The Journey Towards Alzheimer’s Prevention

On April 26-28, 2010, the National Institute for Health, hosted a conference entitled “State-of-the-Science Conference, Preventing Alzheimer’s Disease and Cognitive Decline“. It was open to both professionals and the public.

The goal of the independent panel of health professionals and public officials at the meeting was to assess whether previous research on purported risk or protective factors for Alzheimer’s disease (AD) and cognitive decline is of sufficient strength to warrant specific recommendations for behavioral, lifestyle, and/or pharmaceutical interventions/modifications targeted to these endpoints. I’d like to share my perspective on the reported findings from the conference and how we might move forward from here.

The following draft conclusions were offered by the panel of esteemed professionals:

1. Extensive research over the past 20 years has provided important insights on the nature of Alzheimer’s disease and cognitive decline and the magnitude of the problem. Nevertheless, there remain important and formidable challenges in conducting research on these diseases, particularly in the area of prevention. There are numerous ongoing or planned investigations which may offer promising new insights regarding the causes and prevention of these diseases.

2. cognitive decline and Alzheimer’s disease are major sources of morbidity and mortality worldwide. They pose a significant burden not only on affected individuals, but also on their caregivers and society in general.

3. Firm conclusions cannot be drawn about the association of modifiable risk factors with cognitive decline or Alzheimer’s disease.

4. There is an absence of highly reliable consensus-based diagnostic criteria for cognitive decline, mild cognitive impairment, and Alzheimer’s disease, and the available criteria have not been uniformly applied.

5. There is insufficient evidence to support the use of pharmaceutical agents or dietary supplements to prevent cognitive decline or Alzheimer’s disease. However, ongoing additional studies including (but not limited to) antihypertensive medications, omega-3 fatty acid, physical activity, and cognitive engagement may provide new insight into the prevention or delay of cognitive decline or Alzheimer’s disease.

6. Large-scale population-based studies and RCTs are critically needed to investigate strategies to maintain cognitive function in individuals at risk for decline, to identify factors that may delay the onset of Alzheimer’s disease among individuals at risk, and to identify factors that may slow the progression of Alzheimer’s disease among individuals already diagnosed with the disease.

This story provides a solid picture of the failure of the current scientific paradigms to understand or address the problem of Alzheimer’s disease.

It is correct that there are no known ways to prevent Alzheimer’s disease with 100% certainty. Of course the point is there is no intervention that has been conclusively shown to prevent Alzheimer’s disease. Unfortunately, the scientific field has been driven by the desire to develop treatments without regard to the need to understand what Alzheimer’s disease really is and what causes it, precisely measure its early progression, and then develop rational prevention and risk management strategies.

Since 1906, Alzheimer’s disease has been known as a disease of the brain in which there are formations of neuritic plaques (filled with a protein called beta-amyloid) and neurofibrillary tangles (composed of hyper-phosphorylated tau protein).

The first major breakthrough in this disease was the finding in 1976 of loss of acetylcholine function in the brains of patients with Alzheimer’s disease, which led to most of the current minimally-effective therapies (donepezil, Aricept; galantamine; rivastigmine, Excelon). But, there are several other chemical systems involved, though the only one adequately studied to provide a treatment has been glutamate (leading to the medication meantime, Namenda). The loss of these chemical systems in the brain is due to an attack by the disease on the basic memory neuroplastic mechanisms which are the building blocks of these several chemical systems. I was the first to describe this link between the Alzheimer attack on neuroplasticity and the memory loss in Alzheimer’s patients (Ashford & Jarvik, 1985).

The second major breakthrough in Alzheimer’s disease was the discovery that the disease can be caused by genetic factors. There are relatively specific genetic factors related to the production of beta-amyloid in younger cases. However, the gene related to the production of the protein Apolipoprotein-E (APOE) was discovered in 1994 and accounts for most of the difference between those who get Alzheimer’s disease and those who don’t. Modifying this gene is a nearly sure way to prevent Alzheimer’s disease.

Unfortunately, a genetic approach to prevention is not feasible at this time, though it would seem that trying to understand how APOE is related to Alzheimer’s disease would be the biggest item for study.

Much of the study of Alzheimer’s disease has been directed toward the toxicity of the beta-amyloid protein, and these studies have led to most of the failed treatments for Alzheimer’s disease (on which many billions of dollars have been spent). Paradoxically, it is now becoming clear that beta-amyloid is a normal protein that enhances memory formation. The beta-amyloid forms dense plaque deposits (balls of protein that are bigger than nerve cells) in the brains of Alzheimer patients. However, those deposits are not toxic, but are rather signs of the degeneration of the neurons that produce the beta-amyloid. Actually the beta-amyloid production declines in the earliest stages of Alzheimer’s disease, leading to a decrease in the amount of the free protein usually found in the spinal fluid. It now appears that one of the best ways to detect early Alzheimer’s disease is to examine cerebro-spinal fluid (CSF) for beta-amyloid levels that are below normal. The real need is to see how to maintain the health of the neurons that produce beta-amyloid.

There are many factors that have been shown to be associated with a decreased risk of Alzheimer’s disease, including maintaining low to moderate blood pressure or maintaining an appropriate body weight. Further, higher education is substantially associated with less Alzheimer’s disease. There are many healthy living options that appear to be effective for the prevention of Alzheimer’s based on considerable evidence. Further, there are numerous “common-sense” items that are irrefutably. The rational approaches for attempts to prevent or defer the onset of Alzheimer’s disease at this time, and healthy life-style choices should be considered much more seriously.

My Top 10 recommendations for preventing Alzheimer’s disease have been developing since 1998, and they are unarguably solid.

A significant part of these Alzheimer prevention strategies is exercising the body and the mind. Better exercise habits, which can also keep weight under control, and mental gymnastics (brain training games and programs) are a developing area that must be reasonably considered as an important approach to maximize health and minimize the chances of developing Alzheimer’s disease. Medicine is really an art as much as a science in these areas.

Another important area is the concern each individual has about their own memory function. There are developments in the area of memory screening tests and memory performance monitoring systems to help an individual assess their mental function. A significant project currently underway is the development of the Memtrax program for detecting memory problems. However, the approach of this assessment test is a complement to other brain training programs in that it specifically measures the brain function most directly related to Alzheimer’s disease, which is not addressed by most other approaches. The Memtrax screening test is currently being scientifically tested and calibrated for its precision in providing information about memory in a fast and fun format. I look forward to sharing more about Memtrax as these tests are completed.