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  • 301.
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Inappropriate Drug Use in People with Cognitive Impairment and Dementia: A Systematic Review2015In: Current clinical pharmacology, ISSN 1574-8847, Vol. 10, no 3, p. 178-184Article, review/survey (Refereed)
    Abstract [en]

    The aim of this systematic review was to identify, assess and summarize studies about potentially inappropriate drug use (IDU) in cognitive impairment and dementia and to present findings about whether cognitive impairment and dementia are associated with IDU. The search was made in Medline/PubMed using free terms in the title or abstract. The inclusion criteria were: English language, published until 1 March 2014, original quantitative study and assessment of overall IDU with a consensus based summarized measure. Exclusion criteria were: focus on specific patient group (other than cognitive impairment or dementia), focus on specific drug class and failure to present a prevalence measure of IDU or an effect estimate (i.e. odds ratio). Of the initial 182 studies found in Medline, 22 articles fulfilled the criteria. Most studies used the Beers criteria for assessment of IDU. Prevalence of IDU among individuals with cognitive impairment or dementia ranged from 10.2% to 56.4% and was higher in nursing home settings than in community-dwelling samples. Most studies reported a lower likelihood of IDU in case of cognitive impairment or dementia. To conclude, IDU is highly prevalent among persons with cognitive impairment and dementia, although these conditions seem to be associated with a lower probability of IDU. This might reflect an awareness among clinicians of cautious prescribing to this vulnerable group of patients. More studies on large cohorts of persons with cognitive impairment and dementia are needed to draw conclusions about optimal drug prescribing to this frail group of older persons.

  • 302.
    Johnell, Kristina
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fastbom, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Antiepileptic drug use in community-dwelling and institutionalized elderly: a nationwide study of over 1 300 000 older people2011In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 67, no 10, p. 1069-1075Article in journal (Refereed)
    Abstract [en]

    To investigate whether institutionalization is associated with the use of antiepileptic drugs (AEDs) and to compare the association between use of AEDs and psychotropics in community-dwelling and institutionalized elderly, after adjustment for age, sex and co-morbidity (i.e. number of other drugs). We analyzed data on age, sex and dispensed drugs for individuals aged a parts per thousand yen65 years registered in the Swedish Prescribed Drug Register from July to September 2008, record-linked to the Swedish Social Services Register (n = 1 345 273: 1 258 565 community-dwelling and 86 708 institutionalized elderly). Multivariate logistic regression analysis was used to analyze whether institutionalization and use of psychotropics (i.e. antipsychotics, anxiolytics, hypnotics/sedatives and antidepressants) were associated with the use of AEDs. AEDs were used by 2% of the community-dwelling and 9% of the institutionalized elderly. The most commonly used AEDs were carbamazepine, gabapentin, pregabalin, valproic acid and lamotrigine. Institutionalization was strongly associated with AED use (OR(adjusted) = 3.98; 95% CI 3.86-4.10). In community-dwelling elderly, AED use was associated with an increased probability of use of all types of psychotropics. However, among institutionalized elderly, the associations between use of AEDs and psychotropics showed a mixed pattern. AED use seems to be common among Swedish institutionalized elderly, and institutionalization is a strong determinant of AED use. Our results may also indicate an off-label prescribing of AEDs as an alternative to psychotropics in the institutional setting. This finding needs to be confirmed by others and evaluated with respect to outcomes of this treatment in institutionalized elderly.

  • 303.
    Johnell, Kristina
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fastbom, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Comparison of prescription drug use between community dwelling and institutionalized elderly in Sweden2012In: Drugs & Aging, ISSN 1170-229X, E-ISSN 1179-1969, Vol. 29, no 9, p. 751-758Article in journal (Refereed)
    Abstract [en]

    Background Most previous studies about drug use in the elderly population have either investigated drug use in institutions or in the community-dwelling setting. Hence, very few studies have compared drug use in institutionalized and community-dwelling elderly, maybe because of a lack of sufficiently large databases. Objective The aim of the study was to investigate differences in drug use patterns between community-dwelling and institutionalized elderly, after adjustment for age, gender and number of other drugs (used as a proxy for overall co-morbidity). Methods We analysed data from individuals aged >= 65 years who filled at least one drug prescription between July and September 2008 and were consequently registered in the Swedish Prescribed Drug Register (n = 1,347,564; 1,260,843 community-dwelling and 86,721 institutionalized elderly). A list of current prescriptions was constructed for every individual on the arbitrarily chosen date 30 September 2008. Outcome measures were the 20 most common drug classes and the 20 most common individual drugs. Logistic regression analysis was used to investigate whether institutionalization was associated with use of these drugs, after adjustment for age, gender and number of other drugs. Results Institutionalized elderly were more likely than community-dwelling elderly to use antidepressants, laxatives, minor analgesics, opioids and hypnotics/sedatives, after adjustment for age, gender and number of other drugs. On the contrary, institutionalization was negatively associated with use of lipid modifying agents, angiotensin II antagonists, selective calcium channel blockers, beta-blocking agents and ACE inhibitors, after adjustment for age, gender and number of other drugs. Conclusions Our results indicate that institutionalized elderly are more likely than community-dwelling elderly to use psychotropics, analgesics and laxatives, but less likely to receive recommended cardiovascular drug therapy, which may indicate a need for implementation of evidencebased guidelines for drug treatment in this vulnerable group of elderly patients. Further research is needed to elucidate to what extent the differences in drug use between community-dwelling and institutionalized elderly are explained by different underlying disease patterns and by different prescribing traditions in the different settings.

  • 304.
    Johnell, Kristina
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fastbom, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Gender and use of hypnotics or sedatives in old age: a nationwide register-based study2011In: International Journal of Clinical Pharmacy, ISSN 2210-7703, Vol. 33, no 5, p. 788-793Article in journal (Refereed)
    Abstract [en]

    Objective To investigate whether gender is associated with use of hypnotics or sedatives and with different types of hypnotics or sedatives in older people after adjustment for age, socioeconomic status (i.e., education) and co-morbidity (i.e., number of other drugs). Setting Sweden Method We conducted a register-based analysis of data on gender, age, dispensed drugs, and education from people aged 75-89 years registered in the Swedish Prescribed Drug Register between July and October 2005 (n = 645,429). Main outcome measure The hypnotic or sedative drug classes were benzodiazepines, benzodiazepine related drugs (i.e., Z-drugs) and other types of hypnotics or sedatives. The individual hypnotics or sedatives were nitrazepam, flunitrazepam, triazolam, zopiclone, zolpidem, clomethiazole and propiomazine. Results In the total study population, 27.1% of the women and 18.1% of the men were dispensed at least one hypnotic or sedative drug. The logistic regression analyses of those who used hypnotics or sedatives (n = 151,700) revealed that women were more likely than men to use benzodiazepines (adjusted OR = 1.11; 95% CI 1.07-1.14) and benzodiazepine related drugs (adjusted OR = 1.14; 95% CI 1.12-1.17), whereas men were more likely to use other types of hypnotics or sedatives (adjusted OR = 0.69; 95% CI 0.67-0.71). Among the individual hypnotics or sedatives, the strongest associations with gender was found for nitrazepam (adjusted OR = 1.19; 95% CI 1.14-1.25 for women compared with men), zolpidem (adjusted OR = 1.18; 95% CI 1.16-1.21), clomethiazole (adjusted OR = 0.48; 95% CI 0.46-0.51) and propiomazine (adjusted OR = 0.77; 95% CI 0.75-0.79). Conclusion Use of hypnotics or sedatives in old age seems to be related to female gender. Also, among elderly users of hypnotics or sedatives, women appear to be more likely to use benzodiazepines and benzodiazepine related drugs than men. The explanation to these gender differences merits further investigation.

  • 305.
    Johnell, Kristina
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fischer, Håkan
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Dopaminergic and Serotonergic Drug Use: A Nationwide Register-Based Study of Over 1 300 000 Older People2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 8, p. e23750-Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the use of dopaminergic and serotonergic drugs in elderly people. Methods: We analyzed data on age, sex and dispensed drugs for individuals aged >= 65 years registered in the Swedish Prescribed Drug Register from July to September 2008 (n = 1 347 564; 81% of the total population aged >= 65 years in Sweden). Main outcome measures were dopaminergic (enhancing and/or lowering) and serotonergic (enhancing and/or lowering) drugs and combinations of these. Results: Dopaminergic and serotonergic drugs were used by 5.6% and 13.2% the participants, respectively. Female gender was related to use of both dopaminergic and, particularly, serotonergic drugs. Higher age was associated with use of dopamine lowering drugs and serotonergic drugs, whereas the association with use of dopamine enhancing drugs declined in the oldest old. The occurrence of combinations of dopaminergic and serotonergic drugs was generally low, with dopamine lowering + serotonin lowering drug the most common combination (1.6%). Female gender was associated with all of the combinations of dopaminergic and serotonergic drugs, whereas age showed a mixed pattern. Conclusion: Approximately one out of ten older patients uses serotonergic drugs and one out of twenty dopaminergic drugs. The frequent use of dopaminergic and serotonergic drugs in the elderly patients is a potential problem due to the fact that aging is associated with a down-regulation of both these monoaminergic systems. Future studies are needed for evaluation of the impact of these drugs on different cognitive and emotional functions in old age.

  • 306.
    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, p. 414-420Article 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.

  • 307.
    Johnell, Kristina
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Laflamme, Lucie
    Möller, Jette
    Monarrez-Espino, Joel
    The Role of Marital Status in the Association between Benzodiazepines, Psychotropics and Injurious Road Traffic Crashes: A Register-Based Nationwide Study of Senior Drivers in Sweden2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 1, p. e86742-Article in journal (Refereed)
    Abstract [en]

    Background: Among senior drivers, benzodiazepines (BZDs) have a documented effect on the risk of road traffic crashes (RTCs). It remains unclear however if BZDs play the same role when considering marital status. Therefore, we aimed to investigate the role of marital status in the association between BZD use and injurious RTCs among senior drivers. Methods: Matched case-control study based on five national Swedish registers (n = 154 225). Cases comprised the first non-alcohol-related injurious RTC sustained by drivers aged 50-80 years from July 2005 to December 2009 and controls included registered residents with a valid license who did not crash during that period. Four controls were matched to each case by sex, age and place of residence. Conditional logistic regression analysis for injurious RTC was performed with adjustment for occupation and number of medications. The main exposure was dispensation of BZDs, alone or in combination with other psychotropic medications, 1-30 days prior to the crash date stratified by marital status. Results: BZD use, alone or in combination with other psychotropic medications, increased the risk of being involved in an RTC (BZD only: adjusted OR: 1.26, 95% CI: 1.17-1.36; BZDs and other psychotropics: adjusted OR: 1.25, 95% CI: 1.12-1.41). Compared to married drivers, those divorced (1.48, 1.43-1.53) and widowed (1.54; 1.45-1.63) had higher adjusted ORs. Marital status modified the association between BZDs and RTCs, particularly among younger male drivers. Conclusions: Both BZDs and marital status independently affect the risk for senior drivers to be involved in an RTC. However, marital status plays a role in the association between BZD use and RTCs and this may have implications for targeting risk populations for RTCs among senior drivers.

  • 308.
    Johnell, Kristina
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Parker, Marti G
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Gender differences in medication use by elderly people2011In: From women’s health to gender medicine: an anthology / [ed] Sara Bergqvist Månsson, Stockholm: Swedish Council for Working Life and Social Research , 2011, p. 37-49Chapter in book (Other academic)
  • 309.
    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, p. 239-248Article 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.

  • 310. Jokanovic, Natali
    et al.
    Kautiainen, Hannu
    Bell, J. Simon
    Tan, Edwin C. K.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Monash University, Australia; The University of Sydney, Australia.
    Pitkala, Kaisu H.
    Change in Prescribing forSecondary Prevention of Stroke and Coronary Heart Disease in Finnish Nursing Homes and Assisted Living Facilities2019In: Drugs & Aging, ISSN 1170-229X, E-ISSN 1179-1969, Vol. 36, no 6, p. 571-579Article in journal (Refereed)
    Abstract [en]

    Background

    One quarter of residents in long-term care facilities (LTCFs) have a diagnosis of CHD or stroke and over half use at least one preventative cardiovascular medication. There have been no studies that have investigated the longitudinal change in secondary preventative cardiovascular medication use in residents in LTCFs over time.

    Objective

    The aim of this study was to investigate the change in cardiovascular medication use among residents with coronary heart disease (CHD) and prior stroke in nursing homes (NHs) and assisted living facilities (ALFs) in Finland over time, and whether this change differs according to dementia status.

    Methods

    Three comparable cross-sectional audits of cardiovascular medication use among residents aged 65years and over with CHD or prior stroke in NHs in 2003 and 2011 and ALFs in 2007 and 2011 were compared. Logistic regression analyses adjusted for gender, age, mobility, cancer and length of stay were performed to examine the effect of study year, dementia and their interaction on medication use.

    Results

    Cardiovascular medication use among residents with CHD (NHs: 89% vs 70%; ALFs: 89% vs 84%) and antithrombotic medication use among residents with stroke (NHs: 72% vs 63%; ALFs: 78% vs 69%) declined between 2003 and 2011 in NHs and 2007 and 2011 in ALFs. Decline in the use of diuretics, nitrates and digoxin were found in both groups and settings. Cardiovascular medication use among residents with CHD and dementia declined in NHs (88% [95% CI 85-91] in 2003 vs 70% [95% CI 64-75] in 2011) whereas there was no change among people without dementia. There was no change in cardiovascular medication use among residents with CHD in ALFs with or without dementia over time. Antithrombotic use was lower in residents with dementia compared with residents without dementia in NHs (p<0.001) and ALFs (p=0.026); however, the interaction between dementia diagnosis and time was non-significant.

    Conclusions

    The decline in cardiovascular medication use in residents with CHD and dementia suggests Finnish physicians are adopting a more conservative approach to the management of cardiovascular disease in the NH population.

  • 311. Joling, Karlijn J.
    et al.
    van Eenoo, Liza
    Vetrano, Davide L.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Universita`Cattolica Sacro Cuore, Italy.
    Smaardijk, Veerle R.
    Declercq, Anja
    Onder, Graziano
    van Hout, Hein P. J.
    van der Roest, Henriette G.
    Quality indicators for community care for older people: A systematic review2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 1, article id e0190298Article, review/survey (Refereed)
    Abstract [en]

    Background

    Health care systems that succeed in preventing long term care and hospital admissions of frail older people may substantially save on their public spending. The key might be found in high-quality care in the community. Quality Indicators (QIs) of a sufficient methodological level are a prerequisite to monitor, compare, and improve care quality. This systematic review identified existing QIs for community care for older people and assessed their methodological quality.

    Methods

    Relevant studies were identified by searches in electronic reference databases and selected by two reviewers independently. Eligible publications described the development or application of QIs to assess the quality of community care for older people. Information about the QIs, the study sample, and specific setting was extracted. The methodological quality of the QI sets was assessed with the Appraisal of Indicators through Research and Evaluation (AIRE) instrument. A score of 50% or higher on a domain was considered to indicate high methodological quality.

    Results

    Searches resulted in 25 included articles, describing 17 QI sets with 567 QIs. Most indicators referred to care processes (80%) and measured clinical issues (63%), mainly about follow-up, monitoring, examinations and treatment. About two-third of the QIs focussed on specific disease groups. The methodological quality of the indicator sets varied considerably. The highest overall level was achieved on the domain 'Additional evidence, formulation and usage' (51%), followed by 'Scientific evidence' (39%) and 'Stakeholder involvement' (28%).

    Conclusion

    A substantial number of QIs is available to assess the quality of community care for older people. However, generic QIs, measuring care outcomes and non-clinical aspects are relatively scarce and most QI sets do not meet standards of high methodological quality. This study can support policy makers and clinicians to navigate through a large number of QIs and select QIs for their purposes.

  • 312. Jonasson, Lars S.
    et al.
    Axelsson, Jan
    Riklund, Katrine
    Braver, Todd S.
    Ogren, Mattias
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Nyberg, Lars
    Dopamine release in nucleus accumbens during rewarded task switching measured by [C-11]raclopride2014In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 99, p. 357-364Article in journal (Refereed)
    Abstract [en]

    Reward and motivation have positive influences on cognitive-control processes in numerous settings. Models of reward implicate corticostriatal loops and the dopamine (DA) system, with special emphasis on D-2 receptors in nucleus accumbens (NAcc). In this study, 11 right-handed males (35-40 years) were scanned with positron emission tomography (PET) in a single [C-11]raclopride dynamic scan during rewarded and non-rewarded task switching. Rewarded task switching (relative to baseline task switching) decreased [11C]raclopride binding in NAcc. Decreasing NAcc [C-11]raclopride binding was strongly associated with task reaction time measures that reflect individual differences in effort and control strategies. Voxelwise analyses additionally revealed reward-related DA release in anterodorsal caudate, a region previously associated with task-switching. These PET findings provide evidence for striatal DA release during motivated cognitive control, and further suggest that NAcc DA release predicts the task reaction time benefits of reward incentives.

  • 313. Jones, Lesley
    et al.
    Lambert, Jean-Charles
    Wang, Li-San
    Choi, Seung-Hoan
    Harold, Denise
    Vedernikov, Alexey
    Escott-Price, Valentina
    Stone, Timothy
    Richards, Alexander
    Bellenguez, Celine
    Ibrahim-Verbaas, Carla A.
    Naj, Adam C.
    Sims, Rebecca
    Gerrish, Amy
    Jun, Gyungah
    DeStefano, Anita L.
    Bis, Joshua C.
    Beecham, Gary W.
    Grenier-Boley, Benjamin
    Russo, Giancarlo
    Thornton-Wells, Tricia A.
    Jones, 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 W.
    Dunstan, Melanie L.
    Ruiz, Agustin
    Bihoreau, Marie-Therese
    Reitz, Christiane
    Pasquier, Florence
    Hollingworth, Paul
    Hanon, Olivier
    Fitzpatrick, Annette L.
    Buxbaum, Joseph D.
    Campion, Dominique
    Crane, Paul K.
    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
    Letteneur, Luc
    Kornhuber, Johanes
    Tarraga, Lluis
    Rubinsztein, David C.
    Eiriksdottir, Gudny
    Sleegers, Kristel
    Goate, Alison M.
    Fievet, Nathalie
    Huentelman, Matthew J.
    Gill, Michael
    Emilsson, Valur
    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
    Kehoe, Pat
    Rogaeva, Ekaterina
    Gallacher, John
    St George-Hyslop, Peter
    Clarimon, Jordi
    Lleo, Alberti
    Bayer, Anthony
    Tsuang, Debby W.
    Yu, Lei
    Tsolaki, Magda
    Bossu, Paola
    Spalletta, Gianfranco
    Proitsi, Petra
    Collinge, John
    Sorbi, Sandro
    Garcia, Fiorentino Sanchez
    Fox, Nick
    Hardy, John
    Deniz Naranjo, Maria Candida
    Razquin, Cristina
    Bosco, Paola
    Clarke, Robert
    Brayne, Carol
    Galimberti, Daniela
    Mancuso, Michelangelo
    Moebus, Susanne
    Mecocci, Patrizia
    del Zompo, Maria
    Maier, Wolfgang
    Hampel, Harald
    Pilotto, Alberto
    Bullido, Maria
    Panza, Francesco
    Caffarra, Paolo
    Nacmias, Benedetta
    Gilbert, John R.
    Mayhaus, Manuel
    Jessen, Frank
    Dichgans, Martin
    Lannfelt, Lars
    Hakonarson, Hakon
    Pichler, Sabrina
    Carrasquillo, Minerva M.
    Ingelsson, Martin
    Beekly, Duane
    Alavarez, Victoria
    Zou, Fanggeng
    Valladares, Otto
    Younkin, Steven G.
    Coto, Eliecer
    Hamilton-Nelson, Kara L.
    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.
    Bennett, David A.
    Harris, Tamara B.
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska University Hospital, Sweden.
    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.
    Nails, Michael A.
    Ritchie, Karen
    Lunetta, Kathryn L.
    Kauwe, John S. K.
    Boerwinkle, Eric
    Riemenschneider, Matthias
    Boada, Merce
    Hiltunen, Mikko
    Martin, Eden R.
    Pastor, Pau
    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.
    Farrer, Lindsay A.
    van Duijn, Cornelia M.
    Van Broeckhoven, Christine
    Ramirez, Alfredo
    Schellenberg, Gerard D.
    Seshadri, Sudha
    Amouyel, Philippe
    Williams, Julie
    Holmans, Peter A.
    Convergent genetic and expression data implicate immunity in Alzheimer's disease2015In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, no 6, p. 658-671Article in journal (Refereed)
    Abstract [en]

    Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.

  • 314. Jongstra, Susan
    et al.
    Beishuizen, Cathrien
    Andrieu, Sandrine
    Barbera, Mariagnese
    van Dorp, Matthijs
    van de Groep, Bram
    Guillemont, Juliette
    Mangialasche, Francesca
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    van Middelaar, Tessa
    Moll van Charante, Eric
    Soininen, Hilkka
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Richard, Edo
    Development and Validation of an Interactive Internet Platform for Older People: The Healthy Ageing Through Internet Counselling in the Elderly Study2017In: Telemedicine journal and e-health, ISSN 1530-5627, E-ISSN 1556-3669, Vol. 23, no 2, p. 96-104Article in journal (Refereed)
    Abstract [en]

    Background: A myriad of Web-based applications on self-management have been developed, but few focus on older people. In the face of global aging, older people form an important target population for cardiovascular prevention. This article describes the full development of an interactive Internet platform for older people, which was designed for the Healthy Ageing Through Internet Counselling in the Elderly (HATICE) study. We provide recommendations to design senior-friendly Web-based applications for a new approach to multicomponent cardiovascular prevention. Methods: The development of the platform followed five phases: (1) conceptual framework; (2) platform concept and functional design; (3) platform building (software and content); (4) testing and pilot study; and (5) final product. Results: We performed a meta-analysis, reviewed guidelines for cardiovascular diseases, and consulted end users, experts, and software devel-opers to create the platform concept and content. The software was built in iterative cycles. In the pilot study, 41 people aged >= 65 years used the platform for 8 weeks. Participants used the interactive features of the platform and appreciated the coach support. During all phases adjustments were made to incorporate all improvements from the previous phases. The final platform is a personal, secured, and interactive platform supported by a coach. Discussion: When carefully designed, an interactive Internet platform is acceptable and feasible for use by older people with basic computer skills. To improve acceptability by older people, we recommend involving the end users in the process of development, to personalize the platform and to combine the application with human support. The interactive HATICE platform will be tested for efficacy in a multinational randomized controlled trial (ISRCTN48151589).

  • 315. Julkunen, Valtteri
    et al.
    Niskanen, Eini
    Koikkalainen, Juha
    Herukka, Sanna-Kaisa
    Pihlajamäki, Maija
    Hallikainen, Merja
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Muehlboeck, Sebastian
    Evans, Alan C
    Vanninen, Ritva
    Soininen, Hilkka
    Differences in cortical thickness in healthy controls, subjects with mild cognitive impairment, and Alzheimer's disease patients: a longitudinal study2010In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 21, no 4, p. 1141-1151Article in journal (Refereed)
    Abstract [en]

    In this study, we analyzed differences in cortical thickness (CTH) between healthy controls (HC), subjects with stable mild cognitive impairment (S-MCI), progressive MCI (P-MCI), and Alzheimer's disease (AD), and assessed correlations between CHT and clinical disease severity, education, and apolipoprotein E4 (APOE) genotype. Automated CTH analysis was applied to baseline high-resolution structural MR images of 145 subjects with a maximum followup time of 7.4 years pooled from population-based study databases held in the University of Kuopio. Statistical differences in CTH between study groups and significant correlations between CTH and clinical and demographic factors were assessed and displayed on a cortical surface model. Compared to HC group (n = 26), the AD (n = 21) group displayed significantly reduced CTH in several areas of frontal and temporal cortices of the right hemisphere. Higher education and lower MMSE scores were correlated with reduced CTH in the AD group, whereas no significant correlation was found between CDR-SB scores or APOE genotype and CTH. The P-MCI group demonstrated significantly reduced CTH compared to S-MCI in frontal, temporal and parietal cortices even after statistically adjusting for all confounding variables. Ultimately, analysis of CTH can be used to detect cortical thinning in subjects with progressive MCI several years before conversion and clinical diagnosis of AD dementia, irrespective of their cognitive performance, education level, or APOE genotype.

  • 316.
    Kaboodvand, Neda
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Umeå University, Sweden.
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Nyberg, Lars
    Salami, Alireza
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Umeå University, Sweden.
    The retrosplenial cortex: A memory gateway between the cortical default mode network and the medial temporal lobe2018In: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 39, no 5, p. 2020-2034Article in journal (Refereed)
    Abstract [en]

    The default mode network (DMN) involves interacting cortical areas, including the posterior cingulate cortex (PCC) and the retrosplenial cortex (RSC), and subcortical areas, including the medial temporal lobe (MTL). The degree of functional connectivity (FC) within the DMN, particularly between MTL and medial-parietal subsystems, relates to episodic memory (EM) processes. However, past resting-state studies investigating the link between posterior DMN-MTL FC and EM performance yielded inconsistent results, possibly reflecting heterogeneity in the degree of connectivity between MTL and specific cortical DMN regions. Animal work suggests that RSC has structural connections to both cortical DMN regions and MTL, and may thus serve as an intermediate layer that facilitates information transfer between cortical and subcortical DMNs. We studied 180 healthy old adults (aged 64-68 years), who underwent comprehensive assessment of EM, along with resting-state fMRI. We found greater FC between MTL and RSC than between MTL and the other cortical DMN regions (e.g., PCC), with the only significant association with EM observed for MTL-RSC FC. Mediational analysis showed that MTL-cortical DMN connectivity increased with RSC as a mediator. Further analysis using a graph-theoretical approach on DMN nodes revealed the highest betweenness centrality for RSC, confirming that a high proportion of short paths among DMN regions pass through RSC. Importantly, the degree of RSC mediation was associated with EM performance, suggesting that individuals with greater mediation have an EM advantage. These findings suggest that RSC forms a critical gateway between MTL and cortical DMN to support EM in older adults.

  • 317.
    Kalpouzos, Gregoria
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Umeå University, Sweden.
    Eriksson, Johan
    Memory Self-Efficacy Beliefs Modulate Brain Activity when Encoding Real-World Future Intentions2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 9, article id e73850Article in journal (Refereed)
    Abstract [en]

    Background: While the use of different cognitive strategies when encoding episodic memory information has been extensively investigated, modulation of brain activity by memory self-efficacy beliefs has not been studied yet. Methodology/Principal Findings: Sixteen young adults completed the prospective and retrospective metamemory questionnaire, providing individual subjective judgments of everyday memory function. The day after, using functional magnetic resonance imaging, the participants had to memorize real-world intentions (e. g., return a book to the library), which were performed later on in a virtual environment. Participants also performed offline cognitive tasks evaluating executive functions, working memory, and attention. During encoding, activity was found in medial temporal lobe, left prefrontal cortex, medial parietal regions, occipital areas, and regions involved in (pre) motor processes. Based on results from the questionnaire, the group was split into low and high memory self-efficacy believers. Comparison of encoding-related brain activity between the 2 groups revealed that the low memory self-efficacy believers activated more the hippocampus bilaterally, right posterior parahippocampal cortex, precuneus, and left lateral temporal cortex. By contrast, more activity was found in dorsal anterior cingulate gyrus for the high-memory believers. In addition, the low-memory believers performed more poorly at feature binding and (at trend) manipulating visuospatial information in working memory. Conclusion/Significance: Overall, these findings indicate that memory self-efficacy beliefs modulate brain activity during intentional encoding. Low memory self-efficacy believers activated more brain areas involved in visuospatial operations such as the hippocampus. Possibly, this increase reflects attempts to compensate for poor performance of certain neurocognitive processes, such as feature binding. By contrast, high-memory believers seemed to rely more on executive-like processes involved in cognitive control.

  • 318.
    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, p. 623.e1-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.

  • 319.
    Kalpouzos, Grégoria
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Eriksson, Johan
    Sjölie, Daniel
    Molin, Jonas
    Nyberg, Lars
    Neurocognitive systems related to real-world prospective memory.2010In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, no 10, p. e13304-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Prospective memory (PM) denotes the ability to remember to perform actions in the future. It has been argued that standard laboratory paradigms fail to capture core aspects of PM.

    METHODOLOGY/PRINCIPAL FINDINGS: We combined functional MRI, virtual reality, eye-tracking and verbal reports to explore the dynamic allocation of neurocognitive processes during a naturalistic PM task where individuals performed errands in a realistic model of their residential town. Based on eye movement data and verbal reports, we modeled PM as an iterative loop of five sustained and transient phases: intention maintenance before target detection (TD), TD, intention maintenance after TD, action, and switching, the latter representing the activation of a new intention in mind. The fMRI analyses revealed continuous engagement of a top-down fronto-parietal network throughout the entire task, likely subserving goal maintenance in mind. In addition, a shift was observed from a perceptual (occipital) system while searching for places to go, to a mnemonic (temporo-parietal, fronto-hippocampal) system for remembering what actions to perform after TD. Updating of the top-down fronto-parietal network occurred at both TD and switching, the latter likely also being characterized by frontopolar activity.

    CONCLUSION/SIGNIFICANCE: Taken together, these findings show how brain systems complementary interact during real-world PM, and support a more complete model of PM that can be applied to naturalistic PM tasks and that we named PROspective MEmory DYnamic (PROMEDY) model because of its dynamics on both multi-phase iteration and the interactions of distinct neurocognitive networks.

  • 320.
    Kalpouzos, Grégoria
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fischer, Håkan
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Rieckmann, Anna
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    MacDonald, Stuart W. S.
    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).
    Impact of negative emotion on the neural correlates of long-term recognition in younger and older adults2012In: Frontiers in Integrative Neuroscience, ISSN 1662-5145, E-ISSN 1662-5145, Vol. 6, no 74, p. 1-25Article in journal (Refereed)
    Abstract [en]

    Some studies have suggested that the memory advantage for negative emotional information over neutral information (“negativity effect”) is reduced in aging. Besides the fact that most findings are based on immediate retrieval, the neural underpinnings of long-term emotional memory in aging have so far not been investigated. To address these issues, we assessed recognition of neutral and negative scenes after 1- and 3-week retention intervals in younger and older adults using functional magnetic resonance imaging. We further used an event-related design in order to disentangle successful, false, and true recognition. This study revealed four key findings: (1) increased retention interval induced an increased rate of false recognitions for negative scenes, canceling out the negativity effect (present for hit rates only) on discrimination in both younger and older adults; (2) in younger, but not older, adults, reduced activity of the medial temporal lobe was observed over time for neutral scenes, but not for negative scenes, where stable or increased activity was seen; (3) engagement of amygdala (AMG) was observed in older adults after a 3-week delay during successful recognition of negative scenes (hits vs. misses) in comparison with neutral scenes, which may indicate engagement of automatic processes, but engagement of ventrolateral prefrontal cortex was unrelated to AMG activity and performance; and (4) after 3 weeks, but not after 1 week, true recognition of negative scenes was characterized by more activity in left hippocampus and lateral occipito-temporal regions (hits vs. false alarms). As these regions are known to be related to consolidation mechanisms, the observed pattern may indicate the presence of delayed consolidation of true memories. Nonetheless, older adults’ low performance in discrimination of negative scenes could reflect the fact that overall, after long delays of retention, they rely more on general information rather than on perceptual detail in making recognition judgments.

  • 321.
    Kalpouzos, Grégoria
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Garzón, Benjamín
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Sitnikov, Rouslan
    Heiland, Carmel
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Salami, Alireza
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Umeå University, Sweden.
    Persson, Jonas
    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).
    Higher Striatal Iron Concentration is Linked to Frontostriatal Underactivation and Poorer Memory in Normal Aging2017In: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 27, no 6, p. 3427-3436Article in journal (Refereed)
    Abstract [en]

    In the brain, intracellular iron is essential for cellular metabolism. However, an overload of free iron is toxic, inducing oxidative stress and cell death. Although an increase of striatal iron has been related to atrophy and impaired cognitive performance, the link between elevated iron and altered brain activity in aging remains unexplored. In a sample of 37 younger and older adults, we examined whether higher striatal iron concentration could underlie age-related differences in frontostriatal activity induced by mental imagery of motor and non-motor scenes, and poorer recall of the scenes. Higher striatal iron concentration was linked to underrecruitment of frontostriatal regions regardless of age and striatal volume, the iron-activity association in right putamen being primarily driven by the older adults. In older age, higher striatal iron was related to poorer memory. Altered astrocytic functions could account for the link between brain iron and brain activity, as astrocytes are involved in iron buffering, neurovascular coupling, and synaptic activity. Our preliminary findings, which need to be replicated in a larger sample, suggest a potential frontostriatal target for intervention to counteract negative effects of iron accumulation on brain function and cognition.

  • 322.
    Kalpouzos, Grégoria
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Nyberg, Lars
    Multimodal neuroimaging in normal aging: structure-function interactions2012In: Memory and aging: current issues and future directions / [ed] Moshe Naveh-Benjamin, Nobuo Ohta, New York: Psychology Press, 2012, p. 273-304Chapter in book (Other academic)
  • 323.
    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, p. 188-195Article 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.

  • 324. Karalija, Nina
    et al.
    Jonassson, Lars
    Johansson, Jarkko
    Papenberg, Goran
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Salami, Alireza
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Umeå University, Sweden; Wallenberg Centre for Molecular Medicine, Sweden.
    Andersson, Micael
    Riklund, Katrine
    Nyberg, Lars
    Boraxbekk, Carl-Johan
    High long-term test-retest reliability for extrastriatal C-11-raclopride binding in healthy older adults2019In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016Article in journal (Refereed)
    Abstract [en]

    In vivo dopamine D2-receptor availability is frequently assessed with C-11-raclopride and positron emission tomography. Due to low signal-to-noise ratios for C-11-raclopride in areas with low D2 receptor densities, the ligand has been considered unreliable for measurements outside the dopamine-dense striatum. Intriguingly, recent studies show that extrastriatal C-11-raclopride binding potential (BPND) values are (i) reliably higher than in the cerebellum (where D2-receptor levels are negligible), (ii) correlate with behavior in the expected direction, and (iii) showed good test-retest reliability in a sample of younger adults. The present work demonstrates high seven-month test-retest reliability of striatal and extrastriatal C-11-raclopride BPND values in healthy, older adults (n = 27, age: 64-78 years). Mean C-11-raclopride BPND values were stable between test sessions in subcortical nuclei, and in frontal and temporal cortices (p > 0.05). Across all structures analyzed, intraclass correlation coefficients were high (0.85-0.96), absolute variability was low (mean: 4-8%), and coefficients of variance ranged between 9 and 25%. Furthermore, regional C-11-raclopride BPND values correlated with previously determined F-18-fallypride BPND values (rho = 0.97 and 0.92 in correlations with and without striatal values, respectively, p < 0.01) and postmortem determined D2-receptor densities (including striatum: rho = 0.92; p < 0.001; excluding striatum: rho = 0.75; p = 0.067). These observations suggest that extrastriatal C-11-raclopride measurements represent a true D2 signal.

  • 325. Karalija, Nina
    et al.
    Papenberg, Goran
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wåhlin, Anders
    Johansson, Jarkko
    Andersson, Micael
    Axelsson, Jan
    Riklund, Katrine
    Lövdén, Martin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lindenberger, Ulman
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Nyberg, Lars
    C957T-mediated Variation in Ligand Affinity Affects the Association between C-11-raclopride Binding Potential and Cognition2019In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 31, no 2, p. 314-325Article in journal (Refereed)
    Abstract [en]

    The dopamine (DA) system plays an important role in cognition. Accordingly, normal variation in DA genes has been found to predict individual differences in cognitive performance. However, little is known of the impact of genetic differences on the link between empirical indicators of the DA system and cognition in humans. The present work used PET with C-11-raclopride to assess DA D2-receptor binding potential (BP) and links to episodic memory, working memory, and perceptual speed in 179 healthy adults aged 64-68 years. Previously, the T-allele of a DA D2-receptor single-nucleotide polymorphism, C957T, was associated with increased apparent affinity of C-11-raclopride, giving rise to higher BP values despite similar receptor density values between allelic groups. Consequently, we hypothesized that C-11-raclopride BP measures inflated by affinity rather than D2-receptor density in T-allele carriers would not be predictive of DA integrity and therefore prevent finding an association between C-11-raclopride BP and cognitive performance. In accordance with previous findings, we show that C-11-raclopride BP was increased in T-homozygotes. Importantly, C-11-raclopride BP was only associated with cognitive performance in groups with low or average ligand affinity (C-allele carriers of C957T, n = 124), but not in the high-affinity group (T-homozygotes, n = 55). The strongest C-11-raclopride BP-cognition associations and the highest level of performance were found in C-homozygotes. These findings show that genetic differences modulate the link between BP and cognition and thus have important implications for the interpretation of DA assessments with PET and C-11-raclopride in multiple disciplines ranging from cognitive neuroscience to psychiatry and neurology.

  • 326.
    Karlsson, Björn
    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).
    Sigström, Robert
    Sjöberg, Linnea
    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.
    Depression and Depression Treatment in a Population-Based Study of Individuals Over 60 Years Old Without Dementia2016In: The American journal of geriatric psychiatry, ISSN 1064-7481, E-ISSN 1545-7214, Vol. 24, no 8, p. 615-623Article in journal (Refereed)
    Abstract [en]

    Objective: To estimate the prevalence of depression in a population-based sample of older adults, and to identify the individual profile of people who received depression treatment. Design: Cross-sectional. Setting: Central area (Kungsholmen) in Stockholm, Sweden. Participants: A randomized population-based sample of individuals aged 60 years and older (N = 3,084) without dementia from the Swedish National Study of Aging and Care in Kungsholmen examined between 2001 and 2004. Measurements: Experienced physicians carried out a semi-structured psychiatric examination including the Comprehensive Psychopathological Rating Scale. Depression was diagnosed according to DSM-IV-TR and DSM-5 criteria. Information regarding drug treatment and psychotherapy was collected during the examination and is based on self-report. Results: The prevalence of depression was 5.9% (major depression: 0.8%, minor depression: 5.1%). In the total sample, 8.3% were prescribed an antidepressant and 0.9% were treated with psychotherapy. Among individuals with depression, fewer than one-third received treatment with psychotherapy or antidepressants, but almost half were prescribed anxiolytic or hypnotic drugs. Individuals with self-reported depression and anxiety were more likely to receive depression treatment whereas individuals with depression who reported insomnia were less likely to receive depression treatment. Conclusions: Our findings indicate that even in a central urban area of a country with an advanced healthcare system depression in old age is often unrecognized and untreated. In addition, almost half of those with depression received potentially inappropriate drug treatment with anxiolytics or hypnotics.

  • 327.
    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, p. 1237-1245Article 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.

  • 328.
    Karlsson, Sari
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Rieckmann, Anna
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Karlsson, Per
    Farde, Lars
    Nyberg, Lars
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Relationship of dopamine D1 receptor binding in striatal and extrastriatal regions to cognitive functioning in healthy humans2011In: NeuroImage, ISSN 1053-8119, Vol. 57, no 2, p. 346-351Article in journal (Refereed)
    Abstract [en]

    Dopamine (DA) availability in both striatal and extrastriatal brain regions has been implicated in cognitive performance. Given that different brain regions are neuroanatomically and functionally different, DA receptor binding in different brain regions may be selectively important to specific cognitive functions. Using PET and the radioligand SCH23390, we measured D1 receptor binding potential (BPND) in dorsolateral prefrontal cortex (DLPFC), hippocampus (HC), as well as in sensorimotor (SMST), associative (AST), and limbic (LST) striatum in 20 healthy younger persons. Subjects completed tasks assessing executive functioning, episodic memory, speed, and general knowledge. Unlike previous reports, we found no linear or curvilinear relationships between D1 receptor binding in DLPFC and performance in any cognitive task. However, BPND in HC was positively linked to executive performance as well as to speed and knowledge. With regard to the striatal subregions, D1 BPND in SMST was more strongly related to speed compared to the other striatal subregions, whereas D1 BPND in AST was more strongly linked to general knowledge. These findings provide support for the notion that D1 receptors in separate brain regions are differentially related to performance in tasks tapping various cognitive domains.

  • 329.
    Karp, Anita
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Ebrahimi, Roya
    Marengoni, Alessandra
    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).
    Informal care and voluntary assistance: A systematic literature review of quantitative and qualitative aspects of assistance to elderly persons in Sweden, Italy, the United Kingdom and Canada2010Report (Other academic)
  • 330.
    Karshikoff, Bianka
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska University Hospital, Sweden; Karolinska Institutet, Sweden.
    Jensen, K. B.
    Kosek, E.
    Kalpouzos, Grégoria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Soop, A.
    Ingvar, M.
    Olgart Höglund, C.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska University Hospital, Sweden; Karolinska Institutet, Sweden.
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska University Hospital, Sweden; Karolinska Institutet, Sweden.
    Why sickness hurts: A central mechanism for pain induced by peripheral inflammation2016In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 57, p. 38-46Article in journal (Refereed)
    Abstract [en]

    Low-grade systemic inflammation has been implicated in chronic pain, as well as in comorbid diseases like depression and fatigue. We have previously shown that women's pain perception and regulation is more affected by systemic inflammation than that of men. Here we investigated the neural substrates underlying these effects using an fMRI paradigm previously employed in a clinical population. Fifty-one participants (29 women) were injected with 0.6ng/kg lipopolysaccharide (LPS) or saline to induce a peripheral inflammatory response. The subjects were then tested with a pressure pain fMRI paradigm designed to capture descending pain inhibitory activity 2h after injection, and blood was sampled for cytokine analysis. The subjects injected with LPS became more pain sensitive compared to the placebo group, and the heightened pain sensitivity was paralleled by decreased activity in the ventrolateral prefrontal cortex and the rostral anterior cingulate cortex (rACC) compared to placebo; areas involved in descending pain regulation. The LPS group also had higher activity in the anterior insular cortex, an area underpinning affective and interoceptive pain processing. Women displayed overall less pain-evoked rACC activity compared to men, which may have rendered women less resilient to immune provocation, possibly explaining sex differences in LPS-induced pain sensitivity. Our findings elucidate the pain-related brain circuits affected by experimental peripheral inflammation, strengthening the theoretical link between systemic inflammation and weakened pain regulation in chronic pain disorders. The results further suggest a possible mechanism underlying the female predominance in many chronic pain disorders.

  • 331. Kassebaum, Nicholas J.
    et al.
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Murray, Christopher J. L.
    Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 20152016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 388, no 10053, p. 1603-1658Article in journal (Refereed)
    Abstract [en]

    Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development.

    Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate.

    Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs.

    Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum. Copyright (C) The Author(s). Published by Elsevier Ltd.

  • 332. Kauppi, Karolina
    et al.
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm Brain Institute, Sweden.
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Nyberg, Lars
    Additive genetic effect of APOE and BDNF on hippocampus activity2014In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 89, p. 306-313Article in journal (Refereed)
    Abstract [en]

    Human memory is a highly heritable polygenic trait with complex inheritance patterns. To study the genetics of memory and memory-related diseases, hippocampal functioning has served as an intermediate phenotype. The importance of investigating gene-gene effects on complex phenotypes has been emphasized, but most imaging studies still focus on single polymorphisms. APOE epsilon 4 and BDNF Met, two of the most studied gene variants for variability in memory performance and neuropsychiatric disorders, have both separately been related to poorer episodic memory and altered hippocampal functioning. Here, we investigated the combined effect of APOE and BDNF on hippocampal activation (N = 151). No non-additive interaction effects were seen. Instead, the results revealed decreased activation in bilateral hippocampus and parahippocampus as a function of the number of APOE e4 and.BDNE Met alleles present (neither, one, or both). The combined effect was stronger than either of the individual effects, and both gene variables explained significant proportions of variance in BOLD signal change. Thus, there was an additive gene-gene effect of APOE and BDNF on medial temporal lobe (MTL) activation, showing that a larger proportion of variance in brain activation attributed to genetics can be explained by considering more than one gene variant This effect might be relevant for the understanding of normal variability in memory function as well as memory-related disorders associated with APOE and BDNF.

  • 333.
    Kelfve, S
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Sociology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Thorslund, Mats
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lennartsson, C
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Surveys of the Oldest Old - Who Do They Represent?2011In: 2011 GSA Annual Scientific Meeting Abstracts, 2011Conference paper (Refereed)
  • 334.
    Kelfve, Susanne
    Stockholm University, Faculty of Social Sciences, Department of Sociology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Underestimated health inequalities among older people - A result of non-representative survey samplesManuscript (preprint) (Other academic)
  • 335.
    Kelfve, Susanne
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Sociology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Agahi, Neda
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Mattsson, Alexander Darin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lennartsson, Carin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Increased alcohol use over the past 20 years among the oldest old in Sweden2014In: Nordic Studies on Alcohol and Drugs, ISSN 1455-0725, E-ISSN 1458-6126, Vol. 31, no 3, p. 245-260Article in journal (Refereed)
    Abstract [en]

    AIMS - Increased alcohol consumption among old people, reported in many countries, will likely present a major challenge to public health and policy in the future. In Sweden, current knowledge about old people's alcohol consumption is incomplete because of limited historical data and a dearth of nationally representative studies. We describe the frequency of alcohol consumption among the oldest old in Sweden over a 20-year period by sex, age, education, living situation, mobility and Activities of Daily Living. METHODS - We used repeated cross-sectional survey data from the Swedish Panel Study of Living Conditions of the Oldest Old (SWEOLD), conducted in 1992, 2002 and 2011. The samples were nationally representative of the Swedish population aged 77+, with response rates of 95.4%, 84.4% and 86.2% (total n = 2007). Self-reported consumption frequency was measured with the question How often do you drink alcoholic beverages, such as wine, beer or spirits? RESULTS - Frequency of alcohol consumption increased among the oldest old from 1992 to 2011. The proportion reporting no or less-than-monthly alcohol consumption decreased, whereas the proportion reporting weekly consumption increased. This was true for men, women and most age and educational groups. The period change in consumption frequency was not explained by changes in demographic factors, living situation or functional capacity during the study period. CONCLUSIONS - Alcohol use increased among the oldest old in Sweden during the 20-year study period. More liberal attitudes toward alcohol could contribute to the increased use. The increase in weekly alcohol consumers suggests an increase in the number of older risk consumers.

  • 336.
    Kelfve, Susanne
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Ahacic, Kozma
    Alcohol Consumption­ among the Oldest Old in Sweden – Trends Over Time and Methodological Challenges2012Conference paper (Refereed)
    Abstract [en]

    The overall aim of this study is to describe trends in the frequency of alcohol consumption among the oldest old population in Sweden over the last 20 years. In addition, the methodological challenges involved will be analyzed and discussed. Data from a nationally representative survey of the oldest old population in Sweden (SWEOLD) from 1992, 2002 and 2010/2011 will be used. SWEOLD provides a unique longitudinal database that represents a very high proportion of the population aged 77+ in Sweden. By including institutionalized persons, using proxy interviews and achieving a high response rate, individuals are represented regardless of their health, possible cognitive impairments or place of residence. The prevalence patterns show significant increases in alcohol consumption in all age groups, both in men and women, even when controlling for health status. More individuals are consumers and those who consume drink more often. Less frequent alcohol consumption was associated with high age, women, institutionalized individuals, proxy interviewed persons and those requiring extra effort to recruit. By excluding persons living in institutions or requiring a proxy interview – groups sometimes not represented in surveys – or accepting a lower response rate, the total prevalence of alcohol consumers is likely to be overestimated. A higher percentage of upcoming elderly cohorts in Sweden consume alcohol than previous cohorts. This has been associated with increasing health and financial problems. This emphasizes the importance of including elderly people in research on alcohol consumption and of finding solutions to the methodological challenges posed in surveying the oldest old.

  • 337.
    Kelfve, Susanne
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Sociology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Ahacic, Kozma
    Bias in estimates of alcohol use among older people: selection effects due to design, health, and cohort replacement2015In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 15, article id 769Article in journal (Refereed)
    Abstract [en]

    Background: There is a growing awareness of the need to include the oldest age groups in the epidemiological monitoring of alcohol consumption. This poses a number of challenges and this study sets out to examine the possible selection effects due to survey design, health status, and cohort replacement on estimates of alcohol use among the oldest old. Methods: Analyses were based on three repeated cross-sectional interview surveys from 1992, 2002 and 2011, with relatively high response rates (86 %). The samples were nationally representative of the Swedish population aged 77+ (total n = 2022). Current alcohol use was assessed by the question How often do you drink alcoholic beverages, such as wine, beer or spirits? Alcohol use was examined in relation to survey design (response rate, use of proxy interviews and telephone interviews), health (institutional living, limitations with Activities of Daily Living and mobility problems) and birth cohort (in relation to age and period). Two outcomes were studied using binary and ordered logistic regression; use of alcohol and frequency of use among alcohol users. Results: Higher estimates of alcohol use, as well as more frequent use, were associated with lower response rates, not using proxy interviews and exclusion of institutionalized respondents. When adjusted for health, none of these factors related to the survey design were significant. Moreover, the increase in alcohol use during the period was fully explained by cohort replacement. This cohort effect was also at least partially confounded by survey design and health effects. Results were similar for both outcomes. Conclusions: Survey non-participation in old age is likely to be associated with poor health and low alcohol consumption. Failure to include institutionalized respondents or those who are difficult to recruit is likely to lead to an overestimation of alcohol consumption, whereas basing prevalence on older data, at least in Sweden, is likely to underestimate the alcohol use of the oldest old. Trends in alcohol consumption in old age are highly sensitive for cohort effects. When analysing age-period-cohort effects, it is important to be aware of these health and design issues as they may lead to incorrect conclusions.

  • 338.
    Kelfve, Susanne
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Sociology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fors, Stefan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lennartsson, Carin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Getting better all the time? Selective attrion and compositional changes in longitudinal and life-course studiesManuscript (preprint) (Other academic)
  • 339.
    Kelfve, Susanne
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Linköping University, Sweden.
    Fors, Stefan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lennartsson, Carin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Getting better all the time? Selective attrition and compositional changes in longitudinal and life course studies2017In: Longitudinal and life course studies, ISSN 1124-9064, E-ISSN 1757-9597, Vol. 8, no 1, p. 104-119Article in journal (Refereed)
    Abstract [en]

    Longitudinal surveys are valuable tools for investigating health and social outcomes across the life course. In such studies, selective mortality leads to changes in the social composition of the sample, but little is known about how selective survey participation affects the sample composition, in addition to the selective mortality. In the present paper, we followed a Swedish cohort sample over six waves 1968-2011. For each wave we recalculated the distribution of baseline characteristics in the sample among i) the sample still alive and ii) the sample still alive and with complete follow-up. The results show that the majority of the compositional changes in the cohort were modest and driven mainly by mortality. However, for some characteristics, class in particular, the selection was considerable and in addition, was substantially compounded by survey non-participation. We suggest that sample selections should be taken into account when interpreting the results of longitudinal studies, in particular when researching social inequalities.

  • 340.
    Kelfve, Susanne
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Sociology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lennartsson, Carin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Agahi, Neda
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Modig, Karin
    Do postal health surveys capture morbidity and mortality in respondents aged 65 years and older? A register-based validation study2015In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 43, no 4, p. 348-355Article in journal (Refereed)
    Abstract [en]

    Aims: Non-response to population surveys is a common problem in epidemiological and public health research. Systematic non-response threatens the validity of results. Researchers rarely evaluate the magnitude of systematic non-response because of limited access to population data. This study explores how well morbidity and mortality in postal survey respondents aged 65 years and older represented that of the target population. Methods: The 2010 Stockholm Public Health Survey and the Swedish Population Register were linked to the Cause of Death Register and the National Patient Register in Sweden. Differences were analysed between the response group and the corresponding population in mortality, hospital admission, days spent in hospital and number of diagnoses. Finally, data were weighted for non-response to see if this improved generalizability. Results: Non-response increased with age, and this increase was more pronounced among women than men. Respondents were marginally less often admitted to hospital, hospitalized fewer days and had slightly fewer diagnoses than the population, in particular after age 80. Significantly fewer women died in the response group than in the population as a whole. In terms of mortality among men and in terms of hospitalizations for most age groups, the respondents represented the population fairly well. Non-response weighting adjustment did not improve generalizability. Conclusions: Postal questionnaires are likely to capture morbidity (hospitalization) among women and men aged 65-80 years old and mortality among men, while morbidity after age 80 and mortality in women are likely to be underestimated.

  • 341.
    Kelfve, Susanne
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Sociology. Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Thorslund, Mats
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lennartsson, Carin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Sampling and non-response bias on health-outcomes in surveys of the oldest old2013In: European Journal of Ageing, ISSN 1613-9372, E-ISSN 1613-9380, Vol. 10, no 3, p. 237-245Article in journal (Refereed)
    Abstract [en]

    Surveys of the oldest old population are associated with several design issues. Place of residence and possible physical or cognitive impairments make it difficult to maintain a representative study population. Based on a Swedish nationally representative survey among individuals 77+, the present study analyze the potential bias of not using proxy interviews and excluding the institutionalized part of the population in surveys of the oldest old. The results show that compared to directly interviewed people living at home, institutionalized and proxy interviewed individuals were older, less educated and more likely to be female. They had more problems with health, mobility and ADL, and a significantly increased mortality risk. If the study had excluded the institutionalized part of the population and/or failed to use proxy interviews, the result would have been severely biased and resulted in underestimated prevalence rates for ADL, physical mobility and psychologic problems. This could not be compensated for weighting the data by age and sex. The results from this study imply that accurate population estimates require a representative study population, in which all individuals are included regardless of their living conditions, health status, and cognitive ability.

  • 342.
    Kelfve, Susanne
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Linköping University, Sweden.
    Wastesson, Jonas
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fors, Stefan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Morin, Lucas
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Is the level of education associated with transitions between care settings in older adults near the end of life? A nationwide, retrospective cohort study2018In: Palliative Medicine: A Multiprofessional Journal, ISSN 0269-2163, E-ISSN 1477-030X, Vol. 32, no 2, p. 366-375Article in journal (Refereed)
    Abstract [en]

    Background: End-of-life transitions between care settings can be burdensome for older adults and their relatives. Aim: To analyze the association between the level of education of older adults and their likelihood to experience care transitions during the final months before death. Design: Nationwide, retrospective cohort study using register data. Setting/participants: Older adults (65 years) who died in Sweden in 2013 (n = 75,722). Place of death was the primary outcome. Institutionalization and multiple hospital admissions during the final months of life were defined as secondary outcomes. The decedents' level of education (primary, secondary, or tertiary education) was considered as the main exposure. Multivariable analyses were stratified by living arrangement and adjusted for sex, age at time of death, illness trajectory, and number of chronic diseases. Results: Among community-dwellers, older adults with tertiary education were more likely to die in hospitals than those with primary education (55.6% vs 49.9%; odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.14-1.28), but less likely to be institutionalized during the final month before death (OR = 0.83, 95% CI = 0.76-0.91). Decedents with higher education had greater odds of remaining hospitalized continuously during their final 2 weeks of life (OR = 1.12, 95% CI = 1.02-1.22). Among older adults living in nursing homes, we found no association between the decedents' level of education and their likelihood to be hospitalized or to die in hospitals. Conclusion: Compared with those who completed only primary education, individuals with higher educational attainment were more likely to live at home until the end of life, but also more likely to be hospitalized and die in hospitals.

  • 343.
    Keller Celeste, Roger
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Federal University of Rio Grande do Sul, Brazil.
    Fritzell, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Do socioeconomic inequalities in pain, psychological distress and oral health increase or decrease over the life course? Evidence from Sweden over 43 years of follow-up2018In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 72, no 2, p. 160-167Article in journal (Refereed)
    Abstract [en]

    Background Inequalities over the life course may increase due to accumulation of disadvantage or may decrease because ageing can work as a leveller. We report how absolute and relative socioeconomic inequalities in musculoskeletal pain, oral health and psychological distress evolve with ageing. Methods Data were combined from two nationally representative Swedish panel studies: the Swedish Level-of-Living Survey and the Swedish Panel Study of Living Conditions of the Oldest Old. Individuals were followed up to 43 years in six waves (1968, 1974, 1981, 1991/1992, 2000/2002, 2010/2011) from five cohorts: 1906-1915 (n=899), 1925-1934 (n=906), 1944-1953 (n=1154), 1957-1966 (n=923) and 1970-1981 (n=1199). The participants were 15-62 years at baseline. Three self-reported outcomes were measured as dichotomous variables: teeth not in good conditions, psychological distress and musculoskeletal pain. The fixed-income groups were: (A) never poor and (B) poor at least once in life. The relationship between ageing and the outcomes was smoothed with locally weighted ordinary least squares, and the relative and absolute gaps were calculated with Poisson regression using generalised estimating equations. Results All outcomes were associated with ageing, birth cohort, sex and being poor at least once in live. Absolute inequalities increased up to the age of 45-64 years, and then they decreased. Relative inequalities were large already in individuals aged 15-25years, showing a declining trend over the life course. Selective mortality did not change the results. The socioeconomic gap was larger for current poverty than for being poor at least once in life. Conclusion Inequalities persist into very old age, though they are more salient in midlife for all three outcomes observed.

  • 344.
    Keller, Lina
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Murphy, Charlotte
    Wang, Hui-Xin
    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).
    Olin, Maria
    Gafvels, Mats
    Björkhem, Ingemar
    Graff, Caroline
    Meaney, Steve
    A Functional Polymorphism In The Hmgcr Promoter Affects Transcriptional Activity But Not The Risk For Alzheimer Disease In Swedish Populations2010In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1344, p. 185-91Article in journal (Refereed)
    Abstract [en]

    Variations in genes associated with cholesterol homeostasis have been reported to modify the risk of developing Alzheimer disease (AD). To date there have been few investigations into variations in genes directly involved in cholesterol biosynthesis and AD. We investigated the influence of the -911C>A polymorphism (rs3761740) in the hydroxy-methyl-glutaryl CoA reductase (HMGCR) gene promoter on basal and regulated transcription, plasma cholesterol levels and the association with AD. Under in vitro conditions the A allele was found to be significantly more responsive to SREBP-2 mediated regulation than the C allele. In an age and sex matched case-control study, the genotype distribution and allele frequency of this polymorphism were not associated with AD (OR=1.03; 95% CI=0.72-1.48). However, we did find evidence supporting an interaction between the HMGCR A allele, the APOE E4 allele and an altered risk of AD (OR=2.41; 95% CI=0.93-6.22).

  • 345.
    Keller, Lina
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Welander, Hedvig
    Chiang, Huei-Hsin
    Tjernberg, Lars O
    Nennesmo, Inger
    Wallin, Asa K
    Graff, Caroline
    The PSEN1 I143T mutation in a Swedish family with Alzheimer's disease: clinical report and quantification of Aβ in different brain regions2010In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 18, no 11, p. 1202-1208Article in journal (Refereed)
    Abstract [en]

    Early-onset dominantly inherited forms of Alzheimer's disease (AD) are rare, but studies of such cases have revealed important information about the disease mechanisms. Importantly, mutations in amyloid precursor protein (APP), presenilin 1 (PSEN1) and PSEN2, alter the APP processing and lead to an increased amyloid β-peptide (Aβ) 42/40 ratio. This, together with other studies on pathogenic mechanisms, show that Aβ42 is a major player in the etiology of AD. Here, we present a clinical and neuropathological description of a Swedish family with an I143T mutation in the PSEN1 gene, which gives rise to a severe form of AD. We also performed an extensive investigation on the concentration and distribution of Aβ species of different lengths in six brain regions from two mutation carriers. Our study showed that Aβ42 and a longer peptide, Aβ43, were present both in plaque cores and in total amyloid preparations, and were each clearly more frequent than Aβ40 in all examined regions, as shown by both mass spectrometry and immunohistochemistry.

  • 346.
    Keller, Lina
    et al.
    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).
    Wang, Hui-Xin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Winblad, Bengt
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Graff, Caroline
    The Obesity Related Gene, FTO, Interacts with APOE and is Associated with Alzheimer's Disease Risk: A Prospective Cohort Study2011In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 23, no 3, p. 461-469Article in journal (Refereed)
    Abstract [en]

    The FTO gene has been shown to have a small but robust effect on body mass index (BMI) and to increase the risk for diabetes. Both high BMI and diabetes are vascular risk factors that might play a role in the development of Alzheimer's disease (AD) and dementia. Thus, our aim was to explore the impact of FTO on AD and dementia risk. Nine years of follow-up data was gathered from the Kungsholmen project, a prospective population-based study on 1,003 persons without dementia. Cox-regression models were used to assess the relative risks of developing AD and dementia (DSM-III-R criteria) according to FTO genotypes (rs9939609), taking into account APOE, physical inactivity, BMI, diabetes, and cardiovascular disease (CVD). Compared to carriers of the FTO TT-genotype, AA-carriers had a higher risk for AD (RR 1.58, 95% CI: 1.11-2.24) and for dementia (RR 1.48, 95% CI: 1.09-2.02) after adjustment for age, gender, education, and APOE genotype. This effect remained after additional adjustment for physical inactivity, BMI, diabetes, and CVD. An interaction between FTO and APOE was found, with increased risk for dementia for those carrying both FTO AA and APOE epsilon 4. Importantly, the effect of the AA-genotype on dementia/AD risk seems to act mostly through the interaction with APOE epsilon 4. Our findings suggest that the FTO AA-genotype increases the risk for dementia, and in particular AD, independently of physical inactivity, BMI, diabetes, and CVD measured at baseline. Our results are in line with the recently reported association between FTO and reduced brain volume in cognitively healthy subjects.

  • 347. Kempf, Emmanuelle
    et al.
    Tournigand, Christophe
    Rochigneux, Philippe
    Aubry, Régis
    Morin, Lucas
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Discrepancies in the use of chemotherapy and artificial nutrition near the end of life for hospitalised patients with metastatic gastric or oesophageal cancer. A countrywide, register-based study2017In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 79, p. 31-40Article in journal (Refereed)
    Abstract [en]

    Aim: To evaluate the frequency and the factors associated with the use of chemotherapy and artificial nutrition near the end of life in hospitalised patients with metastatic oesophageal or gastric cancer.

    Methods: Nationwide, register-based study, including all hospitalised adults (>= 20 years) who died with metastatic oesophageal or gastric cancer between 2010 and 2013, in France. Chemotherapy and artificial nutrition during the final weeks of life were considered as primary outcomes.

    Results: A total of 4031 patients with oesophageal cancer and 10,423 patients with gastric cancer were included. While the proportion of patients receiving chemotherapy decreased from 35.9% during the 3rd month before death to 7.9% in the final week (p < 0.001 for trend), the use of artificial nutrition rose from 9.6% to 16.0% of patients. During the last week before death, patients with stomach cancer were more likely to receive chemotherapy (adjusted odds ratio (aOR) = 1.35, 95% CI = 1.17-1.56) but less likely to receive artificial nutrition (aOR = 0.80, 95% CI = 0.73-0.88) than patients with cancer of the oesophagus. The adjusted rates of chemotherapy use during the last week of life varied from 1.6% in rural hospitals to 11.2% in comprehensive cancer centres, while the adjusted probability to receive artificial nutrition varied from 12.1% in private for-profit clinics up to 19.9% in rehabilitation care facilities (p < 0.001).

    Conclusions: Our study shows that in hospitalised patients with metastatic oesophageal or gastric cancer, the use of chemotherapy decreases while the use of artificial nutrition increases as death approaches. This raises important questions, as clinical guidelines clearly recommend to limit the use of artificial nutrition in contexts of limited life expectancy.

  • 348. Kemppainen, Nina
    et al.
    Johansson, Jarkko
    Teuho, Jarmo
    Parkkola, Riitta
    Joutsa, Juho
    Ngandu, Tiia
    Solomon, Alina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska Institutet, Sweden; University of Eastern Finland, Finland.
    Stephen, Ruth
    Liu, Yawu
    Hanninen, Tuomo
    Paajanen, Teemu
    Laatikainen, Tiina
    Soininen, Hilkka
    Jula, Antti
    Rokka, Johanna
    Rissanen, Eero
    Vahlberg, Tero
    Peltoniemi, Julia
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). National Institute for Health and Welfare, Finland; Karolinska Institutet, Sweden; University of Eastern Finland, Finland .
    Rinne, Juha O.
    Brain amyloid load and its associations with cognition and vascular risk factors in FINGER Study2018In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 90, no 3, p. E206-E213Article in journal (Refereed)
    Abstract [en]

    Objective To investigate brain amyloid pathology in a dementia-risk population defined as cardiovascular risk factors, aging, and dementia risk (CAIDE) score of at least 6 but with normal cognition and to examine associations between brain amyloid load and cognitive performance and vascular risk factors.

    Methods A subgroup of 48 individuals from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) main study participated in brain C-11-Pittsburgh compound B (PiB)-PET imaging, brain MRI, and neuropsychological assessment at the beginning of the study. Lifestyle/vascular risk factors were determined as body mass index, blood pressure, total and low-density lipoprotein cholesterol, and glucose homeostasis model assessment. White matter lesions were visually rated from MRIs by a semiquantitative Fazekas score.

    Results Twenty participants (42%) had a positive PiB-PET on visual analysis. The PiB-positive group performed worse in executive functioning tests, included more participants with APOE epsilon 4 allele (50%), and showed slightly better glucose homeostasis compared to PiB-negative participants. PiB-positive and -negative participants did not differ significantly in other cognitive domain scores or other vascular risk factors. There was no significant difference in Fazekas score between the PiB groups.

    Conclusions The high percentage of PiB-positive participants provides evidence of a successful recruitment process of the at-risk population in the main FINGER intervention trial. The results suggest a possible association between early brain amyloid accumulation and decline in executive functions. APOE epsilon 4 was clearly associated with amyloid positivity, but no other risk factor was found to be associated with positive PiB-PET.

  • 349. Kenigsberg, Paul-Ariel
    et al.
    Aquino, Jean-Pierre
    Berard, Alain
    Gzil, Fabrice
    Andrieu, Sandrine
    Banerjee, Sube
    Bremond, Francois
    Buee, Luc
    Cohen-Mansfield, Jiska
    Mangialasche, Francesca
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Platel, Herve
    Salmon, Eric
    Robert, Philippe
    Dementia beyond 2025: Knowledge and uncertainties2016In: Dementia, ISSN 1471-3012, E-ISSN 1741-2684, Vol. 15, no 1, p. 6-21Article in journal (Refereed)
    Abstract [en]

    Given that there may well be no significant advances in drug development before 2025, prevention of dementia-Alzheimer's disease through the management of vascular and lifestyle-related risk factors may be a more realistic goal than treatment. Level of education and cognitive reserve assessment in neuropsychological testing deserve attention, as well as cultural, social, and economic aspects of caregiving. Assistive technologies for dementia care remain complex. Serious games are emerging as virtual educational and pleasurable tools, designed for individual and cooperative skill building. Public policies are likely to pursue improving awareness and understanding of dementia; providing good quality early diagnosis and intervention for all; improving quality of care from diagnosis to the end of life, using clinical and economic end points; delivering dementia strategies quicker, with an impact on more people. Dementia should remain presented as a stand-alone concept, distinct from frailty or loss of autonomy. The basic science of sensory impairment and social engagement in people with dementia needs to be developed. E-learning and serious games programs may enhance public and professional education. Faced with funding shortage, new professional dynamics and economic models may emerge through coordinated, flexible research networks. Psychosocial research could be viewed as an investment in quality of care, rather than an academic achievement in a few centers of excellence. This would help provide a competitive advantage to the best operators. Stemming from care needs, a logical, systems approach to dementia care environment through organizational, architectural, and psychosocial interventions may be developed, to help reduce symptoms in people with dementia and enhance quality of life. Dementia-friendly environments, culture, and domesticity are key factors for such interventions.

  • 350. Kerpershoek, Liselot
    et al.
    Wolfs, Claire
    Verhey, Frans
    Jelley, Hannah
    Woods, Bob
    Bieber, Anja
    Bartoszek, Gabriele
    Stephan, Astrid
    Selbaek, Geir
    Eriksen, Siren
    Sjölund, Britt-Marie
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Gävle, Sweden.
    Hopper, Louise
    Irving, Kate
    Marques, Maria J.
    Goncalves-Pereira, Manuel
    Portolani, Daniel
    Zanetti, Orazio
    Vugt, Marjolein
    Optimizing access to and use of formal dementia care: Qualitative findings from the European Actifcare study2019In: Health & Social Care in the Community, ISSN 0966-0410, E-ISSN 1365-2524Article in journal (Refereed)
    Abstract [en]

    This paper reports on qualitative data from the Actifcare study investigating experiences, attitudes, barriers and facilitators concerning access to and use of formal care. A total of 85 semi-structured in-depth interviews were conducted in eight European countries. Results were analysed with a deductive content analysis, first within country and then integrated in a cross-national analysis. Overall, analysis of the in-depth interviews revealed two major themes with five subcategories. The results can be summarised in an optimal pathway for access to dementia care. This pathway includes fixed factors such as disease-related factors and system-related factors. In addition there are personal factors that are subject to change such as attitudes towards care. An important finding consisted of the necessity of having sufficient information about the disease and available care and having a key contact person to guide you through the process of finding suitable care while monitoring your needs. In addition, it is important to involve your social network as they can take on care-giving tasks. It is helpful to have a diagnosis (in most countries). Concerning decision-making, the person closest to the person with dementia is in the majority of cases the one who makes the ultimate decision to access and use services and he/she should therefore be supported in this process. These results provide insight into the factors that influence the pathway to formal care use and help professionals to enhance access to formal dementia care by focusing on factors that can be modified.

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