Patterns of cortical and subcortical atrophy in early-onset and late-onset Alzheimer's disease

Abstract

Early-onset (EOAD) and late-onset (LOAD) Alzheimer's disease patients commonly present distinct clinical profiles (mainly language, praxis and executive deficits in EOAD patients, primarily memory deficits in LOAD patients). This different phenotype is associated with a distinct pattern of hippocampal and cortical atrophy. Less known is whether subcortical grey matter structures, which have been reported to be affected by AD pathology, are involved in EOAD and LOAD. Subcortical structures modulate some aspects of cognition and behaviour and may therefore be differentially affected in EOAD and LOAD. EOAD and LOAD patients (onset before and after age 65) were assessed with a neuropsychological battery and high-resolution MRI together with 1:1 age- and sex-matched controls. Cortical atrophy was assessed with cortical pattern matching, hippocampal atrophy with region-of-interest-based analysis. In addition, atrophy of the amygdala and nucleus accumbens was assessed on a subsample of patients using a shape analysis approach. In EOAD, severe GM loss was detected in large neocortical areas in all the lobes. In LOAD, GM loss was diffusely milder and showed the strongest effect in the medial temporal lobe and right superior temporal gyrus. Both the amygdala and nucleus accumbens were significantly reduced in EOAD and LOAD, with no significant difference between the two patient groups. The shape analysis however showed a different pattern of local involvement in the nucleus accumbens. In addition, EOAD showed additional atrophy in the amygdalar nuclei connecting to neocortical areas. EOAD and LOAD differ in their typical topographic patterns of brain atrophy. The preliminary results suggest that the differences in subcortical atrophy may be related to the distinct topography of cortical grey matter atrophy in EOAD and LOAD.