Abstract
Background: Neuropsychiatric symptoms (NPS), such as apathy and depression,
commonly accompany cognitive and functional decline in early Alzheimer’s disease (AD).
Prior studies have shown associations between affective NPS and neurodegeneration of
medial frontal and inferior temporal regions in mild cognitive impairment (MCI) and AD
dementia.
Objective: To investigate the association between functional connectivity in
four brain networks and NPS in elderly with MCI.
Methods: NPS were assessed using the Neuropsychiatric Inventory in 42
subjects with MCI. Resting-state functional connectivity in four networks (default mode
network, fronto-parietal control network (FPCN), dorsal attention network, and ventral
attention network) was assessed using seed-based magnetic resonance imaging. Factor
analysis was used to identify two factors of NPS: Affective and Hyperactivity. Linear
regression models were utilized with the neuropsychiatric factors as the dependent
variable and the four networks as the predictors of interest. Covariates included age,
gender, premorbid intelligence, processing speed, memory, head movement, and
signal-to-noise ratio. These analyses were repeated with the individual items of the
affective factor, using the same predictors.
Results: There was a significant association between greater Affective
factor symptoms and reduced FPCN connectivity (p = 0.03). There was no
association between the Hyperactivity factor and any of the networks. Secondary analyses
revealed an association between greater apathy and reduced FPCN connectivity
(p = 0.005), but none in other networks.
Conclusions: Decreased connectivity in the FPCN may be associated with
greater affective symptoms, particularly apathy, early in AD. These findings extend prior
studies, using different functional imaging modalities in individuals with greater disease
severity.
