Parkinson's Disease
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Parkinson's disease is a serious movement disorder in the elderly.  It is much more common in people exposed to heavy metals and toxins like pesticides and herbicides.  It is also more common in people suffering from depression.  Diets higher in animal fats and individuals taking vitamin A supplements have higher rates of the illness.  Men consuming more dairy products have been found in one study to have a higher rate of Parkinson's.  It is less common in coffee drinkers and people with more frequent bowel movements.  Genetics plays a very minor role in Parkinson's disease.

Dementia is common in Parkinson's patients with 42% developing dementia in one Norwegian study after 4 years of follow-up. (J Geriatr Psychiatry Neurol. 2005 Sep;18(3):149-54). 

Diet

Animal Fat, Vitamin A Bad for Parkinsonís: An increase in PD risk with increasing intake was noted for foods that contain animal fat and foods containing vitamin D. Intake of fruits, vegetables, meats, bread and cereals, or foods containing vitamins A, C, E, or iron was not significantly related to PD risk. Vitamin use, in general, was also not found to be related to PD risk, although a significant trend of increasing risk of PD was noted for intake of vitamin A supplements. Mov Disord 1999 Jan;14(1):21-7

Coffee Blocks Parkinsonís in Japanese-Americans: 8,000 Japanese-Americans in Hawaii study found men without coffee were five times more likely have Parkinsonís than those drinking 5 cups per day and 2-3 times more likely than those drinking smaller amounts. JAMA 5/24/00

Coffee Linked to Less Parkinsonís Disease: In a 30 years follow-up of 8004 Japanese-American men ages 45-68 years, 102 men developed Parkinsonís disease. The risk declined consistently with increased amounts of coffee, from 10.4 per 10,000 person-years in men who drank no coffee to 1.9 per 10,000 person-years in men who drank at least 28 oz/d (P<.001). Similar relationships were observed for caffeine from non-coffee sources (P=.03 for trend). Association of coffee and caffeine intake with the risk of Parkinson disease. Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung KH, Tanner CM, Masaki KH, Blanchette PL, Curb JD, Popper JS, White LR. Honolulu VA. JAMA. 2000 May 24-31;283(20):2674-9

Coffee, Tea Protect Against Parkinsonís; Heavy Metals, Toxins Bad: In a case-control study of 300 PD patients and 500 controls, conditional logistic regression analysis demonstrated that amount of coffee drunk (OR 0.79, p=0.006), amount of tea drunk (OR 0.72, p=0.014), number of cigarettes smoked (OR 0.38, p=0.003), history of heavy metal and toxin exposure (OR 11.8, p=0.044), and heart disease (OR 5.5, p=0.016) to be significant factors associated with PD. One unit of coffee and tea (3 cups/day for 10 years) would lead to a 22% and 28% risk reduction of PD. Dose-dependent protective effect of coffee, tea, and smoking in Parkinson's disease: a study in ethnic Chinese. Tan EK, Tan C, Fook-Chong SM, Lum SY, Chai A, Chung H, Shen H, Zhao Y, Teoh ML, Yih Y, Pavanni R, Chandran VR, Wong MC. Singapore General Hospital. J Neurol Sci. 2003 Dec 15;216(1):163-7

Fats, Cholesterol, Lutein, Iron in Parkinsonís disease diet: Detroit case study of 126 with matched controls found OR total fat 1.94, cholesterol 2.11, lutein 2.52, iron 1.88 and author adds saturated fats. CC Johnson, Henry Ford, Int J Epid 12/99 28:1102

Fat and High Transferrin Fat Combo Bad: Among those with high transferrin saturation, risk of PD was two times higher (relative risk, 1.9) for those who reported high intake of animal fat compared with those who reported low intake. Iron intake after caloric adjustment was not associated with an increased risk of PD. However, the previously described association between animal fat intake and PD was modified by iron level stores as measured by transferrin saturation. Mov Disord 1998;13 Suppl 1:13-6

Fruit & Fruit Juices Increase: 34 year follow-up of 8,000 Hawaiians. Speculates could be pesticides in fruit. American Academy of Neurology Annual Meeting in Honolulu, March 29-April 5, 2003.

Iron & Manganese Intake Associated with Increase: Neurology. 6/10/03. 25% with the highest levels of iron intake were 1.7 times more likely to be Parkinson's patients than those in the lowest 25 percent. Higher -- 1.9 times more likely -- for those who had higher-than-normal intakes of both iron and manganese. Sources of iron include cereal, bread, spinach, nuts, beans, meat, poultry and fish. In the United States, many grain products -- such as cereal -- are fortified with iron. Manganese is found in grain products and spinach. Karen Powers

Iron a Cause of Early Onset AD and PD: Tissue iron can promote oxidative damage. Brain iron increases with age and is abnormally elevated early in the disease process in Alzheimer's disease (AD) and Parkinson's disease (PD). Higher iron levels in males may contribute to higher risk for younger-onset PD, The hemochromatosis gene is linked with a younger age at onset of AD. Ferritin iron with MRI found increases in basal ganglia in younger-onset AD and PD but not in older-onset patients. Brain ferritin iron as a risk factor for age at onset in neurodegenerative diseases. Bartzokis G, Tishler TA, Shin IS, Lu PH, Cummings JL. UCLA. Ann N Y Acad Sci. 2004 Mar;1012:224-36

Dairy Products in Men Only Food Linked to Parkinsonís: In a study of diet and PD risk in two large prospective cohorts in which 210 new PD cases in men and 184 in women developed, a positive association was found between dairy intake and PD risk in men (relative risk [RR] comparing extreme categories, 1.8; P = 0.004), but not in women. No other food groups were associated with PD risk. Men showed significant positive associations with PD risk for intakes of several dairy foods as well as dairy calcium (RR, 1.5), dairy vitamin D (RR, 1.6), dairy protein (RR, 1.6), and lactose (RR, 1.8), but not dairy fat. Intakes of calcium, vitamin D, and protein from other dietary or supplemental sources were not related to PD risk in men. Diet and Parkinson's disease: a potential role of dairy products in men. Chen H, Zhang SM, Hernan MA, Willett WC, Ascherio A., Harvard. Ann Neurol. 2002 Dec;52(6):793-801. Prospective health professionals and nurses studies found 2.9 servings vs. under 1 serving per day associated with 80% increase and this level over 6 years associated with 170% increase (2.7 relative risk). Some cases been linked to viruses, toxins, and drugs. Oxidative damage has also been thought to contribute, and some studies have found that antioxidants can protect against the progression of the disease.

Parkinsonís and AD Low in Omega-3s: Essential fatty acids, especially DHA, are low and speculates increase in diet may help. Int J Dev Neurosci. 2000 Jul-Aug;18(4-5):383-99. Other retrospective studies say anti-ox and Vitamin E unlikely to help.

Pesticides May Be a Cause: Rats given rotenone pesticide developed Parkinsonís. Nature Neurosci 12/00.

Insecticides Harmful to Farmers: In a National Institute of Environmental Health Sciences study of 18,726 North Carolina and Iowa farmers investigating lifetime exposure to herbicides, insecticides, fungicides, and fumigants, and their history of 23 neurological symptoms, nearly 3,000 participants had a high lifetime exposure to insecticides, more than 500 days in their lifetime. Nearly 800 of these farmers reported more than 10 neurological symptoms compared to those using insecticides fewer than 50 days. The researchers found no significant association between neurological symptoms and other chemicals, including herbicides or fungicides, and only a weak association between fumigant exposure and neurological symptoms. Some of the pesticides examined, including carbaryl and some pyrethroids, are available to home gardeners, although in different formulations and in lower concentrations, which may make them less hazardous. Freya Kamel, et al. Environmental Health Perspectives 6/05. 

Other Studies

Amantadine Reduces Levodopa Dyskinesia: In a DB PC study of 18 Parkinson's patients, amantadine did not change the hyperkinesia or dystonia, but decreased the duration of LID (p=0.04) and its influence on daily activities (p=0.01) more than placebo. Amantadine reduces the duration of levodopa-induced dyskinesia: A randomized, double-blind, placebo-controlled study. Pereira da Silva-Junior F, et al. Federal University of Ceara, Fortaleza, Brazil. Parkinsonism Relat Disord. 2005 Sep 8.

Citicoline Helped Parkinson's in DB: A DB PC study using citicoline as an add-on to levo-dopa found a 23% decrease in bradykinesia and a 33% decrease in rigidity with a small effect on tremor. New strategies in the management of Parkinson's disease: a biological approach using a phospholipid precursor (CDP-choline). Agnoli A, Ruggieri S, Denaro A, Bruno G. Neuropsychobiology. 1982;8(6):289-96. Neurochirurgie. 1982;28(4):287-90

Coenzyme Q10 Slows Parkinsonís Disease: 1% of Americans over 65 have Parkinson's. Coenzyme Q10 has been found to be low in the disease. CoQ10 helps the functioning of mitochondria and is an anti-oxidant. UCLA. Arch Neurol 10/15/02 Researchers found that 1,200 mg four times a day slowed disease progression over 16 month study by 44%, but 300 and 600 mg were ineffective in a DB study of 80 patients looking at symptom progression. This dosage would require 10 pills four times a day at a cost of over $400 per month. 

Constipation Linked to Later Parkinsonís Disease: In a 12-year follow-up of 6,790 men ages 51-75 in the Honolulu Heart Program, 96 developed Parkinsonís disease. Age-adjusted incidence declined consistently from 18.9/10,000 person-years in men with <1 bowel movement/day to 3.8/10,000 person-years in those with >2/day (p = 0.005). After adjustment for age, pack-years of cigarette smoking, coffee consumption, laxative use, jogging, and the intake of fruits, vegetables, and grains, men with <1 bowel movement/day had a 2.7-fold excess risk of PD versus men with 1/day (p = 0.007). The risk of PD in men with <1 bowel movement/day increased to a 4.1-fold excess when compared with men with 2/day ( p = 0.001) and to a 4.5-fold excess versus men with >2/day (p = 0.025). Frequency of bowel movements and the future risk of Parkinson's disease. Abbott RD, Petrovitch H, White LR, Masaki KH, Tanner CM, Curb JD, Grandinetti A, Blanchette PL, Popper JS, Ross GW. University of Virginia. Neurology. 2001 Aug 14;57(3):456-62. Ed: Frequent bowel movements are probably a measure of more fiber and stool bulk which is probably helping clear out toxins more effectively.

Depressed Three Times More Parkinsonís: Parkinsonís patientsí brains have a lowered level of the neurotransmitter serotonin. Low levels of serotonin play a key role in depression. Serotonin also acts to modulate the release of the neurotransmitter dopamine in the brain. Because the level of dopamine activity is decreased in Parkinsonís, researchers believe the amount of serotonin activity is also decreased in compensation. That reduction increases the risk of depression. Because the reduced serotonin activity already exists before any motor symptoms begin, the risk of depression is also increased long before any Parkinsonís symptoms become apparent. Schuurman, Maasstricht, Netherlands, Neurol 5/28/02.

ECT Might Help Parkinson's disease: A literature review concludes that considerable evidence suggests that ECT improves motor symptoms of Parkinson's disease in patients with and without mood disorders. A few case reports, ranging from one to six patients per disorder, suggest that ECT may ameliorate the motor symptoms of other movement disorders. ECT affects a variety of neurotransmitters that play a role in these diseases. Electroconvulsive therapy in movement disorders: an update. Kennedy R, Mittal D, O'Jile J. University of Mississippi. J Neuropsychiatry Clin Neurosci. 2003 Fall;15(4):407-21.  Ed: While I am not a fan of ECT, this review makes me wonder whether rTMS might also help. 

Estrogen Treatment Lowers Parkinson's Risk After Hysterectomy: 72 female patients who developed Parkinsonís disease found an increase in the disease in women with hysterectomies but the increase offset by estrogen replacement therapy. Men have a 50% higher rate of Parkinson's, possibly due to women being protected by estrogen. Demetrius Maraganore, September 2001 Movement Disorders.

Glial-Cell Derived Neurotrophic Factor May Help: Heywood, Bristol UK, (Nature Medicine) have found success by using a more subtle method of delivering the drug - a pump delivering tiny amounts of GDNF continuously to the brain. One end of the catheter was placed in the striatum while the other was connected to a pump embedded in the abdomen. After a year of treatment, the five patients improved by almost 40 per cent on a standard scale measuring motor abilities, and there were no significant side effects. Parkinson's symptoms are caused by the progressive destruction of cells producing the brain messaging chemical dopamine. The researchers believe that GDNF may halt this decline or even restore dopamine-producing cells. In support of this, PET scans of the patients' brains indicated a 28 per cent increase in dopamine storage where the drug entered the brain. New Scientist 3/31/03

Pesticide Exposure Occupationally Linked: In men, the relative risks of developing Parkinson's disease and Alzheimer's disease for occupational exposure assessed by a job exposure matrix were 5.63 and 2.39, respectively, after confounding factors were taken into account. No association was found with having a primary job in agriculture or with environmental pesticide exposure, nor was an association found in women. Bordeaux. Neurodegenerative diseases and exposure to pesticides in the elderly. Baldi I, Lebailly P, Mohammed-Brahim B, Letenneur L, Dartigues JF, Brochard P. Am J Epidemiol 2003 Mar 1;157(5):409-14

Psychosis from Parkinson Drug Treatment Difficult to Treat:  Aripiprazole (Abilify) was used to treat 8 patients with probable Parkinson disease (PD) with drug-induced psychosis. Two patients were neuroleptic-naive, 5 were "quetiapine (Seroquel) failures", and 1 was switched from olanzapine (Zyprexa). Aripiprazole was started at 5 mg to 10 mg a day and slowly increased over 3 to 7 days until side effects or improvement of psychosis occurred. Only 2 out of 8 patients experienced near complete resolution of their psychosis using aripiprazole. The other six patients discontinued aripiprazole within 40 days, 2 of whom discontinued due to motor worsening. Aripiprazole for drug-induced psychosis in Parkinson disease: preliminary experience. Fernandez HH, Trieschmann ME, Friedman JH. University of Florida. Clin Neuropharmacol. 2004 Jan-Feb;27(1):4-5

L-Dopa Raises Homocysteine: patients with Parkinson disease (PD) may have elevated homocysteine levels resulting from methylation of levodopa and dopamine by catechol O-methyltransferase, an enzyme that uses S-adenosylmethionine as a methyl donor and yields S-adenosylhomocysteine. Since S-adenosylhomocysteine is rapidly converted to homocysteine, levodopa therapy may put patients at increased risk for vascular disease by raising homocysteine levels. 235 pts studied, 200 on l-Dopa. Normal folate, B-12, MMA in L-Dopa pts. Increased CAD of 1.7 for higher quartile homocysteine. Elevated plasma homocysteine levels in patients treated with levodopa: association with vascular disease. Rogers JD, Sanchez-Saffon A, Frol AB, Diaz-Arrastia R. Arch Neurol 2003 Jan;60(1):59-64

Pallidotomy Helps: 36 patients were randomized. Those with usual medical care got 5% worse. Those with unilateral surgery were 32% better at 6 months. Emory. Stayed better at 2 years. Randomized trial of pallidotomy versus medical therapy for Parkinson's disease. Vitek JL, Bakay RA, Freeman A, Evatt M, Green J, McDonald W, Haber M, Barnhart H, Wahlay N, Triche S, Mewes K, Chockkan V, Zhang JY, DeLong MR. Ann Neurol. 2003 May;53(5):558-69

Pramipexole (Mirapex) Better than Pergolide (Permax) for Tremor and Other Symptoms in DB: A small 30 patient DB PC of pramipexole vs. pergolide vs. placebo in patients with an average of 4 years of Parkinson's disease found both medicines better than placebo but 4 of 10 pergolide patients dropped out due to side-effects vs. none of the pramipexole (up to 1.5 mg t.i.d.) patients. The Tremor Index (TI) and Unified Parkinson's Disease Rating Scale (UPDRS) used to measure improvement. Randomized, double-blind, 3-month parallel study of the effects of pramipexole, pergolide, and placebo on Parkinsonian tremor. Navan P, Findley LJ, Jeffs JA, Pearce RK, Bain PG. Mov Disord. 2003 Nov;18(11):1324-31

Stavelo for Parkinsons: Levodopa combined with carbidopa is the most common treatment for Parkinsonís disease, but after 2 to 5 years most patients develop troublesome complications. The newest treatment for Parkinsonís disease patients with end-of-dose "wearing-off" is Stalevo, a combination of the catechol-O-methyltransferase (COMT) inhibitor entacapone (Comtan) with 3 different doses of levodopa/carbidopa. Levodopa is metabolized by 2 enzymes, dopa decarboxylase and COMT. Levodopa is taken with carbidopa, which inhibits decarboxylation of peripheral levodopa, preventing nausea and permitting more levodopa to reach the brain. COMT inhibitors prolong the half-life of levodopa, decreasing the amount of "off" time, but they may increase dyskinesias. Stalevo is bioequivalent to separate but equivalent doses of levodopa/carbidopa (100/25) plus entacapone. RA Hauser, Neurology 2004; 62 suppl 1:S64.

Toluene, Heavy Zinc Exposure Linked: A discrete clustering of Belgium patients with PD in areas with intensive metallurgic frequently employed in metallurgy than controls was found. Furthermore, patients were clearly more exposed to zinc and toluene. Male patients report more prostatectomy-surgery. Eur J Epidemiol. 2003;18(12):1133-42

Genetics and Biochemistry

Little Genetic Influence: Only for the rare early onset before age 51 of Parkinsonian symptoms is there evidence from twin studies of genetic influence. JAMA 1/27/99

Dardarin Mutation Causes 5% of Parkinson's: Mutations in the leucine-rich kinase 2 gene (LRRK2) encoding dardarin, on chromosome 12, are a common cause of familial and sporadic Parkinson's disease. The most common mutation, a heterozygous 6055G>A transition (G2019S) accounts for approximately 3-10% of familial Parkinson's disease and 1-8% sporadic Parkinson's disease. The mutation is found only in Parkinson's disease patients or their relatives and not in those with other neurodegenerative disease. The dardarin G2019S mutation is a common cause of Parkinson's disease but not other neurodegenerative diseases. Hernandez D, et al. National Institutes on Aging, Bethesda, MD. Neurosci Lett. 2005 Aug 12

Brain Protein with Dopamine Toxic: brain protein alpha-synuclein combines with dopamine in nerve cells it can trigger the production of toxic reactive oxygen molecules that kill the nerves, according to a research team led by Dr. Bruce A. Yankner of Harvard. If this process operates in patients the same way it does in the laboratory, it could set scientists on the path to potential treatments. But it also adds to the debate over whether the current use of dopamine in the treatment of Parkinson's. Nature 6/02. Some families with a mutated form of alpha-synuclein have a tendency to develop Parkinson's. Alpha-synuclein is found at the synapses of nerve cells. Earlier studies showed that two mutations in the alpha-synuclein gene cause familial Parkinson's disease, and that this protein is also a major component of Lewy bodies, the characteristic lesion in Parkinson's disease

Too Much Alpha-Synuclein: A rare familial form of early-onset Parkinson's disease have discovered that too much of a normal form of the alpha-synuclein gene may cause Parkinson's disease. In individuals in this family affected by Parkinson's disease, instead of the usual two copies of the Š-synuclein gene in the chromosome 4 pair, the researchers found four copies of the Š-synuclein gene. This multiplication of the Š-synuclein gene (an abnormal triplication of three genes on one chromosome 4 and the normal one copy on the other chromosome 4) results in the individual's having too much synuclein. Andrew Singleton, National Institute on Aging, Matthew Farrer, Mayo Clinic et al, October 31, 2003, Science

Septin4 Also Involved with alpha-Synuclein and Synphilin: Alpha-Synuclein-positive cytoplasmic inclusions are a pathological hallmark of several neurodegenerative disorders including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Here we report that Sept4, a member of the septin protein family, is consistently found in these inclusions, while five other septins (Sept2, Sept5, Sept6, Sept7, and Sept8) are not found in these inclusions. Sept4 and alpha-synuclein can also be co-immunoprecipitated from normal human brain lysates. When co-expressed in cultured cells, FLAG-tagged Sept4 and Myc-tagged alpha-synuclein formed detergent-insoluble complex, and upon treatment with a proteasome inhibitor, they formed Lewy body-like cytoplasmic inclusions. The tagged Sept4 and alpha-synuclein synergistically accelerated cell death induced by the proteasome inhibitor, and this effect was further enhanced by expression of another Lewy body-associated protein, synphilin-1, tagged with the V5 epitope. Moreover, co-expression of the three proteins (tagged Sept4, alpha-synuclein, and synphilin-1) was sufficient to induce cell death. These data raise the possibility that Sept4 is involved in the formation of cytoplasmic inclusions as well as induction of cell death in the alpha-synuclein-associated neurodegenerative disorders. Association of the cytoskeletal GTP-binding protein Sept4/H5 with cytoplasmic inclusions found in Parkinson's disease and other synucleinopathies. Ihara M, Tomimoto H, Kitayama H, Morioka Y, Akiguchi I, Shibasaki H, Noda M, Kinoshita M. Kyoto U, J Biol Chem 2003 Apr 14

Mitochondrial Haplogroup J Form of Complex I Protective: 26% Caucasian vs. 2/3 Asian & 90% Afro have haplogroup J. Study of 609 European-Americans vs. controls found haplogroup J protective, especially for women. Am J Human Genetics 4/03, Duke

Isofuranes Increased in PD & DLB: Duke. IsoFs but not F2-IsoPs in the SN of patients with PD and DLB were significantly higher than those of controls. Levels of IsoFs and F2-IsoPs (Isoprostanes) in the SN of patients with MSA and AD were indistinguishable from those of age-matched controls. This preferential increase in IsoFs in the SN of patients with PD or DLB not only indicates a unique mode of oxidant injury in these two diseases but also suggests different underlying mechanisms of dopaminergic neurodegeneration in PD and DLB from those of MSA. Isofurans, but not F2-isoprostanes, are increased in the substantia nigra of patients with Parkinson's disease and with dementia with Lewy body disease. Fessel JP, Hulette C, Powell S, Roberts LJ, Zhang J. J Neurochem 2003 May;85(3):645-650

Quetiapine (Seroquel) Didn't Help Visual Hallucinations: In a DB PC 12 week study of 31 Parkinson's patients with prominent visual hallucinations and MMSE >21, those on up to 200 mg daily of quetiapine did no better on hallucinations or BPRS scores and no worse on Parkinson's symptoms.  Double-blind, placebo-controlled, unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in Parkinson's disease. Ondo WG, Tintner R, et al. Baylor, Houston, Texas. Mov Disord. 2005 Mar 30