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

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.

Mild behavioral impairment is associated with ß-amyloid but not tau or neurodegeneration in cognitively intact elderly individuals.

INTRODUCTION: Mild behavioral impairment (MBI) is characterized by the emergence of neuropsychiatric symptoms in elderly persons. Here, we examine the associations between MBI and Alzheimer's disease (AD) biomarkers in asymptomatic elderly individuals. METHODS: Ninety-six cognitively normal elderly individuals underwent MRI, [18 F]AZD4694 ß-amyloid-PET, and [18 F]MK6240 tau-PET. MBI was assessed using the MBI Checklist (MBI-C). Pearson's correlations and voxel-based regressions were used to evaluate the relationship between MBI-C score and [18 F]AZD4694 retention, [18 F]MK6240 retention, and gray matter (GM) volume. RESULTS: Pearson correlations revealed a positive relationship between MBI-C score and global and striatal [18 F]AZD4694 standardized uptake value ratios (SUVRs). Voxel-based regression analyses revealed a positive correlation between MBI-C score and [18 F]AZD4694 retention. No significant correlations were found between MBI-C score and [18 F]MK6240 retention or GM volume. CONCLUSION: We demonstrate for the first time a link between MBI and early AD pathology in a cognitively intact elderly population, supporting the use of the MBI-C as a metric to enhance clinical trial enrolment.