Frontal Metabolites and Alzheimer’s Disease Biomarkers in Healthy Older Women and Women Diagnosed with Mild Cognitive Impairment

Article type: Research Article

Authors: Hone-Blanchet, Antoine^{a; b} | Bohsali, Anastasia^a | Krishnamurthy, Lisa C.^{c; d} | Shahid, Salman S.^{a; e} | Lin, Qixiang^a | Zhao, Liping^f | Bisht, Aditya S.^a | John, Samantha E.^g | Loring, David^a | Goldstein, Felicia^a | Levey, Allan^a | Lah, James^a | Qiu, Deqiang^{h; i; *} | Crosson, Bruce^{a; d; h}

Affiliations: [a] Department of Neurology, School of Medicine, Emory University, Atlanta, GA, USA | [b] Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA | [c] Department of Physics & Astronomy, Georgia State University, Atlanta, GA, USA | [d] Center for Visual and Neurocognitive Rehabilitation, Atlanta VAMC, Decatur, GA, USA | [e] Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA | [f] Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA | [g] Department of Brain Health, Population Health & Health Equity Initiative, University of Nevada, Las Vegas, NV, USA | [h] Department of Radiology and Imaging Sciences, School of Medicine, Emory University, Atlanta, GA, USA | [i] Joint Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA

Correspondence: [*] Correspondence to: Deqiang Qiu, Department of Radiology and Imaging Sciences, School of Medicine, Emory University, 100 Woodruff Circle, Atlanta, GA, 30322, USA. Tel.: +1 404 712 0356; E-mail: [email protected].

Abstract: Background:Women account for two thirds of the prevalence and incidence of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Evidence suggest that sex may differently influence the expression of proteins amyloid-beta (Aβ1–42) and tau, for which early detection is crucial in prevention of the disease. Objective:We investigated the effect of aging and cerebrospinal fluid (CSF) levels of Aβ1–42 and tau on frontal metabolites measured with proton magnetic resonance spectroscopy (MRS) in a cohort of cognitively normal older women and women with MCI. Methods:3T single-voxel MRS was performed on the medial frontal cortex, using Point Resolved Spectroscopy (PRESS) and Mescher-Garwood Point Resolved Spectroscopy (MEGA-PRESS) in 120 women (age range 50–85). CSF samples of Aβ1–42 and tau and scores of general cognition were also obtained. Results:Levels of frontal gamma aminobutyric acid (GABA+) were predicted by age, independently of disease and CSF biomarkers. Importantly, levels of GABA+ were reduced in MCI patients. Additionally, we found that levels of N-acetylaspartate relative to myo-inositol (tNAA/mI) predicted cognition in MCI patients only and were not related to CSF biomarkers. Conclusion:This study is the first to demonstrate a strong association between frontal GABA+ levels and neurological aging in a sample consisting exclusively of healthy older women with various levels of CSF tau and Aβ1–42 and women with MCI. Importantly, our results show no correlation between CSF biomarkers and MRS metabolites in this sample.

Keywords: Aging, cerebrospinal fluid biomarkers, frontal cortex, general cognition, magnetic resonance spectroscopy, mild cognitive impairment, women’s health

DOI: 10.3233/JAD-215431

Journal: Journal of Alzheimer's Disease, vol. 87, no. 3, pp. 1131-1141, 2022