Neuropsychiatric Symptoms and Functional Connectivity in Mild Cognitive Impairment

Article type: Research Article

Authors: Munro, Catherine E.^a | Donovan, Nancy J.^{c; d; e; f} | Guercio, Brendan J.^c | Wigman, Sarah E.^{a; e} | Schultz, Aaron P.^a | Amariglio, Rebecca E.^{a; c; d; e; f} | Rentz, Dorene M.^{a; c; d; e; f} | Johnson, Keith A.^{b; c; d; e} | Sperling, Reisa A.^{a; c; d; e} | Marshall, Gad A.^{a; c; d; e; *}

Affiliations: [a] Department of Neurology, Massachusetts General Hospital, Boston, MA, USA | [b] Department of Radiology, Massachusetts General Hospital, Boston, MA, USA | [c] Harvard Medical School, Boston, MA, USA | [d] Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA | [e] Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA | [f] Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

Correspondence: [*] Correspondence to: Gad A. Marshall, MD, Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital, 221 Longwood Avenue, BL-104 H, Boston, MA 02115, USA. Tel.: +1 617 732 8085; Fax: +1 617 264 5212; [email protected]

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.

Keywords: Alzheimer’s disease, apathy, functional magnetic resonance imaging, mild cognitive impairment, neuropsychiatric symptoms

DOI: 10.3233/JAD-150017

Journal: Journal of Alzheimer's Disease, vol. 46, no. 3, pp. 727-735, 2015