Blood markers may help predict dementia risk in Parkinson’s disease

Blood levels of certain protein markers previously linked to Alzheimer’s disease may help predict dementia risk in people with Parkinson’s disease, according to a new study.

Although the findings need to be confirmed in larger studies, the results suggest that these two markers, pTau217 and pTau231, may eventually help doctors better estimate future dementia risk in people with Parkinson’s.

“Our study identifies plasma pTau217 and pTau231 as powerful, independent predictors of dementia conversion in [Parkinson’s disease],” the researchers wrote.

“The integration of these blood-based biomarkers into clinical practice could significantly improve early risk stratification and inform the design of future disease-modifying trials targeting cognitive decline in Parkinson’s disease,” they added.

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An unedited, early-access version of the study, “Plasma pTau217 and pTau231 predict progression to dementia in Parkinson’s disease: a prospective longitudinal study,” was published in npj Parkinson’s Disease. 

Dementia refers to problems with thinking and memory that are severe enough to interfere with daily life. Alzheimer’s disease is the most common form of dementia.

Parkinson’s disease is primarily defined by its motor symptoms, but it can also cause nonmotor problems including changes in thinking and memory. In some people with Parkinson’s, these issues become severe enough to cause dementia, but the timing and course vary widely. Currently, doctors cannot accurately predict who will develop dementia or when, and that uncertainty can be stressful for patients and their families.

Several abnormal protein markers have been linked to Alzheimer’s disease. Researchers in Taiwan investigated whether these markers could also help predict dementia risk in people with Parkinson’s.

The study included 109 people with Parkinson’s who did not have dementia at the start of the study. Researchers collected blood samples to measure Alzheimer’s-associated biomarkers and followed the participants for an average of 5.1 years. During that time, 35 participants, or 32.1%, developed dementia.

The researchers used statistical models to test whether blood levels of any Alzheimer’s-related markers at the start of the study could help predict which participants would develop dementia during follow-up. Two markers, pTau217 and pTau231, were significantly associated with dementia risk and improved prediction beyond age, sex and education alone.

“Our main findings suggest the prognostic performance of [blood levels of] pTau217 and pTau231 in identifying the risk of dementia conversion in [people with Parkinson’s disease],” the scientists wrote. They noted that, in Alzheimer’s, these two markers “are among the most sensitive [and] earliest blood-based biomarkers for [Alzheimer’s-related damage] in the brain, even in the preclinical stage.”

Higher pTau levels tied to greater dementia risk

In the researchers’ models, patients with elevated pTau217 — defined as levels at or above 0.268 picograms/mL — developed dementia at more than five times the rate of those with lower levels over the follow-up period. Patients with the highest pTau217 levels, at or above 0.36 pg/mL, developed dementia at more than 11 times the rate of those with the lowest levels, below 0.2 pg/mL.

In models that accounted for age, sex and education, every 0.1 pg/mL increase in pTau217 levels was associated with a 24% increase in the rate of developing dementia.

Similarly, patients with high pTau231 levels, at or above 2.575 pg/mL, developed dementia at nearly four times the rate of those with lower levels. Those with the highest pTau231 levels developed dementia at nearly six times the rate of those with the lowest levels. Every 1 pg/mL increase in pTau231 was associated with a 25% increase in the rate of developing dementia.

The researchers also assessed neurofilament light chain (NfL), a well-established but nonspecific marker of nerve damage in Parkinson’s, Alzheimer’s, and other neurological diseases. NfL was less accurate than pTau217 and pTau231 at predicting dementia.

“While NfL remains a valuable marker for monitoring overall [nerve damage] progression, [pTau217 and pTau231] offer superior prognostic accuracy” for predicting dementia risk, they said.

The researchers noted that the study was conducted at a single center and had a relatively small sample size. As such, the team said that “validation in larger, multicenter populations is required to confirm the generalizability of our results.”