Penn Neurodegenerative and Genomics Center was fortunate to have Dr. Brad Hyman visit from Boston and give a seminar style presentation on November 29. Dr. Hyman has worked at Massachusetts General Hospital for 25 years seeing patients with Alzheimer’s disease, and he currently serves as the Alzheimer’s Unit Director at the Institute for Neurodegenerative Disease there.

Dr. Hyman’s presentation focused largely on the heterogeneity of Alzheimer’s disease, and he provided some context for his talk with a story about two different patients. The first was a professor at a prominent university who was worried about having to concentrate harder in class than usual. He checked the patient’s memory through a series of tests and found it was fine. 20 years later the professor had Alzheimer’s disease. Dr. Hyman suspected that he had AD when they first met, though there were not any diagnosable signs at the time. The second patient Dr. Hyman spoke about was one that he saw for the first time a year ago. His AD has fully progressed since then and he is now in a 24 hour assisted living home, just one year later.

These two patient examples serve to illustrate how diverse and heterogeneous Alzheimer’s really is, which makes it difficult for researchers and doctors to understand. Causes of the disease’s heterogeneity include clinical mis-diagnoses, mixed causes of cognitive impairment, and clinical-pathological dissociations. There are often discrepancies between clinical and neuropathological diagnoses of AD. The rate of tau propagation can also vary, and different AD cases have different potencies for spread. This leads to the question – are there one or many Alzheimer’s diseases?

With neuropathological and clinical symptoms of AD, 65% are diagnosed as not impaired if there are detectable lesions, only 50% are considered not impaired despite moderate lesions, and 90% with severe lesions are considered impaired. These numbers demonstrate flaws in determining who is affected by the disease, which in turn makes the disease difficult to understand and treat. Dr. Hyman emphasized that there are ways to get around heterogeneity from a clinical standpoint with existing tools, but we will have to be more creative with the approach.

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