White matter degeneration in atypical Alzheimer’s disease (P6.215)

Objective: To assess white matter (WM) tract damage in patients with atypical Alzheimer’s disease (AD), including early age-of-onset AD (EOAD), logopenic variant of primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA) using diffusion tensor (DT) MRI, and to identify similarities and differences across the AD spectrum. Background: AD is not a unitary clinical syndrome. Patients with EOAD can present with a multi-domain cognitive impairment at onset. This cognitive picture is very different from the typical profile of late-onset patients with progressive memory deficit as the central feature. AD can also present as atypical, relatively focal clinical syndromes, more frequently associated with early age-of-onset, i.e., such as PCA and lvPPA. The factors driving AD clinicoanatomical heterogeneity are not well understood. Methods: WM tract damage and cortical atrophy were assessed in 28 EOAD, 12 lvPPA and 13 PCA patients relative to healthy controls. Conjunction and interaction analyses were used to define overlapping and syndrome-specific patterns of brain damage. Results: EOAD, lvPPA and PCA patients shared a common pattern of WM damage involving the body of the corpus callosum, fornix, and main anterior-posterior pathways, and cortical atrophy of the left temporo-parietal regions and precuneus. EOAD patients had also a specific damage to the genu and splenium of the corpus callosum, and parahippocampal tract bilaterally. In all AD patients, particularly in the two focal forms (lvPPA and PCA), WM damage was more severe and widely distributed than expected on the basis of cortical atrophy. Conclusions: In atypical AD clinical phenotypes, the distribution of WM damage exceeds cortical atrophy and may reflect the dissemination of pathology through structural connections from atrophic to unaffected cortical regions. WM degeneration may be an early marker of AD pathology in EOAD and focal AD forms. Study Supported by: Italian Ministry of Health (#GR-2010-2303035).