Authors
Shohei Fujita, Susumu Mori, Kengo Onda, Shouhei Hanaoka, Yukihiro Nomura, Takahiro Nakao, Akifumi Hagiwara, Yasuhiro Hagiwara, Hidemasa Takao, Takeharu Yoshikawa, Osamu Abe
Published in
Brain communications. Volume 8. Issue 5. Pages fcag343. Epub Sep 07, 2026.
Abstract
Brain ageing is a major determinant of cognitive health, yet the extent of inter-individual variability in structural trajectories and its links to lifestyle factors remain incompletely understood. We conducted a single-centre, prospective longitudinal cohort study within an urban academic health screening programme in Japan (November 2006 to April 2021), with up to 15 years of follow-up. Among 10 209 individuals who underwent screening, those with more than 10 years of serial visits were eligible; 186 participants were excluded for major intracranial findings, 3 for cognitive decline during follow-up and 3 for contraindications or ineligibility, yielding 653 cognitively normal adults [207 women (31.6%); mean (SD) age at baseline, 55.1 (9.3) years]. Participants underwent serial magnetic resonance imaging and Mini-Mental State Examination, along with baseline assessments of lifestyle and vascular risk factors including body mass index, blood pressure, smoking exposure and lipid profile. Annual percentage change in whole-brain and regional volumes was estimated using linear mixed-effects models after harmonization for scanner effects, and participants were categorized as rapid atrophy, typical, or atrophy-resistant based on percentile thresholds. Across 7915 MRI scans, whole-brain volume decline accelerated from 0.24% per year in the 40s to 0.44% per year in the 70s. Individuals classified as having rapid atrophy in their 40s exhibited rates of decline of 0.46% per year, comparable to population averages in the 70s, whereas atrophy-resistant individuals in their 70s demonstrated rates as low as 0.27% per year. Faster whole-brain atrophy was associated with higher body mass index [β = 0.027; 95% confidence interval (CI), 0.0058-0.049], greater smoking exposure (β = 0.032; 95% CI, 0.012-0.053), elevated diastolic blood pressure (β = 0.044; 95% CI, 0.021-0.067) and higher low-density lipoprotein cholesterol (β = 0.043; 95% CI, 0.021-0.065) (all P < 0.01). Utilizing an uncommonly long and densely sampled longitudinal design, this study demonstrates that structural brain ageing among cognitively normal adults follows highly heterogeneous trajectories, spanning from marked decline to near-complete resistance. Modifiable lifestyle and vascular risk factors were associated with faster atrophy, supporting opportunities for risk stratification and targeted prevention strategies.
PMID:
42765092
Bibliographic data and abstract were imported from PubMed on 21 Sep 2026.
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