Midlife sleep characteristics and Alzheimer's disease biomarkers 20 years later

INTRODUCTION: Poor sleep characteristics are associated with Alzheimer's disease (AD) among older adults; however, this relationship remains underexplored earlier in life. We investigated how early midlife sleep relates to AD-related biomarkers in late midlife. METHODS: A total of 1325 adults (mean age = 40.3 years) self-reported sleep quality, sleep duration, daytime sleepiness, and insomnia symptoms. Twenty years later, we assessed plasma amyloid beta (Aβ)42/40, tau phosphorylated at threonine 217 (p-tau217), neurofilament light chain (NfL), and magnetic resonance imaging (MRI)-derived Spatial Pattern of Abnormality for Recognition of Early AD (SPARE-AD), characterizing AD-like brain atrophy. RESULTS: After multivariable adjustment, longer sleep duration was associated with lower Aβ42/40, poor sleep quality with higher NfL, daytime sleepiness with both lower Aβ42/40 and higher NfL, and insomnia symptoms with higher SPARE-AD. No associations were observed with sleep and p-tau217. DISCUSSION: Poor sleep in early midlife was associated with unfavorable AD biomarker levels 20 years later, supporting the idea of sleep as a potential modifiable AD risk factor.