According to a new study, the levels of three different proteins found in cerebrospinal fluid, when analyzed together, may be useful in diagnosing Parkinson’s disease (PD). This panel of test results also may help predict whether people with early-stage PD are likely to develop dementia. The results appear in the August 10 online edition of JAMA Neurology.
Doctors diagnose PD by observing a person’s symptoms. But early in the course of disease, it can be difficult to distinguish PD from other, related movement disorders, and to date there is no blood test, scan or other measurement for making a definitive diagnosis. The need for such biomarkers is urgent.
Cerebrospinal fluid is a clear fluid that bathes the brain and spinal cord. A doctor can safely withdraw a tiny amount of the fluid in a procedure called a lumbar puncture or spinal tap. Earlier studies have suggested that several substances found in cerebrospinal fluid might be useful biomarkers both for diagnosing PD and for understanding how dementia — a common nonmotor symptom — develops over the course of the disease.
For the new study, researchers led by David C. Bäckström, M.D., at Umeå University in Sweden, took samples of cerebrospinal fluid from 128 people who came to their clinic with newly diagnosed PD and PD-like diseases, and who had normal cognitive abilities. They measured levels of six potential biomarkers in the fluid, and analyzed them both individually and in combination to look for patterns associated with PD and with dementia. They assessed study participants’ PD every year for between five and nine years, and tested their cognition in detail after one, three and eight years. For comparison, the researchers also collected cerebrospinal fluid from 30 healthy volunteers.
- Based on standard clinical tests, 104 people were diagnosed with Parkinson’s; 11 with multiple system atrophy, and 13 with progressive supranuclear palsy. (These two diseases are considered Parkinson’s plus syndromes).
- The people with early PD had different levels of particular proteins in their cerebrospinal fluid compared with those who had progressive supranuclear palsy and the control participants.
- The researchers found a pattern of three proteins (when participants entered the study) that were associated with a later development of dementia in PD. These protein biomarkers were high levels of neurofilament light chain protein, heart fatty acid–binding protein at baseline and low levels of the Aβ1-42 protein. Combined, these early biomarkers were able to predict the future development of dementia, retrospectively.
What Does It Mean?
The search for biomarkers for PD is an intense area of research. Early accurate diagnosis of PD would help ensure that people get the care they need early in the course of disease. Future therapies to help cognition in PD are likely to be most beneficial when given early, so being able to identify people at risk for dementia is important. In addition, a biomarker for predicting dementia risk would help in the search for new therapies – people with the marker would be most likely to benefit from them, and could be selected as participants in clinical trials for potential neuroprotective therapies.
Before these tests can be used in the doctor’s offices – for example, for people with unclear diagnosis of PD or for those with PD who would want to know their future risk of cognitive impairment – additional research is needed to replicate the findings in additional longitudinal cohorts. That said, the results suggest that analyzing cerebrospinal analysis can aid in diagnosing PD and may one day alert physicians to a person’s risk of developing dementia.
Bäckström DC, Domellöf ME, Linder J, et al. (2015). Cerebrospinal fluid patterns and the risk of future dementia in early, incident Parkinson disease. JAMA Neurology 2015, 72(10):1175-1182. doi:10.1001/jamaneurol.2015.1449