Influence of White Matter Hyperintensities on Baseline and Longitudinal Amyloid-ß in Cognitively Normal Individuals.

BACKGROUND: The associations between small vessel disease (SVD) and cerebrospinal amyloid-ß1-42 (Aß1-42) pathology have not been well-elucidated. OBJECTIVE: Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aß1-42 change in cognitively normal (CN) subjects. The interaction of WMH and Aß1-42 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 Aß1-42 over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and Aß1-42 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 Aß1-42 (p = 0.008) and two-year change in Aß1-42 (p = 0.006). Interaction between higher WMH and lower Aß1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003). CONCLUSION: BL WMH was associated with M24 and longitudinal Aß1-42 change in CN. The interaction between higher WMH and lower Aß1-42 was associated with poorer memory. Since SVD is associated with longitudinal Aß1-42 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.

Cerebral Small Vessel Disease Influences Hippocampal Subfield Atrophy in Mild Cognitive Impairment.

To investigate patterns of hippocampal subfield atrophy among patients with amnestic mild cognitive impairment, stratified by severity of small vessel disease (SVD) and corresponding associations with cognitive domains. One hundred seventy-six MCI subjects (mean age = 65.56 years, SD = 8.77) underwent neuropsychological assessments and magnetic resonance imaging. SVD was rated 0 (no SVD), 1 (mild SVD) and 2 (moderate to severe SVD) based on load of white matter hyperintensities (WMH) and lacunes. Demographics, cerebrovascular risk factors, grey and white matter volumes and hippocampal subfield atrophies were compared across SVD severity through ANCOVA analyses. Subjects were categorized into positive or negative SVD-hippocampal subfield atrophy (HSA) and influence of positive SVD-HSA on episodic memory and frontal executive function was evaluated through ANCOVA analyses. All analyses corrected for covariates and bias-corrected bootstrap estimation with 1000 resamples was applied with Bonferroni correction. Hippocampal subfield atrophy worsened with increasing SVD severity. Positive SVD-HSA was characterised by significant atrophy in the subiculum, CA1, CA4, molecular layer and dentate gyrus. Greater atrophy was seen with moderate to severe SVD compared to mild SVD in these subfields. Atrophy in the five subfields of SVD-HSA was significantly associated with poor episodic memory and frontal executive function. Presence and burden of SVD influences the pattern and severity of hippocampal subfield atrophy. SVD-related hippocampal subfield atrophy is associated with poorer episodic memory and frontal executive function in mild cognitive impairment.