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Integr Med (Encinitas). 2016 April; 15(2): 12–14.
PMCID: PMC4898276

Mild Cognitive Impairment, Neurodegeneration, and Personalized Lifestyle Medicine

Jeffrey Bland, PhD, Associate Editor

Abstract

The takeaway message of this advancing science surrounding the causes and treatment of neurodegenerative diseases is to recognize MCI symptoms early and intervene with a comprehensive, multifaceted, personalized lifestyle medicine program that is designed to improve neurological function and built on the components described above. The present evidence suggests this approach represents the best medicine available today for beating back the rising tide of cognitive impairment and neurodegeneration.

In 1997, the neurologist Oliver Sacks, md, noted author of the book Awakenings, which was made into a movie of the same title starting Robin Williams and Robert De Niro, published a book titled The Island of the Colorblind, in which he described the Chamorro people of the island of Guam, who have a high incidence of a neurodegenerative condition known as lytico-bodig disease. This disease is characterized by the tragic simultaneous presentation of amyotrophic lateral sclerosis (ALS), dementia, and Parkinsonism.

In Guam, working with his colleague Paul Alan Cox, phd, a noted ethnobiologist, Dr Sacks recognized that this neurological disease was not genetic but rather resulted from the dietary consumption of foods that contained an unusual neurotoxic amino acid: β-methylamino-l-alanine (BMAA). What was the source? It was common among this population to eat the meat of the flying fox bat, a large fruit bat that bioconcentrates more than 1000 times the toxic amino acid as a result of one of their primary food sources: the seeds of the cycad palm.1

The world lost a brilliant physician, author, and—really—modern philosopher when Dr Sacks died in 2015. Dr Cox is currently director of the Institute for Ethnomedicine in Jackson Hole, Wyoming. Working with coinvestigators at the Department of Neurology at the University of Miami, Miller School of Medicine, he has further developed a mechanistic understanding as to how BMAA in the diet can result in devastating neurological effects. This team recently published a paper titled “Dietary Exposure to an Environmental Toxin Triggers Neurofibrillary Tangles and Amyloid Deposits in the Brain,” in which they describe the putative mechanism by which BMAA triggers neuronal apoptosis through abnormal protein incorporation in the brain. In a controlled animal trial, they demonstrate that dietary exposure to BMAA results in deposition in the brain of neurofibrillary tangles and β-amyloid, which are clinical hallmarks of both Alzheimer’s and ALS. In addition, they found that when the amino acid serine was supplemented in the animals consuming the diet containing BMAA, there was a 50% reduction in neurofibrillary tangle density.2 Serine is known to be a competitive inhibitor of BMAA incorporation into protein, and therefore its presence can prevent the formation of a “toxic” misfolded protein in the brain.

This research raises important questions and illustrates why concern about the relationship between toxins (environmental and food related) and neurological disease is growing. The history of neurological problems in Minamata, Japan, as a result of the dietary consumption of mercury-laden fish, is another example of how specific food-borne toxins can injure the central nervous system.3 It is also recognized that environmental exposure to agricultural biocides have been linked to Parkinsonism in farm workers,4 as well as users of recreational drugs contaminated with MPTP, as demonstrated in animal models.5

In the 1980s and 1990s, the research work of Glyn Steventon, phd, and Rosemary Waring, phd, of the Neurology Department at Queen Elizabeth Hospital in the United Kingdom found that exposure to specific occupational chemicals and volatile anesthetics are related to Parkinson’s and Alzheimer’s diseases in people who have reduced detoxification ability.6,7,8

What are the first signs of toxic influences on the central nervous system? Data indicate that 10% to 20% of those aged 65 years and older in the United States have signs of mild cognitive impairment (MCI).9 MCI is diagnosed under ICD-10 with the designation F06.7 and is recognized as a transitional stage between normal brain aging and dementia. MCI is characterized by the following:

  1. Evidence of memory impairment.
  2. Preservation of general cognitive and functional abilities.
  3. Absence of diagnosed dementia.10

Mild cognitive impairment has also been identified as one the first signs of more severe neurological disease and is considered a prodromal state to clinical Alzheimer’s disease. There is evidence that both environmental and dietary factors contribute to MCI. It has been reported that mild cognitive impairment was identified in a group of nurses exposed to anesthetic gases,11 as well as in people exposed to various fungi.12 In addition, MCI may possibly result from alterations in the gut microbiome13 and various types of nutritional insufficiencies in older adults.14,15,16 These insufficiencies include inadequate intake of the B-complex vitamins, and specifically concern thiamine, riboflavin, folic acid, cobalamine, and pyridoxine, as well as tocopherol (vitamin E).

There is presently no proven pharmacological treatment of MCI. Two drugs that are used to treat Alzheimer’s disease have been assessed for their ability to treat MCI or prevent the progression to Alzheimer’s disease. Donepezil demonstrated only minor, nonsignificant effects and was associated with adverse side effects17 and rivastigmine failed to stop or slow progression of MCI.18

A recent report in the Journal of the American Medical Association was titled “Lifestyles and Cognitive Health: What Older Individuals Can Do to Optimize Cognitive Outcomes.”19 In this article, the discussion of modifiable lifestyle factors and preservation of cognitive health indicated that factors that have demonstrated an improvement in cognitive health in older adults include the following:

  1. Mental activities that stimulate cognitive function.20
  2. Regular physical activity that includes walking, resistance training, and flexibility exercises.21
  3. Altered diet aligned with the Mediterranean diet concept with nuts and virgin olive oil.22
  4. Personalized health program designed to lower blood pressure and serum lipids when elevated.23

What is not described in this review is the discussion of the neurological risk associated with toxic exposures and how this relates to a person’s detoxification ability. It is well recognized that many older adults are taking numerous medications that can have unknown adverse effects on neurological function with time. The interaction of these medications with one another can overload an individual’s detoxification system, resulting in chronic neurotoxicity.24,25 As an example, neurotoxic effects are observed with various antidepressants in people who have polymorphisms of the detoxification enzyme cytochrome 2D6.26 This demonstrates there is a subtle but important relationship that exists between the neurological and detoxification systems as it relates to adverse effects of specific environmental, dietary, and pharmacological exposures.

The risk involved in exposure to any potential neurotoxic substance is unique to the individual; a benign exposure for one person may be a toxic exposure for another depending on their detoxification status. The effect of toxic exposure on brain function is related not only to impaired detoxification processes, but also to how much exposure results in inflammation of the brain. The brain is made up of both neurons and microglia. The neurons do the “heavy lifting” in functions of the brain, whereas the microglia represents the brain’s immune system. When the brain is exposed to a foreign substance, the microglia responds by “attacking” the foreign substance in attempts to eliminate it. This process results in inflammation of the brain.

It has recently been reported that inflammatory changes in the brain may occur 20 or more years before the onset of genetically related Alzheimer’s disease.27 It is well known that Alzheimer’s disease may have multiple etiologies and is associated with both inherited genetic factors as well as environmental factors that give rise to the sporadic form of Alzheimer’s disease. Well before the diagnosis of Alzheimer’s disease is recognized the brain may be undergoing exposure to increased inflammatory burden that influences its function. These changes are often seen in the early stages of the disease as MCI.

The Clinical Takeaway in Bending the Curve of Cognitive Impairment

This discussion of modifiable factors associated with the reduction of risk to cognitive impairment, and, ultimately, the prevention of neurodegenerative disease, directs us toward a multifaceted clinical program that is personalized to the need of the individual.28

Dale Bredesen, md, a renowned neuroscientist and neurologist at the Buck Institute for Research on Aging, has pioneered a comprehensive approach for the reversal of cognitive decline that he defines as the metabolic enhancement for neurodegeneration (MEND) program. This program is a multicomponent, personalized therapeutic program that focuses on improving metabolism, enhancing nutritional status, improving the microbiome, decreasing toxicity, balancing hormones, and reducing inflammation. In a 2014 article, Dr Bredesen reported on 10 patients he enrolled in an initial study of his program. Nine patients successfully completed the MEND program and had durable improvements in their cognitive function.29 Since his initial study data were published, Dr Bredesen has spoken at a number of medical meetings about his ongoing follow-up. One cannot help but feel this trial may be revolutionary, in that Dr Bredesen describes seeing increased hippocampal volume in several individuals, which is an indication that the condition is potentially reversible in earlier stages. Given these results, a larger and more extensive trial of the therapeutic MEND program is warranted.

Martha Morris, scd, a professor and director of the Section of Nutrition and Nutritional Epidemiology in the Department of Internal Medicine at Rush University, has developed—along with her colleagues—a program they call the Mediterranean-Dietary Approach to Systolic Hypertension (DASH) diet intervention for neurodegenerative delay (MIND) approach for the management of cognitive decline.30,31 The results of her group’s research indicated that the implementation of the MIND dietary program resulted in neuroprotection and improved cognitive performance in a significant percentage of the 960 older participants studied for nearly 5 years.

A recent systematic review of 24 clinical trials on the effect of lifestyle and dietary interventions in people with MCI indicated that the combination of cognitive training, regular activity, and dietary intervention results in improved cognition and a reduction in the loss of cognitive function with time.32 There is now strong evidence that environmental and lifestyle factors play important roles in neurodegeneration and that mild cognitive impairment is often recognized to be the first sign of this condition. Research has revealed that even Huntington’s disease, the neurodegenerative disease that has been regarded as strictly genetically inherited, may be influenced in both its progression and severity by environmental and lifestyle factors.33

The takeaway message of this advancing science surrounding the causes and treatment of neurodegenerative diseases is to recognize MCI symptoms early and intervene with a comprehensive, multifaceted, personalized lifestyle medicine program that is designed to improve neurological function and built on the components described above. The present evidence suggests this approach represents the best medicine available today for beating back the rising tide of cognitive impairment and neurodegeneration.

References

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