From lost hope emerges a new perspective. After more than a century of research into Alzheimer’s disease we have reached a research cul-de-sac. By eradicating the plaques and tangles from the brain, a series of studies reported that the disease worsened 1,2. What this tells us is that the disease is more complex then just a build up of mis-folded proteins.
In panic, the National Institute on Aging, coopting the Alzheimer’s Association, published new guidelines for Alzheimer’s disease in 2011.3 These guidelines effectively transformed a clinical disease--a disease defined by its behavioral manifestations—into a pre-clinical disease. What this means is that now Alzheimer’s disease exists before there are any clinical manifestations. This seems counterintuitive given the studies showing that drugs that cleared the plaques and tangles—the only pre-clinical indicators--did not cure Alzheimer’s disease and in fact made it worse. But the increasing power of the pharmacological industry in establishing the research agenda seems limitless. Now pharmaceutical companies can experiment with patients before they even start showing symptoms of the disease. In effect, curing a disease before the clinical disease emerges. But so far, they have had little success.
Since the early 1990 pharmaceutical companies have been attempting to halt early onset dementia among an unfortunate community in Medellin, Colombia. Discovered by Francisco Lopera in 1984, this heritable variant of Alzheimer's disease share a common ancestor—a 16th-century Spanish colonist who to this day has infected 5,000 patients in 25 families. 4 The reason why this approach—trying to find a biological cause of the disease--has been so resilient despite mounting evidence contradicting this approach, is that there has not been a competing theory to challenge it. Until now.
A crescendo of mounting criticism has established that Alzheimer’s disease is more complex than a cascade of misfolded proteins. That even though people might have the plaques and tangles, some do not express the disease, while some who express Alzheimer’s disease have been shown to have no significant plaques and tangles. In addition, with older adults, multiple studies have shown that the correlation between plaques and tangles and Alzheimer’s disease declines with age. One way to explain these anomalies is to broaden the study of Alzheimer’s disease. One such approach is to see it as a public health disease. 5
A public health perspective argues that there are multiple traumas to the brain. Some of these can be a virus or bacteria, while some are physical (like a concussion). We are seeing more and more how physical trauma causes dementia among NFL football players. But sometimes this trauma is managed and contained. A good example of this process is looking at stroke victims where we see more than 30 percent improving. In such cases, the penumbra—the protective cells that surround the initial trauma—is contained and the death of cells remains localized. Two factors promote this healthy brain. One is blood supply—Perfusion, while the other is growing your brain--Plasticity.
Perfusion allows for the brain to receive adequate nutrients and energy to heal itself. Having a healthy brain improves the chances that a trauma is contained. Plasticity on the other hand ensures that there is enough flexibility in the brain that if the brain needs to contain an area that other parts can take over that lost function. Without these two factors the penumbra will continue to grow and affect larger areas of the brain—and such damage will go beyond plaques and tangles. This broader public health interpretation of Alzheimer’s disease assimilates both the traditional Amyloid Cascade hypothesis and explains the increasing number of studies showing how external factor influence the incidence of Alzheimer’s disease.
The beauty of this public health approach is that we do not have to wait another hundred years before we realize that we are in a research cul-de-sac. We can start implementing programs that reduce and lower the exposure to traumas. Reduction of concussions (in sport, military, recreational activities) should be made a priority. Programs that educate on the effects of smoking and heavy drinking on the brain need to be promoted, as well as programs that address environmental toxicity both in the air and in our water. For perfusion, city walkability programs, and social engagement programs all promote walking, swimming, light exercise, gardening among other activities. While improving plasticity involves social activities, dancing, music and other cognitive exercises.
Pharmaceutical influence can determine federal research policy, but with knowledge, individuals can protect themselves and their family from exposure to this deadly disease that we still do not fully understand.
A version of this article can be found in:
A complete story of this blog can be found in my recently published book:
References.
1. Gilman S., Koller M., Black R.S., Jenkins L., Griffith S.G., Fox N.C, et al. (2005). Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology, 64:1553–62.
2. Boche D., Donald J., Love S., Harris S., Neal J.W., Holmes C., et al. (2010). Reduction of aggregated tau in neuronal processes but not in the cell bodies after Abeta42 immunisation in Alzheimer’s disease. Acta Neuropathol, 120: 13–20.
3. Jack C.R., Albert M.S., Knopman D.S., McKhann G.M. Sperling R.A., Carrillo M.C., ... & Phelps C. H. (2011). Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia, 7(3):257-262.
4. Lopera F., Ardilla A., MartÃnez A., Madrigal L., Arango-Viana J.C., Lemere C.A., ... & Kosik K.S. (1997). Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation. Jama, 277(10): 793-799.
5. Garrett MD & Valle R (2015) A New Public Health Paradigm for Alzheimer’s Disease Research. SOJ Neurol 2(1), 1-9. Page 2 of 9
© USA Copyrighted 2016 Mario D. Garrett
No comments:
Post a Comment