Heterogeneity in imaging‐based spread of tau and atrophy in atypical AD

Abstract

AbstractBackgroundDifferent clinical phenotypes of atypical AD are each associated with characteristic patterns of neurodegeneration and tau deposition on PET. However, longitudinal patterns of tau accumulation and atrophy dissociate and there is significant subject‐level heterogeneity in patterns of progression. We investigate the degree to which heterogeneity in tau progression and atrophy is related to age, apolipoprotein (APOE) genotype and clinical progression.MethodThe Neurodegenerative Research Group (NRG) recruited 138 atypical AD patients (posterior cortical atrophy [PCA] = 57, logopenic progressive aphasia [LPA] = 81), of which 57 underwent longitudinal 3T head MRI and [18F]flortaucipir PET. Region‐of‐interest and voxel‐level analyses were utilized to assess relationships between rates of both atrophy and flortaucipir accumulation with age and APOE ε4 genotype. Principle component analysis using 12 different cognitive tests was used to assess patterns of clinical decline, with the principle components correlated to neuroimaging.ResultFastest rates of tau accumulation were observed in the frontal lobes in PCA and LPA, while fastest rates of atrophy were observed in occipital lobe in PCA and left temporoparietal lobe in LPA. Cortical rates of tau accumulation, particularly in the frontal lobe, were faster in younger patients and in APOE ε4 non‐carriers within LPA and PCA. Spatial patterns of tau accumulation were similar in both carriers and non‐carriers. Cortical rates of atrophy, particularly in parietal regions, were faster in younger patients in PCA and LPA, and in APOE ε4 non‐carriers. Conversely, rates of medial temporal atrophy were faster in older patients and APOE ε4 carriers. Increased rates of tau accumulation across the cortex, but particularly in frontal regions, corresponded to greater severity of clinical decline across tests over time.ConclusionRates of tau accumulation and atrophy are both influenced by age and APOE genotype in atypical AD, but with different regional associations observed for each modality. These findings highlight heterogeneity present in neuroimaging signatures of atypical AD beyond clinical phenotype.