Neuroprotective role of statins in treating Alzheimer's disease: a comparative study of biomedical and clinical trials
Shastri, Darshan N.
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Alzheimer’s disease is a neurodegenerative disorder that occurs most commonly in the elderly. The formation of amyloid plaques and neurofibrillary tangles affects the brain tissue, causing mental deficits ranging in severity from memory loss to incontinence and feeding problems. Currently, the only approved treatments are designed to treat the symptoms of the disease, rather than prevention or slowing the progression. Yet, over the course of the last few decades, researchers have sought new ways of treating the condition. One such drug with promising effects is the cholesterol lowering statin medication. Yet the efficacy shown in the laboratory has not translated to clinical trials to treat AD patients. Therefore, this study analyzed various important biomedical and clinical studies in the literature to elucidate why this disparity exists. On examination of biomedical studies, there was a wide range of support for statins due to its many pleiotropic effects. This drug was shown to be permeable through the blood brain barrier, helping to reverse the damage caused by amyloid plaque formation in brain vessel walls. Other studies showed the link between high cholesterol and AD by analyzing the effects of memory deficits in mice while they attempted various tasks. They used analogs to simulate the disease and found that statins helped delay or reverse some of these changes. On examination of clinical studies, the majority of studies could not find a statistically significant correlation between statin use and neuroprotection against AD. Those that did find a positive correlation needed further study to account for any confounding variables. After examination of these papers it became clear that the disparity between the two realms of study was due to the design of the experiments themselves. The biomedical studies focused on various effects of statins rather than on how the mechanisms of action directly affected AD progression. As of yet not all of the pleiotropic effects have been examined and definitely not within the context of how they effect and complement one another. Thus clinical trials trying to integrate this information have been very discouraging and the designs of these studies, both prospective trials and epidemiological studies further complicate the answers sought. They all varied in the age groups they examined, how early treatment was initiated, which statin was used, and how other confounding variables (such as sociodemographics and smoking) were accounted for. After analyzing the literature, it is in our opinion that statins play a protective role if initiated much earlier than the first clinical signs. However the only way to know how it biochemically may help AD patients is through further study. So, it is our recommendation for more in depth study on the pleiotropic effects of statins on AD, before further clinical intervention occurs.
Thesis (M.A.)--Boston University