Abstract

The neural mechanisms underlying neurodegenerative disorders in the elderly remain elusive, despite extensive neuroimaging research in recent decades. Amnestic type mild cognitive impairment (aMCI) and late-life major depressive disorder (MDD) are two such conditions characterized by intersecting cognitive and affective symptomatology, and they are at a higher risk for Alzheimer's disease. This study analyzed the neural underpinnings of cognitive and depressive symptoms in a cohort comprising 12 aMCI subjects, 24 late-life MDD patients, and 26 healthy controls (HCs). Participants underwent a detailed neuropsychological assessment and completed a visual attentional oddball task during functional magnetic resonance imaging (fMRI), with evaluations at baseline and at 2-year follow-up. Initial findings showed that aMCI subjects had reduced dACC activation during oddball (target) stimulus detection, a pattern that persisted in longitudinal analyses and correlated with cognitive functioning measures. For HCs, subsequent dACC activation was linked to depression scores. Furthermore, in the affective-cognitive altered groups, later dACC activation correlated with oddball and memory performance. These findings enhance our comprehension of the neurobiological basis of cognitive and depressive disturbances in aging, indicating that dACC activation in response to a visual attentional oddball task could serve as a neural marker for assessing cognitive impairment and depression in conditions predisposing to Alzheimer's disease.