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The hippocampus and the overlaying entorhinal cortex are the first brain regions to be affected by the onset of Alzheimers Dementia. This should not be suprising to anyone who has witnessed a close friend or family member go through the early stages of Alzheimers Dementia. While the affected persons older memories of their childhood may remain vividly intact, their more recent attempts to establish new memories may fail dramatically, including attempts to remember whom they just met, what they had for breakfast that morning, and where they left their keys. The later stages of Alzheimers Dementia involve all areas of the brain and deficits in all cognitive, perceptual, and motoric functions. However, the earliest behavioral deficits are in the formation of new memories, much as we see in amnesic patients who have sustained permanent, but stable, damage to their hippocampus and related structures in the medial temporal lobes. Thus, early Alzheimers Dementia looks much like a mild form of anterograde amnesia.
Our colleagues and collaborators at the New York University Medical Center have shown that structural imaging of the hippocampus and entorhinal cortex provide a means for predicting, with moderate accuracy, the future onset of Alzheimers Dementia. Across a population of normal elderly who report mild memory problems, they found that those who showed the greatest degree of atrophy in the hippocampal region (Figure 15) were most likely to go on to develop Alzheimers Dementia in the next few years. While this suggests an exciting possible means for predicting and identifying Alzheimers Dementia at its very onset, it is not really a practical means for screening large populations of people the brain scans take months to analyze, are very labor-intensive, and cost thousands of dollars each. What is needed, instead, is a simple behavioral test or battery of tests that can reliably correlate with this early brain atrophy, and thereby identify people most at risk for Alzheimers Dementia. With Mony DeLeon, Steven Ferris, Alan Kluger, and Jamie Golomb at the NYU Aging and Dementia Center, we have begun collaborating to develop such a battery of tests, based on experimental paradigms, such as the learned irrelevance analog illustrated in Figure 7.
Figure 16 shows the correlation between an aggregate hippocampal function score based on a battery of our tasks and the qualitative measures of hippocampal atrophy based on structural images of the brain. These results are very promising, as the correlation of .8 was significantly higher than that found for any of the standard neuropsychological tests used previously, such as delayed recall information from a paragraph. We are working with the NYU Aging and Dementia Center to extend and refine this battery, as well as testing it against more accurate, quantitative measures of hippocampal atrophy. If successful, such a battery might be useful for identifying subjects at risk for Alzheimers Dementia (and therefore candidates for risky or costly Alzheimers Dementia drugs), or for pharmaceutical companies in assessing and comparing the efficacy of new drugs for delaying the onset of Alzheimers Dementia.