Grey matter and white matter MRI markers of cognitive progression in early and late onset variants of Alzheimer’s disease (P4.090)

Objective: To assess grey (GM) and white matter (WM) MRI measures as predictors of cognitive progression in early-onset (EOAD) and late-onset Alzheimer’s disease (LOAD). Background: MRI-derived measurements of GM and WM damage have been widely studied as potential biomarkers for diagnosis and monitoring of LOAD. Their role in predicting EOAD evolution is less known. Methods: T1-weighted and diffusion tensor (DT) MRI scans were obtained from 48 LOAD and 28 EOAD. Patients were followed prospectively with 6-month clinical and neuropsychological evaluations (mean follow-up: 12.9 months [maximum: 43.4 months]). At baseline, regional GM and WM damage was evaluated. Longitudinal linear models assessed cognitive changes over time and relationships between baseline MRI and cognitive evolution. Results: At a similar stage, EOAD presented with more severe multidomain cognitive deficits, greater brain atrophy, but similar WM tract damage relative to LOAD. Compared with LOAD, EOAD patients showed a faster progression during follow-up, mainly in executive, memory and language domains. In EOAD, baseline atrophy of the cingulum and several regions in the frontotemporal and parietal GM bilaterally was related to the executive function worsening, while damage to the corpus callosum, cingulum bundle, frontotemporal and frontoparietal WM connections bilaterally predicted the visuospatial abilities deterioration. In LOAD, volumes of a few GM regions including the left anterior cingulum, insula, inferior frontal and parietal cortices contributed to the progression of executive deficits, while the memory decline was predicted by damage to corpus callosum, cingulum bundle and frontotemporal and frontoparietal WM tracts bilaterally. Conclusions: In addition to GM atrophy, WM damage contributes to cognitive progression in both LOAD and EOAD, with differences between the two variants probably related to a distinct distribution of pathological abnormalities. DT MRI could be considered an additional biomarker of neurodegeneration predictive of cognitive impairment years later in AD. Supported by: Italian Ministry of Health (#GR-2010-2303035).