Brain Volume Predicts Behavioral and Psychological Symptoms in Alzheimer’s Disease

Article type: Research Article

Authors: Boublay, Nawele^{a; b; c; d; *} | Bouet, Romain^b | Dorey, Jean-Michel^f | Padovan, Catherine^f | Makaroff, Zaza^a | Fédérico, Denis^a | Gallice, Isabelle^h | Barrellon, Marie-Odileⁱ | Robert, Philippe^j | Moreaud, Olivier^k | Rouch, Isabelle^{a; g} | Krolak-Salmon, Pierre^{a; b; c; e} | Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Clinical and Research Memory Center of Lyon, Hospital of Charpennes, Lyon Institute for Elderly, University Hospital of Lyon, Lyon, France | [b] INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, Brain Dynamics and Cognition Team, Lyon, France | [c] University Lyon, Lyon, France | [d] Hospices Civils de Lyon, Pôle Information Médicale Evaluation Recherche, Lyon, France | [e] Clinical Research Center CRC - VCF (Vieillissement – Cerveau - Fragilité), Hospital of Charpennes, University Hospital of Lyon, Lyon, France | [f] Centre Hospitalier Le Vinatier, Bron, France | [g] Center Mémoire de Ressources et de Recherche, Neurology unit, University Hospital of Saint-Etienne, Saint Etienne, France | [h] Center Hospitalier Saint Jean de Dieu, Pôle de Gérontopsychiatrie, Lyon, France | [i] CH de Condrieu Route de la pavie Condrieu, Condrieu, France | [j] CoBTeK lab Clinical and Research Memory Center and CHU of Nice, Université Côte d’Azur, Nice, France | [k] Clinical and Research Memory Center and CHU of Grenoble Arc Alpin, Pôle de Psychiatrie et Neurologie, Laboratoire de Psychologie et Neurocognition, CNRS UMR 5105, Grenoble, France

Correspondence: [*] Correspondence to: Nawele Boublay, PhD, Hôpital des Charpennes, 27 rue Gabriel Péri, 69100 Villeurbanne, France. Tel.: +33 427 856 302; Fax: +33 427 859 267; E-mail: [email protected].

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (https://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: https://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

Abstract: Background:Behavioral and psychological symptoms of dementia (BPSD) are frequent and troublesome for patients and caregivers. Considering possible preventive approaches, a better understanding of underlying neural correlates of BPSD is crucial. Objective:The aim is to assess whether brain regional volume predicts behavioral changes in mild AD. Methods:This work took part from the PACO study, a multicenter and prospective study that included 252 patients with mild AD from 2009 to 2014. Fifty-three patients were retained. Forty healthy matched control subjects from the ADNI cohort were included as controls. Voxel-based morphometry analysis was conducted to assess regional brain volume using baseline MRI scans as a predictor of future behavioral changes over a period of 18 months. Behavior was assessed at baseline and longitudinally at 6-month intervals using the shortened form of the Neuropsychiatric Inventory (NPI). Results:The volume of 23 brain structures in frontal, temporal, parietal, occipital, subcortical regions and cerebellum predicted the evolution of NPI scores. Frontal volume was the most powerful predictor with frontal gyri, anterior cingulate cortex, and orbital gyri being particularly involved. Conclusion:To our knowledge, this is the first study assessing regional brain volumes as predictors of behavioral changes considered at earlier stages of AD. Up to 23 brain structures were associated with an increased risk of developing BPSD. Frontal lobe volume was the strongest predictor of future evolution of NPI. The involvement of multiple structures in the prediction of behavior suggests a role of the main large-scale networks involved in cognition.

Keywords: Alzheimer’s disease, behavioral and psychological symptoms of dementia, Neuropsychiatric Inventory, magnetic resonance imaging, neuroimaging

DOI: 10.3233/JAD-190612

Journal: Journal of Alzheimer's Disease, vol. 73, no. 4, pp. 1343-1353, 2020