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Adaptive Immune Markers for Predicting Cognitive Decline in Parkinson’s Disease

Study Rationale:    
For reasons not well understood, people with Parkinson's disease are at risk for developing dementia, a decline in memory, thinking and/or language abilities severe enough to interfere with daily routines, job performance or social functions. The disease that begins with the loss of a small group of brain cells can eventually affect the entire brain. In this study, we aim to understand why the disease-related changes spread throughout the brain.

We hypothesize that in Parkinson's, the death of brain cells in one brain region can trigger a simmering immune response that attacks the brain and possibly causes dementia. If this is true, signs or markers of inflammation will be present in cerebrospinal fluid, which bathes the brain and the spinal cord. Because cerebrospinal fluid is much easier to examine than the brain itself, finding these markers would be important for understanding the inflammation-related changes in the brain.

Study Design:
Here we are using samples donated by participants with Parkinson’s and control volunteers to validate our previous results from two smaller studies. We will measure inflammation in people with Parkinson’s who enrolled in the study, underwent memory tests and donated blood and cerebrospinal fluid samples. We will test whether more inflammation occurs relative to dementia and whether more severe inflammation leads to a greater memory loss. We also hope to determine whether the severity of inflammation can predict the chance of developing dementia.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
If our hypothesis is correct, we will be able to use a simple test to identify people with Parkinson's who are at a greater risk for developing dementia. More importantly, we can diminish inflammation and possibly prevent dementia with available treatments.

Next Steps for Development:
If results of this study are convincing that inflammation can predict dementia, we will design clinical trials of possible treatments. If they are promising but not conclusive, we would test additional volunteers that enrolled in other studies prior to designing these clinical trials. We will test whether suppressing the immune response can prevent dementia in people whose memory is good and perhaps even stop the progression of dementia in those whose memory has already started to decline.


  • Marion S. Buckwalter, MD, PhD

    Stanford, CA United States

  • Kathleen Lombard Poston, MD, MS

    Stanford, CA United States

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