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Winter 2011
Vitamins and Dementia: Delaying Cognitive Decline?By Jeanette Cavano, PharmD, CGP With the aging of the country’s population, dementia has gained attention as a growing epidemic. The Alzheimer’s Association estimates that 5.3 million people in the United States are currently diagnosed with Alzheimer’s disease (AD), which represents 60% to 80% of all dementias. Prevalence increases significantly with age, and it is estimated that more than 40% of the population aged 85 and older has AD. With its devastating physical, emotional, and financial consequences, the specter of dementia looms large. Direct care for the average dementia patient costs nearly three times more than care for a similar older patient without dementia. Current FDA-approved treatments for AD, including cholinesterase inhibitors and the glutamateric antagonist memantine, have a moderate impact on this illness at best. Researchers are working to develop disease-modifying therapies that could impact the overall disease process or even provide a cure. To date, this work has not yielded any safe and effective commercially available products. Perhaps because of the dearth of curative or dramatically effective treatments, the research in the field of dementia reveals a broad range of alternative agents studied. As an example, in the 1990s, retrospective observational studies promoted estrogen as effective in preventing or delaying the onset of dementia, but this practice was subsequently found to be ineffective and potentially harmful.1 Subjects who received estrogen as part of the Women’s Health Initiative Memory Study had twice the risk of developing dementia as those who received placebo. This serves as a cautionary tale about the interpretation of observational research and should be kept in mind regarding more recent research examining the possible benefits of vitamin therapies in preventing dementia. Vitamin Supplements for DementiaRecent research has suggested certain vitamin supplements may delay the onset of or decline from dementia. It has long been known that vitamin B deficiencies (eg, B12 and thiamine deficiency) can present with symptoms of cognitive impairment that may be reversed by replacing these vitamins. This article will review the studies of the association of vitamins E, C, and D with cognitive impairment. The pathophysiology of dementia reveals inflammatory processes and oxidative damage in the brains of demented individuals, leading researchers to speculate that anti-inflammatory and antioxidant treatments may be effective for preventing or treating such damage. A review of the research on the efficacy and potential risks of vitamin supplementation follows. Vitamin EAs an antioxidant, vitamin E is thought to scavenge free radicals and prevent oxidative damage to neurons such as that seen in AD. In 1997, Mary Sano, PhD, a professor of psychiatry and director of AD research at Mount Sinai School of Medicine, and colleagues published in The New England Journal of Medicine the first randomized controlled trial of vitamin E as a therapy to prevent progression in probable AD. In this study, subjects with probable moderate AD received 1,000 IU of vitamin E twice daily, 5 mg of selegeline twice daily, a combination of these two treatments, or placebo for two years. All treatment groups had significant delays in progression to death, institutionalization, loss of activities of daily living (ADLs), or severe dementia, with the vitamin E group having the greatest delay (230 days). However, the risk of falls and syncope were greater in the treatment groups. The subjects receiving vitamin E were three times more likely to fall than those taking a placebo. Subsequent research has called into question the safety of high doses of vitamin E (more than 400 IU/day) such as those used in this study.2 Unfortunately, little research was done in subsequent years either to support or refute the findings of the Sano study. By 2008, in a review published by the Cochrane Collaboration on the efficacy of vitamin E in dementia, the authors were able to find only two randomized double-blind trials to evaluate. Although the Sano study had positive results, the other study did not, and at that time, the researchers concluded there was “no evidence of efficacy of vitamin E in the prevention or treatment of people with AD or MCI [mild cognitive impairment].” Vitamin CIn a 2004 observational study published in the Archives of Neurology assessing the relationship between vitamin supplement use and the risk of AD, researchers found that subjects who used vitamins E and C in combination had a significantly lower risk of developing AD at three years’ follow-up. This risk reduction was not seen in those who took either vitamin E or vitamin C alone. While this study suggests a benefit from these vitamins, it is imperative to interpret these findings with caution as they are based on observational data and patient reports rather than the gold standard randomized controlled trial. Nevertheless, this study does raise the question of whether vitamin C would be beneficial for reducing AD risk. In a thorough review of the literature up to 2005, authors Lisa Boothby, PharmD, BCPS, and Paul Doering, MS, FAPhA, in an article published in the Annals of Pharmacotherapy, stated that there were insufficient data to recommend vitamin C monotherapy to reduce AD risk. Additionally, the potential for vitamin E to increase adverse cardiovascular outcomes and all-cause mortality precluded further study of this vitamin as a protective agent against AD, according to the article. While vitamin supplementation does not appear to be supported by research, a recent analysis of dietary vitamin intake in subjects from the Rotterdam Study, a population-based prospective cohort study conducted in the Netherlands, found that while a high dietary intake of vitamin E (median 18.5 mg/day, or 28 IU) was associated with a decreased incidence of dementia over 10 years’ follow-up, dietary vitamin C, beta-carotene, and flavonoids showed no such association.3 This may close the chapter on the role of vitamin C in protecting against dementia but again highlights the need for further study of a safe and effective dose of vitamin E. Vitamin DThe most exciting recent research in the field of dementia and vitamin supplementation concerns vitamin D, about which several population-based observational studies have been published in the last few years. These studies compared 25-hydroxy vitamin D levels (a marker of vitamin D stores) with the incidence of dementia or cognitive decline. In all but one of these studies, researchers found a positive correlation between low 25-hydroxy vitamin D levels and dementia or measures of cognitive impairment. Unfortunately, what cannot be gleaned from the research thus far is whether vitamin D supplementation is helpful and if so, at what dose and for what duration. Additionally, the caveat that observational research does not truly answer the question of cause-and-effect must not be overlooked. Nevertheless, the benefits of maintaining sufficient vitamin D levels for bone health and a decreased risk of falls and fractures are well established; the possibility that vitamin D replacement may also help prevent cognitive decline is merely frosting on the cake. Screening and supplementation for vitamin D deficiency should be done broadly for those over the age of 65. Final ThoughtsOlder patients and their families often presume that vitamin supplementation is beneficial in promoting good health. While we strive to promote evidence-based medicine, healthcare professionals must acknowledge the limitations of what has been studied and whether research results truly apply to our patients. Many providers assume that while vitamin supplementation may not necessarily treat the various conditions of aging, it is not likely to produce harm, and thus they avoid the conflict of advising patients to stop taking what they view as health-promoting agents. Various conflicting and superficial reports in the media only serve to add to the confusion. However, we must acknowledge issues of pill burden, out-of-pocket costs for over-the-counter supplements, and the documented potential harms of some supplements. We must make the most of what we do know and provide our patients with a thoughtful interpretation of the evidence available to encourage them to make wise healthcare choices. With this in mind, consider advising patients to get their vitamin D levels checked and obtain a supplement in cases of deficiency to improve bone health and possibly to minimize dementia risk. Conversely, we should advocate for a diet rich in sources of vitamin E while we help our patients appreciate the potential risks of high-dose vitamin E and the relative lack of support for vitamin C as an agent to prevent cognitive decline. — Jeanette Cavano, PharmD, CGP, is fellowship trained in psychiatry and works as a clinical pharmacist at the San Francisco Behavioral Health Center. She is an assistant clinical professor at the University of California, San Francisco School of Pharmacy and trains pharmacy students in didactic and experiential coursework in dementia and geropsychiatry. References
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