Amyloid PET imaging and dementias: potential applications in detecting and quantifying early white matter damage

Positron emission tomography (PET) with amyloid tracers (amy-PET) allows the quantification of pathological amyloid deposition in the brain tissues, including the white matter (WM). Here, we evaluate amy-PET uptake in WM lesions (WML) and in the normal-appearing WM (NAWM) of patients with Alzheimer's disease (AD) and non-AD type of dementia.

Thirty-three cognitively impaired subjects underwent brain magnetic resonance imaging (MRI), Aβ_1-42 (Aβ) determination in the cerebrospinal fluid (CSF) and amy-PET. Twenty-three patients exhibiting concordant results in both CSF analysis and amy-PET for cortical amyloid deposition were recruited and divided into two groups, amyloid positive (A+) and negative (A-). WML quantification and brain volumes' segmentation were performed. Standardized uptake values ratios (SUVR) were calculated in the grey matter (GM), NAWM and WML on amy-PET coregistered to MRI images.

A+ compared to A- showed a higher WML load (p = 0.049) alongside higher SUVR in all brain tissues (p < 0.01). No correlations between CSF Aβ levels and WML and NAWM SUVR were found in A+, while, in A-, CSF Aβ levels were directly correlated to NAWM SUVR (p = 0.04). CSF Aβ concentration was the only predictor of NAWM SUVR (adj R² = 0.91; p = 0.04) in A-. In A+ but not in A- direct correlations were identified between WM and GM SUVR (p < 0.01).

Our data provide evidence on the role of amy-PET in the assessment of microstructural WM injury in non-AD dementia, whereas amy-PET seems less suitable to assess WM damage in AD patients due to a plausible amyloid accrual therein.