Early Symptoms May Predict Future Psychosis in Parkinson’s Patients, Study Finds

Early sleep-related and autonomic symptoms — related to automatic or involuntary body functions — are associated with an increased risk of future psychotic symptoms in Parkinson’s disease patients, according to a recent study.

These symptoms are also associated with a reduction of specific nerve cells in a region of the brain involved in memory, attention, and perception — suggesting these changes could be used as a biomarker to predict psychosis in Parkinson’s patients.

The study, “Baseline symptoms and basal forebrain volume predict future psychosis in early Parkinson disease,” was published in the journal Neurology.

The non-motor symptoms of Parkinson’s disease include cognitive declines; psychiatric disturbances, such as psychosis and depression; autonomic symptoms, related to gastrointestinal, heart, urinary, sexual, and thermoregulation functions; sleep difficulties; and pain.

Psychotic symptoms are a marker of advanced Parkinson’s disease, and strongly reduce the quality of life of patients and caregivers. Identifying baseline predictors of future psychotic symptoms may help identify patients at risk of a more rapidly progressive disease, and provide effective and preventive treatment.

Degeneration or volume reduction of the nucleus basalis of Meynert (NBM) — an area of the brain related to memory, attention, and perception — has been linked to Parkinson’s.

Loss of nerve cells, known as Ch4 nerve cells, which produce acetylcholine — a chemical messenger used for communication between nerve cells — in the NBM region has been associated with cognitive and psychiatric symptoms of Parkinson’s.

University of Virginia researchers studied a group of patients with newly diagnosed, untreated Parkinson’s to identify baseline clinical risk factors for future psychotic symptoms and to investigate the association between the density of Ch4 cells — an indirect measure of NBM volume — and future development of psychotic symptoms.

The study involved 423 untreated Parkinson’s patients, who did not have dementia at the time of enrollment, and 101 healthy individuals included in the Parkinson’s Progression Markers Initiative (PPMI) — a prospective, longitudinal, observational study to identify biomarkers of Parkinson’s progression.

Assessment of Parkinson’s symptoms was performed at the beginning of the study, every three months during the first year, and every six months from one to five years, based on the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). This scale includes an item focused on psychotic symptoms, where a score above zero is considered indicative of these issues.

At the study’s start, researchers also assessed patients’ autonomic symptoms using the Scales for Outcomes in Parkinson’s Disease-Autonomic (SCOPA-AUT), and sleep-related symptoms, such as REM sleep behavior disorder (RBD), through the RBD screening questionnaire, and excessive daytime sleepiness, through the Epworth Sleepiness Scale.

Ch4 cells’ density at baseline was determined for 228 Parkinson’s patients and 101 controls, using brain magnetic resonance imaging (MRI) data from the PPMI database.

Patients’ mean age at enrollment was approximately 61.5 years old, and about one-third of the patients were women. The last visit occurred at a median of 54 months after the start of the study.

The presence of more autonomic symptoms, REM sleep behavior disorder, and excessive daytime sleepiness at baseline was associated with an increased risk for experiencing psychotic symptoms on two or more occasions.

“Our finding that these 3 nonmotor symptoms are linked to future psychotic symptoms validates the prognostic value of these symptoms in predicting worse outcomes early in disease,” the researchers wrote.

Lower Ch4 density was associated with the presence of two to three of these symptoms at baseline, as well as with patients who later reported psychotic symptoms.

“The relationship between this triad of clinical symptoms and lower Ch4 density supports the potential utility of this neuroimaging biomarker to […] predict more rapid disease progression,” the researchers concluded.