Psychosis in Midlife Could Be a Precursor for Dementia Later in Life
Mid-to-late life persistent episodes of psychosis in cognitively normal people increase the risk for dementia, according to several studies presented at the Alzheimer’s Association International Conference.
The researchers, led by Zahinoor Ismail, MD—professor of psychiatry, neurology, epidemiology, and pathology at the Hotchkiss Brain Institute and O’Brien Institute for Public Health at the University of Calgary—and investigators at the College of Health and Medicine at the University of Exeter—have spent ten years developing and testing their mild behavioral impairment (MBI) construct to identify neuropsychiatric symptoms that may be a precursor to cognitive decline and dementia. They found that 5 to 10 percent of cognitively healthy older people report new-onset psychosis, which is one of five domains of MBI.
In one of the studies, presented at the meeting by Byron Creese, PhD, senior lecturer in neuroscience at University of Exeter Medical School, the researchers examined the relationship of first-onset psychotic symptoms in more than 5,000 cognitively normal people over 60 years old who were followed for up to five years as part of the PROTECT study at the University of Exeter.
Using the MBI checklist, which has been incorporated into the PROTECT study, they found that 8 percent (429 people) of the group met criteria for MBI-psychosis (at a mean age of 63), with a three-fold increased rate of cognitive impairment over the longitudinal study period, compared with those with no psychotic symptoms. Interestingly, these study participants also had a nonsignificant but modestly higher number of health problems, including heart disease, high blood pressure, high cholesterol, thyroid disease, or arthritis.
The PROTECT study analysis validated a similar study, also presented at the meeting, using data from the National Alzheimer’s Coordinating Center. The scientists used information from the Neuropsychiatric Inventory Questionnaire across two visits to identify people with persistent delusions and hallucinations, meeting MBI criteria. They identified 58 people out of 3,446 who met criteria for persistent psychosis. Those with MBI-psychosis had a 3.36-fold greater rate of incident dementia compared with those with no psychosis.
These two studies of psychosis relate to another study presented at AAIC, in which the same scientists tested the MBI construct to determine if it could help identify people with Alzheimer’s disease positivity. They used data from the Alzheimer’s Disease Neuroimaging Initiative to see whether people who had new-onset persistent neuropsychiatric symptoms (that is, MBI) over two study visits had higher levels of the blood-based biomarker phosphorylated tau (p-tau181) at baseline, and if they had a greater increase in p-tau181 over a four-year follow up period, in addition to greater cognitive decline and dementia.
In the sample of 571 dementia-free older adults (with a mean age of 72), the MBI group had higher baseline p-tau181, as well as greater increases in p-tau181, greater decline in memory and executive function, and a 3.92-fold greater rate of incident dementia. The researchers believe that including the MBI into the clinical screening process could help identify those with preclinical or prodromal Alzheimer’s disease.
Dr. Ismail said that the MBI syndrome, ideally measured with the MBI checklist, is best used in conjunction with the assessment of cognitive status—for example, normal cognition, subjective cognitive decline, or mild cognitive impairment—to improve specificity in identifying subgroups in each cognitive category at higher risk for dementia.
“If someone comes in with cognitive complaints and psychiatric symptoms, they are either sent home or sent off to a psychiatrist. If we pay attention and the symptoms meet criteria for MBI, it is suggested that we complete a dementia workup, as these symptoms may be sequelae of the underlying neurodegenerative disease. Historically, these patients have been missed," he said.
“It is very important to pay attention to natural history," Dr. Ismail said.
“These findings are not that surprising," said Mary Sano, PhD, director of the Alzheimer’s Disease Research Center and professor in the department of psychiatry at Icahn School of Medicine at Mount Sinai. “In general, psychiatric symptoms prior to dementia are one of the most significant predictors of dementia. Among the MBI items, I would add that this may be truest of psychosis."
“In the presence of new-onset psychosis, I am guessing this is evidence of brain fragility or some underlying problem that triggers the psychosis," Dr. Sano said. “The field is becoming very aware of these behavioral and psychiatric changes as a harbinger of cognitive change."
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