title: Depressive Symptoms and Small Hippocampal Volume Accelerate the Progression to Dementia from Mild Cognitive Impairment.
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.
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.|Multimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Jun Ku
authors.initials: JK
authors.lastname: Chung
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.|Multimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Plitman
authors.affiliation: Multimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Cerebral Imaging Centre, Douglas Mental Health Institute, McGill University, Montreal, PQ, Canada.|Department of Biomedical Engineering, McGill University, Montreal, Quebec, Canada.
authors.forename: M Mallar
authors.initials: MM
authors.lastname: Chakravarty
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.|Multimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Fernando
authors.initials: F
authors.lastname: Caravaggio
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Multimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Gerretsen
authors.affiliation: Multimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Cerebral Imaging Centre, Douglas Mental Health Institute, McGill University, Montreal, PQ, Canada.|Department of Biomedical Engineering, McGill University, Montreal, Quebec, Canada.
authors.forename: Raihaan
authors.initials: R
authors.lastname: Patel
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.|Multimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D060825:Cognitive Dysfunction / Q000150:complications* / Q000473:pathology*; D003704:Dementia / Q000473:pathology; D003863:Depression / Q000209:etiology*; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales
keywords: Dementia; depression; hippocampus; mild cognitive impairment