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| |  IADRD: Pilot Study of Thalidomide for Alzheimer’s Disease Fails to Detect Cognitive Benefit but Finds Effect on TNF-alpha By Peggy Peck Special to DG News STOCKHOLM, SWEDEN -- July 26, 2002 -- In a pilot study of thalidomide for treatment of Alzheimer’s disease, an active drug treatment failed to show any significant effect on cognitive ability or non-cognitive behaviors. The results do suggest, however, that thalidomide treatment is associated with a reduction in peripheral levels of tumor necrosis factor alpha (TNF-a). The research was reported here July 21 at the 8th International Conference on Alzheimer’s Disease and Related Disorders (IADRD). William Burke, MD, of the University of Nebraska, Omaha, Nebraska, United States, and colleagues hypothesized that since thalidomide, an N-phthaloyl-glutamic acid imide, with anti-inflammatory properties, has been shown in laboratory experiments to cause selective inhibition of mononuclear phagocyte secreted TNF-a it might prove beneficial for Alzheimer’s disease. Dr. Burke explained that TNF-a has been shown to mediate neuronal injury and affect neurodegeneration, thus down regulation of TNF-a might be neuroprotective. The study enrolled 12 patients with mild to moderate Alzheimer’s disease as defined by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS/ADRDA). Five patients were assigned to thalidomide 100 mg for the entire study period, five patients were assigned to thalidomide 100 mg for three weeks increased to 200 mg for weeks 4-24, and two patients received placebo. The Dementia Rating Scale, ADAS-Cog, Geriatric Depression Scale, Family Burden Scale, Neuropsychiatric Inventory, and determination of TNF-a and soluble CD40 ligand (sCD40L) levels in patient plasma and sera were completed at baseline, six weeks, three months, and six months. Repeated measures analyses of variance (ANOVAs) on each of the clinical measures, regardless of dose level, detected trends on ADAS-Cog scores, F(3,12)=3.28, p=0.06. and NPI total scores, F(3,12)=2.78, p=0.09. However, each of these trends was in the opposite direction expected. Within groups, (placebo, thalidomide 100 mg, thalidomide 200 mg), repeated measures ANOVAs did not detect a treatment effect over time for those subjects who completed the entire 26-week trial. But Dr. Burke noted that downward trends in sCD40L and TNF-a levels were observed in the thalidomide 200 mg group. He said that the sample size may have been too small to draw any definitive conclusions regarding efficacy, but he suggests that a larger study is warranted to study the effect on TNF-a and to definitively assess efficacy.
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