Cortical and frontal atrophy are associated with cognitive impairment in age-related confluent white-matter lesion
- Vincent Mok1,
- Kelvin K Wong2,
- Yunyun Xiong1,
- Adrian Wong1,
- Reinhold Schmidt3,
- Winnie Chu4,
- Xintao Hu2,
- Eric Yim Lung Leung5,
- Sirong Chen5,
- Yangkun Chen6,
- W K Tang6,
- Xiangyan Chen1,
- Chi Lai Ho5,
- Ka Sing Wong1,
- Stephen T C Wong2
- 1Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, PR China
- 2Bioinformatics and Imaging Programmatic Cores, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, Texas, USA
- 3Department of Neurology, Medical University Graz, Graz, Austria
- 4Department of Radiology & Organ Imaging, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, PR China
- 5Department of Nuclear Medicine, Hong Kong Sanatorium and Hospital, Hong Kong Special Administrative Region, PR China
- 6Department of Psychiatry, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, PR China
- Correspondence to Dr Vincent C T Mok, Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, PR China;
- Received 27 November 2009
- Revised 8 March 2010
- Accepted 21 March 2010
- Published Online First 8 September 2010
Objective Although age-related confluent white-matter lesion (WML) is an important substrate for cognitive impairment, the mechanisms whereby WML induces cognitive impairment are uncertain. The authors investigated cognitive predictors in patients with confluent WML.
Methods Among 100 patients with ischaemic stroke with confluent WML on MRI, the authors assessed executive function and global cognition by the Mattis Dementia Rating Scale—Initiation/Perseveration Subscale (MDRS I/P) and Mini-Mental State Examination (MMSE), respectively. All volumetric measures were corrected for intracranial volume. The authors investigated the association between basic demography, vascular risk factors, APOE status, WML volume, infarct measures (volume, number, location), microbleed number, atrophy measures (global, central, regional) and cognitive performance. The authors also performed Pittsburgh Compound B (PIB) imaging among seven cognitive impaired patients with stroke.
Results WML was no longer related to cognitive performance after adding atrophy into regression equations. Multivariate regression models showed that cortical grey matter volume independently accounted for performance on both the MDRS I/P (β=0.241, p=0.045) and MMSE (β=0.243, p=0.032). Models examining frontal subregions revealed that volumes of both left (β=0.424, p<0.001) and right (β=0.219, p=0.045) lateral frontal orbital gyri predicted MDRS I/P, whereas education (β=0.385, p<0.001) and left lateral frontal orbital gyrus (β=0.222, p=0.037) predicted MMSE. Volumes of WML and cognitively relevant brain regions were significantly associated. Seven patients with PIB imaging showed no uptake pattern typical of Alzheimer's disease, suggesting a predominantly vascular aetiology for the cognitive impairment and brain changes in these patients.
Conclusions Cognitive impairment in patients with confluent WML is mediated by global and frontal cortical atrophy.
Funding This work was supported by 2005/2006 Earmarked Grant CUHK 4317/04M. The funding support for KW, XH and STCW is from the Bioinformatics and Imaging Programmatic Cores, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, Texas, USA.
Competing interests None.
Ethics approval Ethics approval was provided by the Ethics Committee of the Chinese University of Hong Kong.
Provenance and peer review Not commissioned; externally peer reviewed.