Increased Glucose Activity in Subgenual Anterior Cingulate and Hippocampus of High Performing Older Adults, Despite Amyloid Burden

Article type: Research Article

Authors: Borelli, Wyllians Vendramini^{a; b} | Leal-Conceição, Eduardo^a | Andrade, Michele Alberton^{a; c} | Esper, Nathalia Bianchini^{a; b} | Feltes, Paula Kopschina^d | Soder, Ricardo Bernardi^{a; b} | Matushita, Cristina Sebastião^a | Hartmann, Louise Mross^a | Radaelli, Graciane^a | Schilling, Lucas Porcello^a | Moriguchi-Jeckel, Cristina^a | Marques da Silva, Ana Maria^{a; c} | Portuguez, Mirna Wetters^{a; b} | Franco, Alexandre Rosa^{e; f} | da Costa, Jaderson Costa^{a; b; *}

Affiliations: [a] Brain Institute of Rio Grande do Sul (BraIns), PUCRS, Porto Alegre, Brazil | [b] School of Medicine, PUCRS, Porto Alegre, Brazil | [c] School of Science, PUCRS, Porto Alegre, Brazil | [d] Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands | [e] Center for Biomedical Imaging and Neuromodulation, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA | [f] Center for the Developing Brain, Child Mind Institute, New York, NY, USA

Correspondence: [*] Correspondence to: Jaderson Costa da Costa, Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul, Av. Ipiranga, 6690, Porto Alegre, RS, 90610-000, Brazil. Tel.: +5551 3320 5959; E-mail: jcc@pucrs.br.

Abstract: Background:Individuals at 80 years of age or above with exceptional memory are considered SuperAgers (SA), an operationalized definition of successful cognitive aging. SA showed increased thickness and altered functional connectivity in the anterior cingulate cortex as a neurobiological signature. However, their metabolic alterations are yet to be uncovered. Objective:Herein, a metabolic (FDG-PET), amyloid (PIB-PET), and functional (fMRI) analysis of SA were conducted. Methods:Ten SA, ten age-matched older adults (C80), and ten cognitively normal middle-aged (C50) adults underwent cognitive testing and multimodal neuroimaging examinations. Anterior and posterior regions of the cingulate cortex and hippocampal areas were primarily examined, then subregions of anterior cingulate were segregated. Results:The SA group showed increased metabolic activity in the left and right subgenual anterior cingulate cortex (sACC, p < 0.005 corrected, bilateral) and bilateral hippocampi (right: p < 0.0005 and left: p < 0.005, both corrected) as compared to that in the C80 group. Amyloid deposition was above threshold in 30% of SA and C80 (p > 0.05). The SA group also presented decreased connectivity between right sACC and posterior cingulate (p < 0.005, corrected) as compared to that of the C80 group. Conclusion:These results support the key role of sACC and hippocampus in SA, even in the presence of amyloid deposition. It also suggests that sACC may be used as a potential biomarker in older adults for exceptional memory ability. Further longitudinal studies measuring metabolic biomarkers may help elucidate the interaction between these areas in the cognitive aging process.

Keywords: Amyloid deposit, FDG, functional fMRI, high-performing older adults, successful cognitive aging

DOI: 10.3233/JAD-210063

Journal: Journal of Alzheimer's Disease, vol. 81, no. 4, pp. 1419-1428, 2021