Enhanced Association of Tau Pathology and Cognitive Impairment in Mild Cognitive Impairment Subjects with Behavior Symptoms

Background: Mild cognitive impairment (MCI) individuals with neuropsychiatric symptoms (NPS) are more likely to develop dementia. Objective: We sought to understand the relationship between neuroimaging markers such as tau pathology and cognitive symptoms both with and without the presence of NPS during the prodromal period of Alzheimer's disease. Methods: A total of 151 MCI subjects with tau positron emission tomographic (PET) scanning with F-18 AV-1451, amyloid-beta (A beta) PET scanning with florbetapir or florbetaben, magnetic resonance imaging, and cognitive and behavioral evaluations were selected from the Alzheimer's Disease Neuroimaging Initiative. A 4-group division approach was proposed using amyloid (A-/A+) and behavior (B-/B+) status: A-B-, A-B+, A+B-, and A+B+. Pearson's correlation test was conducted for each group to examine the association between tau deposition and cognitive performance. Results: No statistically significant association between tau deposition and cognitive impairment was found for subjects without behavior symptoms in either the A-B- or A+B- groups after correction for false discovery rate. In contrast, tau deposition was found to be significantly associated with cognitive impairment in entorhinal cortex and temporal pole for the A-B+ group and nearly the whole cerebrum for the A+B+ group. Conclusion: Enhanced associations between tauopathy and cognitive impairment are present in MCI subjects with behavior symptoms, which is more prominent in the presence of elevated amyloid pathology. MCI individuals with NPS may thus be at greater risk for further cognitive decline with the increase of tau deposition in comparison to those without NPS.