A Screening Test for Alzheimer’s Disease

A study published in the August 17 issue of the New England Journal of Medicine gives some hope that a test to determine who is at higher risk for Alzheimer’s disease may be on the horizon.

Alzheimer’s disease is the most common cause of dementia (loss of mental, or cognitive, capacity) in the later years of life, affecting 8 percent of those over age 65. Approximately 4 million Americans suffer from the disease, and this figure will rise dramatically as the population ages, since the rate of Alzheimer’s rises with age.

Potential new Alzheimer’s treatments focus on slowing the disease’s progression, since the body is unable to make new brain cells to replace those lost to the disease. Before a decision can be made to start such therapy, it is essential to have some means of determining who will develop the disease before irreversible neuronal (brain nerve cell) death occurs.

One possible marker for Alzheimer’s is the genotype “APOE e-4” (e-4), which is a gene coding for a particular kind of apolipoprotein, a fatty substance in the blood. It has been shown that those who carry the e-4 gene have a higher risk of developing Alzheimer’s disease than those who do not carry this gene.

Researchers from the UCLA Medical Center, led by Susan Bookheimer, Ph.D., studied 30 individuals after determining their apolipoprotein genotype. The subjects were aged 40 to 85 (average age 62), and were neurologically and cognitively (mentally) intact. Fourteen of them carried the e-4 gene, and 16 did not.

The investigators used a novel technique for assessing the potential for their subjects to develop Alzheimer’s: They used a “functional MRI” method. MRI stands for magnetic resonance imaging, a radiological test that has been used for 20 years as a means to outline brain structure. This new use of MRI allowed the authors to measure brain activity while the subjects were at rest, and again while performing a verbal recall test requiring intense mental concentration. It has been shown (using other measuring techniques) that patients with early-stage Alzheimer’s utilize more intense brain activity to accomplish routine tasks involving memory and learning than do people without Alzheimer’s.

In their study, the UCLA group found that the subjects with the e-4 gene (those at higher risk of Alzheimer’s), had significantly more brain activity, with respect to both the number of active sites and the intensity of activity, than those who did not carry the e-4 gene. This difference was especially apparent in those brain areas involving language. The average increase in activity was almost double among the e-4 carriers during periods of active recall, compared to non-carriers.

Fourteen subjects, eight e-4 gene carriers and six non-carriers, were studied again two years later. It was found that the amount of cognitive function lost in the two-year period was directly correlated with the increase in brain activity required in the original recall test.

The authors state that the increase in brain activity among the e-4 carriers is compensatory: Those subjects in the early stages of mental decline have to use additional cognitive resources to bring memory-related performance to a normal level. They refer to their assessment technique using functional MRI and recall tests as a “cognitive stress test.”

The researchers conclude that “as a group, older persons with a genetic risk for [Alzheimer’s disease] have alterations in brain function without obvious morphological [structural] or behavioral indications of impending disease.” Their data indicate that “the baseline level of brain activation can be used to predict subsequent decline in memory.”

This last point is the key to the next step in the early diagnosis and treatment of Alzheimer’s. According to an editorial in the same journal, “To develop new methods to prevent and treat [Alzheimer’s disease], we must be able to diagnose the preclinical stage, before the brain damage becomes irreversible.”

If medical scientists can indeed find a method to reliably diagnose Alzheimer’s disease in its early stages, newer and more effective therapies can be developed and tested. Early interventions (early research on a vaccine was recently reported) may also prove more effective than our currently available drugs, which cannot be used until Alzheimer’s is clearly evident, meaning relatively advanced.