Cortical and frontal atrophy are associated with cognitive impairment in age-related confluent white-matter lesion.
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.
Mok
Vincent
V
Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, PR China. vctmok@cuhk.edu.hk
Wong
Kelvin K
KK
Xiong
Yunyun
Y
Wong
Adrian
A
Schmidt
Reinhold
R
Chu
Winnie
W
Hu
Xintao
X
Leung
Eric Yim Lung
EY
Chen
Sirong
S
Chen
Yangkun
Y
Tang
W K
WK
Chen
Xiangyan
X
Ho
Chi Lai
CL
Wong
Ka Sing
KS
Wong
Stephen T C
ST
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
D006710:Homocysteine