Cross-Sectional Associations of Peripheral Hearing, Brain Imaging, and Cognitive Performance With Speech-in-Noise Performance: The Aging and Cognitive Health Evaluation in Elders Brain Magnetic Resonance Imaging Ancillary Study.

PURPOSE: Population-based evidence in the interrelationships among hearing, brain structure, and cognition is limited. This study aims to investigate the cross-sectional associations of peripheral hearing, brain imaging measures, and cognitive function with speech-in-noise performance among older adults. METHOD: We studied 602 participants in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) brain magnetic resonance imaging (MRI) ancillary study, including 427 ACHIEVE baseline (2018-2020) participants with hearing loss and 175 Atherosclerosis Risk in Communities Neurocognitive Study Visit 6/7 (2016-2017/2018-2019) participants with normal hearing. Speech-in-noise performance, as outcome of interest, was assessed by the Quick Speech-in-Noise (QuickSIN) test (range: 0-30; higher = better). Predictors of interest included (a) peripheral hearing assessed by pure-tone audiometry; (b) brain imaging measures: structural MRI measures, white matter hyperintensities, and diffusion tensor imaging measures; and (c) cognitive performance assessed by a battery of 10 cognitive tests. All predictors were standardized to z scores. We estimated the differences in QuickSIN associated with every standard deviation (SD) worse in each predictor (peripheral hearing, brain imaging, and cognition) using multivariable-adjusted linear regression, adjusting for demographic variables, lifestyle, and disease factors (Model 1), and, additionally, for other predictors to assess independent associations (Model 2). RESULTS: Participants were aged 70-84 years, 56% female, and 17% Black. Every SD worse in better-ear 4-frequency pure-tone average was associated with worse QuickSIN (-4.89, 95% confidence interval, CI [-5.57, -4.21]) when participants had peripheral hearing loss, independent of other predictors. Smaller temporal lobe volume was associated with worse QuickSIN, but the association was not independent of other predictors (-0.30, 95% CI [-0.86, 0.26]). Every SD worse in global cognitive performance was independently associated with worse QuickSIN (-0.90, 95% CI [-1.30, -0.50]). CONCLUSIONS: Peripheral hearing and cognitive performance are independently associated with speech-in-noise performance among dementia-free older adults. The ongoing ACHIEVE trial will elucidate the effect of a hearing intervention that includes amplification and auditory rehabilitation on speech-in-noise understanding in older adults. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25733679.

Hearing Impairment and Physical Activity and Physical Functioning in Older Adults: Baseline Results From the ACHIEVE Trial.

BACKGROUND: Hearing loss is associated with restricted physical activity (PA) and impaired physical functioning, yet the relationship between severity of hearing impairment (HI) and novel PA measures in older adults with untreated HI is not well understood. METHODS: Analyses included 845 participants aged ≥70 years (mean = 76.6 years) with a better-hearing ear pure-tone average (PTA) ≥30 and <70 dB in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study who wore an ActiGraph accelerometer for 7 days. Physical functioning measures included grip strength and the Short Physical Performance Battery (SPPB). Linear regression models estimated the association by HI level (moderate or greater [PTA ≥ 40 dB] vs mild [PTA < 40 dB]) and continuous hearing with total daily activity counts, active minutes/day, activity fragmentation, grip strength, and gait speed. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of poor performance on the SPPB (≤6) and its subtests (≤2). Mixed-effects models estimated differences by HI level in activity by time of day. RESULTS: Participants with moderate or greater HI had poorer physical functioning, particularly balance (OR = 2.17, 95% CI = 1.29-3.67), versus those with mild impairment. There was no association of HI level with activity quantities or fragmentation. For diurnal patterns of activity, participants with moderate or greater HI had fewer activity counts in the afternoon (12:00 pm -05:59 pm). CONCLUSIONS: Older adults with worse hearing had shifted diurnal patterns and poorer balance performance. Exercise programs should be tailored to older adults with different levels of HI to maintain PA and physical functioning, particularly balance control.

Nonalcoholic Fatty Liver Disease and Longitudinal Change in Imaging and Plasma Biomarkers of Alzheimer Disease and Vascular Pathology.

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.

Description of the Baseline Audiologic Characteristics of the Participants Enrolled in the Aging and Cognitive Health Evaluation in Elders Study.

PURPOSE: The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study is a randomized clinical trial designed to determine the effects of a best-practice hearing intervention versus a successful aging health education control intervention on cognitive decline among community-dwelling older adults with untreated mild-to-moderate hearing loss. We describe the baseline audiologic characteristics of the ACHIEVE participants. METHOD: Participants aged 70-84 years (N = 977; Mage = 76.8) were enrolled at four U.S. sites through two recruitment routes: (a) an ongoing longitudinal study and (b) de novo through the community. Participants underwent diagnostic evaluation including otoscopy, tympanometry, pure-tone and speech audiometry, speech-in-noise testing, and provided self-reported hearing abilities. Baseline characteristics are reported as frequencies (percentages) for categorical variables or medians (interquartiles, Q1-Q3) for continuous variables. Between-groups comparisons were conducted using chi-square tests for categorical variables or Kruskal-Wallis test for continuous variables. Spearman correlations assessed relationships between measured hearing function and self-reported hearing handicap. RESULTS: The median four-frequency pure-tone average of the better ear was 39 dB HL, and the median speech-in-noise performance was a 6-dB SNR loss, indicating mild speech-in-noise difficulty. No clinically meaningful differences were found across sites. Significant differences in subjective measures were found for recruitment route. Expected correlations between hearing measurements and self-reported handicap were found. CONCLUSIONS: The extensive baseline audiologic characteristics reported here will inform future analyses examining associations between hearing loss and cognitive decline. The final ACHIEVE data set will be publicly available for use among the scientific community. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24756948.

The Relationship of Neighborhood Disadvantage, Biological Aging, and Psychosocial Risk and Resilience Factors in Heart Failure Incidence Among Black Persons: A Moderated Mediation Analysis.

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 interval = 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.

Depression and Health-Related Quality of Life Among Older Adults With Hearing Loss in the ACHIEVE Study.

Hearing loss is associated with cognitive/physical health; less is known about mental health. We investigated associations between hearing loss severity, depression, and health-related quality of life among older adults with unaided hearing loss. Data (N = 948) were from the Aging and Cognitive Health Evaluation in Elders Study. Hearing was measured by pure-tone average (PTA), Quick Speech-in-Noise (QuickSIN) test, and the Hearing Handicap Inventory for the Elderly (HHIE-S). Outcomes were validated measures of depression and health-related quality of life. Associations were assessed by negative binomial regression. More severe hearing loss was associated with worse physical health-related quality of life (ratio: .98, 95% CI: .96, 1.00). Better QuickSIN was associated with higher mental health-related quality of life (1.01 [1.00, 1.02]). Worse HHIE-S was associated with depression (1.24 [1.16, 1.33]) and worse mental (.97 [.96, .98]) and physical (.95 [ .93, .96]) health-related quality of life. Further work will test effects of hearing intervention on mental health.

Underage Alcohol Use by Intersectional Identity Among Alternative High School Students.

PURPOSE: To examine alcohol use (AU) among intersectional subgroups within a longitudinal cohort of predominantly Hispanic/Latino alternative high school (AHS) students in southern California. METHODS: Past month AU was measured over a period of three years among 1,029 students (mean age 17.5 years, 49.7% female, 76.1% Hispanic/Latino) from 29 AHSs. Multilevel models that adjusted for age, socioeconomic status, parental education, weekly income, sensation seeking, depression, anxiety, and stress estimated trends in AU over time among intersectional subgroups defined by gender, ethnicity, and generational immigration. RESULTS: Students with parents born in the United States had high rates of AU at the baseline that remained stable over time. In contrast, first-generation Hispanic/Latino students had lower levels of AU at the baseline that increased over time. First-generation, female, Hispanic/Latino students exhibited one of the lowest probabilities of AU at the baseline (28.6%, confidence interval [CI]: 15.9%-41.3%) but at the two-year follow-up had one of the highest probabilities (47.4%, CI: 29.3%-65.5%). A similar trend was observed among first-generation, male, Hispanic/Latino students whose probability of past month AU rose between the baseline (23.1%, CI: 12.4%-33.8%) and two-year follow-up (36.0%, CI: 19.2%-52.7%). DISCUSSION: Findings underscore the heterogeneity of AHS students, showing a more nuanced picture of AU by the intersection of gender, ethnicity, and generational immigration. Underage AU prevention efforts among AHS students must provide targeted messages to intersectional identities.

Distinct moderating pathways for psychosocial risk and resilience in the association of neighborhood disadvantage with incident heart failure among Black persons.

Objective: To assess whether psychosocial factors moderate the associations between neighborhood disadvantage and incident heart failure (HF). Methods: Among 1448 Non-Hispanic (NH) Black persons dually enrolled in two community-based cohorts in Jackson, Mississippi who were free of HF as of January 1, 2000, 336 HF events classified by reviewer panel accrued through December 31, 2017. Multilevel, multivariable Cox regression models were used to examine whether optimism and negative affect moderated the associations of two measures of neighborhood characteristics (the national Area Deprivation Index (ADI) and perceived neighborhood problems) on incident hospitalized HF. Results: Optimism moderated the association of the ADI with incident HF. Compared to participants reporting the lowest tertile of optimism, those in the highest tertile of optimism had a 29% lower rate of HF associated with increasing ADI in fully adjusted models. We found no evidence for a moderating effect of negative affect. Conclusions: This study supports optimism as a source of resilience to the detrimental effects of neighborhood disadvantage on HF risk. Population-level strategies to promote sociocultural antecedents to optimism may serve as a viable method of reducing the disproportionate burden of HF among NH Black persons.

Cerebral Microbleed Patterns and Cortical Amyloid-ß: The ARIC-PET Study.

BACKGROUND: Cerebral microbleeds (CMBs) are associated with cognitive decline, but their importance outside of cerebral amyloid angiopathy and the mechanisms of their impact on cognition are poorly understood. We evaluated the cross-sectional association between CMB patterns and cerebral Aß (amyloid-ß) deposition, by florbetapir positron emission tomography. METHODS: The longitudinal ARIC study (Atherosclerosis Risk in Communities) recruited individuals from 4 US communities from 1987 to 1989. From 2012 to 2014, the ARIC-PET (Atherosclerosis Risk in Communities - Positron Emission Tomography) ancillary recruited 322 nondemented ARIC participants who completed 3T brain magnetic resonance imaging with T2*GRE as part of ARIC visit 5 to undergo florbetapir positron emission tomography imaging. Magnetic resonance imaging images were read for CMBs and superficial siderosis; on positron emission tomography, global cortical standardized uptake value ratio >1.2 was considered a positive Aß scan. Multivariable logistic regression models evaluated CMB characteristics in association with Aß positivity. Effect modification by sex, race, APOE status, and cognition was evaluated. RESULTS: CMBs were present in 24% of ARIC-PET participants. No significant associations were found between CMBs and Aß positivity, but a pattern of isolated lobar CMBs or superficial siderosis was associated with over 4-fold higher odds of elevated Aß when compared with those with no CMBs (odds ratio, 4.72 [95% CI, 1.16-19.16]). A similar elevated risk was not observed in those with isolated subcortical or mixed subcortical and either lobar CMBs or superficial siderosis. Although no significant interactions were found, effect estimates for elevated Aß were nonsignificantly lower (P>0.10, odds ratio, 0.4-0.6) for a mixed CMB pattern, and odds ratios were nonsignificantly higher for lobar-only CMBs for 4 subgroups: women (versus men); Black participants (versus White participants), APOE ε4 noncarriers (versus carriers), and cognitively normal (versus mild cognitive impairment). CONCLUSIONS: In this community-based cohort of nondemented adults, lobar-only pattern of CMBs or superficial siderosis is most strongly associated with brain Aß, with no elevated risk for a mixed CMB pattern. Further studies are needed to understand differences in CMB patterns and their meaning across subgroups.

Hearing intervention versus health education control to reduce cognitive decline in older adults with hearing loss in the USA (ACHIEVE): a multicentre, randomised controlled trial.

BACKGROUND: Hearing loss is associated with increased cognitive decline and incident dementia in older adults. We aimed to investigate whether a hearing intervention could reduce cognitive decline in cognitively healthy older adults with hearing loss. METHODS: The ACHIEVE study is a multicentre, parallel-group, unmasked, randomised controlled trial of adults aged 70-84 years with untreated hearing loss and without substantial cognitive impairment that took place at four community study sites across the USA. Participants were recruited from two study populations at each site: (1) older adults participating in a long-standing observational study of cardiovascular health (Atherosclerosis Risk in Communities [ARIC] study), and (2) healthy de novo community volunteers. Participants were randomly assigned (1:1) to a hearing intervention (audiological counselling and provision of hearing aids) or a control intervention of health education (individual sessions with a health educator covering topics on chronic disease prevention) and followed up every 6 months. The primary endpoint was 3-year change in a global cognition standardised factor score from a comprehensive neurocognitive battery. Analysis was by intention to treat. This trial was registered at ClinicalTrials.gov, NCT03243422. FINDINGS: From Nov 9, 2017, to Oct 25, 2019, we screened 3004 participants for eligibility and randomly assigned 977 (32·5%; 238 [24%] from ARIC and 739 [76%] de novo). We randomly assigned 490 (50%) to the hearing intervention and 487 (50%) to the health education control. The cohort had a mean age of 76·8 years (SD 4·0), 523 (54%) were female, 454 (46%) were male, and most were White (n=858 [88%]). Participants from ARIC were older, had more risk factors for cognitive decline, and had lower baseline cognitive scores than those in the de novo cohort. In the primary analysis combining the ARIC and de novo cohorts, 3-year cognitive change (in SD units) was not significantly different between the hearing intervention and health education control groups (-0·200 [95% CI -0·256 to -0·144] in the hearing intervention group and -0·202 [-0·258 to -0·145] in the control group; difference 0·002 [-0·077 to 0·081]; p=0·96). However, a prespecified sensitivity analysis showed a significant difference in the effect of the hearing intervention on 3-year cognitive change between the ARIC and de novo cohorts (pinteraction=0·010). Other prespecified sensitivity analyses that varied analytical parameters used in the total cohort did not change the observed results. No significant adverse events attributed to the study were reported with either the hearing intervention or health education control. INTERPRETATION: The hearing intervention did not reduce 3-year cognitive decline in the primary analysis of the total cohort. However, a prespecified sensitivity analysis showed that the effect differed between the two study populations that comprised the cohort. These findings suggest that a hearing intervention might reduce cognitive change over 3 years in populations of older adults at increased risk for cognitive decline but not in populations at decreased risk for cognitive decline. FUNDING: US National Institutes of Health.

Prediabetes, intervening diabetes and subsequent risk of dementia: the Atherosclerosis Risk in Communities (ARIC) study.

AIMS/HYPOTHESIS: The aim of this work was to evaluate whether the association of prediabetes with dementia is explained by the intervening onset of diabetes. METHODS: Among participants of the Atherosclerosis Risk in Communities (ARIC) study we defined baseline prediabetes as HbA1c 39-46 mmol/mol (5.7-6.4%) and subsequent incident diabetes as a self-reported physician diagnosis or use of diabetes medication. Incident dementia was ascertained via active surveillance and adjudicated. We quantified the association of prediabetes with dementia risk before and after accounting for the subsequent development of diabetes among ARIC participants without diabetes at baseline (1990-1992; participants aged 46-70 years). We also evaluated whether age at diabetes diagnosis modified the risk of dementia. RESULTS: Among 11,656 participants without diabetes at baseline, 2330 (20.0%) had prediabetes. Before accounting for incident diabetes, prediabetes was significantly associated with the risk of dementia (HR 1.12 [95% CI 1.01, 1.24]). After accounting for incident diabetes, the association was attenuated and non-significant (HR 1.05 [95% CI 0.94, 1.16]). Earlier age of onset of diabetes had the strongest association with dementia: HR 2.92 (95% CI 2.06, 4.14) for onset before 60 years; HR 1.73 (95% CI 1.47, 2.04) for onset at 60-69 years; and HR 1.23 (95% CI 1.08, 1.40) for onset at 70-79 years. CONCLUSIONS/INTERPRETATION: Prediabetes is associated with dementia risk but this risk is explained by the subsequent development of diabetes. Earlier age of onset of diabetes substantially increases dementia risk. Preventing or delaying progression of prediabetes to diabetes will reduce dementia burden.

Educational Attainment and Dementia: Mediation by Mid-Life Vascular Risk Factors.

INTRODUCTION: Lower education is associated with higher burden of vascular risk factors in mid-life and higher risk of dementia in late life. We aim to understand the causal mechanism through which vascular risk factors potentially mediate the relationship between education and dementia. METHODS: In a cohort of 13,368 Black and White older adults in the Atherosclerosis Risk in Communities Study, we assessed the relationship between education (grade school, high school without graduation, high school graduate or equivalent, college, graduate/professional school) and dementia among all participants and among those with incident stroke. Cox models were adjusted for age, race-center (a variable stratified by race and field center), sex, apolipoprotein E (APOE) ε4 genotype, and family history of cardiovascular disease. Causal mediation models assessed mediation by mid-life systolic blood pressure, fasting blood glucose, body mass index, and smoking. RESULTS: More education was associated with 8 to 44% lower risk of dementia compared to grade school-level education in a dose-response pattern, while the relationship between education and post-stroke dementia was not statistically significant. Up to 25% of the association between education and dementia was mediated through mid-life vascular risk factors, with a smaller percentage mediated for lower levels of education. INTERPRETATION: A substantial proportion of the relationship between education and dementia was mediated through mid-life vascular risk factors. However, risk factor modification is unlikely to fully address the large educational disparities in dementia risk. Prevention efforts must also address disparities in socioeconomic resources leading to divergent early-life education and other structural determinants of mid-life vascular risk factors. ANN NEUROL 2023;94:13-26.

Aging-Related Multisystem Dysregulation Over the Adult Life Span and Physical Function in Later Life: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Multisystem dysregulation (Dm) shows promise as a metric of aging and predicts mortality. However, Dm needs to be studied with less severe endpoints indicating modifiable aging stages. Physical function, reflecting healthy longevity rather than just longevity, is more relevant to the goals of geroscience but has not been well investigated. METHODS: We tested the association of midlife Dm and its change over ~20 years with physical function in later life in 5 583 the Atherosclerosis Risk in Communities Study cohort participants (baseline mean age 54.7). Dm quantifies the multivariate statistical deviation of 17 physiologically motivated biomarkers relative to their distribution in a young healthy sample at baseline. Physical function was assessed from grip strength and the Short Physical Performance Battery (SPPB). Associations were quantified using linear regression and ordinal logistic regression adjusting for age, sex, race, and education. RESULTS: Each unit increment in midlife Dm was associated with 1.71 times the odds of having a lower SPPB score. Compared to the first quartile of midlife Dm, the odds ratios of having a lower SPPB score were 1.25, 1.56, and 2.45, respectively, for the second-fourth quartiles. Similar graded association patterns were observed for each SPPB component test and grip strength. An inverse monotonic relationship also was observed between the annual growth rate of Dm and physical function. CONCLUSION: Greater Dm and progression in midlife were associated with lower physical function in later life. Future studies on the factors that lead to the progression of Dm may highlight opportunities to preserve physical function.

Decline in Lung Function From Mid-to Late-Life With Central Arterial Stiffness: The Atherosclerosis Risk in Communities Study.

We investigated the association of lung function at mid-life, later in life, and its 20-year decline, with arterial stiffness later in life. We examined 5720 Atherosclerosis Risk in Communities Study participants who attended Visits 1 (1987-1989) and 5 (2011-2013). Lung function measures were forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), obtained at Visits 1, 2 (1990-1992), and 5. Central artery stiffness (carotid-femoral pulse wave velocity [cfPWV]) was measured at Visit 5. We evaluated associations of lung function with later-life central artery stiffness and cfPWV >75th percentile by multivariable linear and logistic regressions. Lung function at Visit 1 (FEV1 ß: -26, 95% Confidence Interval [CI]: -48, -5; FVC ß: -14, 95% CI: -32, 5) and Visit 5 (FEV1 ß: -22, 95% CI: -46, 2; FVC ß: -18, 95% CI: -38, 2) were inversely associated with cfPWV at Visit 5, and with odds of high cfPWV in fully adjusted models. Twenty-year decline in lung function was not associated with continuous or dichotomous measures of arterial stiffness (FEV1 ß: 11, 95% CI: -46, 68; FVC ß: -4, 95% CI: -52, 43). Lung function at mid-life and late-life was inversely associated with arterial stiffness in later life.

Brain Imaging Features Associated with 20-Year Cognitive Decline in a Community-Based Multiethnic Cohort without Dementia.

INTRODUCTION: This study aimed to characterize the association of cognitive decline starting in midlife with brain pathology in late life in the absence of dementia. METHODS: Nondemented Atherosclerosis Risk in Communities participants with brain imaging, all cognitive factor scores (CFSs), and nonmissing covariates were included. CFSs were collected at three visits across 21 years (1990-2013) (short-term cognitive change [1990-1996], long-term cognitive change [1990-2013]), and brain magnetic resonance imaging and florbetapir positron emission tomography (PET) imaging were collected in 2011-13 (PET subset n = 327). Outcomes of interest were total and regional brain volumes (cm3), log2 (white matter hyperintensity volume), white matter integrity (fractional anisotropy, mean diffusivity), ≥1 lacunar infarct (3-20 mm), and elevated brain ß-amyloid (SUVR >1.2). Multivariable linear/logistic regression related outcomes to CFS slopes after adjusting for demographics and total intracranial volume. RESULTS: At baseline, the 1,734 participants had a mean (SD) age of 55 (5.2) years, and were 60% female and 26% Black. After adjustment, a 1-SD larger long-term decline in CFS was associated with a smaller relative total brain volume by 1.2% (95% CI: 1.0, 1.5), a smaller relative temporal lobe meta region volume by 1.9% (1.5, 2.3), a 13% (9, 17) larger volume of white matter hyperintensities, a 1.3-fold (1.2, 1.4) higher odds of having ≥1 lacune, and 1.7-fold (1.3, 2.2) higher odds of elevated brain ß-amyloid deposition and worse white matter integrity. Some long-term associations were also found for midlife short-term declines in CFS. CONCLUSIONS: This study provides evidence that starting in midlife, short-term and long-term declines in cognition are associated with multiple deleterious late-life differences in nondemented brains.

Low Liver Enzymes and Risk of Dementia: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Low levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the low physiologic range, surrogate markers for reduced liver metabolic function, are associated with cerebral hypometabolism, impairment in neurotransmitter production and synaptic maintenance, and a higher prevalence of dementia. It is unknown whether a prospective association exists between low liver enzyme levels and incident dementia. OBJECTIVE: To determine whether low levels of ALT and AST are associated with higher risk of incident dementia. METHODS: Plasma ALT and AST were measured on 10,100 study participants (mean age 63.2 years, 55% female, 22% black) in 1996-1998. Dementia was ascertained from comprehensive neuropsychological assessments, annual contact, and medical record surveillance. Cox proportional hazards regression was used to estimate the association. RESULTS: During a median follow-up of 18.3 years (maximum 21.9 years), 1,857 individuals developed dementia. Adjusted for demographic factors, incidence rates of dementia were higher at the lower levels of ALT and AST. Compared to the second quintile, ALT values <10th percentile were associated with a higher risk of dementia (hazard ratio [HR] 1.34, 95% CI 1.08-1.65). The corresponding HR was 1.22 (0.99-1.51) for AST. CONCLUSION: Plasma aminotransferases <10th percentile of the physiologic range at mid-life, particularly ALT, were associated with greater long-term risk of dementia, advocating for attention to the putative role of hepatic function in the pathogenesis of dementia.

Associations Between Family and Peer E-Cigarette Use With Adolescent Tobacco and Marijuana Usage: A Longitudinal Path Analytic Approach.

INTRODUCTION: Research indicates a link between adolescent e-cigarette use and combustible tobacco cigarette (CTC) initiation, and recent studies suggest their connection with marijuana uptake. Our 3-year longitudinal cohort study investigated the implications of adolescent, peer, and family e-cigarette use with adolescents' expectations and willingness to initiate CTC use, and subsequent CTC and marijuana use. AIMS AND METHODS: Relationships were examined in a secondary analysis of a 3-year longitudinal cohort subsample involving adolescents enrolled in alternative California high schools (N = 1025). Analyses examined responses over three yearly observations. Family, peer, and respondents' e-cigarette use, respondents' positive cigarette expectancies and willingness to use CTCs were assessed in the study's first year (T1). CTC use in the survey's second year (T2) and marijuana use in the third year (T3) were assessed via path analysis. RESULTS: Respondents reporting at least one family member or peer using e-cigarettes were more likely to use e-cigarettes at T1 than those whose peers/family members did not. They reported more positive expectancies about CTCs and greater willingness to initiate use. These variables predicted CTC use at T2, which directly anticipated marijuana use in the survey's third year (T3), as did adolescents' use of e-cigarettes at T1. All model relations were statistically significant. CONCLUSIONS: Analysis demonstrated the strong association of family members' and peers' behaviors with adolescent e-cigarette use, and the temporal precedence of e-cigarette use with subsequent CTC and marijuana uptake. The predictive implications of e-cigarettes for other dangerous substance use should be examined in future prevention campaigns. IMPLICATIONS: The presented study expands upon existing literature connecting adolescent e-cigarette use and later CTC and marijuana use. The findings indicate the significant implications of exposure to e-cigarette use by parents and peers and demonstrate in a longitudinal 4-year panel survey the direct and indirect predictive implications of e-cigarette use for CTC and marijuana uptake. The research illustrates the utility of programs and campaigns that target peer and family groups to maximize impacts on adolescent willingness to try CTCs, positive expectancies, and possible onset of CTC and marijuana use.

A longitudinal analysis of nondaily smokers: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

PURPOSE: Nondaily smoking is increasing in the United States and common among Hispanic/Latino smokers. We characterized factors related to longitudinal smoking transitions in Hispanic/Latino nondaily smokers. METHODS: The Hispanic Community Health Study/Study of Latinos is a population-based cohort study of Hispanics/Latinos aged 18-74 years. Multinomial logistic regression assessed the baseline factors (2008-2011) associated with follow-up smoking status (2014-2017) in nondaily smokers (n = 573), accounting for complex survey design. RESULTS: After ∼6 years, 41% of nondaily smokers became former smokers, 22% became daily smokers, and 37% remained nondaily smokers. Factors related to follow-up smoking status were number of days smoked in the previous month, household smokers, education, income, and insurance. Those smoking 16 or more of the last 30 days had increased risk of becoming a daily smoker [vs. < 4 days; relative risk ratio (RRR) = 5.65, 95% confidence interval (95% CI) = 1.96-16.33]. Greater education was inversely associated with transitioning to daily smoking [>high school vs.

Self-regulation interventions to reduce consumption of sugar-sweetened beverages in adolescents.

This study evaluated the efficacy of self-regulation interventions through the use of drink-specific implementation intentions and drink-specific Go/No-Go training tasks as compensatory strategies to modify inhibitory control to reduce intake of sugar-sweetened beverages (SSB). In a between-subjects randomized manipulation of implementation intentions and Go/No-Go training to learn to inhibit sugary drink consumption, 168 adolescents reporting inhibitory control problems over sugary drinks and foods were recruited from high schools in southern California to participate. Analysis of covariance overall test of effects revealed no significant differences between the groups regarding calories consumed, calories from SSBs, grams of sugar consumed from drinks, or the number of unhealthy drinks chosen. However, subsequent contrasts revealed SSB implementation intentions significantly reduced SSB consumption following intervention while controlling for inhibitory control failure and general SSB consumption during observation in a lab setting that provided SSBs and healthy drinks, as well as healthy and unhealthy snacks. Specifically, during post-intervention observation, participants in the sugar-sweetened beverage implementation intentions (SSB-II) conditions consumed significantly fewer calories overall, fewer calories from drinks, and fewer grams of sugar. No effects were found for the drink-specific Go/No-Go training on SSB or calorie consumption. However, participants in SSB-II with an added SSB Go/No-Go training made fewer unhealthy drink choices than those in the other conditions. Implementation intentions may aid individuals with inhibitory (executive control) difficulties by intervening on pre-potent behavioral tendencies, like SSB consumption.