Detection of Tau-PET Positivity in Clinically Diagnosed Mild Cognitive Impairment with Multidimensional Features

Article type: Research Article

Authors: Li, Bingyu^{a; 1} | Shi, Kening^{a; 1} | Ren, Chao^a | Kong, Min^{b; *} | Ba, Maowen^{a; c; *; *} | for Alzheimer’s Disease Neuroimaging Initiative²

Affiliations: [a] Department of Neurology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China | [b] Department of Neurology, Yantaishan Hospital, Yantai, Shandong, China | [c] Yantai Regional Sub Center of National Center for Clinical Medical Research of Neurological Diseases, Shandong, China

Correspondence: [*] Correspondence to: Maowen Ba, Department of Neurology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, China. Tel.: +86 15949962216; E-mail: bamaowen@163.com and Min Kong, Department of Neurology, Yantaishan Hospital, Yantai, Shandong 264003, China. Tel.: +86 15266547949; E-mail: kk_kmm@sina.com.

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

Note: [2] Data used in the preparation of 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 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 way to evaluate brain tau pathology in vivo is tau positron emission tomography (tau-PET) or cerebrospinal fluid (CSF) analysis. In the clinically diagnosed mild cognitive impairment (MCI), a proportion of tau-PET are negative. Interest in less expensive and convenient ways to detect tau pathology in Alzheimer’s disease has increased due to the high cost of tau-PET and the invasiveness of lumbar puncture, which typically slows down the cost and enrollment of clinical trials. Objective:We aimed to investigate one simple and effective method in predicting tau-PET status in MCI individuals. Methods:The sample included 154 individuals which were dichotomized into tau-PET (+) and tau-PET (–) using a cut-off of >1.33. We used stepwise regression to select the unitary or combination of variables that best predicted tau-PET. The receiver operating characteristic curve was used to assess the accuracy of single and multiple clinical markers. Results:The combined performance of three variables [Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog13), Mini-Mental State Examination (MMSE), ADNI-Memory summary score (ADNI-MEM)] in neurocognitive measures demonstrated good predictive accuracy of tau-PET status [accuracy = 85.7%, area under the curve (AUC) = 0.879]. The combination of clinical markers model (APOE ɛ4, neurocognitive measures and structural MRI imaging of middle temporal) had the best discriminative power (AUC = 0.946). Conclusion:As a noninvasive test, the combination of APOE ɛ4, neurocognitive measures and structural MRI imaging of middle temporal accurately predicts tau-PET status. The finding may provide a non-invasive, cost-effective tool for clinical application in predicting tau pathology among MCI individuals.

Keywords: Alzheimer’s disease, Apolipoprotein E4, magnetic resonance imaging, mild cognitive impairment, positron-emission tomography

DOI: 10.3233/JAD-230180

Journal: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 627-640, 2023