Serotonin Selective Reuptake Inhibitor Treatment Improves Cognition and Grey Matter Atrophy but not Amyloid Burden During Two-Year Follow-Up in Mild Cognitive Impairment and Alzheimer’s Disease Patients with Depressive Symptoms

Article type: Research Article

Authors: Brendel, Matthias^a; | Sauerbeck, Julia^a; | Greven, Sonja^b | Kotz, Sebastian^a | Scheiwein, Franziska^a | Blautzik, Janusch^a | Delker, Andreas^a | Pogarell, Oliver^c | Ishii, Kazunari^d | Bartenstein, Peter^a | Rominger, Axel^{a; e; *} | for the Alzheimer’s Disease Neuroimaging Initiative

Affiliations: [a] Department of Nuclear Medicine, University of Munich, Germany | [b] Department of Statistics, University of Munich, Germany | [c] Department of Psychiatry, University of Munich, Germany | [d] Department of Radiology, Kindai University Faculty of Medicine, Osakasayama City, Osaka, Japan | [e] Department of Nuclear Medicine, Inselspital, University Hospital Bern, Switzerland

Correspondence: [*] Correspondence to: Prof. Dr. Axel Rominger, MD, Department of Nuclear Medicine, University of Bern, Switzerland. Tel.: +41 32 632 26 10; Fax: +41 32 632 76 63; E-mail: axel.rominger@insel.ch.

Note: [1] These authors contributed equally to this work.

Note: [2] 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: Late-life depression, even when of subsyndromal severity, has shown strong associations with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Preclinical studies have suggested that serotonin selective reuptake inhibitors (SSRIs) can attenuate amyloidogenesis. Therefore, we aimed to investigate the effect of SSRI medication on amyloidosis and grey matter volume in subsyndromal depressed subjects with MCI and AD during an interval of two years. 256 cognitively affected subjects (225 MCI/ 31 AD) undergoing [18F]-AV45-PET and MRI at baseline and 2-year follow-up were selected from the ADNI database. Subjects with a positive depression item (DEP(+); n = 73) in the Neuropsychiatric Inventory Questionnaire were subdivided to those receiving SSRI medication (SSRI(+); n = 24) and those without SSRI treatment (SSRI(−); n = 49). Longitudinal cognition (Δ-ADAS), amyloid deposition rate (standardized uptake value, using white matter as reference region (SUVRWM), and changes in grey matter volume were compared using common covariates. Analyses were performed separately in all subjects and in the subgroup of amyloid-positive subjects. Cognitive performance in DEP(+)/SSRI(+) subjects (Δ-ADAS: –5.0%) showed less deterioration with 2-year follow-up when compared to DEP(+)/SSRI(−) subjects (Δ-ADAS: +18.6%, p < 0.05), independent of amyloid SUVRWM at baseline. With SSRI treatment, the progression of grey matter atrophy was reduced (−0.9% versus –2.7%, p < 0.05), notably in fronto-temporal cortex. A slight trend towards lower amyloid deposition rate was observed in DEP(+)/SSRI(+) subjects versus DEP(+)/SSRI(−). Despite the lack of effect to amyloid PET, SSRI medication distinctly rescued the declining cognitive performance in cognitively affected patients with depressive symptoms, and likewise attenuated grey matter atrophy.

Keywords: Alzheimer’s disease, amyloid PET, depressive symptoms, grey matter volume, SSRI

DOI: 10.3233/JAD-170387

Journal: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 793-806, 2018