Association between regional tau pathology and neuropsychiatric symptoms in aging and dementia due to Alzheimer's disease

Abstract

Background: Neuropsychiatric symptoms (NPS) are frequent in aging and Alzheimer's disease (AD). Here we study the relationship between NPS and AD pathologies in vivo. Method: Two hundred and twenty-one individuals from the TRIAD cohort (143 cognitively unimpaired, 52 mild cognitive impairment, and 26 AD) underwent [18F]MK6240-tau-positron emission tomography (PET), [18F]AZD4694-amyloid-PET, magnetic resonance imaging, and neuropsychological evaluations. Spearman correlations and voxel-based regression models evaluated the relationship between Neuropsychiatric Inventory Questionnaire (NPI-Q) scores, and tau-PET, amyloid-PET, and voxel-based morphometry. Results: Fifty percent of individuals presented NPS; these correlated with tau, not amyloid beta or neurodegeneration. Associations between NPI-Q score and tau-PET were stronger in the parietal association area, superior frontal, temporal, and medial occipital lobes. NPI-Q domains associated with distinct patterns of tau uptake. Conclusions: NPS are predominantly related to tau in aging and dementia. Regions affected are part of the behavioral circuits, and vulnerable to early AD pathology. Domain-specific analyses showed NPS are related to the AD pathophysiological processes in a symptom-specific manner.