Amyloid Positive Hydrocephalus: A Hydrocephalic Variant of Alzheimer’s Disease?

Article type: Research Article

Authors: Jang, Hyemin^{a; d; e} | Park, Yu-hyun^{a; e} | Choe, Young Sim^{a; e} | Kang, Sung Hoon^{f; a; d; e} | Kang, Eun-Sook^b | Lee, Seunghoon^c | Seo, Sang Won^{a; d; e; h; i} | Kim, Hee Jin^{a; d; e} | Na, Duk L.^{a; d; e; g; i; *}

Affiliations: [a] Department of Neurology, Sungkyunkwan University School of Medicine, Seoul, Korea | [b] Laboratory Medicine and Genetics, Sungkyunkwan University School of Medicine, Seoul, Korea | [c] Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea | [d] Neuroscience Center, Samsung Medical Center, Seoul, Korea | [e] Samsung Alzheimer Research Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea | [f] Department of Neurology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea | [g] Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, South Korea | [h] Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, Korea | [i] Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea

Correspondence: [*] Correspondence to: Duk L. Na, MD, PhD, Department of Neurology, Sungkyunkwan University School of Medicine, Samsung Medical Center, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea. Tel.: +82 2 3410 6147; Fax: +82 2 3410 0052; E-mail: [email protected].

Abstract: Background:Alzheimer’s disease (AD) and normal pressure hydrocephalus (NPH) commonly coexist. Objective:We aimed to characterize an overlapping syndrome of AD and NPH that presents with gait disturbance, ventriculomegaly on magnetic resonance imaging, and significant amyloid deposition on positron emission tomography (PET). Methods:Of 114 patients who underwent cerebrospinal fluid (CSF) drainage for a possible diagnosis of NPH between 2015 and 2020 in Samsung Medical Center, we identified 24 patients (21.1%) with the NPH patients with amyloid deposition on PET, which we referred to as hydrocephalic AD in this study. We compared their clinical and imaging findings with those of 123 typical AD without hydrocephalic signs/symptoms. We also investigated the frequency and potential predictors of the tap test response in hydrocephalic AD. Results:Evans’ index was 0.36±0.03, and a disproportionately enlarged subarachnoid space was present in 54.2% of the hydrocephalic AD patients. The mean age (75.2±7.3 years) and the APOE4 frequency (68.2%) did not differ from those of AD controls. However, the hydrocephalic AD patients showed better memory and language performance, and a thinner cingulate cortex. About 42% of the hydrocephalic AD patients responded to the tap test, of whom seven underwent shunt surgery. Cognition did not improve, whereas gait improved after shunt surgery in all. Conclusion:Hydrocephalic AD has different neuropsychological and imaging characteristics from typical AD. Future studies are warranted to further investigate the effect of CSF removal on their clinical course and to elucidate the pathophysiological interaction between amyloid and NPH.

Keywords: Alzheimer’s disease, cerebrospinal fluid, hydrocephalus, MRI, PET

DOI: 10.3233/JAD-215110

Journal: Journal of Alzheimer's Disease, vol. 85, no. 4, pp. 1467-1479, 2022