Abstract
BackgroundLate-onset Alzheimer’s disease (AD) is characterized by primary memory impairment, which then progresses towards severe deficits across cognitive domains. Here, we report how performance in cognitive domains relates to patterns of tau deposition and cortical thickness.MethodsWe analyzed data from 131 amyloid-β positive participants (55 cognitively normal, 46 mild cognitive impairment, 30 AD) of the Alzheimer’s Disease Neuroimaging Initiative who underwent magnetic resonance imaging (MRI), flortaucipir (FTP) positron emission tomography, and neuropsychological testing. Surface-based vertex-wise and region-of-interest analyses were conducted between FTP and cognitive test scores, and between cortical thickness and cognitive test scores.ResultsFTP and thickness were differentially related to cognitive performance in several domains. FTP-cognition associations were more widespread than thickness-cognition associations. Further, FTP-cognition patterns reflected cortical systems that underlie different aspects of cognition.ConclusionsOur findings indicate that AD-related decline in domain-specific cognitive performance reflects underlying progression of tau and atrophy into associated brain circuits. They also suggest that tau-PET may have better sensitivity to this decline than MRI-derived measures of cortical thickness.
Highlights
Late-onset Alzheimer’s disease (AD) is characterized by primary memory impairment, which progresses towards severe deficits across cognitive domains
Autopsy data indicate that the spread of tau pathology follows a progressive sequence [12] consistent with the observed clinical course in AD: tau starts in the medial temporal lobe regions that are responsible for learning and memory, into the rest of the cortex to affect the cortical areas that serve other cognitive domains
Three subjects were excluded as their structural magnetic resonance imaging (MRI) did not successfully process through FreeSurfer or their MRI had substantial motion artifact, leaving us with 131 participants to examine
Summary
Late-onset Alzheimer’s disease (AD) is characterized by primary memory impairment, which progresses towards severe deficits across cognitive domains. Assessment of neurodegeneration in vivo has been available with high-resolution magnetic resonance imaging (MRI) measures of cortical thickness to estimate structural atrophy and with fluorodeoxyglucose (FDG)-PET to evaluate regional hypometabolism. Studies using these modalities have consistently shown that AD is characterized by degeneration in temporal and parietal cortices [15,16,17,18] in a pattern similar to tau pathology. In vivo studies of neurodegeneration, like post-mortem studies of tau, have revealed close associations between the distribution of neurodegeneration and cognitive deficits found in patients with AD [3, 19,20,21,22,23]
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