Genetic Liability to Cardiovascular Disease, Physical Activity, and Mortality: Findings from the Finnish Twin Cohort.

PURPOSE: We investigated whether longitudinally assessed physical activity (PA) and adherence specifically to World Health Organization PA guidelines mitigates or moderates mortality risk regardless of genetic liability to cardiovascular disease (CVD). We also estimated the causality of the PA-mortality association. METHODS: The study used the older Finnish Twin Cohort (FTC) with 4,897 participants aged 33-60 years (54.3% women). Genetic liability to coronary heart disease, systolic and diastolic blood pressure was estimated with polygenic risk scores (PRSs) derived from the Pan-UK Biobank (N ≈ 400,000; > 1,000,000 genetic variants). Leisure-time PA was assessed with validated and structured questionnaires three times during 1975-1990. The main effects of adherence to PA guidelines and the PRS × PA interactions were evaluated with Cox proportional hazards models against all-cause and CVD mortality. A co-twin control design with 180 monozygotic twin pairs discordant for meeting the guidelines was used for causal inference. RESULTS: During the 17.4-year (mean) follow-up (85,136 person-years), 1,195 participants died, with 389 CVD deaths. One standard deviation higher PRSs were associated with a 17%-24% higher CVD mortality risk but not with all-cause mortality except for the PRS for diastolic blood pressure. Adherence to PA guidelines did not show significant independent main effects or interactions with all-cause or CVD mortality. Twins whose activity levels adhered to PA guidelines over a 15-year period did not have statistically significantly reduced mortality risk compared to their less active identical twin sibling. The findings were similar among high, intermediate, and low genetic risk levels for CVD. CONCLUSIONS: The genetically informed FTC data could not confirm that adherence to PA guidelines either mitigates or moderates genetic CVD risk or causally reduces mortality risk.

Physical Activity and Cognitive Decline Among Older Adults: A Systematic Review and Meta-Analysis.

Importance: Physical activity is associated with the risk for cognitive decline, but much of the evidence in this domain comes from studies with short follow-ups, which is prone to reverse causation bias. Objective: To examine how length of follow-up, baseline age, physical activity amount, and study quality modify the longitudinal associations of physical activity with cognition. Data Sources: Observational studies of adults with a prospective follow-up of at least 1 year, a valid baseline cognitive measure or midlife cohort, and an estimate of the association of baseline physical activity and follow-up cognition were sought from PsycInfo, Scopus, CINAHL, Web of Science, SPORTDiscus, and PubMed, with the final search conducted on November 2, 2022. Study Selection: Two independent researchers screened titles with abstracts and full-text reports. Data Extraction and Synthesis: Two reviewers independently assessed study quality and extracted data. Pooled estimates of association were calculated with random-effects meta-analyses. An extensive set of moderators, funnel plots, and scatter plots of physical activity amount were examined. This study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: Pooled estimates of the associations between physical activity and global cognition, as well as specific cognitive domains, were examined. Results: A total of 104 studies with 341 471 participants were assessed. Analysis of binary outcomes included 45 studies with 102 452 individuals, analysis of follow-up global cognition included 14 studies with 41 045 individuals, and analysis of change in global cognition included 25 studies with 67 463 individuals. Physical activity was associated with a decreased incidence of cognitive impairment or decline after correction for funnel plot asymmetry (pooled risk ratio, 0.97; 95% CI, 0.97-0.99), but there was no significant association in follow-ups longer than 10 years. Physical activity was associated with follow-up global cognition (standardized regression coefficient, 0.03; 95% CI, 0.02-0.03) and change in global cognition (standardized regression coefficient, 0.01; 95% CI, 0.01 to 0.02) from trim-and-fill analyses, with no clear dose-response or moderation by follow-up length, baseline age, study quality or adjustment for baseline cognition. The specific cognitive domains associated with physical activity were episodic memory (standardized regression coefficient, 0.03; 95% CI, 0.02-0.04) and verbal fluency (standardized regression coefficient, 0.05; 95% CI, 0.03-0.08). Conclusions and Relevance: In this meta-analysis of the association of physical activity with cognitive decline, physical activity was associated with better late-life cognition, but the association was weak. However, even a weak association is important from a population health perspective.

The associations of long-term physical activity in adulthood with later biological ageing and all-cause mortality - a prospective twin study.

Objectives: The association between leisure-time physical activity (LTPA) and a lower risk of mortality is susceptible to bias from multiple sources. We investigated the potential of biological ageing to mediate the association between long-term LTPA and mortality and whether the methods used to account for reverse causality affect the interpretation of this association. Methods: Study participants were twins from the older Finnish Twin Cohort (n=22,750; 18-50 years at baseline). LTPA was assessed using questionnaires in 1975, 1981 and 1990. The mortality follow-up lasted until 2020 and biological ageing was assessed using epigenetic clocks in a subsample (n=1,153) with blood samples taken during the follow-up. Using latent profile analysis, we identified classes with distinct longitudinal LTPA patterns and studied differences in biological ageing between these classes. We employed survival models to examine differences in total, short-term and long-term all-cause mortality, and multilevel models for twin data to control for familial factors. Results: We identified four classes of long-term LTPA: sedentary, moderately active, active and highly active. Although biological ageing was accelerated in sedentary and highly active classes, after adjusting for other lifestyle-related factors, the associations mainly attenuated. Physically active classes had a maximum 7% lower risk of total mortality over the sedentary class, but this association was consistent only in the short term and could largely be accounted for by familial factors. LTPA exhibited less favourable associations when prevalent diseases were exclusion criteria rather than covariate. Conclusion: Being active may reflect a healthy phenotype instead of causally reducing mortality.

Mortality Associations With DNA Methylation-Based Biological Aging and Physical Functioning Measures Across a 20-Year Follow-up Period.

BACKGROUND: Measures of biological aging range from DNA methylation (DNAm)-based estimates to measures of physical abilities. The purpose of this study was to compare DNAm- and physical functioning-based measures of biological aging in predicting mortality. METHODS: We studied 63- to 76-year-old women (N = 395) from the Finnish Twin Study on Aging (FITSA). Participants' biological age (epigenetic clocks DNAm GrimAge and DunedinPACE) was estimated using blood DNAm data. Tests of physical functioning conducted under standardized laboratory conditions included the Timed Up and Go (TUG) test and 10-m walk test. Mortality hazard ratios were calculated per every 1 standard deviation (SD) increase in the predictor. Cox regression models were conducted for individuals and twin pairs, the latter controlling for underlying genetic effects. The models were adjusted for known lifestyle predictors of mortality. RESULTS: During the follow-up period (mean 17.0 years, range 0.2-20.3), 187 participants died. In both the individual-based and pairwise analyses, GrimAge and both functional biomarkers of aging were associated with mortality independent of family relatedness, chronological age, physical activity, body mass index, smoking, education, or chronic diseases. In a model including both the DNAm-based measures and functional biomarkers of aging, GrimAge and TUG remained predictive. CONCLUSIONS: The findings suggest that DNAm GrimAge and the TUG test are strong predictors of mortality independent of each others and genetic influences. DNAm-based measures and functional tests capture different aspects of the aging process and thus complement each other as measures of biological aging in predicting mortality.

Physical activity and health: Findings from Finnish monozygotic twin pairs discordant for physical activity.

Genetic and early environmental differences including early health habits associate with future health. To provide insight on the causal nature of these associations, monozygotic (MZ) twin pairs discordant for health habits provide an interesting natural experiment. Twin pairs discordant for leisure-time physical activity (LTPA) in early adult life is thus a powerful study design to investigate the associations between long-term LTPA and indicators of health and wellbeing. We have identified 17 LTPA discordant twin pairs from two Finnish twin cohorts and summarize key findings of these studies in this paper. The carefully characterized rare long-term LTPA discordant MZ twin pairs have participated in multi-dimensional clinical examinations. Key findings highlight that compared with less active twins in such MZ twin pairs, the twins with higher long-term LTPA have higher physical fitness, reduced body fat, reduced visceral fat, reduced liver fat, increased lumen diameters of conduit arteries to the lower limbs, increased bone mineral density in loaded bone areas, and an increased number of large high-density lipoprotein particles. The findings increase our understanding on the possible site-specific and system-level effects of long-term LTPA.

Physical activity as a protective factor for dementia and Alzheimer's disease: systematic review, meta-analysis and quality assessment of cohort and case-control studies.

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.

Maximal isometric strength indices are associated with the oxygen cost of walking and running in recreationally active men and women.

This study assessed the associations of maximal isometric strength and movement economy in 126 recreationally active men and women. Oxygen consumption was assessed through a graded treadmill test with 4-minute increments (4-12 km∙h-1). Maximal isometric leg extensor, leg flexor and handgrip strength were assessed by isometric dynamometry. Models of best fit for gross oxygen cost and gross caloric unit cost were observed across the majority of velocities when the leg extensor/flexor strength ratio and handgrip strength were combined (R2 = 0.207-0.525 and R2 = 0.152-0.475, respectively). Additionally, the oxygen cost differed statistically for the majority of velocities when participants were split by the median of leg extensor strength (12.3-26.3 ml∙kg-1∙km-1, p < 0.05) and the average of all strength variables (13.9-30.3 ml∙kg-1∙km-1, p < 0.05). Our data underline the importance of maintaining maximal strength in order to perform activities with low to moderate oxygen demands.

Does the epigenetic clock GrimAge predict mortality independent of genetic influences: an 18 year follow-up study in older female twin pairs.

BACKGROUND: Epigenetic clocks are based on DNA methylation (DNAm). It has been suggested that these clocks are useable markers of biological aging and premature mortality. Because genetic factors explain variations in both epigenetic aging and mortality, this association could also be explained by shared genetic factors. We investigated the influence of genetic and lifestyle factors (smoking, alcohol consumption, physical activity, chronic diseases, body mass index) and education on the association of accelerated epigenetic aging with mortality using a longitudinal twin design. Utilizing a publicly available online tool, we calculated the epigenetic age using two epigenetic clocks, Horvath DNAmAge and DNAm GrimAge, in 413 Finnish twin sisters, aged 63-76 years, at the beginning of the 18-year mortality follow-up. Epigenetic age acceleration was calculated as the residuals from a linear regression model of epigenetic age estimated on chronological age (AAHorvath, AAGrimAge, respectively). Cox proportional hazard models were conducted for individuals and twin pairs. RESULTS: The results of the individual-based analyses showed an increased mortality hazard ratio (HR) of 1.31 (CI95: 1.13-1.53) per one standard deviation (SD) increase in AAGrimAge. The results indicated no significant associations of AAHorvath with mortality. Pairwise mortality analyses showed an HR of 1.50 (CI95: 1.02-2.20) per 1 SD increase in AAGrimAge. However, after adjusting for smoking, the HR attenuated substantially and was statistically non-significant (1.29; CI95: 0.84-1.99). Similarly, in multivariable adjusted models the HR (1.42-1.49) was non-significant. In AAHorvath, the non-significant HRs were lower among monozygotic pairs in comparison to dizygotic pairs, while in AAGrimAge there were no systematic differences by zygosity. Further, the pairwise analysis in quartiles showed that the increased within pair difference in AAGrimAge was associated with a higher all-cause mortality risk. CONCLUSIONS: In conclusion, the findings suggest that DNAm GrimAge is a strong predictor of mortality independent of genetic influences. Smoking, which is known to alter DNAm levels and is built into the DNAm GrimAge algorithm, attenuated the association between epigenetic aging and mortality risk.

Twin studies on the association of physical activity with cognitive and cerebral outcomes.

Regular physical activity (PA) offers positive effects on the human body. However, the effects of PA on cognition and in the brain are less clear. In this paper, we narratively review the relationship of PA with cognition and dementia, first from general perspective and then through genetically informed studies on the topic. Then we move on to imaging studies on exercise and brain anatomy first by presenting an overall picture of the topic and then discussing brain imaging studies addressing PA and brain structure in twins in more detailed way. Regarding PA and cognition or dementia, genetically informed studies are uncommon, even though the relationship between PA and cognitive ageing has been extensively studied. It is challenging to find twin pairs discordant for PA and dementia. Concerning brain imaging studies, among PA discordant young adult twin pairs, the more active co-twins showed larger gray matter volumes in striatal, prefrontal, and hippocampal regions and in electrophysiological studies automatic deviance-detection processes differed in brain regions involved with sensorimotor, visual and memory functions.

Motives for physical activity in older men and women: A twin study using accelerometer-measured physical activity.

Motives for physical activity may vary considerably by age, sex, and the level of physical activity. We aimed to examine motives for physical activity in older men and women with different physical activity levels as well as whether genetic and/or environmental factors explain those motives. Finnish twins (mean age 72.9 years, 262 full twin pairs) self-reported their motives for physical activity. Time spent on moderate-to-vigorous physical activity was monitored using a hip-worn accelerometer. Comparisons between the different physical activity groups of older twins (n = 764-791/motive dimension) were analyzed using the Wald test, and effect sizes were calculated as Cohen's d. Quantitative genetic modeling was used to estimate genetic and environmental contributions. For both sexes, the most frequently reported motives for physical activity were physical fitness, health maintenance, and psychological well-being. Conforming to others' expectations was more important for men than for women (P < .001, Cohen's d = 0.38), while appearance (P = .001 Cohen's d = -0.24) and psychological well-being (P = .02, Cohen's d = -0.17) were highlighted by women. Most of the motive dimensions differed significantly between the physically active and inactive individuals. It was estimated that 5%-42% of the variation in motives was contributed by genetic factors and 58%-95% by environmental factors. The result that environmental factors contribute in a great deal to motives indicates that interventions to motivate physically inactive older individuals to be physically active can be successful. However, personalized interventions are needed because sex and the level of physical activity were found to be associated with older individuals' motives for physical activity.

Polygenic Risk Scores and Physical Activity.

PURPOSE: Polygenic risk scores (PRS) summarize genome-wide genotype data into a single variable that produces an individual-level risk score for genetic liability. PRS has been used for prediction of chronic diseases and some risk factors. As PRS has been studied less for physical activity (PA), we constructed PRS for PA and studied how much variation in PA can be explained by this PRS in independent population samples. METHODS: We calculated PRS for self-reported and objectively measured PA using UK Biobank genome-wide association study summary statistics, and analyzed how much of the variation in self-reported (MET-hours per day) and measured (steps and moderate-to-vigorous PA minutes per day) PA could be accounted for by the PRS in the Finnish Twin Cohorts (FTC; N = 759-11,528) and the Northern Finland Birth Cohort 1966 (NFBC1966; N = 3263-4061). Objective measurement of PA was done with wrist-worn accelerometer in UK Biobank and NFBC1966 studies, and with hip-worn accelerometer in the FTC. RESULTS: The PRS accounted from 0.07% to 1.44% of the variation (R) in the self-reported and objectively measured PA volumes (P value range = 0.023 to <0.0001) in the FTC and NFBC1966. For both self-reported and objectively measured PA, individuals in the highest PRS deciles had significantly (11%-28%) higher PA volumes compared with the lowest PRS deciles (P value range = 0.017 to <0.0001). CONCLUSIONS: PA is a multifactorial phenotype, and the PRS constructed based on UK Biobank results accounted for statistically significant but overall small proportion of the variation in PA in the Finnish cohorts. Using identical methods to assess PA and including less common and rare variants in the construction of PRS may increase the proportion of PA explained by the PRS.

The Older Finnish Twin Cohort - 45 Years of Follow-up.

The older Finnish Twin Cohort (FTC) was established in 1974. The baseline survey was in 1975, with two follow-up health surveys in 1981 and 1990. The fourth wave of assessments was done in three parts, with a questionnaire study of twins born during 1945-1957 in 2011-2012, while older twins were interviewed and screened for dementia in two time periods, between 1999 and 2007 for twins born before 1938 and between 2013 and 2017 for twins born in 1938-1944. The content of these wave 4 assessments is described and some initial results are described. In addition, we have invited twin-pairs, based on response to the cohortwide surveys, to participate in detailed in-person studies; these are described briefly together with key results. We also review other projects based on the older FTC and provide information on the biobanking of biosamples and related phenotypes.

Chronic diseases and objectively monitored physical activity profile among aged individuals - a cross-sectional twin cohort study.

INTRODUCTION: High physical activity (PA) at old age indicates good functional capacity enabling independent living. We investigated how different disease conditions are associated with measured PA indicators in old women and men, and whether they recognize this association. MATERIALS AND METHODS: This cross-sectional twin cohort study in Finland comprised 779 individuals (276 complete twin pairs, including 117 monozygotic pairs), who participated in hip-worn accelerometer monitoring of PA and responded to questions on diseases and mobility limitations at mean age of 73 (range 71-75). RESULTS: Of the participants, 23.2% reported having a disease restricting mobility. With sex and age in the regression model, the reported disease restricting mobility explained 11.8% of the variation in moderate-to-vigorous PA (MVPA) and 10.4% of the variation in daily steps. Adding stepwise other self-reported diseases and body mass index to the model increased the explanatory power for MVPA up to 18.5% and 25.5%, and for daily steps up to 16.0% and 20.7%, respectively. In the co-twin control analysis the PA differences were smaller in disease-discordant monozygotic than dizygotic pairs. CONCLUSIONS: Chronic disease conditions are associated with low PA, which individuals may not always recognize. Shared genetic factors may explain part of the associations. Key messages Among community-dwelling older men and women one-fourth of the variation in objectively measured moderate-to-vigorous physical activity is accounted for by age, sex, body mass index and self-reported diseases. Occurrence of chronic diseases is associated with low physical activity and individuals do not always recognize this. Healthcare professionals should pay attention to the low physical activity and mobility of individuals with chronic disease conditions before these result in limitations in independent living.

Self-reported Fitness and Objectively Measured Physical Activity Profile Among Older Adults: A Twin Study.

BACKGROUND: Maintaining good fitness and good level of physical activity are important factors for maintaining physical independence later in life. The aim was to investigate the relationship between self-reported fitness and objectively measured physical activity and sedentary behavior in the elderly. METHODS: Same-sex twin pairs born 1940-1944 in Finland were invited to the study. Altogether 787 individuals (mean age 72.9 years), of whom 404 were female, used a hip-worn triaxial accelerometer for at least 4 days and answered a question on perceived fitness. First, individual differences were studied between four fitness categories. Second, pairwise differences were examined among twin pairs discordant for fitness. RESULTS: Self-reported fitness explained moderately the variation in objectively measured physical activity parameters: R2 for daily steps 26%, for daily mean metabolic equivalent 31%, for daily moderate-to-vigorous activity time 31%, and lower for sedentary behavior time 14% (all p < .001). Better self-reported fitness was associated with more steps taken on average (8,558 daily steps [very good fitness] vs 2,797 steps [poor fitness], p < .001) and with a higher amount of moderate-to-vigorous activity (61 min vs 12 min p < .001, respectively) in the adjusted multivariable model. Among 156 twin pairs discordant for self-reported fitness, co-twins with better fitness took more steps, did more moderate-to-vigorous activity, and had less sedentary behavior (all, p < .05) compared to their less fit co-twins; however, difference was smaller among monozygotic than dizygotic pairs. CONCLUSION: One simple question on self-reported fitness is associated with daily activity profile among community-dwelling older people. However, genetic factors modulate this association to some extent.

Objectively measured physical activity profile and cognition in Finnish elderly twins.

INTRODUCTION: We studied whether objectively measured physical activity (PA) and sedentary behavior (SB) are associated with cognition in Finnish elderly twins. METHODS: This cross-sectional study comprised twins born in Finland from 1940 to 1944 in the Older Finnish Twin Cohort (mean age, 72.9 years; 726 persons). From 2014 to 2016, cognition was assessed with a validated telephonic interview, whereas PA was measured with a waist-worn accelerometer. RESULTS: In between-family models, SB and light physical activity had significant linear associations with cognition after adjusting for age, sex, wearing time, education level, body mass index, and living condition (SB: ß-estimate, -0.21 [95% confidence intervals, -0.42 to -0.003]; light physical activity: ß-estimate, 0.30 [95% confidence intervals, 0.02-0.58]). In within-family models, there were no significant linear associations between objectively measured PA and cognition. DISCUSSION: Objectively measured light physical activity and SB are associated with cognition in Finnish twins in their seventies, but the associations were attributable to genetic and environmental selection.

Long-term leisure-time physical activity and other health habits as predictors of objectively monitored late-life physical activity - A 40-year twin study.

Moderate-to-vigorous physical activity (MVPA) in old age is an important indicator of good health and functional capacity enabling independent living. In our prospective twin cohort study with 616 individuals we investigated whether long-term physical activity assessed three times, in 1975, 1982 and 1990 (mean age 48 years in 1990), and other self-reported health habits predict objectively measured MVPA measured with a hip-worn triaxial accelerometer (at least 10 hours per day for at least 4 days) 25 years later (mean age of 73 years). Low leisure-time physical activity at younger age, higher relative weight, smoking, low socioeconomic status, and health problems predicted low MVPA in old age in individual-based analyses (altogether explaining 20.3% of the variation in MVPA). However, quantitative trait modeling indicated that shared genetic factors explained 82% of the correlation between baseline and follow-up physical activity. Pairwise analyses within monozygotic twin pairs showed that only baseline smoking was a statistically significant predictor of later-life MVPA. The results imply that younger-age physical activity is associated with later-life MVPA, but shared genetic factors underlies this association. Of the other predictors mid-life smoking predicted less physical activity at older age independent of genetic factors.

Leisure-time physical inactivity and association with body mass index: a Finnish Twin Study with a 35-year follow-up.

Background: We investigated the stability and change of leisure-time physical inactivity in adult men and women during a 35-year follow-up. We also analysed the impact of long-term physical inactivity on the development of body mass index (BMI). Methods: : In this population-based cohort study, 5254 Finnish twin individuals (59% women) participated in four surveys in 1975, 1981, 1990 and 2011. Mean age at baseline was 23.9 years. Individual long-term leisure-time physical activity (LTPA) was categorized into seven classes varying from 'persistently inactive' to 'persistently active'. We used the multivariate multilevel mixed-effects linear regression model and paired-sample t-test in the analyses. Co-twin control design was used for examining within-pair associations. Results: : Of men 11%, and of women 8%, were persistently inactive. Among both sexes, the mean BMI slope trajectories were steeper among the persistently inactive and those who became inactive than among those who were persistently active. Overall, the inactive participants gained 1.4 kg/m 2 [95% confidence interval (CI) 1.2 to 1.7] more in weight than did the active participants from 1975 to 2011. Among twin pairs discordant for LTPA, the corresponding difference was 1.4 kg/m 2 (95% CI 0.83 to 2.0) in dizygotic pairs and 0.68 kg/m 2 (95% CI 0.05 to1.3) in monozygotic pairs. Conclusions: Over a 35-year time span from young adulthood, persistently inactive participants and those who had become inactive had greater weight increases than those who were persistently active. This association was also found in twin-pair analyses, although attenuated in monozygotic pairs. This may support the importance of LTPA in weight management, although further causal inference is required.

Midlife Physical Activity and Cognition Later in Life: A Prospective Twin Study.

BACKGROUND: Physical activity has been associated with a reduced risk of cognitive decline but the nature of this association remains obscure. OBJECTIVE: To study associations between midlife physical activity and cognition in old age for a prospective cohort of Finnish twins. METHODS: Physical activity in the Finnish Twin Cohort was assessed using questionnaire responses collected in 1975 and 1981. After a mean follow-up of 25.1 years, the subjects' (n = 3050; mean age 74.2; range 66-97) cognition was evaluated with a validated telephone interview. Both participation in vigorous physical activity, and the volume of physical activity, divided into quintiles, were used as predictors of cognitive impairment. Metrics collected by TELE were used to categorize participants as: cognitively impaired, suffering mild cognitive impairment, or cognitively healthy. RESULTS: Participation in vigorous physical activity compared to non-participation for both 1975 and 1981 was associated with a lower risk of cognitive impairment in individual-based analyses (fully adjusted OR 0.50, 95% CI 0.35-0.73). Pairwise analyses yielded similar but statistically non-significant associations. In terms of the volume of physical activity, the most active quintile of individuals (OR 0.69, 95% CI 0.46-1.04) had a reduced risk of cognitive decline compared with the most sedentary quintile in the fully adjusted model although no clear dose-response was found. CONCLUSION: Vigorous midlife physical activity was associated with less cognitive impairment but without a clear dose-response association between the volume of physical activity and cognition.

Melatonin and cortisol profiles in late midlife and their association with age-related changes in cognition.

Previous studies have reported an association between circadian disturbances and age-related cognitive impairment. The aim was to study the 24-hour profiles of melatonin and cortisol in relation to cognitive function in middle-aged male subjects. Fifty healthy middle-aged males born in 1953 were recruited from a population-based cohort based on previous cognitive assessments in young adulthood and late midlife. The sample included 24 cognitively high-functioning and 26 cognitively impaired participants. Saliva samples were collected every 4 hours over a 24-hour period and analyzed for cortisol and melatonin levels by immunoassay. All participants exhibited clear circadian rhythms of salivary melatonin and cortisol. Salivary melatonin concentrations had a nocturnal peak at approximately 4 am. The median nocturnal melatonin response at 4 am was significantly lower in the cognitively impaired group than in the high-functioning group (-4.6 pg/mL, 95% CI: -7.84, -1.36, P=0.006). The 24-hour mean melatonin concentration (high-functioning group: 4.80±0.70 pg/mL, vs cognitively impaired group: 4.81±0.76 pg/mL; P>0.05) (or the area under the curve, AUC) was not significantly different between the two groups. Cortisol levels were low during the night, and peaked at approximately 8 am. Median cortisol concentrations were similar at all times, as were the 24-hour mean cortisol concentrations and AUC. To the best of our knowledge, ours is the first study to assess circadian measures (ie, melatonin and cortisol) in healthy middle-aged men with different cognitive trajectories in midlife. We found evidence of altered circadian rhythms with a reduced nocturnal melatonin response at 4 am in men with cognitive impairment. The 24-hour concentration and AUC of melatonin and cortisol were similar in the cognitively high-functioning group and in the cognitively impaired.