January 24, 2007

In the Grey Zone

When I went to medical school, the condition “mild cognitive impairment” had not been recognized. Patients either had dementia (which was often referred to as “senility” or “senile dementia” or “senile dementia of the Alzheimer’s type”) or they didn’t. Now we believe that dementia may be twenty years in the making. This makes a lot of sense for Alzheimer’s disease, the most common form of dementia, because Alzheimer’s is due to the abnormal deposition of a normally occurring protein called beta amyloid. If too much beta amyloid accumulates in the brain—and it tends to build up in the part of the brain particularly involved in memory, the hippocampus—the result is amyloid plaques. These plaques are something like dental plaque, but unfortunately there is no easy way to get rid of them. They can’t just be scraped off. In fact, Alzheimer’s disease may result from an imbalance between the deposition of amyloid and its removal. It takes a good long time for enough plaque to build up to result in the problems with memory, thinking, and behavior that constitute Alzheimer’s disease. So it’s not surprising that somewhere along the line, as the process develops, a person might have enough beta amyloid to experience mild memory loss without having enough amyloid to meet the criteria for dementia.

Mild cognitive impairment, or MCI, has been a hot topic of research. Clinicians have tried to define just exactly what MCI is. They have sought to distinguish it from “age-associated memory impairment,” the very slight degree of memory loss that is typically found when comparing old people (especially very old people) to young adults. MCI is now defined as a condition in which patients or families report memory problems which are not sufficient to interferer with daily life. (See R. Petersen, J. Stevens, M. Ganguli et al, “Practice Parameter: Early Detection of Dementia: Mild Cognitive Impairment,” Neurology 2001; 56: 1133.)

Researchers have also tried to figure out whether everyone with MCI is destined to develop dementia. Studies have varied in their findings, but the rate of progression to dementia is somewhere between 6 and 25% per year. Finally, investigators have studied whether any interventions can prevent the development of full blown dementia in people with MCI. One study evaluated the use of Vitamin E and of Donepezil (Aricept), two drugs that are used in the treatment of Alzheimer’s. Unfortunately, Vitamin E had no effect. Donepezil was associated with a lower rate of progression to Alzheimer’s in the first year of treatment, but not subsequently. (See R. Petersen, R. Thomas, M. Grundman et al: “Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment,” New England Journal of Medicine 2005; 352: 2379.)

How should physicians approach patients with MCI? What should families do? What should patients do if they are given this intimidating diagnosis? Right now there is no reliable way to predict who will go on to develop dementia. Magnetic Resonance Imaging (MRI) is a promising technology: patients with degeneration in the hippocampus are at risk of progression to Alzheimer’s. So too are patients with abnormal metabolism in the temporal lobe as measured on a Positron Emission Tomography (PET) scan. But these tests cannot determine with certainty who will progress and who will not. (See K. Blennow, M. de Leon, H. Zetterberg, “Alzheimer’s Disease,” The Lancet 2006; 368: 387.) Until we have treatment that will effectively prevent MCI from progressing, there is little point in trying to predict who is going to get the disease. Patients with MCI should be evaluated regularly, however, to see if they have developed Alzheimer’s or another form of dementia. At that point, treatment may be beneficial. In the mean time, patients with MCI should be sure to appoint a health care proxy to make decisions for them if they lose the capacity to make decisions themselves. And they should take the opportunity to tell their proxy what matters to them—just in case.

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