Michael J Fox Foundation     March 17, 2014

Alpha-synuclein — the protein that clumps in the cells of Parkinson’s patients — is currently the major focus of Parkinson’s biomarker studies. Researchers are analyzing biosamples (spinal fluid, blood, tissue) to make a connection between alpha-synuclein and risk, onset or progression of Parkinson’s disease (PD). The latest findings, published in The American Journal of Pathology, report that patients with higher levels in spinal fluid experienced faster cognitive decline.

In a project funded by The Michael J. Fox Foundation (MJFF), Jing Zhang, MD, PhD, and his team at the University of Washington in Seattle examined samples and data from PD patients obtained in the DATATOP study. Led by the Parkinson’s Study Group in the late 1980s, the deprenyl and tocopherol antioxidative therapy of parkinsonism (DATATOP) study collected samples and clinical data from PD subjects for up to eight years.

In this latest analysis, researchers compared alpha-synuclein levels to scores from tests of cognition, such as verbal learning and memory, visuospatial memory and processing speed, among 304 PD patients. They found that patients with higher levels of alpha-synuclein in spinal fluid had faster cognitive decline.

“This is a surprising conclusion,” says Mark Frasier, PhD, MJFF vice president of research programs. “One would think that people with more cognitive problems would have less alpha-synuclein in spinal fluid because more would be caught up in the brain causing those problems.”

Zhang’s group also reported that while alpha-synuclein levels decreased significantly over two years, that decline could not predict motor symptoms. These findings join a list of observations about how alpha-synuclein in spinal fluid relates to PD. Initial analysis from the MJFF-sponsored Parkinson’s Progression Markers Initiative (PPMI) reported last year that PD patients had lower alpha-synuclein levels in spinal fluid compared to controls. They also found that patients with posture/gait disturbance averaged lower alpha-synuclein than patients with tremor-dominant PD.

Further investigation into alpha-synuclein continues in PPMI and other studies. Zhang and his coauthors cited PPMI as a potential source for validation of their cognition findings. Since PPMI includes healthy controls, researchers could test whether those results are PD-specific or seen in healthy aging adults with cognitive decline, too.

.Parkinson's

 " GRAIN BRAIN" by David Perlmutter.
There are a variety of pharmaceutical interventions offered up for Parkinson’s patients. And each day when I’m seeing a new patient with this disease one of the first questions I ask is, “What are you doing to treat this disorder?"
I typically get a list of drugs, dosages and how often the pills are taken. It’s then that I feel compelled to explain that the potpourri of pills that they’ve been given actually do not treat the disease at all. They simply manage the symptoms. And this distinction is fundamentally important. By and large, giving symptom-managing medications to Parkinson’s patients is about as far as the standard doctor-patient interaction goes. And that’s like treating the smoke and ignoring the fire.
It turns out that lifestyle choices are critically influential in determining how rapidly a patient’s functionality will decline over the longer term. So while medications that can help with the Parkinsonian tremor and rigidity clearly have their place, physicians need to look at the broader picture and ask themselves what information they can provide to patients that can help preserve their ability to participate in life’s activities in the longer term. Recently, an important brain protective chemical was identified that is associated with a dramatic slowing of decline in Parkinson’s patients. This novel chemical has been shown to provide aggressive brain antioxidant protection, helping to reduce the damaging effects of villainous toxins called free radicals. What’s more, it has been discovered that this brain protective substance actually serves as the precursor for such brain supportive chemicals as vitamin D, estrogen, progesterone, and testosterone. It is called cholesterol. Yes, the very same cholesterol that has been demonized for decades as the cause of everything from heart attacks to who-knows-what is actually one of the most important players in brain health. Specifically in relation to Parkinson’s disease, a recent study published by researchers from Pennsylvania State University and Harvard revealed a direct relationship between higher cholesterol levels and slowing in the rate of decline in the 744 Parkinson’s patients they followed. Those whose cholesterol levels were the highest faired significantly better and maintained higher levels of functionality in the long run. We need to take notice of reports like this, as this kind of information will no doubt lead to changes in how we respond to advertisements in medical journals calling for us do everything we can to “aggressively lower cholesterol.” We’ve got to pay attention when the FDA mandates warnings on cholesterol-lowering statin drugs indicating they can affect brain function (as they rightly did in 2012).
As a practicing neurologist, I’m grateful to have medicines that can help control symptoms of Parkinson’s disease. But more needs to be done to gain a fuller understanding of the processes that underlie the actual brain degeneration. And now that this information is coming to light, patients deserve to know the full story. Knowledge is empowering, especially as it relates to putting out the fire. So here are some ideas for Parkinson’s patients to discuss with their treating physicians: 1. Ask one simple question: “Do I really need to lower my cholesterol?” 2. Don’t refrain from foods that contain cholesterol like grass-fed beef, free range chicken, and even free-range eggs. 3. Add supplemental fats to your diet like extra virgin organic olive oil, nuts, seeds, and coconut oil. Add Coenzyme Q10, a nutritional supplement, to your program. We generally recommend at least 400mg daily. Research confirms that this supplement slows the decline in Parkinson’s patients. 4. Reduce carbohydrates in your diet. 5. Get regular aerobic exercise, and concentrate on exercises that move opposite sides of your body in rapid succession like using an elliptical machine.

               6. Make sure you take enough vitamin d to get your blood level up to

 5000 or even 10,000 units of vitamin D3 daily. 

David Perlmutter from his book Grain Brain.


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