Key Points Question Is neighborhood-level socioeconomic status (SES) associated with differences in cognition and dementia risk scores? Findings In this cross-sectional study of 4656 Australian adults aged 40 to 70 years enrolled in the population-based Healthy Brain Project cohort, higher neighborhood-level SES was associated with better memory and lower dementia risk scores. Meaning This study’s findings suggest that dementia research would benefit from including participants living in areas with lower SES to better understand relevant factors and potential interventions.

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Background: Insomnia is one of the most common sleep disorders yet its relationship to the biology of Alzheimer’s disease remains equivocal. Objective: We investigated the cross-sectional relationship between insomnia symptom severity and cerebrospinal fluid (CSF) concentrations of Alzheimer’s disease biomarkers in a cognitively unimpaired middle-aged community sample. Methods: A total of 63 participants from the Healthy Brain Project (age = 59±7 years; 67% women) completed a lumbar puncture and two weeks of actigraphy to measure two of insomnia’s core features: difficulty initiating sleep (prolonged sleep onset latency) and difficulty maintaining sleep (wake after sleep onset [WASO] and number of awakenings). Additionally, the Insomnia Severity Index (ISI) was completed by 58 participants. Linear and Tobit regression were used to estimate the associations between each insomnia variable and CSF Aβ42, phosphorylated tau 181 (p-tau181), total-tau, and neurofilament light chain protein (NfL), adjusting for age, sex, and APOE ɛ4 genotype. Results: Higher ISI score was associated with greater average levels of CSF Aβ 42 (per point: 30.7 pg/mL, 95% CI: 4.17–57.3, p = 0.023), as was higher WASO (per 10 min: 136 pg/mL, 95% CI: 48–223, p = 0.002) and more awakenings (per 5:123 pg/mL, 95% CI = 55–192, p < 0.001). Difficulty initiating sleep was not associated with CSF Aβ 42, nor were insomnia features associated with p-tau181, total-tau, or NfL levels. Conclusion: Insomnia symptoms were associated with higher CSF Aβ 42 levels in this relatively young, cognitively unimpaired sample. These findings may reflect increased amyloid production due to acute sleep disruption.

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