TORONTO—A behavioral syndrome called mild behavioral impairment (MBI) may be a forerunner of Alzheimer’s disease and other neurodegenerative diseases, according to research described at the Alzheimer’s Association International Conference. Investigators have developed a tool for diagnosing it.
MBI, according to the researchers, is a syndrome characterized by new-onset neuropsychiatric symptoms that are sustained for at least six months in patients without dementia who are older than 50. Symptoms can occur in any of the following five domains: motivation, mood, impulse control, social appropriateness, and psychosis.
Zahinoor Ismail, MD, Assistant Professor of Psychiatry and Neurology at the Hotchkiss Brain Institute of the University of Calgary in Canada, described MBI at the conference 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).
Family members or informants rate the presence and severity of their symptoms on a three-point scale. The researchers who developed the MBI-C chose age 50 as the lower age limit because symptoms that emerge at that age can herald the onset of frontotemporal dementia. While the MBI-C is available for clinical and research use, the scoring risk stratification is still being validated. At present, the MBI-C identifies symptoms of concern and monitors change over time, said Dr. Ismail.
Zahinoor Ismail, MD
Changes in personality are often the earliest signs of an emerging neurocognitive disorder and appear well before any problems with memory or cognition. The MBI-C is intended 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,” said Dr. Ismail.
Checklist May Aid Research
In addition to being clinically useful, the checklist will aid research, he added. It could identify a population at greatest risk for neurocognitive decline at a time when any nonpharmacological interventions or 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,” said Dr. Ismail.
Previous studies have linked new-onset neuropsychiatric symptoms with neurocognitive disease, particularly frontotemporal dementia. One study included about 500 subjects enrolled in the ongoing Mayo Clinic Study of Aging. Investigators followed these participants for five years. 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 (MCI). Agitation conferred the highest risk (hazard ratio [HR], 3.06), followed by apathy (HR, 2.6), anxiety (HR, 1.87), irritability (HR, 1.84), and depression (HR, 1.63).
New-onset neuropsychiatric symptoms are common by the time patients enter care for memory concerns. Dr. Ismail presented data on a group of about 300 patients with MCI who attended a memory clinic. About 82% of patients endorsed at least one neuropsychiatric symptom. As measured by the MBI-C, 78% of patients reported mood symptoms, 64% reported impulse-control symptoms, 52% reported apathy, 28% reported social appropriateness, and 9% reported psychotic symptoms.
Validation of MBI-C Is Ongoing
“Our study suggests that this concept of MBI may be a common and clinically relevant syndrome, particularly given that neuropsychiatric symptoms are associated with greater caregiver burden,” said Dr. Ismail.
“This idea of symptoms persisting for at least six months is important,” he continued. “What we’re talking about is a sustained change from baseline personality. But these are still patients without dementia. Function is maintained. Independent activities of daily living are intact.”
The most comprehensive domain encompasses impulse control, agitation, and reward. “This [domain] 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,” said Dr. Ismail.
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.