Clinical Effects of Frontal Behavioral Impairment: Cortical Thickness and Cognitive Decline in Individuals with Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment

Article type: Research Article

Authors: Kim, Seung Joo^{a; f} | Jung, Na-Yeon^g | Kim, Young Ju^a | Park, Seong Beom^a | Kim, KoWoon^h | Kim, Yeshinⁱ | Jang, Hyemin^a | Kim, Si Eun^{a; j} | Cho, Soo Hyun^{a; k} | Kim, Jun Pyo^a | Jung, Young Hee^a | Woo, Sook-Young^l | Kim, Seon Woo^l | Lockhart, Samuel N.^m | Kim, Eun-Jooⁿ | Kim, Hee Jin^a | Lee, Jong-Min^o | Chin, Juhee^a | Na, Duk L.^a | Seo, Sang Won^{a; b; c; d; e; *}

Affiliations: [a] Departments of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea | [b] Neuroscience Center, Samsung Medical Center, Seoul, South Korea | [c] Samsung Alzheimer Research Center, Samsung Medical Center, Seoul, South Korea | [d] Center for Clinical Epidemiology, Samsung Medical Center, Seoul, South Korea | [e] Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea | [f] Departments of Neurology, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, South Korea | [g] Department of Neurology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine and Medical Research Institute, Yangsan, South Korea | [h] Department of Neurology, Chonbuk National University Hospital, Chun-Ju, South Korea | [i] Department of Neurology, Kangwon National University Hospital, Chuncheon, South Korea | [j] Department of Neurology, Inje University College of Medicine, Haeundae Paik Hospital, Busan, South Korea | [k] Department of Neurology, Chonnam National University Hospital, Gwangju, South Korea | [l] Biostatistics team, Samsung Biomedical Research Institute, Seoul, South Korea | [m] Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, USA | [n] Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, South Korea | [o] Department of Biomedical Engineering, Hanyang University, Seoul, South Korea

Correspondence: [*] Correspondence to: Sang Won Seo, MD, PhD, Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. Tel.: +82 2 3410 1233/3599; Fax: +82 2 3410 0052; E-mail: sangwonseo@empal.com.

Abstract: Background:Frontal behavioral impairment (FrBI) is commonly observed in various degenerative diseases and refers to various behavioral symptoms. Objective:We investigated the effects of the presence of FrBI on cortical thickness, and the longitudinal neuropsychological changes in people in the predementia stage. Methods:A total of 794 individuals completed neuropsychological tests and the Frontal Behavioral Inventory (FBI) Questionnaire, and underwent magnetic resonance (MR) scanning. Participants were analyzed and grouped into non-FrBI (FBI = 0) or FrBI (FBI≥1). Cortical thickness was measured on MR images using a surface-based method. Results:In total, 281 people with subjective cognitive decline (SCD) and 513 with amnestic mild cognitive impairment (aMCI) were assessed for FrBI. Relative to people without FrBI, those with FrBI presented reduced cortical thickness in the frontal, anterior temporal and lateral parietal regions (p < 0.05, FDR corrected). People with FrBI developed Alzheimer’s disease, rather than behavioral variant frontotemporal dementia, as observed over seven years. Mixed effects models reported that people with FrBI have greater cognitive decline than those with non-FrBI in multiple domains, including language, memory, and executive functions (p < 0.05, FDR corrected). Furthermore, while negative FrBI symptoms (e.g., deficit behaviors) were associated with greater declines in multiple domains, positive FrBI symptoms (e.g., disinhibition symptoms) were related to declines in visuospatial function and verbal memory. Finally, the occurrence of both types of symptoms correlated with multi-domain cognitive decline. Conclusions:FrBI predicted worse clinical outcomes, including reduced cortical thickness and cognitive decline, which are not necessarily specific to frontal dysfunction.

Keywords: Cognitive decline, cortical thickness, frontotemporal dementia, neuropsychiatric symptoms, neuropsychological tests

DOI: 10.3233/JAD-190007

Journal: Journal of Alzheimer's Disease, vol. 69, no. 1, pp. 213-225, 2019