[ZucchiniFlower]

Two Distinct Parkinson's Networks Identified

Science Daily — The disease that causes tremors, rigidity and slowed movements in a million Americans also targets another brain network that regulates cognitive thought and the ability to carry out everyday tasks.


David Eidelberg, MD, head of the Center for Neurosciences at The Feinstein Institute for Medical Research, and his colleagues measured and quantified this network of brain regions during a five-year study of newly diagnosed Parkinson's patients who agreed to be followed several times over the course of the study. This is the first longitudinal study of Parkinson's disease using a brain scan to follow these Parkinson's network over time.

The technology is now precise enough to diagnose the two brain networks -- one that regulates movement and the other cognition -- in individuals, and Dr. Eidelberg said that it could be used to assess the degenerative disease process and the person's response to treatments. The study also shows that the standard drugs used to treat Parkinson's alter the areas that are involved in movement but not those that regulate cognition.

The network that grows abnormal over time includes an called the pre-frontal cortex, known as the brain's executive secretary; organizing, planning and carrying out tasks in order of importance. It's the same region that is hard-hit in mild cognitive impairment, the precursor to Alzheimer's dementia. But Eidelberg said that the symptoms in the two diseases are quite different. But thinking that medicines used for Alzheimer's might help normalize this network, the scientists gave Parkinson's patients eight weeks of treatment. It didn't work.

"We really don't know precisely what's going on in this newly-identified network, but we can begin to ask questions and figure it out," said Dr. Eidelberg."We don't even know whether this network can be fixed."

In 1999, the researchers recruited 15 patients with early stage Parkinson's and signed them on to get brain scans at different points throughout the study. Some were on medicines and some were not. The first networks to be identified were no surprise: The basal ganglia, thalamus and brain stem that regulate movement. The scans they used measured glucose metabolism -- the brain's fuel -- and identified areas in this motor network that showed decreased metabolic activity and some areas that had increased metabolic activity. Over time, the cognitive network became apparent. And as the disease progressed and symptoms worsened, this network also took its toll.

"The circuits are like a fingerprint of the disease," Dr. Eidelberg said. "As the disease gets worse, the fingerprint is much easier to identify." The circuits are the same in all Parkinson's patients, he added. They are now testing other treatments, including deep brain stimulation, to see if it can impact on the cognitive network. "The cognitive problems are real and have to be addressed," he added. "The medicines for Parkinson's don't seem to do anything to alter these networks and we need new ones to target these symptoms."

He said that the networks could be used as biomarkers to diagnose the disease. The scientists have also developed mathematical computer models to determine how fast the disease will progress. "These scanning techniques may be helpful in determining what treatments work and what don't."

The new report appears in an online version in the journal Brain, and will be published soon in a print version.

http://brain.oxfordjournals.org/cgi/...ull/130/7/1787

[ZucchiniFlower]

Not all PD is the same! People with LRRK2 mutations, for example, usually don't have severe cognitive problems.

Summary


We have previously performed detailed clinical and neuropsychological assessments in a community-based cohort of patients with newly diagnosed parkinsonism, and through analysis of a subcohort with idiopathic Parkinson's disease (PD), we have demonstrated that cognitive dysfunction occurs even at the time of PD diagnosis and is heterogeneous. Longitudinal follow-up of the cohort has now been performed to examine the evolution of cognitive dysfunction within the early years of the disease.

One hundred and eighty (79%) eligible patients from the original cohort with parkinsonism were available for re-assessment at between 3 and 5 years from their initial baseline assessments. PD diagnoses were re-validated with repeated application of the UKPDS Brain Bank criteria in order to maximize sensitivity and specificity, following which a diagnosis of idiopathic PD was confirmed in 126 patients. Thirteen out of 126 (10%) had developed dementia at a mean (SD) of 3.5 (0.7) years from diagnosis, corresponding to an annual dementia incidence of 30.0 (16.4–52.9) per 1000 person-years.

A further 57% of PD patients showed evidence of cognitive impairment, with frontostriatal deficits being most common amongst the non-demented group. However, the most important clinical predictors of global cognitive decline following correction for age were neuropsychological tasks with a more posterior cortical basis, including semantic fluency and ability to copy an intersecting pentagons figure, as well as a non-tremor dominant motor phenotype at the baseline assessment.

This work clarifies the profile of cognitive dysfunction in early PD and demonstrates that the dementing process in this illness is heralded by both postural and gait dysfunction and cognitive deficits with a posterior cortical basis, reflecting probable non-dopaminergic cortical Lewy body pathology.

Furthermore, given that these predictors of dementia are readily measurable within just a few minutes in a clinical setting, our work may ultimately have practical implications in terms of guiding prognosis in individual patients.

[michael7733]

What about those of us who seem to have gotten both packages? I guess I'll be both shaky and cognitively impaired. Will the fun never end? Break out the party hats, and put on some music. My mamma said there would be days like this. Ah well...life goes on.

micha...how do I spell my name?...

[Howardh]

article Zuc...In summary it looks like our disease is no stairway to heaven...On ya Led Zep

GO HARD.......SCIENCE

[AnnT2]

I wonder how much of the cognitive deficits attributed to Parkinson's Disease are actually the result of sleep deprivation caused by Parkinson's. I know I rarely if ever sleep more than six hours since I have had PD. What do you think?

Ann

[ZucchiniFlower]

Ann,

Cognition problems in PD seem to appear because of real changes in the brain. SPECT scans and other scans show differences in PDers with cognition problems and those without them.

Lack of sleep sure doesn't help though. I sleep well. Perhaps it's my tricyclic antidepressant (doxepin) that helps. If I do awaken in the night, I fall asleep immediately.

My main cognition problem is a worsening of my short term memory, which I believe is caused by the artane I take, which reduces my acetylcholine.
The only time it bothers me is when I'm flipping through channels with my remote, and I forget what I was watching.

[oyster]

i had a spect scan a couple months before my pd dx. i would like to compare them with these scans that show pd. i will google it.