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OBJECTIVES: On average, adults racialized as non-Hispanic Black and Hispanic sleep more poorly than adults racialized as non-Hispanic White (hereafter, Black, Hispanic, White), but associations between factors that may moderate sleep-memory associations in these groups, such as neighborhood conditions, are unclear. Poorer neighborhood conditions (e.g. lower neighborhood cohesion) may be negatively associated with sleep quality and multiplicatively influence sleep-memory associations. We hypothesized lower ratings of neighborhood conditions would be associated with poorer sleep quality and moderate the association between sleep quality and episodic memory, especially in Black and Hispanic adults, who are disproportionately situated in poor neighborhood conditions. DESIGN: Seven-hundred-thirty-six adults across the adult lifespan (27-89 years) were recruited from the northern Manhattan community as a part of the Offspring Study of Racial and Ethnic Disparities in Alzheimer's disease. Sleep quality was assessed using a modified version of the Pittsburgh Sleep Quality Index, and episodic memory was evaluated with the Buschke Selective Reminding Test. With multiple regression models, we measured associations between perceived neighborhood conditions and sleep quality and the interaction between sleep quality and neighborhood conditions on episodic memory stratified by racial/ethnic and gender identity groups. RESULTS: Overall, poorer neighborhood conditions were associated with poorer sleep quality. In Black and Hispanic women, the sleep-memory association was moderated by neighborhood conditions. With more favorable neighborhood conditions, Black women showed an association between higher sleep quality and higher memory performance, and Hispanic women showed a protective effect of neighborhood (higher memory even when sleep quality was poor). CONCLUSION: Poorer neighborhood experiences may contribute to poorer sleep quality across groups. In Black and Hispanic women, the association between sleep quality and episodic memory performance was dependent upon neighborhood conditions. These findings may inform tailored, structural level sleep interventions, aimed to improve neighborhood experiences and thereby sleep quality and episodic memory.
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Importance: Hearing loss may contribute to poor functional status via cognitive impairment and social isolation. Hearing aids may play a protective role by attenuating these downstream outcomes. However, population-based evidence is lacking. Objective: To examine the association of hearing loss and hearing aids with functional status. Design, Setting, and Participants: This cross-sectional (2016-2017) and longitudinal (2016-2022) analysis of data from the Atherosclerosis Risk in Communities cohort study included older, community-dwelling adults with complete data. Data were analyzed from June to December 2023. Exposures: The better-hearing ear's pure tone average (BPTA) at speech frequencies (0.5-4 kHz) was modeled categorically (no [BPTA ≤25 dB], mild [26-40 dB], and moderate or greater hearing loss [>40 dB]). Hearing aid use was self-reported. Main Outcomes and Measures: Difficulties in activities of daily living (ADLs; eg, dressing and eating), instrumental activities of daily living (IADLS; eg, household chores and meal preparation), and heavier tasks (eg, walking a quarter of a mile) were self-reported at visit 6. The ability to perform usual activities, walk a half mile, walk up and down stairs, and do heavy housework without help were collected in follow-up surveys. Linear and logistic regression models were used that were adjusted for sociodemographic and health covariates. Results: Among 3142 participants (mean [SD] age, 79.3 [4.6] years; 1828 women [58.2%]), 1013 (32.2%) had no hearing loss, 1220 (38.8%) had mild hearing loss, and 909 (29.0%) had moderate or greater hearing loss. Moderate or greater hearing loss was cross-sectionally associated with difficulty in 1 or more ADLs (odds ratio [OR], 1.27; 95% CI, 1.02-1.58), IADLs (OR, 1.34; 95% CI, 1.05-1.71), and heavier tasks (OR, 1.29; 95% CI, 1.04-1.62) compared with no hearing loss. Over time (mean [SD] follow-up, 1.9 [1.8] years), moderate or greater hearing loss was associated with a faster decline in the number of activities participants were able to do (ß = -0.07 per year; 95% CI, -0.09 to -0.06) and greater odds of reporting inability to do 1 or more of the 4 activities (OR, 1.14; 95% CI, 1.05-1.24). Hearing aid users and nonusers did not differ. Conclusions and Relevance: The results of this study suggest that moderate or greater hearing loss was associated with functional difficulties and may contribute to a faster decline in function longitudinally independent of sociodemographic and health covariates. Hearing aids did not change the association among those with hearing loss.
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Actividades Cotidianas , Audífonos , Pérdida Auditiva , Humanos , Audífonos/estadística & datos numéricos , Femenino , Masculino , Estudios Transversales , Anciano , Pérdida Auditiva/epidemiología , Estado Funcional , Estudios Longitudinales , Vida Independiente , Audiometría de Tonos PurosRESUMEN
Importance: Plasma biomarkers show promise for identifying Alzheimer disease (AD) neuropathology and neurodegeneration, but additional examination among diverse populations and throughout the life course is needed. Objective: To assess temporal plasma biomarker changes and their association with all-cause dementia, overall and among subgroups of community-dwelling adults. Design, Setting, and Participants: In 1525 participants from the US-based Atherosclerosis Risk in Communities (ARIC) study, plasma biomarkers were measured using stored specimens collected in midlife (1993-1995, mean age 58.3 years) and late life (2011-2013, mean age 76.0 years; followed up to 2016-2019, mean age 80.7 years). Midlife risk factors (hypertension, diabetes, lipids, coronary heart disease, cigarette use, and physical activity) were assessed for their associations with change in plasma biomarkers over time. The associations of biomarkers with incident all-cause dementia were evaluated in a subpopulation (n = 1339) who were dementia-free in 2011-2013 and had biomarker measurements in 1993-1995 and 2011-2013. Exposure: Plasma biomarkers of amyloid-ß 42 to amyloid-ß 40 (Aß42:Aß40) ratio, phosphorylated tau at threonine 181 (p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were measured using the Quanterix Simoa platform. Main Outcomes and Measures: Incident all-cause dementia was ascertained from January 1, 2012, through December 31, 2019, from neuropsychological assessments, semiannual participant or informant contact, and medical record surveillance. Results: Among 1525 participants (mean age, 58.3 [SD, 5.1] years), 914 participants (59.9%) were women, and 394 participants (25.8%) were Black. A total of 252 participants (16.5%) developed dementia. Decreasing Aß42:Aß40 ratio and increasing p-tau181, NfL, and GFAP were observed from midlife to late life, with more rapid biomarker changes among participants carrying the apolipoprotein E epsilon 4 (APOEε4) allele. Midlife hypertension was associated with a 0.15-SD faster NfL increase and a 0.08-SD faster GFAP increase per decade; estimates for midlife diabetes were a 0.11-SD faster for NfL and 0.15-SD faster for GFAP. Only AD-specific biomarkers in midlife demonstrated long-term associations with late-life dementia (hazard ratio per SD lower Aß42:Aß40 ratio, 1.11; 95% CI, 1.02-1.21; per SD higher p-tau181, 1.15; 95% CI, 1.06-1.25). All plasma biomarkers in late life had statistically significant associations with late-life dementia, with NfL demonstrating the largest association (1.92; 95% CI, 1.72-2.14). Conclusions and Relevance: Plasma biomarkers of AD neuropathology, neuronal injury, and astrogliosis increase with age and are associated with known dementia risk factors. AD-specific biomarkers' association with dementia starts in midlife whereas late-life measures of AD, neuronal injury, and astrogliosis biomarkers are all associated with dementia.
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AIMS: Few studies investigate whether psychosocial factors (social isolation, social support, trait anger, and depressive symptoms) are associated with cardiovascular health, and none with the American Heart Association's new definition of cardiovascular health, Life's Essential 8 (LE8). Therefore, we assessed the cross-sectional associations of psychosocial factors with Life's Essential 8 and individual components of Life's Essential 8. METHODS: We included 11,311 Atherosclerosis Risk in Communities cohort participants (58% females; 23% Black; mean age 57 (standard deviation: 6) years) who attended Visit 2 (1990-1992) in this secondary data analysis using cross-sectional data from the ARIC cohort study. Life's Essential 8 components included diet, physical activity, nicotine exposure, sleep quality, body mass index, blood lipids, blood glucose, and blood pressure. Life's Essential 8 was scored per the American Heart Association definition (0-100 range); higher scores indicate better cardiovascular health. Associations of categories (high, moderate, and low) of each psychosocial factor with continuous Life's Essential 8 score and individual Life's Essential 8 components were assessed using multivariable linear regressions. RESULTS: 11% of participants had high Life's Essential 8 scores (80-100), while 67% and 22% had moderate (50-79) and low Life's Essential 8 scores (0-49) respectively. Poor scores on psychosocial factor assessments were associated with lower Life's Essential 8 scores, with the largest magnitude of association for categories of depressive symptoms (low ß = Ref.; moderate ß = -3.1, (95% confidence interval: -3.7, -2.5; high ß = -8.2 (95% confidence interval: -8.8, -7.5)). Most psychosocial factors were associated with Life's Essential 8 scores for diet, physical activity, nicotine, and sleep, but psychosocial factors were not associated with body mass index, blood lipids, blood glucose, or blood pressure. CONCLUSION: Less favorable measures of psychosocial health were associated with lower Life's Essential 8 scores compared better measures of psychosocial health among middle-aged males and females.
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Aterosclerosis , Humanos , Femenino , Masculino , Persona de Mediana Edad , Aterosclerosis/psicología , Aterosclerosis/epidemiología , Aterosclerosis/sangre , Estudios Transversales , Factores de Riesgo , Apoyo Social , Depresión/psicología , Depresión/epidemiología , Anciano , Índice de Masa Corporal , Presión Sanguínea , Enfermedades Cardiovasculares/psicología , Enfermedades Cardiovasculares/epidemiología , Ejercicio Físico , Estudios de CohortesRESUMEN
BACKGROUND: Relationships of midlife inflammation with late-life mobility and influences of chronic health conditions, race, and social determinants of health (SDoH) on these relationships are poorly understood. METHODS: Among 4758 community-dwelling participants (41% men, 20% Black), high-sensitivity C-reactive protein (hsCRP) was measured over 20+ years: in midlife at study visit 2 (V2: 1990-1992, 47-68 years); at V4 (1996-1998, 53-74 years); and with concurrent late-life 4-m gait speed at V5 (2011-2013, 67-88 years, mean 75 years). SDoH measures included race, the national-rank area deprivation index, education, and income. We examined associations of late-life gait speed with midlife hsCRP (V2 continuous and clinically high ≥3 mg/L), with 20-year hsCRP history from midlife (V2-V5 average continuous hsCRP and clinically high ≥3 mg/L) and with inflammation accumulation (visits and years with high hsCRP). Regression models adjusted for demographic, cardiovascular, and SDoH measures; effect modification by the presence of other common chronic conditions (obesity, diabetes, hypertension) and race were examined, with and without accounting for SDoH. RESULTS: High midlife hsCRP was associated with slower late-life gait speed, even among those without chronic conditions in midlife: -4.6 cm/s (95% CI: -6.4, -2.8). Importantly, sustained high hsCRP was associated with a 20-year slowing of -10.0 cm/s (-14.9, -5.1) among those who never experienced obesity, diabetes, or hypertension over the 20-year period. Associations were similar between Black participants, -3.8 cm/s (-6.9, -0.7) and White participants -3.3 (-4.5, -2.2) per interquartile range of midlife hsCRP; effect modifications by chronic conditions and race were unsupported throughout. Results were robust to accounting for SDoH or otherwise; however, worse SDoH was associated with higher inflammation and slower gait speed in both Black and White participants. CONCLUSIONS: Inflammation in midlife may contribute to clinically meaningful late-life slowing of gait speed, even among otherwise healthy-appearing adults and regardless of race and socioeconomic disadvantage. Regular monitoring and interventions for inflammation may be warranted from midlife.
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Proteína C-Reactiva , Comorbilidad , Inflamación , Determinantes Sociales de la Salud , Humanos , Masculino , Femenino , Anciano , Inflamación/sangre , Persona de Mediana Edad , Proteína C-Reactiva/análisis , Velocidad al Caminar , Enfermedad Crónica , Limitación de la Movilidad , Vida Independiente , Anciano de 80 o más Años , Estados Unidos/epidemiología , Aterosclerosis/epidemiología , Factores de RiesgoRESUMEN
Importance: Heart failure (HF) and frailty frequently coexist and may share a common pathobiology, although the underlying mechanisms remain unclear. Understanding these mechanisms may provide guidance for preventing and treating both conditions. Objective: To identify shared pathways between incident HF and frailty in late life using large-scale proteomics. Design, Setting, and Participants: In this cohort study, 4877 aptamers (Somascan v4) were measured among participants in the community-based longitudinal Atherosclerosis Risk In Communities (ARIC) cohort study at visit 3 (V3; 1993-1995; n = 10â¯638) and at visit 5 (V5; 2011-2013; n = 3908). Analyses were externally replicated among 3189 participants in the Cardiovascular Health Study (CHS). Data analysis was conducted from February 2022 to June 2023. Exposures: Protein aptamers, measured at study V3 and V5. Main Outcomes and Measures: Outcomes assessed included incident HF hospitalization after V3 and after V5, prevalent frailty at V5, and incident frailty between V5 and visit 6 (V6; 2016-2017; n = 4131). Frailty was assessed using the Fried criteria. Analyses were adjusted for age, gender, race, field center, hypertension, diabetes, smoking status, body mass index, estimated glomerular filtration rate, prevalent coronary heart disease, prevalent atrial fibrillation, and history of myocardial infarction. Mendelian randomization (MR) analysis was performed to assess potential causal effects of candidate proteins on HF and frailty. Results: A total of 4877 protein aptamers were measured among 10â¯638 participants at V3 (mean [SD] age, 60 [6] years; 4886 [46%] men). Overall, 286 proteins were associated with incident HF after V3 (822 events; P < 1.0 × 10-5), 83 of which were also associated with incident after V5 (336 events; P < 1.7 × 10-4). Among HF-free participants at V5 (n = 3908; mean [SD] age, 75 [5] years; 1861 [42%] men), 48 of 83 HF-associated proteins were associated with prevalent frailty (223 cases; P < 6.0 × 10-4), 18 of which were also associated with incident frailty at V6 (152 cases; P < 1.0 × 10-3). These proteins enriched fibrosis and inflammation pathways and demonstrated stronger associations with incident HF with preserved ejection fraction (HFpEF) than HF with reduced ejection fraction. All 18 proteins were associated with both prevalent frailty and incident HF in CHS. MR identified potential causal effects of several proteins on frailty and HF. Conclusions and Relevance: In this study, the proteins associated with risk of HF and frailty enrich for pathways related to inflammation and fibrosis as well as risk of HFpEF. Several of these proteins could potentially contribute to the shared pathophysiology of frailty and HF.
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Fragilidad , Insuficiencia Cardíaca , Proteómica , Humanos , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/sangre , Femenino , Masculino , Anciano , Fragilidad/epidemiología , Fragilidad/sangre , Incidencia , Factores de Riesgo , Persona de Mediana Edad , Biomarcadores/sangreRESUMEN
BACKGROUND: High to moderate levels of physical activity (PA) are associated with low risk of incident cardiovascular disease. However, it is unclear whether the benefits of PA in midlife extend to cardiovascular health following myocardial infarction (MI) in later life. METHODS: Among 1,111 Atherosclerosis Risk in Communities study participants with incident MI during Atherosclerosis Risk in Communities follow-up (mean age 73 [SD 9] years at MI, 54% men, 21% Black), PA on average 11.9 (SD 6.9) years prior to incident MI (premorbid PA) was evaluated as the average score of PA between visit 1 (1987-1989) and visit 3 (1993-1995) using a modified Baecke questionnaire. Total and domain-specific PA (sport, nonsport leisure, and work PA) was analyzed for associations with composite and individual outcomes of mortality, recurrent MI, and stroke after index MI using multivariable Cox models. RESULTS: During a median follow-up of 4.6 (IQI 1.0-10.5) years after incident MI, 823 participants (74%) developed a composite outcome. The 10-year cumulative incidence of the composite outcome was lower in the highest, as compared to the lowest tertile of premorbid total PA (56% vs. 70%, respectively). This association remained statistically significant even after adjusting for potential confounders (adjusted hazard ratio [aHR] 0.80 [0.67-0.96] for the highest vs. lowest tertile). For individual outcomes, high premorbid total PA was associated with a low risk of recurrent MI (corresponding aHR 0.64 [0.44, 0.93]). When domain-specific PA was analyzed, similar results were seen for sport and work PA. The association was strongest in the first year following MI (e.g., aHR of composite outcome 0.66 [95% CI 0.47, 0.91] for the highest vs. lowest tertile of total PA). CONCLUSIONS: Premorbid PA was associated positively with post-MI cardiovascular health. Our results demonstrate the additional prognostic advantages of PA beyond reducing the risk of incident MI.
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Aterosclerosis , Ejercicio Físico , Infarto del Miocardio , Humanos , Masculino , Infarto del Miocardio/epidemiología , Femenino , Pronóstico , Incidencia , Anciano , Aterosclerosis/epidemiología , Ejercicio Físico/fisiología , Estudios de Seguimiento , Estados Unidos/epidemiología , Persona de Mediana Edad , Factores de Riesgo , Actividad Motora/fisiología , Estudios ProspectivosRESUMEN
BACKGROUND AND OBJECTIVES: Mounting evidence supports sex differences in Alzheimer disease (AD) risk. Vascular and hormonal factors may together contribute to AD risk in female adults. We investigated whether age at menopause, vascular risk, and history of hormone therapy (HT) containing estrogens together influence cognition over a 3-year follow-up period. We hypothesized that earlier menopause and elevated vascular risk would have a synergistic association with lower cognitive scores at follow-up and that HT containing estrogens would attenuate this synergistic association to preserve cognition. METHODS: We used data from postmenopausal female participants and age-matched male participants in the Canadian Longitudinal Study on Aging. Vascular risk was calculated using a summary score of elevated blood pressure, antihypertensive medications, elevated low-density lipoprotein cholesterol, diabetes, smoking, and obesity. Cognition was measured with a global cognitive composite at baseline and 3-year follow-up. Linear models tested independent and interactive associations of age at menopause, vascular risk, and HT history with cognition at 3-year follow-up, adjusting for baseline cognition, baseline age, years of education, and test language (English/French). RESULTS: We included 8,360 postmenopausal female participants (mean age at baseline = 65.0 ± 8.53 years, mean age at menopause = 50.1 ± 4.62 years) and 8,360 age-matched male participants for comparison. There was an interaction between age at menopause and vascular risk, such that earlier menopause and higher vascular risk were synergistically associated with lower cognitive scores at follow-up (ß = 0.013, 95% CI 0.001-0.025, p = 0.03). In stratified analyses, vascular risk was associated with lower cognitive scores in female participants with earlier menopause (menopausal ages 35-48 years; ß = -0.044, 95% CI -0.066 to -0.022, p < 0.001), but not average (ages 49-52 years; ß = -0.007, 95% CI -0.027 to 0.012, p = 0.46) or later menopause (ages 53-65 years; ß = 0.003, 95% CI -0.020 to 0.025, p = 0.82). The negative association of vascular risk with cognition in female participants with earlier menopause was stronger than the equivalent association in age-matched male participants. HT history did not further modify the synergistic association of age at menopause and vascular risk with follow-up cognition (ß = -0.005, 95% CI -0.032 to 0.021, p = 0.69). DISCUSSION: Endocrine and vascular processes may synergistically contribute to increased risk of cognitive decline in female adults. These findings have implications for the development of sex-specific dementia prevention strategies.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Femenino , Humanos , Masculino , Envejecimiento , Enfermedad de Alzheimer/tratamiento farmacológico , Canadá/epidemiología , Cognición , Disfunción Cognitiva/tratamiento farmacológico , Estrógenos/uso terapéutico , Estudios Longitudinales , Menopausia , Persona de Mediana Edad , AncianoRESUMEN
INTRODUCTION: This study aimed to assess whether social relationships in mid-life reduce the risk of dementia related to amyloid burden. METHODS: Participants in the Atherosclerosis Risk in Communities (ARIC) study were assessed for social support and isolation (visit 2; 1990-1992). A composite measure, "social relationships," was generated. Brain amyloid was evaluated with florbetapir positron emission tomography (PET); (visit 5; 2012-2014). Incident dementia cases were identified following visit 5 through 2019 using ongoing surveillance. Relative contributions of mid-life social relationships and elevated brain amyloid to incident dementia were evaluated with Cox regression models. RESULTS: Among 310 participants without dementia, strong mid-life social relationships were associated independently with lower dementia risk. Elevated late-life brain amyloid was associated with greater dementia risk. DISCUSSION: Although mid-life social relationships did not moderate the relationship between amyloid burden and dementia, these findings affirm the importance of strong social relationships as a potentially protective factor against dementia.
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BACKGROUND AND OBJECTIVES: Prospective measures of plasma and cerebral MRI biomarkers of Alzheimer disease (AD) and vascular neuropathology provide an opportunity to investigate possible mechanisms linking liver disease and dementia. We aimed to quantify the association of midlife nonalcoholic fatty liver disease (NAFLD) with change in plasma and brain MRI biomarkers of AD and vascular neuropathology. METHODS: We included participants from the Atherosclerosis Risk in Communities Study with brain MRI measurements of white matter hyperintensity (WMH) volume and temporal-parietal lobe cortical thickness meta region of interest (ROI) at up to 2 different visits, in 2011-13 and 2016-19, and plasma biomarkers of ß-amyloid (Aß)42:40, phosphorylated tau at threonine 181, and neurofilament light (NfL) were measured up to 3 times in 1993-95, 2011-13, and 2016-19. NAFLD was categorized using the fatty liver index in 1990-92. Multivariate linear regression was performed for associations between midlife NAFLD and change in plasma and brain MRI biomarkers of AD and vascular neuropathology. The primary models adjusted for demographics, Apolipoprotein E, alcohol use, and kidney function. RESULTS: Among 1,706 participants (mean age 56 years, 62% female, 28% Black), midlife NAFLD vs no NAFLD was associated with greater late-life WMH volume (difference per SD 0.19, 95% CI 0.06-0.31) and faster late-life WMH increase over 6 years (difference in annual change, SD 0.28, 95% CI 0.05-0.51), suggesting accumulating vascular pathology. Midlife NAFLD vs no NAFLD was also associated with AD biomarkers in midlife (lower Aß42:40 [SD -0.21, 95% CI -0.39 to -0.04] measured in 1993-95) and late life (lower Aß42:40 [SD -0.13, 95% CI -0.23 to -0.03] and lower temporal-parietal lobe cortical thickness meta ROI [SD -0.16, 95% CI -0.28 to -0.05] measured in 2011-13). Although midlife NfL was lower in individuals with vs without midlife NAFLD, those with NAFLD exhibited a faster rate of NfL increase that accelerated over time. DISCUSSION: Midlife NAFLD shows associations with AD and accumulating vascular pathology, revealing potential pathways linking liver function to dementia. Plasma biomarkers of neuropathology and neuronal injury may serve as easily measurable and dynamic indicators for monitoring the impacts of impaired liver function on brain health.
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Enfermedad de Alzheimer , Enfermedad del Hígado Graso no Alcohólico , Humanos , Femenino , Persona de Mediana Edad , Masculino , Enfermedad de Alzheimer/patología , Estudios Prospectivos , Encéfalo/patología , Péptidos beta-Amiloides/metabolismo , Biomarcadores , Proteínas tau/metabolismoRESUMEN
Background: Psychosocial factors are modifiable risk factors for Alzheimer's disease (AD). One mechanism linking psychosocial factors to AD risk may be through biological measures of brain amyloid; however, this association has not been widely studied. Objective: To determine if mid-life measures of social support and social isolation in the Atherosclerosis Risk in Communities (ARIC) Study cohort are associated with late life brain amyloid burden, measured using florbetapir positron emission tomography (PET). Methods: Measures of social support and social isolation were assessed in ARIC participants (visit 2: 1990-1992). Brain amyloid was evaluated with florbetapir PET standardized uptake value ratios (SUVRs; visit 5: 2012-2014). Results: Among 316 participants without dementia, participants with intermediate (odds ratio (OR), 0.47; 95% CI, 0.25-0.88), or low social support (OR, 0.43; 95% CI, 0.22-0.83) in mid-life were less likely to have elevated amyloid SUVRs, relative to participants with high social support. Participants with moderate risk for social isolation in mid-life (OR, 0.32; 95% CI, 0.14-0.74) were less likely to have elevated amyloid burden than participants at low risk for social isolation. These associations were not significantly modified by sex or race. Conclusions: Lower social support and moderate risk of social isolation in mid-life were associated with lower odds of elevated amyloid SUVR in late life, compared to participants with greater mid-life psychosocial measures. Future longitudinal studies evaluating mid-life psychosocial factors, in relation to brain amyloid as well as other health outcomes, will strengthen our understanding of the role of these factors throughout the lifetime.
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Enfermedad de Alzheimer , Aterosclerosis , Disfunción Cognitiva , Glicoles de Etileno , Humanos , Amiloide/metabolismo , Compuestos de Anilina , Tomografía de Emisión de Positrones/métodos , Encéfalo/metabolismo , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/psicología , Proteínas Amiloidogénicas , Factores de Riesgo , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/epidemiología , Péptidos beta-Amiloides/metabolismoRESUMEN
BACKGROUND AND AIMS: Coronary artery calcium (CAC) is validated for risk prediction among middle-aged adults, but there is limited research exploring implications of CAC among older adults. We used data from the Atherosclerosis Risk in Communities (ARIC) study to evaluate the association of CAC with domains of healthy and unhealthy aging in adults aged ≥75 years. METHODS: We included 2,290 participants aged ≥75 years free of known coronary heart disease who underwent CAC scoring at study visit 7. We examined the cross-sectional association of CAC = 0, 1-999 (reference), and ≥1000 with seven domains of aging: cognitive function, hearing, ankle-brachial index (ABI), pulse-wave velocity (PWV), forced vital capacity (FVC), physical functioning, and grip strength. RESULTS: The mean age was 80.5 ± 4.3 years, 38.6% male, and 77.7% White. 10.3% had CAC = 0 and 19.2% had CAC≥1000. Individuals with CAC = 0 had the lowest while those with CAC≥1000 had the highest proportion with dementia (2% vs 8%), hearing impairment (46% vs 67%), low ABI (3% vs 18%), high PWV (27% vs 41%), reduced FVC (34% vs 42%), impaired grip strength (66% vs 74%), and mean composite abnormal aging score (2.6 vs 3.7). Participants with CAC = 0 were less likely to have abnormal ABI (aOR:0.15, 95%CI:0.07-0.34), high PWV (aOR:0.57, 95%CI:0.41-0.80), and reduced FVC (aOR:0.69, 95%CI:0.50-0.96). Conversely, participants with CAC≥1000 were more likely to have low ABI (aOR:1.74, 95%CI:1.27-2.39), high PWV (aOR:1.52, 95%CI:1.15-2.00), impaired physical functioning (aOR:1.35, 95%CI:1.05-1.73), and impaired grip strength (aOR:1.46, 95%CI:1.08-1.99). CONCLUSIONS: Our findings highlight CAC as a simple measure broadly associated with biological aging, with clinical and research implications for estimating the physical and physiological aging trajectory of older individuals.
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Enfermedad de la Arteria Coronaria , Calcificación Vascular , Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Estudios Transversales , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/diagnóstico , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/epidemiología , Calcificación Vascular/fisiopatología , Índice Tobillo Braquial , Fuerza de la Mano , Medición de Riesgo , Envejecimiento Saludable , Estados Unidos/epidemiología , Cognición , Vasos Coronarios/diagnóstico por imagen , Factores de Edad , Envejecimiento , Análisis de la Onda del Pulso , Factores de Riesgo , Aterosclerosis/epidemiología , Aterosclerosis/fisiopatología , Evaluación Geriátrica , Capacidad VitalRESUMEN
BACKGROUND: Older adults have the highest rates of head injury and are at the greatest risk for subsequent dysfunction, yet research on subsequent physical decline is limited. We sought to examine cross-sectional and prospective associations of head injury with physical functioning and frailty among older adults. METHODS: A total of 5 598 Atherosclerosis Risk in Communities Study participants from Visit 5 (2011-13) underwent assessments of physical functioning (Short Physical Performance Battery [SPPB], comprised of gait speed, chair stands, and balance) and frailty (defined using established criteria) were followed through Visit 7 (2018-19). Head injury was self-reported or based on ICD-9 codes. Adjusted linear and multinomial logistic regression models were used to estimate associations. Prospective models incorporated inverse probability of attrition weights to account for death or attrition. RESULTS: Participants were a mean age of 75 years, 58% were women, 22% were Black, and 27% had a prior head injury. Compared to individuals without head injury, individuals with head injury had worse physical functioning (SPPB total score, ß-coefficientâ =â -0.22, 95% CI: -0.35 to -0.09) and were more likely to be pre-frail (ORâ =â 1.19, 95% CI: 1.04 to 1.35) or frail (ORâ =â 1.40, 95% CI: 1.08 to 1.80) compared to robust. Prospectively, head injury was associated with a 0.02 m/s greater decline (95% CI: -0.04 to -0.01) in gait speed over a median of 5 years. Among baseline robust individuals (nâ =â 1 847), head injury was associated with increased odds of becoming pre-frail (ORâ =â 1.32, 95% CI: 1.04 to 1.67) or frail (ORâ =â 1.92, 95% CI: 1.05 to 3.51) compared to robust. CONCLUSIONS: Older adults with prior head injury had worse physical functioning and greater frailty at baseline and were more likely to become frail and walk slower over time, compared to individuals without head injury.
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Fragilidad , Humanos , Femenino , Anciano , Masculino , Fragilidad/epidemiología , Estudios Transversales , Caminata , Velocidad al Caminar , Examen Físico , Anciano FrágilRESUMEN
Habitual physical activity (PA) impacts the plasma proteome and reduces the risk of developing type 2 diabetes (T2D). Using a large-scale proteome-wide approach in Atherosclerosis Risk in Communities study participants, we aimed to identify plasma proteins associated with PA and determine which of these may be causally related to lower T2D risk. PA was associated with 92 plasma proteins in discovery (P < 1.01 × 10-5), and 40 remained significant in replication (P < 5.43 × 10-4). Eighteen of these proteins were independently associated with incident T2D (P < 1.25 × 10-3), including neuronal growth regulator 1 (NeGR1; hazard ratio per SD 0.85; P = 7.5 × 10-11). Two-sample Mendelian randomization (MR) inverse variance weighted analysis indicated that higher NeGR1 reduces T2D risk (odds ratio [OR] per SD 0.92; P = 0.03) and was consistent with MR-Egger, weighted median, and weighted mode sensitivity analyses. A stronger association was observed for the single cis-acting NeGR1 genetic variant (OR per SD 0.80; P = 6.3 × 10-5). Coupled with previous evidence that low circulating NeGR1 levels promote adiposity, its association with PA and potential causal role in T2D shown here suggest that NeGR1 may link PA exposure with metabolic outcomes. Further research is warranted to confirm our findings and examine the interplay of PA, NeGR1, adiposity, and metabolic health.
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Moléculas de Adhesión Celular Neuronal , Diabetes Mellitus Tipo 2 , Humanos , Proteínas Sanguíneas/genética , Diabetes Mellitus Tipo 2/complicaciones , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Proteoma/genética , Factores de Riesgo , Moléculas de Adhesión Celular Neuronal/metabolismoRESUMEN
OBJECTIVE: Few studies have comprehensively examined how health and disease risk influence Alzheimer's disease (AD) biomarkers. The present study examined the association of 14 protein-based health indicators with plasma and neuroimaging biomarkers of AD and neurodegeneration. METHODS: In 706 cognitively normal adults, we examined whether 14 protein-based health indices (ie, SomaSignal® tests) were associated with concurrently measured plasma-based biomarkers of AD pathology (amyloid-ß [Aß]42/40 , tau phosphorylated at threonine-181 [pTau-181]), neuronal injury (neurofilament light chain [NfL]), and reactive astrogliosis (glial fibrillary acidic protein [GFAP]), brain volume, and cortical Aß and tau. In a separate cohort (n = 11,285), we examined whether protein-based health indicators associated with neurodegeneration also predict 25-year dementia risk. RESULTS: Greater protein-based risk for cardiovascular disease, heart failure mortality, and kidney disease was associated with lower Aß42/40 and higher pTau-181, NfL, and GFAP levels, even in individuals without cardiovascular or kidney disease. Proteomic indicators of body fat percentage, lean body mass, and visceral fat were associated with pTau-181, NfL, and GFAP, whereas resting energy rate was negatively associated with NfL and GFAP. Together, these health indicators predicted 12, 31, 50, and 33% of plasma Aß42/40 , pTau-181, NfL, and GFAP levels, respectively. Only protein-based measures of cardiovascular risk were associated with reduced regional brain volumes; these measures predicted 25-year dementia risk, even among those without clinically defined cardiovascular disease. INTERPRETATION: Subclinical peripheral health may influence AD and neurodegenerative disease processes and relevant biomarker levels, particularly NfL. Cardiovascular health, even in the absence of clinically defined disease, plays a central role in brain aging and dementia. ANN NEUROL 2024;95:260-273.
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Enfermedad de Alzheimer , Enfermedades Cardiovasculares , Enfermedades Renales , Enfermedades Neurodegenerativas , Adulto , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Proteómica , Péptidos beta-Amiloides , Biomarcadores , Proteínas tauRESUMEN
BACKGROUND: Physical function and its decline in older age may be connected to treatable vascular risk factors in mid-life. This study aimed to evaluate whether these factors affect the underlying rate of decline. METHODS: This prospective cohort included 5 481 older adults aged 67-91 in the Atherosclerosis Risk in Communities Study (mean [standard deviation {SD}] ageâ =â 75.8 [5.0], 58% women, 21% Black race) without a history of stroke. The main outcome was the rate of Short Physical Performance Battery (SPPB) decline over a median late-life follow-up of 4.8 years. Primary mid-life (aged 45-64) exposures were Visit 1 hypertension (>140/90 mm Hg or treatment), diabetes (>126 mg/dL or treatment), high cholesterol (>240 mg/dL or treatment), and smoking, and number of decades of vascular risk exposure across Visits 1-4. RESULTS: The average adjusted rate of SPPB decline (points per 5 years) for older adults was -0.79 (confidence interval [CI]: -0.87, 0.71) and was accelerated by mid-life hypertension (+57% decline vs normotension: additional decline of -0.47, 95% CI: -0.64, -0.30), diabetes (+73% decline vs no diabetes: additional decline of -0.67, 95% CI: -1.09, -0.24), elevated systolic blood pressure (+17% decline per SD: -0.16, 95% CI: -0.23, -0.10), and elevated fasting blood glucose (+16% decline per SD: -0.015, 95% CI: -0.24, -0.06). Each decade greater mid-life exposure to hypertension (+32% decline: -0.93, 95% CI: -1.25, -0.61) and diabetes (+35% decline: -1.03, 95% CI: -1.68, -0.38) was associated with faster SPPB decline. CONCLUSIONS: Mid-life control of blood pressure and diabetes may offset aging-related functional decline.
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Aterosclerosis , Demencia , Diabetes Mellitus , Hipertensión , Humanos , Femenino , Anciano , Masculino , Estudios Prospectivos , Hipertensión/epidemiología , Diabetes Mellitus/epidemiología , Aterosclerosis/epidemiologíaRESUMEN
OBJECTIVES: Previous studies suggest an association between central arterial stiffness (CAS) and intracranial atherosclerotic disease (ICAD) among Asian participants with stroke or hypertension; this association has not been evaluated in United States populations. We assessed the cross-sectional association of CAS with ICAD presence and burden in late-life, and differences in association by age, sex, and race. MATERIALS AND METHODS: We conducted a cross-sectional analysis of 1,285 Atherosclerosis Risk in Communities Study participants [mean age 75 (standard deviation: 5) years, 38 % male, 20 % Black] at Visit 5 (2011-2013). CAS was measured as carotid-femoral pulse wave velocity (cfPWV) using the Omron VP-1000 Plus. ICAD was assessed using high-resolution vessel wall MRI and MR angiography. We evaluated associations of a 1 standard deviation (SD) cfPWV (3.02 m/s) and high vs. non-high cfPWV (≥ 13.57 m/s vs. < 13.57 m/s) with presence of plaques (yes/no) and plaque number (0, 1-2, and >2) using multivariable logistic and ordinal logistic regression models adjusted for covariates. RESULTS: Each one SD greater cfPWV was associated with higher odds of plaque presence (odds ratio (OR)=1.32, 95 % confidence interval (CI): 1.22, 1.43), and an incrementally higher odds of number of plaques (OR 1-2 vs. 0 plaques = 1.21, 95 % CI: 1.10, 1.33; OR >2 vs. 0 plaques = 1.51, 95 % CI: 1.33,1.71). Results suggested differences by race, with greater magnitude associations among Black participants. CONCLUSIONS: CAS was positively associated with ICAD presence and burden; cfPWV may be a useful subclinical vascular measure for identification of individuals who are at high risk for cerebrovascular disease.
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Aterosclerosis , Arteriosclerosis Intracraneal , Placa Aterosclerótica , Rigidez Vascular , Humanos , Masculino , Estados Unidos/epidemiología , Anciano , Femenino , Factores de Riesgo , Análisis de la Onda del Pulso/métodos , Estudios Transversales , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/epidemiología , Arteriosclerosis Intracraneal/complicaciones , Arteriosclerosis Intracraneal/diagnóstico por imagen , Arteriosclerosis Intracraneal/epidemiologíaRESUMEN
Aging adults experience increased health vulnerability and compromised abilities to cope with stressors, which are the clinical manifestations of frailty. Frailty is complex, and efforts to identify biomarkers to detect frailty and pre-frailty in the clinical setting are rarely reproduced across cohorts. We developed a predictive model incorporating biological and clinical frailty measures to identify robust biomarkers across data sets. Data were from two large cohorts of older adults: "Invecchiare in Chianti (Aging in Chianti, InCHIANTI Study") (n = 1453) from two small towns in Tuscany, Italy, and replicated in the Atherosclerosis Risk in Communities Study (ARIC) (n = 6508) from four U.S. communities. A complex systems approach to biomarker selection with a tree-boosting machine learning (ML) technique for supervised learning analysis was used to examine biomarker population differences across both datasets. Our approach compared predictors with robust, pre-frail, and frail participants and examined the ability to detect frailty status by race. Unique biomarker features identified in the InCHIANTI study allowed us to predict frailty with a model accuracy of 0.72 (95% confidence interval (CI) 0.66-0.80). Replication models in ARIC maintained a model accuracy of 0.64 (95% CI 0.66-0.72). Frail and pre-frail Black participant models maintained a lower model accuracy. The predictive panel of biomarkers identified in this study may improve the ability to detect frailty as a complex aging syndrome in the clinical setting. We propose several concrete next steps to keep research moving toward detecting frailty with biomarker-based detection methods.
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Fragilidad , Humanos , Anciano , Fragilidad/diagnóstico , Anciano Frágil , Biomarcadores , Envejecimiento , Italia/epidemiologíaRESUMEN
OBJECTIVES: Deprived living environments contribute to greater heart failure (HF) risk among non-Hispanic Black persons, who disproportionately occupy disadvantaged neighborhoods. The mechanisms for these effects are not fully explicated, partially attributable to an insufficient understanding of the individual factors that contribute additional risk or resilience to the impact of neighborhood disadvantage on health. The objective of this study was, therefore, to clarify the complex pathways over which such exposures act to facilitate more targeted, effective interventions. Given the evidence for a mediating role of biological age and a moderating role of individual psychosocial characteristics in the neighborhood disadvantage-HF link, we tested a moderated mediation mechanism. METHODS: Using multilevel causal moderated mediation models, we prospectively examined whether the association of neighborhood disadvantage with incident HF mediated through accelerated biological aging, captured by the GrimAge epigenetic clock, is moderated by hypothesized psychosocial risk (negative affect) and resilience (optimism) factors. RESULTS: Among a sample of 1,448 Black participants in the shared Jackson Heart Study-Atherosclerosis Risk in Communities cohort (mean age 64.3 years), 334 adjudicated incident hospitalized HF events occurred over a median follow-up of 18 years. In models adjusted for age and sex, the indirect (GrimAge-mediated) effect of neighborhood disadvantage was moderated by psychosocial risk such that for every standard deviation increase in negative affect the hazards of HF was 1.18 (95% confidence intervalâ =â 1.05, 1.36). No moderated mediation effect was detected for optimism. DISCUSSION: Findings support the necessity for multilevel interventions simultaneously addressing neighborhood and individual psychosocial risk in the reduction of HF among Black persons.
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Envejecimiento , Insuficiencia Cardíaca , Características del Vecindario , Resiliencia Psicológica , Humanos , Negro o Afroamericano , Insuficiencia Cardíaca/epidemiología , Incidencia , Análisis de Mediación , Factores de Riesgo , Persona de Mediana EdadRESUMEN
BACKGROUND: Hearing loss is associated with adverse health outcomes among older adults. Lower physical activity levels may partly explain these observations, yet the association between hearing loss, hearing aid use, and physical activity among older adults is understudied. METHODS: Cross-sectional analysis of National Health and Aging Trends Study (2021) participants. The better-hearing ear pure-tone average (BPTA) at speech frequencies (0.5-4 kHz) was modeled continuously (10-dB increments) and categorically (no: ≤25 dB, mild: 26-40 dB, moderate or greater: >40 dB hearing loss). Activity measures were wrist accelerometry-derived (Actigraph) total activity counts, daily active minutes, activity fragmentation (using active-to-sedentary transition probability), and self-reported participation in vigorous activities and walking for exercise in the last month. We used multivariable regression adjusted for sociodemographic and health covariates. RESULTS: Among 504 participants excluding hearing aid users (mean age = 79 years, 57% female, 9% Black), 338 (67%) had hearing loss. Worse hearing (continuously and categorically) was associated with fewer counts and active minutes, more fragmented activity, and greater odds of not reporting recent vigorous activities. Among 472 participants with hearing loss including hearing aid users, nonusers (n = 338) had more fragmented activity and greater odds of not reporting walking for exercise compared to users. CONCLUSIONS: Older adults with hearing loss are less physically active. This may mediate the association between hearing loss and other adverse outcomes. Recognition of this potential association is essential for providers to better support older adults in maintaining an active lifestyle. Future research is warranted to understand the impact of hearing interventions.