Research Brief: Last Word From NIH Panel on AD Prevention

Controversy swirled last year when a State-of-the-Science panel convened by the National Institutes of Health found insufficient evidence to recommend any health intervention to prevent Alzheimer’s disease (see ARF related news story and subsequent commentary). Many in the field argued that this conclusion sent the wrong message to the public. The Alzheimer’s Association, among others, pointed out that epidemiological evidence does support the benefits of a healthy, active lifestyle in delaying cognitive decline, and suggested that clinicians should promote this safe intervention to their patients. The continuing questions have led to a new publication in the May Archives of Neurology. The panel previously published their findings in the Annals of Internal Medicine (see Daviglus et al., 2010) as well as through an NIH statement (see Daviglus et al., 2010). In addition, researchers led by John Williams at Duke University, Durham, North Carolina, who prepared the data for the panel, published their similar but independent, conclusions as well (see Williams et al., 2010).

Panel members and Duke researchers collaborated on the new paper, which was written in response to requests from journal editors for a joint publication, said first author Martha Daviglus at Northwestern University, Chicago, Illinois. This fourth paper on the same topic reflects how hotly the issue has been debated in the field.

As have the other papers, the new paper concludes that there is not enough evidence to forge firm links between any lifestyle choice or health condition and AD risk. Nonetheless, the panel conceded that the data do show some consistent if weak associations of higher risk with diabetes mellitus (the studies did not distinguish between type 1 and type 2), hyperlipidemia in midlife, and current tobacco use. It also found an association with lower risk for healthy habits such as physical and cognitive exercise, low to moderate alcohol intake, folic acid intake, and a heart-healthy diet. Even so, the panel rated the quality of the evidence as “low” for all these associations, meaning that further research might change the conclusions. The authors stress that existing studies are inadequate to nail down these associations, and more research is urgently needed. The authors also take care to note that, “carefully designed future studies may yet establish significant associations between these same factors with prevention of AD.” They conclude, “Until more conclusive results are available, individuals should continue to aim for a physically and mentally active and healthy lifestyle and prevention of the well-known major risk factors for chronic diseases.”

The panel reviewed data from 1984 through October 2009; no newer studies were considered in this latest publication. Recent work since then has strengthened the association between physical exercise and cognitive health (see, e.g., ARF related news story on Erickson et al., 2011; ARF related news story on Erickson et al., 2010). These new studies are encouraging, Daviglus told ARF, and the benefits of exercise deserve further research. She pointed out, however, that “the panel made their recommendations and conclusions based on a body of research; it was not only a few studies.” Daviglus suggested that in the next few years, the AD field may produce enough high-quality evidence to justify revisiting this issue, and scientists might be able to make firm health recommendations at that time.—Madolyn Bowman Rogers

Comments

  1. I am a patient with early Alzheimer's disease who thinks of myself as a "survivor," now six years since diagnosis, having cobbled together a lifestyle regimen of risk reduction strategies with the hope that it will slow the progression of my disease. After all, besides the existing medications, and until we do have an effective disease-modifying treatment some five or 10 years from now, lifestyle risk reduction is my treatment of choice. It certainly improves the quality of my life, and might even give me more time.

    Dr. Kosik's book The Alzheimer's Solution has provided lots of support for my approach. I'm so pleased with the clarity of his comment above on the recent NIH article calling for research of Alzheimer's prevention. His message is so important that the Alzheimer's awareness and advocacy community should ensure that it gets to the public and to policymakers to undo the damage the NIH panel's report may have done.

    View all comments by Wantand Smith

  2. Given the importance of magnesium (Mg) to brain function (Slutsky et al., 2010), it would seem to make sense to make sure older people are getting enough of this critical mineral. Mg plays an important role in protein kinases. Tyrosine-specific protein kinase and protein kinase M ζ are crucial to memory function. Protein kinase M ζ is also involved in insulin-stimulated glucose transport. Mg and insulin tightly regulate each other. (This is where Suzanne Craft's work on insulin and AD comes in.) Mildred Seelig found an interesting relationship among Mg, Ca, and estrogen (Seelig, 1990). It would be worth investigating if the current clinical recommendations for the treatment of osteoporosis are contributing to Mg deficiency and therefore aggravating the problem of dementia in the elderly. It would also be interesting to see if there is a correlation between AD and osteoporosis. Part of prevention should be making sure the elderly are getting enough Mg.

    References:

    Slutsky I, Abumaria N, Wu LJ, Huang C, Zhang L, Li B, Zhao X, Govindarajan A, Zhao MG, Zhuo M, Tonegawa S, Liu G. Enhancement of learning and memory by elevating brain magnesium. Neuron. 2010 Jan 28;65(2):165-77. PubMed.

    Seelig MS. Increased need for magnesium with the use of combined oestrogen and calcium for osteoporosis treatment. Magnes Res. 1990 Sep;3(3):197-215. PubMed.

    View all comments by Amy Duffield

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References

News Citations

  1. NIH Calls for More (and Different) Research on Preventive Measures
  2. Get Moving—Walking Enlarges Hippocampus, Preserves Memory in Seniors
  3. Research Brief: To Preserve Your Gray Matter, Take a Hike

Paper Citations

  1. Daviglus ML, Bell CC, Berrettini W, Bowen PE, Connolly ES, Cox NJ, Dunbar-Jacob JM, Granieri EC, Hunt G, McGarry K, Patel D, Potosky AL, Sanders-Bush E, Silberberg D, Trevisan M. National Institutes of Health State-of-the-Science Conference statement: preventing alzheimer disease and cognitive decline. Ann Intern Med. 2010 Aug 3;153(3):176-81. PubMed.
  2. Daviglus ML, Bell CC, Berrettini W, Bowen PE, Connolly ES, Cox NJ, Dunbar-Jacob JM, Granieri EC, Hunt G, McGarry K, Patel D, Potosky AL, Sanders-Bush E, Silberberg D, Trevisan M. NIH State-of-the-Science Conference Statement: Preventing Alzheimer's Disease and Cognitive Decline. NIH Consens State Sci Statements. 2010 Apr 28;27(4) PubMed.
  3. Williams JW, Plassman BL, Burke J, Benjamin S. Preventing Alzheimer's disease and cognitive decline. Evid Rep Technol Assess (Full Rep). 2010 Apr;(193):1-727. PubMed.
  4. Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, Martin SA, Pence BD, Woods JA, McAuley E, Kramer AF. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):3017-22. PubMed.
  5. Erickson KI, Raji CA, Lopez OL, Becker JT, Rosano C, Newman AB, Gach HM, Thompson PM, Ho AJ, Kuller LH. Physical activity predicts gray matter volume in late adulthood: the Cardiovascular Health Study. Neurology. 2010 Oct 19;75(16):1415-22. PubMed.

Further Reading

Papers

  1. Daviglus ML, Bell CC, Berrettini W, Bowen PE, Connolly ES, Cox NJ, Dunbar-Jacob JM, Granieri EC, Hunt G, McGarry K, Patel D, Potosky AL, Sanders-Bush E, Silberberg D, Trevisan M. National Institutes of Health State-of-the-Science Conference statement: preventing alzheimer disease and cognitive decline. Ann Intern Med. 2010 Aug 3;153(3):176-81. PubMed.
  2. Daviglus ML, Bell CC, Berrettini W, Bowen PE, Connolly ES, Cox NJ, Dunbar-Jacob JM, Granieri EC, Hunt G, McGarry K, Patel D, Potosky AL, Sanders-Bush E, Silberberg D, Trevisan M. NIH State-of-the-Science Conference Statement: Preventing Alzheimer's Disease and Cognitive Decline. NIH Consens State Sci Statements. 2010 Apr 28;27(4) PubMed.
  3. Williams JW, Plassman BL, Burke J, Benjamin S. Preventing Alzheimer's disease and cognitive decline. Evid Rep Technol Assess (Full Rep). 2010 Apr;(193):1-727. PubMed.

Primary Papers

  1. Daviglus ML, Plassman BL, Pirzada A, Bell CC, Bowen PE, Burke JR, Connolly ES, Dunbar-Jacob JM, Granieri EC, McGarry K, Patel D, Trevisan M, Williams JW. Risk factors and preventive interventions for Alzheimer disease: state of the science. Arch Neurol. 2011 Sep;68(9):1185-90. PubMed.

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