Investigating Heterogeneity and Neuroanatomic Correlates of Longitudinal Clinical Decline in Atypical Alzheimer Disease.

To compare rates of longitudinal change in neurological and neuropsychological test performance between the logopenic progressive aphasia (LPA) and posterior cortical atrophy (PCA) variants of atypical Alzheimer's disease (AD) and use unbiased principal component analysis to assess heterogeneity in patterns of change and relationships to demographics and concurrent brain atrophy. Patients with posterior cortical atrophy (PCA) or logogenic progressive aphasia (LPA) that were positive for amyloid and tau AD biomarkers and had undergone serial neurological and neuropsychological assessments and structural MRI were identified. Rates of change in 13 clinical measures were compared between groups in a case-control design, and principal component analysis was used to assess patterns of clinical change unbiased by clinical phenotype. Components were correlated with rates of regional brain atrophy using tensor-based morphometry. Twenty-eight PCA patients and 27 LPA patients were identified. LPA showed worse baseline performance and faster rates of decline in naming, repetition and working memory, as well as faster rates of decline in verbal episodic memory, compared to PCA. Conversely, PCA showed worse baseline performance in tests of visuospatial and perceptual function and on the Clinical dementia rating scale, and faster rates of decline in visuoperceptual function, compared to LPA. The principal component analysis showed that patterns of clinical decline were highly heterogeneous across the cohort, with 10 principal components required to explain over 90% of the variance. The first principal component reflected overall severity, with higher scores in LPA than PCA reflecting faster decline in LPA and was related to left temporoparietal atrophy. The second and third principal components were not related to clinical phenotype but showed some relationship to regional atrophy. No relationships were identified between the principal components and age, sex, disease duration, amyloid PET findings or apolipoprotein genotype. Longitudinal patterns of clinical decline differ between LPA and PCA but are heterogeneous and related to different patterns of topographic spread. PCA is associated with a more slowly progressive course than LPA.

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