Medial Temporal Atrophy in Amyloid-Negative Amnestic Type Dementia Is Associated with High Cerebral White Matter Hyperintensity

Article type: Research Article

Authors: Wong, Benjamin Yi Xin^a | Yong, Ting Ting^a | Lim, Levinia^a | Tan, Jayne Yi^a | Ng, Adeline Su Lyn^a | Ting, Simon Kang Seng^a | Hameed, Shahul^a | Ng, Kok Pin^a | Zhou, Juan Helen^b | Kandiah, Nagaendran^{a; c; *}

Affiliations: [a] Department of Neurology, National Neuroscience Institute, Singapore, Singapore | [b] Center for Cognitive Neuroscience, Neuroscience and Behavioral Disorders Program, Duke-NUS Medical School, Singapore, Singapore | [c] Duke-NUS Medical School, Singapore, Singapore

Correspondence: [*] Correspondence to: A/Prof Nagaendran Kandiah, Level 3, Clinical Staff Office, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433. Tel.: +65 6357 7171; Fax: +65 6357 7137; E-mail: nagaendran.kandiah@singhealth.com.sg.

Abstract: Background:Non-amyloid mechanisms behind neurodegeneration and cognition impairment are unclear. Cerebrovascular disease (CVD) may play an important role in suspected non-Alzheimer’s pathophysiology (SNAP), especially in Asia. Objective:To examine the association between CVD and medial temporal lobe atrophy (MTA) in amyloid-β negative patients with mild amnestic type dementia. Methods:Thirty-six mild dementia patients with complete neuropsychological, cerebrospinal fluid (CSF) biomarker, and neuroimaging information were included. Only patients with clinically significant MTA were recruited. Patients were categorized based on their CSF Aβ levels. Neuroimaging and neuropsychological variables were analyzed. Results:Despite comparable MTA between Aβ positive and negative patients, Aβ-negative patients had significantly greater white matter hyperintensities (WMH; Total Fazekas Rating) than their Aβ-positive counterparts (6.42 versus 4.19, p = 0.03). A larger proportion of Aβ-negative patients also had severe and confluent WMH. Regression analyses controlling for baseline characteristics yielded consistent results. Conclusion:Our findings demonstrate that MTA is associated with greater CVD burden among Aβ-negative patients with amnestic type dementia. CVD may be an important mechanism behind hippocampal atrophy. This has implications on clinical management strategies, where measures to reduce CVD may slow neurodegeneration and disease progression.

Keywords: Cerebrovascular disease, medial temporal lobe, neurodegeneration, suspected non-Alzheimer’s pathophysiology, white matter hyperintensity, young onset dementia.

DOI: 10.3233/JAD-181261

Journal: Journal of Alzheimer's Disease, vol. 70, no. 1, pp. 99-106, 2019