Specific Biomarkers May Help to Distinguish Parkinson’s Dementia from Dementia with Lewy Bodies

José Lopes, PhD avatar

by José Lopes, PhD |

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The levels of specific protein biomarkers in the cerebrospinal fluid (CSF) — the liquid surrounding the brain and spinal cord — can distinguish patients with Parkinson’s disease dementia (PDD) from those with dementia with Lewy bodies (DLB) regardless of dementia stage, according to a new study.

The research, “Cerebrospinal fluid markers analysis in the differential diagnosis of dementia with Lewy bodies and Parkinson’s disease dementia,” appeared in the journal European Archives of Psychiatry and Clinical Neuroscience.

Brain protein clumps known as Lewy bodies are characteristic of both Parkinson’s and DLB.

Current practice gives a DLB diagnosis if dementia occurs before or during the first year of parkinsonism, a general term for neurological disorders that cause movement problems similar to those of Parkinson’s patients.

As such, a follow-up is essential to differentiate between PDD and DLB. However, the overlap of clinical symptoms and the difficulty in establishing when specific symptoms start make this distinction challenging and impacts treatment.

A percentage of DLB cases share a varying extent of pathological features with Alzheimer’s. But, unlike in that disease, no specific CSF biomarkers  have been validated for DLB and PDD. Researchers, for this reason, assessed the diagnostic potential of widely accepted CSF biomarkers across dementia stages to differentiate between DLB and PDD.

A total of 136 patients, all being treated at University Medical Center, Göttingen, Germany, underwent routine laboratory testing and a spinal tap to collect CSF. Cognitive examinations were preformed using the Mini-Mental State Exam (MMSE), and 65% of these patients were also tested with the Montreal Cognitive Assessment (MoCA), and the Clinical Dementia Rating (CDR).

The group included 51 people (31 men) with a diagnosis of probable DLB — 6 later confirmed — 53 with Parkinson’s, and 32 who were cognitively intact. Thirty-one of the Parkinson’s patients met the criteria for PDD (16 women and 15 men). Patients exhibiting dementia were classified as mild, moderate or severe.

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CSF samples were tested for the proteins amyloid-beta1–42, tau, phoshorylated tau (a modified form of the tau protein), neuron-specific enolase (NSE) — a predictor of severity and neurobehavioral outcome after acute stroke, and implicated in Alzheimer’s — and S100B, a marker of brain damage. Of note, both amyloid-beta and phoshorylated tau form clumps in the brains of Alzheimer’s and Parkinson’s patients.

Levels of tau and amyloid-beta1–42, as well as the phosphorylated tau/total tau ratio were helpful in distinguishing between DLB and Parkinson’s patients with or without dementia.

Specifically, tau levels were higher in DLB than in Parkinson’s patients regardless of cognitive status, and were also higher in Parkinson’s patients with dementia than those without it.

DLB patients had lower levels of both amyloid-beta1–42 and phosphorylated tau/total tau ratio than did Parkinson’s dementia patients. This ratio was lower in DLB patients with mild and moderate dementia.

Levels of tau and phosphorylated tau protein in patients’ CSF reflected the severity of dementia in both DLB and PDD patients. Tau ratio enabled a distinction between Parkinson’s patients with mild and moderate dementia, and was lower in those with severe dementia than those with mild dementia.

Lower levels of amyloid-beta1–42 correlated with a rapid disease course in DLB but not in PDD. Both DLB and Parkinson’s patients with dementia showed elevated levels of S100B in comparison to healthy controls — indicating brain damage.

For both DLB and PDD, patients with less than a year of disease duration showed a trend toward higher tau, phosphorylated tau and NSE as opposed to lower amyloid-beta1–42  when compared to those whose disease had been diagnosed earlier.

Nevertheless, only values for amyloid-beta1–42 were lower in DLB patients whose dementia was confirmed less than one year after their primary diagnosis, compared to those diagnosed with PDD.

“These results have clinical relevance by suggesting that the descent of CSF [amyloid-beta1–42] values mainly in rapid disease course might have a prognostic significance,” the researchers wrote.

“[W]e conclude that CSF profile with the appropriate clinical context could be effective in distinguishing DLB from PDD patients, regardless of the severity of dementia,” they added.

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