White Matter Lesions May Aid in Differentiating Idiopathic Normal Pressure Hydrocephalus and Alzheimer’s Disease

Article type: Research Article

Authors: Kuroda, Takeshi^a | Honma, Motoyasu^b | Mori, Yukiko^a | Futamura, Akinori^a | Sugimoto, Azusa^a | Kasai, Hideyo^a | Yano, Satoshi^a | Hieda, Sotaro^a | Kasuga, Kensaku^c | Ikeuchi, Takeshi^c | Ono, Kenjiro^{a; d; *}

Affiliations: [a] Division of Neurology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan | [b] Department of Physiology, Showa University School of Medicine, Tokyo, Japan | [c] Department of Molecular Genetics, Brain Research Institute, Niigata University, Chuo-ku, Niigata, Japan | [d] Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan

Correspondence: [*] Correspondence to: Kenjiro Ono, 1-5-8 Hatanodai, Shina-gawa-ku, Tokyo 142-8666, Japan. Tel.: +81 3 3784 8710; Fax: +81 3784 8710; E-mail: onoken@med.showa-u.ac.jp.

Abstract: Background:Idiopathic normal pressure hydrocephalus (iNPH) is often misdiagnosed as Alzheimer’s disease (AD) due to overlapping pathophysiology and similar imaging characteristics, including ventricular enlargement and increased white matter lesions (WMLs). Objective:To compare the extent and distribution of WMLs directly between iNPH and AD and examine the association with underlying pathophysiology. Methods:Twelve patients with iNPH (mean age: 78.08 years; 5 females), 20 with AD (mean age: 75.40 years; 13 females), and 10 normal cognition (NC) participants (mean age: 76.60 years; 7 females) were recruited. The extent and distribution of WMLs and the lateral ventricular volume (LV-V) were evaluated on MRI using voxel-based morphometry analysis. Concentrations of cerebrospinal fluid biomarkers, such as amyloid-β protein (Aβ)42, Aβ40, Aβ38, and tau species, were also measured. Risk factors for small vessel disease (SVD) were assessed by blood examination and medical records. Results:The periventricular WML volume (PWML-V) and deep WML volume (DWML-V) were significantly larger in iNPH than in AD and NC. The DWML-V was dominant in iNPH, while the PWML-V was dominant in AD and NC. GM-V was significantly smaller in AD than in iNPH and NC. The LV-V positively correlated with WML-V in all participants. There was a significant negative correlation between LV-V and Aβ38 in iNPH. Furthermore, there was no significant difference in SVD risk factors between the groups. Conclusion:The differences in the extent and distribution of WMLs between iNPH and AD, especially predominance of DWML-V over PWML-V in iNPH, may reflect decreased fluid and Aβ clearance.

Keywords: Alzheimer disease, amyloid, cerebrospinal fluid, glymphatic system, hydrocephalus, white matter

DOI: 10.3233/JAD-215187

Journal: Journal of Alzheimer's Disease, vol. 85, no. 2, pp. 851-862, 2022