Abstract
OBJECTIVES: To examine whether depression and apathy are independently associated with longitudinal trajectories of cortical atrophy in the entorhinal cortex compared with frontal subregions previously implicated in late-life mood disturbance. METHODS: Data from 334 participants classified as having mild cognitive impairment in the Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed by using multilevel models for change adjusted for age, global cognitive status, and total intracranial volume at enrollment. Participants in ADNI were recruited from >50 clinical research sites in the United States and Canada. Depression and apathy were identified by informants using the Neuropsychiatric Inventory Questionnaire. Serial magnetic resonance imaging was performed on 1.5-Tesla scanners according to the standardized ADNI-1 protocol on an average of 5 occasions over an average of 30.5 months. Regional cortical thickness values were derived from longitudinal data processing in FreeSurfer version 4.4. RESULTS: Depression was associated with reduced cortical thickness in the entorhinal cortex at baseline and accelerated atrophy in the anterior cingulate cortex. Similar relationships between depression and the orbitofrontal cortex and between apathy and the anterior cingulate cortex were not significant. CONCLUSIONS: In mild cognitive impairment, depression signs are a better marker of longitudinal cortical atrophy than apathy. Results are consistent with hypotheses that depression is an early sign of a more aggressive neurodegenerative process or that depression lowers brain reserve capacity, allowing for more rapid progression of Alzheimer disease neuropathology.