Tom Morrione, MD examines the poll results and supporting research behind the best methods for slowing the progression of cognitive decline.

by Tom Morrione, MD

Which choice do you believe best slows the progression of cognitive decline?

Poll Results:
Exercise 47%
Omega 3 28%
Aricept 2%
Vitamin E 4%
Statins 1%
None of the above 19%

There is no clear answer to the above question.  In fact, there is some evidence for each of the above interventions depending on the degree of cognitive impairment.  Certainly the mainstay for treatment of Alzheimer’s dementia (AD) is a cholinesterase inhibitor such as Aricept.  Various studies have demonstrated an improvement in cognition, function and behavior with patients with mild AD.  The effect is small, however, clinically significant.  The role of the medication is to slow the progression of the memory loss.  The frustration is that it becomes difficult for a patient or family to appreciate a relative decrease in the loss of cognition on the medication.  Often, expectations are unreasonable and, in the absence of improvement in cognition, the medication is stopped prematurely, resulting in either a precipitous decline or a loss of opportunity for continued treatment.  The pivotal long-term efficacy study done in 1998 by Roger and Friedhoff showed a 28-week delay in cognitive impairment, shifting the curve to the right where it resumed the same rate of decline.  For example, a mean change from baseline in ADAS-cog score of 6 stretched from 28-weeks to over 60 weeks for a difference of 8 months.  Outcomes were the same, just time to outcome increased. 

The most popular response, exercise, has been in the news fairly frequently.  Often recommended by practitioners for general preventive health and treatment for various medical conditions including arthritis, cardiovascular disease and diabetes, the recommendation commonly extends to everyone for both the prevention of developing cognitive impairment, but also to assist in slowing the progression.  A Mayo Clinic study took on the question and enrolled 868 participants, ages between 70 and 89, 128 of which tested with mild cognitive impairment (MCI) and the remaining in the normal range.  Through a survey, the study gathered data on the level of physical activity of the participants from the ages of 50 to 65 and the year before the survey.  Analysis demonstrated an associated risk reduction for cognitive impairment with moderate physical exercise between 50 and 65.  Interestingly, this was not shown for exercise during the year prior to the survey.  Another recent study looked at the “very old”, age > 85, and showed an 88% risk reduction in cognitive impairment for those who exercise 4 or more hours a week.  Sixty-six elders, age > 85, were followed for 5 years.  Fifty-eight percent developed cognitive impairment.  Of those, less active women had a five-fold increased risk of cognitive impairment than their active counterparts.  Just another reason in a long list to add exercise to the treatment regimen.

Vitamin E was first touted as an effective supplement for warding off AD.  Several studies have long-since refuted the claim, however, there are some interesting findings for continued use in selected cases especially with selegiline.  Sano et al. published a study in the New England Journal of Medicine in 1997 looking at selegiline and vitamin E in treating AD.  It was found that 2000 IU of vitamin E daily might delay the progression from moderate to severe AD by about six months.  It was not found to be efficacious in those with severe disease.  Taking vitamin E alone appeared to improve the ability to perform ADLs and require less supervision as well as delay admission to a nursing home care by about 230 days.  In 2003, Klatte et al. further showed that long-term combination therapy with Aricept and vitamin E might help slow cognitive decline in patients with Alzheimer’s disease.  Before you through it on the pile for your patient, there have since been some studies showing an increase in all-cause mortality for unhealthy patients taking high-dose vitamin E.

Regarding omega-3, the Natural Standard Database found conflicting evidence and states that further clinical trials are needed before recommending supplementation for the prevention of cognitive impairment or dementia.  That may be the case, but the supplementation is much like the current explosion with vitamin D, a lot of potential benefit with very little downside.  It is a standard recommendation of mine for folks to add it to their supplementation.

Statin drugs, including Lipitor and Zocor, are used to lower cholesterol levels. Recent studies indicate the possible risk reduction of developing AD.  Recently, a prospective observational study suggested that a statin may protect against the development of dementia.  In July 2008, Cramer looked at 1674 Mexican Americans in the Sacramento area, of which 27% where taking a statin medication.  The data showed a 44% reduction in the rate of developing dementia or cognitive impairment in the statin users suggesting the need for a future randomized control study.

In summary, for most of us out there looking to stave off the potential memory loss or cognitive impairment, there seems to be little risk in adding a good exercise regimen supplemented by omega-3.  For those with more advanced impairment, MCI, early, or moderate dementia, adding vitamin E may help delay the progression with select patients.  For those with a diagnosis of dementia, a cholinesterase inhibitor may help slow the progression but is not shown to be of benefit preventing the progression of MCI to dementia (about a 15% annual risk).  Lastly, the jury is still out on statins and not something I recommend for my patients with the exception of risk factor modification with vascular dementia.  Now if I could just remember the question…

Dr. Tom


American Academy of Neurology, news release, April 16, 2008.

Aleksandra Sumic, MPH, Yvonne L. Michael, ScD, Nichole E. Carlson, PhD, Diane B. Howieson, PhD, Jeffrey A. Kaye, MD, PhD. Physical Activity and the Risk of Dementia in Oldest Old. Journal of Aging and Health, Vol. 19, No. 2, 242-259 (2007).

Bjelakovic G, Nikolova D, Gluud LL, et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 2007;297:842-57.

Cramer C et al. Use of statins and incidence of dementia and cognitive impairment without dementia in a cohort study. Neurology 2008 Jul 29; 71:344.

Klatte ET, Scharre DW, Nagaraja HN, et al. Combination therapy of donepezil and vitamin E in Alzheimer disease. Alzheimer Dis Assoc Disord 2003;17:113-6

Lonn E, Bosch J, Yusuf S, et al. HOPE and HOPE-TOO Trial Investigators. Effects of Long-term Vitamin E Supplementation on Cardiovascular Events and Cancer: A Randomized Controlled Trial. JAMA 2005;293:1338-47.

Miller ER 3rd, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: High-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005;142:60520-53.

Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. N Engl J Med 1997;336:1216-22.