Association of vascular brain injury, neurodegeneration, amyloid, and cognitive trajectory
Open accessAbstract
OBJECTIVE: To determine whether vascular and neurodegenerative factors influence cognition before clinically relevant Alzheimer disease pathology, we analyzed MRI measures and amyloid imaging in an ethnoracially diverse cohort of cognitively normal individuals older than 60 years. METHODS: Participants (n = 154; mean age 74.15 ± 6.94; 50% female; 54% Caucasian, 22.1% Hispanic, 14.9% African American) were recruited from the University of California, Davis Alzheimer's Disease Research Center, who were cognitively normal at baseline, time of PET, and MRI, and received yearly cognitive assessment for 6.23 ± 4.16 years. Mixed model regression with random slope and intercept was calculated for episodic memory and executive function, adjusting for age, sex, education, and ethnicity. RESULTS: Vascular burden score was associated with total white matter hyperintensity (WMH) volume (β, 0.171; 95% confidence interval [CI], 0.024-0.318). WMH volume was associated with low baseline executive function (-0.115; -0.226 to -0.003) and rate of change in memory (-0.029; -0.045 to -0.012). Hippocampal volume was associated with the rate of change in memory (0.040; 0.021-0.059) and executive function (0.024; 0.008-0.039). Continuous measures of amyloid status influenced change in memory (-0.026; -0.044 to -0.008) and executive function (-0.033; -0.046 to -0.021) independently of MRI measures. CONCLUSION: Vascular brain injury and neurodegeneration are associated with baseline cognitive performance and the rate of longitudinal change independent of amyloid status among community-dwelling, ethnicity diverse cognitively normal individuals, supporting the role of vascular diseases as risk factors for later-life dementia.
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WMHs play an important role as a risk factor for future memory decline even if they may not affect baseline memory performance at the stage of pAD.
“These findings emphasize the important role of WMHs as a risk factor for future memory decline even if they may not affect baseline memory performance at the stage of pAD [11,49].”
From Amyloid-PET and White Matter Hyperintensities Have Independent Effects on Baseline Cognitive Function and Synergistic Effects on Longitudinal Executive Function (2023) · cites this paper as [11]
The Results section (page not available) reports that WMH volume was associated with later episodic-memory trajectories, while no brain measure was associated with baseline episodic memory. However, the study examined cognitively normal individuals, not people at the pAD stage, so it does not establish the claim for that population. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn cognitively normal participants with low WMH volumes, memory performance underwent low to no changes independent of amyloid burden.
“One previous study showed that CN participants with low WMH volumes underwent low to no changes in memory performance, independent of amyloid burden [11].”
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References 52 · Cited by 49
- Authors
- Han, J. W., Maillard, P., Harvey, D., Fletcher, E., Martinez, O., Johnson, D. K., Olichney, J. M., Farias, S. T., Villeneuve, S., Jagust, W., Mungas, D., & DeCarli, C.
- Affiliations
- Seoul National University (KR)
- ORCID
- Venue
- Neurology
- Published
- 2020-11-10
- Volume
- 95
- Issue
- 19
- Pages
- e2622-e2634
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC7713731
- OpenAlex
- W3045649192
- Cited by
- 49
- References
- 52
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 8 · 2023: 7 · 2022: 9 · 2021: 9
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (AG12435, P01 AG12435, AG10129, AG031563)
- National Institute on Aging (P30AG010129, R01AG047827, R01AG031563, P30AG066546)
- National Institute of Neurological Disorders and Stroke (R01NS017950)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Keywords
- vascular brain injury, neurodegeneration, amyloid, cognitive trajectories, white matter hyperintensities, hippocampal volume, executive function, episodic memory, vascular burden, dementia risk, cognitively normal older adults, amyloid PET, longitudinal cognitive change
- MeSH terms
- Aged, Aged, 80 and over, Aniline Compounds, Brain, Cerebrovascular Disorders, Cognition, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Memory Disorders, Neuropsychological Tests, Organ Size, Thiazoles, Amyloid beta-Peptides, Disease Progression, Positron-Emission Tomography, Executive Function, Independent Living, Plaque, Amyloid, Cognitive Dysfunction, Memory, Episodic, White Matter
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