Social Isolation and Loneliness in a Population Study of Cognitive Impairment: The MYHAT Study.

In this study, we examined associations of social isolation and loneliness with cognitive impairment among older adults from a Rust Belt region in Southwest Pennsylvania. We used data from the population-based Monongahela-Youghiogheny Healthy Aging Team (MYHAT) study. We found that (a) 11 items combined into two reliable composites of social isolation and loneliness; (b) unique to this study, providing unpaid help to others was an indicator of reduced social isolation; (c) social isolation and loneliness were positively associated with cognitive impairment; and (d) these associations were appreciably attenuated by general health and physical functional status and depressive symptoms, respectively. We concluded that social isolation and loneliness are differentially associated with older adults' cognitive health, and that their effects might operate through separate pathways. Approaches to address social isolation and loneliness should consider the community context and its implications for older adults' cognitive health.

Social connections and risk of incident mild cognitive impairment, dementia, and mortality in 13 longitudinal cohort studies of ageing.

INTRODUCTION: Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers. METHODS: We used individual participant data (N = 39271, Mage  = 70.67 (40-102), 58.86% female, Meducation  = 8.43 years, Mfollow-up  = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes. RESULTS: We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality. DISCUSSION: Different aspects of social connections - structure, function, and quality - are associated with benefits for healthy aging internationally. HIGHLIGHTS: Social connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI. Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia. Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality. Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality.

Dose-response relationship between late-life physical activity and incident dementia: A pooled analysis of 10 cohort studies of memory in an international consortium.

INTRODUCTION: Though consistent evidence suggests that physical activity may delay dementia onset, the duration and amount of activity required remains unclear. METHODS: We harmonized longitudinal data of 11,988 participants from 10 cohorts in eight countries to examine the dose-response relationship between late-life physical activity and incident dementia among older adults. RESULTS: Using no physical activity as a reference, dementia risk decreased with duration of physical activity up to 3.1 to 6.0 hours/week (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.67 to 1.15 for 0.1 to 3.0 hours/week; HR 0.68, 95% CI 0.52 to 0.89 for 3.1 to 6.0 hours/week), but plateaued with higher duration. For the amount of physical activity, a similar pattern of dose-response curve was observed, with an inflection point of 9.1 to 18.0 metabolic equivalent value (MET)-hours/week (HR 0.92, 95% CI 0.70 to 1.22 for 0.1 to 9.0 MET-hours/week; HR 0.70, 95% CI 0.53 to 0.93 for 9.1 to 18.0 MET-hours/week). DISCUSSION: This cross-national analysis suggests that performing 3.1 to 6.0 hours of physical activity and expending 9.1 to 18.0/MET-hours of energy per week may reduce dementia risk.

Psychosocial implications of early COVID-19 restrictions on older adults in a small-town region in Southwestern, Pennsylvania (USA).

OBJECTIVES: The restrictions put in place in 2020 to mitigate the spread of the coronavirus disease 2019 limited or eliminated social connections that are vital for psychosocial well-being. The objectives of this research were to examine the impact of early pandemic-related restrictions on feelings of loneliness, depression, and anxiety as well as social activity disruption and their concomitant associations in a sample of community-dwelling older adults residing in a small-town region in the USA. DESIGN AND SETTING: Cross-sectional data collected from an ongoing population-based cohort study in Southwestern, Pennsylvania. PARTICIPANTS: Analyses included 360 adults aged 65 years and older whose annual study assessment occurred during the first 120 days of pandemic-related restrictions. MEASUREMENTS: Self-reported feelings of loneliness, depression, and anxiety due to the pandemic-related restrictions were each measured using a single question. Depressive symptoms and anxiety were also assessed with the modified Center for Epidemiologic Studies-Depression and Generalized Anxiety Disorder-7 item tools. Disruption in a variety of common social activities was also assessed. RESULTS: Feeling lonely affected 36% of participants who were more likely to be female, not currently married, and living alone. Giving up in-person visits with family was associated with significantly higher odds of feeling lonely, and feeling lonely was associated with significantly higher odds of feelings of anxiety and depression. CONCLUSIONS: Loneliness is a serious outcome of pandemic-related restrictions among older adults, potentially linked to loss of connection with family, and may be associated with increased feelings of depression and anxiety.

Associations between social connections and cognition: a global collaborative individual participant data meta-analysis.

BACKGROUND: Poor social connections (eg, small networks, infrequent interactions, and loneliness) are modifiable risk factors for cognitive decline. Existing meta-analyses are limited by reporting aggregate responses, a focus on global cognition, and combining social measures into single constructs. We aimed to investigate the association between social connection markers and the rate of annual change in cognition (ie, global and domain-specific), as well as sex differences, using an individual participant data meta-analysis. METHODS: We harmonised data from 13 longitudinal cohort studies of ageing in North America, South America, Europe, Africa, Asia, and Australia. Studies were eligible for inclusion if they had baseline data for social connection markers and at least two waves of cognitive scores. Follow-up periods ranged from 0 years to 15 years across cohorts. We included participants with cognitive data for at least two waves and social connection data for at least one wave. We then identified and excluded people with dementia at baseline. Primary outcomes were annual rates of change in global cognition and cognitive domain scores over time until final follow-up within each cohort study analysed by use of an individual participant data meta-analysis. Linear mixed models within cohorts used baseline social connection markers as predictors of the primary outcomes. Effects were pooled in two stages using random-effects meta-analyses. We assessed the primary outcomes in the main (partially adjusted) and fully adjusted models. Partially adjusted models controlled for age, sex, and education; fully adjusted models additionally controlled for diabetes, hypertension, smoking, cardiovascular risk, and depression. FINDINGS: Of the 40 006 participants in the 13 cohort studies, we excluded 1392 people with dementia at baseline. 38 614 individual participants were included in our analyses. For the main models, being in a relationship or married predicted slower global cognitive decline (b=0·010, 95% CI 0·000-0·019) than did being single or never married; living with others predicted slower global cognitive (b=0·007, 0·002-0·012), memory (b=0·017, 0·006-0·028), and language (b=0·008, 0·000-0·015) decline than did living alone; and weekly interactions with family and friends (b=0·016, 0·006-0·026) and weekly community group engagement (b=0·030, 0·007-0·052) predicted slower memory decline than did no interactions and no engagement. Never feeling lonely predicted slower global cognitive (b=0·047, 95% CI 0·018-0·075) and executive function (b=0·047, 0·017-0·077) decline than did often feeling lonely. Degree of social support, having a confidante, and relationship satisfaction did not predict cognitive decline across global cognition or cognitive domains. Heterogeneity was low (I2=0·00-15·11%) for all but two of the significant findings (association between slower memory decline and living with others [I2=58·33%] and community group engagement, I2=37·54-72·19%), suggesting robust results across studies. INTERPRETATION: Good social connections (ie, living with others, weekly community group engagement, interacting weekly with family and friends, and never feeling lonely) are associated with slower cognitive decline. FUNDING: EU Joint Programme-Neurodegenerative Disease Research grant, funded by the National Health and Medical Research Council Australia, and the US National Institute on Aging of the US National Institutes of Health.

Education, Occupational Complexity, and Incident Dementia: A COSMIC Collaborative Cohort Study.

BACKGROUND: Education and occupational complexity are main sources of mental engagement during early life and adulthood respectively, but research findings are not conclusive regarding protective effects of these factors against late-life dementia. OBJECTIVE: This project aimed to examine the unique contributions of education and occupational complexity to incident dementia, and to assess the mediating effects of occupational complexity on the association between education and dementia across diverse cohorts. METHOD: We used data from 10,195 participants (median baseline age = 74.1, range = 58∼103), representing 9 international datasets from 6 countries over 4 continents. Using a coordinated analysis approach, the accelerated failure time model was applied to each dataset, followed by meta-analysis. In addition, causal mediation analyses were performed. RESULT: The meta-analytic results indicated that both education and occupational complexity were independently associated with increased dementia-free survival time, with 28%of the effect of education mediated by occupational complexity. There was evidence of threshold effects for education, with increased dementia-free survival time associated with 'high school completion' or 'above high school' compared to 'middle school completion or below'. CONCLUSION: Using datasets from a wide range of geographical regions, we found that both early life education and adulthood occupational complexity were independently predictive of dementia. Education and occupational experiences occur during early life and adulthood respectively, and dementia prevention efforts could thus be made at different stages of the life course.

Exercise and the Risk of Mild Cognitive Impairment: Does the Effect Depend on Vascular Factors?

INTRODUCTION: Although exercise is associated with a lower risk for mild cognitive impairment (MCI), it is unclear whether its protective effect depends on the presence or absence of vascular factors. METHODS: In an exploratory study of data from a population-based cohort, 1254 participants aged 65+ years were followed for 10 years for incident MCI. The main effect of baseline total minutes of exercise per week (0 vs. 1 to 149 vs. 150+), and its interaction with several vascular factors, on risk for incident MCI was examined using Cox proportional hazards regression models, adjusting for demographics. RESULTS: Compared with no exercise, 1 to 149 minutes [hazard ratio (HR)=0.90; 95% confidence interval (95% CI), 0.69-1.16] and 150 or more minutes per week (HR=0.84; 95% CI, 0.66-1.07) of exercise lowered risk for incident MCI in a dose-dependent manner. The majority of interactions were not statistically significant, but risk reduction effect sizes of <0.75 suggested that exercise may have stronger effects among those without high cholesterol, never smoking, and not currently consuming alcohol; also, those with arrhythmia, coronary artery disease, and heart failure. Overall, there was a pattern of exercise being associated with lower MCI risk among those without vascular factors. CONCLUSIONS: Spending more time engaging in exercise each week may offer protection against MCI in late life, with some variation among those with different vascular conditions and risk factors. Our findings may help target subgroups for exercise recommendations and interventions, and also generate hypotheses to test regarding underlying mechanisms.

Aging and Functional Health Literacy: A Population-based Study.

OBJECTIVES: To investigate functional health literacy and its associated factors among older adults drawn from a disadvantaged area. DESIGN: Cross-sectional epidemiologic study. SETTING: Population-based cohort randomly selected from the voter registration lists. PARTICIPANTS: Individuals aged 65+ (N=1066). MEASUREMENTS: The Short Test of Functional Health Literacy in Adults (S-TOFHLA); demographics; self-rated health; number of prescription drugs; modified Center for Epidemiologic Studies- Depression scale; Mini-Mental State Examination; Wechsler Test of Adult Reading; Clinical Dementia Rating; cognitive domain composite scores; independence in Instrumental Activities of Daily Living and medication management; health services utilization (emergency/urgent care visits and hospitalizations). RESULTS: Low (inadequate or marginal) S-TOFHLA scores were obtained by 7.04% of the sample. In unadjusted analyses, participants with low S-TOFHLA scores were significantly more likely than those with higher scores to be older, male, non-White, with lesser education and lower household income, to have lower scores on the Wechsler Test of Adult Reading, the Mini-Mental State Examination, and all cognitive domains; to be more dependent in Instrumental Activities of Daily Living and be taking more prescription drugs. In a multiple regression model including all covariates, only older age, male sex, and lower reading level were independently associated with inadequate or marginal S-TOFHLA scores. CONCLUSION: In a population-based sample of older adults, low functional health literacy was associated with age, sex, education, and reading ability. Basic functional health literacy is essential for understanding health information and instructions. Clinicians should formally or informally assess health literacy in their older patients to ensure effective communication and enhance health outcomes.

Education and the moderating roles of age, sex, ethnicity and apolipoprotein epsilon 4 on the risk of cognitive impairment.

BACKGROUND: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4). METHODS: Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School. RESULTS: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers. CONCLUSION: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.

Predictors of Dementia in the Oldest Old: A Novel Machine Learning Approach.

BACKGROUND: Incidence of dementia increases exponentially with age; little is known about its risk factors in the ninth and 10th decades of life. We identified predictors of dementia with onset after age 85 years in a longitudinal population-based cohort. METHODS: On the basis of annual assessments, incident cases of dementia were defined as those newly receiving Clinical Dementia Rating (CDR) ≥1. We used a machine learning method, Markov modeling with hybrid density-based and partition-based clustering, to identify variables associated with subsequent incident dementia. RESULTS: Of 1439 participants, 641 reached age 85 years during 10 years of follow-up and 45 of these became incident dementia cases. Using hybrid density-based and partition-based, among those aged 85+ years, probability of incident dementia was associated with worse self-rated health, more prescription drugs, subjective memory complaints, heart disease, cardiac arrhythmia, thyroid disease, arthritis, reported hypertension, higher systolic and diastolic blood pressure, and hearing impairment. In the subgroup aged 85 to 89 years, risk of dementia was also associated with depression symptoms, not currently smoking, and lacking confidantes. CONCLUSIONS: An atheoretical machine learning method revealed several factors associated with increased probability of dementia after age 85 years in a population-based cohort. If independently validated in other cohorts, these findings could help identify the oldest-old at the highest risk of dementia.

APOE ε4 and the Influence of Sex, Age, Vascular Risk Factors, and Ethnicity on Cognitive Decline.

We aimed to examine the relationship between Apolipoprotein E ε4 (APOE*4) carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow-up duration ranging between 1.2 and 10.7 years. Two-step individual participant data meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors, and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (ie, 62 years) and older (ie, 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.

Executive function predicts decline in mobility after a fall: The MYHAT study.

BACKGROUND: Evidence suggests that better cognitive functioning is associated with better mobility in older age. It is unknown whether older adults with better cognitive function are more resilient to mobility decline after a fall. METHODS: Participants from the Monongahela Youghiogheny Healthy Aging Team (MYHAT) study were followed annually for up to 9 years for incident falls. We examined one-year (mean 1.0 year, SD 0.1) change in mobility pre- to post-fall using the Timed Up and Go (TUG) in relation to pre-fall cognition (executive function, attention, memory, and visuospatial function) among incident fallers (n = 598, mean age 79.1, SD = 7.0). Linear regression models tested the association of cognition with change in TUG. Interaction terms were tested to explore if age, sex, body mass index, physical activity, depressive symptoms, or visual acuity modified the associations of cognition and mobility among fallers. The association between cognition and one-year change in TUG was also tested in a comparison sample of non-fallers (n = 442, mean age 76.3, SD = 7.2). RESULTS: Overall, mobility decline was greater in fallers compared to non-fallers. In fully-adjusted models, higher executive function, but not attention, memory, or visuospatial function, was associated with less decline in mobility among incident fallers. The effect was significantly stronger for those who were older, sedentary, and had lower body mass index. Higher scores in memory tests, but not in other domains, was associated with less mobility decline among non-fallers. CONCLUSIONS: Higher executive function may offer resilience to mobility decline after a fall, especially among older adults with other risk factors for mobility decline. Future studies should assess whether executive function may be a helpful risk index of fall-related physical functional decline in geriatric settings.

Blood Pressure and Memory: Novel Approaches to Modeling Nonlinear Effects in Longitudinal Studies.

BACKGROUND: Linear models cannot capture nonlinear associations when the relationships between cognition and risk factors vary across risk levels. We demonstrate a method of modelling nonlinear associations using the example of blood pressure (BP) and memory. METHODS: We measured memory and BP (in mm Hg) annually for 10 years in a population-based cohort (N=1982) aged 65+. We evaluated the relationship between BP and memory at the same time points using both linear mixed models and generalized additive mixed models with smoothing splines, adjusting for relevant covariates. RESULTS: Linear mixed models found no significant associations. Generalized additive mixed models detected different associations between BP and memory across baseline BP categories (normotensive, hypertensive, hypotensive). Among normotensives, systolic blood pressure (SBP)/diastolic blood pressure (DBP) around 140/80 was associated with the highest, while SBP/DBP around 110/60 was associated with the lowest, predicted memory scores. Among hypertensives, SBP/DBP around 130/85 was associated with the highest, while SBP/DBP around 150/65 was associated with the lowest, predicted memory scores. Among hypotensives, no significant association was found. Among both normotensives and hypertensives, a DBP >75 was associated with better memory. CONCLUSIONS: By modelling nonlinear associations, we showed that the relationship between BP and memory performance varied by baseline BP among normotensives and hypertensives.

Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study.

BACKGROUND: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. METHODS AND FINDINGS: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. CONCLUSIONS: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.

Mild Cognitive Impairment that Does Not Progress to Dementia: A Population-Based Study.

BACKGROUND/OBJECTIVE: In population studies, most individuals with mild cognitive impairment (MCI) do not progress to dementia in the near term, but rather remain stable MCI or revert to normal cognition. Here, we characterized MCI subgroups with different outcomes over 5 years. SETTING/PARTICIPANTS: A population-based cohort (N=1603). MEASUREMENTS: Clinical Dementia Rating (CDR); self-reported medical conditions, subjective cognitive concerns, self-rated health, depressive symptoms, blood pressure, medications, blood pressure, APOE genotype, cognitive domain composite scores. DESIGN: We compared 3 MCI subgroups who progressed to dementia (n=86), stabilized at MCI (n=384), or reverted to normal (n=252), to those who remained consistently normal (n=881), defining MCI as CDR = 0.5 and dementia as CDR≥1. Using multinomial logistic regression models adjusted for demographics, we examined the associations of each group with selected baseline characteristics. RESULTS: With the normal group for reference, worse subjective cognitive concerns, functional impairments, self-rated health, and depressive symptoms were associated with being in any MCI group. Taking more prescription medications was associated with being in the stable MCI and reverter groups; diabetes and low diastolic blood pressure were associated with stable MCI. The APOE4 genotype was associated with stable and progressive MCI; stroke was associated with progressive MCI. All MCI subgroups were likely to have lower mean composite scores in all cognitive domains and more operationally defined impairments in attention, language, and executive function; reverters were more likely to lack memory and visuospatial impairments. CONCLUSIONS: MCI subgroups with different 5-year outcomes had some distinct characteristics suggesting different underlying causes. The progressors, unlike the reverters, had a profile broadly typical of Alzheimer's disease; the stable MCIs had other, including vascular, morbidity. These data shed light on the heterogeneity of MCI in the population. J Am Geriatr Soc 67:232-238, 2019.

Declining Incident Dementia Rates Across Four Population-Based Birth Cohorts.

BACKGROUND: Incidence rates of dementia appear to be declining in high-income countries according to several large epidemiological studies. We aimed to describe declining incident dementia rates across successive birth cohorts in a U.S. population-based sample and to explore the influences of sex and education on these trends. METHODS: We pooled data from two community-sampled prospective cohort studies with similar study aims and contiguous sampling regions: the Monongahela Valley Independent Elders Survey (1987-2001) and the Monongahela-Youghiogheny Healthy Aging Team (2006-Ongoing). We identified four decade-long birth cohorts spanning birth years 1902-1941. In an analysis sample of 3,010 participants (61% women, mean baseline age = 75.7 years, mean follow-up = 7.1 years), we identified 257 cases of incident dementia indicated by a Clinical Dementia Rating of 1.0 or higher. We used Poisson regression to model incident dementia rates by birth cohort, age, sex, education, and interactions of Sex × Cohort and Sex × Education. We further examined whether cohort effects varied by education, testing a Cohort × Education interaction and stratifying the models by education. RESULTS: Compared to the earliest birth cohort (1902-1911), each subsequent cohort had a significantly lower incident dementia rate (1912-1921: incidence rate ratio [IRR] = 0.655, 95% confidence interval [95% CI] = 0.477-0.899; 1922-1931: IRR = 0.387, 95% CI = 0.265-0.564; 1932-1941: IRR = 0.233, 95% CI = 0.121-0.449). We observed no significant interactions of either sex or education with birth cohort. CONCLUSIONS: A decline in incident dementia rates was observed across successive birth cohorts independent of sex, education, and age.

Risk of progression from subjective cognitive decline to mild cognitive impairment: The role of study setting.

INTRODUCTION: We compared risk of progression from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) in an academic memory clinic versus a population-based study. METHODS: Older adults presenting at a memory clinic were classified as SCD (n = 113) or as noncomplainers (n = 82). Participants from a population study were classified as SCD (n = 592) and noncomplainers (n = 589) based on a memory complaint score. Annual follow-up performed for a mean of 3 years. RESULTS: The adjusted hazard ratio for SCD was 15.97 (95% confidence interval: 6.08-42.02, P < .001) in the memory clinic versus 1.18 (95% confidence interval: 1.00-1.40, P = .047) in the population study, where reported "worry" about memory further increased SCD-associated risk for MCI. DISCUSSION: SCD is more likely to progress to MCI in a memory clinic than the general population; participants' characteristics vary across settings. Study setting should be considered when evaluating SCD as a risk state for MCI and dementia.

Change in Engagement in Cognitive Activity and Risk for Mild Cognitive Impairment in a Cohort of Older Adults: The Monongahela-Youghiogheny Healthy Aging Team (MYHAT) Study.

Engagement in cognitively stimulating activities is gaining prominence as a potential strategy to maintain cognitive functioning in old age. In a population-based cohort of individuals aged 65+ years, we examined patterns of change in frequency of engagement in total cognitive activity (TCA), higher cognitive activity (HCA), and frequent cognitive activity (FCA) based on the Florida Cognitive Activities Scale over an average of 3.62 years, and whether these patterns were associated with incident mild cognitive impairment (MCI) during this same period. Among 867 cognitively normal participants, 129 (15%) progressed to MCI. Latent class trajectory modeling identified high and stable, slowly, and quickly declining patterns for TCA; high and stable, slowly declining, and slowing increasing patterns for FCA; and high and stable, and slowly declining patterns for HCA. Separate, adjusted Cox proportional hazard models, revealed that compared with the high, stable pattern, both slow decline [hazard ratio (HR), 2.5; 95% confidence interval (CI), 1.5-4.0] and quick decline (HR, 11.0; 95% CI, 6.3-19.2) in TCA, and slow decline in the FCA (HR, 8.7; 95% CI, 5.3-14.3) and HCA (HR, 3.4; 95% CI, 2.0-5.6) subscales increased risk for incident MCI. Maintaining engagement in cognitive activities may be protective against progression to MCI, alternatively, declining engagement may be a marker for impending cognitive impairment.

Cohort effects in verbal memory function and practice effects: a population-based study.

BACKGROUND: In many developed countries, cognitive functioning (as measured by neuropsychological tests) appears to be improving over time in the population at large, in parallel with the declining age-specific incidence of dementia. Here, we investigated cohort effects in the age-associated trajectories of verbal memory function in older adults. We sought to determine whether they varied by decade of birth and, if so, whether the change would be explained by increasing educational attainment. METHODS: Pooling data from two prospective US population-based studies between 1987 and 2015, we identified four birth cohorts born 1902-1911, 1912-1921, 1922-1931, and 1932-1943. Among these cohorts, we compared age-associated trajectories both of performance and of practice effects on immediate and delayed recall of a 10-item Word List. We used mixed effects models, first including birth cohorts and cohort X age interaction terms, and then controlling for education and education X age interaction. RESULTS: We observed significant cohort effects in performance (baseline and age-associated trajectories) in both immediate recall and delayed recall, with function improving between the earliest- and latest-born cohorts. For both tests, we also observed cohort effects on practice effects with the highest levels in the latest-born cohorts. Including education in the models did not attenuate these effects. CONCLUSIONS: In this longitudinal population study, across four decade-long birth cohorts, there were significant improvements in test performance and practice effects in verbal memory tests, not explained by education. Whether this reflects declining disease incidence or other secular trends awaits further investigation.

Do Subjective Memory Complaints Lead or Follow Objective Cognitive Change? A Five-Year Population Study of Temporal Influence.

The relationship between subjective memory complaints (SM) and objective memory (OM) performance in aging has been variably characterized in a substantial literature, to date. In particular, cross-sectional studies often observe weak or no associations. We investigated whether subjective memory complaints and objectively measured cognition influence each other over time, and if so, which is the stronger pathway of change-objective to subjective, or subjective to objective-or whether they are both important. Using bivariate latent change score modeling in data from a population study (N=1980) over 5 annual assessment cycles, we tested four corresponding hypotheses: (1) no coupling between SM and OM over time; (2) SM as leading indicator of change in OM; (3) OM as leading indicator of change in SM; (4) dual coupling over time, with both SM and OM leading subsequent change in the other. We also extended objective cognition to two other domains, language and executive functions. The dual-coupling models best fit the data for all three objective cognitive domains. The SM-OM temporal dynamics differ qualitatively compared to other domains, potentially reflecting changes in insight and self-awareness specific to memory impairment. Subjective memory and objective cognition reciprocally influence each other over time. The temporal dynamics between subjective and objective cognition in aging are nuanced, and must be carefully disentangled to shed light on the underlying processes.