title: Cortical and frontal atrophy are associated with cognitive impairment in age-related confluent white-matter lesion.
abstract: 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.
authors.affiliation: Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, PR China. vctmok@cuhk.edu.hk
authors.forename: Vincent
authors.initials: V
authors.lastname: Mok
authors.forename: Kelvin K
authors.initials: KK
authors.lastname: Wong
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Xiong
authors.forename: Adrian
authors.initials: A
authors.lastname: Wong
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schmidt
authors.forename: Winnie
authors.initials: W
authors.lastname: Chu
authors.forename: Xintao
authors.initials: X
authors.lastname: Hu
authors.forename: Eric Yim Lung
authors.initials: EY
authors.lastname: Leung
authors.forename: Sirong
authors.initials: S
authors.lastname: Chen
authors.forename: Yangkun
authors.initials: Y
authors.lastname: Chen
authors.forename: W K
authors.initials: WK
authors.lastname: Tang
authors.forename: Xiangyan
authors.initials: X
authors.lastname: Chen
authors.forename: Chi Lai
authors.initials: CL
authors.lastname: Ho
authors.forename: Ka Sing
authors.initials: KS
authors.lastname: Wong
authors.forename: Stephen T C
authors.initials: ST
authors.lastname: Wong
mesh_terms: D000368:Aged; D000375:Aging / Q000473:pathology* / Q000523:psychology*; D001284:Atrophy; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology*; D003072:Cognition Disorders / Q000473:pathology* / Q000523:psychology*; D004311:Double-Blind Method; D056344:Executive Function / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000473:pathology*; D006710:Homocysteine / Q000037:antagonists & inhibitors; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D012044:Regression Analysis; D020521:Stroke / Q000517:prevention & control
chemical_list: D006710:Homocysteine