Associations of Anxiety with Amyloid, Tau, and Neurodegeneration in Older Adults without Dementia: A Longitudinal Study.

Background: The pathophysiological process of amyloid-β, tau deposition, and neurodegeneration of Alzheimer's disease (AD) begin in a preclinical phase, while anxiety is associated with an increased risk of AD in preclinical phase.

Objective: To examine the relationships between anxiety and amyloid-β, tau deposition, and neurodegeneration. To test the hypothesis that anxiety could predict clinical progression in the elderly without dementia.

Methods: 1,400 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included in the study and were studied over a median period of 3 years. In multivariable models, the cross-sectional and longitudinal associations between anxiety and amyloid-β PET, tau PET, and FDG PET SUVRs in participants without dementia were explored using Spearman rank correlation, logistic regression model, multiple linear regression model, Kaplan-Meier survival curves, and Cox proportional hazards model. The association between baseline anxiety and clinical progression was also explored.

Results: There was a positive correlation between anxiety and amyloid-β deposition (r = 0.11, p = 0.0017) and a negative correlation between anxiety and neurodegeneration (r = -0.13, p = 0.00022). MCI participants with anxiety showed a faster clinical progression of dementia (HR = 1.56, p = 0.04). Non-anxious participants with more amyloid-β deposition or more severe neurodegeneration displayed accelerated development into anxiety (HR = 2.352, p < 0.0001; HR = 2.254, p < 0.0001).

Conclusion: Anxiety was associated with amyloid-β deposition and neurodegeneration in non-dementia elderly. Anxiety in MCI predicted conversion to dementia. Anxiety may play a selective role and prediction of disease progression in the early phase of AD.