Paula Iso-Markku

Objectives: In short follow-up studies, greater leisure-time physical activity (LTPA) has been associated with better cognition in old age, but more longitudinal studies are needed. Our aim was to identify long-term LTPA trajectories from midlife to late old age and examine whether these trajectories are associated with nonagenarians’ cognition. Methods: In total, 125 participants from the NONAGINTA—Memory and Health in Nonagenarians study were included. The participants responded to health surveys of the older Finnish Twin Cohort study, including LTPA at the mean ages of 45, 52, 59, and 91 years. Cognition was assessed at the mean age of 91 years (standard deviation 1.54) via telephone interview (global cognitive function, episodic memory, and semantic fluency). We identified LTPA trajectories with K-means clustering for longitudinal data, and we used generalized estimating equations models to investigate differences in cognition among the LTPA trajectories. Covariates included age, sex, and education. Results: We found 3 LTPA trajectories from midlife to nonagenarian age. The largest proportion of participants belonged to the Constant low trajectory (52%), characterized by a stable low level of physical activity throughout the follow-up. Two other trajectories were Starting low and increasing (25%) and Starting high and decreasing (23%). Nonagenarians’ cognitive measures did not differ among the LTPA trajectories. Discussion: Longitudinal physical activity behavior may not preserve cognitive function in those who survive to nonagenarian age but larger studies are warranted.

Based on short follow-up studies, greater leisure-time physical activity (LTPA) has been associated with better cognition in old age, but more longitudinal studies are needed. Our aim was to identify long-term LTPA trajectories from midlife to late old age and examine whether these trajectories are associated with nonagenarians’ cognition. In total, 125 participants from the NONAGINTA – Memory and Health in Nonagenarians study were included. The participants responded to health surveys of the older Finnish Twin Cohort study including LTPA at the mean ages of 45, 52, 59 and 91 years. Cognition was assessed at the mean age of 91 years (standard deviation 1.54) via telephone interview (global cognitive function, episodic memory, and semantic fluency). We identified LTPA trajectories with K-means clustering for longitudinal data and we used generalized estimating equations models to investigate differences in cognition among the LTPA trajectories. Covariates included age, sex, and education. We found three LTPA trajectories from midlife to nonagenarian age. The largest proportion of participants belonged to the Constant low trajectory (52%), characterized by a stable low level of physical activity throughout the follow-up. Two other trajectories were Starting low and increasing (25%) and Starting high and decreasing (23%). Cognitive measures at the mean age of 91 did not differ among the LTPA trajectories. To conclude, we found three different trajectories of LTPA from midlife to late old age within a period of 46 years. There were no significant differences in cognition by distinct LTPA trajectories when age, sex, and education were considered.

INTRODUCTION: Research on whether physical activity (PA) is associated with cognition is abundant but very few studies have examined the extent to which prior cognitive ability may account for PA participation in midlife.METHODS: Over 800 men self‐reported PA at average ages of 40 and 56. General cognitive ability (GCA) was assessed at an average age of 20. Specific cognitive abilities and GCA were assessed at average ages of 56 and 68. Relationships among age 20 GCA, midlife PA, and cognitive functioning in mid‐ and late‐life were examined with generalized estimating equations.RESULTS: Age 20 GCA was significantly associated with age 56 leisure metabolic equivalent of energy expenditure (MET)‐hours of PA (b = 0.14, p = 0.027). Age 56 leisure MET‐hours were positively (b = 0.04, p = 0.021) and age 40 vigorous leisure PA was inversely (b = −0.10, p = 0.012) associated with age 68 GCA (b = 0.04, p = 0.021).DISCUSSION: There are reciprocal associations between PA and cognitive functioning.Highlights: Young adult general cognitive ability (GCA) predicts midlife physical activity (PA). Midlife PA and cognition were not associated after adjusting for young adult GCA. Midlife PA is associated with later‐life cognition, adjusted for young adult GCA. Work‐related PA was inversely associated with later‐life cognitive functioning. The relationship between PA and cognitive function is bidirectional.

We examined the associations of midlife and old-age cardiovascular risk factors, education, and midlife dementia risk scores with cognition at 90+ years, using data from a population-based study with 48 years of follow-up. Participants were 96 individuals aged 90-97 from the older Finnish Twin Cohort study. Cardiovascular risk factors assessed via questionnaires in 1975, 1981, 1990, and 2021-2023 included blood pressure, body mass index, physical activity, and cholesterol, and self-reported educational attainment. The Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score and an educational-occupational attainment score were used as midlife dementia risk scores. Cognitive assessments included semantic fluency, and immediate and delayed recall from a 10-word list learning task. Regression analyses were conducted with dementia risk factors predicting cognition at 90+ years, adjusting for age, sex, education, follow-up time, and apolipoprotein E genotype (ε4-carrier vs non-carriers). Results showed that higher education and higher educational occupational score were associated with better cognitive performance in all cognitive measures. Those with high midlife blood pressure scored significantly higher in all cognitive tests than those with normal blood pressure. Conversely, those with high old-age blood pressure scored lower in semantic fluency but not in immediate or delayed recall. Other cardiovascular risk factors and the CAIDE score did not show consistent associations with cognition. Education appears to have a long-lasting protective effect in aging, whereas midlife and old-age cardiovascular risk factors showed no consistent associations with cognition in this older population.

Introduction A better understanding of the earliest stages of Alzheimer’s disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among THL Biobank donors according to TWINGEN study criteria. Methods and analysis A multi-centre study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behaviour and sleep. A subcohort is being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. The data collected in TWINGEN will be returned to THL Biobank from where it can later be requested for other biobank studies such as FinnGen that supported TWINGEN. Ethics and dissemination This recall study consists of FTC/THL Biobank/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83.

Extensive research links physical activity with better cognitive outcomes across the lifespan¹ and a decreased risk of dementia.^2,3 Many different specific cognitive domains have been suggested to be associated with physical activity, but the evidence is inconsistent.^4,5 Despite the optimism surrounding physical activity as a means to preserve or improve cognition, many recent high-quality interventional studies urge caution in claims linking cognitive benefits to physical activity,^6-8 and most existing evidence comes from observational studies with short follow-ups and no information on preceding levels of cognition.

Background: Most studies on the association between educational attainment and dementia have been conducted in unrelated individuals. Dementia‐discordant twin pairs can inform if the protective effect of education on dementia is evident when controlling for environmental and genetic effects. We investigated the association of educational attainment on all‐cause dementia, vascular dementia (VaD), and Alzheimer’s disease (AD) mortality in a population‐based sample of dizygotic (DZ) and monozygotic (MZ) pairs.Method: Participants were from a population‐based longitudinal older Finnish Twin Cohort study with baseline questionnaire in 1975 (N = 29,784; mean age = 36.9±14.9years). Education was coded as <12 years versus ≥12 years. Registry‐based cause of death data until year 2020 was based on the International Classification of Diseases. We ran individual‐level cox proportional hazard models with sex as a covariate and conditional within‐twin‐pair models for education predicting all‐cause dementia, VaD, and AD mortality. We report hazard ratios (HR) with 95% confidence intervals (CI).Result: In individual‐level analyses higher education was associated with a decreased risk of all‐cause dementia (HR = .935, 95%CI = .934;.936, p<.001) and VaD (HR = .638, 95%CI = .637;.640, p<.001), but with an increased risk of AD (HR = 1.276, 95%CI = 1.275;1.277, p<.001). In co‐twin analyses of discordant DZ and MZ twin pairs, co‐twins with higher education had lower – although non‐significant – risk of all‐cause dementia (N = 52, HR = .688, 95%CI = .319;1.481, p = .339) or AD (N = 36, HR = .600, 95%CI: .218;1.651, p = .323). Co‐twin analyses were not done for VaD due to small number of discordant pairs (N = 6).Conclusion: This large population‐based sample showed that higher education is related to lower risk of all‐cause dementia and VaD mortality. Unexpectedly, higher education was related to higher AD mortality, but discordant twin pair analyses were informative regarding this counterintuitive result. This case‐control design, controlling for genetic and environmental effects, did not support any causality from higher education to higher AD risk. Despite the large sample, twin pairs – especially MZ twins – discordant for dementia are rare. Meta‐ or mega‐analysis of multiple large twin studies is needed to clarify if secondary education is related to lower risk of dementia, VaD, and AD mortality when controlling for genetic effects.

Introduction: A better understanding of the earliest stages of Alzheimer’s disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among Finnish biobank donors according to TWINGEN study criteria. Methods and analysis: A multi-center study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behavior and sleep. A sub-cohort are being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. TWINGEN data will be transferred to Finnish Institute of Health and Welfare (THL) biobank and we aim to further to transfer it to the FinnGen study where it will be combined with health registry data for prediction of AD. Ethics and dissemination: This recall study consists of FTC/THL/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83. Article summary: Strengths and limitations of this study: A large sample of individuals is recruited from a representative biobank database Using health registry information, we exclude those with documented AD or other neurological or psychiatric diseases that can affect cognition. Pre-screening limits the sending of unnecessary invitations and saves costs Participants have up to 48 years of follow-up questionnaire and clinical data from the Finnish Twin Cohort study and these data can be combined with multifaceted Finnish health registry information. Previous genotype data is available in the biobank from all TWINGEN study participants. We assess the feasibility of remote cognitive testing and blood samples in large-scale screening of AD risk, translating to the requirements of intervention trials and clinical practice Limitations of the study are a lack of gold standard biomarkers (cerebrospinal fluid, positron emission tomography imaging) and neurological examinations

Objective Physical activity (PA) is associated with a decreased incidence of dementia, but much of the evidence comes from short follow-ups prone to reverse causation. This meta-analysis investigates the effect of study length on the association. Design A systematic review and meta-analysis. Pooled effect sizes, dose–response analysis and funnel plots were used to synthesise the results. Data sources CINAHL (last search 19 October 2021), PsycInfo, Scopus, PubMed, Web of Science (21 October 2021) and SPORTDiscus (26 October 2021). Eligibility criteria Studies of adults with a prospective follow-up of at least 1 year, a valid cognitive measure or cohort in mid-life at baseline and an estimate of the association between baseline PA and follow-up all-cause dementia, Alzheimer’s disease or vascular dementia were included (n=58). Results PA was associated with a decreased risk of all-cause dementia (pooled relative risk 0.80, 95% CI 0.77 to 0.84, n=257 983), Alzheimer’s disease (0.86, 95% CI 0.80 to 0.93, n=128 261) and vascular dementia (0.79, 95% CI 0.66 to 0.95, n=33 870), even in longer follow-ups (≥20 years) for all-cause dementia and Alzheimer’s disease. Neither baseline age, follow-up length nor study quality significantly moderated the associations. Dose–response meta-analyses revealed significant linear, spline and quadratic trends within estimates for all-cause dementia incidence, but only a significant spline trend for Alzheimer’s disease. Funnel plots showed possible publication bias for all-cause dementia and Alzheimer’s disease. Conclusion PA was associated with lower incidence of all-cause dementia and Alzheimer’s disease, even in longer follow-ups, supporting PA as a modifiable protective lifestyle factor, even after reducing the effects of reverse causation.

Higher educational attainment and less midlife cardiovascular risk factors are related to better old-age cognition. Whether education moderates the association between cardiovascular risk factors and late-life cognition is not known. We studied if higher education provides resilience against the deteriorative effects of higher middle-age body mass index (BMI) and a combination of midlife cardiovascular risk factors on old-age cognition. the study population is the older Finnish Twin Cohort (n = 4,051, mean age [standard deviation, SD] = 45.5 years [6.5]). Cardiovascular risk factors and education were studied at baseline with questionnaires in 1975, 1981 and/or 1990 (participation rates of 89, 84 and 77%, respectively). Cognition was evaluated with telephone interviews (participation rate 67%, mean age [SD] =73.4 [2.9] years, mean follow-up [SD] = 27.8 [6.0] years) in 1999–2017. We studied the main and interactive effects of education and BMI/dementia risk score on late-life cognition with linear regression analysis. The study design was formulated before the pre-defined analyses. years of education moderated the association between BMI with old-age cognition (among less educated persons, BMI-cognition association was stronger [B = −0.24 points per BMI unit, 95% CI −0.31, −0.18] than among more educated persons [B = −0.06 points per BMI unit, 95% CI −0.16, 0.03], P_interaction < 0.01). There was a similar moderating effect of education on dementia risk score consisting of cardiovascular risk factors (P < 0.001). our results support the cognitive reserve hypothesis. Those with higher education may tolerate the deteriorative effects of midlife cardiovascular risk factors on old-age cognition better than those with lower education.