# Dose–Response Relationship Between Sleep Regularity Index and Stage-Specific Alzheimer’s Disease: Cross-Sectional Evidence from Japanese Adults

**Authors:** Yue Cao, Jaehee Lee, Jaehoon Seol, Kenji Tsunoda, Kyohei Shibuya, Jieun Yoon, Tetsuaki Arai, Tomohiro Okura

PMC · DOI: 10.3390/geriatrics11020032 · 2026-03-18

## TL;DR

This study finds that maintaining regular sleep patterns may help reduce the risk of Alzheimer's disease progression in Japanese adults.

## Contribution

The study identifies a non-linear dose-response relationship between sleep regularity and Alzheimer's disease stages.

## Key findings

- Prevalence ratios of cognitive impairment decline beyond a Sleep Regularity Index (SRI) of 60.
- Participants with SRI above 60 showed lower prevalence ratios of poorer executive function.
- Results were independent of age, sleep duration, and depression risk.

## Abstract

Background/Objectives: Daily sleep patterns are associated with cognitive health and Alzheimer’s disease (AD). However, it remains unclear how suboptimal irregular sleep manifests in AD from the preclinical stage to dementia. This study aimed to establish the dose–response association between sleep irregularity and psychometrically defined stage-specific AD as well as executive dysfunction, among adults with subjective cognitive and sleep issues. Methods: Cross-sectional data were obtained from 532 Japanese adults (mean age = 63.9 years) between March 2023 and April 2024. Sleep irregularity was quantified using the Sleep Regularity Index (SRI) with 24/7 accelerometer data. A modified Poisson regression with cubic splines was performed to establish the dose–response association. Results: This study identified novel non-linear associations. The prevalence ratios of cognitive impairment, defined as being in the preclinical and more advanced stages of AD, significantly declined beyond a median SRI of 60. Participants within this SRI range also showed significantly lower prevalence ratios of poorer Trail Making Test B performance. All results were independent of age, sleep duration, and risk of depression. Conclusions: Maintaining balanced-to-regular daily sleep patterns might be optimal for AD progress from its preclinical stages, with a potential benchmark at SRI of 60, especially for those individuals at risk for cognitive decline and sleep disorders. Further research is needed to replicate this benchmark in diverse populations and to evaluate the effect of rigid sleep regularity on cognitive health.

## Linked entities

- **Diseases:** Alzheimer’s disease (MONDO:0004975), depression (MONDO:0002050)

## Full-text entities

- **Genes:** TPSG1 (tryptase gamma 1) [NCBI Gene 25823] {aka PRSS31, TMT, trpA}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}
- **Diseases:** stroke (MESH:D020521), injury to (MESH:D014947), THLS (MESH:D017204), MCI (MESH:D060825), Executive Dysfunction (MESH:D006331), SRI (MESH:C566784), Depression (MESH:D003866), sleep disorders (MESH:D012893), Cognitive Impairment (MESH:D003072), irregular (MESH:D008599), fragmentation (MESH:D012892), cardiac, or musculoskeletal disease (MESH:D009140), Dementia (MESH:D003704), Insomnia (MESH:D007319), physical disability (MESH:D059445), sleep disruptions (MESH:D019958), weight loss (MESH:D015431), AD (MESH:D000544), memory complaints (MESH:D008569)
- **Chemicals:** SRI (-), alcohol (MESH:D000438)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13010776/full.md

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Source: https://tomesphere.com/paper/PMC13010776