Regional Amyloid Accumulation and White Matter Integrity in Cognitively Normal Individuals

Recent studies have shown that amyloid-β (Aβ) burden influenced white matter (WM) integrity before the onset of dementia.

To assess whether the effects of Aβ burden on WM integrity in cognitively normal (CN) individuals were regionally specific.

Our cohort consisted of 71 CNs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database who underwent both AV45 amyloid-PET and diffusion tensor imaging. Standardized uptake value ratio (SUVR) was computed across four bilateral regions of interest (ROIs) corresponding to four stages of in vivo amyloid staging model (Amyloid stages I-IV). Linear regression models were conducted in entire CN group and between APOEɛ4 carriers and non-carriers.

Our results indicated that higher global Aβ-SUVR was associated with higher mean diffusivity (MD) in the entire CN group (p = 0.023), and with both higher MD (p = 0.015) and lower fractional anisotropy (FA) (p = 0.026) in APOEɛ4 carriers. Subregion analysis showed that higher Amyloid stage I-II Aβ-SUVRs were associated with higher MD (Stage-1: p = 0.030; Stage-2: p = 0.016) in the entire CN group, and with both higher MD (Stage-1: p = 0.004; Stage-2: p = 0.010) and lower FA (Stage-1: p = 0.022; Stage-2: p = 0.014) in APOEɛ4 carriers. No associations were found in APOEɛ4 non-carriers and in Amyloid stage III-IV ROIs.

Our results indicated that the effects of Aβ burden on WM integrity in CNs might be regionally specific, particularly in Amyloid stage I-II ROIs, and modulated by APOEɛ4 status.