June 22, 2011

Warding Off Dementia: Major NIH Study Finds No Evidence That Anything Really Works

With all my recent research on dementia, how on earth did I miss this study?

A year ago, NIH recapped an in-depth review of past studies to answer this question: Can anything -- dietary supplement, prescription med, exercise, Mediterranean diet, strong social network (just to mention several "benefits" we've recently discussed) -- prevent or delay Alzheimer's or cognitive decline?

The disheartening  answer: "No evidence of even moderate scientific quality exists to support the association of any modifiable factor (such as nutritional supplements, herbal preparations, dietary factors, prescription or nonprescription drugs, social or economic factors, medical conditions, toxins or environmental exposures) with reduced risk of Alzheimer's disease."

Let's take a closer look at the report.
How The Study Was Conducted
NIH assembled a "jury" of 15 independent scientists with no vested interest in previous research. For a day and a half, they listened to researchers describe the earlier studies and the evidence for their conclusions. The jury also heard from Duke University scientists who had been commissioned to evaluate the hundreds of past studies.

The review was restricted to studies involving humans (no mice) in developed countries with sample sizes of at least 50 for randomized, controlled trials, and 300 participants for observational studies.

What Factors Are Associated with Reducing the Risk of Alzheimer's?

The answer (quoted above), was that "no evidence of even moderate scientific validity" supports claims that any modifiable factor could prevent or delay Alzheimer's.

The panel did find strong evidence that a non-modifiable factor -- our genes -- plays a part. The apolipoprotein E  (ApoE) gene variation, in particular, is associated with a risk of Alzheimer's. The "jury" endorsed genetic studies for their possible use in developing effective therapies down the road. (Such studies are being given high priority by researchers funded by the Michael J. Fox Foundation and the Parkinson's Foundation.)

As far as the choices we control are concerned, the study found "the overall quality of the scientific evidence is low" that any of the following might be connected with Alzheimer's:

  • Chronic diseases and conditions, like diabetes, high cholesterol levels, and depression. 
  • Dietary and lifestyle factors and medications, such as folic acid intake, low saturated fat consumption, high fruit and vegetable consumption, use of statins, light to moderate alcohol consumption, education, cognitive engagement, and physical exercise.
  • Other claimed lifestyle associations, such as current smoking, never having been married, and lacking social support.
  • And finally these factors: Other vitamins, fatty acids, the metabolic syndrome, blood pressure, plasma homocysteine level, obesity and body mass index, antihypertensive medications, nonsteiroidal anti-inflammatory drugs, gonadal steroids, or exposure to solvents, electromagnetic fields, lead, or aluminum.
Son of a gun! We'd been feeling hopeful about a lot of those "benefits."   :-)

What's the basic problem with most of the past studies?
Here's a key observation in the NIH report:
The primary limitation of most of these studies is the distinction between association and causality. Diseases are complex; they are determined and shaped by many variables, and associations often involve correlated factors. For example, individuals with higher levels of education are also more likely to have greater cognitive engagement, making it difficult to determine whether either factor (or both factors) has a causal role.
What About Studies of Cognitive Decline?
The NIH report didn't just consider studies related to Alzheimer's; it also reviewed reports dealing with dementia and cognitive decline. But those conclusions were fundamentally the same as the Alzheimer's findings: For most factors, past studies either show no association with cognitive decline, or provide inconclusive evidence. Where a possible association was shown, the quality of the evidence was questionable.
  • Nutrition and dietary factors:  While none of the studies had evidence that satisfied the reviewers, the closest were the studies showing a possible association between fish consumption and a reduced risk for dementia. For other factors, the evidence varied from almost nonexistent for vitamin B, vitamin E, vitamin C, folate and B-carotene, to very limited for low saturated fat and high vegetable diets.
  • Medical factors:  Again the reviewers weren't satisfied with any of the evidence. Still, they gave the best rating to the studies suggesting a connection with high blood pressure. Next were the studies of diabetes where the evidence of a link with dementia was "modest and less consistent." Findings of past studies have been inconclusive regarding obesity. 
  • Psychological and mental health:  The reviewers noted consistent findings (although none that met their standards) showing an association between depression and depressive symptoms with mild cognitive impairment. 
  • Medications: The reviewers looked at studies involving statins, antihypertensive medications, anti-inflammatory drugs, cholinesterase inhibitors, and estrogen, without finding reliable evidence of a connection to cognitive decline.
  • Socioeconomic factors: Childhood socioeconomic status or cognitive milieu does not appear to strongly influence cognitive decline later in life. Evidence on the putative association between years of education and cognitive decline is inconsistent.
  • Social and cognitive engagement: Findings are inconsistent on the impact of living alone -- or being without a partner -- on cognitive impairment. However, there is a robust connection between the loss of a spouse and cognitive decline. Also, evidence is limited but inconclusive that increased involvement in cognitive activites later in life can slow decline or reduce the risk for mild impairment.
  • Physical activity and other leisure activities: Preliminary evidence suggests beneficial associations of physical activity and leisure activities (like club membership, religious services, painting, or gardening) with preservation of cognitive function. Yes! Back to the garden center!
  • Tobacco and alcohol use: Current smokers, evidence suggests, carry an increased risk for cognitive decline. For past smokers, the evidence is less consistent. There is no consistent finding of association between alcohol use and cognitive decline.
My Take on This Report
Stay tuned. I'll collect my thoughts for a subsequent posting. In the meantime, what's YOUR take? 

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