Brain Metabolism and Microglia Activation in Mild Cognitive Impairment: A Combined [¹⁸F]FDG and [¹¹C]-(R)-PK11195 PET Study

Article type: Research Article

Authors: Tondo, Giacomo^{a; b; 1} | Boccalini, Cecilia^{a; b; 1} | Caminiti, Silvia Paola^{a; b} | Presotto, Luca^c | Filippi, Massimo^{a; d} | Magnani, Giuseppe^d | Frisoni, Giovanni Battista^{e; f} | Iannaccone, Sandro^g | Perani, Daniela^{a; b; c; *}

Affiliations: [a] Vita-Salute San Raffaele University, Milan, Italy | [b] In vivo human molecular and structural neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy | [c] Nuclear Medicine Unit, San Raffaele Hospital, Milan, Italy | [d] Department of Neurology and INSPE, San Raffaele Scientific Institute, Milan, Italy | [e] IRCCS Istituto Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy | [f] Memory Clinic and LANVIE- Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland | [g] Department of Rehabilitation and Functional Recovery, San Raffaele Hospital, Milan, Italy

Correspondence: [*] Correspondence to: Prof. Daniela Perani, MD, Vita-Salute San Raffaele University, Division of Neuroscience, IRCCS San Raffaele Scientific Institute; Nuclear Medicine Unit, IRCCS San Raffaele Hospital, Via Olgettina 60, Milan, Italy. Tel.: +39 02 2643 2224; E-mail: perani.daniela@hsr.it.

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

Abstract: Background:Mild cognitive impairment (MCI) is a transitional condition between normal cognition and dementia. [18F]FDG-PET reveals brain hypometabolism patterns reflecting neuronal/synaptic dysfunction, already in the prodromal MCI phase. Activated microglia is part of the pathogenetic processes leading to neurodegeneration. Objective:Using [11C]-(R)-PK11195 and [18F]FDG-PET, we aimed to in vivo investigate the presence of microglial activation, and the relationship with brain glucose metabolism, in single MCI subjects. Methods:Eight MCI subjects underwent both [18F]FDG-PET and [11C]-(R)-PK11195 PET. We used validated quantification methods to obtain brain hypometabolism maps and microglia activation peaks in single subjects. We investigated both the spatial overlap and the relationship between brain glucose hypometabolism and microglia activation, by means of Dice similarity coefficient and using Pearson’s correlation at single subject level. Results:Each MCI showed a specific brain hypometabolism pattern indicative of different possible etiologies, as expected in MCI population (i.e., Alzheimer’s disease-like, frontotemporal dementia-like, hippocampal-type, normal aging type). [11C]-(R)-PK11195 PET analysis revealed a spatial concordance with regional hypometabolism in all subjects with several clusters of significant microglia activation showing an inverse correlation with the regional metabolism. This was proportional to the strength of between-signals correlation coefficient (β  =  –0.804; p = 0.016). Conclusion:Microglia activation is present in the prodromal MCI phase of different underlying etiologies, showing spatial concordance and inverse correlation with brain glucose metabolism at single-subject level. These findings suggest a possible contribution of activated microglia to neurodegeneration, showing important implications for local immune activity in the early neurodegenerative processes.

Keywords: Alzheimer’s disease, cognitive dysfunction, dementia, metabolism, microglia, positron emission tomography, tauopathies

DOI: 10.3233/JAD-201351

Journal: Journal of Alzheimer's Disease, vol. 80, no. 1, pp. 433-445, 2021