In comparison to late-onset Alzheimer’s disease (LO-AD, onset
> 65), early age-of-onset Alzheimer’s disease (EO-AD, onset<65
years) more often presents with language, visuospatial and/or executive
impairment, often occurring earlier than a progressive memory deficit. The
logopenic variant of primary progressive aphasia (lv-PPA) and the posterior
cortical atrophy (PCA) have recently been described as possible atypical
variants of EO-AD. Lv-PPA is characterized by isolated language deficit,
while PCA is characterized by predominant visuospatial deficits. Severe
hemispheric grey matter (GM) atrophy associated with EO-AD, lv-PPA and PCA
has been described, but regional patterns of white matter (WM) damage are
still poorly understood.
Using structural MRI and voxel-based morphometry, we investigated WM
damage in 16 EO-AD, 13 PCA, 10 lv-PPA, and 14 LO-AD patients at
presentation, and 72 age-matched controls.
In EO-AD, PCA and lv-PPA patients, WM atrophy was centered on lateral
temporal and parietal regions, including cingulum and posterior corpus
callosum. Compared to controls, lv-PPA patients showed a more severe left
parietal damage, and PCA showed a more severe occipital atrophy. Moreover,
EO-AD had greater cingulum atrophy compared with LO-AD. LO-AD showed WM
damage in medial temporal regions and less extensive hemispheric
Patterns of WM damage in EO-AD, lv-PPA and PCA are consistent with
the clinical syndromes and GM atrophy patterns. WM injury in AD atypical
variants may contribute to symptoms and disease pathogenesis.