Blood Test May Help Predict Cognitive Decline in Parkinson’s, Study Shows

A blood test may be able to predict early cognitive decline in people with Parkinson’s disease by measuring the length of chromosomal telomeres (the “tips” of chromosomes) in immune cells and the presence of inflammatory markers, a study shows.

The study, “Senescence and Inflammatory Markers for Predicting Clinical Progression in Parkinson’s Disease: The ICICLE-PD Study,” was published in the IOS Press Journal of Parkinson’s Disease.

Cognitive impairment is a well-known non-motor symptom of Parkinson’s disease. Biological markers identifying those at highest risk of early cognitive decline may help better predict disease progression of newly diagnosed Parkinson’s patients. 

Telomeres are a protective region of DNA at the end of each chromosome that facilitates proper genome replication. As people age, the ends of telomeres shorten with each cell division. Telomere shortening and dysfunction can also be indicators of disease processes in the brain.

However, studies that have used telomere length as a marker for Parkinson’s incidence and progression have reported conflicting results. 

Telomere shortening in humans can also trigger cellular senescence, a process characterized by the irreversible shutdown of cell division, and the release of pro-inflammatory signaling proteins and tumor-suppressor proteins such as p21 and p16. 

The senescence of different types of brain cells is associated with neurodegeneration and inflammation, and while the potential of both p21 and p16 as biomarkers for age-related diseases has been investigated, their use as markers for Parkinson’s disease progression and early cognitive decline has not been explored. 

Thus, researchers based at Newcastle University, in the United Kingdom, designed a three-year study to compare the length of immune cell telomeres isolated from newly diagnosed Parkinson’s patients and healthy controls over time. The team also examined whether blood-derived markers of cell senescence and inflammation are associated with cognitive and motor function. 

The authors previously published work in 2016 about the Incidence of Cognitive Impairments in Cohorts with Longitudinal Evaluation-Parkinson’s Disease (ICICLE-PD) study, which found that inflammatory markers in the blood measured at diagnosis were linked to more rapid cognitive and motor decline.

Continuing this line of investigation, the team studied 154 newly diagnosed Parkinson’s patients who had been part of the ICICLE-PD study, along with 99 age- and gender-matched control subjects. The average age of both groups was around 67 years. 

The participants were assessed at 18-month intervals in which demographic information, blood samples, and cognitive and clinical data were collected. The average telomere length in immune cells and senescence markers p21 and p16 were measured at two time points, baseline and 18 months. An additional five inflammatory markers were also included from the first ICICLE-PD study.

The results revealed that Parkinson’s patients had significantly shorter telomere length at baseline compared to controls, and their telomere length shortened faster over the 18-month period. 

Over 36 months of follow-up, 11 Parkinson’s patients (15.5%) developed dementia. They had significantly shorter telomeres at baseline and at 18 months, compared to those without dementia.  

Significantly lower levels of p21 were found in Parkinson’s patients compared to controls at baseline, and there was no difference in change with time. The differences between the levels of p16 at baseline or the rate of change over time was not statistically significant. However, unexpectedly, higher p16 levels at baseline predicted slower motor and cognitive decline over 36 months. 

The examination of the five inflammatory markers found significantly higher levels of pro-inflammatory signaling proteins TNF-alpha and interleukin-10 in the Parkinson’s group than in the controls. 

A baseline composite inflammatory score based on all five markers found a significant difference between the groups as well. This score was able to predict cognitive decline at 36 months, consistent with the first ICICLE-PD study.

“In summary, our study demonstrates that telomere lengths at baseline and 18 months were lower in [Parkinson’s disease] patients compared to age-matched healthy controls with shorter telomere length at baseline and at 18 months also associated with development of dementia within 36 months,” the researchers wrote. 

“A baseline inflammatory score consisting of five different cytokines gave the best prediction for cognitive scores of [Parkinson’s disease] cases 3 years later, while lower p16 gene expression predicted a more rapid disease progression over the same period in relation to both cognitive and motor scores,” they added.

Of note, gene expression is the process by which information in a gene is synthesized to create a working product, such as a protein.

“The markers that we have identified need to be validated in further studies but could ultimately help with planning more targeted management for patients earlier in their disease course,” said lead investigator Gabriele Saretzki, PhD, in a press release.

“Furthermore, a better understanding of the biological changes that predict disease course has implications for possible future therapies for the disease,” she added.