Metformin in Amnestic Mild Cognitive Impairment: Results of a Pilot Randomized Placebo Controlled Clinical Trial.

Diabetes and hyperinsulinemia may be risk factors for Alzheimer's disease (AD). We conducted a pilot study of metformin, a medication efficacious in treating and preventing diabetes while reducing hyperinsulinemia, among persons with amnestic mild cognitive impairment (aMCI) with the goal of collecting preliminary data on feasibility, safety, and efficacy. Participants were 80 men and women aged 55 to 90 years with aMCI, overweight or obese, without treated diabetes. We randomized participants to metformin 1000 mg twice a day or matching placebo for 12 months. The co-primary clinical outcomes were changes from baseline to 12 months in total recall of the Selective Reminding Test (SRT) and the score of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). The secondary outcome was change in relative glucose uptake in the posterior cingulate-precuneus in brain fluorodeoxyglucose positron emission tomography. Change in plasma Aß42 was an exploratory outcome. The mean age of participants was 65 years. Fifty percent of participants were women. The only baseline variable that was different between the arms was the ADAS-Cog. Metformin could not be tolerated by 7.5% of participants; 15% tolerated 500 mg/day, 35% tolerated 1000 mg/day, 32.5% tolerated 1500 mg/day, and only 10% tolerated the maximum dose. There were no serious adverse events related to metformin. The 7.5% of persons who did not tolerate metformin reported gastrointestinal symptoms. After adjusting for baseline ADAS-cog, changes in total recall of the SRT favored the metformin group (9.7±8.5 versus 5.3±8.5; p = 0.02). Differences for other outcomes were not significant. A larger trial seems warranted to evaluate the efficacy and cognitive safety of metformin in prodromal AD.

A stroke preparedness RCT in a multi-ethnic cohort: design and methods.

BACKGROUND: Tissue plasminogen activator (tPA), the only approved treatment for acute ischemic stroke (IS), is significantly underutilized likely due to poor lay information about stroke as an emergency. In order to improve outcomes in acute IS, it is critical to raise awareness and recognition of stroke symptoms particularly among minority populations. This manuscript describes the application of a stroke preparedness behavioral intervention and includes baseline information in a multi-ethnic population of stroke and transient ischemic attack (TIA) survivors. METHODS: In the Stroke Warning Information and Faster Treatment Study (SWIFT), we prospectively identified, and randomized IS and TIA patients to determine efficacy of a culturally tailored interactive stroke preparedness strategy. Data collected at baseline included acute stroke parameters, stroke knowledge, severity, social resources and vascular risk assessment. RESULTS: Of the 736 enrolled to date, 76% were IS and 24% TIA events. The cohort was 51% female: 45% Hispanic, 26% White and 25% Black. Over 75% reported hypertension, 36% diabetes, and 16% cardiac disease. Mean time from onset to emergency department (ED) arrival was 46h (median 13h) differing significantly between Whites (mean 52h, median 11h) and Blacks (mean 52h, median 17h) versus Hispanics (mean 39h, median 11h). Knowledge that a stroke occurs in the brain differed significantly by between Whites (85%), Blacks (64%), Hispanics (66%, p<0.000). CONCLUSIONS: Disparities remain in both action and knowledge surrounding acute stroke. Use of written information has not proven an effective means of changing health behaviors. We propose an interactive culturally tailored intervention to address behavioral change in acute stroke.