Regional White Matter Hyperintensity Influences Grey Matter Atrophy in Mild Cognitive Impairment

Article type: Research Article

Authors: Vipin, Ashwati^{a; 1} | Foo, Heidi Jing Ling^{b; 1} | Lim, Joseph Kai Wei^a | Chander, Russell Jude^b | Yong, Ting Ting^b | Ng, Adeline Su Lyn^b | Hameed, Shahul^c | Ting, Simon Kang Seng^c | Zhou, Juan^{a; d; 2; *} | Kandiah, Nagaendran^{b; 2; *}

Affiliations: [a] Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Programme, Duke-NUS Medical School, Singapore | [b] Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore | [c] Department of Neurology, Singapore General Hospital, Singapore | [d] Clinical Imaging Research Centre, The Agency for Science, Technology and Research and National University of Singapore, Singapore

Correspondence: [*] Correspondence to: Associate Professor Nagaendran Kandiah, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore. Tel.: +65 63577171; Nagaendran_Kandiah@nni.com.sg and Assistant Professor Juan Zhou, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore. Tel.: +65 66012392; E-mail: helen.zhou@duke-nus.edu.sg.

Note: [1] These authors contributed equally to this work.

Note: [2] Joint senior authors.

Abstract: The association between cerebrovascular disease pathology (measured by white matter hyperintensities, WMH) and brain atrophy in early Alzheimer’s disease (AD) remain to be elucidated. Thus, we investigated how WMH influence neurodegeneration and cognition in prodromal and clinical AD. We examined 51 healthy controls, 35 subjects with mild cognitive impairment (MCI), and 30 AD patients. We tested how total and regional WMH is related to specific grey matter volume (GMV) reductions in MCI and AD compared to controls. Stepwise regression analysis was further performed to investigate the association of GMV and regional WMH volume with global cognition. We found that total WMH volume was highest in AD but showed the strongest association with lower GMV in MCI. Frontal and parietal WMH had the most extensive influence on GMV loss in MCI. Additionally, parietal lobe WMH volume (but not hippocampal atrophy) was significantly associated with global cognition in MCI while smaller hippocampal volume (but not WMH volume) was associated with lower global cognition in AD. Thus, although WMH volume was highest in AD subjects, it had a more pervasive influence on brain structure and cognitive impairment in MCI. Our study thus highlights the importance of early detection of cerebrovascular disease, as its intervention at the MCI stage might potentially slow down neurodegeneration.

Keywords: Alzheimer’s disease, cognition, grey matter, white matter hyperintensity

DOI: 10.3233/JAD-180280

Journal: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 533-549, 2018