Predictors for cognitive decline in patients with confluent white matter hyperintensities Vincent Mok a, *, Yunyun Xiong a , Kelvin K. Wong b , Adrian Wong a , Reinhold Schmidt c , Winnie W. C. Chu d , Xintao Hu b , Eric Yim Lung Leung e , Sirong Chen e , Yangkun Chen f , Wai Kwong Tang f , Xiangyan Chen a , Chi Lai Ho e , Ka Sing Wong a , Stephen T. C. Wong b a Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, People’s Republic of China b Bioinformatics and Imaging Programmatic Cores, The Methodist Hospital ResearchInstitute, Weill Cornell Medical College, Houston, TX, USA c Department of Neurology, Medical University Graz, Austria d Department of Radiology and Organ Imaging, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, People’s Republic of China e Department of Nuclear Medicine, Hong Kong Sanatorium and Hospital, Hong Kong Special Administrative Region, People’s Republic of China f Department of Psychiatry, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, People’s Republic of China Abstract Background: Although patients harboring confluent white matter hyperintensities (WMH) are at high risk of cognitive decline, this risk varies among individuals. We investigated the predictors for cognitive decline in stroke patients with confluent WMH. Methods: We followed up 100 stroke patients with confluent WMH who were participants of the VITAmins TO Prevent Stroke study for 2 years. We investigated the association between clinical features, apolipoprotein E status, imaging measures (infarcts, microbleeds, volumes of WMH, cortical gray matter [cGM], lateral ventricles, and hippo- campi), and B vitamins with changes in cognitive measures (clinical dementia rating scale, Mini- Mental State Examination, Mattis dementia rating scale—initiation/perseveration subscale). We performed Pittsburgh compound B imaging among dementia converters. Results: Multivariate regression analysis showed that increase in clinical dementia rating scale grade was associated with cGM atrophy, absence of hyperlipidemia, and lower diastolic blood pressure at baseline. cGM atrophy and absence of hyperlipidemia were also associated with deterioration in Mini-Mental State Examination and Mattis dementia rating scale—initiation/perseveration subscale scores. Pittsburgh compound B retention typical of Alzheimer’s disease was found only in 10% of dementia converters. Incident stroke and B vitamins were not associated with cognitive decline. Conclusions: Among stroke patients with confluent WMH, cGM atrophy and absence of hyperlip- idemia are important predictors for cognitive decline. Significant cognitive decline can occur in the absence of incident stroke or Alzheimer’s pathology. Ó 2012 The Alzheimer’s Association. All rights reserved. Keywords: White matter hyperintensities; Cognitive decline; Stroke; Alzheimer’s disease; PiB 1. Introduction Age-related white matter hyperintensities (WMH) are considered a manifestation of cerebral small-vessel disease (SVD). Severity of WMH may vary from small punctate to more diffuse confluent lesions. In stroke patients, prevalence of confluent WMH varies from 9% to 30% [1,2]. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) magnetic resonance imaging (MRI) substudy showed that dementia-free stroke subjects harboring conflu- ent WMH at baseline have eight times higher risk for signif- icant cognitive decline relative to those without WMH over 4 The authors have no conflicts of interest to report. *Corresponding author. Tel.: 852-2632 3131; Fax: 852-2649 3761. E-mail address: vctmok@cuhk.edu.hk 1552-5260/$ - see front matter Ó 2012 The Alzheimer’s Association. All rights reserved. doi:10.1016/j.jalz.2011.10.004 Alzheimer’s & Dementia 8 (2012) S96–S103