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

Article type: Research Article

Authors: Ge, Xinting^{a; b; c; 1} | Qiao, Yuchuan^{a; 1} | Choi, Jiyoon^d | Raman, Rema^d | Ringman, John M.^e | Shi, Yonggang^{a; *} | for Alzheimer’s Disease Neuroimaging Initiative²

Affiliations: [a] Laboratory of Neuro Imaging (LONI), Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA | [b] School of Information Science and Engineering, Shandong Normal University, Jinan, Shandong, China | [c] School of Medical Imaging, Xuzhou Medical University, Xuzhou, Jiangsu, China | [d] Alzheimer’s Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego, CA, USA | [e] Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

Correspondence: [*] Correspondence to: Yonggang Shi, PhD, Laboratory of Neuro Imaging (LONI), Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, 2025 Zonal Avenue, Los Angeles, CA 90033, USA. Tel.: +1 323 442 7246; E-mail: yshi@loni.usc.edu.

Note: [1] These authors contributed equally to this work.

Note: [2] Data used in preparation of this article were partly obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (https://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 analysis or writing of this report. A complete listing of ADNI investigators can be found at: https://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

Abstract: 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 18F AV-1451, amyloid-β (Aβ) 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.

Keywords: Alzheimer’s disease, cognitive impairment, neuropsychiatric symptoms, tau-PET imaging

DOI: 10.3233/JAD-215555

Journal: Journal of Alzheimer's Disease, vol. 87, no. 2, pp. 557-568, 2022