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  • 1. Exalto, Lieza G
    et al.
    Quesenberry, Charles P
    Barnes, Deborah
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Biessels, Geert Jan
    Whitmer, Rachel A
    Midlife risk score for the prediction of dementia four decades later2013In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 10, no 5, p. 562-570Article in journal (Refereed)
    Abstract [en]

    Objective

    The objective of this study was to obtain external validation of the only available midlife dementia risk score cardiovascular risk factors , aging and dementia study (CAIDE) constituting age, education, hypertension, obesity, and hyperlipidemia in a larger, more diverse population. Our second aim was to improve the CAIDE risk score by additional midlife risk factors.

    Methods

    This retrospective cohort study was conducted in an integrated health care delivery system. A total of 9480 Kaiser Permanente members who participated in a health survey study (age range, 40–55 years) from 1964 to 1973 were included in this study. Dementia diagnoses from primary care and medical specialist visits were collected from January 1, 1994 to January 16, 2006, using International Classification of Diseases 9 codes 290.0, 290.1 for “possible dementia,” and 331.0 and 290.4 for “specialist confirmed dementia.” Risk model prediction and validation were examined with the C statistic, net reclassification improvement, and integrated discrimination improvement. Dementia risk per sum score was calculated with Kaplan-Meier estimates.

    Results

    A total of 2767 participants (25%) were diagnosed with any type of dementia, of which 1011 diagnoses (10.7%) were specialist-confirmed diagnoses. Average time between midlife examination and end of follow-up was 36.1 years. The CAIDE risk score replicated well with a C statistic of 0.75, quite similar to the original CAIDE C statistic of 0.78. The CAIDE score also predicted well within different race strata. Other midlife risk factors (central obesity, depressed mood, diabetes mellitus, head trauma, lung function, and smoking) did not improve predictability. The risk score allowed stratification of participants into those with 40-year low (9%) and high (29%) dementia risk.

    Conclusions

    A combination of modifiable vascular risk factors in midlife is highly predictive of the likelihood of dementia decades later. Possible dementia prevention strategies should point to a life course perspective on maintaining vascular health.

  • 2.
    Grande, Giulia
    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). Stockholm Gerontology Research Centre, Sweden.
    Vetrano, Davide L.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Catholic University, Italy; Fondazione Policlinico “A. Gemelli” IRCCS, Italy.
    Marseglia, Anna
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Vanacore, Nicola
    Laukka, Erika J.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Welmer, Anna-Karin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Centre, Sweden.
    Cognitive and physical markers of prodromal dementia: A 12-year-long population study2020In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 16, no 1, p. 153-161Article in journal (Refereed)
    Abstract [en]

    Introduction: The aim is to test whether adding a simple physical test such as walking speed (WS) to the neuropsychological assessment increases the predictive ability to detect dementia.

    Methods: The 2546 dementia-free people from the SNAC-K study were grouped into four profiles: (1) healthy profile; (2) isolated cognitive impairment, no dementia (CIND, scoring 1.5 standard deviation below age-specific means on >= 1 cognitive domains); (3) isolated slow WS (<0.8 m/s); (4) CIND+ slow WS. The hazard of dementia (Cox regression), the positive and negative predictive values (PPV, NPV), and the area under the curve (AUC) were estimated.

    Results: Participants with CIND +slow WS demonstrated the highest hazard of dementia (3.4; 95% confidence interval [CI]: 2.5-4.8). The AUC increased from 0.69 for isolated CIND to 0.83 for CIND+ slow WS. Such an increase was due to the improvement of the PPV, the NPV remaining optimal.

    Discussion: Adding WS to the cognitive assessment dramatically increases the diagnostic accuracy of prodromal dementia.

  • 3. 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.

  • 4. Kivimäki, Mika
    et al.
    Luukkonen, Ritva
    Batty, G. David
    Ferrie, Jane E.
    Pentti, Jaana
    Nyberg, Solja T.
    Shipley, Martin J.
    Alfredsson, Lars
    Fransson, Eleonor
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden; Jönköping University, Sweden.
    Goldberg, Marcel
    Knutsson, Anders
    Koskenvuo, Markku
    Kuosma, Eeva
    Nordin, Maria
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Umeå University, Sweden.
    Suominen, Sakari B.
    Theorell, Töres
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Vuoksimaa, Eero
    Westerholm, Peter
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Zins, Marie
    Kivipelto, Miia
    Vahtera, Jussi
    Kaprio, Jaakko
    Singh-Manoux, Archana
    Jokela, Markus
    Body mass index and risk of dementia: Analysis of individual-level data from 1.3 million individuals2018In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 14, no 5, p. 601-609Article in journal (Refereed)
    Abstract [en]

    Introduction: Higher midlife body mass index (BMI) is suggested to increase the risk of dementia, but weight loss during the preclinical dementia phase may mask such effects.

    Methods: We examined this hypothesis in 1,349,857 dementia-free participants from 39 cohort studies. BMI was assessed at baseline. Dementia was ascertained at follow-up using linkage to electronic health records (N = 6894). We assumed BMI is little affected by preclinical dementia when assessed decades before dementia onset and much affected when assessed nearer diagnosis.

    Results: Hazard ratios per 5-kg/m2 increase in BMI for dementia were 0.71 (95% confidence interval = 0.66-0.77), 0.94 (0.89-0.99), and 1.16 (1.05-1.27) when BMI was assessed 10 years, 10-20 years, and >20 years before dementia diagnosis.

    Conclusions: The association between BMI and dementia is likely to be attributable to two different processes: a harmful effect of higher BMI, which is observable in long follow-up, and a reverse-causation effect that makes a higher BMI to appear protective when the follow-up is short.

  • 5.
    Kivipelto, Miia
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Eastern Finland, Finland; National Institute for Health and Welfare, Finland; Karolinska Institutet, Sweden.
    Solomon, Alina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Eastern Finland, Finland; Karolinska Institutet, Sweden.
    Ahtiluoto, Satu
    Ngandu, Tiia
    Lehtisalo, Jenni
    Antikainen, Riitta
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Hanninen, Tuomo
    Jula, Antti
    Laatikainen, Tiina
    Lindström, Jaana
    Mangialasche, Francesca
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Nissinen, Aulikki
    Paajanen, Teemu
    Pajala, Satu
    Peltonen, Markku
    Rauramaa, Rainer
    Stigsdotter-Neely, Anna
    Strandberg, Timo
    Tuomilehto, Jaakko
    Soininen, Hilkka
    The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER): Study design and progress2013In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 9, no 6, p. 657-665Article in journal (Refereed)
    Abstract [en]

    Background: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a multi-center, randomized, controlled trial ongoing in Finland. Materials: Participants (1200 individuals at risk of cognitive decline) are recruited from previous population-based non-intervention studies. Inclusion criteria are CAIDE Dementia Risk Score >= 6 and cognitive performance at the mean level or slightly lower than expected for age (but not substantial impairment) assessed with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery. The 2-year multidomain intervention consists of: nutritional guidance; exercise; cognitive training and social activity; and management of metabolic and vascular risk factors. Persons in the control group receive regular health advice. The primary outcome is cognitive performance as measured by the modified Neuropsychological Test Battery, Stroop test, and Trail Making Test. Main secondary outcomes are: dementia (after extended follow-up); disability; depressive symptoms; vascular risk factors and outcomes; quality of life; utilization of health resources; and neuroimaging measures. Results: Screening began in September 2009 and was completed in December 2011. All 1200 persons are enrolled and the intervention is ongoing as planned. Baseline clinical characteristics indicate that several vascular risk factors and unhealthy lifestyle related factors are present, creating a window of opportunity for prevention. The intervention will be completed during 2014. Conclusions: The FINGER is at the forefront of international collaborative efforts to solve the clinical and public health problems of early identification of individuals at increased risk of late-life cognitive impairment, and of developing intervention strategies to prevent or delay the onset of cognitive impairment and dementia.

  • 6. Lehtisalo, Jenni
    et al.
    Levälahti, Esko
    Lindström, Jaana
    Hänninen, Tuomo
    Paajanen, Teemu
    Peltonen, Markku
    Antikainen, Riitta
    Laatikainen, Tiina
    Strandberg, Timo
    Soininen, Hilkka
    Tuomilehto, Jaakko
    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; Imperial College London, United Kingdom.
    Ngandu, Tiia
    Dietary changes and cognition over 2 years within a multidomain intervention trial-The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER)2019In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 15, no 3, p. 410-417Article in journal (Refereed)
    Abstract [en]

    Introduction: Association between healthy diet and better cognition is well established, but evidence is limited to evaluate the effect of dietary changes adopted in older age.

    Methods: We investigated the role of dietary changes in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) with 1260 at-risk participants (60-77 years) who were randomized to intensive multidomain intervention (including dietary counseling) or regular health advice for 2 years. Parallel process latent growth curves of adherence to dietary recommendations and cognitive performance were analyzed.

    Results: Adherence to healthy diet at baseline predicted improvement in global cognition, regardless of intervention allocation (P = .003). Dietary improvement was associated with beneficial changes in executive function, especially in the intervention group (P = .008; P = .051 for groups combined).

    Discussion: Dietary changes initiated during the intervention were related to changes in executive function in 2 years. Long-term diet appeared more influential for global cognition.

  • 7. Leuzy, Antoine
    et al.
    Rodriguez-Vieitez, Elena
    Saint-Aubert, Laure
    Chiotis, Konstantinos
    Almkvist, Ove
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Biological psychology. Karolinska Institutet, Sweden; Karolinska University Hospital, Sweden.
    Savitcheva, Irina
    Jonasson, My
    Lubberink, Mark
    Wall, Anders
    Antoni, Gunnar
    Nordberg, Agneta
    Longitudinal uncoupling of cerebral perfusion, glucose metabolism, and tau deposition in Alzheimer's disease2018In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 14, no 5, p. 652-663Article in journal (Refereed)
    Abstract [en]

    Introduction: Cross-sectional findings using the tau tracer [F-18] THK5317 (THK5317) have shown that [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET) data can be approximated using perfusion measures (early-frame standardized uptake value ratio; ratio of tracer delivery in target to reference regions). In this way, a single PET study can provide both functional and molecular information. Methods: We included 16 patients with Alzheimer's disease who completed follow-up THK5317 and FDG studies 17 months after baseline investigations. Linear mixed-effects models and annual percentage change maps were used to examine longitudinal change. Results: Limited spatial overlap was observed between areas showing declines in THK5317 perfusion measures and FDG. Minimal overlap was seen between areas showing functional change and those showing increased retention of THK5317. Discussion: Our findings suggest a spatiotemporal offset between functional changes and tau pathology and a partial uncoupling between perfusion and metabolism, possibly as a function of Alzheimer's disease severity.

  • 8. Lövheim, Hugo
    et al.
    Gilthorpe, Jonathan
    Adolfsson, Rolf
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Umeå University, Sweden.
    Elgh, Fredrik
    Reactivated herpes simplex infection increases the risk of Alzheimer's disease2015In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, no 6, p. 593-599Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies have suggested a link between herpes simplex virus (HSV) type 1 and the development of Alzheimer's disease (AD). Methods: The present analysis included 3432 persons (53.9% women, mean age at inclusion 62.7 +/- 14.4 years) with a mean follow-up time of 11.3 years. The number of incident AD cases was 245. Serum samples were analyzed for anti-HSV antibodies (immunoglobulin (Ig)G and IgM) by enzyme-linked immunosorbent assays. Results: The presence of anti-HSV IgG antibodies was not associated with an increased risk for AD, controlled for age and sex (hazard ratio, HR, 0.993, P = .979). However, the presence of anti-HSV IgM at baseline was associated with an increased risk of developing AD (HR 1.959, P = .012). Conclusion: Positivity for anti-HSV IgM, a sign of reactivated infection, was found to almost double the risk for AD, whereas the presence of anti-HSV IgG antibodies did not affect the risk.

  • 9.
    Marseglia, Anna
    et al.
    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.
    Kalpouzos, Grégoria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wang, Rui
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Bäckman, Lars
    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). Tianjin Medical University, China.
    Prediabetes and diabetes accelerate cognitive decline and predict microvascular lesions: A population-based cohort study2019In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 15, no 1, p. 25-33Article in journal (Refereed)
    Abstract [en]

    Introduction: The impact of prediabetes and diabetes on cognitive decline and the potential underlying mechanisms remain unclear. We investigated whether prediabetes and diabetes accelerate cognitive decline and brain aging, and the initial pathological changes linked to microvascular processes.

    Methods: Nine-year longitudinal data from the Swedish National Study on Aging and Care-Kungsholmen (n = 2746, age >= 60 years) and the magnetic resonance imaging subsample (n = 455) were used. Cognitive function was assessed with Mini-Mental State Examination. Brain magnetic resonance imaging markers included total brain tissue, white matter, gray matter, white matter hyperintensities, and hippocampal volumes.

    Results: Compared with diabetes-free status, prediabetes and diabetes were independently associated with accelerated cognitive decline. Prediabetes was cross-sectionally associated with smaller total brain tissue volume (P < .01), particularly smaller white matter volume. Diabetes was associated with larger white matter hyperintensities volume. Longitudinally, diabetes was associated with faster white matter hyperintensities accumulation. No associations between prediabetes or diabetes and hippocampal volume were found.

    Discussion: Diabetes and prediabetes accelerate cognitive decline and might predict microvascular lesions among dementia-free older adults.

  • 10. Rosenberg, Anna
    et al.
    Ngandu, Tiia
    Rusanen, Minna
    Antikainen, Riitta
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Havulinna, Satu
    Hänninen, Tuomo
    Laatikainen, Tiina
    Lehtisalo, Jenni
    Levälahti, Esko
    Lindström, Jaana
    Paajanen, Teemu
    Peltonen, Markku
    Soininen, Hilkka
    Stigsdotter-Neely, Anna
    Strandberg, Timo
    Tuomilehto, Jaakko
    Solomon, Alina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Eastern Finland, Finland; Karolinska Institutet, Sweden.
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Eastern Finland, Finland; National Institute for Health and Welfare, Finland; Karolinska Institutet, Sweden; Stockholms Sjukhem, Sweden .
    Multidomain lifestyle intervention benefits a large elderly population at risk for cognitive decline and dementia regardless of baseline characteristics: The FINGER trial2018In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 14, no 3, p. 263-270Article in journal (Refereed)
    Abstract [en]

    Introduction: The 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) multidomain lifestyle intervention trial (NCT01041989) demonstrated beneficial effects on cognition. We investigated whether sociodemographics, socioeconomic status, baseline cognition, or cardiovascular factors influenced intervention effects on cognition.

    Methods: The FINGER recruited 1260 people from the general Finnish population (60-77 years, at risk for dementia). Participants were randomized 1: 1 to multidomain intervention (diet, exercise, cognition, and vascular risk management) and regular health advice. Primary outcome was change in cognition (Neuropsychological Test Battery z-score). Prespecified analyses to investigate whether participants' characteristics modified response to intervention were carried out using mixed-model repeated-measures analyses.

    Results: Sociodemographics (sex, age, and education), socioeconomic status (income), cognition (Mini-Mental State Examination), cardiovascular factors (body mass index, blood pressure, cholesterol, fasting glucose, and overall cardiovascular risk), and cardiovascular comorbidity did not modify response to intervention (P-values for interaction > .05).

    Conclusions: The FINGER intervention was beneficial regardless of participants' characteristics and can thus be implemented in a large elderly population at increased risk for dementia.

  • 11. Rönnlund, Michael
    et al.
    Sundström, Anna
    Adolfsson, Rolf
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Umeå University, Sweden.
    Subjective memory impairment in older adults predicts future dementia independent of baseline memory performance: Evidence from the Betula prospective cohort study2015In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, no 11, p. 1385-1392Article in journal (Refereed)
    Abstract [en]

    Introduction: The objective was to examine whether subjective memory impairment (SMI) predicts all-cause dementia or Alzheimer's disease (AD) in a population-based study with long-term followup (median = 10 years).

    Methods: A total of 2043 initially dementia-free participants (>= 60 years) made three memory ratings (compared with others, compared with five years ago, and complaints from family/friends) at baseline. During follow-up, 372 participants developed dementia (208 with AD).

    Results: Cox regression revealed that subjective memory impairment ratings predicted all-cause dementia in models adjusting for age and sex (hazard ratio or HR from 2.04 to 3.94), with even higher values for AD (HR from 2.29 to 5.74). The result persisted in models including other covariates, including baseline episodic memory performance, and in analyses restricted to participants with long time to dementia diagnosis (>= 5 years).

    Discussion: The findings underscore the usefulness of subjective memory assessment in combination with other factors in identifying individuals at risk for developing dementia.

  • 12.
    Shakersain, Behnaz
    et al.
    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).
    Larsson, Susanna C.
    Faxen-Irving, Gerd
    Fastbom, Johan
    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.
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Tianjin Medical University, China.
    Prudent diet may attenuate the adverse effects of Western diet on cognitive decline2016In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 12, no 2, p. 100-109Article in journal (Refereed)
    Abstract [en]

    Introduction: The influence of mixed dietary patterns on cognitive changes is unknown. Methods: A total of 2223 dementia-free participants aged >= 60 were followed up for 6 years to examine the impact of dietary patterns on cognitive decline. Mini-mental state examination (MMSE) was administered. Diet was assessed by a food frequency questionnaire. By factor analysis, Western and prudent dietary patterns emerged. Mixed-effect models for longitudinal data with repeated measurements were used. Results: Compared with the lowest adherence to each pattern, the highest adherence to prudent pattern was related to less MMSE decline (beta = 0.106, P = .011), whereas the highest adherence to Western pattern was associated with more MMSE decline (beta = -0.156, P < .001). The decline associated withWestern diet was attenuated when accompanied by high adherence to prudent pattern. Discussion: High adherence to prudent diet may diminish the adverse effects of high adherence to Western diet on cognitive decline.

  • 13.
    Sindi, Shireen
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska Institutet, Sweden; Imperial College London, United Kingdom.
    Kåreholt, Ingemar
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Jönköping University, Sweden.
    Johansson, Lena
    Skoog, Johan
    Sjöberg, Linnea
    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). Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Johansson, Boo
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Soininen, Hilkka
    Solomon, Alina
    Skoog, Ingmar
    Kivipelto, Miia
    Sleep disturbances and dementia risk: A multicenter study2018In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 14, no 10, p. 1235-1242Article in journal (Refereed)
    Abstract [en]

    Introduction

    Few longitudinal studies assessed whether sleep disturbances are associated with dementia risk.

    Methods

    Sleep disturbances were assessed in three population-based studies (H70 study and Kungsholmen Project [Sweden]; Cardiovascular Risk Factors, Aging and Dementia study [Finland]). Late-life baseline analyses (3–10 years follow-up) used all three studies (N = 1446). Baseline ages ≈ 70 years (Cardiovascular Risk Factors, Aging and Dementia, H70), and ≈84 years (Kungsholmen Project). Midlife baseline (age ≈ 50 years) analyses used Cardiovascular Risk Factors, Aging and Dementia (21 and 32 years follow-up) (N = 1407).

    Results

    Midlife insomnia (fully adjusted hazard ratio = 1.24, 95% confidence interval = 1.02–1.50) and late-life terminal insomnia (fully adjusted odds ratio = 1.94, 95% confidence interval = 1.08–3.49) were associated with a higher dementia risk. Late-life long sleep duration (>9 hours) was also associated with an increased dementia risk (adjusted odds ratio = 3.98, 95% confidence interval = 1.87–8.48).

    Discussion

    Midlife insomnia and late-life terminal insomnia or long sleep duration were associated with a higher late-life dementia risk.

  • 14.
    Solomon, Alina
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Eastern Finland.
    Ngandu, Tiia
    Soininen, Hilkka
    Hallikainen, M. Merja
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Eastern Finland.
    Laatikainen, Tiina
    Validity dementia and Alzheimer's disease diagnoses in Finnish national registers2014In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 10, no 3, p. 303-309Article in journal (Refereed)
    Abstract [en]

    Background: We investigated dementia and Alzheimer disease (AD) diagnoses in three national registers in Finland: the Hospital Discharge Register (HDR), the Drug Reimbursement Register, and the Causes of Death Register (CDR). Methods: The Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study was used as the gold standard. Participants were first evaluated in 1972 to 1987, and were reexamined in 1998 and in 2005 to 2008. Results: Two approaches were used for the HDR: with a time restriction (considering positive only those cases recorded in the HDR before CAIDE study evaluations) and without a time restriction. Sensitivity of the HDR was 13.7% with time restriction and 51% without time restriction (dementia), and 15.6% with time restriction 55.6% without time restriction (AD). The positive predictive value (PPV) was 87.5% with time restriction and 96.3% without time restriction (dementia), and 100% for AD. Sensitivity and PPV of the HDR were greater after 1998. For AD in the Drug Reimbursement Register alone, sensitivity was 63.5% and PPV was 97.1%; together with the HDR, sensitivity became 65.4% with time restriction and 71.1% without time restriction, and PPV was 100%. For dementia in the CDR, sensitivity was 62.2% and PPV was 100%. Conclusions: Diagnoses in registers have very good accuracy, but underestimation of dementia/AD occurrence may cause an underestimation of associations with risk/protective factors.

  • 15.
    Tan, Edwin C. K.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Monash University, Australia.
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Garcia-Ptacek, Sara
    Haaksma, Miriam L.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Radboud University Medical Center, the Netherlands.
    Fastbom, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Bell, J. Simon
    Eriksdotter, Maria
    Acetylcholinesterase inhibitors and risk of stroke and death in people with dementia2018In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 14, no 7, p. 944-951Article in journal (Refereed)
    Abstract [en]

    Introduction: The aim of this study was to investigate the association between acetylcholinesterase inhibitor (AChEI) use and risk of ischemic stroke and death in people with dementia.

    Methods: A cohort study of 44,288 people with dementia registered in the Swedish Dementia Registry from 2007 to 2014. Propensity score-matched competing risk regression models were used to compute hazard ratios and 95% confidence intervals for the association between time-dependent AChEI use and risk of stroke and death.

    Results: Compared with matched controls, AChEI users had a lower risk of stroke (hazard ratio: 0.85, 95% confidence interval: 0.75-0.95) and all-cause death (hazard ratio: 0.76, 95% confidence interval: 0.72-0.80). After considering competing risk of death, high doses (>= 1.33 defined daily doses) of AChEI remained significantly associated with reduced stroke risk.

    Discussion: The use of AChEIs in people with dementia may be associated with reduced risk of ischemic stroke and death. These results call for a closer examination of the cardiovascular effects of AChEIs.

  • 16. Tolppanen, Anna-Maija
    et al.
    Solomon, Alina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Eastern Finland, Finland; Karolinska Institutet, Sweden.
    Kulmala, Jenni
    Kåreholt, Ingemar
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Jönköping University, Sweden.
    Ngandu, Tiia
    Rusanen, Minna
    Laatikainen, Tiina
    Soininen, Hilkka
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). University of Eastern Finland, Finland; Karolinska Institutet, Sweden; National Institute for Health and Welfare, Finland.
    Leisure-time physical activity from mid- to late life, body mass index, and risk of dementia2015In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, no 4, p. 434-443Article in journal (Refereed)
    Abstract [en]

    Background: Physical activity may be beneficial for cognition, but the effect may vary depending on personal characteristics. Methods: We investigated the associations between leisure-time physical activity (LTPA) from mid- to late life, the risk of dementia, and the role of body mass index, sex, and APOE in the CALDE study during 28-year follow-up. Cognitive function of a random subsample was assessed at a mean age of 78.8 years (n = 1511), and dementia/Alzheimer's disease (AD) diagnoses were identified from national registers for the entire target population (n = 3559). Results: Moderate (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.08-1.99) and low levels of midlife LTPA (BR, 1.39; 95% CI, 0.99-1.95) were associated with higher risk of dementia in comparison with the most active category. The benefits were more pronounced among men, overweight individuals, and APOE epsilon 4 noncarriers. Maintaining high LTPA (HR, 0.16; 95% CI, 0.06-0.41) or increasing LTPA (HR, 0.19; 95% CI, 0.09-0.40) after midlife was associated with lower dementia risk Similar results were observed for AD. Conclusions: The window of opportunity for preventive physical activity interventions may extend from midlife to older ages.

  • 17.
    Wang, Rui
    et al.
    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.
    Kalpouzos, Gregoria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Lövdén, Martin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Laukka, Erika J.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Bronge, Lena
    Wahlund, Lars-Olof
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Sweden.
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Mixed brain lesions mediate the association between cardiovascular risk burden and cognitive decline in old age: A population-based study2017In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 13, no 3, p. 247-256Article in journal (Refereed)
    Abstract [en]

    Introduction: The underlying pathological mechanisms linking cardiovascular burden to cognitive decline remain unclear. Methods: We investigated the associations of the Framingham general cardiovascular risk score (FGCRS), apolipoprotein E (APOE) 64, and brain structure with the Mini-Mental State Examination (MMSE) decline using the 9-year follow-up data from Swedish National Study on Aging and Care in Kungsholmen (n = 2189, age >= 60) and the embedded magnetic resonance imaging (MRI) (n = 448) studies. Volumes of white matter hyperintensities (WMHs), total gray matter, ventricles, and hippo campus were assessed in the MRI sample. Results: A higher FGCRS was associated with faster MMSE decline in young-old people (60-72 years) but not in old-old (>= 78 years). Larger volumes of cerebral WMHs and ventricles and smaller volumes of total gray matter and hippocampus were all associated with accelerated MMSE decline (P <.01); these associations were stronger among APOE epsilon 4 carriers than noncarriers. Simultaneously entering multiple brain lesion markers as mediators in the model substantially attenuated the association between FGCRS and MMSE decline. Discussion: The effect of cardiovascular risk burden on cognitive deterioration in old age is largely mediated by mixed brain lesions.

  • 18.
    Wimo, Anders
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Karolinska Institutet, Sweden; Uppsala University/County Council of Gävleborg, Sweden.
    Guerchet, Maelenn
    Ali, Gemma-Claire
    Wu, Yu-Tzu
    Prina, A. Matthew
    Winblad, Bengt
    Jonsson, Linus
    Liu, Zhaorui
    Prince, Martin
    The worldwide costs of dementia 2015 and comparisons with 20102017In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 13, no 1, p. 1-7Article in journal (Refereed)
    Abstract [en]

    Introduction: In 2010, Alzheimer's Disease International presented estimates of the global cost of illness (COI) of dementia. Since then, new studies have been conducted, and the number of people with dementia has increased. Here, we present an update of the global cost estimates. Methods: This is a societal, prevalence-based global COI study. Results: The worldwide costs of dementia were estimated at United States (US) $818 billion in 2015, an increase of 35% since 2010; 86% of the costs occur in high-income countries. Costs of informal care and the direct costs of social care still contribute similar proportions of total costs, whereas the costs in the medical sector are much lower. The threshold of US $1 trillion will be crossed by 2018. Discussion: Worldwide costs of dementia are enormous and still inequitably distributed. The increase in costs arises from increases in numbers of people with dementia and in increases in per person costs.

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