Neuropsychiatric Symptoms, Alpha-Synuclein Levels May Help Distinguish Dementia-Related Diseases

Neuropsychiatric symptoms, combined with levels of alpha-synuclein, can be used to distinguish dementia with Lewy bodies from Parkinson’s disease dementia and Alzheimer’s disease, a study shows.

The study, “Neuropsychiatric symptoms and α-Synuclein profile of patients with Parkinson’s disease dementia, dementia with Lewy bodies and Alzheimer’s disease,” was published in the Journal of Neurology.

Lewy body dementia is the second most common type of degenerative dementia after Alzheimer’s disease. It includes two clinical diagnoses, dementia with Lewy bodies and Parkinson’s disease dementia, which share essentially the same array of symptoms, and are associated with the formation of Lewy bodies and subsequent nerve cell death. Lewy bodies are abnormal aggregates of alpha-synuclein protein that develop inside nerve cells.

Based on international consensus, when cognitive impairment begins within one year of the onset of parkinsonian motor signs, the patient is diagnosed with dementia with Lewy bodies, whereas the diagnosis is Parkinson’s disease if cognitive impairment develops more than a year after the appearance of motor symptoms.

Dementia with Lewy bodies, Parkinson’s disease dementia, and Alzheimer’s disease have similar behavioral and psychological symptoms, which can be challenging for an accurate diagnosis.

Researchers in this study evaluated whether neuropsychiatric symptoms and/or alpha-synuclein levels could be used to distinguish between these dementia-related disorders.

Between 2013 and 2015, the team recruited 63 participants, with a mean age of 71.5, from the register-based database of the Memory and Movement Disorder Inpatient Unit at Eginition University Hospital in Athens, Greece.

Of these patients, 28 had dementia with Lewy bodies, 19 had Alzheimer’s disease, and 16 had Parkinson’s disease dementia. Patients’ demographic and clinical characteristics were collected.

Neuropsychiatric symptoms were assessed through the 12-item Neuropsychiatric Inventory (NPI), a reliable instrument for screening the frequency of dementia-related behavioral symptoms, including delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, sleeping problems, and eating/appetite behavior.

Participants’ caregivers were interviewed by a trained neuropsychologist to assess NPI scores on the basis of observations within the past month.

Levels of alpha-synuclein were assessed in samples of cerebrospinal fluid — the fluid that fills the brain and spinal cord — of each patient.

Patients with Parkinson’s disease dementia and dementia with Lewy bodies had significantly more hallucinations than Alzheimer’s patients. Those who had dementia with Lewy bodies had significantly more agitation and sleeping problems than patients with Parkinson’s disease dementia and Alzheimer’s patients, respectively.

In fact, patients with dementia with Lewy bodies showed significantly higher total NPI scores and levels of alpha-synuclein than other patients.

Additional analysis showed that the combination of high burden of neuropsychiatric symptoms — reflected in elevated NPI scores — and increased levels of alpha-synuclein could strongly predict a diagnosis of dementia with Lewy bodies among all patients.

This suggests that these two parameters could be used to distinguish dementia with Lewy bodies from Parkinson’s disease dementia and Alzheimer’s disease.

“If verified in future studies, these novel findings could serve to pave the way for a more accurate diagnosis of DLB [dementia with Lewy bodies] based on the combination of biomarkers and neuropsychiatric profile,” the researchers wrote.