ArticleAlzheimer's research & therapy2023
APOE4 carrier status determines association between white matter disease and grey matter atrophy in early-stage dementia.
Article in Alzheimer's research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- The role of APOE ε4 in modulating the relationship between non-genetic risk factors and dementia: a system review and meta-analysis.Journal of neurology · 2025Pooled it
- Exploring the role of apolipoprotein ε4 in progressive myoclonic epilepsy type 1.Epileptic disorders : international epilepsy journal with videotape · 2026Article
- Data-driven subtypes of mild cognitive impairment and their modifiable determinants: latent profile analysis of the BIOCIS cohort.NPJ dementia · 2026Article
- White matter hyperintensity drives EEG microstate abnormalities in arteriosclerotic cerebral small vessel disease.Frontiers in neuroscience · 2026Article
- Synergistic effect between cortical cerebral microinfarcts and brain atrophy on cognitive decline.Brain : a journal of neurology · 2025Article
- Apolipoprotein ε4 exacerbates white matter impairment in a mouse model of Aβ amyloidosis by decreasing actively myelinating oligodendrocytes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Longitudinal effects of sex differences and apolipoprotein E genotype on white matter engagement among elderly.Brain communications · 2025Article
- Association between white matter hyperintensities and gray matter volume in cerebral small vessel disease: insights from periventricular and deep white matter lesions.Frontiers in neurology · 2025Article
- Article
- Biomarkers and Cognition Study, Singapore (BIOCIS): Protocol, Study Design, and Preliminary Findings.The journal of prevention of Alzheimer's disease · 2024Article
- Blood pressure variability, central autonomic network dysfunction and cerebral small vessel disease in APOE4 carriers.medRxiv : the preprint server for health sciences · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWhite matter hyperintensities, a neuroimaging marker of small-vessel cerebrovascular disease and apolipoprotein ε4 (APOE4) allele, are important dementia risk factors. However, APOE4 as a key effect modifier in the relationship between white matter hyperintensities and grey matter volume needs further exploration.
methodsOne hundred ninety-two early-stage dementia (including mild cognitive impairment and mild dementia) and 259 cognitively unimpaired participants from a neurocognitive research cohort with neuroimaging data, APOE genotyping, and neuropsychological assessments were studied. We investigated independent and interactive effects of white matter hyperintensities and APOE4 on whole-brain voxel-wise grey matter volume using voxel-based morphometry (uncorrected p < 0.001; minimum cluster size = 100 voxels). We further assessed interactive effects between APOE4 and white matter hyperintensities on global cognition, memory, and executive function in early-stage dementia and cognitively unimpaired participants.
resultsIndependent of APOE4 status, higher white matter hyperintensity load was associated with greater grey matter atrophy across frontal, parietal, temporal, and occipital lobes in cognitively unimpaired and early-stage dementia subjects. However, interaction analyses and independent sample analyses revealed that APOE4 non-carriers demonstrated greater white matter hyperintensity-associated grey matter atrophy compared to APOE4 carriers in both cognitively unimpaired and early-stage dementia groups. Additional confirmatory analyses among APOE4 non-carriers demonstrated that white matter hyperintensities resulted in widespread grey matter loss. Analyses of cognitive function demonstrated that higher white matter hyperintensity load was associated with worse global (Mini-Mental State Examination, Montreal Cognitive Assessment) and executive function (Color Trails 2) in APOE4 non-carriers compared to APOE4 carriers in early-stage dementia but not cognitively unimpaired participants.
conclusionsThe association between white matter hyperintensities and grey matter loss is more pronounced in APOE4 non-carriers than APOE4 carriers in the cognitively unimpaired and early-stage dementia stages. Furthermore, white matter hyperintensity presence results in poorer executive function in APOE4 non-carriers compared to APOE4 carriers. This finding may have significant impact on the design of clinical trials with disease modifying therapies.
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