Vascular Effects on Depressive Symptoms in Cognitive Impairment

Article type: Research Article

Authors: Kim, Yeshin^{a; b; c} | Jang, Hyemin^{a; b} | Kim, Seung Joo^{a; b} | Cho, Soo Hyun^{a; b} | Kim, Si Eun^{a; b; d} | Kim, Sung Tae^e | Kim, Hee Jin^{a; b} | Moon, Seung Hwan^{b; f} | Ewers, Michael^g | Im, Kiho^h | Kwon, Hunkiⁱ | Na, Duk L.^{a; b; j; k} | Seo, Sang Won^{a; b; j; l; *}

Affiliations: [a] Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea | [b] Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea | [c] Department of Neurology, Kangwon National University Hospital, Kangwon National University College of Medicine, Chuncheon, Republic of Korea | [d] Department of Neurology, Inje University College of Medicine, Haeundae Paik Hospital, Busan, Republic of Korea | [e] Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea | [f] Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea | [g] Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany | [h] Division of Newborn Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA | [i] Department of Neurology, Yale University School of Medicine, New Haven, CT, USA | [j] Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea | [k] Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul ,South Korea | [l] Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea

Correspondence: [*] Correspondence to: Sang Won Seo, MD, PhD, Department of Neurology, Sungkyunkwan University School of Medicine, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea. Tel.: +82 2 3410 6147; Fax: +82 2 3410 0052; E-mail: sangwonseo@empas.com.

Abstract: Late life depression is related to pathologic burdens, such as cerebral small vascular disease (CSVD) and amyloid, which are associated with brain network changes and cortical thinning. To examine the associations of various CSVD imaging markers, amyloid, and network changes with depression in cognitively impaired patients, we prospectively recruited 228 cognitively impaired patients having various degrees of amyloid and CSVD who underwent diffuse tensor image and PiB PET. Greater CSVD burden was associated with greater Geriatric Depression Scale (GDS) (white matter hyperintensities, WMH: p = 0.025, lacunes: p < 0.001) but not with amyloid (p = 0.095), and cortical thinning (p = 0.630) was not associated with greater GDS. The changes in white matter networks were related to GDS with decreasing integration (global efficiency: p < 0.001) and increasing segregation (clustering coefficient: p = 0.009). The network changes mediated the relationships of WMH and lacunes with GDS. Our findings provide insight to better understand how CSVD burdens contribute to depression in cognitively impaired patients having varying degrees of amyloid and vascular burdens.

Keywords: Depression, network, small vessel disease

DOI: 10.3233/JAD-180394

Journal: Journal of Alzheimer's Disease, vol. 65, no. 2, pp. 597-605, 2018