Influence of White Matter Hyperintensities on Baseline and Longitudinal Amyloid-β in Cognitively Normal Individuals
Fennie Choy Chin Wong1, Seyed Ehsan Saffari1,2, Chathuri Yatawara1
1Department of Neurology, National Neuroscience Institute, Singapore, Singapore.
Background:
The associations between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology have not been well-elucidated.
Objective:
Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aβ1-42 change in cognitively normal (CN) subjects. The interaction of WMH and Aβ1-42 on memory and executive function were also examined.
Methods:
This study included 72 subjects from the Alzheimer's Disease Neuroimaging Initiative. Multivariable linear regression models evaluated associations between baseline WMH/intracranial volume ratio, M24 and change in Aβ1-42 over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and Aβ1-42 on memory and executive function.
Results:
Mean age of the subjects (Nmales = 36) = 73.80 years, SD = 6.73; mean education years = 17.1, SD = 2.4. BL WMH was significantly associated with M24 Aβ1-42 (p = 0.008) and two-year change in Aβ1-42 (p = 0.006). Interaction between higher WMH and lower Aβ1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003).
Conclusion:
BL WMH was associated with M24 and longitudinal Aβ1-42 change in CN. The interaction between higher WMH and lower Aβ1-42 was associated with poorer memory. Since SVD is associated with longitudinal Aβ1-42 pathology, and the interaction of both factors is linked to poorer cognitive outcomes, the mitigation of SVD may be correlated with reduced amyloid pathology and milder cognitive deterioration in Alzheimer's disease.
Insights
Small vessel disease, indicated by white matter hyperintensities, is linked to amyloid-β changes in cognitively normal individuals. Managing small vessel disease may slow Alzheimer's progression.
Area of Science:
- Neurology
- Neuroimaging
- Alzheimer's Disease Research
Background:
- The relationship between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology remains unclear.
- Investigating these associations is crucial for understanding early Alzheimer's disease mechanisms.
Purpose of the Study:
- To examine the association between baseline white matter hyperintensities (WMH) and longitudinal changes in Aβ1-42 in cognitively normal subjects.
- To investigate the combined effect of WMH and Aβ1-42 on memory and executive function.
Main Methods:
- Utilized data from 72 cognitively normal subjects in the Alzheimer's Disease Neuroimaging Initiative.
- Employed multivariable linear regression and linear mixed-effects models to analyze WMH, Aβ1-42 levels, and cognitive performance.
Main Results:
- Baseline WMH significantly correlated with both month-24 Aβ1-42 levels and its two-year change.
- An interaction between higher WMH and lower Aβ1-42 at baseline was associated with poorer memory at baseline and 24 months.
Conclusions:
- Baseline WMH is associated with longitudinal Aβ1-42 changes in cognitively normal individuals.
- The interaction of WMH and Aβ1-42 negatively impacts memory, suggesting SVD mitigation could reduce amyloid pathology and cognitive decline in Alzheimer's disease.
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