Evidence map›Paper›PMID 41699639›Full record

ArticleAlzheimer's research & therapy2026

Associations of white matter hyperintensity regression and progression with cognitive and structural brain changes: a population-based cohort study.

Jiajia Zhang, Xuejia Jia, Haibin Li, Xiuqin Jia, Qi Yang

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Article in Alzheimer's research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Jiajia ZhangDepartment of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, No.8 Gongti South Road, Chaoyang District, Beijing, 100020, China.
Xuejia JiaDepartment of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, No.8 Gongti South Road, Chaoyang District, Beijing, 100020, China.
Haibin LiDepartment of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, No.8 Gongti South Road, Chaoyang District, Beijing, 100020, China.
Xiuqin Jia *Department of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, No.8 Gongti South Road, Chaoyang District, Beijing, 100020, China. xqjia2014@163.com.
Qi Yang *Department of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, No.8 Gongti South Road, Chaoyang District, Beijing, 100020, China. yangyangqiqi@gmail.com.

Funding

Beijing Hospitals Authority's Ascent Plan DFL20220303Beijing Municipal Natural Science Foundation L252089Changping Laboratory 2025B-07-32National Natural Science Foundation of China 82025018National Natural Science Foundation of China U24A20753
6 · The paper itself

Abstract

backgroundWhite matter hyperintensities (WMHs) of presumed vascular origin are common neuroimaging markers of brain aging. While WMHs typically progress over time, WMHs regression is increasingly being reported. However, its clinical relevance remains unclear, particularly in community-based populations. We investigated associations of WMHs regression and progression, including total WMH, periventricular (PWMHs), and deep WMHs (DWMHs), with longitudinal cognitive decline and structural brain atrophy.

methodsWe analyzed longitudinal data from 2496 UK Biobank participants (median [IQR] age 61 [56–67] years, 52.8% female) without dementia or conditions confounding WMH measures. Brain MRI and cognitive assessments were conducted at baseline and follow-up (2–3 years apart). Absolute WMH volume change was categorized into tertiles representing regression (Tertile 1), stability (Tertile 2), and progression (Tertile 3). Cognitive outcomes included processing speed (reaction time) and fluid intelligence; brain structural outcomes included volumes (% intracranial volume) of total brain, gray matter, white matter, and hippocampi. Associations were examined using multivariable-adjusted linear mixed-effects models, with moderation analyses for age and sex.

resultsAt baseline, WMH regression and progression groups showed larger WMH volumes than the stable group (p < 0.001). Over the follow-up, total WMH regression (β = 0.029 [95% CI 0.003 to 0.054], p = 0.027) and PWMH regression (β = 0.029 [0.003 to 0.054], p = 0.027) were associated with slower decline in processing speed, but not significantly associated with decline in fluid intelligence or brain structures (all p > 0.05). In contrast, PWMH progression was associated with faster declines in total brain (β=−0.078 [− 0.143 to − 0.012], p = 0.020) and white matter volumes (β=−0.048 [− 0.092 to − 0.005], p = 0.030). Progression in total WMH (β=−0.0016 [− 0.002 to − 0.001], p < 0.001), PWMH (β=−0.0019 [− 0.003 to − 0.001], p < 0.001), and DWMH (β=−0.0008 [− 0.001 to − 0.0002], p = 0.011) was linked to accelerated hippocampal atrophy, with the effects of total WMH and PWMH progression significant only in participants < 65 years (p-interaction < 0.05). DISCUSSION: Compared with stable WMH, WMH regression was associated with improved processing speed and comparable brain structure, whereas WMH progression was associated with accelerated brain atrophy, particularly hippocampal atrophy. These associations were predominantly driven by periventricular lesions. These findings highlight the dynamic nature and potential reversibility of microvascular injury, supporting WMH regression as a promising intervention target for preserving cognition and brain integrity.

Indexed as

BrainCognitionCognitive DysfunctionWhite MatterAgedAgingAtrophyCohort StudiesDisease ProgressionFemaleHumansLongitudinal StudiesMagnetic Resonance ImagingMaleMiddle AgedNeuropsychological TestsBrain agingBrain atrophyCognitive declineProcessing speedWhite matter hyperintensity regression

Identifiers

PMID41699639
PMCPMC13014974

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.