By James J. Kenney, PhD, FACN
Alzheimer’s Disease (AD) is a growing health problem in the United States and many other countries as the proportion of older people in most populations continues to increase. The aging of Baby Boomers has resulted in a rapidly rising number of Americans with declining cognitive function. Since there is no cure or even any effective treatments for advanced AD there is a growing need for ways to prevent or at least delay the onset of AD and senility. AD and vascular dementia (#1 and #2 causes of senility) both share many of the risk factors associated with the development of stroke. Both AD and vascular dementia are more common in people who are obese, especially if they develop insulin resistance and type 2 DM. Elevated blood pressure, nonHDL-C levels, and inflammatory markers are all also associated with an increased risk of stroke and a more rapid loss of cognitive function over time.
Moderately elevated levels of serum homocysteine (Hcy) levels are also positively associated with a greater risk of stroke and heart disease and a more rapid decline of cognitive function over time. There is little debate about whether or not lowering nonHDL-C, blood pressure, reducing inflammatory markers, losing excess weight, exercise, and avoiding tobacco can help prevent stroke and likely also substantially cut the risk of senility. However, several well designed large clinical trials using B-vitamin supplements to lower serum Hcy levels all failed to find a significant reduction in either stroke or total CVD events. This was also the case with smaller clinical trials in patients with kidney disease who are at high risk for CVD events and tend to have elevated serum Hcy levels because their kidneys clear it more slowly from the blood. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651913/]. This certainly suggests taking B-vitamin supplements (typically folate, pyridoxine, and vitamin B-12) even in those with elevated levels has little hope of cutting stroke and CVD events even though they do lower Hcy levels.
Do B-Vitamin Supplements Slow Loss of Cognitive Function?
Moderately elevated levels of Hcy certainly correlate with both an increased risk of stroke, vascular dementia, and AD. But correlation does not prove causation as demonstrated by the fact that taking B-vitamin supplements to lower serum Hcy levels lowered serum Hcy levels but failed to reduce the risk of CVD events. However, one cannot assume that just because taking B-vitamin supplements to lower serum Hcy levels failed to reduce CVD does not mean these B-vitamins may not help prevent loss of brain function in patients at risk of AD and vascular dementia because they already have mild cognitive decline (MCD). Indeed, it appears that the fortification of more foods with folic acid in the USA has already resulted in some decline in both average serum Hcy levels and the development of AD. [Larson EB, Yaffe K, Langa KM. New Insights into the Dementia Epidemic. N Engl J Med. 2013;369(24):2275-7. PMID 24283198]. Many population studies have observed a significantly greater risk of AD and/or vascular dementia and higher levels of serum Hcy levels. [Seshardi S, et. al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med 2002;346:476-83]. However, studies examining the impact of B-vitamin supplements in patients with MCD have so far yielded mixed results. [Wald DS, Kasturirante A, Simmonds M. Effect of folic acid with and without other B-vitamins on cognitive decline. Am J Med 2010;123(6):522-7 and Ford AH, Almeida OP. Effect of homocysteine lowering treatment on cognitive function: J Alzheimers Dis 2012;29:133-49].
One problem with past studies that used neuropsychological testing to assess changes in cognitive function over time is that such measurement can vary from day to day and depend to some extent on the skill of the testers. So a more accurate and objective measure of brain changes over time may be a more precise way to assess the impact of B-vitamins and Hcy levels on brain changes linked to AD progression. Dr. Douaud and associates examined subjects from a randomized controlled clinical trial that measured MCI with neuropsychological testing but also used brain MRIs to look for physical changes in the brain associated with the development of AD. After two years they observed a significantly smaller loss of brain tissue in areas of the brain linked to the progression of AD in those taking either a B-vitamin supplement containing folic acid (800mcg), pyridoxine (20mg), and vitamin B-12 (500mcg) or a look-a-like placebo. This slow down in brain atrophy in the B-vitamin group was particularly significant in those whose initial serum Hcy levels were above 11 micromoles/L. In the placebo group the authors noted that those with higher serum Hcy levels saw greater declines in brain grey matter indicative of AD. And the slowed loss of brain grey matter occurred in the same parts of the brain that are most highly correlated with declining cognitive function over time. It is important to note that the B-vitamin supplements had little impact in subjects who already had low serum Hcy levels. People with serum Hcy levels below 10micromoles/L showed little or no benefit.
Bottom Line: Pharmaceutical treatments for AD continue to prove completely ineffective or at best only transiently and marginally effective at best and do not appear to slow the progression of the disease. A more plant based minimally processed foods diet that is low in salt combined with regular exercise likely not only reduces the risk of CVD, type 2 DM, and several types of cancer but likely reduces the loss of cognitive function. In people already showing MCD it seems wise to check serum Hcy levels and if elevated recommend supplements of B-vitamins to lower serum Hcy levels. Dr. Douaud's study certainly suggests such supplements may slow the loss of grey matter and slow the rate of cognitive decline.
Stephanie Ronco has been editing in a professional capacity for the past 10 years. In addition to her work as an editor, Ronco has also served as a ghostwriter and writing tutor. A voracious reader, Ronco loves watching language evolve and change. When she’s not delving into her latest project, Ronco can be found teaching acting classes, performing in community theater, or sailing with her husband.