Longitudinal Association between White Matter Hyperintensities and White Matter Beta-Amyloid Deposition in Cognitively Unimpaired Elderly

Background: White matter (WM) beta-amyloid uptake has been used as a reference region to calculate the cortical standard uptake value ratio (SUVr). However, white matter hyperintensities (WMH) may have an influence on WM beta-amyloid uptake. Our study aimed to investigate the associations between WMH and WM beta-amyloid deposition in cognitively unimpaired elderly.

Methods: Data from 83 cognitively unimpaired individuals in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset were analyzed. All participants had complete baseline and four-year follow-up information about WMH volume, WM 18F-AV-45 SUVr, and cognitive function, including ADNI-Memory (ADNI-Mem) and ADNI-Executive function (ADNI-EF) scores. Cross-sectional and longitudinal linear regression analyses were used to determine the associations between WMH and WM SUVr and cognitive measures.

Results: Lower WM 18F-AV-45 SUVr at baseline was associated with younger age (β=0.01, P=0.037) and larger WMH volume (β=-0.049, P=0.048). The longitudinal analysis found an annual increase in WM 18F-AV-45 SUVr was associated with an annual decrease in WMH volume (β=-0.016, P=0.041). An annual decrease in the ADNI-Mem score was associated with an annual increase in WMH volume (β=-0.070, P=0.001), an annual decrease in WM 18F-AV-45 SUVr (β=0.559, P=0.030), and fewer years of education (β=0.011, P=0.044). There was no significant association between WM 18F-AV-45 SUVr and ADNI-EF (P>0.05).

Conclusion: Reduced beta-amyloid deposition in WM was associated with higher WMH load and memory decline in cognitively unimpaired elderly. WMH volume should be considered when WM 18F-AV-45 SUVr is used as a reference for evaluating cortical 18F-AV-45 SUVr.