ArticleAnnals of neurology2022
Association of Apolipoprotein E ɛ4 Allele with Enlarged Perivascular Spaces.
Article in Annals of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- The Impact of Vascular Risk Factors on Cerebral Amyloid Angiopathy: A Cohort Study in Hereditary Cerebral Amyloid Angiopathy and a Systemic Review in Sporadic Cerebral Amyloid Angiopathy.Cerebrovascular diseases (Basel, Switzerland) · 2025Pooled it
- A Quantitative Assessment of MRI-Visible Perivascular-Space Burden Across the Cognitive Spectrum: Associations with APOE ε4 Status and Venous Sinus Volume.Diagnostics (Basel, Switzerland) · 2026Article
- Periventricular diffusivity reflects APOE ε4-modulated amyloid accumulation and cognitive impairment in the Alzheimer's disease continuum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Glymphopathy and Reduced Processing Speed in Community-Dwelling Adults with Silent Cerebral Small Vessel Disease: A DTI-ALPS Study.Journal of clinical medicine · 2025Article
- Relation of MRI visible perivascular spaces with global and regional brain structural connectivity measures: The Framingham Heart Study (FHS).Neurobiology of aging · 2025Article
- Article
- Increased burden of enlarged perivascular spaces in patients with patent foramen ovale.Neuroradiology · 2025Article
- Pathophysiologic similarities between autism spectrum disorder and Alzheimer's disease: therapeutic possibilities.Frontiers in neuroscience · 2025Article
- A cell-autonomous role for border-associated macrophages in ApoE4 neurovascular dysfunction and susceptibility to white matter injury.Nature neuroscience · 2024Article
- Impaired kidney function, cerebral small vessel disease and cognitive disorders: the Framingham Heart Study.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Article
- Cell autonomous role of border associated macrophages in ApoE4 neurovascular dysfunction and susceptibility to white matter injury.Research square · 2023Article
- Association of Different Combinations ofInternational journal of general medicine · 2023Article
- Association of MRI Visible Perivascular Spaces and Neurofilament Light Chain: The Framingham Heart Study.Journal of Alzheimer's disease : JAD · 2023Article
- Biomarkers involved in the pathogenesis of cerebral small-vessel disease.Frontiers in neurology · 2022Review
- Association of enlarged perivascular spaces with cognitive function in dementia-free older adults: A population-based study.Alzheimer's & dementia (Amsterdam, Netherlands)Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveEnlarged perivascular spaces have emerged as markers of cerebral small vessel disease and are linked to perivascular drainage dysfunction. The apolipoprotein E-ɛ4 (APOE-ɛ4) allele is the strongest genetic risk factor for cerebral amyloid angiopathy and Alzheimer's neuropathology, but the underlying mechanisms remain unclear. We studied the relationship between APOE-ɛ4 and the topography and burden of enlarged perivascular spaces to elucidate underlying mechanisms between APOE-ɛ4 and adverse clinical outcomes.
methodsWe included 3,564 Framingham Heart Study participants with available genotypes and magnetic resonance imaging. Enlarged perivascular spaces in the basal ganglia and centrum semiovale were rated using a validated scale. We related APOE-ɛ4 allele presence to high burden of enlarged perivascular spaces in each region and a mixed score reflecting high burden in both regions using multivariable logistic regression. Exploratory analyses incorporated presence of cerebral microbleeds and assessed effect modification by hypertension.
resultsMean age was 60.7 years (SD = 14.6), 1,644 (46.1%) were men, 1,486 (41.8%) were hypertensive, and 836 (23.5%) participants were APOE-ɛ4 carriers. APOE-ɛ4 was associated with high burden of enlarged perivascular spaces in the centrum semiovale (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 1.16, 1.81) and mixed regions (OR = 1.37, 95% CI = 1.11, 1.68). Associations were slightly stronger in hypertensive subjects.
interpretationThe APOE-ɛ4 allele plays a modest role in the burden of enlarged perivascular spaces in the centrum semiovale. Further studies are needed to clarify the underlying small vessel disease type in community-dwelling individuals with predominant centrum semiovale enlarged perivascular spaces, which may be hypertensive angiopathy in our sample. ANN NEUROL 2022;92:23-31.
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