Structural Brain Differences Between Cognitively Impaired Patients With and Without Apathy

Abstract

Objective: Since apathy increases in prevalence with severity of dementia pathology, we sought to distinguish concomitant neurodegenerative processes from brain differences associated with apathy in persons with mild cognitive impairment (MCI) and Alzheimer's Disease (AD). We examined relative structural brain differences between case-control matched cognitively impaired patients with and without apathy.

Design: Cross-sectional case-control study.

Setting: Fifty-eight clinical sites in phase 2 of the AD Neuroimaging Initiative across the United States and Canada.

Participants: The ≥ 55 years of age with MCI or AD dementia and no major neurological disorders aside from suspected incipient AD dementia. Participants with apathy (n=69) were age-, sex-, apolipoprotein E ε4 allele carrier status-, Mini-Mental State Exam score-, and MCI or AD dementia diagnosis-matched to participants without apathy (n=149).

Interventions: The 3-tesla T1-weighted MRI scan and neurocognitive assessments. Using the Neuropsychiatric Inventory apathy domain scores, participants were dichotomized into a with-apathy group (score ≥ 1) and a without-apathy group (score = 0).

Measurements: Cortical thicknesses from 24 a priori regions of interest involved in frontostriatal circuits and frontotemporal association areas.

Results: False-discovery rate adjusted within-group comparisons between participants with apathy and participants without apathy showed thinner right medial orbitofrontal (mOFC; meandifference(MD)±standarderrorofMD(SE)=-0.0879±0.0257mm; standardizedMD(d)=-0.4456) and left rostral anterior cingulate (rACC; MD±SE=-0.0905±0.0325mm; d=-0.3574) cortices and thicker left middle temporal cortices (MTC; MD±SE=0.0688±0.0239mm; d=0.3311) in those with apathy.

Conclusion: Atrophy of the right mOFC and left rACC and sparing of atrophy in the left MTC are associated with apathy in cognitively impaired persons.

Keywords: ADNI; Alzheimer's Disease; Structural MRI; apathy; case-control; cognitively normal; cortical thickness; dementia; frontostriatal circuits; frontotemporal association areas; healthy controls; matching; mild cognitive impairment; mixed models; region of interest analysis.