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Abstract
Objectives: Assuming the involvement of homocysteine in a generalized small-vessel disease, we investigated the association of homocysteine levels with progression of white matter lesions, lacunar infarcts, and kidney disease.
Methods: Within the SMART-MR (Second Manifestations of ARTerial disease–Magnetic Resonance) Study, a prospective cohort study on brain aging in patients with symptomatic atherosclerotic disease, 663 patients (aged 57 ± 9 years) had vascular screening and 1.5-tesla MRI at baseline and after a mean follow-up of 3.9 years. Multiple regression analysis was used to estimate the longitudinal association between total homocysteine level, defined as a continuous variable and as hyperhomocysteinemia (the highest quintile of homocysteine), and progression of white matter lesion volume, lacunar infarcts, and estimated glomerular filtration rate.
Results: After adjusting for age, sex, follow-up time, and vascular risk factors, hyperhomocysteinemia was significantly associated with increased risk of white matter lesion progression (odds ratio 2.4, 95% confidence interval [CI] 1.5–4.1) and lower estimated glomerular filtration rate at follow-up (B = −3.4 mL/min, 95% CI −5.9 to −0.9) and borderline significantly associated with new lacunar infarcts (odds ratio 1.8, 95% CI 0.9–3.4).
Conclusions: Our findings implicate a role for homocysteine in the development of a generalized small-vessel disease in which both brain and kidney are affected.
GLOSSARY
- AAA=
- abdominal aortic aneurysm;
- CI=
- confidence interval;
- CSVD=
- cerebral small-vessel disease;
- eGFR=
- estimated glomerular filtration rate;
- FLAIR=
- fluid-attenuated inversion recovery;
- IMT=
- intima-media thickness;
- OR=
- odds ratio;
- SMART-MR=
- Second Manifestations of ARTerial disease–Magnetic Resonance;
- TE=
- echo time;
- tHcy=
- total homocysteine;
- TR=
- repetition time;
- WML=
- white matter lesion
Footnotes
SMART Study Group coinvestigators are listed on the Neurology® Web site at www.neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at www.neurology.org
- Received June 19, 2013.
- Accepted in final form November 25, 2013.
- © 2014 American Academy of Neurology
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