Neuropsychiatric Meeting Explores Atypical Alzheimer’s Disease
Abstract
From Auguste to Alice, scientists at the ANPA meeting discuss the symptoms and classification of a disease that is anything but typical.
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.
At the ANPA’s 26th Annual Meeting, ANPA President Sheldon Benjamin, M.D. (right), presents Robert Robinson, M.D., a professor of psychiatry at the University of Iowa Carver College of Medicine, with the Gary J. Tucker Award for Lifetime Achievement in Neuropsychiatry. Robinson was honored for his seminal work on the neuropsychiatry of stroke and psychosomatic medicine.
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.
ANPA Research Committee Analyzes Role of NCBCs in AD
Regardless of whether a case of Alzheimer’s disease (AD) may be typical or atypical, the noncognitive behavioral changes (NCBCs) associated with the disease—such as mood and psychotic disorders—are just as deserving of attention as the memory loss. NCBCs are key determinants for patient institutionalization as well as patients’ and caregivers’ quality of life; they also sometimes predate future cognitive problems, offering diagnostic clues.
But how much do scientists know about NCBCs and their influence on AD onset and/or progression? As part of a report from the ANPA Committee on Research, Jeff Victoroff, M.D., a professor of clinical neurology and psychiatry at the University of Southern California, discussed some findings from a systematic analysis of the past 20 years of imaging studies related to the six most common NCBCs in AD: depression, agitation, psychosis, apathy, anxiety, and sleep disorders. (Though also common, euphoria was not included due to a lack of studies, highlighting an unmet research need.)
Overall, the findings indicate that cognitive and noncognitive changes follow relatively independent clinical courses during AD, suggesting they have independent biological influences. No specific biological cause was identified as being critical for any NCBC, though several were associated with cerebrovascular problems like stroke, pointing to cardiovascular health as an area for intervention.
Though current imaging technology has yet to uncover much information related to NCBCs, Victoroff noted he believed imaging research still held potential for identifying how to prevent or treat these disabling disorders.
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.” ■
More information on the ANPA, including past and future meetings, can be accessed here.
