Mild Cognitive Impairment May Signal Alzheimer's; Antioxidants Might Help Prevent It

Alzheimer's disease (AD) is a growing concern for millions of Americans. Many are already engaged in the day-to day struggle of caring for a parent or partner with Alzheimer's, while many more - especially those approaching late middle age - wonder if lost keys and forgotten names signal the early stages of dementia. For most of us, the worst will not occur. But for some, the small lapses in memory will lengthen into the shadow of a disease that ravages the mind. If there was a way to identify the earliest stages of Alzheimer's disease, it might be possible to apply promising therapies to slow or halt its progression.

Two studies that appeared in the Archives of Neurology in 2004 help shed light on the early signs of AD and suggest that antioxidant vitamins might help decrease the risk of developing it.

In the first study, Mild Cognitive Impairment Can Be Distinguished from Alzheimer Disease and Normal Aging for Clinical Trials (Arch Neurol 2004; 61:59-66), researchers involved with the Alzheimer's Disease Cooperative Study Group recruited 769 adults aged 55 to 90 to participate in a battery of tests assessing their mental function. These participants already met the criteria for mild cognitive impairment (MCI), meaning they had memory deficits but experienced normal cognition, were in good general health and had few or no problems with daily activities.

Participants were assessed using a variety of well-established tools including the Clinical Dementia Rating, the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), a Mini-Mental State Examination and various tests evaluating operations such as judgment, orientation and personal care.

The researchers compared the scores of the MCI group with three other groups: a control group of healthy elderly adults who were cognitively normal, a group with very mild Alzheimer's disease, and a group with mild Alzheimer's. They found that although the MCI group demonstrated primarily memory deficits, there were also slight signs of impairment in other areas. In every category, for example, the ADAS-Cog scores of the MCI group fit neatly between those of the control group and those with Alzheimer's disease. The ADAS-Cog tests functions such as word list recall, naming objects and figures, following commands, comprehension, and spoken language.

The authors conclude that "profiles of patients with MCI are all consistent with a transitional stage between the cognitive changes of normal aging and very mild AD."

By identifying the subtle differences between people with normal cognition, mild cognitive impairment, and Alzheimer's, the researchers were able to solidify the criteria for a definitive MCI category. It's hoped that this will help to identify people with very early-stage Alzheimer's disease.

"MCI has been a difficult clinical issue for practitioners because there have not been clear diagnostic criteria," says Diana Kerwin, MD, Medical College of Wisconsin Assistant Professor of Medicine (Geriatrics and Gerontology). "However, MCI is still not an easy diagnosis because the changes seen in patients with MCI are subtle and difficult to detect on a routine physical exam. Often the patient will have mild, self-reported complaints of memory loss and will need to be referred to a specialist for full evaluation to determine if these changes are normal aging, an underlying reversible medical condition such as hypothyroidism, mild cognitive impairment or early dementia."

Antioxidants Might Help in Prevention
While establishing solid criteria is helpful in terms of identifying an early disease state, this information becomes even more valuable if there's knowledge available that might have the potential to keep Alzheimer's disease from gaining ground.

It's been suggested that antioxidants might contribute to the prevention of Alzheimer's disease. Antioxidants such as beta-carotene and vitamins C, E, and A may protect cells from the type of damage that leads to aging in the brain and other tissues.

For the second study, Reduced Risk of Alzheimer Disease in Users of Antioxidant Vitamin Supplements (Arch Neurol 2004; 61:82-88), authors Peter P. Zandi, PhD, et. al., analyzed data from 4740 elderly Utah residents to look for any relationships between supplement use and the incidence of Alzheimer's disease.

The participants had been assessed for dementia in 1995 and again between 1998 and 2000; standard criteria were used to diagnose Alzheimer's disease or other types of dementia when appropriate. Researchers also asked about vitamins, then grouped participants according to their vitamin use. People who took a vitamin E supplement or a multivitamin with more than 400 IU of vitamin E were considered vitamin E users; those who took a vitamin C supplement or a multivitamin with at least 500 mg of ascorbic acid were considered vitamin C users.

Although there was "no notable reduction in risk of incident AD with vitamin E or vitamin C alone or with multivitamins," the authors found fewer Alzheimer's cases among people who took vitamins C and E in combination, leading them to state, "By far, the strongest inverse association with AD prevalence was observed with use of both vitamin E and vitamin C, with or without concomitant use of multivitamins." In other words, the higher the use of vitamins E and C, the lower the incidence of AD.

"Both vitamin C and E are antioxidants which likely reduce oxidative stress and injury in the central nervous system; this may reduce the amyloid plaque deposition in the neuronal cells," Dr. Kerwin explains. Amyloid plaques are the abnormal clumps in brain tissue that signal the presence of Alzheimer's disease.

The authors of the study suggest that "vitamins E and C may offer protection against AD when taken together in the higher doses available from individual supplements," and theorize that the two vitamins might work better in combination than alone because water-soluble vitamin C might help to break down fat-soluble vitamin E for use by the body.

They conclude that "Use of vitamin E and vitamin C supplements in combination is associated with reduced prevalence and incidence of AD."

Dr. Kerwin notes that while the supplements might be beneficial, "I recommend making healthy lifestyle choices because there is also good data that a healthy diet such as a Mediterranean type of diet, moderate exercise, and moderate alcohol intake may also reduce risk" for Alzheimer's disease. "Supplements should be used in addition to healthy diet and exercise, not as a substitute," she says. "Alzheimer's is a complicated disease and we do not yet entirely know all of the risk factors, but as more data comes out it is apparent that common sense healthy lifestyle choices are never wrong."

Eileen Early, BA, BSN, RN
HealthLink Editor

Each year, Medical College of Wisconsin physicians care for more than 180,000 patients, representing nearly 500,000 patient visits. Medical College physicians practice at Children's Hospital of Wisconsin, Froedtert Memorial Lutheran Hospital, the Milwaukee VA Medical Center, and many other hospitals and clinics in Milwaukee and southeastern Wisconsin.