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Updated: Aug 6, 2025
Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases
Published on: December 6, 2016
Apathy in Patients With Cerebral Amyloid Angiopathy: A Multimodal Neuroimaging Study
Anthipa Chokesuwattanaskul1, Maria Clara Zanon Zotin2, Dorothée Schoemaker2
1From the Department of Neurology (A.C., M.C.Z.Z., D.S., L.S., M.E.G., S.M.G., A.V.), J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston; Division of Neurology (A.C.), King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand; Cognitive Clinical and Computational Neuroscience Research Unit (A.C.), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Department of Medical Imaging (M.C.Z.Z.), Center for Imaging Sciences and Medical Physics, Hematology and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil; Division of Neurology, Department of Clinical Neurosciences (L.S.), Geneva University Hospital, Faculty of Medicine, University of Geneva, Switzerland. anthipa.c@chula.ac.th.
Background And Objective:
To analyze the prevalence and associated clinical characteristics of apathy in sporadic cerebral amyloid angiopathy and investigate whether apathy was associated with disease burden and disconnections of key structures in the reward circuit through a structural and functional multimodal neuroimaging approach.
Methods:
Thirty-seven participants with probable sporadic cerebral amyloid angiopathy without symptomatic intracranial hemorrhage or dementia (mean age, 73.3 ± 7.2 years, % male = 59.5%) underwent a detailed neuropsychological evaluation, including measures of apathy and depression, and a multimodal MR neuroimaging study. A multiple linear regression analysis was used to assess the association of apathy with conventional small vessel disease neuroimaging markers. A voxel-based morphometry with a small volume correction within regions previously associated with apathy and a whole-brain tract-based spatial statistics were performed to identify differences in the gray matter and white matter between the apathetic and nonapathetic groups. Gray matter regions significantly associated with apathy were further evaluated for their functional alterations as seeds in the seed-based resting-state functional connectivity analysis. Potential confounders, namely, age, sex, and measures of depression, were entered as covariates in all analyses.
Results:
A higher composite small vessel disease marker score (CAA-SVD) was associated with a higher degree of apathy (standardized coefficient = 1.35 (0.07-2.62), adjusted R2 = 27.90, p = 0.04). Lower gray matter volume of the bilateral orbitofrontal cortices was observed in the apathetic group than in the nonapathetic group (F = 13.20, family-wise error-corrected p = 0.028). The apathetic group demonstrated a widespread decrease in white matter microstructural integrity compared with the nonapathetic group. These tracts connect key regions within and between related reward circuits. Finally, there were no significant functional alterations between the apathetic and nonapathetic groups.
Discussion:
Our findings revealed the orbitofrontal cortex as a key region in the reward circuit associated with apathy in sporadic cerebral amyloid angiopathy, independent from depression. Apathy was shown to be associated with a higher CAA-SVD score and an extensive disruption of white matter tracts, which suggested that a higher burden of CAA pathology and the disruption in large-scale white matter networks may underlie manifestations of apathy.
