HONOLULU—Why would anyone consider using a cholesterol-lowering agent for multiple sclerosis (MS), acute ischemic stroke, or Alzheimer’s disease–related cognitive decline? Because it just might work, suggest the results of three studies presented at the 55th Annual Meeting of the American Academy of Neurology.

“We had a 43% reduction in the mean number of gadolinium- enhanced [brain] lesions from the pretreatment phase to the posttreatment phase,” said Timothy L. Vollmer, MD, lead investigator of an open-label, single-arm study of simvastatin for MS. The patients with MS in the study also showed a mean decrease in gadolinium-enhanced brain lesion volume of about 40% following simvastatin treatment.

Dr. Vollmer and colleagues did not undertake the study because they thought cholesterol contributes substantially to MS pathogenesis. Rather, animal models have hinted that statins may help to treat MS by reducing the central nervous system inflammation present in the disease, related Dr. Vollmer, a Lecturer in the Department of Neurology at the Yale University School of Medicine in New Haven, Connecticut.

Forty-five patients with relapsing-remitting MS, ages 18 to 55 (average age, 45), were enrolled in the study. The patients had at least one gadolinium-enhanced brain lesion on MRI and had relapsed at least once within two years of study entry. At baseline, they had respective mean scores of 0.133 and 3.0 on the MS Functional Composite and Expanded Disability Status Scale, and average disease duration of five years.

Of this population, 30 patients (mean age, 44) participated in the treatment phase of the study, which consisted of 80 mg of simvastatin daily for six months. Among those who completed the study, the annualized rates of clinically significant MS relapses before and after treatment were 0.43 and 0.32, respectively. The pretreatment and posttreatment means for the number of gadolinium-enhanced brain lesions per patient were 2.35 and 1.31; these lesions averaged about 238 mL in volume before treatment versus 142 mL after. However, simvastatin did not significantly alter the total burden of disease, and a slight decrease in the average brain volume was observed after six months. The study drug produced no serious adverse effects, though.

STATINS FOR ACUTE ISCHEMIC STROKE

Treatment with a statin may also be beneficial in acute ischemic stroke, found Majaz Moonis, MD, and colleagues. “Poststroke statins are associated with a significant amount of improvement in outcome at three months,” related Dr. Moonis, Director of the Stroke Prevention Clinic at the University of Massachusetts Memorial Medical Center in Worcester.

His study focused on three outcomes—stroke patients’ scores on the Modified Rankin Scale (MRS), National Institutes of Health Stroke Scale (NIHSS), and the Barthel Index (BI). MRS and NIHSS scores of 2 or less and a BI of 90 or more three months after an acute ischemic stroke were defined as favorable outcomes. Higher scores were considered unfavorable outcomes.

The investigators assessed the chance of favorable outcomes among the 852 acute ischemic stroke patients in a citicoline database depending on whether these patients were on statins before their stroke, started taking statins within two weeks of their stroke, or did not receive the drugs at all during the three-month study period (the “untreated” group). At baseline, the prestroke statin, poststroke statin, and untreated groups had mean NIHSS scores of 13.1±3.8, 12.9±4.1, and 13.1±3.7, respectively. There was no significant difference in the distribution of citicoline across the three stroke groups.

In a multivariate logistic regression analysis, the poststroke statin group had odds ratios (OR) for favorable outcomes on the MRS, NIHSS, and BI of 1.72, 1.84, and 1.57, respectively; small-vessel stroke was also associated with a substantially greater chance of scoring 2 or less on the MRS (OR, 1.82). Prestroke statin use did not predict outcome.

Older age at stroke onset and diabetes were equal predictors of unfavorable outcomes on the three study measures included, followed by previous stroke or transient ischemic attack. “The results are highly significant and are unlikely to be explained by differences in the baseline NIHSS scores,” emphasized the investigators.

A POSITIVE EFFECT ON COGNITION

Because some research has linked statins to a procognitive effect in the elderly that may be due to protection against Alzheimer’s disease, Charles B. Bernick, MD, and colleagues studied the association in 3,712 elderly adults 65 or older. And they did indeed find a slight reduction in cognitive decline among the statin users.

“The disappearance of this finding when participants with dementia were excluded from [the] analysis suggests that statins may exert their effect by modulating the course of Alzheimer’s disease,” said the investigators. Lead investigator Dr. Bernick is an Associate Professor of Medicine and Chief of the Division of Neurology at the University of Nevada School of Medicine in Las Vegas.

The study participants, part of the Cardiovascular Health Study, a longitudinal investigation of coronary heart disease and stroke in elderly people, were classified as statin users or nonusers. Of the latter group, those who should have been taking statins based on the recommendations of the National Cholesterol Education Program were slightly older, less likely to be on estrogen replacement therapy than the statin users, and had higher serum cholesterol levels.

During the mean follow-up period of seven years, the investigators regularly assessed cognitive function by yearly modified Mini-Mental State Examination (MMSE). Additionally, screening for dementia was carried out on most, but not all, of the cohort. Individuals with incident stroke were excluded from analysis.

Compared with the statin nonusers where lipid-lowering treatment was recommended, the statin users had a 46% lower rate of cognitive decline based on their modified MMSE scores. “This effect remained after controlling for serum cholesterol levels,” Dr. Bernick and colleagues reported. “However, when individuals with dementia—primarily Alzheimer’s disease—were excluded from the analysis, leaving 2,286 participants, there was no decline in modified MMSE scores in any group.”

Notably, MRI scans of 1,640 study subjects four years apart showed no significant difference between statin users and nonusers in measures of white matter grade or atrophy, the researchers added.

NR

—Timothy Begany

Suggested Reading
Crisby M, Carlson LA, Winblad B. Statins in the prevention and treatment of Alzheimer disease. Alzheimer Dis Assoc Disord. 2002;16:131-136.
Lalouschek W, Lang W, Greisenegger S, Mullner M. Determination of lipid profiles and use of statins in patients with ischemic stroke or transient ischemic attack. Stroke. 2003;34:105-110.
Neuhaus O, Strasser-Fuchs S, Fazekas F, et al. Statins as immunomodulators: comparison with interferon-beta 1b in MS. Neurology. 2002;59:990-997.
Petanceska SS, DeRosa S, Olm V, et al. Statin therapy for Alzheimer’s disease: will it work? J Mol Neurosci. 2002; 19:155-161.

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