Relationship Between Body Mass Index, ApoE4 Status, and PET-Based Amyloid and Neurodegeneration Markers in Amyloid-Positive Subjects with Normal Cognition or Mild Cognitive Impairment

Article type: Research Article

Authors: Blautzik, Janusch^{a; 1} | Kotz, Sebastian^{a; 1} | Brendel, Matthias^a | Sauerbeck, Julia^a | Vettermann, Franziska^a | Winter, Yaroslav^b | Bartenstein, Peter^a | Ishii, Kazunari^c | Rominger, Axel^{a; *} | for the Alzheimer’s Disease Neuroimaging Initiative²

Affiliations: [a] Department of Nuclear Medicine, Ludwig-Maximilians-University Munich, Munich, Germany | [b] Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany | [c] Department of Radiology, Kindai University Hospital, Osaka, Japan

Correspondence: [*] Correspondence to: Prof. Dr. Axel Rominger, MD, Department of Nuclear Medicine, University of Munich, Munich, Germany. Tel.: +49 89 4400 74650; Fax: +49 89 4400 77646; E-mail: [email protected].

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

Note: [2] 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: Body weight loss in late-life is known to occur at a very early stage of Alzheimer’s disease (AD). Apolipoprotein E4 (ApoE4) represents a major genetic risk factor for AD and is linked to an increased cortical amyloid-β (Aβ) accumulation. Since the relationship between body weight, ApoE4, and AD pathology is poorly investigated, we aimed to evaluate whether ApoE4 allelic status modifies the association of body mass index (BMI) with markers of AD pathology. A total of 368 Aβ-positive cognitively healthy or mild cognitive impaired subjects had undergone [18F]-AV45-PET, [18F]-FDG-PET, and T1w-MRI examinations. Composite cortical [18F]-AV45 uptake and [18F]-FDG uptake in posterior cingulate cortex were calculated as surrogates of cortical Aβ load and glucose metabolism, respectively. Multiple linear regressions were performed to assess the relationships between these PET biomarkers with BMI, present cognitive performance, and cognitive changes over time. Multivariate analysis of covariance was conducted to test for statistical differences between ApoE4/BMI categories on the PET markers and cognitive scores. In carriers of the ApoE4 allele only, BMI was inversely associated with cortical amlyoid load (β= –0.193, p < 0.005) and recent cognitive decline (β= –0.209, p < 0.05), and positively associated with cortical glucose metabolism in an AD-vulnerable region (β= 0.145, p < 0.05). ApoE4/BMI category analyses demonstrated lower Aβ load, higher posterior cingulate glucose metabolism, improved cognitive performance, and lower progression of cognitive decline in obese ApoE4 carriers. The effect of ApoE4 in promoting the accumulation of cortical amyoid, which may itself be a driver for weight loss, may be moderated by altering leptin signaling in the hypothalamus.

Keywords: Alzheimer’s disease, amyloid-β PET, ApoE4, body mass index, FDG-PET, markers of AD pathology

DOI: 10.3233/JAD-170064

Journal: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 781-791, 2018