Depressive Symptoms and Small Hippocampal Volume Accelerate the Progression to Dementia from Mild Cognitive Impairment

Article type: Research Article

Authors: Chung, Jun Ku^{a; b} | Plitman, Eric^{a; b} | Nakajima, Shinichiro^{b; c; d; e} | Chakravarty, M. Mallar^{f; g} | Caravaggio, Fernando^{a; b} | Takeuchi, Hiroyoshi^{c; d} | Gerretsen, Philip^{b; c; e} | Iwata, Yusuke^{b; d} | Patel, Raihaan^{f; g} | Mulsant, Benoit H.^c | Graff-Guerrero, Ariel^{a; b; c; e; *} | for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada | [b] Multimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada | [c] Department of Psychiatry, University of Toronto, Toronto, ON, Canada | [d] Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan | [e] Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, ON, Canada | [f] Cerebral Imaging Centre, Douglas Mental Health Institute, McGill University, Montreal, PQ, Canada | [g] Department of Biomedical Engineering, McGill University, Montreal, Quebec, Canada

Correspondence: [*] Correspondence to: Dr. Ariel Graff-Guerrero, MD, PhD, Multimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada. Tel.: +1 416 535 8501/Ext. 4834; E-mail: [email protected]

Note: [1] Some 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: Previous studies have highlighted that decreased hippocampal volume, an early neural correlate of dementia, is commonly observed in patients with mild cognitive impairment (MCI). However, it is unclear whether neurodegenerative and resultant clinical trajectories are accelerated in MCI patients with concomitant depressive symptoms, leading to a faster conversion to dementia stages than those who are not depressed. No longitudinal study has investigated whether depressed amnestic MCI (DEP+aMCI) patients show an earlier onset of progression to dementia than non-depressed amnestic MCI (DEP-aMCI) patients and whether progressive hippocampal volume reductions are related in the conversion process. Using data from Alzheimer’s Disease Neuroimaging Initiative, we examined 2-year follow-up data from 38 DEP+aMCI patients and 38 matched DEP-aMCI patients and compared their ages of conversion from aMCI to AD and trajectories of progressive hippocampal volume changes. DEP+ and DEP- patients were defined as having baseline Geriatric Depression Scale scores of 5 or above and 0, respectively. DEP+ converters showed earlier ages of conversion to dementia (p = 0.009) and greater left hippocampal volume loss than both DEP- converters and DEP+ non-converters over the 2-year period (p = 0.003, p = 0.001, respectively). These findings could not be explained by changes in total brain volume, differences in their clinical symptoms of dementia, daily functioning, or apolipoprotein E4 genotypes. No difference in conversion rate to dementia or progressive hippocampal volume change was found between DEP+ patients and DEP-patients, which suggested depressive symptoms themselves may not lead to progression of dementia from MCI. In conclusion, there is a synergistic effect of depressive symptoms and smaller left hippocampal volume in MCI patients that accelerates conversion to dementia.

Keywords: Dementia, depression, hippocampus, mild cognitive impairment

DOI: 10.3233/JAD-150679

Journal: Journal of Alzheimer's Disease, vol. 49, no. 3, pp. 743-754, 2016