Associations between white matter lesions, cerebrovascular risk factors, and low CSF Abeta42.
OBJECTIVE
To analyze a putative relationship between white matter lesions (WMLs), risk factors for WMLs, and Alzheimer disease (AD) as measured with the surrogate marker CSF Abeta42.


METHODS
The authors analyzed effects of acquired risk factors for cerebrovascular disease and WMLs on AD as measured with an intermediate marker, CSF Abeta42. A total of 127 consecutive patients with subjective memory impairment (mean age 66 years; 57 women) investigated at a university-based memory clinic had brain MRI scans. WMLs were rated on a 12-point scale with a semiquantitative procedure. They used path analysis with established and possible risk factors for WMLs and for reduced CSF Abeta42 (age, hypertension, hyperhomocysteinemia, hypercholesterolemia, APOE-epsilon4) as variables.


RESULTS
The WML score was 1.5 points higher (p < 0.05) in hypertensive than in nonhypertensive patients and 1.9 points higher (p < 0.05) in patients with hyperhomocysteinemia than in those with normal homocysteine levels. Hypercholesterolemia increased the probability of low CSF Abeta42 levels by 0.2 (p < 0.05). For each point increase in WML score, the probability of low CSF Abeta42 levels increased by 0.03 (p < 0.05). APOE-epsilon4 was associated with reduced CSF Abeta42 (p < 0.01).


CONCLUSIONS
Both hypercholesterolemia and white matter lesions may contribute to low CSF Abeta42 by independent mechanisms.
Stenset
V
V
Department of Neurology, Akershus University Hospital, Sykehusveien 27, NO-1478 Lørenskog, Norway. vidar.stenset@medisin.uio.no
Johnsen
L
L
Kocot
D
D
Negaard
A
A
Skinningsrud
A
A
Gulbrandsen
P
P
Wallin
A
A
Fladby
T
T
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000150:complications / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001921:Brain / Q000473:pathology*; D001930:Brain Injuries / Q000134:cerebrospinal fluid*; D002561:Cerebrovascular Disorders / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008569:Memory Disorders / Q000134:cerebrospinal fluid / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D008954:Models, Biological; D012307:Risk Factors; D012720:Severity of Illness Index
D016229:Amyloid beta-Peptides