Sleep Quality Moderates Age-Related Decline in Hippocampal-Dependent Memory in Midlife Adults

TL;DR

Poor sleep quality worsens age-related memory decline in midlife adults, especially those with a family history of Alzheimer's.

Contribution

This study identifies sleep quality as a moderator of hippocampal-dependent memory decline in midlife adults.

Findings

Poorer sleep quality is linked to steeper age-related decline in hippocampal-dependent memory performance.

The Mnemonic Similarity Task (MST) is effective in detecting subtle cognitive changes in midlife.

Higher PSQI scores correlate with worse memory outcomes in older midlife adults.

Abstract

The hippocampus, critical for learning and memory, is vulnerable to age-related decline. Evidence suggests that sleep is associated with hippocampal integrity and cognitive function in older adults. However, few studies have examined whether sleep quality moderates age-related decline in hippocampal-dependent memory in midlife—a critical time point for detecting preclinical cognitive changes. In this cross-sectional study, we tested the hypothesis that poor sleep quality would be linked to steeper age-related decline in hippocampal-dependent memory performance in midlife. We analyzed data from cognitively normal midlife adults with a family history of Alzheimer’s disease (N = 180; Age= 40–65 years [M = 56.13±6.35 years]; 89% females, MoCA=27.9±1.7) enrolled in a clinical trial (NCT03876314). Participants completed the Pittsburg Sleep Quality Index (PSQI) and Mnemonic Similarity Task (MST)—a sensitive test of hippocampal-dependent memory function. Multiple linear regression was fitted while controlling for potential covariates (e.g., sex, education, APOE-ε4 carriage, and pulse pressure). There was a significant Age × PSQI interaction (b=–0.0017, p=.037) with lure discrimination index (LDI) as the outcome, such that higher PSQI scores (poorer sleep quality) were associated with steeper age-related decline in hippocampal-dependent memory performance. Simple slopes analysis showed that age predicted lower LDI in participants with average (b = −0.01, p=.01) and higher (+1 SD) PSQI (b = −0.01, p<.01), but not those with lower (–1 SD) PSQI (p=.81). These findings suggest the potential role of sleep quality in protecting hippocampal-dependent memory function against age-related decline in midlife and support the utility of the MST for detecting subtle cognitive changes during this critical life stage.