A Nomogram for Predicting Amyloid PET Positivity in Amnestic Mild Cognitive Impairment

Article type: Research Article

Authors: Kim, Si Eun^{a; c} | Woo, Sookyoung^b | Kim, Seon Woo^b | Chin, Juhee^a | Kim, Hee Jin^a | Lee, Byung In^c | Park, Jinse^c | Park, Kyung Won^d | Kang, Do-Young^e | Noh, Young^f | Ye, Byoung Seok^g | Yoo, Han Soo^g | Lee, Jin San^h | Kim, Yeshin^{a; i} | Kim, Seung Joo^a | Cho, Soo Hyun^a | Na, Duk L.^a | Lockhart, Samuel N.^j | Jang, Hyemin^a | Seo, Sang Won^{a; *}

Affiliations: [a] Department of Neurology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea | [b] Statistics and Data Center, Samsung Medical Center, Seoul, Korea | [c] Department of Neurology, Inje University College of Medicine, Haeundae Paik Hospital, Busan, Korea | [d] Department of Neurology, Dong-A University College of Medicine, Dong-A University Medical Center, Busan, Korea | [e] Department of Nuclear Medicine, Dong-A University College of Medicine, Dong-A University Medical Center, Busan, Korea | [f] Department of Neurology, Gachon University Gil Medical Center, Incheon, Korea | [g] Department of Neurology, Yonsei University School of Medicine, Severance hospital, Seoul, Korea | [h] Department of Neurology, Kyung Hee University Hospital, Seoul, Korea | [i] Department of Neurology, Kangwon National University College of Medicine, Chuncheon-si, Gangwon-do, Korea | [j] Department of Internal Medicine, Division of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA

Correspondence: [*] Correspondence to: Sang Won Seo, MD, PhD, Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Kangnam-ku, Seoul 06351, Korea. Tel.: +82 2 3410 1233; Fax: +82 2 3410 0052; E-mail: [email protected].

Abstract: Background:Most clinical trials focus on amyloid-β positive (Aβ+) amnestic mild cognitive impairment (aMCI), but screening failures are high because only a half of patients with aMCI are positive on Aβ PET. Therefore, it becomes necessary for clinicians to predict which patients will have Aβ biomarker. Objective:We aimed to compare clinical factors, neuropsychological (NP) profiles, and apolipoprotein E (APOE) genotype between Aβ+ aMCI and Aβ–aMCI and to develop a clinically useful prediction model of Aβ positivity on PET (PET-Aβ+) in aMCI using a nomogram. Methods:We recruited 523 aMCI patients who underwent Aβ PET imaging in a nation-wide multicenter cohort. The results of NP measures were divided into following subgroups: 1) Stage (Early and Late-stage), 2) Modality (Visual, Verbal, and Both), 3) Recognition failure, and 4) Multiplicity (Single and Multiple). A nomogram for PET-Aβ+ in aMCI patients was constructed using a logistic regression model. Results:PET-Aβ+ had significant associations with NP profiles for several items, including high Clinical Dementia Rating Scale Sum of Boxes score (OR 1.47, p = 0.013) and impaired memory modality (impaired both visual and verbal memories compared with visual only, OR 3.25, p = 0.001). Also, presence of APOE ɛ4 (OR 4.14, p < 0.001) was associated with PET-Aβ+. These predictors were applied to develop the nomogram, which showed good prediction performance (C-statistics = 0.79). Its prediction performances were 0.77/0.74 in internal/external validation. Conclusions:The nomogram consisting of NP profiles, especially memory domain, and APOE ɛ4 genotype may provide a useful predictive model of PET-Aβ+ in patients with aMCI.

Keywords: Amnestic mild cognitive impairment, amyloid PET positivity, neuropsychological tests, nomogram, prediction

DOI: 10.3233/JAD-180048

Journal: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 681-691, 2018