Alzheimer’s disease (AD) is a complex disorder that remains biologically mysterious and symptomatically diverse. At this year’s American Neuropsychiatric Association (ANPA) Annual Meeting in Orlando, Fla., experts gathered to discuss that diversity, with lectures aimed at thinking beyond the “typical” view of AD.
Ask almost anyone to define AD and you will probably get a description of a disease characterized by progressive memory loss and the buildup of plaques in the brain that mainly affects seniors.
But, as many of the presenters stressed, older people aren’t the only ones affected by AD.
As Mario Mendez, M.D., Ph.D., a professor of neurology and psychiatry and biobehavioral sciences at the David Geffen School of Medicine at the University of California, Los Angeles, noted, “Think back to the first patient described by Alois Alzheimer; that was very much an atypical presentation of the disease.”
Indeed, Auguste Deter began showing behavioral and cognitive changes in her 40s, and her psychoses—such as jealousy and paranoia—were the most notable signs of her disorder.
Auguste may have been the first atypical case identified, but more recently Alice (as played by Julienne Moore in the 2014 film “Still Alice”) has increased public awareness that AD does not just affect the elderly. In the century in between, however, many questions about these early-onset cases remain.
Early-onset AD can prove challenging to diagnose because these cases frequently display more atypical symptoms, Bradford Dickerson, M.D., an associate professor of neurology at Massachusetts General Hospital, explained in his lecture.
Dickerson highlighted “dysexecutive-predominant AD” as one example of an atypical Alzheimer’s affecting younger people; while cognition is still affected, the deficits primarily arise in working memory (needed for problem solving and decision making) instead of general memory.
In his talk, Mendez discussed another unusual type of AD known as posterior cortical atrophy (PCA), also known as type 2 Alzheimer’s. This condition is considered a disorder of mid-level visual perception, so that basic sight stays intact while acuities like localization or depth perception worsen. As a result, patients will bump into objects as they walk or fail to find specific items in a refrigerator.
Mendez noted that PCA is particularly difficult for patients as they have more perceived insight into their condition as their vision deteriorates, and depression is extremely common in these cases.
Of course, these are just two examples of the many subtypes of atypical AD, which account for about 30 percent of all early-onset dementias. “It goes without saying that early detection is critical in these cases,” said Alireza Atri, M.D., Ph.D., the Ray Dolby Endowed Chair in Brain Health Research at Harvard Medical School. “But how do we disentangle all the diversity?”
New imaging tools might prove valuable, and Dickerson described an approach to visualize amyloid buildup using the tracer Florbetapir F18. Though studies have shown that Florbetapir imaging can predict AD pathology fairly well based on plaque accumulation, more work needs to be done before it can replace spinal fluid exams as a standard (and reimbursable) test.
Melissa Murray, Ph.D., an assistant professor of neuroscience at the Mayo Clinic in Rochester, Minn., discussed her research on developing a classification system for AD based on the density and distribution of the fibrous brain tangles, suggesting that AD cases can cluster into three main types—typical, hippocampal sparing, and limbic predominant—that show some discrete clinical differences.
“From genetics to pathology to imaging, our tools are maturing at a variety of levels, and that includes clinical,” Dickerson said. “And our ability to distinguish the various forms of atypical AD is improving.” ■
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