Mild cognitive impairment at Parkinson disease diagnosis linked with higher risk for early dementia

Mar. 25, 2013 — Mild cognitive impairment at the time of Parkinson disease (PD) diagnosis appears to be associated with an increased risk for early dementia in a Norwegian study, according to a report published Online First by JAMA Neurology, a JAMA Network publication.

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Patients with PD have an increased risk for dementia (PDD) compared with healthy individuals and researchers sought to examine the course of mild cognitive impairment (MCI) and its progression to dementia in a group of patients with PD. The Norwegian ParkWest study is an ongoing population-based study of the incidence, neurobiology and prognosis of PD in western and southern Norway, according to the study background.

The study by Kenn Freddy Pedersen, M.D., Ph.D., of Stavanger University Hospital, Norway, included 182 patients with PD monitored for three years. More patients with MCI than without MCI at baseline (10 of 37 [27 percent] vs. 1 of 145 [0.7 percent]) progressed to dementia during follow-up. Of those with MCI at baseline, 8 of 37 (21.6 percent) had MCI that reverted to normal cognition during follow-up, according to the study results.

The results also show that mild cognitive impairment at the one-year visit was associated with a similar progression rate to dementia (10 of 36 patients [27.8 percent] and reversion rate to normal cognition (7 of 36 [19.4 percent]). Of the 22 patients with persistent MCI at baseline and the one-year visit, 10 (45.5 percent) developed dementia and only two (9.1 percent) had MCI that reverted to normal cognition by the end of the study.

"This prospective population-based study of an incident PD cohort demonstrates that MCI within the first year of PD diagnosis signals a highly increased risk for early incident dementia. More than 25 percent of patients with MCI at diagnosis of PD developed dementia within three years of follow-up compared with less than 1 percent of patients without MCI at PD diagnosis. Among patients with MCI at baseline and one year of follow-up, almost half progressed to dementia. These findings support the validity of the MCI concept in patients with early PD," the study authors conclude.

Editorial: Can Mild Cognitive Impairment in Parkinson Predict Dementia

In a related editorial, Brian J. Copeland, M.D., and Mya C. Schiess, M.D., of the University of Texas Medical School at Houston, write: "The term mild cognitive impairment (MCI) emerged in the 1990s, defining a transition state from normal cognitive function and forcing our appreciation of cognitive changes not attributable to age, education, sex, race, ethnicity, language, or culture, but rather to a well-defined disease process or related pathology."

"Cognitive impairment in PD is common, and the use of uniform criteria for the PD-MCI diagnosis is important in furthering research, predicting the development of dementia, and developing clinical trials to test therapeutic interventions. Stable PD-MCI over time may be a prognostic factor in the later development of PDD. However, the findings from the study by Pedersen and colleagues are based on a homogenous population of patients with early PD, and generalization of the results is uncertain," they conclude.

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Blood biomarker could mark severe cognitive decline, quicker progression among Parkinson’s patients

Sep. 18, 2013 — A genetic mutation, known as GBA, that leads to early onset of Parkinson’s disease and severe cognitive impairment (in about 4 to 7 percent of all patients with the disease) also alters how specific lipids, ceramides and glucosylceramides are metabolized. Mayo Clinic researchers have found that Parkinson’s patients who do not carry the genetic mutation also have higher levels of these lipids in the blood. Further, those who had Parkinson’s and high blood levels were also more likely to have cognitive impairment and dementia. The research was recently published online in the journal PLOS ONE.

 

The discovery could be an important warning for those with Parkinson’s disease. Parkinson’s is the second most common neurodegenerative disease after Alzheimer’s disease. There is no biomarker to tell who is going to develop the disease -- and who is going to develop cognitive impairment after developing Parkinson’s, says Michelle Mielke, Ph.D., a Mayo Clinic researcher and first author of the study.

Cognitive impairment is a frequent symptom in Parkinson’s disease and can be even more debilitating for patients and their caregivers than the characteristic motor symptoms. The early identification of Parkinson’s patients at greatest risk of developing dementia is important for preventing or delaying the onset and progression of cognitive symptoms. Changing these blood lipids could be a way to stop the progression of the disease, says Dr. Mielke.

There is a suggestion this blood lipid marker also could help to predict who will develop Parkinson’s disease and this research is ongoing.

“There is currently no cure for Parkinson’s, but the earlier we catch it -- the better chance we have to fight it,” says Dr. Mielke. “It’s particularly important we find a biomarker and identify it in the preclinical phase of the disease, before the onset even begins.”

Dr. Mielke’s lab is researching blood-based biomarkers for Parkinson’s disease because blood tests are less invasive and cheaper than a brain scan or spinal tap -- other tools used to research the disease.

 

Higher vitamin D levels associated with better cognition, mood in Parkinson's disease patients

Jan. 16, 2014 — A new study exploring vitamin D levels in patients with Parkinson's disease (PD) opens up the possibility of a new avenue of early intervention that may delay or prevent the onset of cognitive impairment and depression. The findings are published in the Journal of Parkinson's Disease.

Investigators conducted a cross-sectional analysis of 286 patients with PD and found that higher plasma vitamin D levels were associated with lower symptom severity, better cognition, and less depression in the entire group, but the relationships were even stronger in those who were not demented.

"About 30% of persons with PD suffer from cognitive impairment and dementia, and dementia is associated with nursing home placement and shortened life expectancy," says Amie L. Peterson, MD, of the Oregon Health and Sciences University. "We know mild cognitive impairment may predict the future development of dementia. Intervening in the development of dementia has the potential to improve morbidity and mortality in persons with PD."

In this analysis, which was an add-on study to an ongoing longitudinal study of neuropsychiatric function in people with PD, patients were given a battery of tests measuring global cognitive function, verbal memory, semantic verbal fluency, executive function, and depression. On the same day, serum 25-hydroxyvitamin D levels were measured. Of the 286 subjects, 61 were considered to be demented by a consensus panel based on the Diagnostic and Statistical Manual of the American Psychiatric Association (4th edition) and 225 were not demented.

For the entire group, significant negative associations were found between vitamin D levels and disease severity, as measured both by the Hoehn and Yahr Scale and the United Parkinson's Disease Rating Scale motor section. Mean vitamin D3 levels were higher in those who were not demented, although the differences did not reach statistical significance.

Investigators found that for the entire group, higher levels of serum vitamin D3 were associated with greater fluency for naming vegetables and animals and immediate and delayed recall on a verbal learning test. When the group was divided into those who were demented or not, significant findings with vitamin D were found for fluency and verbal learning only for those who were not demented. "The fact that the relationship between vitamin D concentration and cognitive performance seemed more robust in the non-demented subset suggests that earlier intervention before dementia is present may be more effective," says Dr. Peterson.

A significant negative association was also found for vitamin D levels and depression, as measured by the Geriatric Depression Scale, for both the entire group and those who were not demented. No significant relationship was found for those who were demented.

The authors point out that a cross-sectional study cannot determine causation: for instance, does low vitamin D affect cognitive performance, or are persons with more advanced PD and worse cognition less ambulatory, get less sun exposure, and subsequently have lower vitamin D? The study also did not consider if patients were taking vitamin D supplements.

Vitamin D's role in health has been a subject of considerable scrutiny in recent years. Low levels increase the risk of type 2 diabetes mellitus, multiple sclerosis, hypertension, cancer, and infections. Vitamin D receptors and its final converting enzyme have been found in human brain tissue, including the hippocampus, which plays a significant role in memory and learning.

PD is the second most common neurodegenerative disorder in the United States, affecting approximately one million Americans and five million people worldwide. Its prevalence is projected to double by 2030. The most obvious symptoms are movement-related, such as involuntary shaking and muscle stiffness. Non-motor symptoms, such as worsening depression, anxiety, and sleep disturbances, can appear prior to the onset of motor symptoms.

 

The DDT Story

The DDT Story

DDT Spray

If there is a single pesticide almost everyone can name, it's DDT.

DDT was one of the first chemicals in widespread use as a pesticide. Following World War II, it was promoted as a wonder-chemical, the simple solution to pest problems large and small. Today, nearly 40 years after DDT was banned in the U.S., we continue to live with its long-lasting effects:

·         Food supplies: USDA found DDT breakdown products in 60% of heavy cream samples, 42% of kale greens, 28% of carrots and lower percentages of many other foods.

·         Body burden: DDT breakdown products were found in the blood of 99% of the people tested by CDC.

·         Health impacts: Girls exposed to DDT before puberty are 5 times more likely to develop breast cancer in middle age, according to the President’s Cancer Panel.

Banned for agricultural uses worldwide by the 2001 Stockholm Convention on Persistent Organic Pollutants, the use of DDT is still permitted in small quantities in countries that need it, with support mobilized for the transition to safer and more effective alternatives. The treatment of DDT under the Stockholm Convention is strongly supported by PAN and our international partners.

Rachel Carson highlighted the dangers of DDT in her groundbreaking 1962 book Silent Spring. Carson used DDT to tell the broader story of the disastrous consequences of the overuse of insecticides, and raised enough concern from her testimony before Congress to trigger the establishment of the Environmental Protection Agency (EPA).

Her work attracted outrage from the pesticide industry and others. Her credibility as a scientist was attacked, and she was derided as “hysterical,” despite her fact-based assertions and calm and scholarly demeanor. Following the hearings, President Kennedy convened a committee to review the evidence Carson presented. The committee's review completely vindicating her findings.

One of the new EPA's first acts was to ban DDT, due to both concerns about harm to the environment and the potential for harm to human health. There was also evidence linking DDT with severe declines in bald eagle populations due to thinning eggshells. Since DDT was banned in the U.S., bald eagles have made a dramatic recovery. 

Recently, Carson's work has again been targeted by conservative groups. Capitalizing on the iconic status of DDT, these groups are promoting widespread use of the chemical for malaria control as part of a broader effort to manufacture doubt about the dangers of pesticides, and to promote their anti-regulatory, free market agenda while attempting to undermine and roll back the environmental movement's legacy.

Many DDT promoters are also in the business of denying climate change.

Attacks on Carson from groups like The Competitive Enterprise Institute and Africa Fighting Malaria portray DDT as the simple solution to malaria, and blame Carson for “millions of deaths in Africa.” Many of these DDT promoters are also in the business of denying climate change and defended the tobacco industry by denying the health harms of smoking.

Human Health Harms

The science on DDT's human health impacts has continued to mount over the years, with recent studies showing harm at very low levels of exposure. Studies show a range of human health effects linked to DDT and its breakdown product, DDE:

·         breast & other cancers

·     male infertility

·     miscarriages & low birth weight

·     developmental delay

·     nervous system & liver damage

No 'Silver Bullet' for Malaria Control

The only remaining legal use of DDT is to control malaria-carrying mosquitoes. A devastating disease, malaria kills more than 800,000 people every year, the majority of deaths among children in Sub-Saharan Africa. Indoor spraying with DDT is one of a number of tools being used to control malaria around the world. Only in rare cases is it the most effective choice. 

Successful malaria control programs have been built all over the world using a variety of approaches that are affordable and appropriate to local needs. All include community involvement, appropriate technology and investment in public health capacity and education. These community-based, integrated solutions have proven successful in places as diverse as Mexico, Kenyaand Vietnam.

Unfortunately, vocal groups such as Africa Fighting Malaria continue to promote a simplistic "DDT or nothing" debate, ignoring on-the-ground evidence from around the world that more effective approaches are saving lives without putting communities in harm's way from exposure to the long-lasting chemical.

PAN works with international allies, governments and on-the-ground groups in Africa to mobilize resources and political will to combat malaria, and remains active in international legal processes to support the global phase out of DDT and promote the safest and most effective malaria control solutions. 

THE PREVALENCE OF MUSCULOSKELETAL PROBLEMS IN PARKINSON'S DISEASE

8th January 2014 - New research

Parkinsonism Related Disorders [2013] 19 (7) : 666-669 (Y.E.Kim, W.W.Lee, J.Y.Yun, H.J.Yang, H.J.Kim, B.S. Jeon)

The prevalence of musculoskeletal problems was found to be significantly higher Parkinson's Disease. Around two thirds of people with Parkinson's Disease have them. Only just over a quarter of people with Parkinson's Disease answered that their musculoskeletal problems were recovering.  Musculoskeletal problems also tended to receive less treatment when people had Parkinson's Disease.

Common sites of musculoskeletal problems were the lower back, shoulder and knee in that order. The lower back was the site of musculoskeletal problems in nearly half of people with Parkinson's Disease. The shoulder and knee were affected far less often. Among the past diagnoses associated with musculoskeletal problems, frozen shoulder, low back pain, osteoporosis and fracture were more common in people with Parkinson's Disease. Older age, being female, and having a higher score on the Unified Parkinson's Disease Rating Scale were associated with more musculoskeletal problems. 

L-DOPA PRODRUG FOR PARKINSON'S DISEASE

Movement Disorders [2013] Dec 13 [Epub ahead of print (P.A.Lewitt, F.J.Huff, R.A.Hauser, D.Chen, D.Lissin, K.Zomorodi, K.C.Cundy)  
XP21279 is a new L-dopa prodrug being developed by Xenoport for the treatment of Parkinson's Disease. It uses naturally occurring, high capacity nutrient transporters in the gastrointestinal tract to generate active and efficient absorption into the body.
XP21279-carbidopa sustained-release bilayer tablets were developed to provide more continuous exposure to L-dopa. Once absorbed, XP21279 is rapidly converted into L-dopa. In a clinical trial of XP21279, people with Parkinson's Disease were given either XP21279 with carbidopa, or L-dopa with carbidopa, which as Sinemet is the most common means of treating Parkinson's Disease.

The average daily off time was reduced more when using XP21279 but only by 18 minutes. There was little difference between the two in their effect on dyskinesia. However, XP21279 significantly reduced the variability of L-dopa concentration that occurs when using Sinemet (L-dopa and carbidopa). This was achieved by taking XP21279 only three times per day, instead of the four to five times a day that the L-dopa with carbidopa was taken. Therefore, overall, although L-dopa and carbidopa as Sinemet is the most common means of treating Parkinson's Disease, XP21279 was found to be more advantageous. 

FEMALE REPRODUCTIVE FACTORS AND THE RISK OF PARKINSON'S DISEASE

28th December 2013 - New research
SON'S DISEASE
Movement Disorders [2013] Dec 18 [Epub ahead of print] (R.Liu, D.Baird, Y.Park, N.D.Freedman, X.Huang, A.Hollenbeck, A.Blair, H.Chen) 
In the largest ever study of its kind, researchers examined female reproductive factors and the risk of Parkinson's Disease. The study involved nearly 120,000 postmenopausal women aged 50 to 71 years.  The risk of developing Parkinson's Disease was not significantly associated with female reproductive factors including age at first menstruation, age at first live birth, and age at menopause generally.

However, there was a tendency for an increased risk of Parkinson's Disease in those women who reached menopause when they were 55 or older. Current hormone users for less than 5 years showed a higher risk of developing Parkinson's Disease, which was anywhere between 11% more likely to more than twice as likely. However, this association disappeared for current hormone users after 5 years of use.  Oral contraceptive use for ten years was associated with a lower risk of Parkinson's Disease, down to 59% of what would otherwise be expected.

PESTICIDES ON AIRCRAFT AS A CAUSE OF PARKINSON'S DISEASE

Flight attendants who have developed Parkinson's Disease have taken legal action to try to prove that they have developed Parkinson's Disease because of the insecticides that are routinely sprayed inside  aircraft. 
Those pesticides that are known to cause, or be highly associated with Parkinson's Disease are Dieldrin, Rotenone and Organophosphorus pesticides. The fungicides Maneb and Paraquat are also known causes of Parkinson's Disease. Evidence in support of Permathrin, which is used in aircraft, is presently restricted to three animal studies.

Dieldrin levels are above normal in brains of people with Parkinson's Disease. Dieldrin was the most frequently detected Organochlorine pesticide in people with Parkinson's Disease thereby suggesting that dieldrin is associated with Parkinson's Disease. Organophosphorus pesticides are significantly associated with Parkinson's Disease. The frequent use of household pesticides containing Organophosphorus chemicals increased the chances of developing Parkinson's Disease by 71%. Exposure can lead to Parkinsonism. Rotenone can cause the neurochemical, neuropathological and behavioural features of Parkinson's disease, including hypokinesia and rigidity.

ANTIBODIES FOR THE TREATMENT OF PARKINSON'S DISEASE

14th December 2013 - News release


Roche and Prothena are collaborating to co-develop antibodies for the treatment of Parkinson's Disease. Prothena's antibody for the treatment of Parkinson's disease, PRX002,  targets alpha-synuclein. PRX002 is currently in preclinical development. It is expected to enter Phase 1 clinical trials in people with Parkinson's Disease in 2014. PRX002 has already been tested in various cellular and animal models of synuclein-related disease.

Synuclein proteins are found throughout the body. One protein from this family, alpha-synuclein, is found extensively in neurons and characterize several neurodegenerative disorders, including Parkinson's Disease, dementia with Lewy bodies, neurodegeneration with brain iron accumulation type 1, and multiple system atrophy, which collectively are termed synucleinopathies. As part of the agreement, Roche and Prothena will initiate a research collaboration focused on including incorporation of Roche's proprietary Brain Shuttle technology to increase delivery of therapeutic antibodies to the brain. 

FUNGAL CAUSE OF PARKINSON'S DISEASE

17th November 2013 - New research

Proceedings of the National Academy of Sciences USA [2013] Nov 11 [Epub ahead of print] (A.A.Inamdar, M.M.Hossain, A.I.Bernstein, G.W.Miller, J.R.Richardson, J.W.Bennett)

Octenol (1-octen-3-ol), which is commonly known as mushroom alcohol,,is produced by several plants and fungi. For information go too Octenol. In Drosophila melanogaster (the common fruit fly) Octenol reduces the levels of dopamine, the substance whose deficiency causes Parkinson's Disease.

Although it has not yet conclusively been proven to have caused Parkinson's Disease in humans, further experiments in human cells revealed that Octenol interfered with two genes involved in the creation of dopamine - the human plasma membrane dopamine transporter (DAT) and the human VMAT ortholog (VMAT2). This demonstrates that 1-octen-3-ol exerts toxicity via disruption of dopamine homeostasis and so may represent a naturally occurring cause of Parkinsonism. Octenol can often be inhaled by humans after being produced in damp, mouldy or water damaged buildings.