Homocysteine and the brain in midadult life: evidence for an increased risk of leukoaraiosis in men.
BACKGROUND
High serum homocysteine (HCY) levels have been associated with thromboembolic cerebrovascular disease, but their relationship to microvascular disease is uncertain. Homocysteine also has a direct neurotoxic effect and has been linked to brain atrophy and an increased risk of Alzheimer disease.


OBJECTIVE
To examine the relationship of HCY levels to brain and cognitive measures in a healthy community sample.


METHODS
Cross-sectional study.


METHODS
Individuals residing in Canberra and Queanbeyan, Australia, who were participating in the longitudinal PATH Through Life Project.


METHODS
Individuals aged 60 to 64 years selected randomly from the community, 196 men and 189 women.


METHODS
Regression coefficients with HCY level as the putative determinant and various magnetic resonance imaging measures (brain atrophy index, ventricle-brain ratios, volume of periventricular and deep white matter hyperintensities) and cognitive measures (information processing speed, verbal memory, fine motor speed) as dependent measures.


RESULTS
Homocysteine levels did not have a significant relationship with brain atrophy index or ventricle-brain ratios. High HCY levels were related to increased deep white matter hyperintensities but not periventricular white matter hyperintensities, after correcting for levels of folate, vitamin B(12), creatinine, and thyrotropin; hypertension; smoking; and diabetes, the relationship being significant only in men. Homocysteine levels were related to impairment in verbal memory and fine motor speed but not after the previously mentioned correction.


CONCLUSIONS
Total HCY level is independently related to leukoaraiosis in middle-aged men, and this may be functionally relevant in the form of mild cognitive impairment. The remediation of hyperhomocysteinemia should begin early in life if its deleterious effects on the brain are to be prevented.
Sachdev
Perminder
P
School of Psychiatry, University of New South Wales, Sydney, Australia. p.sachdev@unsw.edu.au
Parslow
Ruth
R
Salonikas
Chris
C
Lux
Ora
O
Wen
Wei
W
Kumar
Rajeev
R
Naidoo
Daya
D
Christensen
Helen
H
Jorm
Anthony
A
D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology* / Q000502:physiology; D001927:Brain Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D003071:Cognition / Q000502:physiology*; D003430:Cross-Sectional Studies; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011859:Radiography; D012044:Regression Analysis; D012737:Sex Factors
D006710:Homocysteine