TORONTO – Researchers have described a behavioral syndrome that they say can be a forerunner of Alzheimer’s disease and other neurodegenerative diseases and released a tool for diagnosing it.
Mild behavioral impairment (MBI) defines a syndrome of new-onset neuropsychiatric symptoms that appear in nondemented people older than 50, and are sustained for at least 6 months. Symptoms can occur in any of five domains: apathy/drive/motivation; mood/affect/anxiety; impulse control/agitation/reward; social appropriateness; and thoughts/perception.
Zahinoor Ismail, MD, described the concept of MBI for the first time at the Alzheimer’s Association International Conference 2016, and unveiled the MBI Checklist (MBI-C), a two-page screen that identifies and scores these symptoms. The MBI-C is a project of the Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART), and is still being validated, although is available for clinical use now, said Dr. Ismail of the University of Calgary (Alta.).
Changes in personality are often the earliest signs of an emerging neurocognitive disorder, appearing well before any problems with memory or cognition. The MBI-C will allow clinicians to identify and track these changes in patients.
“We can now describe this preclinical dementia phenotype and use this tool to diagnose it and to capture change over time,” Dr. Ismail said.
In addition to being clinically useful, he said the checklist will wield great power in research: It could target a population at the greatest risk for neurocognitive decline, at a time where any future disease-modifying drugs could be most beneficial.
“We all know that dementia is much more than memory or cognitive impairment alone. The neuropsychiatric symptoms of dementia are associated with functional impairment, caregiver burden, institutionalization, accelerated rates of progression, and a greater burden of plaques and tangles. There is a great need to identify people early on, people in whom we might be able to change the course of illness. These patients, who present with early neuropsychiatric symptoms, may be a population we can examine to see if that is possible.”
A large body of research has already linked new-onset neuropsychiatric symptoms with neurocognitive disease, particularly frontotemporal dementia, Dr. Ismail said. One of the most compelling studies comprised about 500 subjects enrolled in the ongoing Mayo Clinic Study of Aging, who were followed for 5 years (Am J Psychiatry. 2014;171;572-81). This study found that the emergence of neuropsychiatric symptoms in cognitively normal older adults was associated with significant increases in the risk of developing mild cognitive impairment. Agitation conferred the highest risk (hazard ratio, 3.06), followed by apathy (HR, 2.6), anxiety (HR, 1.87), irritability (HR, 1.84), and depression (HR, 1.63).
Dr. Ismail said new-onset neuropsychiatric symptoms are already quite common by the time patients enter care for memory concerns. At the meeting, he presented data on a group of about 300 patients with mild cognitive impairment who attended a memory clinic. A total of 82% endorsed at least one neuropsychiatric symptom. When sorted into the five MBI-C domains, 78% of patients expressed mood symptoms; 64% impulse control symptoms; 52% apathy symptoms; 28% social appropriateness symptoms; and 9% psychotic symptoms.
“Our study suggests that this concept of mild behavioral impairment may be a common and clinically relevant syndrome, particularly given that neuropsychiatric symptoms are associated with greater caregiver burden,” Dr. Ismail said.
Dr. Ismail did not address how the screen should be scored or interpreted. It is composed of five overall domains, each asking about the emergence of a new, persistent symptom. Patients rate the presences and severity of those symptoms on a 3-point scale. The researchers who developed it chose age 50 as the cutoff point because symptoms that emerge at that age can herald the onset of frontotemporal dementia in relatively young patients.
“This idea of symptoms persisting for at least 6 months is important,” Dr. Ismail said. “What we’re talking about is a sustained change from baseline personality. But these are still nondemented patients. Function is maintained. Independent activities of daily living are intact.”
The most comprehensive domain is impulse control, agitation, and reward. “This captures a lot of function with regard to agitation in dementia, new-onset substance abuse, irritability, new-onset road rage … things we might not otherwise capture.”
The social appropriateness domain examines symptoms like a loss of the ability to share appropriately, acting out sexually, and loss of social judgment. The psychosis domain inquires about feelings of aggrandizement, persecution, and suspicion, as well as auditory and visual hallucinations.
The mood domain asks about new-onset anxiety, panic, and depression. The motivation domain asks about the development of apathy or disinterest in family, friends, and activities.