ArticleAlzheimer's research & therapy2024
Small vessel cerebrovascular disease is associated with cognition in prospective Alzheimer's clinical trial participants.
Article in Alzheimer's research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.
- Elevated temporal tau PET predicts faster cognitive decline in women than men: A meta-analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Pooled it
- Deep Learning for Brain MRI Artifact Correction: Current Challenges and Future Directions.Bioengineering (Basel, Switzerland) · 2026Review
- Elevated plasma klotho levels attenuate Alzheimer's disease pathologies and cognitive decline in APOE ε4 carriers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Cerebrovascular disease in Alzheimer's disease: Brain structure as a critical mediator of cognitive decline.The journal of prevention of Alzheimer's disease · 2025Article
- Hypertensive disorders of pregnancy and neuroimaging markers of dementia risk: A pilot study.Pregnancy (Hoboken, N.J.) · 2025Article
- The Interaction Between Cognitive Abilities and White Matter Hyperintensity Phenotypes: A Novel Perspective on Bidirectional Causality.Brain and behavior · 2025Article
- Pilot implementation of the revised criteria for staging of Alzheimer's disease by the Alzheimer's Association Workgroup in a tertiary memory clinic.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundSecondary prevention clinical trials for Alzheimer's disease (AD) target amyloid accumulation in asymptomatic, amyloid-positive individuals, but it is unclear to what extent other pathophysiological processes, such as small vessel cerebrovascular disease, account for participant performance on the primary cognitive outcomes in those trials. White matter hyperintensities are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) that reflect small vessel cerebrovascular disease. They are associated with cognitive functioning in older adults and with clinical presentation and course of AD, particularly when distributed in posterior brain regions. The purpose of this study was to examine to what degree regional WMH volume is associated with performance on the primary cognitive outcome measure in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, a secondary prevention trial.
methodsData from 1791 participants (59.5% women, mean age (SD) 71.6 (4.74)) in the A4 study and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) companion study at the screening visit were used to quantify WMH volumes on T2-weighted fluid-attenuated inversion recovery (FLAIR) MR images. Cognition was assessed with the preclinical Alzheimer cognitive composite (PACC). We tested the association of total and regional WMH volumes with PACC performance, adjusting for age, education, and amyloid positivity status, with general linear models. We also considered interactions between WMH and amyloid positivity status.
resultsIncreased frontal and parietal lobe WMH volume was associated with poorer performance on the PACC. While amyloid positivity was also associated with lower cognitive test scores, WMH volumes did not interact with amyloid positivity status.
conclusionThese results highlight the potential of small vessel cerebrovascular disease to drive AD-related cognitive profiles. Measures of small vessel cerebrovascular disease should be considered when evaluating outcome in trials, both as potential effect modifiers and as a possible target for intervention or prevention.
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Registered trials
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.