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Neural Precursors of Apathy and Depressive Symptoms in Amnestic Mild Cognitive Impairment

Abstract
Depressive symptoms and apathy are common in amnestic mild cognitive impairment (aMCI) and are associated with increased risk of conversion to Alzheimer’s disease (AD). The shared neuropathological model of neuropsychiatric symptoms (NPS) in AD suggests that symptoms of depression and anxiety represent noncognitive manifestations of neuropathological changes. Neurodegeneration in aMCI occurs in areas of the brain that support emotion regulation, including the limbic system and prefrontal control regions. Depression and apathy in aMCI have been linked to atrophy in the limbic system and prefrontal cortex and reduced connectivity in resting-state networks. However, it is not yet established whether neural changes in emotion centers in the brain predict symptoms of depression and apathy in persons with aMCI, or whether neural precursors in the limbic system and prefrontal cortex are associated with higher risk of conversion from aMCI to AD. The current study utilized longitudinal clinical and neuroimaging data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to determine whether change in neural structure and function in emotion centers predicted symptoms of depression and apathy in aMCI and conversion to AD. Depressive symptoms and apathy increased over time, and cortical volume in emotion centers in the brain decreased over time, especially in the MCI group. The slope of change in neural markers was not correlated with the slope of change in depressive symptoms or with the presence versus absence of apathy. Presence of apathy, slope of change in depressive symptoms, and speed of atrophy in the amygdala and cingulate cortex predicted progression of disease. Overall, results provided limited support for the shared neuropathological model of NPS in aMCI, primarily related to amygdala atrophy. Future research is needed to further define the role of neurodegeneration in emotion centers in the brain in the development and/or worsening of NPS in aMCI.
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