Apathy in Patients With Cerebral Amyloid Angiopathy: A Multimodal Neuroimaging Study.

ObjectiveTo 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 multi-modal neuroimaging approach.MethodsThirty-seven probable sporadic cerebral amyloid angiopathy participants without symptomatic intracranial hemorrhage or dementia (mean age, 73.3 ± 7.2, % 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 done to identify differences in the gray matter and white matter between the apathetic and the non-apathetic 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, gender, and measures of depression were entered as covariates in all analyses.ResultsA 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 R = 27.90, p = 0.04). Lower gray matter volume of the bilateral orbitofrontal cortices was observed in the apathetic group than the non-apathetic group (F = 13.20, family-wise error corrected p = 0.028). The apathetic group demonstrated a widespread decrease in white matter microstructural integrity compared to the non-apathetic group. These tracts connect key regions within and between related reward circuits. Finally, there was no significant functional alterations between the apathetic and the non-apathetic groups.ConclusionsOur 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.