Background:The effect of an intensive lifestyle intervention (ILI) on Alzheimer's disease (AD) blood-based biomarker levels and cognitive outcomes among individuals with type 2 diabetes (T2D) is unknown. We examined AD biomarkers and cognitive outcomes in the Look AHEAD Study. Method: Participants aged 45-76 years were randomized at baseline to a 10-year ILI or a diabetes support and education (DSE) condition. Cognitive assessments at years 8-18 included measures of attention, executive function, global function, and memory. Mild cognitive impairment (MCI) and probable dementia were adjudicated by an expert panel. Stored baseline and end-of-intervention plasma samples were analyzed with the Quanterix Simoa HD-X Analyzer. Changes in Aβ 42 /Aβ 40, ptau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were evaluated in relation to randomization status, demographic characteristics, and cognitive outcomes. Cognitive scores and biomarker levels were converted to z-scores. Cognitive trajectories were evaluated using mixed models to account for repeated measures; logistic regression was used for a composite outcome of MCI/dementia. Models were adjusted for baseline characteristics (age, sex, education, race/ethnicity, body mass index (BMI), CVD history, hypertension, diabetes duration, eGFR), APOE-ε4, randomization arm, time from randomization, and time between blood draw and cognitive testing. Result:The mean age of 779 participants was 61.4 years; 56% = female, 22.8% = APOE ε4+, mean BMI = 34.8, baseline diabetes duration >5 years = 57%, 16.7% Black, 12.5% Hispanic, 66.2% White, and 4.7% other racial and ethnic groups. There were no associations between the intervention and biomarker levels at baseline or biomarker change over time. Increases in NfL levels significantly predicted lower memory (-0.04 ±0.01; p = 0.002), global cognition scores (-0.05 ±0.02; p = 0.011), executive function (-0.04 ±0.01; p = 0.01), as well as increased risk of MCI/probable dementia (odds ratio [OR]
BACKGROUND: Daytime sleepiness is common in older adults and may result from poor nighttime sleep due to sleep disordered breathing, fragmented sleep, or other sleep disorders. Daytime sleepiness may be associated with cognition in older adults. OBJECTIVES: We investigated the association between selfreported daytime sleepiness and cognitive function in the Look AHEAD clinical trial. DESIGN: Observational follow-up of a randomized clinical trial of an intensive lifestyle intervention. SETTING: Clinic. Participants: Participants (n=1,778) aged 45-76 years at baseline with type 2 diabetes and overweight or obesity. INTERVENTIONS: Participants were randomized to an intensive lifestyle intervention for weight loss or a control condition of diabetes support and education. MEASUREMENTS: Participants provided self-reported levels of daytime sleepiness at baseline and years 12-13. Cognitive function was assessed with a neurocognitive battery at years 12-13 and 18-20.RESULTS: Participants who reported having frequent daytime sleepiness (often or always) performed significantly worse than others on the cognitive composite (-0.35; p-value=0.014) after controlling for covariates. When stratified by intervention arm, participants assigned to the intensive lifestyle intervention who reported often/always having daytime sleepiness performed worse on Digit Symbol Coding (-0.63; p-value=0.05) and Trail Making Part-B (-0.56; p-value=0.02) after controlling for covariates. Statistical interactions revealed associations between daytime sleepiness and the following covariates: race and ethnicity, APOE ε4 carrier status, baseline history of cardiovascular disease, and depression. CONCLUSIONS: Daytime sleepiness over ~13 years predicted poorer cognitive performance in older individuals who, by virtue of having diabetes and overweight/obesity, are at high risk for sleep disorders and cognitive impairment.
BackgroundEarly‐life disadvantage may increase the risk for later cognitive decline. Recently, other aspects of early‐life adversity (ELA) have received attention but their associations with cognitive decline in later life has not been widely studied. Due to the sensitivity of such questions and the potential for systematic bias, we examined (1) predictors of response patterns to ELA questions, and (2) among those who completed ELA questions, we examined whether responses were associated with cognitive decline in the Multi‐Ethnic Study of Atherosclerosis (MESA).MethodELA was self‐reported via a 7‐item telephone assessment of socioemotional and physical threat or deprivation at MESA annual follow‐up call in 2019. Descriptive statistics were grouped by completion status: not completed, partially completed, and fully completed. Continuous variables were compared across groups with t‐tests; categorical variables were compared with chi‐square tests. Cognitive function was measured using the Cognitive Abilities Screening Instrument (CASI) at MESA Exams 5 (2010‐2012) and 6 (2016‐2018). Multinomial logistic regression was used to determine predictors of completion group membership. Cognitive decline from Exam 5 to 6 by completion group was assessed using multivariable linear regression.ResultOf the 3,990 participants interviewed, the mean age was 59.2y (SD = 8.8), 55% were female, and 40% were White (n = 1,604), 13% Chinese (n = 508), 26% Black (n = 1,036), and 21% Hispanic/Latino (n = 842). The odds of partial response was higher for those born outside of the U.S. (2.17, CI 95%: 1.53‐3.09), and among participants who spoke Spanish (2.82, CI 95%: 1.74‐4.58) or Chinese (2.04, CI 95%: 1.08‐3.88) at baseline. Among participants with completed ELA (n = 3,173), one component of childhood adversity: how often was your household well‐organized/managed, was associated with better Exam 6 CASI score (β = 0.80, SE = 0.33; p = 0.015) adjusting for age, race, education, gender, language, years in the U.S., socio‐economic status (SES), and parental birthplace. There was no significant association between cognitive change from Exam 5 to Exam 6 and ELA completion.ConclusionFactors associated with acculturation including country of participant’s birth and language preference predicted completion status on questions of ELA. Future studies should be mindful of the potentially differential response patterns and the implications for interpretation when analyzing ELA data.
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