Brain Regions Involved in Arousal and Reward Processing are Associated with Apathy in Alzheimer’s Disease and Frontotemporal Dementia

Article type: Research Article

Authors: Huey, Edward D.^{a; b; c; d; *} | Lee, Seonjoo^{d; e} | Cheran, Gayathri^c | Grafman, Jordan^{f; g} | Devanand, Davangere P.^{b; d} | for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Taub Institute and Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, USA | [b] Division of Geriatric Psychiatry, Department of Psychiatry, Columbia University, College of Physicians and Surgeons and New York State Psychiatric Institute, New York, NY, USA | [c] Department of Neurology, Columbia University, College of Physicians and Surgeons, New York, NY, USA | [d] Department of Psychiatry, Columbia University, College of Physicians and Surgeons and New York State Psychiatric Institute, Columbia University, New York, NY, USA | [e] Department of Biostatistics, Columbia University, College of Physicians and Surgeons, New York, NY, USA | [f] Brain Injury Research Program, Rehabilitation Institute of Chicago, Chicago, IL, USA | [g] Northwestern University, Chicago, IL, USA

Correspondence: [*] Correspondence to: Edward D. Huey, Taub Institute and Gertrude H. Sergievsky Center, Columbia University Medical Center, 630W 168th St, P&S Box 16, New York, NY 10032, USA. Tel.: +1 212 305 1134; Fax: +1 212 305 2426; E-mail: [email protected].

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

Abstract: Background: Apathy is a common and problematic symptom of several neurodegenerative illnesses, but its neuroanatomical bases are not understood. Objective: To determine the regions associated with apathy in subjects with mild Alzheimer’s disease (AD) using a method that accounts for the significant co-linearity of regional atrophy and neuropsychiatric symptoms. Methods: We identified 57 subjects with mild AD (CDR = 1) and neuropsychiatric symptoms in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. We performed a multivariate multiple regression with LASSO regularization on all symptom subscales of the Neuropsychiatric Inventory and the whole-brain ROI volumes calculated from their baseline MRIs with FreeSurfer. We compared our results to those from a previous study using the same method in patients with frontotemporal dementia (FTD) and corticobasal syndrome (CBS). Results: Of neuropsychiatric symptoms, apathy showed the most robust neuroanatomical associations in the AD subjects. Atrophy of the following regions were independently associated with apathy: the ventromedial prefrontal cortex; ventrolateral prefrontal cortex; posterior cingulate cortex and adjacent lateral cortex; and the bank of the superior temporal sulcus. These results replicate previous studies using FTD and CBS patients, mostly agree with the previous literature on apathy in AD, and correspond to the Medial and Orbital Prefrontal Cortex networks identified in non-human primates. Conclusion: The current study, previous studies from our laboratory, and the previous literature suggest that impairment of the same brain networks involved in arousal, threat response, and reward processing are associated with apathy in AD and FTD.

Keywords: Apathy, Alzheimer’s disease, frontotemporal dementia, magnetic resonance imaging, neuropsychiatry

DOI: 10.3233/JAD-160107

Journal: Journal of Alzheimer's Disease, vol. 55, no. 2, pp. 551-558, 2017