Primary Symptom at Dementia Onset May Predict Later Neuropsychiatric Symptom Profiles
According to a new retrospective longitudinal study published in JAMA Network Open, the initial cognitive phenotype of dementia is correlated with specific patterns of neuropsychiatric symptoms. This study of 2,400 people with brain autopsy and clinical records available in the National Alzheimer Coordinating Center database is the first to show a relationship between presenting symptoms and later neuropsychiatric profiles.
“This is the first study to show that the presenting clinical phenotype — along with neuropathology and a patient’s age and sex — predicts the likelihood of subsequently developing specific behavioral and psychological symptoms,” says the study’s lead author, Jagan Pillai, MD, PhD, staff neurologist with Cleveland Clinic Lou Ruvo Center for Brain Health. “Awareness of these associations can help inform patients and their caregivers of the probable course of their disease and help guide management.”
Memory loss as a primary presenting symptom was most common (77%). Language impairment, executive function problems, and visuospatial symptoms were the other primary presentations at diagnosis. Compared with amnestic presentations,
• initial language symptoms correlated with:
o lower likelihood of developing depression, REM sleep behavior symptoms, and visual hallucinations
o higher risk of personality changes
• initial executive function symptoms correlated with:
o higher likelihood of developing apathy, delusions, disinhibition, visual hallucinations, personality changes, and REM sleep behavior changes
• initial visuospatial symptoms correlated with:
o higher likelihood of developing visual hallucinations and REM sleep behavior changes
Lewy body disease (LBD) pathology alone correlated with less agitation, disinhibition, and irritability and increased apathy, depression, behavior changes, auditory and visual hallucinations, and REM sleep behavior changes. With mixed AD-LBD pathology, delusions, REM sleep behavior changes, and hallucinations were more frequent than with AD pathology alone. Mixed AD-LBD pathology was, in contrast, less likely to correlate with visual hallucinations and REM behavior sleep changes compared with LBD pathology alone.
Earlier onset of dementia was associated with higher risk and greater severity of NPS. For those with AD or AD-LBD pathology, male sex, earlier onset, and lower educational attainment also correlated with greater severity of NPS. Female individuals had a higher risk of depression and lower risk of agitation, apathy, visual hallucinations, irritability, and REM sleep behavior change.
"These findings collectively provide an important window into the heterogeneity of cortical changes in dementia,” Dr. Pillai concluded, saying, “This is useful to clinicians as they plan patient care and counsel caregivers and family of patients with dementia.”
Data analyzed in this study came from 2,422 individuals (59.7% male, mean age 74.4). Brain autopsy samples confirmed diagnoses of Alzheimer disease (AD) (n = 1,187), Lewy body dementia (LBD) (n = 331), or combined AD-LBD pathology (n = 904). The mean (± SD) interval from presentation to autopsy was 5.5 ± 2.8 years. Data from the Neuropsychiatric Inventory Questionnaire was used to determine severity of neuropsychiatric symptoms.