Cognitive and Brain Metabolism Profiles of Mild Cognitive Impairment in Prodromal Alpha-Synucleinopathy

Article type: Research Article

Authors: Mattioli, Pietro^{a; *} | Pardini, Matteo^{a; b} | Girtler, Nicola^{a; c} | Brugnolo, Andrea^{a; c} | Orso, Beatrice^a | Donniaquio, Andrea^a | Calizzano, Francesco^a | Mancini, Raffaele^a | Massa, Federico^a | Terzaghi, Michele^{d; e} | Bauckneht, Matteo^{b; f} | Morbelli, Silvia^{b; f} | Sambuceti, Gianmario^{b; f} | Nobili, Flavio^{a; b} | Arnaldi, Dario^{a; b}

Affiliations: [a] Department of Neuroscience, University of Genoa, Genoa, Italy | [b] IRCCS Ospedale Policlinico San Martino, Genoa, Italy | [c] Clinical Psychology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy | [d] Unit of Sleep Medicine and Epilepsy, IRCCS Mondino Foundation, Pavia, Italy | [e] Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy | [f] Nuclear Medicine Unit, Department of Health Sciences, University of Genoa, Genoa, Italy

Correspondence: [*] Correspondence to: Pietro Mattioli, MD, Clinical Neurology, Department of Neuroscience (DINOGMI), University of Genoa, Italy Largo P. Daneo, 3, 16132 Genova, Italy. Tel.: +39 010 5557290; Fax: +39 010 5556893; E-mail: [email protected].

Abstract: Background:Mild cognitive impairment (MCI) is a heterogeneous condition. Idiopathic REM sleep behavior disorder (iRBD) can be associated with MCI (MCI-RBD). Objective:To investigate neuropsychological and brain metabolism features of patients with MCI-RBD by comparison with matched MCI-AD patients. To explore their predictive value toward conversion to a full-blown neurodegenerative disease. Methods:Seventeen MCI-RBD patients (73.6±6.5 years) were enrolled. Thirty-four patients with MCI-AD were matched for age (74.8±4.4 years), Mini-Mental State Exam score and education with a case-control criterion. All patients underwent a neuropsychological assessment and brain 18F-FDG-PET. Images were compared between groups to identify hypometabolic volumes of interest (MCI-RBD-VOI and MCI-AD-VOI). The dependency of whole-brain scaled metabolism levels in MCI-RBD-VOI and MCI-AD-VOI on neuropsychological test scores was explored with linear regression analyses in both groups, adjusting for age and education. Survival analysis was performed to investigate VOIs phenoconversion prediction power. Results:MCI-RBD group scored lower in executive functions and higher in verbal memory compared to MCI-AD group. Also, compared with MCI-AD, MCI-RBD group showed relative hypometabolism in a posterior brain area including cuneus, precuneus, and occipital regions while the inverse comparison revealed relative hypometabolism in the hippocampus/parahippocampal areas in MCI-AD group. MCI-RBD-VOI metabolism directly correlated with executive functions in MCI-RBD (p = 0.04). MCI-AD-VOI metabolism directly correlated with verbal memory in MCI-AD (p = 0.001). MCI-RBD-VOI metabolism predicted (p = 0.03) phenoconversion to an alpha-synucleinopathy. MCI-AD-VOI metabolism showed a trend (p = 0.07) in predicting phenoconversion to dementia. Conclusion:MCI-RBD and MCI-AD showed distinct neuropsychological and brain metabolism profiles, that may be helpful for both diagnosis and prognosis purposes.

Keywords: Alpha-synucleinopathies, Alzheimer’s disease, brain metabolism, mild cognitive impairment, REM sleep behavior disorder

DOI: 10.3233/JAD-220653

Journal: Journal of Alzheimer's Disease, vol. 90, no. 1, pp. 433-444, 2022