Barbara
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Collins, Stephen
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Cognitive decline, dietary factors and gut-brain interactions2014In: Mechanisms of Ageing and Development, ISSN 0047-6374, E-ISSN 1872-6216, Vol. 136, 59-69 p.Article in journal (Refereed)
    Abstract [en]

    Cognitive decline in elderly people often derives from the interaction between aging-related changes and age-related diseases and covers a large spectrum of clinical manifestations, from intact cognition through mild cognitive impairment and dementia. Epidemiological evidence supports the hypothesis that modifiable lifestyle-related factors are associated with cognitive decline, opening new avenues for prevention. Diet in particular has become the object of intense research in relation to cognitive aging and neurodegenerative disease. We reviewed the most recent findings in this rapidly expanding field. Some nutrients, such as vitamins and fatty acids, have been studied longer than others, but strong scientific evidence of an association is lacking even for these compounds. Specific dietary patterns, like the Mediterranean diet, may be more beneficial than a high consumption of single nutrients or specific food items. A strong link between vascular risk factors and dementia has been shown, and the association of diet with several vascular and metabolic diseases is well known. Other plausible mechanisms underlying the relationship between diet and cognitive decline, such as inflammation and oxidative stress, have been established. In addition to the traditional etiological pathways, new hypotheses, such as the role of the intestinal microbiome in cognitive function, have been suggested and warrant further investigation.

  • 10. Cermakova, Pavla
    et al.
    Fereshtehnejad, Seyed-Mohammad
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Winblad, Bengt
    Eriksdotter, Maria
    Religa, Dorota
    Cardiovascular medication burden in dementia disorders: a nationwide study of 19,743 dementia patients in the Swedish Dementia Registry2014In: Alzheimer's research & therapy, ISSN 1758-9193, Vol. 6, no 3, 34- p.Article in journal (Refereed)
    Abstract [en]

    Introduction: Administration of several cardiovascular drugs has an effect on dementia. We aimed to investigate whether there are differences in the use of cardiovascular medication between different dementia disorders. Methods: We obtained information about dementia patients from the Swedish Dementia Registry. Patients were diagnosed with one of these dementia disorders: Alzheimer's disease (n = 8,139), mixed dementia (n = 5,203), vascular dementia (n = 4,982), Lewy body dementia (n = 605), frontotemporal dementia (n = 409) and Parkinson's disease dementia (n = 405). Multivariate logistic regression analysis was performed to investigate the association between use of cardiovascular medication and dementia disorders, after adjustment for age, gender, living alone, cognitive status and total number of drugs (a proxy for overall co-morbidity). Results: Seventy percent of all the dementia patients used cardiovascular medication. Use of cardiovascular drugs is common in patients with vascular and mixed dementia. Male gender, higher age, slightly better cognitive status and living with another person was associated with use of cardiovascular medication. Conclusions: Cardiovascular medication is used extensively across dementia disorders and particularly in vascular and mixed dementia. Future research should investigate the tolerability and effectiveness of these drugs in the different dementia disorders.

  • 11. Chiotis, Konstantinos
    et al.
    Saint-Aubert, Laure
    Savitcheva, Irina
    Jelic, Vesna
    Andersen, Pia
    Jonasson, My
    Eriksson, Jonas
    Lubberink, Mark
    Almkvist, Ove
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Biological psychology. Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden.
    Wall, Anders
    Antoni, Gunnar
    Nordberg, Agneta
    Imaging in-vivo tau pathology in Alzheimer's disease with THK5317 PET in a multimodal paradigm2016In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, no 9, 1686-1699 p.Article in journal (Refereed)
    Abstract [en]

    Purpose The aim of this study was to explore the cerebral distribution of the tau-specific PET tracer [F-18]THK5317 (also known as (S)-[F-18]THK5117) retention in different stages of Alzheimer's disease; and study any associations with markers of hypometabolism and amyloid-beta deposition. Methods Thirty-three individuals were enrolled, including nine patients with Alzheimer's disease dementia, thirteen with mild cognitive impairment (MCI), two with non-Alzheimer's disease dementia, and nine healthy controls (five young and four elderly). In a multi-tracer PET design [F-18]THK5317, [C-11] Pittsburgh compound B ([C-11]PIB), and [F-18]FDG were used to assess tau pathology, amyloid-beta deposition and cerebral glucose metabolism, respectively. The MCI patients were further divided into MCI [C-11]PIB-positive (n=11) and MCI [C-11]PIB-negative (n=2) groups. Results Test-retest variability for [F-18]THK5317-PET was very low (1.17-3.81 %), as shown by retesting five patients. The patients with prodromal (MCI [C-11]PIB-positive) and dementia-stage Alzheimer's disease had significantly higher [F-18]THK5317 retention than healthy controls (p=0.002 and p=0.001, respectively) in areas exceeding limbic regions, and their discrimination from this control group (using the area under the curve) was >98 %. Focal negative correlations between [F-18]THK5317 retention and [F-18]FDG uptake were observed mainly in the frontal cortex, and focal positive correlations were found between [F-18]THK5317 and [C-11] PIB retentions isocortically. One patient with corticobasal degeneration syndrome and one with progressive supranuclear palsy showed no [C-11]PIB but high [F-18]THK5317 retentions with a different regional distribution from that in Alzheimer's disease patients. Conclusions The tau-specific PET tracer [F-18]THK5317 images in vivo the expected regional distribution of tau pathology. This distribution contrasts with the different patterns of hypometabolism and amyloid-beta deposition.

  • 12. Clerici, Francesca
    et al.
    Caracciolo, Barbara
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Cova, Ilaria
    Fusari Imperatori, Susanna
    Maggiore, Laura
    Galimberti, Daniela
    Scarpini, Elio
    Mariani, Claudio
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Does Vascular Burden Contribute to the Progression of Mild Cognitive Impairment to Dementia?2012In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 34, no 3-4, 235-243 p.Article in journal (Refereed)
    Abstract [en]

    Aims: To investigate the contribution of vascular risk factors (VRFs), vascular diseases (VDs) and white matter lesions (WMLs) to the progression of mild cognitive impairment (MCI) to dementia and Alzheimer’s disease (AD). Methods: Two hundred forty-five consecutive subjects with MCI (age 74.09 ± 6.92 years) were followed for an average of 2.4 years. The Hachinski Ischemic Score and the Framingham Stroke Risk Profile were used to summarize VRFs and VDs. WMLs were graded using the Age-Related White Matter Changes Scale. Results: One hundred twenty-nine (52.6%) out of 245 subjects at risk converted to dementia, including 87 cases of AD. When hypertension occurred in MCI with deep WMLs, a 1.8-fold increased risk of dementia was observed (95% CI = 1.0–3.4). When deep WMLs occurred in MCI with high scores (≥4) on the Hachinski scale, a 3.5-fold (95% CI = 1.6–7.4) and 3.8-fold (95% CI = 1.2–11.5) risk of progression to dementia and AD was observed, respectively. Analogously, the joint effect of WMLs and high scores (≥14) on the Framingham scale nearly doubled the risk of dementia (hazard ratio = 1.9, 95% CI = 1.1–3.3). Conclusions: Accelerated progression of MCI to dementia and AD is to be expected when VRFs and VDs occur together with WMLs.

  • 13. Cova, Ilaria
    et al.
    Clerici, Francesca
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). ‘Luigi Sacco' Hospital, University of Milan, Italy.
    Maggiore, Laura
    Pomati, Simone
    Cucumo, Valentina
    Ghiretti, Roberta
    Galimberti, Daniela
    Scarpini, Elio
    Mariani, Claudio
    Caracciolo, Barbara
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Body Mass Index Predicts Progression of Mild Cognitive Impairment to Dementia2016In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 41, no 3-4, 172-180 p.Article in journal (Refereed)
    Abstract [en]

    Aims: To examine the relationship between body mass index (BMI) and progression to dementia and Alzheimer's disease (AD) in mild cognitive impairment (MCI). Materials and Methods: Two hundred and twenty-eight MCI subjects (mean age 74.04 +/- 6.94 years; 57% female) from a memory clinic were followed for 2.40 +/- 1.58 years. Baseline height and weight were used to calculate the BMI. The main outcome was progression to dementia (DSM-IV criteria) and AD (NINCDS-ADRDA criteria). Cox proportional hazard models were used to assess the longitudinal association of BMI with dementia and AD, adjusting for a comprehensive set of covariates, including vascular risk factors/diseases and neuroimaging profiles. Results: Out of 228 subjects with MCI, 117 (51.3%) progressed to dementia. Eighty-nine (76%) of the incident dementia cases had AD. In both unadjusted and multi-adjusted models, a higher BMI was associated with a reduced risk of dementia (multi-adjusted HR 0.9; 95% CI 0.8-0.9) and AD (multi-adjusted HR 0.9; 95% CI 0.8-0.9). Being underweight increased the risk of all types of dementia (multi-adjusted HR 2.5; 95% CI 1.2-5.1) but was not specifically associated with AD (multi-adjusted HR 2.2; 95% CI 0.9-5.3). Conclusions: BMI predicted progression of MCI to dementia and AD. In particular, a higher BMI was associated with a lower risk of dementia and AD, and underweight was associated with a higher risk of dementia. BMI assessment may improve the prognostic accuracy of MCI in clinical practice.

  • 14. Damian, M.
    et al.
    Almkvist, Ove
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Single-Domain Amnestic Mild Cognitive Impairment Identified by Cluster Analysis Predicts Alzheimer's Disease in the European Prospective DESCRIPA Study2013In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 36, no 1-2, 1-19 p.Article in journal (Refereed)
    Abstract [en]

    Background/Aims: To identify prodromal Alzheimer's disease (AD) subjects using a data-driven approach to determine cognitive profiles in mild cognitive impairment (MCI).Methods: A total of 881 MCI subjects were recruited from 20 memory clinics and followed for up to 5 years. Outcome measures included cognitive variables, conversion to AD, and biomarkers (e.g. CSF, and MRI markers). Two hierarchical cluster analyses (HCA) were performed to identify clusters of subjects with distinct cognitive profiles. The first HCA included all subjects with complete cognitive data, whereas the second one selected subjects with very mild MCI (MMSE ≥28). ANOVAs and ANCOVAs were computed to examine whether the clusters differed with regard to conversion to AD, and to AD-specific biomarkers. Results: The HCAs identified 4-cluster solutions that best reflected the sample structure. One cluster (aMCIsingle) had a significantly higher conversion rate (19%), compared to subjective cognitive impairment (SCI, p < 0.0001), and non-amnestic MCI (naMCI, p = 0.012). This cluster was the only one showing a significantly different biomarker profile (Aβ42, t-tau, APOE ε4, and medial temporal atrophy), compared to SCI or naMCI. Conclusion: In subjects with mild MCI, the single-domain amnestic MCI profile was associated with the highest risk of conversion, even if memory impairment did not necessarily cross specific cut-off points. A cognitive profile characterized by isolated memory deficits may be sufficient to warrant applying prevention strategies in MCI, whether or not memory performance lies below specific z-scores. This is supported by our preliminary biomarker analyses. However, further analyses with bigger samples are needed to corroborate these findings.

  • 15. Darreh-Shori, Taher
    et al.
    Forsberg, Anton
    Modiri, Negar
    Andreasen, Niels
    Blennow, Kaj
    Kamil, Chelenk
    Ahmed, Hiba
    Almkvist, Ove
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Långström, Bengt
    Nordberg, Agneta
    Differential levels of apolipoprotein E and butyrylcholinesterase show strong association with pathological signs of Alzheimer's disease in the brain in vivo2011In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 32, no 12, 2320.e15-2320.e32 p.Article in journal (Refereed)
    Abstract [en]

    Recently, we reported that 3 of the known risk factors of Alzheimer's disease (AD), i.e., advanced age, apolipoprotein E (ApoE) ε4, and female gender, are associated with differential levels of ApoE proteins and butyrylcholinesterase (BuChE) in the cerebrospinal fluid (CSF) of AD patients. The ApoE ε4 allele and certain BuChE polymorphisms synergistically affect the conversion rate of mild cognitive impairment (MCI) to AD. Here, we investigated interrelationships between ApoE and BuChE levels, and pathological markers of AD in vivo. CSF from patients with probable AD, assessed for cerebral glucose metabolism (CMRglc; n = 50) and Pittsburgh compound B (PIB) retention (β-amyloid [Aβ] load, n = 29) by positron emission tomography (PET), was used for measurement of BuChE, ApoE, Aβ, tau, phosphorylated tau (P-tau) and interleukin-1β (IL-1β) levels. Levels of ApoE and BuChE strongly correlated with CMRglc (fluorodeoxyglucose [FDG]-PET, r = 0.54, p < 0.0001, n = 50), cerebral Aβ load (PIB retention, r = 0.73, p < 0.0001, n = 29), and CSF P-tau (r = 0.73, p < 0.0001, n = 33). High ApoE protein was tied to low CMRglc and high PIB retention and P-tau. BuChE levels had opposite relationships. Other CSF covariates were levels of interleukin-1β and Aβ42peptide. The pattern of the patients' cognitive Z-scores strongly supported these observations. High ApoE protein was also linked to changes in 3 of the biodynamic properties of BuChE. In vitro analysis indicated that high ApoE protein levels were related to an increased pool of dormant BuChE molecules with an abnormally high intrinsic catalytic rate in CSF, which was “turned on” by excess Aβ peptides. The findings suggest that abnormally high levels of ApoE may play a causative role in the pathological events of AD, particularly those involving the early cholinergic deficit in the AD brain, through modulation of cholinesterases activities, hence disturbing the acetylcholine-dependent activity of neurons and nonexcitable cells such as glial cells.

  • 16. Dekhtyar, Serhiy
    et al.
    Wang, Hui-Xin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Scott, Kirk
    Goodman, Anna
    Koupil, Ilona
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Herlitz, Agneta
    How to Prove that Good Learning Outcomes in Childhood Is an Independent Factor Strengthening the Cognitive Reserve Response2015In: The American journal of geriatric psychiatry, ISSN 1064-7481, E-ISSN 1545-7214, Vol. 23, no 11, 1204-1206 p.Article in journal (Refereed)
  • 17.
    Ding, Mozhu
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wang, Rui
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Patterns of cardiovascular drugs prescribed for an elderly Swedish population2014In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 177, no 3, 1091-1094 p.Article in journal (Refereed)
  • 18. Ebner, Natalie C.
    et al.
    Horta, Marilyn
    Lin, Tian
    Feifel, David
    Fischer, Håkan
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Cohen, Ronald A.
    Oxytocin modulates meta-mood as a function of age and sex2015In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 7, 175Article in journal (Refereed)
    Abstract [en]

    Attending to and understanding one's own feelings are components of meta mood and constitute important socio-affective skills across the entire lifespan. Growing evidence suggests a modulatory role of the neuropeptide oxytocin on various socio-affective processes. Going beyond previous work that almost exclusively examined young men and perceptions of emotions in others, the current study investigated effects of intranasal oxytocin on meta-mood in young and older men and women. In a double-blind between-group design, participants were randomly assigned to self-administer either intranasal oxytocin or a placebo before responding to items from the Trait Meta Mood Scale (TMMS) about attention to feelings and clarity of feelings. In contrast to older women, oxytocin relative to placebo increased attention to feelings in older men. Oxytocin relative to placebo enhanced meta-mood in young female participants but reduced it in older female participants. This pattern of findings supports an age- and sex-differential modulatory function of the neuropeptide oxytocin on meta-mood, possibly associated with neurobiological differences with age and sex.

  • 19.
    Ekström, Ingrid
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Perception and psychophysics.
    Sjölund, Sara
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Perception and psychophysics.
    Nordin, Steven
    Nordin Adolfsson, Annelie
    Adolfsson, Rolf
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Cognitive psychology.
    Larsson, Maria
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Perception and psychophysics.
    Olofsson, Jonas K.
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Perception and psychophysics. Swedish Collegium for Advanced Study, Sweden.
    Smell Loss Predicts Mortality Risk Regardless of Dementia Conversion2017In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 65, no 6, 1238-1243 p.Article in journal (Refereed)
    Abstract [en]

    Objectives

    To determine whether dementia could explain the association between poor olfactory performance and mortality risk within a decade-long follow-up period.

    Design

    Prospective cohort study.

    Setting

    Betula Study, Umeå, Sweden.

    Participants

    A population-based sample of adult participants without dementia at baseline aged 40 to 90 (N = 1,774).

    Measurements

    Olfactory performance using the Scandinavian Odor-Identification Test (SOIT) and self-reported olfactory function; several social, cognitive, and medical risk factors at baseline; and incident dementia during the following decade.

    Results

    Within the 10-year follow-up, 411 of 1,774 (23.2%) participants had died. In a Cox model, the association between higher SOIT score and lower mortality was significant (hazard ratio (HR) = 0.74 per point interval, 95% confidence interval (CI) = 0.71-0.77, P < .001). The effect was attenuated, but remained significant, after controlling for age, sex, education, and health-related and cognitive variables (HR = 0.92, 95% CI = 0.87-0.97, P = .001). The association between SOIT score and mortality was retained after controlling for dementia conversion before death (HR = 0.92, 95% CI = 0.87-0.97, P = .001). Similar results were obtained for self-reported olfactory dysfunction.

    Conclusion

    Poor odor identification and poor self-reported olfactory function are associated with greater likelihood of future mortality. Dementia does not attenuate the association between olfactory loss and mortality, suggesting that olfactory loss might mark deteriorating health, irrespective of dementia.

  • 20. Enache, Daniela
    et al.
    Solomon, Alina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska Institutet, Sweden; University of Eastern Finland, Finland.
    Cavallin, Lena
    Kåreholt, Ingemar
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Jönköping University, Sweden.
    Gregoric Kramberger, Milica
    Aarsland, Dag
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden; University of Eastern Finland, Finland.
    Eriksdotter, Maria
    Winblad, Bengt
    Jelic, Vesna
    CAIDE Dementia Risk Score and biomarkers of neurodegeneration in memory clinic patients without dementia2016In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 42, 124-131 p.Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to explore cross-sectional associations between Cardiovascular Risk Factors, Aging and Dementia Study (CAIDE) Dementia Risk Score and dementia-related cerebrospinal fluid and neuroimaging biomarkers in 724 patients without dementia from the Memory Clinic at Karolinska University Hospital, Huddinge, Sweden. We additionally evaluated the score's capacity to predict dementia. Two risk score versions were calculated: one including age, gender, obesity, hyperlipidemia, and hypertension; and one additionally including apolipoprotein E (APOE) epsilon 4 carrier status. Cerebrospinal fluid was analyzed for amyloid beta (A beta), total tau, and phosphorylated tau. Visual assessments of medial temporal lobe atrophy (MTA), global cortical atrophy-frontal subscale, and Fazekas scale for white matter changes (WMC) were performed. Higher CAIDE Dementia Risk Score (version without APOE) was significantly associated with higher total tau, more severe MTA, WMC, and global cortical atrophy-frontal subscale. Higher CAIDE Dementia Risk Score (version with APOE) was associated with reduced A beta, more severe MTA, and WMC. CAIDE Dementia Risk Score version with APOE seemed to predict dementia better in this memory clinic population with short follow-up than the version without APOE.

  • 21. Escott-Price, Valentina
    et al.
    Bellenguez, Celine
    Wang, Li-San
    Choi, Seung-Hoan
    Harold, Denise
    Jones, Lesley
    Holmans, Peter
    Gerrish, Amy
    Vedernikov, Alexey
    Richards, Alexander
    DeStefano, Anita L.
    Lambert, Jean-Charles
    Ibrahim-Verbaas, Carla A.
    Naj, Adam C.
    Sims, Rebecca
    Jun, Gyungah
    Bis, Joshua C.
    Beecham, Gary W.
    Grenier-Boley, Benjamin
    Russo, Giancarlo
    Thornton-Wells, Tricia A.
    Denning, Nicola
    Smith, Albert V.
    Chouraki, Vincent
    Thomas, Charlene
    Ikram, M. Arfan
    Zelenika, Diana
    Vardarajan, Badri N.
    Kamatani, Yoichiro
    Lin, Chiao-Feng
    Schmidt, Helena
    Kunkle, Brian
    Dunstan, Melanie L.
    Vronskaya, Maria
    Johnson, Andrew D.
    Ruiz, Agustin
    Bihoreau, Marie-Therese
    Reitz, Christiane
    Pasquier, Florence
    Hollingworth, Paul
    Hanon, Olivier
    Fitzpatrick, Annette L.
    Buxbaum, Joseph D.
    Campion, Dominique
    Crane, Paul K.
    Baldwin, Clinton
    Becker, Tim
    Gudnason, Vilmundur
    Cruchaga, Carlos
    Craig, David
    Amin, Najaf
    Berr, Claudine
    Lopez, Oscar L.
    De Jager, Philip L.
    Deramecourt, Vincent
    Johnston, Janet A.
    Evans, Denis
    Lovestone, Simon
    Letenneur, Luc
    Hernandez, Isabel
    Rubinsztein, David C.
    Eiriksdottir, Gudny
    Sleegers, Kristel
    Goate, Alison M.
    Fievet, Nathalie
    Huentelman, Matthew J.
    Gill, Michael
    Brown, Kristelle
    Kamboh, M. Ilyas
    Keller, Lina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Barberger-Gateau, Pascale
    McGuinness, Bernadette
    Larson, Eric B.
    Myers, Amanda J.
    Dufouil, Carole
    Todd, Stephen
    Wallon, David
    Love, Seth
    Rogaeva, Ekaterina
    Gallacher, John
    St George-Hyslop, Peter
    Clarimon, Jordi
    Lleo, Alberto
    Bayer, Anthony
    Tsuang, Debby W.
    Yu, Lei
    Tsolaki, Magda
    Bossu, Paola
    Spalletta, Gianfranco
    Proitsi, Petra
    Collinge, John
    Sorbi, Sandro
    Garcia, Florentino Sanchez
    Fox, Nick C.
    Hardy, John
    Deniz Naranjo, Maria Candida
    Bosco, Paolo
    Clarke, Robert
    Brayne, Carol
    Galimberti, Daniela
    Scarpini, Elio
    Bonuccelli, Ubaldo
    Mancuso, Michelangelo
    Siciliano, Gabriele
    Moebus, Susanne
    Mecocci, Patrizia
    Del Zompo, Maria
    Maier, Wolfgang
    Hampel, Harald
    Pilotto, Alberto
    Frank-Garcia, Ana
    Panza, Francesco
    Solfrizzi, Vincenzo
    Caffarra, Paolo
    Nacmias, Benedetta
    Perry, William
    Mayhaus, Manuel
    Lannfelt, Lars
    Hakonarson, Hakon
    Pichler, Sabrina
    Carrasquillo, Minerva M.
    Ingelsson, Martin
    Beekly, Duane
    Alvarez, Victoria
    Zou, Fanggeng
    Valladares, Otto
    Younkin, Steven G.
    Coto, Eliecer
    Hamilton-Nelson, Kara L.
    Gu, Wei
    Razquin, Cristina
    Pastor, Pau
    Mateo, Ignacio
    Owen, Michael J.
    Faber, Kelley M.
    Jonsson, Palmi V.
    Combarros, Onofre
    O'Donovan, Michael C.
    Cantwell, Laura B.
    Soininen, Hilkka
    Blacker, Deborah
    Mead, Simon
    Mosley, Thomas H., Jr.
    Bennett, David A.
    Harris, Tamara B.
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Holmes, Clive
    de Bruijn, Renee F. A. G.
    Passmore, Peter
    Montine, Thomas J.
    Bettens, Karolien
    Rotter, Jerome I.
    Brice, Alexis
    Morgan, Kevin
    Foroud, Tatiana M.
    Kukull, Walter A.
    Hannequin, Didier
    Powell, John F.
    Nalls, Michael A.
    Ritchie, Karen
    Lunetta, Kathryn L.
    Kauwe, John S. K.
    Boerwinkle, Eric
    Riemenschneider, Matthias
    Boada, Merce
    Hiltunen, Mikko
    Martin, Eden R.
    Schmidt, Reinhold
    Rujescu, Dan
    Dartigues, Jean-Francois
    Mayeux, Richard
    Tzourio, Christophe
    Hofman, Albert
    Noethen, Markus M.
    Graff, Caroline
    Psaty, Bruce M.
    Haines, Jonathan L.
    Lathrop, Mark
    Pericak-Vance, Margaret A.
    Launer, Lenore J.
    Van Broeckhoven, Christine
    Farrer, Lindsay A.
    van Duijn, Cornelia M.
    Ramirez, Alfredo
    Seshadri, Sudha
    Schellenberg, Gerard D.
    Amouyel, Philippe
    Williams, Julie
    Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 6, e94661- p.Article in journal (Refereed)
    Abstract [en]

    Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

  • 22.
    Fastbom, Johan
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    National Indicators for Quality of Drug Therapy in Older Persons: the Swedish Experience from the First 10 Years2015In: Drugs & Aging, ISSN 1170-229X, E-ISSN 1179-1969, Vol. 32, no 3, 189-199 p.Article, review/survey (Refereed)
    Abstract [en]

    Inappropriate drug use is an important health problem in elderly persons. Beginning with the Beers' criteria in the early 1990s, explicit criteria have been extensively used to measure and improve quality of drug use in older people. This article describes the Swedish indicators for quality of drug therapy in the elderly, introduced in 2004 and updated in 2010. These indicators were designed to be applied to people aged 75 years and over, regardless of residence and other characteristics. The indicators are divided into drug specific, covering choice, indication and dosage of drugs, polypharmacy, drug-drug interactions (DDIs), drug use in decreased renal function and in some symptoms; and diagnosis specific, covering the rational, irrational and hazardous drug use in common disorders in elderly people. During the 10 years since introduction, the Swedish indicators have several applications. They form the basis for recommendations for drug therapy in older people, are implemented in prescribing supports and drug utilisation reviews, are used in national benchmarking of the quality of Swedish healthcare and have contributed to initiatives from pensioner organisations. The indicators have also been used in several pharmacoepidemiological studies. Since 2005, there have been signs of improvement of the quality of drug prescribing to elderly persons in Sweden. For example, the prescribing of drugs that should be avoided in older persons decreased by 36 % between 2006 and 2012 in persons aged 80 years and older. Similarly, drug combinations that may cause DDIs decreased by 26 % and antipsychotics by 41 %. The indicators have likely contributed to this.

  • 23. Feng, Lei
    et al.
    Yan, Zhongrui
    Sun, Binglun
    Cai, Chuanzhu
    Jiang, Hui
    Kua, Ee-Heok
    Ng, Tze-Pin
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Tea Consumption and Depressive Symptoms in Older People in Rural China2013In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 61, no 11, 1943-1947 p.Article in journal (Refereed)
    Abstract [en]

    ObjectivesTo examine the association between tea consumption and depressive symptoms in Chinese older people and to explore the mediating role of cerebrovascular disease in the association. DesignPopulation-based cross-sectional study. SettingA rural community near Qufu in Shandong, China. ParticipantsCommunity-dwelling individuals aged 60 and older (mean 68.6; 59.3% female) from the Confucius Hometown Aging Project (N=1,368). MeasurmentsData were collected through interviews, clinical examinations, and psychological testing, following a standard procedure. Presence of high depressive symptoms was defined as a score of 5 or greater on the 15-item Geriatric Depression Scale. ResultsOf the 1,368 participants, 165 (12.1%) were weekly and 489 (35.7%) were daily tea consumers. Compared with no or irregular tea consumption, controlling for age, sex, education, leisure activities, number of comorbidities, and Mini-Mental State Examination score, the odds ratios of having high depressive symptoms were 0.86 (95% confidence interval (CI)=0.56-1.32) for weekly and 0.59 (95% CI=0.43-0.81) for daily tea consumption (P for linear trend=.001); the linear trend of the association remained statistically significant when further controlling for history of stroke, transient ischemic attacks, and presence of carotid plaques. ConclusionsDaily tea consumption is associated with a lower likelihood of depressive symptoms in Chinese older people living in a rural community. The association appears to be independent of cerebrovascular disease and atherosclerosis.

  • 24.
    Ferencz, Beata
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Jonsson Laukka, Erika
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Welmer, Anna-Karin
    Kalpouzos, Grégoria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Angleman, Sara
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Keller, Lina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska Institutet, Sweden.
    Graff, Caroline
    Lövdén, Martin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    The Benefits of Staying Active in Old Age: Physical Activity Counteracts the Negative Influence of PICALM, BIN1, and CLU Risk Alleles on Episodic Memory Functioning2014In: Psychology and Aging, ISSN 0882-7974, E-ISSN 1939-1498, Vol. 29, no 2, 440-449 p.Article in journal (Refereed)
    Abstract [en]

    PICALM, BIN1, CLU, and APOE are top candidate genes for Alzheimer's disease, and they influence episodic memory performance in old age. Physical activity, however, has been shown to protect against age-related decline and counteract genetic influences on cognition. The aims of this study were to assess whether (a) a genetic risk constellation of PICALM, BIN1, and CLU polymorphisms influences cognitive performance in old age; and (b) if physical activity moderates this effect. Data from the SNAC-K population-based study were used, including 2,480 individuals (age range = 60 to 100 years) free of dementia at baseline and at 3- to 6-year follow-ups. Tasks assessing episodic memory, perceptual speed, knowledge, and verbal fluency were administered. Physical activity was measured using self-reports. Individuals who had engaged in frequent health-or fitness-enhancing activities within the past year were compared with those who were inactive. Genetic risk scores were computed based on an integration of risk alleles for PICALM (rs3851179 G allele, rs541458 T allele), BIN1 (rs744373 G allele), and CLU (rs11136000 T allele). High genetic risk was associated with reduced episodic memory performance, controlling for age, education, vascular risk factors, chronic diseases, activities of daily living, and APOE gene status. Critically, physical activity attenuated the effects of genetic risk on episodic memory. Our findings suggest that participants with high genetic risk who maintain a physically active lifestyle show selective benefits in episodic memory performance.

  • 25.
    Ferrari, Camilla
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Xu, Wei-Li
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wang, Hui-Xin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Winblad, Bengt
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Sorbi, Sandro
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    How can elderly apolipoprotein E epsilon 4 carriers remain free from dementia?2013In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 34, no 1, 13-21 p.Article in journal (Refereed)
    Abstract [en]

    Apolipoprotein E (APOE) epsilon 4 is a major risk factor for Alzheimer's disease (AD) and dementia, but not all epsilon 4 carriers develop dementia. We sought to identify factors that may play a role in modifying the risk of dementia due to epsilon 4. A cognitively intact cohort (n = 932, age >= 75) was followed for 9 years to detect incident dementia cases. At baseline, information on education, leisure activities, and vascular risk factors was collected, and APOE was genotyped. During the follow-up, 324 subjects developed dementia, including 247 AD cases. The hazard ratio (HR, 95% confidence interval [95% CI]) of dementia related to the epsilon 4 was 1.39 (1.11-1.76), while the risk was reduced when epsilon 4 carriers had high education, no vascular risk factors, or high score of leisure activities. Among epsilon 4 carriers, the multiadjusted HRs of dementia that were associated with high education, high level of leisure activities, and absence of vascular risk factors were 0.59 (0.40-0.87), 0.49 (0.29-0.85), and 0.61 (0.41-0.90), respectively. The epsilon 4 carriers with these factors had about 1.2 years delayed time to dementia onset compared with those without these factors. High education, active leisure activities, or maintaining vascular health seems to reduce the risk of dementia related to APOE epsilon 4. The epsilon 4 carriers with these characteristics appear to have similar dementia-free survival time to non-epsilon 4 carriers.

  • 26. Garcia-Ptacek, Sara
    et al.
    Kåreholt, Ingemar
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Jönköping University, Sweden.
    Cermakova, Pavla
    Rizzuto, Debora
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Religa, Dorota
    Eriksdotter, Maria
    Causes of Death According to Death Certificates in Individuals with Dementia: A Cohort from the Swedish Dementia Registry2016In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 64, no 11, E137-E142 p.Article in journal (Refereed)
    Abstract [en]

    Objectives

    The causes of death in dementia are not established, particularly in rarer dementias. The aim of this study is to calculate risk of death from specific causes for a broader spectrum of dementia diagnoses.

    Design

    Cohort study.

    Setting

    Swedish Dementia Registry (SveDem), 2007–2012.

    Participants

    Individuals with incident dementia registered in SveDem (N = 28,609); median follow-up 741 days. Observed deaths were 5,368 (19%).

    Measurements

    Information on number of deaths and causes of mortality was obtained from death certificates. Odds ratios for the presence of dementia on death certificates were calculated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox hazards regression for cause-specific mortality, using Alzheimer's dementia (AD) as reference. Hazard ratios for death for each specific cause of death were compared with hazard ratios of death from all causes (P-values from t-tests).

    Results

    The most frequent underlying cause of death in this cohort was cardiovascular (37%), followed by dementia (30%). Dementia and cardiovascular causes appeared as main or contributory causes on 63% of certificates, followed by respiratory (26%). Dementia was mentioned less in vascular dementia (VaD; 57%). Compared to AD, cardiovascular mortality was higher in individuals with VaD than in those with AD (HR = 1.82, 95% CI = 1.64–2.02). Respiratory death was higher in individuals with Lewy body dementia (LBD, including Parkinson's disease dementia and dementia with Lewy bodies, HR = 2.16, 95% CI = 1.71–2.71), and the risk of respiratory death was higher than expected from the risk for all-cause mortality. Participants with frontotemporal dementia were more likely to die from external causes of death than those with AD (HR = 2.86, 95% CI = 1.53–5.32).

    Conclusion

    Dementia is underreported on death certificates as main and contributory causes. Individuals with LBD had a higher risk of respiratory death than those with AD.

  • 27. Garcia-Ptacek, Sara
    et al.
    Kåreholt, Ingemar
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Jönkoping University, Sweden.
    Farahmand, Bahman
    Cuadrado, Maria Luz
    Religa, Dorota
    Eriksdotter, Maria
    Dementia and Obesity Paradox: Reply to the Letter by Dr Moga et al.2015In: Journal of the American Medical Directors Association, ISSN 1525-8610, E-ISSN 1538-9375, Vol. 16, no 1, 79-81 p.Article in journal (Refereed)
  • 28. Garcia-Ptacek, Sara
    et al.
    Kåreholt, Ingemar
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Jönköping University, Sweden.
    Farahmand, Bahman
    Luz Cuadrado, Maria
    Religa, Dorota
    Eriksdotter, Maria
    Body-Mass Index and Mortality in Incident Dementia: A Cohort Study on 11,398 Patients From SveDem, the Swedish Dementia Registry2014In: Journal of the American Medical Directors Association, ISSN 1525-8610, E-ISSN 1538-9375, Vol. 15, no 6, 447.e1- p.Article in journal (Refereed)
    Abstract [en]

    Background: Body mass index (BMI) is used worldwide as an indirect measure of nutritional status and has been shown to be associated with mortality. Controversy exists over the cut points associated with lowest mortality, particularly in older populations. In patients suffering from dementia, information on BMI and mortality could improve decisions about patient care. Objectives: The objective was to explore the association between BMI and mortality risk in an incident dementia cohort. Design: Cohort study based on SveDem, the Swedish Quality Dementia Registry; 2008-2011. Setting: Specialist memory clinics, Sweden. Participants: A total of 11,398 patients with incident dementia with data on BMI (28,190 person-years at risk for death). Main outcome measures: Hazard ratios and 95% confidence intervals for mortality associated with BMI were calculated, controlling for age, sex, dementia type, results from Mini-Mental State Examination, and number of medications. BMI categories and linear splines were used. Results: Higher BMI was associated with decreased mortality risk, with all higher BMI categories showing reduced risk relative to patients with BMI of 18.5 to 22.9 kg/m(2), whereas underweight patients (BMI <18.5 kg/m(2)) displayed excess risk. When explored as splines, increasing BMI was associated with decreased mortality risk up to BMI of 30.0 kg/m(2). Each point increase in BMI resulted in an 11% mortality risk reduction in patients with BMI less than 22.0 kg/m(2), 5% reduction when BMI was 22.0 to 24.9 kg/m(2), and 3% risk reduction among overweight patients. Results were not significant in the obese weight range. Separate examination by sex revealed a reduction in mortality with increased BMI up to BMI 29.9 kg/m(2) for men and 24.9 kg/m(2) for women. Conclusion: Higher BMI at the time of dementia diagnosis was associated with a reduction in mortality risk up to and including the overweight category for the whole cohort and for men, and up to the normal weight category for women.

  • 29. Garcia-Ptacek, Sara
    et al.
    Nilsson Modeer, Ingrid
    Kåreholt, Ingemar
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Jönköping University, Sweden.
    Fereshtehnejad, Seyed-Mohammad
    Farahmand, Bahman
    Religa, Dorota
    Eriksdotter, Maria
    Differences in diagnostic process, treatment and social Support for Alzheimer's dementia between primary and specialist care: resultss from the Swedish Dementia Registry2017In: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 46, no 2, 314-319 p.Article in journal (Refereed)
    Abstract [en]

    Background: the increasing prevalence of Alzheimer's dementia (AD) has shifted the burden of management towards primary care (PC). Our aim is to compare diagnostic process and management of AD in PC and specialist care (SC). Design: cross-sectional study. Subjects: a total of, 9,625 patients diagnosed with AD registered 2011-14 in SveDem, the Swedish Dementia Registry. Methods: descriptive statistics are shown. Odds ratios are presented for test performance and treatment in PC compared to SC, adjusted for age, sex, Mini-Mental State Examination (MMSE) and number of medication. Results: a total of, 5,734 (60%) AD patients from SC and 3,891 (40%) from PC. In both, 64% of patients were women. PC patients were older (mean age 81 vs. 76; P < 0.001), had lower MMSE (median 21 vs. 22; P < 0.001) and more likely to receive home care (31% vs. 20%; P < 0.001) or day care (5% vs. 3%; P < 0.001). Fewer diagnostic tests were performed in PC and diagnostic time was shorter. Basic testing was less likely to be complete in PC. The greatest differences were found for neuroimaging (82% in PC vs. 98% in SC) and clock tests (84% vs. 93%). These differences remained statistically significant after adjusting for MMSE and demographic characteristics. PC patients received less antipsychotic medication and more anxiolytics and hypnotics, but there were no significant differences in use of cholinesterase inhibitors between PC and SC. Conclusion: primary and specialist AD patients differ in background characteristics, and this can influence diagnostic work-up and treatment. PC excels in restriction of antipsychotic use. Use of head CT and clock test in PC are areas for improvement in Sweden.

  • 30. Gerritsen, Lotte
    et al.
    Wang, Hui-Xin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Reynolds, Chandra A.
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Gatz, Margaret
    Pedersen, Nancy L.
    Influence of Negative Life Events and Widowhood on Risk for Dementia2017In: The American journal of geriatric psychiatry, ISSN 1064-7481, E-ISSN 1545-7214, Vol. 25, no 7, 766-778 p.Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of the current study was to examine the effect of negative life events and widowhood on the incidence of dementia. Methods: Data were from four Swedish longitudinal cohort studies with a total of nearly 2,000 participants and 8-25 years of follow-up. Seven stressful events were examined for which data were available in all cohorts. Clinical dementia diagnoses were made through medical and psychological examinations. Cox proportional hazards models were used to estimate the association between life events and dementia, adjusting for lifestyle and cardiovascular risk factors. Results: The experience of one stressful life event was not associated with dementia incidence, but two or more negative life events at baseline predicted higher risk for dementia (pooled HR:2.00). This was most apparent for the incidence of vascular dementia (pooled HR: 3.60) but not for Alzheimer disease (pooled HR: 1.29). Moreover, persons who were widowed and had experienced one or more negative life events were found to have a threefold risk for dementia. Conclusion: Widowhood augments the effect of negative life events on dementia incidence and negative life events specifically increase the risk for vascular dementia.

  • 31. Ghisletta, Paolo
    et al.
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Bertram, Lars
    Brandmaier, Andreas Markus
    Gerstorf, Denis
    Liu, Tian
    Lindenberger, Ulman
    The Val/Met Polymorphism of the Brain-Derived Neurotrophic Factor (BDNF) Gene Predicts Decline in Perceptual Speed in Older Adults2014In: Psychology and Aging, ISSN 0882-7974, E-ISSN 1939-1498, Vol. 29, no 2, 384-392 p.Article in journal (Refereed)
    Abstract [en]

    The brain-derived neurotrophic factor (BDNF) promotes activity-dependent synaptic plasticity, and contributes to learning and memory. We investigated whether a common Val66Met missense polymorphism (rs6265) of the BDNF gene is associated with individual differences in cognitive decline (marked by perceptual speed) in old age. A total of 376 participants of the Berlin Aging Study, with a mean age of 83.9 years at first occasion, were assessed longitudinally up to 11 times across more than 13 years on the Digit-Letter task. Met carriers (n = 123, 34%) showed steeper linear decline than Val homozygotes (n = 239, 66%); the corresponding contrast explained 2.20% of the variance in change in the entire sample, and 3.41% after excluding individuals at risk for dementia. These effects were not moderated by sex or socioeconomic status. Results are consistent with the hypothesis that normal aging magnifies the effects of common genetic variation on cognitive functioning.

  • 32. Gorbach, Tetiana
    et al.
    Pudas, Sara
    Lundquist, Anders
    Orädd, Greger
    Josefsson, Maria
    Salami, Alireza
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Umeå University, Sweden.
    de Luna, Xavier
    Nyberg, Lars
    Longitudinal association between hippocampus atrophy and episodic-memory decline2017In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 51, 167-176 p.Article in journal (Refereed)
    Abstract [en]

    There is marked variability in both onset and rate of episodic-memory decline in aging. Structural magnetic resonance imaging studies have revealed that the extent of age-related brain changes varies markedly across individuals. Past studies of whether regional atrophy accounts for episodic-memory decline in aging have yielded inconclusive findings. Here we related 15-year changes in episodic memory to 4-year changes in cortical and subcortical gray matter volume and in white-matter connectivity and lesions. In addition, changes in word fluency, fluid IQ (Block Design), and processing speed were estimated and related to structural brain changes. Significant negative change over time was observed for all cognitive and brain measures. A robust brain-cognition change-change association was observed for episodic-memory decline and atrophy in the hippocampus. This association was significant for older (65-80 years) but not middle-aged (55-60 years) participants and not sensitive to the assumption of ignorable attrition. Thus, these longitudinal findings highlight medial-temporal lobe system integrity as particularly crucial for maintaining episodic-memory functioning in older age.

  • 33.
    Grande, G.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Milan, Italy.
    Tramacere, I.
    Vetrano, D. L.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Catholic University of Rome, Italy.
    Clerici, F.
    Pomati, S.
    Mariani, C.
    Filippini, G.
    Role of anticholinergic burden in primary care patients with first cognitive complaints2017In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, no 7, 950-955 p.Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Drugs with anticholinergic properties might have a negative impact on cognition, but findings are still conflicting. The association was evaluated between anticholinergic drugs and cognitive performance in primary care patients with first cognitive complaints. Methods: From April 2013 to March 2014, 353 general practitioners administered the Mini-Mental State Examination (MMSE) to patients presenting with first cognitive complaints. Drug history was collected and the anticholinergic cognitive burden (ACB) was scored and categorized as ACB 0, ACB 1 and ACB 2+. A mixed effect linear regression model was used to assess the association between ACB and MMSE score. Results: Of 4249 subjects entering the study (mean age 77 +/- 8.2 years, 66.4% women and mean years of schooling 8.9 +/- 4.5), 25.8% received at least one drug with anticholinergic action. According to multivariate analysis, and after adjustment for several confounders, subjects with ACB 2+ had a statistically significant lower MMSE score compared with those with ACB 0 (beta -0.63; 95% confidence interval -1.19; -0.07). Subjects with ACB 1 had a non-statistically significant lower MMSE score than those with ACB 0 (beta -0.11; 95% confidence interval -0.37; 0.15). Conclusions: Anticholinergic medication might affect cognitive function in people with first cognitive complaints. Alternatives should be taken into account when possible, balancing the benefits and harms of these medications.

  • 34.
    Grande, Giulia
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Milan, Italy.
    Morin, Lucas
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Vetrano, Davide Liborio
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Catholic University of Rome, Italy.
    Fastbom, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Drug Use in Older Adults with Amyotrophic Lateral Sclerosis Near the End of Life2017In: Drugs & Aging, ISSN 1170-229X, E-ISSN 1179-1969, Vol. 34, no 7, 529-533 p.Article in journal (Refereed)
    Abstract [en]

    Background Amyotrophic lateral sclerosis (ALS), with its certain prognosis and swift progression, raises concerns regarding the adequacy of pharmacological treatment, including the risk-benefit profiles of prescribed drugs. Objective Our objective was to evaluate the use of prescription drugs over the course of the last year of life in older adults with ALS. Methods We conducted a nationwide retrospective cohort study of older adults who died with ALS in Sweden between 2007 and 2013. The primary outcome was the number of prescription drugs to which individuals were exposed during the last 12 months before death. Results The overall proportion of individuals receiving ten or more different prescription drugs increased from 19% at 12 months before death to 37% during the last month of life. Institutionalization was independently associated with polypharmacy near the end of life (odds ratio 1.84; 95% confidence interval 1.42-2.39). Conclusion Future research is needed to assess the time to benefit of treatments and to develop guidelines for medication discontinuation in advanced ALS.

  • 35. Gutiérrez-Valencia, Marta
    et al.
    Martinez-Velilla, Nicolas
    Liborio Vetrano, Davide
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Catholic University of Rome, Italy.
    Corsonello, Andrea
    Lattanzio, Fabrizia
    Ladron-Arana, Sergio
    Onder, Graziano
    Anticholinergic burden and health outcomes among older adults discharged from hospital: results from the CRIME study2017In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 73, no 11, 1467-1474 p.Article in journal (Refereed)
    Abstract [en]

    Purpose The purpose of this study is to investigate whether there is an association between anticholinergic burden and mortality or rehospitalization in older adults discharged from hospital. Methods Prospective multicenter cohort study carried out with patients aged 65 and older discharged from seven acute care hospitals. The primary outcomes of the study were rehospitalization and mortality within 1 year after discharge. The study population was classified in three groups according to the anticholinergic exposure measured by the Anticholinergic Risk Scale (ARS) and Duran's list at the time of hospital discharge: without risk (ARS/Duran = 0), low risk (ARS/Duran = 1), and high risk (ARS/Duran >= 2). Predictors of hospitalizations and mortality were examined using regression models adjusting for important covariates. Results The mean age of the 921 participants was 81.2 years (SD = 7.4 years). Prevalence of exposure to medications with anticholinergic activity ranged from 19.6% with ARS to 32.1% with Duran's list. During the follow-up period, 30.4% of participants were hospitalized and 19.4% died. Multivariate regression analysis showed that low anticholinergic burden quantified according to Duran's list was significantly associated with all-cause mortality (OR 1.69, 95% CI 1.02-2.82). This association was not present after adjustment when using ARS. No statistically significant association was found between anticholinergic burden and hospitalizations. Conclusions Taking medications with anticholinergic activity is associated with greater risk of mortality in older adults discharged from acute care hospitals. Strategies to reduce anticholinergic burden in vulnerable elders could be useful to improve health outcomes. Further research is required to assess the association between anticholinergic burden and hospitalizations in older patients.

  • 36. Hahn, Elizabeth A.
    et al.
    Wang, Hui-Xin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Andel, Ross
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    A Change in Sleep Pattern May Predict Alzheimer Disease2014In: The American journal of geriatric psychiatry, ISSN 1064-7481, E-ISSN 1545-7214, Vol. 22, no 11, 1262-1271 p.Article in journal (Refereed)
    Abstract [en]

    Objective: Sleep problems may adversely affect neuronal health. We examined a subjective report of change (reduced duration and/or depth) in sleep pattern in relation to subsequent risk of incident all-cause dementia and Alzheimer disease (AD) over 9 years. Methods: This longitudinal study used data from a population-based sample of 214 Swedish adults aged 75 and over who were dementia-free both at baseline and at first follow-up (3 years later). The sample was 80% female and, on average, 83.4 years of age at baseline. All participants underwent a thorough clinical examination to ascertain all-cause dementia and AD. Results: Forty percent of participants reported a change in sleep duration at baseline. Between the 6th and 9th year after baseline, 28.5% were diagnosed with all-cause dementia, 22.0% of whom had AD. Reduced sleep was associated with a 75% increased all-cause dementia risk (hazard ratio: 1.75; 95% confidence interval: 1.04-2.93; Wald = 4.55, df = 1, p = 0.035) and double the risk of AD (hazard ratio: 2.01; 95% confidence interval: 1.12-3.61; Wald = 5.47, df = 1, p = 0.019) after adjusting for age, gender, and education. The results remained after adjusting for lifestyle and vascular factors but not after adjusting for depressive symptoms. No evidence supported a moderating effect of the use of sleeping pills, and the sleepedementia relationship remained after controlling for the presence of the apolipoprotein E epsilon 4 allele. Conclusion: Self-reported sleep problems may increase the risk for dementia, and depressive symptoms may explain this relationship. Future research should determine whether treatment, in particular, behavioral or nonpharmacologic treatment, may represent one avenue toward reduction of dementia risk in late life.

  • 37. Hallgren, Jenny
    et al.
    Fransson, Eleonor I.
    Kåreholt, Ingemar
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Jönköping University, Sweden.
    Reynolds, Chandra A.
    Pedersen, Nancy L.
    Dahl Aslan, Anna K.
    Factors associated with hospitalization risk among community living middle aged and older persons: Results from the Swedish Adoption/Twin Study of Aging (SATSA)2016In: Archives of gerontology and geriatrics (Print), ISSN 0167-4943, E-ISSN 1872-6976, Vol. 66, 102-108 p.Article in journal (Refereed)
    Abstract [en]

    The aims of the present study were to: (1) describe and compare individual characteristics of hospitalized and not hospitalized community living persons, and (2) to determine factors that are associated with hospitalization risk over time. We conducted a prospective study with a multifactorial approach based on the population-based longitudinal Swedish Adoption/Twin Study of Aging (SATSA). A total of 772 Swedes (mean age at baseline 69.7 years, range 46-103, 59.8% females) answered a postal questionnaire about physical and psychological health, personality and socioeconomic factors. During nine years of follow-up, information on hospitalizations and associated diagnoses were obtained from national registers. Results show that 484 persons (63%) had at least one hospital admission during the follow-up period. The most common causes of admission were cardiovascular diseases (25%) and tumors (22%). Cox proportional hazard regression models controlling for age, sex and dependency within twin pairs, showed that higher age (HR = 1.02, p < 0.001) and more support from relatives (HR = 1.09, p = 0.028) were associated with increased risk of hospitalization, while marital status (unmarried (HR = 0.75, p = 0.033) and widow/widower (HR = 0.69, p < 0.001)) and support from friends (HR = 0.93, p = 0.029) were associated with lower risk of hospitalization. Social factors were important for hospitalization risk even when medical factors were controlled for in the analyses. Number of diseases was not a risk in the final regression model. Hospitalization risk was also different for women and men and within different age groups. We believe that these results might be used in future interventions targeting health care utilization.

  • 38. Hampel, Harald
    et al.
    Schneider, Lon S.
    Giacobini, Ezio
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska Institutet, Sweden; University of Eastern Finland, Finland.
    Sindi, Shireen
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska Institutet, Sweden.
    Dubois, Bruno
    Broich, Karl
    Nistico, Robert
    Aisen, Paul S.
    Lista, Simone
    Advances in the therapy of Alzheimer's disease: targeting amyloid beta and tau and perspectives for the future2015In: Expert Review of Neurotherapeutics, ISSN 1473-7175, E-ISSN 1744-8360, Vol. 15, no 1, 83-105 p.Article, review/survey (Refereed)
    Abstract [en]

    Worldwide multidisciplinary translational research has led to a growing knowledge of the genetics and molecular pathogenesis of Alzheimer's disease (AD) indicating that pathophysiological brain alterations occur decades before clinical signs and symptoms of cognitive decline can be diagnosed. Consequently, therapeutic concepts and targets have been increasingly focused on early-stage illness before the onset of dementia; and distinct classes of compounds are now being tested in clinical trials. At present, there is a growing consensus that therapeutic progress in AD delaying disease progression would significantly decrease the expanding global burden. The evolving hypothesis- and evidence-based generation of new diagnostic research criteria for early-stage AD has positively impacted the development of clinical trial designs and the characterization of earlier and more specific target populations for trials in prodromal as well as in pre- and asymptomatic at-risk stages of AD.

  • 39. Hedman, Annicka
    et al.
    Nygård, Louise
    Almkvist, Ove
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Kottorp, Anders
    Patterns of functioning in older adults with mild cognitive impairment: a two-year study focusing on everyday technology use2013In: Aging & Mental Health, ISSN 1360-7863, E-ISSN 1364-6915, Vol. 17, no 6, 679-688 p.Article in journal (Refereed)
    Abstract [en]

    Objectives: Early detection is vital for persons with mild cognitive impairment (MCI) who are at risk of activity and participation limitations, and crosssectional studies suggest the ability to use everyday technology (ET) to be a sensible tool. However, group level analyses fail to inform us about how functioning can vary over time for individuals. This study aimed at exploring and describing patterns of functioning over two years in a sample newly classified with MCI, with a special focus on perceived difficulty in ET use and involvement in everyday activities. In addition, cognitive functioning and conversion to dementia were studied. Method: 37 older adults (aged 55) with MCI were assessed at inclusion, and at 6, 12, and 24 months. Longitudinal case plots for the variables under study were analyzed based on strict criteria using a person-oriented approach. Paired t-tests from baseline and 24 months were also conducted to analyze change. Results: The 32 participants who remained in the study after two years showed three distinct patterns of functioning over time: stable/ascending (n = 10), fluctuating (n = 10), and descending (n = 12), with the highest conversion to dementia in the descending pattern (58%). The perceived ability to use ET decreased or fluctuated in 50% of the sample. However, on a group level, a significant difference between baseline and 24 months was found only regarding cognitive function. Conclusion: As the need for support is individual and likely to alter over time, repeated evaluations of activity involvement and difficulty in ET use are suggested to target timely interventions for persons with MCI.

  • 40.
    Heiland, Emerald G.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wang, Rui
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Santoni, Giola
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Liang, Yajun
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Welmer, Anna-Karin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Cardiovascular Risk Burden and Future Risk of Walking Speed Limitation in Older Adults2017In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 65, no 11, 2418-2424 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To explore the association between cardiovascular risk factor (CRF) burden and limitation in walking speed, balance, and chair stand and to verify whether these associations vary according to age and cognitive status.

    DESIGN: Longitudinal population-based study.

    SETTING: Urban area of Stockholm, Sweden.

    PARTICIPANTS: Individuals aged 60 and older who participated in the Swedish National Study on Aging and Care in Kungsholmen and were free of limitations in walking speed (n = 1,441), balance (n = 1,154), or chair stands (n = 1,496) at baseline (2001-04).

    MEASUREMENTS: At baseline, data on demographic characteristics, CRFs, other lifestyle factors, C-reactive protein, and cognitive function were collected. CRF burden was measured using the Framingham general cardiovascular risk score (FRS). Limitations in walking speed (<0.8 m/s), balance (<5 seconds), and chair stand (inability to rise 5 times) were determined at 3-, 6-, and 9-year follow-up. Data were analyzed using Cox proportional hazards models stratified according to age (<78, >= 78).

    RESULTS: During follow-up, 326 persons developed limitations in walking speed, 303 in balance, and 374 in chair stands. An association between the FRS and walking speed limitation was evident only in adults younger than 78 (for each 1-point increase in FRS: hazard ratio (HR) = 1.09, 95% confidence interval (CI) = 1.02-1.17) after controlling for potential confounders including cognitive function (correspondingly, in adults aged >= 78: HR = 0.98, 95% CI = 0.92-1.03). Also, higher FRS was significantly associated with faster decline in walking speed (P<.001).

    CONCLUSION: A higher FRS is associated with greater risk of subsequent development of walking speed limitation in adults younger than 78, independent of cognitive function. Interventions targeting multiple CRFs in younger-old people may help in maintaining mobility function.

  • 41.
    Heiland, Emerald G.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Welmer, Anna-Karin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wang, Rui
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Santoni, Giola
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Angleman, Sara
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Qu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Association of mobility limitations with incident disability among older adults: a population-based study2016In: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 45, no 6, 812-819 p.Article in journal (Refereed)
    Abstract [en]

    Background: mobility-related limitations predict future disability; however, the extent to which individual and combined mobility tests may predict disability remains unclear.

    Objectives: to estimate the odds of developing disability in activities of daily living (ADL) according to limitations in walking speed, balance or both; and explore the role of chronic diseases and cognitive function.

    Design: a prospective cohort study.

    Setting: urban area of Stockholm, Sweden.

    Subjects: one thousand nine hundred and seventy-one disability-free persons (age >= 60 years, 63% women) from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K), who underwent baseline examination in 2001-04 and follow-up assessments for 6 years.

    Measurements: mobility limitation was defined as a one-leg balance stand <5 s or walking speed <0.8 m/s. ADL disability was defined as the inability to complete one or more ADL: bathing, dressing, using the toilet, transferring and eating.

    Results: during a total of 11,404 person-years (mean per person 5.8 years, SD 0.30) of follow-up, 119 (incidence 1.5/100 person-years) participants developed ADL disability. The demographic adjusted odds ratios (OR) (95% confidence intervals, CI) of incident ADL disability related to balance stand and walking speed limitations were 3.8 (2.3-6.3) and 8.4 (5.2-13.3), respectively. The associations remained statistically significant after controlling for number of chronic diseases and cognitive status. People with limitations in both balance and walking speed had an OR of 12.9 (95% CI 7.0-23.7) for incident disability compared with no limitation.

    Conclusion: balance and walking speed tests are simple clinical procedures that can indicate hierarchical risk of ADL dependence in older adults.

  • 42.
    Herlitz, Agneta
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lovén, Johanna
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Cognition2012In: Handbook of clinical gender medicine / [ed] Karin Schenck Gustafsson, Paula DeCola, Donald W. Pfaff, David S. Pisetsky, Basel: S. Karger, 2012, 504-507 p.Chapter in book (Refereed)
    Abstract [en]

    There are sex differences favoring men in visuospatial abilities and mathematical problem solving, whereas women outperform men on verbal production tasks, verbal episodic memory tasks, and face recognition. These differences are present in childhood, adolescence, and middle and old age, and the pattern is also seen in non-Western societies. Social and cultural factors affect the magnitude of these differences, but not the pattern. Prenatal levels of androgens affect play behavior, but have little influence on cognitive performance. For older adults, hormone treatment of estradiol and testosterone does not seem to affect cognitive sex differences or cognitive performance.

  • 43. Hertzog, Christopher
    et al.
    Lövdén, Martin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lindenberger, Ulman
    Schmiedek, Florian
    Age Differences in Coupling of Intraindividual Variability in Mnemonic Strategies and Practice-Related Associative Recall Improvements2017In: Psychology and Aging, ISSN 0882-7974, E-ISSN 1939-1498, Vol. 32, no 6, 557-571 p.Article in journal (Refereed)
    Abstract [en]

    The importance of encoding strategies for associative recall is well established, but there have been no studies of aging and intraindividual variability (IAV) in strategy use during extended practice. We observed strategy use and cued-recall test performance over 101 days of practice in 101 younger adults (M = 25.6 years) and 103 older adults (M = 71.3 years) sandwiched by a pretest and posttest battery including an associative recall test. Each practice session included 2 lists of 12 number-noun paired-associate (PA) items (e.g., 23-DOGS), presented for brief exposures titrated to maintain below-ceiling performance throughout practice. Participants reported strategy use (e.g., rote repetition, imagery) after each test. Substantial IAV in strategy use was detected that was coupled with performance; lists studied with normatively effective strategies (e.g., imagery) generated higher PA recall than lists studied with less effective strategies (e.g., rote repetition). In comparison to younger adults, older adults' practice (a) relied more on repetition and less on effective strategies, (b) showed lower levels of IAV in effective strategy use, and (c) had lower within-person strategy-recall coupling, especially late in practice. Individual differences in pretest-posttest gains in PA recall were predicted by average level of effective strategy use in young adults but by strategy-recall coupling in older adults. Results are consistent with the hypothesis that experiencing variability in strategic outcomes during practice helps hone the effectiveness of strategic encoding behavior, and that older adults' reduced degree of pretest-posttest gains is influenced by lower likelihood of using and optimizing effective strategies through practice.

  • 44.
    Hooshmand, Babak
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lokk, Johan
    Solomon, Alina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Mangialasche, Francesca
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Miralbell, Julia
    Spulber, Gabriela
    Annerbo, Sylvia
    Andreasen, Niels
    Winblad, Bengt
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Cedazo-Minguez, Angel
    Wahlund, Lars-Olof
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Vitamin D in Relation to Cognitive Impairment, Cerebrospinal Fluid Biomarkers, and Brain Volumes2014In: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 69, no 9, 1132-1138 p.Article in journal (Refereed)
    Abstract [en]

    Background. Low vitamin D status is associated with poorer cognitive function in older adults, but little is known about the potential impact on cerebrospinal fluid (CSF) biomarkers and brain volumes. The objective of this study was to examine the relations between plasma 25-hydroxyvitamin D (25(OH)D) and cognitive impairment, CSF biomarkers of Alzheimer's disease (AD), and structural brain tissue volumes. Methods. A total of 75 patients (29 with subjective cognitive impairment, 28 with mild cognitive impairment, 18 with AD) referred to the Memory Clinic at Karolinska University Hospital, Huddinge, Sweden were recruited. Plasma 25(OH)D, CSF levels of amyloid beta (A beta(1-42)), total-tau, and phosphorylated tau, and brain tissue volumes have been measured. Results. After adjustment for several potential confounders, the odds ratios (95% confidence interval) for cognitive impairment were as follows: 0.969 (0.948-0.990) per increase of 1 nmol/L of 25(OH) D and 4.19 (1.30-13.52) for 24(OH) D values less than 50 nmol/L compared with values greater than or equal to 50 nmol/L. Adjusting for CSF A beta(1-42) attenuated the 25(OH) D-cognition link. In a multiple linear regression analysis, higher 25(OH)D levels were related to higher concentrations of CSF A beta(1-42) and greater brain volumes (eg, white matter, structures belonging to medial temporal lobe). The associations between 25(OH)D and tau variables were not significant. Conclusions. This study suggests that vitamin D may be associated with cognitive status, CSF A beta(1-42) levels, and brain tissue volumes.

  • 45.
    Håkansson, Krister
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Ledreux, Aurelie
    Daffner, Kirk
    Terjestam, Yvonne
    Bergman, Patrick
    Carlsson, Roger
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Winblad, Bengt
    Granholm, Ann-Charlotte
    Mohammed, Abdul Kadir H.
    BDNF Responses in Healthy Older Persons to 35 Minutes of Physical Exercise, Cognitive Training, and Mindfulness: Associations with Working Memory Function2017In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 55, no 2, 645-657 p.Article in journal (Refereed)
    Abstract [en]

    Brain-derived neurotrophic factor (BDNF) has a central role in brain plasticity by mediating changes in cortical thickness and synaptic density in response to physical activity and environmental enrichment. Previous studies suggest that physical exercise can augment BDNF levels, both in serum and the brain, but no other study has examined how different types of activities compare with physical exercise in their ability to affect BDNF levels. By using a balanced cross over experimental design, we exposed nineteen healthy older adults to 35-minute sessions of physical exercise, cognitive training, and mindfulness practice, and compared the resulting changes in mature BDNF levels between the three activities. We show that a single bout of physical exercise has significantly larger impact on serum BDNF levels than either cognitive training or mindfulness practice in the same persons. This is the first study on immediate BDNF effects of physical activity in older healthy humans and also the first study to demonstrate an association between serum BDNF responsivity to acute physical exercise and working memory function. We conclude that the BDNF increase we found after physical exercise more probably has a peripheral than a central origin, but that the association between post-intervention BDNF levels and cognitive function could have implications for BDNF responsivity in serum as a potential marker of cognitive health.

  • 46.
    Johnell, Kristina
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Jonasdottir Bergman, Gudrun
    Fastbom, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Danielsson, Bengt
    Borg, Natalia
    Salmi, Peter
    Psychotropic drugs and the risk of fall injuries, hospitalisations and mortality among older adults2017In: International Journal of Geriatric Psychiatry, ISSN 0885-6230, E-ISSN 1099-1166, Vol. 32, no 4, 414-420 p.Article in journal (Refereed)
    Abstract [en]

    Objective

    To investigate whether psychotropics are associated with an increased risk of fall injuries, hospitalizations, and mortality in a large general population of older adults.

    Methods

    We performed a nationwide matched (age, sex, and case event day) case–control study between 1 January and 31 December 2011 based on several Swedish registers (n = 1,288,875 persons aged ≥65 years). We used multivariate conditional logistic regression adjusted for education, number of inpatient days, Charlson co-morbidity index, dementia and number of other drugs.

    Results

    Antidepressants were the psychotropic most strongly related to fall injuries (ORadjusted: 1.42; 95% CI: 1.38–1.45) and antipsychotics to hospitalizations (ORadjusted: 1.22; 95% CI: 1.19–1.24) and death (ORadjusted: 2.10; 95% CI: 2.02–2.17). Number of psychotropics was associated with increased the risk of fall injuries, (4 psychotropics vs 0: ORadjusted: 1.53; 95% CI: 1.39–1.68), hospitalization (4 psychotropics vs 0: ORadjusted: 1.27; 95% CI: 1.22–1.33) and death (4 psychotropics vs 0: ORadjusted: 2.50; 95% CI: 2.33–2.69) in a dose–response manner. Among persons with dementia (n = 58,984), a dose–response relationship was found between number of psychotropics and mortality risk (4 psychotropics vs 0: ORadjusted: 1.99; 95% CI: 1.76–2.25).

    Conclusions

    Our findings support a cautious prescribing of multiple psychotropic drugs to older patients. © 2016 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons, Ltd.

  • 47.
    Johnell, Kristina
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Religa, Dorota
    Eriksdotter, Maria
    Differences in Drug Therapy between Dementia Disorders in the Swedish Dementia Registry: A Nationwide Study of over 7,000 Patients2013In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 35, no 5-6, 239-248 p.Article in journal (Refereed)
    Abstract [en]

    Background/Aims: We aimed to study whether there are differences between dementia disorders and the use of anti-dementia drugs and antipsychotics (neuroleptics) in a large population of dementia patients. Methods: Information about dementia disorders was obtained from the national Swedish Dementia Registry (SveDem) 2007-2010 (n = 7,570). Multivariate logistic regression analysis was performed to investigate the association between dementia disorders and the use of anti-dementia drugs and antipsychotics, after adjustment for age, sex, residential setting, living alone, MMSE score and number of other drugs (a proxy for overall co-morbidity). Results: More than 80% of the Alzheimer's disease (AD) and 86% of dementia with Lewy bodies (DLB) patients used anti-dementia drugs. Women were more likely than men to be treated with cholinesterase inhibitors. A higher MMSE score was positively associated with the use of cholinesterase inhibitors, but negatively associated with NMDA receptor antagonists and antipsychotics. Use of antipsychotics was 6% overall; however, it was 16% in DLB patients with an adjusted odds ratio of 4.2 compared to AD patients. Conclusion: Use of anti-dementia drugs in AD was in agreement with Swedish guidelines. However, use of antipsychotics in DLB patients was high, which might be worrying given the susceptibility of DLB patients to antipsychotics.

  • 48.
    Kalpouzos, Gregoria
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Local brain atrophy accounts for functional activity differences in normal aging2012In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 33, no 3, 623.e1- p.Article in journal (Refereed)
    Abstract [en]

    Functional brain imaging studies of normal aging typically show age-related under-and overactivations during episodic memory tasks. Older individuals also undergo nonuniform gray matter volume (GMv) loss. Thus, age differences in functional brain activity could at least in part result from local atrophy. We conducted a series of voxel-based blood oxygen level-dependent (BOLD)-GMv analyses to highlight whether age-related under-and overrecruitment was accounted for by GMv changes. Occipital GMv loss accounted for underrecruitment at encoding. Efficiency reduction of sensory-perceptual mechanisms underpinned by these areas may partly be due to local atrophy. At retrieval, local GMv loss accounted for age-related overactivation of left dorsolateral prefrontal cortex, but not of left dorsomedial prefrontal cortex. Local atrophy also accounted for age-related overactivation in left lateral parietal cortex. Activity in these frontoparietal regions correlated with performance in the older group. Atrophy in the overrecruited regions was modest in comparison with other regions as shown by a between-group voxel-based morphometry comparison. Collectively, these findings link age-related structural differences to age-related functional under-as well as overrecruitment.

  • 49.
    Kalpouzos, Grégoria
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Rizzuto, Debora
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Keller, Lina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska Institutet, Sweden.
    Fastbom, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Santoni, Giola
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Angleman, Sara
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Graff, Caroline
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska University Hospital Huddinge, Sweden; Stockholm Gerontology Research Center, Sweden.
    Telomerase Gene (hTERT) and Survival: Results From Two Swedish Cohorts of Older Adults2016In: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 71, no 2, 188-195 p.Article in journal (Refereed)
    Abstract [en]

    Telomere length has been associated with longevity. As telomere length is partly determined by the human telomerase reverse transcriptase (hTERT), we investigated the association between an hTERT polymorphism located in its promoter region ((-) (1327)T/C) and longevity in two cohorts of older adults. Participants from the Kungsholmen project (KP; n = 1,205) and the Swedish National study of Aging and Care in Kungsholmen (SNAC-K; n = 2,764) were followed for an average period of 7.5 years. The main outcomes were hazard ratios (HR) of mortality and median age at death. In both cohorts, mortality was lower in female T/T carriers, aged 75+ years in KP (HR = 0.8, 95% CI: 0.5-0.9) and 78+ years in SNAC-K (HR = 0.6, 95% CI: 0.4-0.8) compared with female C/C carriers. T/T carriers died 1.8-3 years later than the C/C carriers. This effect was not present in men, neither in SNAC-K women aged 60-72 years. The association was not modified by presence of cancer, cardiovascular diseases, number of chronic diseases, or markers of inflammation, and did not interact with APOE genotype or estrogen replacement therapy. The gender-specific increased survival in T/T carriers can be due to a synergistic effect between genetic background and the life-long exposure to endogenous estrogen.

  • 50.
    Karlsson, Björn
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Gothenburg, Sweden.
    Sigström, Robert
    Östling, Svante
    Waern, Margda
    Börjesson-Hanson, Anne
    Skoog, Ingmar
    DSM-IV and DSM-5 Prevalence of Social Anxiety Disorder in a Population Sample of Older People2016In: The American journal of geriatric psychiatry, ISSN 1064-7481, E-ISSN 1545-7214, Vol. 24, no 12, 1237-1245 p.Article in journal (Refereed)
    Abstract [en]

    Objectives: To examine the prevalence of social anxiety disorders (SAD) with (DSM-IV) and without (DSM-5) the person's own assessment that the fear was unreasonable, in a population sample of older adults. Further, to determine whether clinical and sociodemographic correlates of SAD differ depending on the criteria applied. Design: Cross-sectional. Setting: General population in Gothenburg, Sweden. Participants: A random population-based sample of 75- and 85-year olds (N = 1200) without dementia. Measurements: Psychiatric research nurses carried out a semi-structured psychiatric examination including the Comprehensive Psychopathological Rating Scale. DSM-IV SAD was diagnosed with the Mini International Neuropsychiatric Interview. SAD was diagnosed according to DSM-IV and DSM-5 criteria. The 6-month duration criterion in DSM-5 was not applied because of lack of information. Other assessments included the Global Assessment of Functioning (GAF), the Brief Scale for Anxiety (BSA), and the Montgomery Asberg Depression Rating Scale (MADRS). Results: The 1-month prevalence of SAD was 2.5% (N = 30) when the unreasonable fear criterion was defined in accordance with DSM-IV and 5.1% (N = 61) when the DSM-5 criterion was applied. Clinical correlates (GAF, MADRS, and BSA) were worse in SAD cases identified by either procedure compared with all others, and ratings for those reporting unreasonable fear suggested greater (albeit nonsignificant) overall psychopathology. Conclusions: Shifting the judgment of how reasonable the fear was, from the individual to the clinician, doubled the prevalence of SAD. This indicates that the DSM-5 version might increase prevalence rates of SAD in the general population. Further studies strictly applying all DSM-5 criteria are needed in order to confirm these findings.

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