Week 7: Statin Studies

May 01, 2020

Welcome back, everyone! It’s been quite a productive week for me as I took a closer look at the use of statins in preventing the aggregation of Aß. At the very end of my last post, I included a chart that included previous studies from 2000 to 2017 that looked at the use of statins on reducing cognitive impairments in both humans and animals. This week, I thought it might be helpful to take a closer look at a few of them and then ultimately connect my findings back to my research question.

  1. Geifman et al. 2017 – This study does not just look at a broad population of AD patients. Instead, it analyzes the effectiveness of statins on subgroups of the AD population. ApoE, a regulator of lipid metabolism, is key to this study.                                                                                                              An average of 58-67% people participating in clinical trials for AD are APoE4 positive, which is associated with higher cholesterol levels. It is believed that APoE4 increases the amount of Aß produced. When analyzing continual use of statins on 1,393 subjects, it was found that the ADAS-cog scores were significantly higher for those who were treated with statins. Atorvastatin was the most effective as subjects who used it received a mean score of 23.5 ± 9.6 SD compared to 4.9 ± 9.4 SD for nonusers. Furthermore, in groups that were homozygous for APoE4, there showed far less cognitive impairment in a 10-year period.
  2. Zissimopoulos et al. 2017 – This study specifically looked at whether the effectiveness of statins on reducing cognitive impairment differed based on race, age, and sex. The study found that the incidence of AD among nonusers was 1.99%, whereas higher levels of statins meant subjects were 10% less likely to develop AD. It was also found that the effectiveness of statins varied across race and sex. Hispanic men, white women, and white men all showed the greatest reduction in the risk of AD. More specifically, different statins were effective for different populations. Simvastatin was most effective for men and women of all races. Atorvastatin was associated with the greatest reduced AD risk among white women, Hispanic women, and Hispanic men. Pravastatin and rosuvastatin were only associated with reduced risk for AD in white women.

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After looking at these two studies I decided to look further into exactly what statins were shown to be effective. Geifman had shown that simvastatin, the most commonly used statin, was not as effective as other types. Meanwhile, Zissimopolous had made the complete opposite conclusion. However, what I gathered is that statins likely reduced the risk of dementia and AD but was by no means preventative.

The hypothesis, and the ultimate importance of all of this to my research question, is the following: A high-cholesterol diet or elevated cholesterol levels are risk factors for AD. Hypercholesterolemia can cause the degradation of APP, resulting in ß-amyloid deposits and neuronal failure, resulting in AD. Statins could help limit the emergence of AD by decreasing the formation of toxic ß-amyloid. Statins have proved especially effective for those at risk for high cholesterol by possessing the APoE4 allele.

With just 1 more week before I begin working on my final presentation, I think it is important to look at everything I have studied from the beginning of this Senior Project until now and tie up any loose ends. I look forward to the next week!

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