Body Mass Index Decrease Has a Distinct Association with Alzheimer’s Disease Pathophysiology in APOE ɛ4 Carriers and Non-Carriers

Article type: Research Article

Authors: Li, Anqi^a | Du, Jing^a | Cai, Yue^a | Chen, Xuhui^b | Sun, Kun^c | Guo, Tengfei^{a; d; *} | for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Institute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, China | [b] Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, China | [c] Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, China | [d] Institute of Biomedical Engineering, Peking University Shenzhen Graduate School, Shenzhen, China

Correspondence: [*] Correspondence to: Tengfei Guo, PhD, Institute of Biomedical Engineering, Shenzhen Bay Laboratory, No.5 Kelian Road, Shenzhen, 518132, China. Tel.: + 86 0755 2684 9264; E-mail: tengfei.guo@szbl.ac.cn; ORCID: 0000-0003-2982-0865.

Note: [1] Data used in 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:Body mass index (BMI) changes may be related to Alzheimer’s disease (AD) alterations, but it is unclear how the apolipoprotein E ɛ4 (APOE ɛ4) allele affects their association. Objective:To explore the association of BMI changes with AD pathologies in APOE ɛ4 carriers and non-carriers. Methods:In 862 non-demented ADNI participants with≥2 BMI measurements, we investigated the relationships between BMI slopes and longitudinal changes in amyloid-β (Aβ) accumulation, neurodegeneration and cognition, and follow-up tau deposition in different Aβ and APOE ɛ4 statuses. Results:In Aβ+ APOE ɛ4 non-carriers, faster BMI declines were associated with faster rates of Aβ accumulation (standardized β (βstd) = –0.29, p = 0.001), AD meta regions of interest (metaROI) hypometabolism (βstd = 0.23, p = 0.026), memory declines (βstd = 0.17, p = 0.029), executive function declines (βstd = 0.19, p = 0.011), and marginally faster Temporal-metaROI cortical thinning (βstd = 0.15, p = 0.067) and higher follow-up Temporal-metaROI tau deposition (βstd = –0.17, p = 0.059). Among Aβ- individuals, faster BMI decreases were related to faster Aβ accumulation (βstd = –0.25, p = 0.023) in APOE ɛ4 carriers, whereas predicted faster declines in memory and executive function in both APOE ɛ4 carriers (βstd = 0.25, p = 0.008; βstd = 0.32, p = 0.001) and APOE ɛ4 non-carriers (βstd = 0.11, p = 0.030; βstd = 0.12, p = 0.026). Conclusions:This study highlights the significance of tracking BMI data in older adults by providing novel insights into how body weight fluctuations and APOE ɛ4 interact with AD pathology and cognitive decline.

Keywords: Alzheimer’s disease, apolipoprotein E ɛ4, body mass index, cognitive decline, neurodegeneration

DOI: 10.3233/JAD-230446

Journal: Journal of Alzheimer's Disease, vol. 96, no. 2, pp. 643-655, 2023