Age-Related Trajectories of General Fluid Cognition and Functional Decline in the Health and Retirement Study: A Bivariate Latent Growth Analysis.

There have been few studies on associations between age-related declines in fluid cognition and functional ability in population-representative samples of middle-aged and older adults. We used a two-stage process (longitudinal factor analysis followed by structural growth modeling) to estimate bivariate trajectories of age-related changes in general fluid cognition (numeracy, category fluency, executive functioning, and recall memory) and functional limitation (difficulties in daily activities, instrumental activities, and mobility). Data came from the Health and Retirement Study (Waves 2010-2016; N = 14,489; ages 50-85 years). Cognitive ability declined on average by -0.05 SD between ages 50-70 years, then -0.28 SD from 70-85 years. Functional limitation increased on average by +0.22 SD between ages 50-70 years, then +0.68 SD from 70-85 years. Significant individual variation in cognitive and functional changes was observed across age windows. Importantly, cognitive decline in middle age (pre-age 70 years) was strongly correlated with increasing functional limitation (r = -.49, p < .001). After middle age, cognition declined independently of change in functional limitation. To our knowledge, this is the first study to estimate age-related changes in fluid cognitive measures introduced in the HRS between 2010-2016.

Corrigendum: Examining the intersection of cognitive and physical function measures: Results from the brain networks and mobility (B-NET) study.

[This corrects the article DOI: 10.3389/fnagi.2023.1090641.].

Predictors of cognitive and physical decline: Results from the Health Aging and Body Composition Study.

Background: Risk factors for cognitive decline and physical decline have been studied independently, however older adults might experience decline in both areas i.e., dual decline. Risk factors associated with dual decline are largely unknown and have significant implications on health outcomes. The aim of this study is to explore risk factors associated with dual decline. Methods: Using data from the Health, Aging and Body Composition (Health ABC) study, a longitudinal prospective cohort study, we examined trajectories of decline based on repeated measures of the Modified Mini-Mental State Exam (3MSE) and the Short Physical Performance Battery (SPPB) across 6 years (n=1,552). We calculated four mutually exclusive trajectories of decline and explored predictors of decline: cognitive decline (n = 306) = lowest quartile of slope on the 3MSE or 1.5 SD below mean at baseline, physical decline (n = 231) = lowest quartile of slope on the SPPB or 1.5 SD below mean at baseline, dual decline (n = 110) = lowest quartile in both measures or 1.5 SD below mean in both measures at baseline. Individuals who did not meet criteria for one of the decline groups were classified as the reference group. (n= 905). Results: Multinomial logistic regression tested the association of 17 baseline risk factors with decline. Odds of dual decline where significantly higher for individuals at baseline with depressive symptoms (CES-D >16) (Odds Ratio (OR)=2.49, 95% Confidence Interval (CI): 1.05-6.29), ApoE-ε4 carrier (OR= 2.09, 95% CI: 1.06-1.95), or if individuals had lost 5+lbs in past year (OR=1.79, 95% CI: 1.13-2.84). Odds were significantly lower for individuals with a higher score on the Digit Symbol Substitution Test per standard deviation (OR per SD: 0.47, 95% CI 0.36-0.62) and faster 400-meter gait (OR per SD= 0.49, 95% CI: 0.37-0.64). Conclusion: Among predictors, depressive symptoms at baseline significantly increased the odds of developing dual decline but was not associated with decline in the exclusively cognitive or physical decline groups. APOE-ε4 status increased the odds for cognitive decline and dual decline but not physical decline. More research on dual decline is needed because this group represents a high risk, vulnerable subset of older adults.

Cognitive-behavioral therapy and exercise training in adolescent females with elevated depression symptoms and at-risk for type 2 diabetes: Protocol for a randomized controlled trial.

BACKGROUND: Adolescent-onset type 2 diabetes (T2D) is a major public health concern of growing proportions. Prevention, therefore, is critical. Unfortunately, standard-of-care treatment for T2D prevention (e.g., exercise training) show insufficient effectiveness and do not address key modifiable barriers (e.g., depression symptoms) to exercise engagement. Depression symptoms are associated with both poorer physical fitness and greater insulin resistance, the key risk factor in adolescent-onset T2D. Thus, a targeted prevention approach that addresses depression symptoms in combination with exercise training may offer a novel approach to mitigating T2D risk. METHODS: This manuscript describes the design and study protocol for a multi-site, four-arm randomized controlled trial comparing the efficacy of group cognitive-behavioral therapy, group exercise training, and their combinations for the targeted prevention of worsening insulin resistance in N = 300 adolescent females at-risk for T2D with BMI ≥85th percentile and elevated depression symptoms. All four intervention arms will run in parallel and meet weekly for 1 h per week for 6-week to 6-week segments (12 weeks total). Outcomes are assessed at baseline, 6-week mid-treatment, 12-week follow-up, and 1-year follow-up. RESULTS: The primary outcome is insulin resistance. Key secondary outcomes include insulin sensitivity, cardiorespiratory fitness, physical activity, depression symptoms, and body measurements. CONCLUSION: Study findings will guide the ideal sequencing of two brief T2D prevention interventions for ameliorating the course of insulin resistance and lessening T2D risk in vulnerable adolescents. These interventions will likely be cost-effective and scalable for dissemination, having the potential for significant public health impact on communities at risk for T2D.

Examining the intersection of cognitive and physical function measures: Results from the brain networks and mobility (B-NET) study.

Background and objectives: Although evidence exists that measures of mobility and cognition are correlated, it is not known to what extent they overlap, especially across various domains. This study aimed to investigate the intersection of 18 different objective cognitive and physical function measures from a sample of unimpaired adults aged 70 years and older. Research design and methods: Canonical correlation analysis was utilized to explore the joint cross-sectional relationship between 13 cognitive and 6 physical function measures in the baseline visit of the Brain Networks and Mobility Function (B-NET) Study (n = 192). Results: Mean age of participants was 76.4 years. Two synthetic functions were identified. Function 1 explained 26.3% of the shared variability between the cognition and physical function variables, whereas Function 2 explained 19.5%. Function 1 termed "cognitive and physical speed" related the expanded Short Physical Performance Battery (eSPPB), 400-m walk speed, and Dual Task gait speed measures of physical function to semantic fluency animals scores, Digit Symbol Coding (DSC), and Trail Making Test B. Function 2 termed "complex motor tasks and cognitive tasks" related the Force Plate Postural Sway Foam Task and Dual Task to the following cognitive variables: MoCA Adjusted Score, Verbal Fluency L words, Craft story immediate and delayed recall, and Trail Making Test B. Discussion and implications: We identified groups of cognitive and physical functional abilities that were linked in cross-sectional analyses, which may suggest shared underlying neural network pathway(s) related to speed (Function 1) or complexity (Function 2). Translational significance: Whether such neural processes decline before measurable functional losses or may be important targets for future interventions that aim to prevent disability also remains to be determined.

Predictors of depression among middle-aged and older men and women in Europe: A machine learning approach.

Background: The high prevalence of depression in a growing aging population represents a critical public health issue. It is unclear how social, health, cognitive, and functional variables rank as risk/protective factors for depression among older adults and whether there are conspicuous differences among men and women. Methods: We used random forest analysis (RFA), a machine learning method, to compare 56 risk/protective factors for depression in a large representative sample of European older adults (N = 67,603; ages 45-105y; 56.1% women; 18 countries) from the Survey of Health, Ageing and Retirement in Europe (SHARE Wave 6). Depressive symptoms were assessed using the EURO-D questionnaire: Scores ≥ 4 indicated depression. Predictors included a broad array of sociodemographic, relational, health, lifestyle, and cognitive variables. Findings: Self-rated social isolation and self-rated poor health were the strongest risk factors, accounting for 22.0% (in men) and 22.3% (in women) of variability in depression. Odds ratios (OR) per +1SD in social isolation were 1.99x, 95% CI [1.90,2.08] in men; 1.93x, 95% CI [1.85,2.02] in women. OR for self-rated poor health were 1.93x, 95% CI [1.81,2.05] in men; 1.98x, 95% CI [1.87,2.10] in women. Difficulties in mobility (in both sexes), difficulties in instrumental activities of daily living (in men), and higher self-rated family burden (in women) accounted for an additional but small percentage of variance in depression risk (2.2% in men, 1.5% in women). Interpretation: Among 56 predictors, self-perceived social isolation and self-rated poor health were the most salient risk factors for depression in middle-aged and older men and women. Difficulties in instrumental activities of daily living (in men) and increased family burden (in women) appear to differentially influence depression risk across sexes. Funding: This study was internally funded by Colorado State University through research start-up monies provided to Stephen Aichele, Ph.D.

Heterogeneity in Association Between Cognitive Function and Gait Speed Among Older Adults: An Integrative Data Analysis Study.

BACKGROUND: Increasing evidence shows that cognition and gait speed are associated and are important measures of health among older adults. However, previous studies have used different methods to assess these 2 outcomes and lack sufficient sample size to examine heterogeneity among subgroups. This study examined how the relationship between global cognitive function and gait speed are influenced by age, gender, and race utilizing an integrated data analysis approach. METHOD: Data on cognition (Montreal Cognitive Assessment [MoCA], Mini-Mental Status Examination [MMSE], and Modified Mini-Mental State Examination [3MSE]) and gait speed (range: 4-400 m) were acquired and harmonized from 25 research studies (n = 2802) of adults aged 50+ from the Wake Forest Older American Independence Center. Multilevel regression models examined the relationship between predicted values of global cognitive function (MoCA) and gait speed (4-m walk), including heterogeneity by age, race, and gender. RESULTS: Global cognitive function and gait speed exhibited a consistent positive relationship among whites with increasing age, while this was less consistent for African Americans. That is, there was a low correlation between global cognitive function and gait speed among African Americans aged 50-59, a positive correlation in their 60s and 70s, then a negative correlation thereafter. CONCLUSION: Global cognition and gait speed exhibited a curvilinear U-shaped relationship among whites; however, the association becomes inverse in African Americans. More research is needed to understand this racial divergence and could aid in identifying interventions to maintain cognitive and gait abilities across subgroups.

Association Between Physical Performance and Cognitive Function in Older Adults Across Multiple Studies: A Pooled Analysis Study.

BACKGROUND AND OBJECTIVES: While several studies have examined the association between cognitive and physical function, the consistency of these associations across functional contexts is unclear. The consistency of the association between cognitive and physical function performance was examined at baseline across 17 clinical studies with diverse and heterogeneous conditions such as overweight/obese, sedentary, at risk for a mobility disability, osteoarthritis, low vitamin D, or had signs of cognitive impairment. RESEARCH DESIGN AND METHODS: Data are from 1,388 adults 50 years and older who completed a cognitive and physical function assessment as part of a research study at the Wake Forest Alzheimer's Disease Research Center or the Wake Forest Older Americans Independence Center. Linear regression models were used to relate cognitive measures (Mini-Mental Status Examination, Montreal Cognitive Assessment, and the Digit Symbol Substitution Task) and physical measures (the Short Physical Performance Battery and hand grip strength) for the whole sample and treat each study as a fixed effect. All models controlled for age, sex, race, and body mass index. RESULTS: Overall, there was a significant association between higher scores on the Mini-Mental Status Examination (per standard deviation) and better physical function performance (Short Physical Performance Battery score b = 0.24, p < .001) and its components (gait speed, chair rise, and standing balance; ps < .05). Higher scores on the Montreal Cognitive Assessment produced similar results (Short Physical Performance Battery score b = 0.31, p ≤ .001), and higher scores on the Digit Symbol Substitution Task were also significantly associated with a better Short Physical Performance Battery score (b = 0.75, p < .001). The relationship between Digit Symbol Substitution Task and physical function performance demonstrated a stronger magnitude of association compared to the Mini-Mental Status Examination or Montreal Cognitive Assessment. DISCUSSION AND IMPLICATIONS: Older adults with heterogeneous health conditions showed a consistent pattern between better cognitive function and better physical function performance with the strongest association among Digit Symbol Substitution Task scores.

Cognitive Function as a Predictor of Major Mobility Disability in Older Adults: Results From the LIFE Study.

BACKGROUND AND OBJECTIVES: Many cross-sectional studies have confirmed a link between gait speed and cognitive function. However, it is unknown whether cognitive function plays a role in the onset of major mobility disability (MMD) and if the effects are independent of physical function. This study examined cognitive and physical function as predictors of MMD across an average of 2.6 years of follow-up in community-dwelling older adults with compromised mobility. RESEARCH DESIGN AND METHOD: Data were collected from 1,635 participants in the Lifestyle Interventions and Independence for Elders (LIFE) study ages 70-89 years free of MMD at baseline. MMD was assessed every 6 months and defined as the inability to walk 400 m in ≤15 min without assistance or sitting. Cognitive function was assessed at baseline, 18 months, and 24 months using a cognitive battery categorized into four domains: global cognitive function, processing speed, verbal memory, and executive function. RESULTS: Across the study duration of 2.6 years, 536 participants (32.8%) developed MMD. Cox Proportional Hazard models indicated a protective relationship for higher baseline processing speed (Hazard Ratio [HR] per standard deviation: 0.86, p = .006), executive function (HR: 0.86, p = .002), and global cognition (HR: 0.85, p = .001) on incidence of MMD adjusted for demographics, intervention, and comorbidities. Results were not significant after adjustment for gait speed. In adjusted longitudinal models, a positive change in processing speed was significantly associated with reduced risk of MMD (HR: 0.52, p < .001) while other domains were not. DISCUSSION AND IMPLICATIONS: In the LIFE study, processing speed at baseline and follow-up was a significant predictor of subsequent MMD although the observed association may be explained by physical function as reflected in gait speed. More studies are needed to understand how cognitive function, alone and in combination with physical function, influences risk of MMD.

Can Nutrition or Inflammation Moderate the Age-Cognition Association Among Older Adults?

Objectives: Previous research has shown that nutrition can influence cognitive abilities in older adults. We examined whether nutritional factors or inflammatory biomarkers moderate the age-cognition association. Method: Analyses included 1,308 participants (age ≥60) from the National Health and Nutrition Examination Survey III. Macronutrients (% of calories from fat, protein, and carbohydrates), micronutrients/amino acids (blood serum values: Vitamins B12, C, D, E, folate, iron, homocysteine, and ß-carotene), and inflammatory biomarkers (serum C-reactive protein, plasma fibrinogen, and serum ferritin) were examined as moderators with cognition. Cognition was measured by six tasks: immediate and delayed story recall, immediate and delayed word memory, digit subtraction, and questions about place/orientation. Results: Higher values of serum folate were significantly associated with better cognitive scores. Specifically, the interaction between age-cognition and folate indicated the associations of higher age and lower global cognition and lower immediate story recall were weaker in those with higher folate values (p's < .05). A significant interaction between age and plasma fibrinogen indicated that the association between age and worse digit subtraction was stronger with values >3.1 g/L. Discussion: Folate and fibrinogen were significant moderators between age and cognition. Further research into the relationship between nutrition, inflammation, and cognitive aging is needed.

Neighborhoods, sleep quality, and cognitive decline: Does where you live and how well you sleep matter?

INTRODUCTION: We evaluated the association between neighborhood socioeconomic status (NSES) and sleep quality on cognitive decline in the Health and Retirement Study. METHODS: Health and Retirement Study participants (n = 8090), aged 65+ with DNA and multiple biennial cognitive observations (abbreviated Telephone Interview for Cognitive Status), were included. Participants were grouped into quartiles of NSES and sleep quality scores. We adjusted for apolipoprotein E ε4, demographic, and cardiovascular risk factors. Random effects modeling evaluated cognitive change over time. RESULTS: NSES and sleep were significantly associated with cognitive decline, and there was a significant interaction between them (P = .02). Significant differences between high/low NSES and high/low sleep quality (P < .0001) were found. DISCUSSION: Sleep and NSES were associated with cognitive decline; the association between sleep and cognition appeared stronger among those with low NSES. The association between low NSES, poor sleep quality, and cognitive decline was roughly equivalent to the association between apolipoprotein E ε4 and cognitive decline.

Exercise's effect on mobility disability in older adults with and without obesity: The LIFE study randomized clinical trial.

OBJECTIVE: Some data suggest that obesity blunts the benefits of exercise on mobility in older adults. This study tested the homogeneity of the effect of a physical activity intervention on major mobility disability (MMD) across baseline obesity classifications in the Lifestyle Interventions and Independence for Elders (LIFE) Study. LIFE randomized 1,635 sedentary men and women aged 70 to 89 years to a moderate-intensity physical activity (PA) or health education program. METHODS: MMD, defined as the inability to walk 400 m, was determined over an average follow-up of 2.6 years. Participants were divided into four subgroups: (1) nonobese (BMI < 30 kg/m2 ; n = 437); (2) nonobese with high waist circumference (WC > 102 cm [men], > 88 cm [women]; n = 434); (3) class 1 obesity (30 kg/m2 ≤ BMI < 35 kg/m2 ; n = 430); and (4) class 2 + obesity (BMI ≥ 35 kg/m2 ; n = 312). Cox proportional hazard modeling was used to test an obesity by intervention interaction. RESULTS: The PA intervention had the largest benefit in participants with class 2 + obesity (hazard ratio 0.69, 95% confidence interval 0.48, 0.98). However, there was no statistically significant difference in benefit across obesity categories. CONCLUSIONS: A structured PA program reduced the risk of MMD even in older adults with extreme obesity.

Midlife Alcohol Consumption and Risk of Dementia Over 43 Years of Follow-Up: A Population-Based Study From the Swedish Twin Registry.

BACKGROUND: Midlife alcohol consumption (beer, wine, and spirits) was examined in relation to dementia incidence over 43 years. METHODS: Participants were 12,326 members of the population-based Swedish Twin Registry born during 1907-1925 who responded to items about alcohol consumption in 1967/1970, subsequently classified as nondrinking (0 grams of ethanol per day), light (1-5g/d), moderate (5-12g/d), heavy (12-24g/d), and very heavy (>24g/d) drinking. Dementia was identified from the National Patient and Cause of Death Registries. Cox proportional hazard models adjusted for cluster-correlated data were used in cohort analyses. Conditional logistic regression (dementia-discordant pairs) and mixed effects models (dementia-concordant pairs) were used in twin analyses. RESULTS: Overall, nondrinkers did not differ from light drinkers in dementia risk. Heavy drinking (hazard ratio = 1.10, p = .028) and very heavy drinking (hazard ratio = 1.18, p = .033) were associated with increased dementia risk controlling for sociodemographic, lifestyle, and cardiovascular factors. More alcohol from spirits was related to increased risk of dementia, whereas more alcohol from wine with decreased risk, although the association for wine reversed direction at high amounts. Relative to co-twins drinking light amounts, moderate-to-heavy drinking twins had (a) greater risk of dementia by 57% (p = .006, 300% in monozygotic pairs only) and (b) reduced time to dementia by 4.76 years (p = .019, 4.78 years in monozygotic pairs only). CONCLUSION: Averaging more than 12 grams of alcohol per day may increase risk of dementia. Alcohol from spirits appears particularly important for the increased dementia risk. Genetic and/or familial factors do not explain these associations. Alcohol use reduction may be a useful population-wide intervention strategy.

Alcohol consumption at midlife and risk of stroke during 43 years of follow-up: cohort and twin analyses.

BACKGROUND AND PURPOSE: Although alcohol-stroke association is well known, the age-varying effect of alcohol drinking at midlife on subsequent stroke risk across older adulthood has not been examined. The effect of genetic/early-life factors is also unknown. We used cohort and twin analyses of data with 43 years of follow-up for stroke incidence to help address these gaps. METHODS: All 11 644 members of the population-based Swedish Twin Registry born 1886 to 1925 with alcohol data aged ≤60 years were included. The interaction of midlife alcohol consumption by age at stroke was evaluated in Cox-regression and analyses of monozygotic twins were used. Covariates were baseline age, sex, cardiovascular diseases, diabetes mellitus, stress reactivity, depression, body mass index, smoking, and exercise. RESULTS: Altogether 29% participants developed stroke. Compared with very-light drinkers (<0.5 drink/d), heavy drinkers (>2 drinks/d) had greater risk of stroke (hazard ratio, 1.34; P=0.02) and the effect for nondrinkers approached significance (hazard ratio, 1.11; P=0.08). Age increased stroke risk for nondrinkers (P=0.012) and decreased it for heavy drinkers (P=0.040). Midlife heavy drinkers were at high risk from baseline until the age of 75 years when hypertension and diabetes mellitus grew to being the more relevant risk factors. In analyses of monozygotic twin-pairs, heavy drinking shortened time to stroke by 5 years (P=0.04). CONCLUSIONS: Stroke-risk associated with heavy drinking (>2 drinks/d) in midlife seems to predominate over well-known risk factors, hypertension and diabetes, until the age of ≈75 years and may shorten time to stroke by 5 years above and beyond covariates and genetic/early-life factors. Alcohol consumption should be considered an age-varying risk factor for stroke.