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1.	Barbera, Mariagnese, et al. (author) A multimodal precision-prevention approach combining lifestyle intervention with metformin repurposing to prevent cognitive impairment and disability: the MET-FINGER randomised controlled trial protocol 2024 In: Alzheimer's Research & Therapy. - : BioMed Central Ltd. - 1758-9193. ; 16 Journal article (peer-reviewed)abstract Background: Combining multimodal lifestyle interventions and disease-modifying drugs (novel or repurposed) could provide novel precision approaches to prevent cognitive impairment. Metformin is a promising candidate in view of the well-established link between type 2 diabetes (T2D) and Alzheimer’s Disease and emerging evidence of its potential neuro-protective effects (e.g. vascular, metabolic, anti-senescence). MET-FINGER aims to test a FINGER 2.0 multimodal intervention, combining an updated FINGER multidomain lifestyle intervention with metformin, where appropriate, in an APOE ε4-enriched population of older adults (60–79 years) at increased risk of dementia.Methods: MET-FINGER is an international randomised, controlled, parallel-group, phase-IIb proof-of-concept clinical trial, where metformin is included through a trial-within-trial design. 600 participants will be recruited at three sites (UK, Finland, Sweden). Participants at increased risk of dementia based on vascular risk factors and cognitive screening, will be first randomised to the FINGER 2.0 intervention (lifestyle + metformin if eligible; active arm) or to receive regular health advice (control arm). Participants allocated to the FINGER 2.0 intervention group at risk indicators of T2D will be additionally randomised to receive metformin (2000 mg/day or 1000 mg/day) or placebo. The study duration is 2 years. The changes in global cognition (primary outcome, using a Neuropsychological Test Battery), memory, executive function, and processing speed cognitive domains; functional status; lifestyle, vascular, metabolic, and other dementia-related risk factors (secondary outcomes), will be compared between the FINGER 2.0 intervention and the control arm. The feasibility, potential interaction (between-groups differences in healthy lifestyle changes), and disease-modifying effects of the lifestyle-metformin combination will be exploratory outcomes. The lifestyle intervention is adapted from the original FINGER trial (diet, physical activity, cognitive training, monitoring of cardiovascular/metabolic risk factors, social interaction) to be consistently delivered in three countries. Metformin is administered as Glucophage®XR/SR 500, (500 mg oral tablets). The metformin/placebo treatment will be double blinded. Conclusion: MET-FINGER is the first trial combining a multimodal lifestyle intervention with a putative repurposed disease-modifying drug for cognitive impairment prevention. Although preliminary, its findings will provide crucial information for innovative precision prevention strategies and form the basis for a larger phase-III trial design and future research in this field.
2.	Barbera, Mariagnese, et al. (author) Designing an Internet-Based Multidomain Intervention for the Prevention of Cardiovascular Disease and Cognitive Impairment in Older Adults : The HATICE Trial 2018 In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 62:2, s. 649-663 Journal article (peer-reviewed)abstract Background: Many dementia and cardiovascular disease (CVD) cases in older adults are attributable to modifiable vascular and lifestyle-related risk factors, providing opportunities for prevention. In the Healthy Aging Through Internet Counselling in the Elderly (HATICE) randomized controlled trial, an internet-based multidomain intervention is being tested to improve the cardiovascular risk (CVR) profile of older adults. Objective: To design a multidomain intervention to improve CVR, based on the guidelines for CVR management, and administered through a coach-supported, interactive, platform to over 2500 community-dwellers aged 65+ in three European countries. Methods: A comparative analysis of national and European guidelines for primary and secondary CVD prevention was performed. Results were used to define the content of the intervention. Results: The intervention design focused on promoting awareness and self-management of hypertension, dyslipidemia, diabetes mellitus, and overweight, and supporting smoking cessation, physical activity, and healthy diet. Overall, available guidelines lacked specific recommendations for CVR management in older adults. The comparative analysis of the guidelines showed general consistency for lifestyle-related recommendations. Key differences, identified mostly in methods used to assess the overall CVR, did not hamper the intervention design. Minor country-specific adaptations were implemented to maximize the intervention feasibility in each country. Conclusion: Despite differences inCVRmanagement within the countries considered, itwas possible to design and implement the HATICE multidomain intervention. The study can help define preventative strategies for dementia and CVD that are applicable internationally.
3.	Ekman, Urban, et al. (author) Evaluation of a Novel Psychological Intervention Tailored for Patients With Early Cognitive Impairment (PIPCI) : Study Protocol of a Randomized Controlled Trial 2020 In: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 11 Journal article (peer-reviewed)abstract Background: Individuals with early phase cognitive impairment are frequently affected by existential distress, social avoidance and associated health issues (including symptoms of stress, anxiety, and depression). The demand for efficient psychological support is crucial from both an individual and a societal perspective. We have developed a novel psychological intervention (Psychological Intervention tailored for Patients with Cognitive Impairment, PIPCI) manual for providing a non-medical path to enhanced psychological health in the cognitively impaired population. The current article provides specific information on the randomized controlled trial (RCT)-design and methods. The main hypothesis is that participants receiving PIPCI will increase their psychological flexibility (the ability to notice and accept interfering thoughts, emotions, and bodily sensations without acting on them, when this serves action in line with personal values) compared to participants in the active control (cognitive training) group and the waiting list control group. The secondary hypotheses are that participants receiving PIPCI will improve psychological health (stress measures, quality of life, depression, and general health) compared to participants in the active control group and the waiting list control group.Materials and Methods: This three-arm RCT will recruit participants from the cognitive centers at Karolinska University Hospital in Stockholm and randomize approximately 120 individuals in the early phase of cognitive impairment to either an experimental group (psychological intervention once a week for 10 weeks), an active control group (cognitive training once a week for 10 weeks) or a waiting list control group. Intervention outcome will be evaluated with self-report questionnaires on physical and psychological aspects of health, cognitive assessment, biological markers (obtained from blood and saliva) and health care costs. Assessments will be performed at pre- (1 week before the interventions) and post-intervention (1 week after the interventions), as well as at a 6-month follow-up.Discussion: The development of a potentially feasible and effective psychological intervention tailored for early phase cognitive impairment (PIPCI) has the potential to advance the non-pharmacological intervention field. This is especially important given the extensive burden for many affected individuals and their families and the current lack of effective treatments. If the psychological intervention discussed here shows feasibility and efficacy, there is potential for far-reaching healthcare implications for patients with early cognitive impairment at risk of developing dementia.
4.	Eskelinen, Marjo H, et al. (author) Midlife healthy-diet index and late-life dementia and Alzheimer's disease 2011 In: Dementia and Geriatric Cognitive Disorders Extra. - Basel : S. Karger. - 1664-5464. ; 1:1, s. 103-112 Journal article (peer-reviewed)abstract AIM: To study long-term effects of dietary patterns on dementia and Alzheimer's disease (AD). METHODS: Of 525 subjects randomly selected from population-based cohorts surveyed at midlife, a total of 385 (73%) subjects were re-examined 14 years later in the CAIDE study. A healthy-diet index (range 0-17) was constructed including both healthy and unhealthy dietary components. RESULTS: Persons with a healthy diet (healthy-diet index >8 points) had a decreased risk of dementia (OR 0.12, 95% CI 0.02-0.85) and AD (OR 0.08, 95% CI 0.01-0.89) compared with persons with an unhealthy diet (0-8 points), adjusting for several possible confounders. CONCLUSIONS: Healthy diet at midlife is associated with a decreased risk of dementia/AD in late life. These findings highlight the importance of dietary patterns and may make more effective measures for dementia/AD prevention or postponement possible.
5.	Hoevenaar-Blom, Marieke P., et al. (author) Improving data sharing in research with context-free encoded missing data 2017 In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:9 Journal article (peer-reviewed)abstract Lack of attention to missing data in research may result in biased results, loss of power and reduced generalizability. Registering reasons for missing values at the time of data collection, or-in the case of sharing existing data-before making data available to other teams, can save time and efforts, improve scientific value and help to prevent erroneous assumptions and biased results. To ensure that encoding of missing data is sufficient to understand the reason why data are missing, it should ideally be context-free. Therefore, 11 context-free codes of missing data were carefully designed based on three completed randomized controlled clinical trials and tested in a new randomized controlled clinical trial by an international team consisting of clinical researchers and epidemiologists with extended experience in designing and conducting trials and an Information System expert. These codes can be divided into missing due to participant and/or participation characteristics (n = 6), missing by design (n = 4), and due to a procedural error (n = 1). Broad implementation of context-free missing data encoding may enhance the possibilities of data sharing and pooling, thus allowing more powerful analyses using existing data.
6.	Hooshmand, Babak, et al. (author) Serum Insulin and Cognitive Performance in Older Adults : A Longitudinal Study 2019 In: American Journal of Medicine. - : Elsevier BV. - 0002-9343 .- 1555-7162. ; 132:3, s. 367-373 Journal article (peer-reviewed)abstract PurposeThe aim of this study was to examine the association of serum glucose, insulin, and insulin resistance with cognitive functioning 7 years later in a longitudinal population-based study of Finnish older adults.MethodsSerum glucose and insulin were measured at baseline in 269 dementia-free individuals aged 65-79 years, from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study. Insulin resistance was estimated with the homeostasis model assessment (HOMA-IR). Participants were reexamined 7 years later, and global cognition, episodic memory, executive functioning, verbal expression, and psychomotor speed were assessed, both at baseline and at follow-up. Multiple linear regression was used to investigate the associations with cognitive performance at follow-up, after adjusting for several potential confounders, including common vascular risk factors.ResultsIn the multivariable-adjusted linear regression models, no associations of insulin resistance with cognitive functioning were observed. After excluding 19 incident dementia cases, higher baseline HOMA-IR values were related to worse performance in global cognition (beta [standard error (SE)] -.050 [0.02]; P =.043) and psychomotor speed (beta [SE] -.064 [. 03]; P = [.043]) 7 years later. Raised serum insulin levels were associated with lower scores on global cognition (b [SE] -.054 [.03]; P =.045) and tended to relate to poorer performance in psychomotor speed (beta [SE] -.061 [.03]; P =.070).ConclusionsSerum insulin and insulin resistance may be independent predictors of cognitive performance 7 years later in elderly individuals without dementia. Randomized controlled trials are needed to determine this issue.
7.	Håkansson, Krister, 1952-, et al. (author) The Patient with Cognitive Impairment 2018 In: Treatable and Potentially Preventable Dementias. - New York : Cambridge University Press. - 9781107157460 ; , s. 52-80 Book chapter (peer-reviewed)
8.	Janssen, Niels, et al. (author) Association Between Cognition, Health Related Quality of Life, and Costs in a Population at Risk for Cognitive Decline 2022 In: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 89:2, s. 623-632 Journal article (peer-reviewed)abstract Background: The association between health-related quality of life (HRQoL) and care costs in people at risk for cognitive decline is not well understood. Studying this association could reveal the potential benefits of increasing HRQoL and reducing care costs by improving cognition. Objective: In this exploratory data analysis we investigated the association between cognition, HRQoL utilities and costs in a well-functioning population at risk for cognitive decline. Methods: An exploratory data analysis was conducted using longitudinal 2-year data from the FINGER study (n= 1,120). A change score analysis was applied using HRQoL utilities and total medical care costs as outcome. HRQoL utilities were derived from the Short Form Health Survey-36 (SF-36). Total care costs comprised visits to a general practitioner, medical specialist, nurse, and days at hospital. Analyses were adjusted for activities of daily living (ADL) and depressive symptoms. Results: Although univariable analysis showed an association between cognition and HRQoL utilities, multivariable analysis showed no association between cognition, HRQoL utilities and total care costs. A one-unit increase in ADL limitations was associated with a -0.006 (p <0 .001) decrease in HRQoL utilities and a one-unit increase in depressive symptoms was associated with a -0.004 (p < 0.001) decrease in HRQoL utilities. Conclusion: The level of cognition in people at-risk for cognitive decline does not seem to be associated with HRQoL utilities. Future research should examine the level at which cognitive decline starts to affect HRQoL and care costs. Ideally, this would be done by means of cross-validation in populations with various stages of cognitive functioning and decline.
9.	Jiang, Ziying, et al. (author) Red Cell Distribution Width and Dementia Among Rural-Dwelling Older Adults : The MIND-China Study 2021 In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 83:3, s. 1187-1198 Journal article (peer-reviewed)abstract Background: Evidence has emerged that anemia is associated with dementia, but data on the relationships of red blood cell distribution width (RDW) with dementia and cognitive function in older adults are sparse.Objective: We sought to investigate the associations of RDW with dementia and global cognitive performance among rural-dwelling Chinese older adults and further to examine their associations by anemia status.Methods: This population-based cross-sectional study included 5,115 participants (age≥65 years, 57.0%women) in the baseline examination (March-September 2018) of the Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-CHINA). We collected data through face-to-face interviews, clinical examinations, and laboratory tests. Global cognitive function was evaluated using the Mini-Mental State Examination (MMSE). We defined dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) following the respective international criteria. Data were analyzed using multinomial logistic and general linear regression models.Results: Of all participants, 300 were diagnosed with dementia, including 195 with AD and 95 VaD. The multiple-adjusted odds ratio of dementia associated with quartiles of RDW were 1.45 (95%CI: 0.87–2.44), 1.00 (reference), 1.77 (1.07–2.93), and 2.28 (1.40–3.72). Similar J-shaped patterns existed for the association of RDW with odds ratio of AD and VaD. Anemia was not significantly associated with dementia. The J-shaped associations of RDW with dementia and subtypes were statistically evident only among participants without anemia. There was an inverted J-shaped relationship between RDW quartiles and β-coefficients of MMSE score.Conclusion: There is a J-shaped association between RDW level and likelihood of dementias among rural-dwelling Chinese older adults, especially among people without anemia.
10.	Kemppainen, Nina, et al. (author) Brain amyloid load and its associations with cognition and vascular risk factors in FINGER Study 2018 In: Neurology. - 0028-3878 .- 1526-632X. ; 90:3, s. E206-E213 Journal article (peer-reviewed)abstract 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.
11.	Kivipelto, Miia, et al. (author) Apolipoprotein E epsilon 4 magnifies lifestyle risks for dementia : a population-based study 2008 In: Journal of Cellular and Molecular Medicine (Print). - : Wiley. - 1582-1838 .- 1582-4934. ; 12:6B, s. 2762-2771 Journal article (peer-reviewed)abstract The risk of dementia and Alzheimer's disease (AD) probably results from an interaction between genetic and environmental factors. The aim of this study was to investigate the effects and putative interactions between the apoE epsilon 4 allele and lifestyle related risk factors for dementia and AD. Participants of the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study were derived from random, population-based samples previously studied in 1972, 1977, 1982 or 1987. After an average follow-up of 21 years, 1449 individuals (72.5%) aged 65-79 years were re-examined in 1998. The apoE epsilon 4 allele was an independent risk factor for dementia/AD even after adjustments for sociodemographic, lifestyle and vascular factors (odds ratio [OR] = 2.83, 95% confidence interval [CI] epsilon 1.61-4.97). Physical inactivity, alcohol drinking and smoking increased the risk of dementia/AD particularly among the apoE epsilon 4 carriers. Furthermore, low-moderate intake of polyunsaturated, and moderate-high intake of saturated fats were associated with an increased risk of dementia/AD more pronouncedly among apoE epsilon 4 carriers. Composite effect of the lifestyle factors was particularly seen among the epsilon 4 carriers (OR = 11.42, 95% CI = 1.94-67.07 in the 4(th) quartile). Physical inactivity, dietary fat intake, alcohol drinking and smoking at midlife are associated with the risk of dementia and AD, especially among the apoE epsilon 4 carriers. The apoE epsilon 4 carriers may be more vulnerable to environmental factors, and thus, lifestyle interventions may greatly modify dementia risk particularly among the genetically susceptible individuals.
12.	Kivipelto, Miia, et al. (author) Fokus på tidig diagnos och förebyggande i Alzheimer forskning 2013 In: Finska Läkaresällskapets Handlingar. - Helsingfors. - 0015-2501. ; 173:2, s. 11-19 Research review (peer-reviewed)abstract Alzheimers sjukdom identifieras traditionellt med demenssyndrom. De nya förslagen till diag- noskriterier öppnar ett nytt perspektiv där sjukdomen kan identifieras innan patienterna får demens. Tidig diagnos innebär bättre möjligheter till att hitta effektiva läkemedel och andra demensförebyggande interventioner. Epidemiologiska studier har visat att förutom hög ålder och genetiska faktorer finns det många påverkbara vaskulära, livsstilsrelaterade och psyko- sociala riskfaktorer för Alzheimers sjukdom. I Finland har steget redan tagits från observation till intervention, med fokus på stora multifaktoriella interventionsstudier där flera riskfaktorer och mekanismer påverkas samtidigt (t.ex. FINGER-studien). Tillsammans med två liknande studier i Frankrike och Nederländerna ingår FINGER i European Dementia Prevention Initiative. Resultaten av detta internationella samarbete kommer att leda fram till rekommendationer om en hälsosam livsstil för förebyggande av kognitiv svikt och demens hos äldre. Sådana rekommendationer behövs både för folkhälsan och inom sjukvården.
13.	Kivipelto, Miia, et al. (author) Lifestyle interventions to prevent cognitive impairment, dementia and Alzheimer disease 2018 In: Nature Reviews Neurology. - : Springer Science and Business Media LLC. - 1759-4758 .- 1759-4766. ; 14:11, s. 653-666 Research review (peer-reviewed)abstract Research into dementia prevention is of paramount importance if the dementia epidemic is to be halted. Observational studies have identified several potentially modifiable risk factors for dementia, including hypertension, dyslipidaemia and obesity at midlife, diabetes mellitus, smoking, physical inactivity, depression and low levels of education. Randomized clinical trials are needed that investigate whether interventions targeting these risk factors can reduce the risk of cognitive decline and dementia in elderly adults, but such trials are methodologically challenging. To date, most preventive interventions have been tested in small groups, have focused on a single lifestyle factor and have yielded negative or modest results. Given the multifactorial aetiology of dementia and late-onset Alzheimer disease, multidomain interventions that target several risk factors and mechanisms simultaneously might be necessary for an optimal preventive effect. In the past few years, three large multidomain trials (FINGER, MAPT and PreDIVA) have been completed. The FINGER trial showed that a multidomain lifestyle intervention can benefit cognition in elderly people with an elevated risk of dementia. The primary results from the other trials did not show a statistically significant benefit of preventive interventions, but additional analyses among participants at risk of dementia showed beneficial effects of intervention. Overall, results from these three trials suggest that targeting of preventive interventions to at-risk individuals is an effective strategy. This Review discusses the current knowledge of lifestyle-related risk factors and results from novel trials aiming to prevent cognitive decline and dementia. Global initiatives are presented, including the World Wide FINGERS network, which aims to harmonize studies on dementia prevention, generate high-quality scientific evidence and promote its implementation.
14.	Kivipelto, Miia, et al. (author) The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) : Study design and progress 2013 In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 9:6, s. 657-665 Journal article (peer-reviewed)abstract 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.
15.	Kivipelto, Miia, et al. (author) World-Wide FINGERS Network : A global approach to risk reduction and prevention of dementia 2020 In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:7, s. 1078-1094 Journal article (peer-reviewed)abstract Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies.
16.	Kulmala, Jenni, et al. (author) Midlife self-rated health and fitness in relation to white matter lesions and grey matter volume 20 years later 2014 In: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; , s. 592- Conference paper (peer-reviewed)
17.	Lehtisalo, Jenni, et al. (author) Changes in Lifestyle, Behaviors, and Risk Factors for Cognitive Impairment in Older Persons During the First Wave of the Coronavirus Disease 2019 Pandemic in Finland : Results From the FINGER Study 2021 In: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 12 Journal article (peer-reviewed)abstract Aims: This study aimed to describe how the first phase of the coronavirus disease 2019 (COVID-19) pandemic affected older persons from the general Finnish population who are at risk of developing or have cognitive impairment, specifically, to describe whether participants experienced a change in risk factors that are relevant for the prevention of cognitive decline including diet, physical activity, access to medical care, socially and cognitively stimulating activities, and emotional health and well-being.Method: A postal survey was sent in June 2020 to 859 participants from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), an ongoing longitudinal study. The survey was developed to assess the effect of the COVID-19 pandemic and related infection-control measures on daily life, specifically commitment to distancing measures, access to health care and social services, daily activities, and changes in cognitive and social activities.Results: By September 2020, 613 (71%) participants responded (mean age = 77.7 years, 32% lived alone, and 80% had at least one chronic condition). Three quarters adopted some distancing practices during the first months of the pandemic. Older participants were more likely to practice total isolation than younger ones (29 vs. 19%; p = 0.003). Non-acute health-care visits were canceled for 5% of the participants who needed appointments, but cancellations in dental health care (43%), home aid (30%), and rehabilitative services (53%) were more common. Pandemic-related changes were reported in social engagements, for example, less contact with friends (55%) and family (31%), or less frequent attendance in cultural events (38%) or associations (25%), although remote contact with others increased for 40%. Feelings of loneliness increased for 21%, particularly those who were older (p = 0.023) or living alone (p < 0.001). Physical activity reduced for 34%, but dietary habits remained stable or improved. Pandemic-related changes in lifestyle and activities were more evident among those living alone.Conclusions: Finnish older persons generally reported less negative changes in lifestyles and behaviors during the pandemic than expected. Older people and those living alone seemed more susceptible to negative changes. It is important to compare how coping strategies may compare with other European countries to identify factors that may help older individuals to maintain healthy lifestyles during future waves of COVID-19.
18.	Lehtisalo, Jenni, et al. (author) Diabetes, glycaemia, and cognitiona secondary analysis of the Finnish Diabetes Prevention Study 2016 In: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 32:1, s. 102-110 Journal article (peer-reviewed)abstract Background: Type 2 diabetes is linked with cognitive dysfunction and dementia in epidemiological studies, but these observations are limited by lack of data on the exact timing of diabetes onset. We investigated diabetes, dysglycaemia, and cognition in the Finnish Diabetes Prevention Study, in which the timing and duration of diabetes are well documented.Methods: The Finnish Diabetes Prevention Study comprised middle-aged, overweight participants with impaired glucose tolerance but no diabetes at baseline (n=522), randomized to lifestyle intervention or a control group. After an intervention period (mean duration 4years) and follow-up (additional 9years), cognitive assessment with the CERAD test battery and Trail Making Test A (TMT) was executed twice within a 2-year interval. Of the 364 (70%) participants with cognitive assessments, 171 (47%) had developed diabetes.Results: Cognitive function did not differ between those who developed diabetes and those who did not. Lower mean 2-h glucose at an oral glucose tolerance test (OGTT) and HbA(1C) during the intervention period predicted better performance in the TMT (p=0.012 and 0.024, respectively). Those without diabetes or with short duration of diabetes improved in CERAD total score between the two assessments (p=0.001) whereas those with long duration of diabetes did not (p=0.844).Conclusions: Better glycemic control among persons with baseline impaired glucose tolerance predicted better cognitive performance 9years later in this secondary analysis of the Finnish Diabetes Prevention Study population. In addition, learning effects in cognitive testing were not evident in people with long diabetes duration.
19.	Lehtisalo, Jenni, et al. (author) Dietary changes and cognition over 2 years within a multidomain intervention trial-The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) 2019 In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:3, s. 410-417 Journal article (peer-reviewed)abstract 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.
20.	Lehtisalo, Jenni, et al. (author) Nutrient intake and dietary changes during a 2-year multi-domain lifestyle intervention among older adults : secondary analysis of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) randomised controlled trial 2017 In: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 118:4, s. 291-302 Journal article (peer-reviewed)abstract Advancing age increases the risk for diseases and health concerns like cognitive decline, constituting a major public health challenge. Lifestyle, especially healthy diet, affects many risk factors related to chronic diseases, and thus lifestyle interventions among older adults may be beneficial in promoting successful ageing. We completed a randomised 2-year multi-domain lifestyle intervention trial aiming at prevention of cognitive decline among 631 participants in the intervention and 629 in the control group, aged 60-77 years at baseline. Dietary counselling was one of the intervention domains together with strength exercise, cognitive training and management of CVD risk factors. The aim of this paper was to describe success of the intervention -that is, how an intervention based on national dietary recommendations affected dietary habits as a part of multi-intervention. Composite dietary intervention adherence score comprising nine distinct goals (range 0-9 points from none to achieving all goals) was 5.0 at baseline, and increased in the intervention group after the 1st (P< 0.001) and 2nd (P = 0.005) year. The difference in change compared with the control group was significant at both years (P < 0.001 and P= 0.018). Intake of several vitamins and minerals decreased in the control group but remained unchanged or increased in the intervention group during the 2 years. Well-targeted dietary counselling may prevent age-related decline in diet quality and help in preventing cognitive decline.
21.	Levak, Nicholas, et al. (author) Nutrition guidance within a multimodal intervention improves diet quality in prodromal Alzheimer’s disease: Multimodal Preventive Trial for Alzheimer’s Disease (MIND-ADmini) 2024 In: Alzheimer's Research & Therapy. - : Springer. - 1758-9193. ; 16:1 Journal article (peer-reviewed)abstract BackgroundMultimodal lifestyle interventions can benefit overall health, including cognition, in populations at-risk for dementia. However, little is known about the effect of lifestyle interventions in patients with prodromal Alzheimer’s disease (AD). Even less is known about dietary intake and adherence to dietary recommendations within this population making it difficult to design tailored interventions for them.MethodA 6-month MIND-ADmini pilot randomized controlled trial (RCT) was conducted among 93 participants with prodromal AD in Sweden, Finland, Germany, and France. Three arms were included in the RCT: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management, and social stimulation); 2) multimodal lifestyle intervention + medical food product; and 3) regular health advice (control group). Adherence to dietary advice was assessed with a brief food intake questionnaire by using the Healthy Diet Index (HDI) and Mediterranean Diet Adherence Screener (MEDAS). The intake of macro- and micronutrients were analyzed on a subsample using 3-day food records.ResultsThe dietary quality in the intervention groups, pooled together, improved compared to that of the control group at the end of the study, as measured with by HDI (p = 0.026) and MEDAS (p = 0.008). The lifestyle-only group improved significantly more in MEDAS (p = 0.046) and almost significantly in HDI (p = 0.052) compared to the control group, while the lifestyle + medical food group improved in both HDI (p = 0.042) and MEDAS (p = 0.007) during the study. There were no changes in macro- or micronutrient intake for the intervention groups at follow-up; however, the intakes in the control group declined in several vitamins and minerals when adjusted for energy intake.ConclusionThese results suggest that dietary intervention as part of multimodal lifestyle interventions is feasible and results in improved dietary quality in a population with prodromal AD. Nutrient intakes remained unchanged in the intervention groups while the control group showed a decreasing nutrient density.Trial registrationClinicalTrials.gov NCT03249688, 2017–07-08.
22.	Liang, Yajun, et al. (author) Cardiovascular health metrics from mid- to late-life and risk of dementia : A population-based cohort study in Finland 2020 In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 17:12 Journal article (peer-reviewed)abstract BackgroundVery few studies have explored the patterns of cardiovascular health (CVH) metrics in midlife and late life in relation to risk of dementia. We examined the associations of composite CVH metrics from midlife to late life with risk of incident dementia.Methods and findingsThis cohort study included 1,449 participants from the Finnish Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study, who were followed from midlife (baseline from1972 to 1987; mean age 50.4 years; 62.1% female) to late life (1998), and then 744 dementia-free survivors were followed further into late life (2005 to 2008). We defined and scored global CVH metrics based on 6 of the 7 components (i.e., smoking, physical activity, and body mass index [BMI] as behavioral CVH metrics; fasting plasma glucose, total cholesterol, and blood pressure as biological CVH metrics) following the modified American Heart Association (AHA)’s recommendations. Then, the composite global, behavioral, and biological CVH metrics were categorized into poor, intermediate, and ideal levels. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Data were analyzed with Cox proportional hazards and the Fine and Gray competing risk regression models. During the follow-up examinations, dementia was diagnosed in 61 persons in 1998 and additional 47 persons in 2005 to 2008. The fully adjusted hazard ratio (HR) of dementia was 0.71 (95% confidence interval [CI]: 0.43, 1.16; p = 0.174) and 0.52 (0.29, 0.93; p = 0.027) for midlife intermediate and ideal levels (versus poor level) of global CVH metrics, respectively; the corresponding figures for late-life global CVH metrics were 0.60 (0.22, 1.69; p = 0.338) and 0.91 (0.34, 2.41; p = 0.850). Compared with poor global CVH metrics in both midlife and late life, the fully adjusted HR of dementia was 0.25 (95% CI: 0.08, 0.86; p = 0.028) for people with intermediate global CVH metrics in both midlife and late life and 0.14 (0.02, 0.76; p = 0.024) for those with midlife ideal and late-life intermediate global CVH metrics. Having an intermediate or ideal level of behavioral CVH in both midlife and late life (versus poor level in both midlife and late life) was significantly associated with a lower dementia risk (HR range: 0.03 to 0.26; p < 0.05), whereas people with midlife intermediate and late-life ideal biological CVH metrics had a significantly increased risk of dementia (p = 0.031). Major limitations of this study include the lack of data on diet and midlife plasma glucose, high rate of attrition, as well as the limited power for certain subgroup analyses.ConclusionsIn this study, we observed that having the ideal CVH metrics, and ideal behavioral CVH metrics in particular, from midlife onwards is associated with a reduced risk of dementia as compared with people having poor CVH metrics. Maintaining life-long health behaviors may be crucial to reduce late-life risk of dementia.
23.	Marengoni, Alessandra, et al. (author) The Effect of a 2-Year Intervention Consisting of Diet, Physical Exercise, Cognitive Training, and Monitoring of Vascular Risk on Chronic Morbidity-the FINGER Randomized Controlled Trial 2018 In: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610 .- 1538-9375. ; 19:4, s. 355-360 Journal article (peer-reviewed)abstract Objective: To verify whether a multidomain intervention lowers the risk of developing new chronic diseases in older adults. Methods: Multicenter, double-blind randomized controlled trial started in October 2009, with 2-year follow-up. A total of 1260 people aged 60 to 77 years were enrolled in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). Participants were randomly assigned in a 1:1 ratio to a 2-year multidomain intervention (n = 631) (nutritional guidance, exercise, cognitive training, and management of metabolic and vascular risk factors) or a control group (n = 629) (general health advice). Data on most common chronic diseases were collected by a physician at baseline and 2 years later. Results: At 2-year follow-up, the average number of new chronic diseases was 0.47 [standard deviation (SD) 0.7] in the intervention group and 0.58 (SD 0.8) in the control group (P < .01). The incidence rate per 100 person-years for developing 1+ new disease(s) was 17.4 [95% confidence interval (CI) = 15.1-20.1] in the intervention group and 20.5 (95% CI = 18.0-23.4) in the control group; for developing 2+ new diseases, 4.9 (95% CI = 3.7-6.4) and 6.1 (95% CI = 4.8-7.8); and for 3+ new diseases, 0.7 (95% CI = 0.4-1.5) and 1.8 (95% CI = 1.1-2.8), respectively. After adjustment for age, sex, education, current smoking, alcohol intake, and the number of chronic diseases at baseline, the intervention group had a hazard ratio ranging from 0.80 (0.66-0.98) for developing 1+ new chronic disease(s) to 0.38 (0.16-0.88) for developing 3+ new chronic diseases compared to the control group. Conclusions: Findings from this randomized controlled trial suggest that a multidomain intervention could reduce the risk of developing new chronic diseases in older people.
24.	Neuvonen, Elisa, et al. (author) Late-life cynical distrust, risk of incident dementia, and mortality in a population-based cohort 2014 In: Neurology. - 0028-3878 .- 1526-632X. ; 82:24, s. 2205-2212 Journal article (peer-reviewed)abstract Objective:We investigated the association between late-life cynical distrust and incident dementia and mortality (mean follow-up times of 8.4 and 10.4 years, respectively) in the Cardiovascular Risk Factors, Aging and Dementia Study.Methods:Cynical distrust was measured based on the Cook-Medley Scale and categorized into tertiles. Cognitive status was evaluated with a 3-step protocol including screening, clinical phase, and differential diagnostic phase. Dementia was diagnosed according to DSM-IV criteria. Complete data on exposure, outcome, and confounders were available from 622 persons (46 dementia cases) for the dementia analyses and from 1,146 persons (361 deaths) for the mortality analyses. Age, sex, systolic blood pressure, total cholesterol, fasting glucose, body mass index, socioeconomic background, smoking, alcohol use, self-reported health, and APOE genotype were considered as confounders.Results:Cynical distrust was not associated with dementia in the crude analyses, but those with the highest level of cynical distrust had higher risk of dementia after adjusting for confounders (relative risk 3.13; 95% confidence interval [CI] 1.15-8.55). Higher cynical distrust was associated with higher mortality in the crude analyses (hazard ratio 1.40; 95% CI 1.05-1.87) but the association was explained by confounders (adjusted hazard ratio 1.19; 95% CI 0.86-1.61).Conclusions:Higher cynical distrust in late life was associated with higher mortality, but this association was explained by socioeconomic position, lifestyle, and health status. Association between cynical distrust and incident dementia became evident when confounders were considered. This novel finding suggests that both psychosocial and lifestyle-related risk factors may be modifiable targets for interventions. We acknowledge the need for larger replication studies.
25.	Ngandu, Tiia, et al. (author) A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER) : a randomised controlled trial 2015 In: The Lancet. - 0140-6736 .- 1474-547X. ; 385:9984, s. 2255-2263 Journal article (peer-reviewed)abstract Background Modifiable vascular and lifestyle-related risk factors have been associated with dementia risk in observational studies. In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a proof-of-concept randomised controlled trial, we aimed to assess a multidomain approach to prevent cognitive decline in at-risk elderly people from the general population.Methods In a double-blind randomised controlled trial we enrolled individuals aged 60-77 years recruited from previous national surveys. Inclusion criteria were CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age. We randomly assigned participants in a 1: 1 ratio to a 2 year multidomain intervention (diet, exercise, cognitive training, vascular risk monitoring), or a control group (general health advice). Computer-generated allocation was done in blocks of four (two individuals randomly allocated to each group) at each site. Group allocation was not actively disclosed to participants and outcome assessors were masked to group allocation. The primary outcome was change in cognition as measured through comprehensive neuropsychological test battery (NTB) Z score. Analysis was by modified intention to treat (all participants with at least one post-baseline observation). This trial is registered at ClinicalTrials.gov, number NCT01041989.Findings Between Sept 7, 2009, and Nov 24, 2011, we screened 2654 individuals and randomly assigned 1260 to the intervention group (n=631) or control group (n=629). 591 (94%) participants in the intervention group and 599 (95%) in the control group had at least one post-baseline assessment and were included in the modified intention-to-treat analysis. Estimated mean change in NTB total Z score at 2 years was 0.20 (SE 0.02, SD 0.51) in the intervention group and 0.16 (0.01, 0.51) in the control group. Between-group difference in the change of NTB total score per year was 0.022 (95% CI 0.002-0.042, p=0.030). 153 (12%) individuals dropped out overall. Adverse events occurred in 46 (7%) participants in the intervention group compared with six (1%) participants in the control group; the most common adverse event was musculoskeletal pain (32 [5%] individuals for intervention vs no individuals for control).Interpretation Findings from this large, long-term, randomised controlled trial suggest that a multidomain intervention could improve or maintain cognitive functioning in at-risk elderly people from the general population.
26.	Ngandu, Tiia (author) Lifestyle-related risk factors in dementia and mild cognitive impairment : a population-based study 2006 Doctoral thesis (other academic/artistic)abstract As an increasing number of individuals survive into advanced age, dementia and milder cognitive impairments takes on growing public health importance. The aetiology of dementia and Alzheimer's disease (AD), which is the most common cause of dementia, is considered to be multifactorial, resulting from both genetic and environmental factors. The present thesis project aimed at obtaining a comprehensive understanding of the role of lifestyle-related factors in the development of dementia and cognitive impairment. Special attention was paid to possible interactions between lifestyle-related and genetic risk factors. The general hypothesis was that a healthy lifestyle could reduce the risk of dementia and cognitive impairment. All five studies were based on the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) project. The participants in the CAIDE project were derived from four independent population-based random samples studied within the framework of the North Karelia Project and the FINMONICA study in 1972, 1977, 1982 or 1987. A random sample of 2000 individuals aged 65-79 years and living in two geographically defined areas in Kuopio and Joensuu in eastern Finland were invited for the reexamination in 1998, and altogether 1449 people (73 %) participated. In study 1, obesity at midlife was associated with an increased risk of dementia and AD. Midlife obesity, high cholesterol, and high systolic blood pressure were all significant risk factors for dementia with ORs of around 2 for each parameter, and they increased the risk additively. In study 2, we observed a U-shaped association between midlife alcohol drinking and the risk of mild cognitive impairment (MCI) in late-life, so that the participants who did not drink alcohol, as well as those who drank alcohol frequently, had a two-fold risk of having MCI when compared with those participants who drank alcohol infrequently. The presence of the apolipoprotein E (ApoE) epsilon4 allele modified the association between alcohol drinking and dementia: ApoE epsilon4 carriers showed an increased risk of dementia with increasing alcohol drinking frequency, whereas this was not the case for the ApoE epsilon4 non-carriers. In study 3, we investigated the relationship of midlife alcohol drinking to cognitive functions in late-life among the non-demented individuals. The participants who did not drink alcohol at midlife, had poorer performance compared to infrequent and frequent drinkers in episodic memory, psychomotor speed, and executive function in late-life. In study 4 low income level in late-life but not at midlife was related to the risk of dementia. Dementia was also associated with decreasing income level from midlife to old age. Low educational level and the ApoE FA allele independently increased the risk of dementia. In study 5 we examined whether the association between education and dementia was due to the presence of unhealthier lifestyles or more cardiovascular risk factors among the less educated persons. High education was associated with a lower risk of dementia and AD, and it remained unchanged after adjustments for a wide range of lifestyle factors. In summary, this set of studies showed that unhealthy lifestyle-related factors at midlife, such as obesity, hypertension and hypercholesterolemia increase the risk of developing dementia and AD later in life. Especially among ApoE epsilon4 allele carriers, alcohol drinking increases the risk of dementia. On the other hand, in non-demented individuals, alcohol drinkers exhibit better cognitive performance compared to abstainers. However, it is not clear whether this association is causal, or what is the optimal level of alcohol consumption to achieve the best cognitive function. High education is associated with a decreased risk of dementia whereas a high income level at midlife is not a contributary factor. A reduction in relative income level between midlife and late-life might well be a consequence of the dementing disease process. Educated persons may have a greater cognitive reserve that leads to a postponement of the clinical manifestation of dementia. The unhealthy lifestyle options may independently contribute to the depletion of this reserve or directly induce the pathologic processes underlying dementia and AD.
27.	Ngandu, Tiia, et al. (author) Recruitment and Baseline Characteristics of Participants in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) : A Randomized Controlled Lifestyle Trial 2014 In: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 11:9, s. 9345-9360 Journal article (peer-reviewed)abstract Our aim is to describe the study recruitment and baseline characteristics of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) study population. Potential study participants (age 60-77 years, the dementia risk score >= 6) were identified from previous population-based survey cohorts and invited to the screening visit. To be eligible, cognitive performance measured at the screening visit had to be at the mean level or slightly lower than expected for age. Of those invited (n = 5496), 48% (n = 2654) attended the screening visit, and finally 1260 eligible participants were randomized to the intervention and control groups (1: 1). The screening visit non-attendees were slightly older, less educated, and had more vascular risk factors and diseases present. The mean (SD) age of the randomized participants was 69.4 (4.7) years, Mini-Mental State Examination 26.7 (2.0) points, systolic blood pressure 140.1 (16.2) mmHg, total serum cholesterol 5.2 (1.0) mmol/L for, and fasting glucose 6.1 (0.9) mmol/L for, with no difference between intervention and control groups. Several modifiable risk factors were present at baseline indicating an opportunity for the intervention. The FINGER study will provide important information on the effect of lifestyle intervention to prevent cognitive impairment among at risk persons.
28.	Ngandu, Tiia, et al. (author) The effect of adherence on cognition in a multidomain lifestyle intervention (FINGER) 2022 In: Alzheimer's & Dementia. - : John Wiley & Sons. - 1552-5260 .- 1552-5279. ; 18:7, s. 1325-1334 Journal article (peer-reviewed)abstract Introduction: Lifestyle interventions may prevent cognitive decline, but the sufficient dose of intervention activities and lifestyle changes is unknown. We investigated how intervention adherence affects cognition in the FINGER trial (pre-specified subgroup analyses).Methods: FINGER is a multicenter randomized controlled trial examining the efficacy of multidomain lifestyle intervention (ClinicalTrials.gov NCT01041989). A total of 1260 participants aged 60 to 77 with increased dementia risk were randomized to a lifestyle intervention and control groups. Percentage of completed intervention sessions, and change in multidomain lifestyle score (self-reported diet; physical, cognitive, and social activity; vascular risk) were examined in relation to change in Neuropsychological Test Battery (NTB) scores.Results: Active participation was associated with better trajectories in NTB total and all cognitive subdomains. Improvement in lifestyle was associated with improvement in NTB total and executive function.Discussion: Multidomain lifestyle changes are beneficial for cognitive functioning, but future interventions should be intensive enough, and supporting adherence is essential.
29.	Norgren, Jakob, et al. (author) Capillary blood tests may overestimate ketosis : triangulation between three different measures of beta-hydroxybutyrate 2020 In: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 318:2, s. e184-E188 Journal article (peer-reviewed)abstract The ketone body beta-hydroxybutyrate (BHB), assessed by a point-of-care meter in venous whole blood (BHBv), was used as the main outcome in a study on nutritional ketosis in healthy older adults. Two other BHB measures were also used in the study for validation and exploratory purposes, and here we report findings on correlation and agreement between those three methods. Ketosis in the range of 0-1.5 mmol/L was induced in 15 healthy volunteers by intake of medium-chain fatty acids after a 12-h fast. BHBv was assessed at 12 time points for 4 h. The same point-of-care meter was also used to test capillary blood (BHBc) at three time points, and a laboratory test determined total ketones (TK) in plasma (BHBp + acetoacetate) at four time points. A total of 180 cases included simultaneous data on BHBv, BHBc, BHBp, and TK. TK correlated with BHBp (Pearson's r = 0.99), BHBv (r = 0.91), and BHBc (r = 0.91), all P < 0.0001. BHBv and BHBp had good agreement in absolute values. However, the slope between BHBc and BHBv, measured with the same device, was in the range of 0.64-0.78 in different regression models, indicating substantially higher BHB concentrations in capillary versus venous blood. We conclude that all three methods are valid to detect relative changes in ketosis, but our results highlight the importance of method considerations and the possible need to adjust cutoffs, e.g., in the management of ketoacidosis and in the evaluation and comparison of dietary interventions.
30.	Norgren, Jakob, et al. (author) Ketosis After Intake of Coconut Oil and Caprylic Acid-With and Without Glucose : A Cross-Over Study in Healthy Older Adults 2020 In: Frontiers in Nutrition. - : Frontiers Media SA. - 2296-861X. ; 7 Journal article (peer-reviewed)abstract Introduction: Medium-chain-triglycerides (MCT), formed by fatty acids with a length of 6-12 carbon atoms (C6-C12), constitute about two thirds of coconut oil (Coc). MCT have specific metabolic properties which has led them to be described as ketogenic even in the absence of carbohydrate restriction. This effect has mainly been demonstrated for caprylic acid (C8), which constitutes about 6-8% of coconut oil. Our aim was to quantify ketosis and blood glucose after intake of Coc and C8, with and without glucose intake. Sunflower oil (Suf) was used as control, expected to not break fasting ketosis, nor induce supply-driven ketosis. Method: In a 6-arm cross-over design, 15 healthy volunteers-age 65-73, 53% women-were tested once a week. After a 12-h fast, ketones were measured during 4 h after intake of coffee with cream, in combination with each of the intervention arms in a randomized order: 1. Suf (30 g); 2. C8 (20 g) + Suf (10 g); 3. C8 (20 g) + Suf (10 g) + Glucose (50 g); 4. Coc (30 g); 5. Coc (30 g) + Glucose (50 g); 6. C8 (20 g) + Coc (30 g). The primary outcome was absolute blood levels of the ketone beta-hydroxybutyrate, area under the curve (AUC). ANOVA for repeated measures was performed to compare arms. Results: beta-hydroxybutyrate, AUC/time (mean +/- SD), for arms were 1: 0.18 +/- 0.11; 2: 0.45 +/- 0.19; 3: 0.28 +/- 0.12; 4: 0.22 +/- 0.12; 5: 0.08 +/- 0.04; 6: 0.45 +/- 0.20 (mmol/L). Differences were significant (all p <= 0.02), except for arm 2 vs. 6, and 4 vs. 1 & 3. Blood glucose was stable in arm 1, 2, 4, & 6, at levels slightly below baseline (p <= 0.05) at all timepoints hours 1-4 after intake. Conclusions: C8 had a higher ketogenic effect than the other components. Coc was not significantly different from Suf, or C8 with glucose. In addition, we report that a 16-h non-carbohydrate window contributed to a mild ketosis, while blood glucose remained stable. Our results suggest that time-restricted feeding regarding carbohydrates may optimize ketosis from intake of MCT.
31.	Norgren, Jakob, et al. (author) Serum proBDNF Is Associated With Changes in the Ketone Body β-Hydroxybutyrate and Shows Superior Repeatability Over Mature BDNF : Secondary Outcomes From a Cross-Over Trial in Healthy Older Adults 2021 In: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 13 Journal article (peer-reviewed)abstract Background: β-hydroxybutyrate (BHB) can upregulate brain-derived neurotrophic factor (BDNF) in mice, but little is known about the associations between BHB and BDNF in humans. The primary aim here was to investigate whether ketosis (i.e., raised BHB levels), induced by a ketogenic supplement, influences serum levels of mature BDNF (mBDNF) and its precursor proBDNF in healthy older adults. A secondary aim was to determine the intra-individual stability (repeatability) of those biomarkers, measured as intra-class correlation coefficients (ICC).Method: Three of the arms in a 6-arm randomized cross-over trial were used for the current sub-study. Fifteen healthy volunteers, 65–75 y, 53% women, were tested once a week. Test oils, mixed in coffee and cream, were ingested after a 12-h fast. Labeled by their level of ketosis, the arms provided: sunflower oil (lowK); coconut oil (midK); caprylic acid + coconut oil (highK). Repeated blood samples were collected for 4 h after ingestion. Serum BDNF levels were analyzed for changes from baseline to 1, 2 and 4 h to compare the arms. Individual associations between BHB and BDNF were analyzed cross-sectionally and for a delayed response (changes in BHB 0–2 h to changes in BDNF at 0–4 h). ICC estimates were calculated from baseline levels from the three study days.Results: proBDNF increased more in highK vs. lowK between 0 and 4 h (z-score: β = 0.25, 95% CI 0.07–0.44; p = 0.007). Individual change in BHB 0–2 h, predicted change in proBDNF 0–4 h, (β = 0.40, CI 0.12–0.67; p = 0.006). Change in mBDNF was lower in highK vs. lowK at 0–2 h (β = −0.88, CI −1.37 to −0.40; p < 0.001) and cumulatively 0–4 h (β = −1.01, CI −1.75 to −0.27; p = 0.01), but this could not be predicted by BHB levels. ICC was 0.96 (95% CI 0.92–0.99) for proBDNF, and 0.72 (CI 0.47–0.89) for mBDNF.Conclusions: The findings support a link between changes in peripheral BHB and proBDNF in healthy older adults. For mBDNF, changes differed between arms but independent to BHB levels. Replication is warranted due to the small sample. Excellent repeatability encourages future investigations on proBDNF as a predictor of brain health.Clinical Trial Registration: ClinicalTrials.gov, NCT03904433.
32.	Pekkala, Timo, et al. (author) Association of Peripheral Insulin Resistance and Other Markers of Type 2 Diabetes Mellitus with Brain Amyloid Deposition in Healthy Individuals at Risk of Dementia 2020 In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 76:4, s. 1243-1248 Journal article (peer-reviewed)abstract We explored the association of type 2 diabetes related blood markers with brain amyloid accumulation on PiB-PET scans in 41 participants from the FINGER PET sub-study. We built logistic regression models for brain amyloid status with12 plasma markers of glucose and lipid metabolism, controlled for diabetes and APOE ɛ4 carrier status. Lower levels of insulin, insulin resistance index (HOMA-IR), C-peptide, and plasminogen activator (PAI-1) were associated with amyloid positive status, although the results were not significant after adjusting for multiple testing. None of the models found evidence for associations between amyloid status and fasting glucose or HbA1c.
33.	Pentikainen, Heikki, et al. (author) Cardiorespiratory Fitness and Cognition : Longitudinal Associations in the FINGER Study 2019 In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 68:3, s. 961-968 Journal article (peer-reviewed)abstract Background: Previous studies have found positive associations between cardiorespiratory fitness (CRF) and cognitive performance in older people but data are inconsistent and have methodological limitations. Objective: Our aimwas to study the longitudinal associations of CRF with executive functions, processing speed and memory as well as with the overall cognitive function in older people at risk for cognitive impairment. Methods: Participants (n = 421), mean age 69.0, were a sub-sample of The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER). To be eligible, individuals were required to be 60-77 years old with a CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age. CRF was assessed as peak oxygen uptake (VO2peak, L/min) measured directly in a symptom-limited maximal exercise test on cycle ergometer at baseline and at 24 months. Cognitive performance was assessed using an extensive neuropsychological test battery (NTB) at baseline and at 24 months. NTB data were standardized to Z scores, and analyzed with the linear mixed model. Results: Over two years, VO2peak was associated with NTB total score (beta = 0.12, p = 0.01), executive functions (beta = 0.16, p = 0.01), and processing speed (beta = 0.25, p < 0.001), but not with memory (beta = 0.11, p = 0.12). Conclusion: Over two years follow-up, CRF was associated with executive functions and processing speed, and was related also to the overall cognitive function.
34.	Pentikäinen, Heikki, et al. (author) Cardiorespiratory fitness and brain volumes in men and women in the FINGER study 2017 In: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 46:2, s. 310-314 Journal article (peer-reviewed)abstract Background: high cardiorespiratory fitness (CRF) is associated with larger brain volumes but data on sex differences in the association of CRF with brain volumes are scarce. We investigated whether the association of CRF with total grey matter (GM) and white matter volumes as well as medial temporal lobe and striatum volumes is different between men and women at increased risk for Alzheimer's disease (AD). Methods: we used baseline data from The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in which the inclusion criteria were set to select individuals with cognitive performance at the mean level or slightly lower than expected for age according to Finnish population norms. Our sub-study included 39 randomly selected men and 29 women aged 61-75 years. CRF was assessed as peak oxygen consumption (VO2peak) measured in a maximal exercise test on cycle ergometer. Brain structural imaging was performed using a 1.5-T scanner. Results: in men, VO2peak was associated with cortical GM volume (beta = 0.56, P = 0.001) and total GM volume (beta = 0.54, P = 0.001). In women, no associations were found between VO2peak and brain volumes. VO2peak accounted for 23% and 1% of total variance of cortical GM volume as well as 25% and 4% of total variance of total GM volume in men and women, respectively. Conclusion: CRF is associated with cortical GM and total GM volumes in elderly men at increased risk for AD, but not in women.
35.	Ren, Yifei, et al. (author) Multimorbidity, cognitive phenotypes, and Alzheimer's disease plasma biomarkers in older adults : A population-based study 2024 In: Alzheimer's & Dementia. - 1552-5260 .- 1552-5279. ; 20:3, s. 1550-1561 Journal article (peer-reviewed)abstract INTRODUCTION: To examine the burden and clusters of multimorbidity in association with mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD)-related plasma biomarkers among older adults.METHODS: This population-based study included 5432 participants (age ≥60 years); of these, plasma amyloid beta (Aβ), total tau, and neurofilament light chain (NfL) were measured in a subsample (n = 1412). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We diagnosed dementia and MCI following international criteria. Data were analyzed using logistic and linear regression models.RESULTS: The number of chronic diseases was associated with dementia (multivariable-adjusted odds ratio = 1.22; 95% confidence interval [CI] = 1.11 to 1.33), AD (1.13; 1.01 to 1.26), vascular dementia (VaD) (1.44; 1.25 to 1.64), and non-amnestic MCI (1.25; 1.13 to 1.37). Metabolic cluster was associated with VaD and non-amnestic MCI, whereas degenerative ocular cluster was associated with AD (p < 0.05). The number of chronic diseases was associated with increased plasma Aβ and NfL (p < 0.05).DISCUSSION: Multimorbidity burden and clusters are differentially associated with subtypes of dementia and MCI and AD-related plasma biomarkers in older adults.
36.	Richard, Edo, et al. (author) Healthy Ageing Through Internet Counselling in the Elderly : the HATICE randomised controlled trial for the prevention of cardiovascular disease and cognitive impairment 2016 In: BMJ Open. - : BMJ. - 2044-6055. ; 6:6 Journal article (peer-reviewed)abstract Introduction Cardiovascular disease and dementia share a number of risk factors including hypertension, hypercholesterolaemia, smoking, obesity, diabetes and physical inactivity. The rise of eHealth has led to increasing opportunities for large-scale delivery of prevention programmes encouraging self-management. The aim of this study is to investigate whether a multidomain intervention to optimise self-management of cardiovascular risk factors in older individuals, delivered through an coach-supported interactive internet platform, can improve the cardiovascular risk profile and reduce the risk of cardiovascular disease and cognitive decline. Methods and analysis HATICE is a multinational, multicentre, prospective, randomised, open-label blinded end point (PROBE) trial with 18months intervention. Recruitment of 2600 older people (65years) at increased risk of cardiovascular disease will take place in the Netherlands, Finland and France. Participants randomised to the intervention condition will have access to an interactive internet platform, stimulating self-management of vascular risk factors, with remote support by a coach. Participants in the control group will have access to a static internet platform with basic health information. The primary outcome is a composite score based on the average z-score of the difference between baseline and 18months follow-up values of systolic blood pressure, low-density-lipoprotein and body mass index. Main secondary outcomes include the effect on the individual components of the primary outcome, the effect on lifestyle-related risk factors, incident cardiovascular disease, mortality, cognitive functioning, mood and cost-effectiveness.
37.	Richard, Edo, et al. (author) Healthy ageing through internet counselling in the elderly (HATICE) : a multinational, randomised controlled trial 2019 In: The Lancet Digital Health. - 2589-7500. ; 1:8, s. e424-e434 Journal article (peer-reviewed)abstract Background Although web-based interventions have been promoted for cardiovascular risk management over the past decade, there is limited evidence for effectiveness of these interventions in people older than 65 years. The healthy ageing through internet counselling in the elderly (HATICE) trial aimed to determine whether a coach-supported internet intervention for self-management can reduce cardiovascular risk in community-dwelling older people.Methods This prospective open-label, blinded endpoint clinical trial among people age 65 years or over at increased risk of cardiovascular disease randomly assigned participants in the Netherlands, Finland, and France to an interactive internet intervention stimulating coach-supported self-management or a control platform. Primary outcome was the difference from baseline to 18 months on a standardised composite score (Z score) of systolic blood pressure, LDL cholesterol, and body-mass index (BMI). Secondary outcomes included individual risk factors and cardiovascular endpoints. This trial is registered with the ISRCTN registry, 48151589, and is closed to accrual.Findings Among 2724 participants, complete primary outcome data were available for 2398 (88%). After 18 months, the primary outcome improved in the intervention group versus the control group (0.09 vs 0.04, respectively; mean difference -0.05, 95% CI -0.08 to -0.01; p=0.008). For individual components of the primary outcome, mean differences (intervention vs control) were systolic blood pressure -1.79 mm Hg versus -0.67 mm Hg (-1.12, -2.51 to 0.27); BMI -0.23 kg/m(2) versus -0.08 kg/m(2) (-0.15, -0.28 to -0.01); and LDL -0.12 mmol/L versus -0.07 mmol/L (-0.05, -0.11 to 0.01). Cardiovascular disease occurred in 30 (2.2%) of 1382 patients in the intervention versus 32 (2.4%) of 1333 patients in the control group (hazard ratio 0.86, 95% CI 0.52 to 1.43).Interpretation Coach-supported self-management of cardiovascular risk factors using an interactive internet intervention is feasible in an older population, and leads to a modest improvement of cardiovascular risk profile. When implemented on a large scale this could potentially reduce the burden of cardiovascular disease.
38.	Rosenberg, Anna, et al. (author) Multidomain lifestyle intervention benefits a large elderly population at risk for cognitive decline and dementia regardless of baseline characteristics : The FINGER trial 2018 In: Alzheimer's & Dementia. - New York : Elsevier. - 1552-5260 .- 1552-5279. ; 14:3, s. 263-270 Journal article (peer-reviewed)abstract 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.
39.	Rusanen, Minna, et al. (author) Chronic Obstructive Pulmonary Disease and Asthma and the Risk of Mild Cognitive Impairment and Dementia : A Population Based CAIDE Study 2013 In: CURRENT ALZHEIMER RESEARCH. - : Bentham Science Publishers Ltd.. - 1567-2050 .- 1875-5828. ; 10:5, s. 549-555 Journal article (peer-reviewed)abstract Background: Previous research indicates that persons with chronic obstructive pulmonary disease (COPD) and asthma may have more cognitive impairment compared to persons without these diseases. However, there are no previous studies regarding long-term effects of these diseases on the risk of clinically diagnosed mild cognitive impairment (MCI) and dementia. We examined the association between midlife and late-life self-reported COPD and asthma and the lifelong risk of cognitive impairment (MCI/dementia) in a population-based study with a follow-up of over 25 years. Methods: Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study includes 2000 participants who were randomly selected from four separate, population-based samples originally studied in midlife (1972, 1977, 1982 or 1988). Re-examinations were carried out in 1998 and 2005-8 (N=1511, 75.6 %) during which 172 persons were diagnosed with MCI and 117 with dementia. Results: Midlife COPD (HR 1.85, 95% CI 1.05 - 3.28), asthma (HR 1.88, 95% CI 0.77 - 4.63) and both pulmonary diseases combined (HR 1.94, 95% CI 1.16 - 3.27) increased the later risk of cognitive impairment even after full adjustments. However, pulmonary diseases diagnosed later in life seemed to be inversely related to cognitive impairment (fully adjusted model for both pulmonary diseases combined HR 0.42, 95% CI 0.19 - 0.93). Conclusions: In this population-based study, with more than 25 years of follow-up, midlife COPD and asthma were associated with an almost two-fold risk of MCI and dementia later in life. Pulmonary diseases diagnosed later in life seemed to have an inverse relationship with cognitive impairment probably reflecting survival bias.
40.	Rusanen, Minna, et al. (author) Heart diseases and long-term risk of dementia and Alzheimer's disease : a population-based CAIDE study. 2014 In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 42:1, s. 183-91 Journal article (peer-reviewed)abstract BACKGROUND: Many cardiovascular risk factors are shown to increase the risk of dementia and Alzheimer's disease (AD), but the impact of heart disease on later development of dementia is still unclear.OBJECTIVE: The aim of the study was to investigate the long-term risk of dementia and Alzheimer's disease (AD) related to midlife and late-life atrial fibrillation (AF), heart failure (HF), and coronary artery disease (CAD) in a population-based study with a follow-up of over 25 years.METHODS: Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study includes 2000 participants who were randomly selected from four separate, population-based samples originally studied in midlife (1972, 1977, 1982, or 1987). Re-examinations were carried out in 1998 and 2005-2008. Altogether 1,510 (75.5%) persons participated in at least one re-examination, and 127 (8.4%) persons were diagnosed with dementia (of which 102 had AD).RESULTS: AF in late-life was an independent risk factor for dementia (HR 2.61, 95% CI 1.05-6.47; p = 0.039) and AD (HR 2.54, 95% CI 1.04-6.16; p = 0.040) in the fully adjusted analyses. The association was even stronger among the apolipoprotein E (APOE) ε4 non-carriers. Late-life HF, but not CAD, tended to increase the risks as well. Heart diseases diagnosed at midlife did not increase the risk of later dementia and AD.CONCLUSION: Late-life heart diseases increase the subsequent risk of dementia and AD. Prevention and effective treatment of heart diseases may be important also from the perspective of brain health and cognitive functioning.
41.	Rydstrom, Anders, et al. (author) The role of brain integrity in the association between occupational complexity and cognitive performance in subjects with increased risk of dementia 2023 In: Gerontology. - : S. Karger. - 0304-324X .- 1423-0003. ; 69:8, s. 972-985 Journal article (peer-reviewed)abstract Introduction: Mechanisms underlying the positive association between occupational mental demands and late-life cognition are poorly understood. The objective of this study was to assess whether the association between occupational complexity and cognition is related to and moderated by brain integrity in individuals at-risk for dementia. Brain integrity was appraised throughout structural measures (Magnetic Resonance Imaging, MRI) and amyloid accumulation (Pittsburgh Compound B (PiB)-positron emission tomography, PiB-PET).Methods: Participants from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) neuroimaging sample -MRI (N=126), PiB-PET (N=41)- were included in a post-hoc cross-sectional analysis. Neuroimaging parameters comprised the Alzheimer ' s Disease signature cortical thickness (ADS, Freesurfer 5.3), medial temporal atrophy (MTA), and amyloid accumulation (PiB-PET). Cognition was assessed using the Neuropsychological Test Battery. Occupational complexity with data, people, and substantive complexity were classified through the Dictionary of Occupational Titles. Linear regression models included cognition as dependent variable, occupational complexity, measures of brain integrity, and their interaction terms as predictors.Results: Occupational complexity with data and substantive complexity were associated with better cognition (overall cognition, executive function) when adjusting for ADS and MTA (independent association). Significant interaction effects between occupational complexity and brain integrity were also found, indicating that, for some indicators of brain integrity and cognition (e.g., overall cognition, processing speed), the positive association between occupational complexity and cognition occurred only among persons with higher brain integrity (moderated association).Conclusion: Among individuals at-risk for dementia, occupational complexity does not seem to contribute towards resilience against neuropathology. These exploratory findings require validation in larger populations.
42.	Rydström, Anders, et al. (author) Occupational complexity and cognition in the FINGER multidomain intervention trial 2022 In: Alzheimer's & Dementia. - : John Wiley & Sons. - 1552-5260 .- 1552-5279. ; 18:12, s. 2438-2447 Journal article (peer-reviewed)abstract Introduction Lifetime exposure to occupational complexity is linked to late-life cognition, and may affect benefits of preventive interventions. Methods In the 2-year multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), we investigated, through post hoc analyses (N = 1026), the association of occupational complexity with cognition. Occupational complexity with data, people, and substantive complexity were classified through the Dictionary of Occupational Titles. Results Higher levels of occupational complexity were associated with better baseline cognition. Measures of occupational complexity had no association with intervention effects on cognition, except for occupational complexity with data, which was associated with the degree of intervention-related gains for executive function. Discussion In older adults at increased risk for dementia, higher occupational complexity is associated with better cognition. The cognitive benefit of the FINGER intervention did not vary significantly among participants with different levels of occupational complexity. These exploratory findings require further testing in larger studies.
43.	Röhr, Susanne, et al. (author) Multidomain interventions for risk reduction and prevention of cognitive decline and dementia : current developments 2022 In: Current Opinion in Psychiatry. - 0951-7367 .- 1473-6578. ; 35:4, s. 285-292 Research review (peer-reviewed)abstract Purpose of review The potential for dementia prevention is deemed substantial if modifiable risk factors were addressed. First large-scale multidomain lifestyle interventions aiming at reducing risk of cognitive decline and dementia have yielded mixed but promising evidence.Recent findings Despite the impact of the COVID-19 pandemic on trials conduction, causing interruptions and delays, the research landscape on multidomain interventions is growing rapidly. The successful Finish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) has led to an adaptation of the FINGER model in trials underway or being planned in over 40 countries. Recent studies identified barriers and facilitators of and adherence to multidomain interventions, showed the suitability of dementia risk scores as surrogate outcomes, and suggested mechanisms. Multidomain interventions are increasingly conducted in the Global South, and study protocols are increasingly testing expanded FINGER models, for example, with pharmacological components, in digital/remote settings and co-designed personalized interventions.Summary Though results remain mixed, the many ongoing trials will provide more conclusive evidence within the next few years and help to optimize interventions. Continued international collaboration is pivotal to scale and accelerate the development and implementation of effective multidomain interventions as part of larger public health strategies to counteract the global dementia increase.
44.	Sindi, Shireen, et al. (author) Effects of a multidomain lifestyle intervention on telomere length : The FINGER trial 2018 In: International Journal of Behavioral Medicine. - : Springer. - 1070-5503 .- 1532-7558. ; 25, s. S153-S154 Journal article (peer-reviewed)
45.	Sindi, Shireen, et al. (author) Healthy Dietary Changes in Midlife Are Associated with Reduced Dementia Risk Later in Life 2018 In: Nutrients. - : MDPI AG. - 2072-6643. ; 10:11 Journal article (peer-reviewed)abstract Diet is an important modifiable lifestyle factor related to dementia risk. Yet, the role of midlife dietary changes is unclear. The goal is to investigate whether midlife healthy dietary changes are associated with late-life dementia risk. Data were collected within the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) population-based cohort study (n = 2000) (mean baseline age = 56 years). Participants returned for two late-life re-examinations (mean age = 70 and 78 years). Self-reported midlife diet was measured in a sub-sample (n = 341) (mean total follow-up = 16.8 years). Changes in specific dietary components (fats, vegetables, sugar, salt) were measured in midlife. Dementia diagnoses were ascertained with detailed examinations. Analyses adjusted for potential confounders. Total midlife healthy dietary changes (improving quality of fats, increasing vegetables, decreasing sugar and salt) were associated with a reduced risk of dementia (fully adjusted odds ratio (OR) 0.41, 95% confidence interval (CI) = 0.20-0.85). In contrast, when each factor was assessed individually, associations were not significant. This study is the first to show that beneficial midlife dietary changes are associated with a reduced dementia risk later in life. The results highlight the importance of targeting dietary patterns, where various food items may have synergistic effects.
46.	Solomon, Alina, et al. (author) Effect of the Apolipoprotein E Genotype on Cognitive Change During a Multidomain Lifestyle Intervention A Subgroup Analysis of a Randomized Clinical Trial 2018 In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 75:4, s. 462-470 Journal article (peer-reviewed)abstract IMPORTANCE The role of the apolipoprotein E (APOE) epsilon 4 allele as an effect modifier in lifestyle interventions to prevent cognitive impairment is still unclear. OBJECTIVE To examine whether the APOE epsilon 4 allele modifies the previously reported significant cognitive benefits of a multidomain lifestyle intervention (prespecified subgroup analysis). DESIGN, SETTING, AND PARTICIPANTS The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a randomized clinical trial in 6 centers across Finland (screening and randomization performed from September 7, 2009, through November 24, 2011; intervention duration, 2 years). Data analysis was performed from August 1, 2015, to March 31, 2016. The study population was at-risk older individuals from the general population. Inclusion criteria were age of 60 to 77 years; Cardiovascular Risk Factors, Aging, and Dementia risk score of at least 6 points; and cognition at a mean level or slightly lower than expected for age. Individuals with dementia or substantial cognitive impairment and conditions that prevented cooperation or safe engagement in the intervention were excluded. APOE genotype data were available for 1175 of the 1260 participants. INTERVENTIONS Participants were randomly assigned in a 1: 1 ratio to a multidomain intervention group (diet, exercise, cognitive training, and vascular risk management) or a control group (general health advice). Group allocation was not actively disclosed to participants, and outcome assessors were masked to group allocation. MAIN OUTCOMES AND MEASURES Primary outcome was change in cognition measured through a comprehensive neuropsychological test battery. Analysis was based on modified intention to treat (participants with at least 1 postbaseline assessment). RESULTS A total of 1109 participants (mean [SD] age, 69.3 [4.7] years; 514 [46.3%] female) were included in the analysis: 362 APOE epsilon 4 allele carriers (173 intervention and 189 control) and 747 noncarriers (380 intervention and 367 control). The APOE epsilon 4 carriers and noncarriers were not significantly different at baseline (except for serum cholesterol level). The difference between the intervention and control groups in annual neuropsychological test battery total score change was 0.037 (95% CI, 0.001 to 0.073) among carriers and 0.014 (95% CI, -0.011 to 0.039) among noncarriers. Intervention effect was not significantly different between carriers and noncarriers (0.023; 95% CI, -0.021 to 0.067). CONCLUSIONS AND RELEVANCE Healthy lifestyle changesmay be beneficial for cognition in older at-risk individuals even in the presence of APOE-related genetic susceptibility to dementia. Whether such benefits are more pronounced in APOE epsilon 4 carriers compared with noncarriers should be further investigated. The findings also emphasize the importance of early prevention strategies that target multiple modifiable risk factors simultaneously.
47.	Solomon, Alina, et al. (author) Validity dementia and Alzheimer's disease diagnoses in Finnish national registers 2014 In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 10:3, s. 303-309 Journal article (peer-reviewed)abstract 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.
48.	Thunborg, Charlotta, 1965-, et al. (author) Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer’s disease: the MIND-ADmini randomized controlled trial 2024 In: Alzheimer's Research & Therapy. - : Springer. - 1758-9193. ; 16:1 Journal article (peer-reviewed)abstract BackgroundThe Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer’s disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear.MethodsMIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60–85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale.ResultsDuring September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (βLifestyle×Time = 1.11, P = 0.038; βLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions.ConclusionsThe multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial.Trial registrationClinicalTrials.gov NCT03249688.
49.	Thunborg, Charlotta, 1965-, et al. (author) Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer’s disease: the MIND-ADmini randomized controlled trial 2024 In: Alzheimer's Research & Therapy. - : Springer Nature. - 1758-9193. ; 16 Journal article (peer-reviewed)abstract Background: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer’s disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear.Methods: MIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60–85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale.Results: During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (βLifestyle×Time = 1.11, P = 0.038; βLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions.Conclusions: The multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial.
50.	Tian, Na, et al. (author) Triglyceride-glucose index, Alzheimer's disease plasma biomarkers, and dementia in older adults : The MIND-China study 2023 In: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - 2352-8729. ; 15:2 Journal article (peer-reviewed)abstract Introduction: Population-based studies have rarely explored the associations of the triglyceride–glucose (TyG) index, a surrogate marker of insulin resistance, with dementia and plasma biomarkers for amyloid beta (Aβ) and neurodegeneration.Methods: This population-based study included 5199 participants (age ≥ 65 years); of these, plasma Aβ, total tau, and neurofilament light chain (NfL) were measured in 1287 persons. Dementia and subtypes were diagnosed following the international criteria. TyG index was calculated as ln(fasting triglyceride(mg/dL) × fasting glucose[mg/dL]/2). Data were analyzed using logistic and general linear regression models.Results: Dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were diagnosed in 301, 195, and 95 individuals, respectively. A high TyG index was significantly associated with increased likelihoods of dementia and AD; the significant association with dementia remained among participants without cardiovascular disease or diabetes. In the biomarker subsample, a high TyG index was correlated with elevated plasma Aβ, but not with total tau or NfL.Discussion: High TyG index is associated with dementia, possibly via Aβ pathology.

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Type of publication: journal article (51); research review (3); conference paper (1); doctoral thesis (1); book chapter (1)

Type of content: peer-reviewed (56); other academic/artistic (1)

Author/Editor: Ngandu, Tiia (57); Kivipelto, Miia (53); Soininen, Hilkka (40); Tuomilehto, Jaakko (23); Solomon, Alina (22); Laatikainen, Tiina (21); show more...; Lehtisalo, Jenni (19); Mangialasche, France ... (17); Strandberg, Timo (13); Sindi, Shireen (11); Peltonen, Markku (11); Coley, Nicola (9); Andrieu, Sandrine (9); Stigsdotter Neely, A ... (8); Kåreholt, Ingemar, 1 ... (7); Bäckman, Lars (7); Lindström, Jaana (7); Rosenberg, Anna (6); Qiu, Chengxuan (6); Jula, Antti (5); Guillemont, Juliette (5); Richard, Edo (5); Brayne, Carol (5); Wang, Yongxiang (5); Du, Yifeng (5); Akenine, Ulrika (4); Barbera, Mariagnese (4); Launer, Lenore J (4); Rauramaa, Rainer (4); Hou, Tingting (4); Stigsdotter-Neely, A ... (4); Wimo, Anders (3); Backman, Lars (3); Kåreholt, Ingemar (3); Winblad, Bengt (3); Nordin, Karin (3); Beishuizen, Cathrien ... (3); Thunborg, Charlotta, ... (3); Andersen, Pia (3); Jongstra, Susan (3); van Charante, Eric P ... (3); Lindstrom, Jaana (3); Hallikainen, Merja (3); Wang, Rui (3); Liu, Cuicui (3); Cong, Lin (3); Dong, Yi (3); Han, Xiaolei (3); Liu, Rui (3); Rydström, Anders (3); show less...

University: Karolinska Institutet (50); Stockholm University (46); Jönköping University (10); Umeå University (8); Karlstad University (8); Luleå University of Technology (3); show more...; University of Gävle (3); Linnaeus University (2); Uppsala University (1); Örebro University (1); The Swedish School of Sport and Health Sciences (1); show less...

Language: English (56); Swedish (1)

Research subject (UKÄ/SCB): Medical and Health Sciences (53); Social Sciences (5); Natural sciences (3)

Year

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