In the late 1890s, a railroad worker in Frankfurt Germany noticed that his wife, Auguste Deter, was behaving oddly. Gradually her anxiety and mood changes gave way to memory loss, delusions and other signs of dementia. Committed to an institution in the care of Dr. Alois Alzheimer, Deter became the first person diagnosed with Alzheimer’s disease. A new study establishes that even her subtle, early shifts in behavior — mild behavioral impairment — were scientifically linked to what was to come.
In the study, published in Alzheimer’s and Dementia, scientists found that cognitively healthy adults with mild behavioral impairment (MBI) are more likely to have higher levels of Alzheimer’s hallmark beta-amyloid, abnormal proteins that are closely linked to Alzheimer’s.
“If you are screening a number of people who have subtle cognitive changes for biomarker positivity, the hit rate is probably about one in 10. That’s an extraordinarily expensive approach to find preclinical dementia,” Dr. Zahinoor Ismail of the University of Calgary told Being Patient. Selecting for MBI, he added, could offer a good alternative.
Ismail and a group of researchers enrolled 96 healthy participants to test whether the questionnaire MBI Checklist could predict Alzheimer’s biomarkers. The primary informant of the participants—usually a spouse—rated whether the participants’ mild behavioral impairment which manifested as apathy, anxiety and social inappropriateness persisted for at least six months.
While researchers have known for some time that neuropsychiatric symptoms like depression and delusions are core features of Alzheimer’s, the broad definition of the different psychological symptoms was too broad for researchers to develop drug targets.
After scientists first described MBI in 2003, Ismail and a group of researchers developed more stringent criteria for diagnosing MBI in a study published in 2016. Then, in a 2017 study, the team created the MBI checklist survey to screen for healthy adults with MBI, described as the emergence of neuropsychiatric symptoms for adults aged 50 years or older.
In the most recent study, the team conducted brain scans of the participants and found that participants who scored higher on the rating scale had higher levels of beta-amyloid.
The researchers say that the findings provide further evidence that scientists should adopt the study’s checklist to screen for people with preclinical dementia. After all, some people with neurodegenerative diseases like Alzheimer’s first develop psychiatric symptoms before their cognitive functions become impaired.
Additionally, patients with neurodegenerative diseases who don’t show obvious cognitive impairment are often misdiagnosed with psychiatric diseases, delaying proper treatments, according to Ismail.
Because MBI is easier to screen for than subtle cognitive changes, Ismail said the research can be used to help clinical trials more effectively recruit cognitively healthy people with early stages of dementia.
Ismail said that he and colleagues will soon publish a paper showing that people with MBI have higher rates of accumulated neurofilament light chain (NfL) — proteins that are released when neurons are damaged. In the future, they will examine the long-term link between MBI and the accumulation of beta-amyloid and misfolded tau proteins.