RÉSUMÉ
INTRODUCTION: The Health and Retirement Study International Partner Surveys (HRS IPS) have rich longitudinal data, but the brevity of cognitive batteries is a limitation. METHODS: We used data from a substudy of the English Longitudinal Study of Ageing (ELSA) administering detailed cognitive assessments with the Harmonized Cognitive Assessment Protocol (ELSA-HCAP) (N = 1273) to inform approaches for estimating cognition in ELSA (N = 11,213). We compared two novel approaches: confirmatory factor analysis (CFA)- and regression-based prediction. RESULTS: Compared to estimates from the full HCAP battery, estimated cognitive functioning derived using regression models or CFA had high correlations (regression: r = 0.85 [95% confidence interval [CI]: 0.83 to 0.87]; CFA: r = 0.83 [95% CI: 0.81 to 0.85]) and reasonable mean squared error (regression: 0.25 [0.22 to 0.27]; CFA: 0.29 [0.26 to 0.32]) in held-out data. The use of additional items from waves 7 to 9 improved performance. DISCUSSION: Both approaches are recommended for future research; the similarity in approaches may be due to the brevity of available cognitive assessments in ELSA. HIGHLIGHTS: Estimates of cognitive functioning informed by English Longitudinal Study of Ageing-Harmonized Cognitive Assessment Protocol (ELSA-HCAP) data had an adequate performance. Standard errors were smaller for associations with example risks when using measures informed by ELSA-HCAP. Performance was better when including additional cognitive measures available in waves 7 to 9. Conceptual advantages to the confirmatory factor analysis (CFA) approach were not important in practice due to the brevity of the ELSA cognitive battery.
RÉSUMÉ
Gender is an observed effect modifier of the association between loneliness and memory aging. However, this effect modification may be a result of information bias due to differential loneliness under-reporting by gender. We applied probabilistic bias analyses to examine whether effect modification of the loneliness-memory decline relationship by gender is retained under three simulation scenarios with various magnitudes of differential loneliness under-reporting between men and women. Data were from biennial interviews with adults aged 50+ in the US Health and Retirement Study from 1996-2016 (5,646 women and 3,386 men). Loneliness status (yes vs. no) was measured from 1996-2004 using the CES-D loneliness item and memory was measured from 2004-2016. Simulated sensitivity and specificity of the loneliness measure were informed by a validation study using the UCLA Loneliness Scale as a gold standard. The likelihood of observing effect modification by gender was higher than 90% in all simulations, although the likelihood reduced with an increasing difference in magnitude of the loneliness under-reporting between men and women. The gender difference in loneliness under-reporting did not meaningfully affect the observed effect modification by gender in our simulations. Our simulation approach may be promising to quantify potential information bias in effect modification analyses.
RÉSUMÉ
OBJECTIVES: To examine clinically important adverse events (AEs) associated with methylphenidate (MPH) treatment of apathy in Alzheimer's Disease (AD) versus placebo, including weight loss, vital signs, falls, and insomnia. METHODS: The Apathy in Dementia Methylphenidate Trial 2 (ADMET2) trial was a multicenter randomized, placebo-controlled trial of MPH to treat apathy in individuals with apathy and AD. Participants in ADMET2 had vital signs and weight measured at monthly visits through 6 months. AEs, including insomnia, falls, and cardiovascular events, were reported at every visit by participants and families using a symptom checklist. RESULTS: The study included 98 participants in the MPH group and 101 in the placebo group. Participants in the MPH group experienced greater weight loss on average than the placebo through the 6-month follow-up, with a difference in change between MPH and placebo of 2.8 lb (95% confidence interval, CI: 0.7, 4.9 lb). No treatment group differences in change during the trial were found in systolic and diastolic blood pressure. More participants in the MPH group reported falls during the follow-up, 10 versus 6 in MPH and placebo groups, respectively. No differences in post-baseline insomnia were observed between the treatment groups. No participants reported instances of myocardial infarction, congestive heart failure, arrhythmia, stroke, or cardiomyopathy throughout the study period. CONCLUSIONS: MPH use in AD patients for treating apathy is relatively safe, particularly notable given the many medical comorbidities in this population. There was a statistically significant but modest weight loss associated with MPH use, and clinicians are thus advised to monitor weight during MPH treatment.
Sujet(s)
Chutes accidentelles , Maladie d'Alzheimer , Apathie , Stimulants du système nerveux central , Méthylphénidate , Perte de poids , Humains , Maladie d'Alzheimer/traitement médicamenteux , Méthylphénidate/usage thérapeutique , Méthylphénidate/effets indésirables , Femelle , Mâle , Apathie/effets des médicaments et des substances chimiques , Sujet âgé , Stimulants du système nerveux central/usage thérapeutique , Stimulants du système nerveux central/effets indésirables , Sujet âgé de 80 ans ou plus , Perte de poids/effets des médicaments et des substances chimiques , Chutes accidentelles/statistiques et données numériques , Méthode en double aveugle , Troubles de l'endormissement et du maintien du sommeil/induit chimiquement , Troubles de l'endormissement et du maintien du sommeil/traitement médicamenteuxRÉSUMÉ
INTRODUCTION: The contribution of neuropsychological assessments to risk assessment for incident dementia is underappreciated. METHODS: We analyzed neuropsychological testing results in dementia-free participants in the Atherosclerosis Risk in Communities (ARIC) study. We examined associations of index domain-specific neuropsychological test performance with incident dementia using cumulative incidence curves and Cox proportional hazards models. RESULTS: Among 5296 initially dementia-free participants (mean [standard deviation] age of 75.8 [5.1] years; 60.1% women, 22.2% Black) over a median follow-up of 7.9 years, the covariate-adjusted hazard ratio varied substantially depending on the pattern of domain-specific performance and age, in an orderly manner from single domain language abnormalities (lowest risk) to single domain executive or memory abnormalities, to multidomain abnormalities including memory (highest risk). DISCUSSION: By identifying normatively defined cognitive abnormalities by domains based on neuropsychological test performance, there is a conceptually orderly and age-sensitive spectrum of risk for incident dementia that provides valuable information about the likelihood of progression. HIGHLIGHTS: Domain-specific cognitive profiles carry enhanced prognostic value compared to mild cognitive impairment. Single-domain non-amnestic cognitive abnormalities have the most favorable prognosis. Multidomain amnestic abnormalities have the greatest risk for incident dementia. Patterns of domain-specific risks are similar by sex and race.
Sujet(s)
Démence , Tests neuropsychologiques , Humains , Femelle , Mâle , Démence/épidémiologie , Démence/diagnostic , Sujet âgé , Tests neuropsychologiques/statistiques et données numériques , Appréciation des risques , Dysfonctionnement cognitif/épidémiologie , Dysfonctionnement cognitif/diagnostic , Incidence , Facteurs de risque , Sujet âgé de 80 ans ou plus , Troubles de la cognition/épidémiologie , Troubles de la cognition/diagnostic , Modèles des risques proportionnelsRÉSUMÉ
Background: It is unclear how post-stroke cognitive trajectories differ by stroke type and ischemic stroke subtype. We studied associations between stroke types (ischemic, hemorrhagic), ischemic stroke subtypes (cardioembolic, large artery atherosclerotic, lacunar/small vessel, cryptogenic/other determined etiology), and post-stroke cognitive decline. Methods: This pooled cohort analysis from four US cohort studies (1971-2019) identified 1,143 dementia-free individuals with acute stroke during follow-up: 1,061 (92.8%) ischemic, 82 (7.2%) hemorrhagic, 49.9% female, 30.8% Black. Median age at stroke was 74.1 (IQR, 68.6, 79.3) years. Outcomes were change in global cognition (primary) and changes in executive function and memory (secondary). Outcomes were standardized as T-scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Median follow-up for the primary outcome was 6.0 (IQR, 3.2, 9.2) years. Linear mixed-effects models estimated changes in cognition after stroke. Results: On average, the initial post-stroke global cognition score was 50.78 points (95% CI, 49.52, 52.03) in ischemic stroke survivors and did not differ in hemorrhagic stroke survivors (difference, -0.17 points [95% CI, -1.64, 1.30]; P=0.82) after adjusting for demographics and pre-stroke cognition. On average, ischemic stroke survivors showed declines in global cognition, executive function, and memory. Post-stroke declines in global cognition, executive function, and memory did not differ between hemorrhagic and ischemic stroke survivors. 955 ischemic strokes had subtypes: 200 (20.9%) cardioembolic, 77 (8.1%) large artery atherosclerotic, 207 (21.7%) lacunar/small vessel, 471 (49.3%) cryptogenic/other determined etiology. On average, small vessel stroke survivors showed declines in global cognition and memory, but not executive function. Initial post-stroke cognitive scores and cognitive declines did not differ between small vessel survivors and survivors of other ischemic stroke subtypes. Post-stroke vascular risk factor levels did not attenuate associations. Conclusion: Stroke survivors had cognitive decline in multiple domains. Declines did not differ by stroke type or ischemic stroke subtype.
RÉSUMÉ
BACKGROUND: We investigated the effects of apolipoprotein E (APOE) ε4 and its interactions with sociodemographic characteristics on cognitive measures in South Asians from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD). METHODS: Linear regression was used to assess the association between APOE ε4 and global- and domain-specific cognitive function in 2563 participants (mean age 69.6 ± 7.3 years; 53% female). Effect modification by age, sex, and education were explored using interaction terms and subgroup analyses. RESULTS: APOE ε4 was inversely associated with most cognitive measures (p < 0.05). This association was stronger with advancing age for the Hindi Mental State Examination (HMSE) score (ßε4×age = -0.44, p = 0.03), orientation (ßε4×age = -0.07, p = 0.01), and language/fluency (ßε4×age = -0.07, p = 0.01), as well as in females for memory (ßε4×male = 0.17, p = 0.02) and language/fluency (ßε4×male = 0.12, p = 0.03). DISCUSSION: APOE ε4 is associated with lower cognitive function in South Asians from India, with a more pronounced impact observed in females and older individuals. HIGHLIGHTS: APOE ε4 carriers had lower global and domain-specific cognitive performance. Females and older individuals may be more susceptible to ε4 effects. For most cognitive measures, there was no interaction between ε4 and education.
Sujet(s)
Apolipoprotéine E4 , Cognition , Humains , Femelle , Mâle , Sujet âgé , Apolipoprotéine E4/génétique , Inde/ethnologie , Cognition/physiologie , Études longitudinales , Tests neuropsychologiques/statistiques et données numériques , Asiatiques , Adulte d'âge moyen , Facteurs sociodémographiques , Populations d'Asie du SudRÉSUMÉ
INTRODUCTION: Informant reports are a critical component of dementia diagnoses, but the comparability of informant reports across countries is not well understood. METHODS: We compared the performance of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) using population-representative surveys in the United States (N = 3183), England (N = 1050), and India (N = 4047). RESULTS: Analyses of regression splines and comparisons of model fit showed strong associations between IQCODE and objective cognition at low cognitive functioning in the United States and England; in India, the association was weaker but consistent over the range of cognition. Associations between IQCODE score and informant generation (analysis of variance [ANOVA] p = 0.001), caregiver status (p < 0.001), and years known by the informant (p = 0.015) were different across countries after adjusting for objective cognition. DISCUSSION: In India, the IQCODE was less sensitive to impairments at the lowest levels of cognitive functioning. Country-specific adjustments to IQCODE scoring based on informant characteristics may improve cross-national comparisons. HIGHLIGHTS: Associations between IQCODE and cognitive testing were similar in the United States and England but differed in India. In India, the IQCODE may be less sensitive to impairments among those with low cognition and no education. Informant characteristics may differentially impact informant reports of decline across countries. Adjustments or culturally sensitive adaptations may improve cross-national comparability.
Sujet(s)
Dysfonctionnement cognitif , Démence , Humains , Mâle , Femelle , Démence/diagnostic , Démence/épidémiologie , Sujet âgé , Enquêtes et questionnaires , Dysfonctionnement cognitif/diagnostic , États-Unis , Inde , Angleterre , Vieillissement cognitif/physiologie , Comparaison interculturelle , Aidants/psychologie , Aidants/statistiques et données numériques , Tests neuropsychologiques/statistiques et données numériques , Sujet âgé de 80 ans ou plusRÉSUMÉ
Strategies to prevent or delay Alzheimer's disease and related dementias (AD/ADRD) are urgently needed, and blood pressure (BP) management is a promising strategy. Yet the effects of different BP control strategies across the life course on AD/ADRD are unknown. Randomized trials may be infeasible due to prolonged follow-up and large sample sizes. Simulation analysis is a practical approach to estimating these effects using the best available existing data. However, existing simulation frameworks cannot estimate the effects of BP control on both dementia and cardiovascular disease. This manuscript describes the design principles, implementation details, and population-level validation of a novel population-health microsimulation framework, the MIchigan ChROnic Disease SIMulation (MICROSIM), for The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP-COG) study of the effect of BP levels over the life course on dementia and cardiovascular disease. MICROSIM is an agent-based Monte Carlo simulation designed using computer programming best practices. MICROSIM estimates annual vascular risk factor levels and transition probabilities in all-cause dementia, stroke, myocardial infarction, and mortality in a nationally representative sample of US adults 18+ using the National Health and Nutrition Examination Survey (NHANES). MICROSIM models changes in risk factors over time, cognition and dementia using changes from a pooled dataset of individual participant data from 6 US prospective cardiovascular cohort studies. Cardiovascular risks were estimated using a widely used risk model and BP treatment effects were derived from meta-analyses of randomized trials. MICROSIM is an extensible, open-source framework designed to estimate the population-level impact of different BP management strategies and reproduces US population-level estimates of BP and other vascular risk factors levels, their change over time, and incident all-cause dementia, stroke, myocardial infarction, and mortality.
Sujet(s)
Simulation numérique , Humains , Michigan/épidémiologie , Maladie chronique , Mâle , Démence/épidémiologie , Sujet âgé , Femelle , Facteurs de risque , Méthode de Monte Carlo , Pression sanguine , Adulte d'âge moyen , Maladies cardiovasculaires/épidémiologie , Adulte , Maladie d'Alzheimer , Sujet âgé de 80 ans ou plusRÉSUMÉ
BACKGROUND: The large and increasing number of adults living with dementia is a pressing societal priority, which may be partially mitigated through improved population-level blood pressure (BP) control. We explored how tighter population-level BP control affects the incidence of atherosclerotic cardiovascular disease (ASCVD) events and dementia. METHODS: Using an open-source ASCVD and dementia simulation analysis platform, the Michigan Chronic Disease Simulation Model, we evaluated how optimal implementation of 2 BP treatments based on the Eighth Joint National Committee recommendations and SPRINT (Systolic Blood Pressure Intervention Trial) protocol would influence population-level ASCVD events, global cognitive performance, and all-cause dementia. We simulated 3 populations (usual care, Eighth Joint National Committee based, SPRINT based) using nationally representative data to annually update risk factors and assign ASCVD events, global cognitive performance scores, and dementia, applying different BP treatments in each population. We tabulated total ASCVD events, global cognitive performance, all-cause dementia, optimal brain health, and years lived in each state per population. RESULTS: Optimal implementation of SPRINT-based BP treatment strategy, compared with usual care, reduced ASCVD events in the United States by ≈77â 000 per year and produced 0.4 more years of stroke- or myocardial infarction-free survival when averaged across all Americans. Population-level gains in years lived free of ASCVD events were greater for SPRINT-based than Eighth Joint National Committee-based treatment. Survival and years spent with optimal brain health improved with optimal SPRINT-based BP treatment implementation versus usual care: the average patient with hypertension lived 0.19 additional years and 0.3 additional years in optimal brain health. SPRINT-based BP treatment increased the number of years lived without dementia (by an average of 0.13 years/person with hypertension), but increased the total number of individuals with dementia, mainly through more adults surviving to advanced ages. CONCLUSIONS: Tighter BP control likely benefits most individuals but is unlikely to reduce dementia prevalence and might even increase the number of older adults living with dementia.
Sujet(s)
Antihypertenseurs , Pression sanguine , Cognition , Démence , Hypertension artérielle , Humains , Cognition/effets des médicaments et des substances chimiques , Antihypertenseurs/usage thérapeutique , Hypertension artérielle/traitement médicamenteux , Hypertension artérielle/diagnostic , Hypertension artérielle/épidémiologie , Hypertension artérielle/physiopathologie , Hypertension artérielle/mortalité , Pression sanguine/effets des médicaments et des substances chimiques , Sujet âgé , Mâle , Démence/épidémiologie , Démence/diagnostic , Démence/mortalité , Femelle , Résultat thérapeutique , Adulte d'âge moyen , Facteurs de risque , Appréciation des risques , Incidence , Facteurs temps , Sujet âgé de 80 ans ou plus , Michigan/épidémiologie , Simulation numérique , Athérosclérose/épidémiologie , Athérosclérose/diagnostic , Athérosclérose/traitement médicamenteux , États-Unis/épidémiologieRÉSUMÉ
Sensory impairment and brain atrophy is common among older adults, increasing the risk of dementia. Yet, the degree to which multiple co-occurring sensory impairments (MSI across vision, proprioception, vestibular function, olfactory, and hearing) are associated with brain morphometry remain unexplored. Data were from 208 cognitively unimpaired participants (mean age 72 ± 10 years; 59% women) enrolled in the Baltimore Longitudinal Study of Aging. Multiple linear regression models were used to estimate cross-sectional associations between MSI and regional brain imaging volumes. For each additional sensory impairment, there were associated lower orbitofrontal gyrus and entorhinal cortex volumes but higher caudate and putamen volumes. Participants with MSI had lower mean volumes in the superior frontal gyrus, orbitofrontal gyrus, superior parietal lobe, and precuneus compared to participants with < 2 impairments. While MSI was largely associated with lower brain volumes, our results suggest the possibility that MSI was associated with higher basal ganglia volumes. Longitudinal analyses are needed to evaluate the temporality and directionality of these associations.
Sujet(s)
Vieillissement , Encéphale , Humains , Femelle , Sujet âgé , Mâle , Encéphale/imagerie diagnostique , Encéphale/anatomopathologie , Études longitudinales , Études transversales , Vieillissement/physiologie , Vieillissement/anatomopathologie , Baltimore , Sujet âgé de 80 ans ou plus , Imagerie par résonance magnétique , Adulte d'âge moyen , Taille d'organe , AtrophieRÉSUMÉ
Background and Objectives: Consumer credit has shown increasing relevance to the health of older adults; however, studies have not been able to assess the extent to which creditworthiness influences future health or health influences future creditworthiness. We assessed the relationships between 4-year pre and postmorbid consumer credit history and self-rated physical and mental health outcomes among older adults. Research Design and Methods: Generalized estimating equations models assessed pre and postmorbid credit history (credit scores, derogatory accounts, and unpaid accounts in collections) and the onset of poor self-rated health (SF-36 score <50) among 1,740 participants aged 65+ in the Advanced Cognitive Training for Independent and Vital Elderly study from 2001 to 2017, linked to TransUnion consumer credit data. Results: In any given year, up to 1/4 of participants had a major derogatory, unpaid, or collections account, and up to 13% of the sample had poor health. Each 50-point increase in credit score trended toward a 5% lower odds of poor health in the next 1 year, a 6% lower odds in the next 2 years, and a statistically significant finding of 13% lower odds by 3 years. A drop in credit score was associated with a 10% greater odds of poor health in the next year, and having a major derogatory account was associated with an 86% greater odds of poor health in the next 3 years. After poor health onset, credit scores continued to see significant losses up to the 3 years, with larger decrements over time. Discussion and Implications: Having a major derogatory account or a sudden loss in credit may be a time to monitor older adults for changes in health. After a downturn in health, supporting older adults to manage their debt may help stabilize their credit.
RÉSUMÉ
INTRODUCTION: Age-related sensory and motor impairment are associated with risk of dementia. No study has examined the joint associations of multiple sensory and motor measures on prevalence of early cognitive impairment (ECI). METHODS: Six hundred fifty participants in the Baltimore Longitudinal Study of Aging completed sensory and motor function tests. The association between sensory and motor function and ECI was examined using structural equation modeling with three latent factors corresponding to multisensory, fine motor, and gross motor function. RESULTS: The multisensory, fine, and gross motor factors were all correlated (r = 0.74 to 0.81). The odds of ECI were lower for each additional unit improvement in the multisensory (32%), fine motor (30%), and gross motor factors (12%). DISCUSSION: The relationship between sensory and motor impairment and emerging cognitive impairment may guide future intervention studies aimed at preventing and/or treating ECI. HIGHLIGHTS: Sensorimotor function and early cognitive impairment (ECI) prevalence were assessed via structural equation modeling. The degree of fine and gross motor function is associated with indicators of ECI. The degree of multisensory impairment is also associated with indicators of ECI.
Sujet(s)
Dysfonctionnement cognitif , Humains , Études longitudinales , Dysfonctionnement cognitif/épidémiologie , Vieillissement , BaltimoreRÉSUMÉ
INTRODUCTION: India, with its rapidly aging population, faces an alarming burden of dementia. We implemented DSM-5 criteria in large-scale, nationally representative survey data in India to characterize the prevalence of mild and major Neurocognitive disorder. METHODS: The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) (N = 4,096) is a nationally representative cohort study in India using multistage area probability sampling methods. Using neuropsychological testing and informant reports, we defined DSM-5 mild and major neurocognitive disorder, reported its prevalence, and evaluated criterion and construct validity of the algorithm using clinician-adjudicated Clinical Dementia Ratings (CDR)®. RESULTS: The prevalence of mild and major neurocognitive disorder, weighted to the population, is 17.6% and 7.2%. Demographic gradients with respect to age and education conform to hypothesized patterns. Among N = 2,390 participants with a clinician-adjudicated CDR, CDR ratings and DSM-5 classification agreed for N = 2,139 (89.5%) participants. DISCUSSION: The prevalence of dementia in India is higher than previously recognized. These findings, coupled with a growing number of older adults in the coming decades in India, have important implications for society, public health, and families. We are aware of no previous Indian population-representative estimates of mild cognitive impairment, a group which will be increasingly important in coming years to identify for potential therapeutic treatment.
Sujet(s)
Dysfonctionnement cognitif , Démence , Humains , Sujet âgé , Études de cohortes , Prévalence , Démence/diagnostic , Démence/épidémiologie , Démence/psychologie , Dysfonctionnement cognitif/diagnostic , Dysfonctionnement cognitif/épidémiologie , Dysfonctionnement cognitif/psychologie , Vieillissement , Tests neuropsychologiques , Inde/épidémiologieRÉSUMÉ
INTRODUCTION: We examined the association of both midlife occupation and age at retirement with cognitive decline in the Atherosclerosis Risk in Communities (ARIC) biracial community-based cohort. METHODS: Current or most recent occupation at ARIC baseline (1987-1989; aged 45-64 years) was categorized based on 1980 US Census major occupation groups and tertiles of the Nam-Powers-Boyd occupational status score (n = 14,090). Retirement status via annual follow-up questionnaires administered ascertained in 1999-2007 was classified as occurring before or after age 70 (n = 7,503). Generalized estimating equation models were used to examine associations of occupation and age at retirement with trajectories of global cognitive factor scores, assessed from visit 2 (1990-1992) to visit 5 (2011-2013). Models were a priori stratified by race and sex and adjusted for demographics and comorbidities. RESULTS: Low occupational status and blue-collar occupations were associated with low baseline cognitive scores in all race-sex strata. Low occupational status and homemaker status were associated with faster decline in white women but slower decline in black women compared to high occupational status. Retirement before age 70 was associated with slower cognitive decline in white men and women and in black men. Results did not change substantially after accounting for attrition. CONCLUSION: Low occupational status was associated with cognitive decline in women but not in men. Earlier retirement was associated with a slower cognitive decline in white participants and in black men. Further research should explore reasons for the observed associations and race-sex differences.
Sujet(s)
Athérosclérose , Dysfonctionnement cognitif , Professions , Retraite , Humains , Mâle , Femelle , Adulte d'âge moyen , Dysfonctionnement cognitif/épidémiologie , Retraite/statistiques et données numériques , Professions/statistiques et données numériques , Athérosclérose/épidémiologie , Facteurs âges , /statistiques et données numériques , Sujet âgé , États-Unis/épidémiologie , Facteurs de risque , Études de cohortesRÉSUMÉ
Background: The size/magnitude of cognitive changes after incident heart failure (HF) are unclear. We assessed whether incident HF is associated with changes in cognitive function after accounting for pre-HF cognitive trajectories and known determinants of cognition. Methods: This pooled cohort study included adults without HF, stroke, or dementia from six US population-based cohort studies from 1971-2019: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study. Linear mixed-effects models estimated changes in cognition at the time of HF (change in the intercept) and the rate of cognitive change over the years after HF (change in the slope), controlling for pre-HF cognitive trajectories and participant factors. Change in global cognition was the primary outcome. Change in executive function and memory were secondary outcomes. Cognitive outcomes were standardized to a t-score metric (mean [SD], 50 [10]); a 1-point difference represented a 0.1-SD difference in cognition. Results: The study included 29,614 adults (mean [SD] age was 61.1 [10.5] years, 55% female, 70.3% White, 22.2% Black 7.5% Hispanic). During a median follow-up of 6.6 (Q1-Q3: 5-19.8) years, 1,407 (4.7%) adults developed incident HF. Incident HF was associated with an acute decrease in global cognition (-1.08 points; 95% CI -1.36, -0.80) and executive function (-0.65 points; 95% CI -0.96, -0.34) but not memory (-0.51 points; 95% CI -1.37, 0.35) at the time of the event. Greater acute decreases in global cognition after HF were seen in those with older age, female sex and White race. Individuals with incident HF, compared to HF-free individuals, demonstrated faster declines in global cognition (-0.15 points per year; 95% CI, -0.21, -0.09) and executive function (-0.16 points per year; 95% CI -0.23, -0.09) but not memory ( -0.11 points per year; 95% CI -0.26, 0.04) compared with pre-HF slopes. Conclusions: In this pooled cohort study, incident HF was associated with an acute decrease in global cognition and executive function at the time of the event and faster declines in global cognition and executive function over the following years.
RÉSUMÉ
The Harmonized Cognitive Assessment Protocol (HCAP) is a major innovation that provides, for the first time, harmonized data for cross-national comparisons of later-life cognitive functions that are sensitive to linguistic, cultural, and educational differences across countries. However, cognitive function does not lend itself to direct comparison across diverse populations without careful consideration of the best practices for such comparisons. This perspective discusses theoretical and methodological considerations and offers a set of recommended best practices for conducting cross-national comparisons of risk factor associations using HCAP data. Because existing and planned HCAP studies provide cognition data representing an estimated 75% of the global population ≥65 years of age, these recommended best practices will support high-quality comparative analyses of cognitive aging around the world. The principles described in this perspective are applicable to any researcher aiming to integrate or compare harmonized data on cognitive outcomes and their risk and protective factors across diverse populations.
Sujet(s)
Cognition , Humains , Facteurs de risqueRÉSUMÉ
OBJECTIVES: Identifying social policies that can promote cognitive health is crucial for reducing the global burden of dementia. We evaluated the importance of educational attainment for later-life cognitive function in various social and geographic settings. METHODS: Using harmonized data for individuals aged ≥65 years from the United States Health and Retirement Study (HRS) and its international partner studies in England, Mexico, China, and India, and each study's respective Harmonized Cognitive Assessment Protocol (HCAP), we conducted a cross-national comparative study to examine the role of educational attainment in later-life cognitive function across countries (n = 14,980, 2016-2019). We used multivariable-adjusted regression to estimate associations between educational attainment and harmonized global cognitive function scores. RESULTS: In Mexico, China, and India, the general cognitive function scores on average are approximately one standard deviation of the HRS-HCAP cognitive function score distribution lower compared to the United States and England, paralleling patterns of educational attainment across countries. In all countries, higher educational attainment was associated with progressively higher later-life cognitive function scores. Population-level differences in educational attainment explained about 50%-90% of the observed differences in cognitive function scores across countries. DISCUSSION: The relationship between education and later-life cognitive function across social and geographic contexts underscores the crucial role of education to promote cognitive health and reduce dementia risk. Continual improvement of educational attainment in low- and middle-income settings may yield a significant pay-off in later-life cognitive health.
Sujet(s)
Réussite universitaire , Démence , Humains , États-Unis/épidémiologie , Pays en voie de développement , Niveau d'instruction , Cognition , Démence/diagnosticRÉSUMÉ
The prevalence of dementia among South Asians across India is approximately 7.4% in those 60 years and older, yet little is known about genetic risk factors for dementia in this population. Most known risk loci for Alzheimer's disease (AD) have been identified from studies conducted in European Ancestry (EA) but are unknown in South Asians. Using whole-genome sequence data from 2680 participants from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD), we performed a gene-based analysis of 84 genes previously associated with AD in EA. We investigated associations with the Hindi Mental State Examination (HMSE) score and factor scores for general cognitive function and five cognitive domains. For each gene, we examined missense/loss-of-function (LoF) variants and brain-specific promoter/enhancer variants, separately, both with and without incorporating additional annotation weights (e.g., deleteriousness, conservation scores) using the variant-Set Test for Association using Annotation infoRmation (STAAR). In the missense/LoF analysis without annotation weights and controlling for age, sex, state/territory, and genetic ancestry, three genes had an association with at least one measure of cognitive function (FDR q<0.1). APOE was associated with four measures of cognitive function, PICALM was associated with HMSE score, and TSPOAP1 was associated with executive function. The most strongly associated variants in each gene were rs429358 (APOE ε4), rs779406084 (PICALM), and rs9913145 (TSPOAP1). rs779406084 is a rare missense mutation that is more prevalent in LASI-DAD than in EA (minor allele frequency=0.075% vs. 0.0015%); the other two are common variants. No genes in the brain-specific promoter/enhancer analysis met criteria for significance. Results with and without annotation weights were similar. Missense/LoF variants in some genes previously associated with AD in EA are associated with measures of cognitive function in South Asians from India. Analyzing genome sequence data allows identification of potential novel causal variants enriched in South Asians.
RÉSUMÉ
BACKGROUND: Poor motor function is associated with brain atrophy and cognitive impairment. Less is known about the relationship between motor domains and brain atrophy and whether associations are affected by cerebrovascular burden and/or physical activity. METHODS: We analyzed data from 726 Baltimore Longitudinal Study of Aging participants (mean age 70.6â ±â 10.1 years, 56% women, 27% Black), 525 of whom had repeat MRI scans over an average of 5.0â ±â 2.1 years. Two motor domains, manual dexterity and gross motor, were operationalized as latent variables. Associations between the latent variables and cortical and subcortical brain volumes of interest were examined using latent growth curve modeling, adjusted for demographics, white matter hyperintensities, and physical activity. RESULTS: Both higher manual dexterity and gross motor function were cross-sectionally associated with smaller ventricular volume and greater white matter volumes in the frontal, parietal, and temporal lobes (all pâ <â .05). Manual dexterity was also cross-sectionally associated with parietal gray matter (Bâ =â 0.14; 95% CI: 0.05, 0.23), hippocampus (Bâ =â 0.10; 95% CI: 0.01, 0.20), postcentral gyrus (Bâ =â 0.11; 95% CI: 0.01, 0.20), and occipital white matter (Bâ =â 0.10; 95% CI: 0.01, 0.21) volumes, and gross motor function with temporal gray matter volume (Bâ =â 0.16; 95% CI: 0.05, 0.26). Longitudinally, both higher manual dexterity and gross motor function were associated with less temporal white matter and occipital gray matter atrophy (all pâ <â .05). Manual dexterity was also associated with a slower rate of ventricular enlargement (Bâ =â -0.17; 95% CI: -0.29, -0.05) and less atrophy of occipital white matter (Bâ =â 0.39; 95% CI: 0.04, 0.71). CONCLUSIONS: Among cognitively normal middle- and older-aged adults, manual dexterity and gross motor function exhibited shared as well as distinct associations with brain atrophy over time.