The brain of a healthy person is constantly changing. Neurons and glial cells constantly die and get replaced with new cells. More than 30,000 proteins constantly misfold and get degraded, they are cleared from the brain. Constant mini injuries to the brain are accommodated without change in capacity. Where memories are constantly re-imaged and prioritized. Where cognitive functions are shifted from one area of the brain to another. All of these events define the daily functioning of our brain. The question that needs to be asked is why does this ongoing maintenance stops or becomes overwhelmed?
The emerging conclusion—that Alzheimer’s disease is a syndrome—derives from a century of anomalies in research. The National Institute on Aging’s and Alzheimer’s Association (NIA/AA) new guidelines, based on the Amyloid Cascade hypothesis (Jack et al, 2011) are incomplete. Emerging evidence is elaborating a more complex process. More than one cause, or type of causes, may result in similar or different outcomes. The initial injury might or might not progress. The neurological disease might or might not affect cognition. The chorus of scientists voicing this approach to Alzheimer’s disease is unremitting. These valid criticisms remain shunned from NIA/AA new research agenda.
So far, after a century of confusion in studying Alzheimer’s disease, it is time to stop repeating the same mistakes in the hope of coming up with new results. We need a new methodology that might provide different results. This new approach comes from Complexity Theory. Complexity Theory is an open theory—many variables, some known others still unknown influence the outcome. The utility of broadening the theory is to allow for a more inclusive approach that allows diverse literature to be included rather than to remain ignored. A simplified view of the brain states that by looking at individual components you can understand the whole machine--as with the Amyloid Cascade hypothesis (Hardy & Higgins, 1992). Such a mechanistic approach—that harks back to the 14th century—is too limited to explain a behavioral disease such as Alzheimer’s disease.
Such models are useful in generating hypotheses but limited in furthering our understanding of how the brain functions. Especially because of non-linear effects, a large change might result in a small effect and a small change a large effect. We cannot predict what the effect will be. In strokes for example—where a blockage in the blood vessels destroys an area/s of the brain—we might find a large stroke resulting in little diminished capacity or a small stroke with debilitating results. We cannot predict the outcome with certainty even if we know the area of the trauma. Each stroke is unique, as is Alzheimer’s disease.
Within this theory, systems or units exist, seemingly independent from each other that nevertheless rely on each other, communicating directly within a hierarchy of networks. We know these networks exist because of the presence of hormones, neurotransmitters and cytokines mediated in the body by hundreds of different types of lipids, phospholipids, amino acids, monoamines, proteins, glycoproteins, or gases (Mohamed et al, 2005; Clarke & Sperandio, 2005). Additionally, the system changes and evolves.
A Complexity Theory would address these variances and how the body maintains these systems in balance—a balance that is unique for each individual. This homoeostasis is based on an internal set of regulators, defined by both past experiences and unique adaptive responses to new stimuli from the environment. The theory would also need to refrain from separating our beliefs, expectations, and behavior from the wider social, political, and cultural systems in which we exist. These units interact within the whole system in (as yet) unknown ways (Doidge, 2015; Merzenich, 2013). In such an open system, both established and new external forces can, and do, impinge on its internal activity. The best example of this is psychosomatic illness where although the disease is caused by the psychology of the person—psychogenic—the physical effects are real (Shorter, 2008).
Because Complexity Theory utilizes input from a variety of disciplines, it is necessarily transdisciplinary (Albrecht et al., 1998). It may help address the philosophical complexity exposed by postmodernist philosophy (Cilliers, 1998; Henrickson & McKelvey, 2002). Complexity theory addresses situations where linear cause and effect do not apply. Examples of such complex theories have been applied to biology, management, computer science, psychology, and other fields. In medicine, Complexity Theory has been applied to immunology (eg. Efroni, Harelb & Cohenb, 2005). Brown & Moon (2002) note that the new public health has “advocated a multi-causal approach that saw infectious and chronic, degenerative disorders as being the result of a complex interaction between biophysical, social or psychological factors.” (pp. 362–363.
The theory’s “complexity” is because it is composed of many parts (sub-units) that interconnect in known and unknown ways (Sussman, 1999) and intricate ways (Moses, 2006), where cause and effect are subtle and change over time (Senge, 2014).
In Alzheimer’s disease research, Complexity Theory might explain why many causes may exist although the disease is expressed uniformly. It might also be that depending on where you are in your lifespan, the disease expresses itself differently, evolving across time (Coveney & Highfield, 1995). Complexity Theory attempt to reconcile the unpredictability of different systems—in this case, areas of the brain interact together in ways as yet unknown—with a sense of underlying order and structure (Levy, 2000). Complexity Theory can be the foundation for understanding all types of Alzheimer’s disease. It can easily be adapted to anomalies in research in a way that makes the theory predict outcomes. At the same time, the theory must be able to explain existing anomalies.
How does a theory of Alzheimer’s disease deal with such confounders? Under Complexity Theory these processes are inclusive, and can be mediated and moderated by other variables. For example, Alzheimer’s disease can be mediated by protecting against injuries (e.g. head injuries, toxicity, radiation). It might also be mediated by maintaining a healthy lifestyle (and the effect this has on supplying the brain with oxygen—cerebral perfusion), or eating a healthy balanced and varied diet that provides all the nutrients and bacterial flora that we require at older ages (Bredesen, 2014). While a century of work has looked at how plasticity, neurogenesis and capacity can delay or protect against Alzheimer’s disease. All these factors—injury, penumbra, perfusion, plasticity—become important processes and sub-units in discussing the etiology of the disease under a Complexity Theory.
But perhaps we are not the first to request this: ”….demonstrate to us in an impressive way how difficult it is to define disease solely with respect to their clinical features, especially in the case of those mental disorders which are caused by an organic disease process. (Alzheimer, 1912, p) Fox, Freeborough & Rossor (1996) conclude by saying that “…no clear cut distinction exists between senile Alzheimer’s disease and normal aging as far as the clinical and anatomo-pathological elements are concerned” (p. 146). If this is true then we are back to square one with Alzheimer’s disease. It is a disease of old age.
Reference.
Garrett MD (2015). Politics of Anguish: How Alzheimer’s disease become the malady of the 21st century. http://www.amazon.com/Politics-Anguish-Alzheimers-disease-century/dp/1518892930
© USA Copyrighted 2016 Mario D. Garrett
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