Mild Behavioral Impairment: Harbinger of Dementia?

By Jaimie Lazare

Researchers have introduced mild behavioral impairment as a new patient status that may serve as an early warning sign of neurodegeneration and progression to dementia.

Alzheimer's disease (AD), a neurodegenerative condition marked by progressive memory loss and a decline in activities of daily living, affects more than 5.4 million people in the United States. Every 67 seconds, an individual will develop AD; by midcentury, every 33 seconds, an individual will develop the disease.1

Diagnosing AD requires a thorough medical workup that includes performing cognitive tests such as the Mini-Mental Status Exam and using positron emission tomography to identify amyloid plaques—one of the hallmarks of the disease. Now researchers are proposing the creation of a new diagnostic criterion, mild behavioral impairment (MBI), which may be an early indicator of progression to dementia.

What Is MBI?
At the Alzheimer's Association International Conference 2016 (AAIC 2016) in Toronto, researchers proposed that MBI should be specified as a new diagnostic construct; it encompasses neuropsychiatric symptoms (NPS) that may serve as early prognosticators of the development of dementia in advance of signs of cognitive decline. In addition to the new criterion, researchers also presented a checklist that divides these noncognitive symptoms into five domains: interest, motivation, and drive; mood or anxiety symptoms; control over behavior and impulses; social graces, tact, and empathy; and thoughts and perception.2 Experts in the NPS Professional Interest Area, a group under the auspices of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment, developed the MBI Checklist (MBI-C), which can be viewed here.

The NPS professional interest group helped to develop the idea that these patients not only present with memory problems, often the most common element considered in terms of Alzheimer's disease or certain types of dementias, but also develop behavioral changes, says Dean Hartley, PhD, director of science initiatives, medical and scientific relations at the Alzheimer's Association. "What they are trying to do is develop a checklist that physicians can use to look at these symptoms and get a baseline on people to know whether they are changing in some way," he says.

The diagnostic criteria for MBI include observed changes in behavior or personality among patients who are functionally independent and typically younger (≥50) than dementia patients.2 These changes differ from the patient's usual behavior and aren't attributed to other factors such as a medical condition or traumatic experience. Furthermore, the behavioral changes must be severe enough to affect at least one area of the patient's life, eg, interpersonal relationships or workplace performance.

Mild behavioral impairment is very explicit because it describes later life onset of neuropsychiatric symptoms that are sustained for at least six months and are impactful on a person's life, says Zahinoor Ismail, MD, lead researcher and a neuropsychiatrist at the University of Calgary. "If you take two groups of dementia patients and divide them up on whether or not they have NPS, those who have neuropsychiatric symptoms have greater caregiver burden, higher rates of institutionalization, faster cognitive decline, and faster progression to severe dementia and death, and then upon autopsy they have a greater neuropathological burden of plaques and tangles," Ismail says.

"The overall rate of progression from MCI to dementia is about 13% per year, but if the patient also has NPS, the conversion to dementia increases to about 25% per year. So there's something about the comorbid presence of neuropsychiatric symptoms that results in greater disease severity," Ismail says.

Ismail adds that the MBI criteria and MBI-C allow researchers to operationalize and measure the population of patients who are cognitively normal, subjectively cognitively impaired, or have mild cognitive impairment with NPS. Directing attention to this group of patients with behavioral impairments enables better monitoring and treatment, which is a real step forward because clinicians have not been doing that in a systematic way historically, he explains.

Further studies are warranted to determine whether MBI domains are powerful predictors for the progression toward dementia, and the only way to assess that is to systematically apply the MBI criteria to a larger population and follow them over time, Ismail says. He says that validation studies for the rating scale are ongoing and team members across the globe are now moving forward with studies.

Imaging in biomarker studies are under way at the University of Calgary. Ismail, as the lead researcher, and his team were able to get an early start on these studies in order to understand how factors such as a patient's apolipoprotein E status, genetic risks, and imaging markers may be associated with patients' overall scores and individual MBI domains.

Caregiver Insights
At the AAIC, Ismail says that the feedback from family members was remarkable because they expressed that the neuropsychiatric symptoms discussed represented what they saw in their parents before they developed dementia. So many of the caregivers felt empowered and believed they were heard in a way they hadn't been before they attended the conference, he says.

Ismail says the MBI-C was designed with the caregiver in mind because a lot of valuable information comes from family members. Without taking the time to obtain information from family members, clinicians often miss many of the behavioral signs that occur early on, he says.

"It's the family members who are going to observe these behavioral changes," Ismail says. By not including the family in the patient's care, clinicians are missing the big picture. One of the fundamental changes that need to happen from the development of the MBI checklist is ensuring that physicians also speak to family members," he says.

Hartley notes that clinicians can direct patients and their loved ones to the Alzheimer's Association's website, which provides free information about the disease and what caregivers need to know. Physicians should also ask caregivers during office visits how they're doing because the year-round care they provide can affect their own health. Although physicians may not be providing medical care to their patients' caregivers, it's important to address how caregivers may be coping with stress, he says.

Benefits of Early Diagnosis
Although there's no cure for Alzheimer's disease, MBI may help to identify patients earlier in the disease trajectory. The benefits of early diagnosis include providing patients and their families with treatment and supportive resources sooner rather than later.

The majority of Alzheimer's patients, however, report that they have not been informed by their clinicians about being diagnosed with dementia.3,4 The reasons for not disclosing a dementia diagnosis include issues such as the complexity and uncertainty about the diagnosis, time constraints in an office visit, and family members requesting that patients not be informed about their diagnosis.1

The average course of Alzheimer's disease extends between four and eight years, but some people may live with the disease for as long as 20 years. So it's important to make an early diagnosis because it can help patients and their families develop a care plan, Hartley says.

To underscore the importance of early diagnosis, the Centers for Medicare & Medicaid Services proposed the implementation of The Health Outcomes, Planning, and Education (HOPE) for Alzheimer's Act that allows physicians to bill for care planning sessions under Medicare.5 HOPE would help millions of Americans diagnosed with dementia and their caregivers by ensuring that a dementia diagnosis is documented in the patient's medical record, developing a comprehensive care plan that takes into account the patient's comorbidities, and educating providers on how to address barriers that patients may face in their care planning efforts.

Offering physicians a billing code that allows them to provide families with a care plan will be helpful because dementia specialists may provide care for which there is no way to bill, Hartley says. The reticence in providing a dementia diagnosis is a complex issue, but it's important to hone in on providing these patients with the healthiest life that they can have, he says.

The Alzheimer's Association is a great free resource to start patients and their families thinking about what's coming and how to plan, Hartley says. Early diagnosis provides an opportunity to put a care plan in place, including getting finances in order, particularly because dementia can be an expensive disease to manage. Caring for an Alzheimer's patient in a long term care facility can cost approximately $70,000 to $100,000 per year, he says.

Another benefit of early diagnosis is the potential for enrolling patients in clinical trials. By volunteering in studies, patients benefit from the medication and receive excellent medical care at specialized facilities, Hartley says. Early diagnosis is a key aspect in helping to keep people diagnosed with dementia healthy for as long as possible, he says.

— Jaimie Lazare is a freelance writer based in Brooklyn, New York.

References
1. Alzheimer's Association. 2015 Alzheimer's disease facts and figures. Alzheimers Dement. 2015;11(3):332-384.

2. Ismail Z, Smith EE, Geda Y, et al. Neuropsychiatric symptoms as early manifestations of emergent dementia: provisional diagnostic criteria for mild behavioral impairment. Alzheimers Dement. 2016;12(2):195-202.

3. Campbell KH, Stocking CB, Hougham GW, Whitehouse PJ, Danner DD, Sachs GA. Dementia, diagnostic disclosure, and self‐reported health status. J Am Geriatr Soc. 2008;56(2):296-300.

4. Fisk JD, Beattie BL, Donnelly M, Byszewski A, Molnar FJ. Disclosure of the diagnosis of dementia. Alzheimers Dement.2007;3(4):404-410.

5. The HOPE for Alzheimer's Act. Alzheimer's Association website. http://act.alz.org/site/PageNavigator/Advocacy_PublicPolicy/HOPEforAlzheimersAct.html. Accessed August 11, 2016.