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Through a novel use of functional magnetic resonance imaging (fMRI), researchers at the Columbia Presbyterian Center of New York Presbyterian Hospital have provided evidence of two distinct memory decline patterns in the elderly. In the future clinicians hope to use this technique to diagnose patients in the very early stages of Alzheimer's disease and implement early intervention strategies to slow the condition's progression.

The results of the Columbia Presbyterian Center study were presented in Toronto at the 51st Annual Meeting of the American Academy of Neurology by Scott A. Small, MD, Associate Professor of Neurology at the Gertrude H. Sergievsky Center of the Columbia University College of Physicians & Surgeons, Clinical Assistant Neurologist at New York Presbyterian Hospital, and author of the study.

Memory decline with age is common, with some reports suggesting that more than 40 percent of people over age 60 have some memory impairment. But not all age-related memory decline inevitably leads to the development of Alzheimer's disease. "Both Alzheimer's disease and other age-dependent physiologic changes probably contribute to memory decline in the elderly. A key question for researchers is, 'how do we distinguish between these processes?' A test that could do so would be extremely helpful in identifying individuals in the early stages, when the main focus of treatment is halting progression—the earlier, the better," says Dr. Small.

The Columbia Presbyterian Center researchers used fMRI, a noninvasive modification of traditional MRI, to analyze changes in the hippocampus region of the brain during memory tests. It's been known for decades that the hippocampus is integral to the brain's memory function. Other functional imaging techniques, such as positron emission tomography (PET), have been used to study brain changes related to memory function, but these techniques have been unable to selectively assess different regions within the hippocampus and thus cannot show how specific areas of the brain alter as memory declines. The study led by Dr. Small is the first to document functional changes in various areas in the hippocampal formation.

"The hippocampus is the first brain structure to be targeted by Alzheimer's disease; therefore, detection of changes in this area would provide early diagnosis of the condition. Through the use of fMRI, we were able to show two distinct patterns of age-related memory decline in the healthy, nondemented elderly. We believe that those individuals with dysfunction in the entorhinal region of the hippocampus have early Alzheimer's disease, while those with dysfunction in other regions of the hippocampus do not," notes Dr. Small.

The study first evaluated memory function in three groups of individuals over age 65: four patients with normal memory, 13 with isolated memory decline, and four with mild Alzheimer's disease. All of the study participants viewed photographic portraits for four minutes while undergoing a brain MRI. Study participants were selected from the Washington Heights Inwood Aging Project, a long-term, community-based random aging project of elderly residents of northern Manhattan. They were followed for at least three years.

The researchers then conducted fMRI and memory testing on the 13 individuals with isolated memory decline. Results showed that five had decreased activation of the entorhinal cortex region of the hippocampus (-EC group), while the remaining eight had normal activation (+EC group). Moreover, the -EC group also had diminished activation in both the subiculum region and hippocampus proper, while the +EC group had diminished activation in only the subiculum region.

"This regional activation pattern in the -EC group was indistinguishable from the pattern we documented earlier in the patients with Alzheimer's disease, making it quite likely that these patients are in the initial disease stage. But because the entorhinal cortex is the first brain region that's targeted by Alzheimer's disease, the +EC group, which had no evidence of change in this area, is unlikely to have early disease," explains Dr. Small.

The -EC group also had greater decline in abstract reasoning and language function over time when compared to the +EC group. Studies have shown that memory decline in conjunction with a decline in abstract reasoning skills predicts progression to Alzheimer's disease.

While the underlying causes of non-Alzheimer's disease-related memory decline remain unknown, there are several possibilities. Age-dependent changes in adrenal and gonadal hormones, as well as changes in cerebrovascular blood supply, may somehow impair cells in the hippocampus and result in memory impairment.

"We believe that the results of our study show that fMRI may in the future be developed both as a screening tool for detecting Alzheimer's disease in its initial stages, which would permit early intervention, and as reassurance for patients with the non-Alzheimer's disease-related pattern that their memory decline is not associated with that disease," concludes Dr. Small.