Lifetime History of Depression Predicts Increased Amyloid-β Accumulation in Patients with Mild Cognitive Impairment

Article type: Research Article

Authors: Chung, Jun Ku^{a; b} | Plitman, Eric^{a; b} | Nakajima, Shinichiro^{b; c; d; e} | Chow, Tiffany W.^{a; c; e} | Chakravarty, M. Mallar^{f; g} | Caravaggio, Fernando^{a; b} | Gerretsen, Philip^{b; c; e} | Brown, Eric E.^{b; c} | Iwata, Yusuke^{b; d} | Mulsant, Benoit H.^c | Graff-Guerrero, Ariel^{a; b; c; d; e; *} | for the Alzheimer's Disease Neuroimaging Initiative

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

Correspondence: [*] Correspondence to: 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].

Abstract: Mounting evidence associates a lifetime history of major depression (LMD) with an increased risk for Alzheimer's disease (AD). Studies have shown that major depression (MD) is strongly linked to pathophysiological markers of AD, such as cortical amyloid-β (Aβ) burden. However, no imaging studies have shown in vivo whether an LMD is linked to increased Aβ accumulation in patients with mild cognitive impairment (MCI) in four cortical regions that have been highly associated with increased Aβ deposition in previous literature: frontal, cingulate, parietal, and temporal. Drawing from the ADNI database, we found that patients with amnestic MCI (aMCI) and an LMD (n = 39) had significantly higher 18F-Florbetapir standardized uptake value ratios, a surrogate measure of Aβ deposition, mainly in the bilateral frontal cortex, compared to patients with aMCI without an LMD (n = 39) (p = 0.02). This difference was not explained by current depressive symptoms, vascular risk factors, or the use of different PET scanners. The results were reliable employing two independent methods for analysis: region-of-interest and voxel-based analyses. Increased Aβ in the bilateral frontal lobes may be a biomarker of depressive symptomology in aMCI patients. Further studies should test whether higher Aβ predicts future conversion into AD in this population.

Keywords: Alzheimer's disease, amyloid-β, major depression, mild cognitive impairment, positron emission tomography

DOI: 10.3233/JAD-142931

Journal: Journal of Alzheimer's Disease, vol. 45, no. 3, pp. 907-919, 2015