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

Article type: Research Article

Authors: Cai, Wen-Jie^a | Tian, Yan^b | Ma, Ya-Hui^b | Dong, Qiang^a | Tan, Lan^{b; *} | Yu, Jin-Tai^{a; *} | Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China | [b] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China

Correspondence: [*] Correspondence to: Jin-Tai Yu, MD, PhD, Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12th Wulumuqi Zhong Road, Shanghai 200040, China. Tel.: +86 21 52888160; Fax: +86 21 62483421; E-mail: jintai_yu@fudan.edu.cn. and Lan Tan, MD, PhD, Qingdao Municipal Hospital, Qingdao University, China. E-mail: dr.tanlan@163.com.

Note: [1] The longitudinal data used in preparation for this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Abstract: 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.

Keywords: Alzheimer’s disease, amyloid-β, anxiety, biomarkers, dementia, neurodegeneration, tauopathies

DOI: 10.3233/JAD-210020

Journal: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 273-283, 2021