Parkinson Disease Therapy

Parkinson Diseases Manual By Lianna Marie

This is a complete guide to the best ways of dealing with a Parkinson's diagnosis for yourself or a loved one. Packed with a huge number of tips that you can use to make Parkinson's less of an uphill struggle, and all arranged into handy sections that allow you to implement them in every aspect of your life with the minimum of fuss. You'll learn exactly what Parkinson's Disease is, what causes it and its symptoms. You'll also learn how to deal with these symptoms and associated conditions. In addition, you'll get vital information on medications and treatments you should and shouldn't take as well as what alternative treatments can help alleviate symptoms. Even better, there's valuable advice on how to handle the stress and frustration the disease can cause. Your order will also entitle you to four free ebooks which will provide you with even more useful advice and information to ensure that your loved one. Pain and Parkinson's will provide you with practical tips to help reduce pain and discomfort; A Helpful Guide For Caregivers is essential reading for anyone looking after somebody with Parkinson's. Continue reading...

All About Parkinsons Disease Overview

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Contents: Ebook 109 Pages
Author: Lianna Marie
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My All About Parkinsons Disease Review

Highly Recommended

The author presents a well detailed summery of the major headings. As a professional in this field, I must say that the points shared in this book are precise.

When compared to other e-books and paper publications I have read, I consider this to be the bible for this topic. Get this and you will never regret the decision.

What is Parkinson disease

Parkinson disease (PD) is a journey a journey that, once started, will last a lifetime. Many people have taken this journey, have described the pitfalls, and have mapped the course. It is not a journey you will take alone Your family, friends, and neighbors will come with you. You will meet many travelers along the way and will have several doctors who will serve as guides to help you through the rough places, to point out the dangers, and to provide assurance and understanding. The many travelers who have taken this journey know it well and can tell you how they overcame the obstacles Don't neglect them listen to them Although the journey is not a pleasure cruise, you can be comforted because you are not alone. What is PD you ask. Is it an infection, like a virus No, it's not an infection. It's a chronic condition, an imbalance like diabetes. In diabetes, you lack insulin. In PD, you lack a chemical dopamine. Diabetes is a disease of the glands PD is a disease of the brain. A lack of...

Frequency Of Autonomic Dysfunction In Parkinsons Disease

Although the focus of routine follow-up visits between PD patients and neurologists is typically on motor symptoms of the disease, autonomic problems are frequently present and can be identified if patients are specifically asked. In one study of 48 men with PD, 89 had at least one autonomic symptom compared with 43 of elderly control subjects (2). Autonomic symptoms seen in these men with PD included erectile dysfunction (60 ), urinary urgency (46 ), constipation (44 ), dysphagia (23 ), and orthostatism (22 ), and each of these symptoms was more common in PD patients than controls. Siddiqui et al. (3) performed a comprehensive symptom survey of autonomic symptoms in 44 patients with PD, comparing the frequency and severity of these symptoms with 24 aged-matched controls. Using a five point scale to rate symptom severity, the authors tabulated the severity of symptoms in each of five areas GI, urinary, sexual dysfunction, cardiovascular, and thermoregulatory. They found that PD...

The Role Of Neuropsychology In The Management Of Parkinsons Disease

Neuropsychology provides an important contribution to the management of patients with PD. Neuropsychological evaluation delineates the nature and extent of cognitive changes, if any, and a profile of relative neuropsychological strengths and weaknesses. Such knowledge is helpful in Given the prevalence of cognitive and behavioral changes in PD, every patient would, in ideal circumstances, receive a baseline evaluation when first diagnosed with PD. Such a baseline neuropsychological evaluation would facilitate the accurate detection and diagnosis of subsequent neurobehavioral changes and permit the evaluation of treatment effects. This, however, occurs rarely and probably reflects cost-effectiveness issues in a managed care environment and the reluctance of many patients to contemplate in the early disease stages the threat of later, possibly significant, cognitive compromise. In the absence of an early baseline evaluation, a neuropsychological evaluation in the context of cognitive...

Neuropsychological Findings In Parkinsons Disease

Parkinson (20) contended that patients with shaking palsy did not exhibit significant intellectual changes however, by the late 1800s, investigators had begun to recognize the presence of cognitive deficits in patients with PD (21). Mild neuropsychological changes are widely accepted to occur in early PD. Increasingly, it is recognized that cognitive alterations, especially in executive functions and or memory, may already be present at the time of disease diagnosis. Recent studies estimate that one-quarter to one-third of patients may have deficits detectable on careful neuropsychological testing at the time of disease diagnosis (22,23). Cognitive declines early in the disease most often include deficient information processing speed, visuospatial abilities, verbal fluency, recall, and executive functions (24,25). The neuropsychological dysfunction associated with early PD is hypothesized to reflect nigrostriatal dopamine depletion and disruption of mesocortical and mesolimbic...

Neuropsychological Dysfunction in Parkinsons Disease Without Dementia

In reviewing the PD literature, Lieberman (29) reported that 17 to 53 of treated and untreated PD patients without dementia demonstrate cognitive dysfunction. Unfortunately, few of the studies reported formal criteria for determining what did or did not constitute dementia, thus making it difficult to determine whether patients were in the early stages of dementia. As noted earlier, more recent studies suggest that formal neuropsychological testing may uncover mild cognitive deficits in 25 to 36 of PD patients at the time of diagnosis (22,23). When present in early PD, cognitive dysfunction is typically mild and most commonly involves bradyphre-nia (a slowness of thought) and subtle deficits in executive functions, recall, and or visuoperceptual spatial functions (30).

Neuropsychological Dysfunction in Parkinsons Disease with Dementia

The annual incidence of clinically diagnosed dementia in PD (PDD) is about 3 for individuals younger than 60 years and 15 or less for those 80 years and older (66,67). Estimates of dementia prevalence in patients with PD vary between 9 and 93 , depending on which diagnostic criteria, ascertainment methods, and sampling methods are implemented (24). The methodologically soundest studies yield prevalence estimates of about 25 (68). Dementia is very rarely present early in the disease course moreover, dementia that precedes or accompanies the evolution of motor symptoms should raise concern that the dementia might be related to factors other than PD, for example, AD, LBD, or depression. Recently revised diagnostic criteria for LBD (69) propose that the clinical diagnostic term PD with dementia be reserved for individuals who have a clinical diagnosis of PD and have had only motor symptoms for at least 12 months before developing fluctuating cognition and other neuropsychiatric symptoms...

Risk Factors for Dementia in Parkinsons Disease

TABLE 3 Risk Factors for Dementia in Parkinson's Disease Lower socioeconomic status Family history of Parkinson's dementia Disease severity Susceptibility to levodopa-induced psychosis or confusion patients with PD on verbal fluency, attentional, and visuospatial tasks was associated with subsequent development of dementia. Woods and Tr ster (93) found that nondemented PD patients who met criteria for dementia at one-year follow-up evaluation demonstrated poorer baseline performance on measures of word-list learning and recognition, complex auditory attention, and executive function.

Levodopa and Dopamine Agonists

Findings concerning the impact of levodopa on cognitive functions are inconsistent, with studies showing improvement, decrements, and an absence of significant cognitive changes associated with levodopa therapy or its withdrawal (124). Despite these inconsistent findings, evidence is accumulating that levodopa has short-term effects on certain aspects of memory and executive functions, perhaps as mediated by disease stage. Kulisevsky et al. (125) reported that short-term improvements in learning and memory, visuoperception, and certain executive functions were associated with dopamine replacement therapies, but stated that these cognitive improvements were not maintained over time. Owen et al. (126) found that only certain aspects of executive functioning (i.e., planning accuracy) were improved with levodopa therapy early in the disease, whereas other aspects (response latency) remained relatively unaffected. That levodopa affects only certain components of cognitive functions is...

Neuropsychological Aspects Of Parkinsonplus Syndromes And Essential Tremor

Parkinson-plus syndromes traditionally include PSP, MSA, and corticobasal degeneration (CBD). Although sparse, preliminary neuropsychological studies indicate that the cognitive impairment profiles likely differ across the parkinson-plus syndromes (172). A summary of key differences is presented in Table 4. TABLE 4 Comparison of Neurobehavioral Features of Parkinson's Disease with Dementia, Lewy Body Dementia, Corticobasal Degeneration, Progressive Supranuclear Palsy, and Multiple System Atrophy TABLE 4 Comparison of Neurobehavioral Features of Parkinson's Disease with Dementia, Lewy Body Dementia, Corticobasal Degeneration, Progressive Supranuclear Palsy, and Multiple System Atrophy Abbreviations 0, impairment absent -, mild to moderate impairment --, moderate to severe impairment , questionable PDD, Parkinson's disease with dementia LBD, Lewy body dementia CBD, corticobasal degeneration PSP, progressive supranuclear palsy MSA, multiple system atrophy. Abbreviations 0, impairment...

Parkinsons Disease Diagnosis Accuracy

The diagnosis of PD is currently based primarily on clinical judgment. However, the variability of disease presentation, progression, and response to medications often makes the diagnosis uncertain. In a population-based study, at least 15 of patients with a diagnosis of PD did not meet strict diagnostic criteria, and approximately 20 of patients with PD who had medical attention had not been diagnosed with PD (48). Prevalence studies of parkinsonism suggest a diagnostic accuracy of 80 after examination and application of clinical diagnostic criteria (49-51). Long-term clinico-pathologic studies evaluating the diagnostic accuracy of PD demonstrate that the diagnoses most commonly mistaken for PD are progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) (52,53). However, early in the course of PD, the most common misdiagnoses include essential tremor, vascular parkinsonism, drug-induced parkinsonism, and Alzheimer's disease (54,55). It has been estimated that the...

Parkinsons Disease Differential Diagnosis And Severity

The initial questions of an imaging ligand are whether it reliably distinguishes between subjects with and without a known pathology (a marker for disease trait) and whether the changes in the imaging outcomes correlate with disease severity (a marker for disease state). In several studies, dopamine and vesicular transporter ligands and 18F-DOPA discriminated between individuals with PD and healthy subjects, with a sensitivity greater than 95 (11,13,20,72-74). These studies take advantage of the relatively greater dopaminergic loss in the putamen to enhance the discriminant function. Furthermore, the reduction in both dopamine and vesicular transporter and 18F-DOPA imaging activity correlated with well-defined clinical rating scales of PD severity (16,20,28,75). Interestingly, when specific PD symptoms were compared, the loss of dopaminergic activity measured by imaging correlated with bradykinesia but not with tremor (20,76). Cross-sectional studies show that In clinical practice,...

Parkinsons Disease Progression

The rate of clinical progression of PD is highly variable and unpredictable (77). In clinical studies, several clinical endpoints for progressive functional decline in PD have been used, including the Unified Parkinson's Disease Rating Scale (UPDRS) in the defined off state or after drug washout up to two weeks, time to need for dopaminergic therapy, or time to development of motor fluctuations (85-89). Clinical rating scales are extremely useful, but ratings may be investigator-dependent and are frequently confounded by changes in symptomatic treatment. Pathological studies investigating rate of progression have been limited and rely entirely on cross-sectional data (63,64). These studies have in general considered patients with severe illness of long duration. In vivo imaging studies provide the opportunity to evaluate patients longitudinally from early to late disease using an objective biomarker for dopaminergic degeneration. In several studies, neuroreceptor imaging of the...

Preclinical Parkinsons Disease

Estimates based on postmortem studies suggest that for every patient who presents with PD, there may be up to 15 cases of preclinical PD (development of Lewy body pathology without clinical signs of PD) (111). Neuroreceptor imaging studies provide a window into this preclinical period of PD, the time during which neurodegeneration has begun, but symptoms have not yet become manifest. Preclinical identification of affected subjects is particularly important if intervention exists, which may prevent progression of disease. The most extensive preclinical imaging data is from studies imaging patients with hemi-PD. In several imaging studies, there is a significant reduction in putamen DAT or 18F-DOPA uptake of about 25 to 30 in the presymptomatic striatum in these patients who are known to progress to bilateral disease (11,66,67). Most studies of the preclinical period have focused on potential at risk individuals for PD, such as family members or unaffected twins of PD patients. In a...

Why is carbidopa always given with levodopa

When levodopa was first introduced, its major side effects were nausea and vomiting. In spite of its remarkable benefits, many patients could not or would not take it. The problem was in the conversion of L-dopa or levodopa to dopamine. The L-dopa or levodopa was changed in the stomach by an enzyme called dopa-decarboxylase (DDC) into dopamine. Dopamine in the stomach and circulating in the blood cannot cross the blood brain barrier to reach the sub-stantia nigra. However, dopamine in the stomach and circulating in the blood was reacting with the brain's trigger zone for nausea. To prevent the levodopa from being changed to dopamine outside the brain, car-bidopa was added as a way to block the enzyme DDC. Carbidopa does not pass through the blood brain barrier and insures that the conversion of levodopa to dopamine will take place in the substantia nigra, well past the nausea trigger zone. The addition of car-bidopa prevents nausea and allows a smaller amount of levodopa to be used....

Parkinsons Disease Dementia

Pathological findings considered to account for dementia in PD include severe pathology in monoaminergic and cholinergic nuclei that project to the cortex producing a subcortical dementia (39 ), coexistent Alzheimer's disease (AD) (29 ), and diffuse cortical Lewy bodies (26 ) (22). The basal forebrain cholinergic system is the subcortical region most often implicated in dementia, and neurons in this region are damaged in both AD and Lewy body dementia. Neuronal loss in the basal nucleus is consistently found in PD, especially PD with dementia (23). Cholinergic deficits are common in PD (24) and they may contribute to dementia in PD in those cases that do not have concurrent AD or cortical Lewy bodies. While virtually all PD brains have a few cortical Lewy bodies (22), they are usually neither widespread nor numerous in PD patients who were not demented. Several studies have shown, however, that cortical Lewy bodies are numerous and widespread in PD with dementia (25-27) and that the...

Postencephalitic Parkinsonism

Parkinsonism following encephalitis lethargica during the influenza pandemic between 1916 and 1926 is known as postencephalitic parkinsonism (PEP). During the recovery phase of the acute viral encephalitis, parkinsonian rigidity developed with the most characteristic clinical features being oculogyric crises. The PEP brain has NFTs in the cortex, basal ganglia, thalamus, hypothalamus, substantia nigra, brainstem tegmentum, and cerebellar dentate nucleus (48). The distribution of the pathology overlaps with PSP and, in some studies, it has not been possible to distinguish the two disorders by histopathologic analysis alone (48). Biochemical studies of abnormal insoluble tau in PEP have features similar to AD with three major bands (68, 64 and 60 kDa) on western blot studies, and electron microscopy shows paired helical filaments similar to those in AD (49).

Guam Parkinsondementia Complex

A characteristic parkinsonism with dementia Parkinson dementia complex (PDC) with a number of features that overlap with PSP (50) has been reported in the native Chamorro population of Guam since the 1950s (51). The frequency of PDC is declining in recent years for unknown reasons, and the etiology is unknown. The gross findings in PDC are notable for cortical atrophy affecting frontal and temporal lobes, as well as atrophy of the hippocampus and the tegmentum of the rostral brainstem (52). These areas typically have neuronal loss and gliosis with many NFTs in residual neurons.

Vesicular Monoamine Transporter And Dopamine Transporters In The Substantia Nigra Pars Compacta

The dopaminergic synaptic transmission is terminated by the transportation of 95 of synaptic dopamine into the nigrostriatal terminals by the dopamine transporter (DAT) molecule (20). DAT also plays a major role in the neurotoxic effects of MPTP by transporting MPP+, the active mitochondrial toxic metabolite of MPTP, into the dopamine neuron terminals. DAT is an important and a specific marker for dopaminergic neurons (20,21). The intensity of expression of DAT mRNA in primate and human nigra is maximal at the caudal, ventral, and lateral group of dopamine neurons and gradually decreases medially in the VTA regions (19-23), corresponding with the pattern of dopaminergic cells that are highly melanized in the SNpc. The SNpc cells that express DAT very densely are the most severely affected in PD, and those VTA neurons expressing DAT less intensely demonstrate a less severe pattern of degeneration. The level of expression of DAT mRNA in the dopaminergic neurons of the arcuate and...

Pharmacologicalinduced Models Of Parkinsons Disease

Pharmacological manipulation of the dopaminergic system can take on two basic forms either targeting dopamine biosynthesis or destruction of nigrostriatal dopaminergic neurons. Both reserpine and alpha-methyl-para-tyrosine (AMPT) interfere with dopamine production and result in a temporary dopamine depletion lasting hours to days, whereas neurotoxicants such as 6-hydroxydopamine (6-OHDA) and (MPTP) result in midbrain dopaminergic cell death. Methamphetamine (METH) is a class of compound that selectively destroys axonal terminals of nigrostriatal dopaminergic neurons usually without significant cell death. Recently, other compounds, particularly pesticides and proteasome inhibitors, have been utilized as selective toxins targeting the dopaminergic system since the mitochondria of these cells display enhanced vulnerability during chronic exposure. The utility of compounds to generate animal models of parkinsonism are discussed in the following sections.

Neurotoxicantinduced Models Of Parkinsons Disease 6Hydroxydopamine

Hydroxyl radicals and impairment of mitochondrial energy production (5,6). The 6-OHDA-induced rat model of PD was initially carried out by Ungerstedt in 1968, using stereotaxic bilateral intracerebral injections into the substantia nigra or lateral hypothalamus targeting the medial forebrain bundle (7). The bilateral administration of 6-OHDA resulted in catalepsy, generalized inactivity, aphagia, adipsia, and a high degree of animal morbidity and mortality. Consequently, the administration of 6-OHDA was modified to a unilateral intracerebral lesion targeting the substantia nigra and or medial forebrain bundle. With unilateral lesioning, there was minimal postoperative morbidity, behavioral asymmetry, and a nonlesioned side to serve as a control (8,9). An additional modification of 6-OHDA administration is using chronic low dose striatal injections. This can lead to progressive dopaminergic cell death thought to more closely resemble the human condition (10). An important caveat of...

What else can I do to cope with PD

Another difficulty is responding to the unkind looks or remarks from others, particularly strangers. Although they may never have known anyone with PD, their rudeness or pity is unwelcome. Education improving public awareness and media coverage or making information about PD available to others is important. If you have the opportunity and the courage, you could explain to them that you have a neurologic disorder that affects your walking and balance. The Parkinson Disease Society of Great Britain has a small card that can be handed to people that says I have Parkinson disease. I may be slow to move or unsteady on my feet. I may have difficulty speaking and writing clearly. I can hear and understand you. Please allow time. in research and treatment of PD. Friends made in support groups can keep you from feeling alone in your circumstances.

Spontaneous Rodent Models for Parkinsons Disease

There are several naturally occurring spontaneous mutations in rodents that are of particular interest in PD. Spontaneous rodent models include the weaver, lurcher, reeler, Tshrhyt, tottering, and coloboma mice and the AS AGU and circling (ci) rat. These models possess unique characteristics that may provide insight into neurodegener-ative processes of PD and related disorders. Several of these spontaneous rodent models display altered dopaminergic function or neurodegeneration, and have Another naturally occurring mutation is the aphakia mouse. This mutation affects a gene called Pitx3, which is a developmentally regulated homeobox containing transcription factor necessary for the establishment of midbrain dopaminer-gic neurons (138). Mice carrying mutations in Pitx3 display behavioral and neurochemical characteristics similar to the anatomical and functional deficits seen in PD, including cell loss in the substantia nigra dopaminergic neurons, a feature not seen in most transgenic...

Considering pramipexole and ropinirole Parkinsons drugs may offer pain relief

Some studies have indicated that two drugs that are technically called dopamine receptor agonists and that are used by patients with Parkinson's disease (a degenerative disease of the nervous system) may also be helpful in decreasing the chronic pain of individuals with FMS. Requip (generic name ropinirole), another drug used to treat patients with Parkinson's disease, has also been found to be effective in reducing the pain

Geographic Differences In Rates Of Parkinsons Disease

Although the findings are inconsistent, a higher prevalence of PD in urban areas argues for byproducts of industrialization as risk factors for PD. Several studies suggest that increasing industrialization may increase PD risk. Schoenberg et al. compared the prevalence of PD in Copiah County, Mississippi, U.S.A. (341 100,000 over age 39) to Igbo-Ora, Nigeria (67 100,000 over age 39) using similar methodology, and studying genetically similar populations. They concluded that environmental factors may be responsible for the observed higher prevalence in the industrialized U.S. population (26). In contrast, a study (27) of PD in Estonia found a similar prevalence of PD in urban and rural regions, although the definitions of urban and rural were unclear. A small study (25) conducted in a health district in Canada found a lower risk of PD in industrialized areas of the district. In a population-based mortality study, Rybicki et al. (28) demonstrated that counties in Michigan, U.S.A. with a...

Clinical Trials Of Levodopa

The initial therapeutic studies of levodopa in PD were carried out in the 1960s and early 1970s. The subjects were of varying disease durations, some quite advanced with dementia, and standard measures such as the Unified Parkinson's Disease Rating Scale (UPDRS) were not yet devised however, the results were dramatic (3). In 1967, Cotzias et al. (11) demonstrated the definitive effectiveness of high-dose L-Dopa (as opposed to D, L-Dopa). These investigators examined 28 patients in an open-label manner with intermittent blinded replacement with placebo and utilized levodopa without a dopa decarboxylase inhibitor. The duration of disease ranged from 1 to 30 years (mean 10 years). All patients responded, with 20 having a marked to dramatic improvement. All motor features improved. Some patients developed fluctuations and dyskinesia quickly and it was suggested that these problems related to duration of disease. Many studies followed which supported these findings (13,42-44). An example...

Does Tolerance Develop to Levodopa

The lay literature is replete with information suggesting that levodopa loses its effect after about five years. This leads to some trepidation on the part of the patient and physician in initiating therapy. If that were the case, it would indicate that tolerance is a possible concern and would argue for delaying treatment. It is conceivable that, when all nigrostriatal cells are depleted, levodopa would lose all effectiveness since these are the cells that convert levodopa and release dopamine. Lesser et al. (70) found that longer duration of disease did not appear to adversely affect response to levodopa at the time of initiation of therapy, yet they demonstrated deterioration in response that did not correlate with duration of disease. Those receiving levodopa longer had more severe disease. The assumption made by the authors was that PD patients developed tolerance. Despite these findings, the authors did not rule out the possibility that those receiving levodopa longer had a more...

Mortality of Parkinsons Disease with Levodopa

Several studies performed in the 1970s demonstrated that levodopa therapy improved mortality in PD. These studies compared the survival of levodopa-treated patients to the mortality rate demonstrated in the pre-levodopa Hoehn and Yahr study (122), which demonstrated that mortality was three times greater than the normal population. Nearly all studies indicated that levodopa improved survival with rates of 1.4 to 2.4 (119,120,123,124). Some investigators suggested that survival approached normal, whereas others indicated that the effect was only seen in the early years of therapy and then disappeared, suggesting that improvement was based on symptomatic responses. However, many of the studies have been criticized due to methodological flaws, problems with patient selection, and possible biases. One study (125) utilized a population-based study design (retrospective) to avoid many of these flaws and examined the change in survival related to levodopa therapy. The study included patients...

Is There an Association Between Levodopa Therapy and Melanoma

The connection between levodopa therapy, PD, and malignant melanoma has been a matter of debate for three decades. It originally derived from the biochemistry of the drug. Levodopa is a substrate for the development of dopamine, which, in turn, develops into neuromelanin in CNS nigral neurons. It is the dopaquinones derived from levodopa that are oxidized to form neuromelanin in these cells (126). Hence, it has been proposed that levodopa may also affect the activity of melanocytes in the skin, possibly promoting malignant transformation, although this connection has never been proven. In addition, it is now known that 70 of melanoma cases in the general population appear to be connected with a genetic mutation unrelated to PD. Thus, it would seem unlikely that there would be a connection between PD, lev-odopa, and melanoma. Nevertheless, reports of melanoma in patients treated in the 1970s led the FDA to require language in the package insert that cautions against the use of levodopa...

Levodopa And Homocysteine

An evolving concern with levodopa therapy relates to its association with elevated homocysteine (HC) levels. Since the late 1990s, several studies have indicated that levodopa dose correlates with elevation of HC. Postuma and Lang (131) reviewed this literature, and the relevance of the increase of HC to PD and patient health remains unclear. The concern relates to data suggesting that elevated HC levels increase the risk of stroke, coronary artery disease, and dementia (132-134). HC is metabolized from dietary methionine through two intermediates SAM (s-adenosylmethionine) and SAH (s-adenosylhomocysteine). HC is metabolized back to methionine via methylene tetrahydrofolate reductase (MTHFR) or to cysteine via other mechanisms. These enzymatic reactions occur in the presence of folate and vitamins B12 and B6. Hence, deficiency of any of these could lead to elevated HC. This is true for the presence of the C677T MTHFR polymorphism, which decreases metabolism of HC. In PD, it is the...

Levodopa Preparations

Levodopa is available with carbidopa as immediate release carbidopa levodopa 10 100, 25 100, and 25 250. It is also available in a sustained-release form as car-bidopa levodopa 25 100 and 50 200. An orally dissolvable form of immediate release carbidopa levodopa (Parcopa ) is available as 10 100, 25 100, and 25 250. Finally, levodopa is available with the COMT inhibitor, entacapone, in the following combinations Stalevo 50 (carbidopa 12.5mg levodopa 50mg entacapone 200 mg), Stalevo 100 (carbidopa 25 levodopa 100 entacapone 200), and Stalevo 150 (carbidopa 37.5 levodopa 150 entacapone 200).

Other Trials in Early Parkinsons Disease

Palhagen et al. (72) reported a study of selegiline in 157 de novo PD subjects. Selegiline 10 mg day delayed the need for levodopa by four months compared with placebo (P 0.028). There was a wash-in effect at six weeks and three months, with total and motor UPDRS scores significantly better in the selegiline group. At six months, the rate of disease progression was significantly slower for both total UPDRS (-1.9 vs. 3.5 P < 0.001) and motor UPDRS (-1.5 vs. 2.5 P < 0.001) (negative numbers refer to improvement and positive numbers refer to worsening). Between baseline and the end of an eight week washout period, there was significantly slower progression of total UPDRS scores in the selegiline group (11.3) compared with the placebo group (14.2), when length of time to reach the endpoint was used as a covariate (P 0.033) (72). The French Selegiline Multicenter Trial (77) randomized 93 de novo PD subjects to selegiline 10 mg day or placebo. Significant improvements in total and motor...

Advanced Parkinsons Disease

Selegiline has mild to moderate benefit as adjunct therapy to levodopa in advanced PD patients and is approved by the FDA in the United States for this indication. In a small double-blind placebo-controlled trial (79) of selegiline 10mg day in PD subjects (n 38) on stable levodopa doses, selegiline reduced daily levodopa dosage requirements (P < 0.05) and significantly improved tremor (P 0.02) over eight weeks. Thirty subjects (selegiline n 18, placebo n 12) completed a 16-month follow-up (79). Both mean levodopa dosage (-133 mg day) and dosing frequency were significantly reduced in the selegiline-treated group. Significantly less end-of-dose akinesia was reported in double-blind crossover trials with selegiline (80,81). Golbe et al. (82) randomized 96 PD patients with motor fluctuations that could not be improved with levodopa adjustments to selegiline 10 mg day or placebo. Mean hourly symptom control in subjects randomized to selegiline was significantly improved compared to...

Levodopa Methyl Ester

Levodopa methyl-ester carbidopa effervescent tablets (CNP-1512) are currently approved for rescue therapy in PD in Italy (Chiesi Farmaceutici). Outside of Italy, the drug (V1512) is owned by Vernalis Pharmaceuticals. This preparation is approximately 250 times more soluble in water and can thus be easily dissolved and orally administered. Studies comparing the drug with standard levodopa preparations demonstrate a faster onset of action (by a mean of 8.5 minutes) and a longer total duration of action (mean 15 minutes longer) with fewer dose failures. A large 39-center European trial compared levodopa methyl-ester with standard levodopa in patients already on levodopa who were experiencing at least two hours of off time. At 12 weeks, subjects on levodopa methyl-ester tended to have less off time than levodopa (-39.4 vs. +3.4 minutes, P 0.07). No unexpected adverse events have been noted. Phase III North American and European studies are planned (4).

Parkinsons Self Help Organizations in the United States

American Parkinson Disease Association, Inc. (APDA) 60 Bay Street, Suite 401 Staten Island, NY 10301 718-981-8001 800-223-2732 www.apdaparkinson.org Central Ohio Parkinson Society 3166 Redding Road Columbus, OH 43221 614-481-8829 Michigan Parkinson Foundation 3990 John Road Detroit, MI 48201 313-745-2000 National Parkinson Foundation, Inc. Miami, FL 33136-1494 305-547-6666 800-327-4545 www.parkinson.org (NPF affiliate chapters are in Orange County, Calif. Mt. Diablo, Walnut Creek, Calif. Redding, Calif. the Sacramento Valley, Calif. Kansas City, Mo. Topeka, Kan. Cape Cod, Mass. and Washington, D.C.) Parkinson's Disease Foundation (PDF) Parkinson's Educational Program 3501 Lake Eastbrook Boulevard Parkinson's Support Groups of United Parkinson Foundation and the International Tremor Foundation 833 West Washington Boulevard Chicago, IL 60607 312-733-1893 Young Parkinson's Support Network of California APDA Young Parkinson's I & R Michael J. Fox Foundation for Parkinson's Research...

Causes of dysphagia in PD

The etiology of dysphagia in PD is complex. It appears to be related to changes in the interaction between the basal ganglia, higher cortical regions, corticospinal and corticobulbar motor tracts, the sensorimotor trigeminal system, the dorsal vagal nucleus, the reticular formation, and other areas.

How do I meet other people with PD

You are not alone PD has a large and extensive support network. Several large national organizations, such as The National Parkinson Foundation, the Parkinson Disease Foundation (now merged into The Parkinson Foundation) and the American Parkinson Disease Association, that sponsor support groups throughout the country for PD patients and their families. Many hospitals and regional health centers also have support groups, and many patients have started groups of their own. A support group can be an important asset to your survival a lot can happen when a group of determined people rally around one uniting cause In addition to sharing their experiences with you, members of support groups can often teach you about services available in the community and other local resources. People in support groups stay well informed on the newest and best types of treatments or know when and where a new trial or study on PD is taking place. Support groups work to educate the community or promote...

Caffeine Parkinsons Disease

Caffeine may lower the risk of Parkinson's disease, say researchers at the U.S. Department of Veterans Affairs in Honolulu. Robert Abbott and colleagues studied more than 8,000 Hawaiian men of Japanese ancestry who were asked about their diets when they entered the Honolulu Heart Program in the mid-1960s and again in the early 1970s. Over the next 30 years, 102 of the men were diagnosed with Parkinson's disease. Those who drank no coffee had a two to three times greater risk of Parkinson's than coffee drinkers. Caffeine from other foods was also linked to a lower risk of the disease, but coffee was the largest source of caffeine among the men. While caffeine is the cause of many health problems, this connection with Parkinson's is interesting. People who have a predisposition to Parkinson's or early stages of the disease may have a dislike for coffee, says Abbott. Or, caffeine may delay the degeneration of neurons in the brain. The loss of neurons that produce the neurotransrnitter...

Perceptual and Phonetic Characteristics of Voice and Speech Disorders in Parkinsons Disease

Darley et al. (3) reported one of the first systematic descriptions of perceptual characteristics of speech and voice in individuals with PD (3,31,32). They identified reduced loudness, monopitch, monoloudness, reduced stress, breathy, hoarse voice quality, imprecise articulation, and short rushes of speech as the most characteristic of the speech and voice disorders in PD. They termed these symptoms hypoki-netic dysarthria. Logemann et al. (2) used phonetic and perceptual analyses to characterize voice and speech abnormalities in 200 nonmedicated individuals with PD. Of these individuals, 89 were found to have voice quality problems such as breathiness, hoarseness, roughness, and tremor and 45 also had speech prosody or articulation problems. Ho et al. (1) used perceptual and phonetic methods to characterize voice and speech problems in 200 individuals with PD. They found that voice problems were first to occur, with other speech problems (prosody, articulation, and fluency)...

Acoustic Measures of Abnormal Voice and Speech in Parkinsons Disease

Acoustic analyses of voice and speech in individuals with PD have confirmed the perceptual descriptions of hypokinetic dysarthria. Fox and Ramig (33) documented reduced vocal sound pressure level (vocSPL) by 2 to 4 dB (at 30 cm) on a number of speech tasks in 29 individuals with PD, compared with age- and gender-matched controls, which is equal to a 40 change in vocal loudness. Ho et al. (34) found vocSPL in PD to decay much faster than in neurologically normal speakers. They interpreted this fading as symptomatic of frontostriatal dysfunction. Rosen et al. (35) examined intensity decay in the phonation of persons with and without PD on various speech tasks. They found that vocSPL declined more rapidly in PD than in normal, age-matched speakers during syllable repetition speech diadochokinesis (DDK) . They also found that in some of the individuals with PD, there were abnormally abrupt changes in vocSPL during conversation. However, during sustained vowel phonation, vocSPL did not...

Physiologic Measures of Laryngeal Dysfunction in Parkinsons Disease

Additional data to support the laryngeal closure problems in PD come from analyses of EGG signals. Gerratt et al. (43) reported abnormally large speed quotient and poorly defined closing period in PD patients. Blumin et al. (44) used videostro-boscopy and fiberoptic endoscopic techniques, as well as a voice handicap index (VHI) questionnaire, to assess laryngeal function in 15 individuals with severe PD. Of these individuals, 13 (87 ) had significant vocal fold bowing and 14 (93 ) self-reported significant voice handicap. These observations were consistent with the slow vocal fold opening relative to the rate of closure and incomplete closure of the vocal folds. EMG studies of the laryngeal muscles provided further information regarding laryngeal pathology in PD. Hirose and Joshita (45) studied the EMG data from the thyroarytenoid (TA) muscles in an individual with PD who had limited vocal fold movement. They observed no reduction in the number of motor unit discharges and no...

Respiratory Dysfunction in Parkinsons Disease

A number of studies have provided evidence, through various aerodynamic measurements, for disordered respiratory function in individuals with PD. These disorders include reduced vital capacity, reduced total amount of air expended during maximum phonation tasks, reduced intraoral air pressure during consonant vowel productions, and abnormal airflow patterns (48-50). The origins of these airflow abnormalities are not clear but they may be related to variations in airflow resistance due to abnormal movements of the vocal folds and supralaryngeal area (50) or abnormal chest wall movements and respiratory muscle activation patterns (23,48,51). Articulatory and Velopharyngeal Disorders Acoustic and Kinematic Correlates of Articulatory Abnormalities in Parkinson's Disease Acoustic correlates of disordered articulation include problems with timing of vocal onsets and offsets (voicing during normally voiceless closure intervals of voiceless stops) (24) and spirantization (presence of...

Disordered vs Compensated Rate of Speech in Parkinsons Disease

Disordered rate of speech has been reported in some individuals with PD, and rapid rate or short rushes of speech have been reported in 6 to 13 of individuals with PD. Palilalia or stuttering-like speech disfluencies have been observed in a small percent of individuals with parkinsonism (30,31). The discrepant findings of speech rate in parkinsonian speech (slow vs. rapid) may be related to the presence or absence of compensatory mechanisms. Caliguiri (55) found, using kinematic analyses, that lip movements were normal when individuals with PD spoke at a rate of 3 to 5 syllable sec, but hypokinetic when the rate increased to 5 to 7 syllable sec, which is the typical rate of conversational speech. Similarly, Ackermann et al. (53) described a

Effect Of Medical Treatments For Parkinsons Disease On Speech And Swallowing

Although neuropharmacologic and neurosurgical approaches have had positive effects on the primary symptoms of PD, their effects on voice, speech, and swallowing have been inconsistent. Several studies have assessed the effects of levodopa and dopamine agonists on voice and speech functions in PD. Gallena et al. (47) studied the effects of levodopa on laryngeal function in six persons with early PD who were not receiving medication. They found that levodopa reduced excessive laryngeal muscle activity and vocal fold bowing and improved voice onset and offset control during speech in some patients. De Letter et al. (80) reported significant improvement in speech intelligibility with levodopa. Goberman et al. (81) examined the acoustic-phonatory characteristics of speech in nine individuals with PD and motor fluctuations before and after taking levodopa. They found that the voice F0 variability in vowels and mean F0 were higher, and intensity range was lower when on-medication, compared...

Effect Of Surgical Treatments For Parkinsons Disease On Speech And Swallowing Deep Brain Stimulation

Many studies of deep brain stimulation (DBS) of the subthalamic nucleus (STN), globus pallidus internus (GPi), and ventral intermediate (Vim) nucleus of the thalamus have reported dysarthria and dysphagia as side effects (88-90). Several studies examined specific aspects of voice, speech, swallowing and related orofacial, and respira-tory-laryngeal functions associated with DBS treatment of PD. Santens et al. (91) found that left-brain stimulation had a profound negative effect on prosody, articulation, and intelligibility not seen with right-brain stimulation. With bilateral stimulation, no differences in speech characteristics were observed on- and off-stimulation. Wang et al. (92) also studied the effects of unilateral STN DBS on respiratory phonatory subsystems of speech production in PD. Speech recordings were made in the medication-off state at baseline and three months post-DBS with stimulation-on and -off, in six right-handed patients. Three patients who received left-brain...

Behavioral Speech Voice And Swallowing Treatment For Parkinsons Disease

Although the incidence of speech and voice disorders in individuals with PD is extremely high, only 3 to 4 receive speech treatment (112). One explanation for this is that carryover and long-term treatment outcomes have been disappointing and consequently the primary challenges in the treatment of hypokinetic dysarthria associated with PD. Clinicians have long been aware that when dysarthric PD patients are receiving direct stimulation, prodding, or feedback from the speech clinician or an external cue (113,114), they are likely to show a dramatic improvement in speech and voice production and overall intelligibility. However, maintaining these improvements without these external cues is extremely difficult for most of these individuals. One explanation for the inability of individuals with PD to maximize and maintain treatment gains may be their deficits in internal cueing, vigilance, scaling amplitude of vocal output, and self-perception and self-regulation of vocal loudness and...

Intensive Voice Treatment for Parkinsons Disease

It is hypothesized that there are three features underlying the voice disorder in individuals with PD (i) an overall amplitude scale down (75,76) to the speech mechanism (reduced amplitude of neural drive to the muscles of the speech mechanism), which results in hypophonia, hypoprosodia, and hypokinetic articulation (ii) problems in the perception of vocal loudness and effort (77), which prevent the individuals with PD from accurately monitoring and scaling their vocal output and (iii) difficulty in independently generating (internal cueing scaling) the right amount of effort (78) to produce adequate vocal output (loudness, prosodic inflection, and amplitude of articulatory movement). The LSVT has been designed to address these problems.

Swallowing Treatment for Parkinsons Disease

Treatment of swallowing disorders in PD has not been well studied. Conventional techniques have included oral motor exercises to improve muscle strength, range of motion and coordination, and behavioral modifications such as effortful breath-hold, chin positioning, double swallow, the Mendelsohn maneuver, swallow cough, effortful swallow, and diet and liquid modifications (13,127). Effectiveness of these techniques varies and can be dependent on patient motivation and cooperation, family support, and the timeliness of the referral for a swallowing evaluation. Efficacy studies of the impact of behavioral treatment on dysphagia in PD are lacking (128). The effects of LSVT on swallowing dysfunction in individuals with PD have been studied by Sharkawi et al. (8). These researchers found that the LSVT reduced swallowing motility disorders by 51 . Some temporal measures of swallowing were also reduced, as was the amount of residue. This is the first study to find positive changes in both...

Complementary Therapies For Parkinsons Disease What Do We Really Know

There are very few well-designed studies and consequently very little evidence to support or refute the use of most complementary therapies for the treatment of PD. This does not mean that alternative therapies cannot help someone with PD, but for Western-trained healthcare providers treating someone with PD who is considering alternative therapies, it is difficult to know what and how to advise them. The first rule in medicine is do no harm, so if a particular therapy such as massage therapy is not thought to be harmful then it might be recommended. On the other hand, ingesting an herb, injecting glutathione, or ingesting a homeopathic remedy without any proof that it is beneficial and without knowing the potential harmful effects or drug interactions may not be in the best interest of a person with PD. Specific complementary therapies that are commonly prescribed by alternative practitioners are reviewed in the following section. As the majority of these therapies, especially those...

Multiple System Atrophy and Striatonigral Degeneration

MSA is a variant of PD characterized by a combination of clinical symptoms involving cerebellar, extra-pyramidal, and autonomic systems. The predominant subtype of MSA is striatonigral degeneration (SND), a form of levodopa unresponsive parkin-sonism. Neuropathological changes of SND include degeneration of the nigrostri-atal pathway, medium spiny striatal GABAergic projection pathways (putamen greater then caudate), as well as other regions of the brainstem, cerebellum, and spinal cord. Inclusion-like aggregates that immuno-stain for ubiquitin and alpha-synuclein are seen in oligodendrocytes and neurons. The basis for developing an animal model for SND emerged from established animal models for both parkinsonism having SNpc pathology and Huntington's disease (HD) with striatal pathology. For example, rodent models for SND have been Motor deficits in models for MSA and SND are assessed by ipsilateral and contralateral motor tasks (including stepping response, impaired paw reaching,...

Levodopa Challenge Test

It can be difficult to accurately differentiate PD from other forms of parkinsonism, especially during the early stages of disease. Levodopa administration can be used for diagnostic purposes, as PD patients respond more frequently and robustly to levodopa compared with other forms of parkinsonism. Clarke and Davies (145) reviewed 13 studies that examined whether an acute levodopa or apomorphine challenge test could aid in the diagnosis of PD. Four studies examined de novo patients and nine examined patients with clinically established PD. Although there was significant variability in the methodologies employed, abstracted sensitivity and specificity data were summarized from the studies and the two challenge tests compared as to their ability to accurately predict patients' diagnosis. The sensitivity for the diagnosis of established PD for apomorphine was 0.86 95 confidence interval (CI) , acute levodopa 0.75 (95 CI), and chronic levodopa therapy 0.91 (95 CI). The specificity for the...

Basic Concepts for Living with Parkinsons Disease

Being diagnosed with a chronic progressive illness like Parkinson's disease (PD) changes your life forever. Don't give up or give in to the disease Today is a very hopeful time for people with PD. I hope these thoughts and observations will help you. Staying Positive While Living with Parkinson's Disease 1. Learn about your illness. Don't be afraid to read about Parkinson's disease or talk to others who have it. Remember that no two cases are exactly alike, and no one can predict exactly how the disease will progress or affect you. Likewise, no two people respond exactly the same to treatments and medications. Gathering information about your illness, through books, medical journals, and the Internet, will empower you to make informed decisions about your medical care and the treatment options open to you. If you don't have Internet access at home, visit your local library and ask a librarian how to visit helpful web sites. See if there is a Parkinson's disease or movement disorder...

Parkinsons disease facts and figures

Parkinson's disease (PD) was first formally described by James Parkinson in an 1817 report (earlier records include a Shakespeare character with the condition). He described tremor, gait disorder, and brady-kinesia which he confused with paralysis, contributing to the misnomer 'paralysis agitans'. He was a general practitioner in Shoreditch, England. In a large population-based study in Rochester, Minnesota, the overall age-adjusted incidence of PD was relatively stable from 1979-1990. However, there was an increase for those aged 70-99 years, mainly due to drug-induced parkinsonism. The estimated standardized mortality rate (the ratio of number of deaths in PD patients to controls) varies between 1.5 and 2.4. Follow-up of 15-18 years of 149 patients in the Sydney multi-centre study reported a standardized mortality rate of 1.86. Hoehn and Yahr (who reported in the 1960s) found a standardized mortality rate of 2.9 (95 confidence interval (CI) 2.4-3.6), but this predated levodopa...

Parkinsons Disease PD

In PD, there is a loss of neurons in the substantia nigra and elsewhere in the brain in association with the presence of protein deposits in the cytoplasm of neurons (Lewy bodies) and thread-like proteinaceous inclusions within Lewy neurites. For years, it was thought that environmental factors, possibly toxins, were the cause of PD. In 1997, a gene associated with the disease was identified. Mutations in certain genes (the parkin or synuclein gene) can result from environmental toxins, such as exposure to pesticides. The LRRK2 gene was isolated by Andrew Singleton, Ph.D., of the National Institute on Aging at the NIH. A mutation of this gene is found in 5 of patients with inherited PD. Tatiana Foroud of the Indiana University School of Medicine examined 767 patients with PD from 358 families. The LRRK2 gene, located on chromosome 12, is one of five genes in patients with PD that are abnormal. There is a decrease in neuromelanin in the substantia nigra. There is proliferation of...

Sensorimotor and Perceptual Deficits Underlying Motor Dysfunction in Parkinsons Disease

Sensory problems in PD have been recognized for years (66), and these problems may underlie some of the disorders of the speech system. Sensorimotor deficits in the orofacial system (62,63,67) and abnormal auditory, temporal, and perceptual processing of voice and speech (26,27,53,68) have been documented in PD (28,63) and have been implicated as important etiologic factors in hypokinetic dysarthria secondary to PD (69). Schneider et al. (63) found marked sensorimotor deficits in the orofacial and limb systems of individuals with PD. They observed that individuals with PD, compared with age-matched controls, showed greater deficits in tests of sensory function and sensorimotor integration. They suggested that PD patients might have complex deficits in the utilization of specific sensory inputs to organize and guide movements due to abnormal sensory gating or filtering associated with basal ganglia motor dysfunction. Caliguiri and Abbs (62) described abnormal orofacial reflexes in some...

Does Levodopa Cause Motor Fluctuations

It has been known since the early days of levodopa therapy for PD that motor fluctuations and dyskinesia were associated with drug therapy (12). Barbeau (61) referred to it as the long-term levodopa syndrome. At that time, with no alternative treatments available, he indicated that its existence did not counterbalance the great usefulness of the drug. The questions are what causes their onset and progression and what are the key risk factors The main issues in the debate address whether they are a result of disease progression or primarily levodopa itself (or the manner in which it is delivered to the brain) or both. The answer is not totally clear, but this question has been examined extensively by (i) evaluating patient populations and examining which of the two factors correlates with the onset of fluctuations and dyskinesia and (ii) examining the actual response fluctuations in a controlled setting to determine possible etiologic explanations. In a retrospective study, Lesser et...

Symptoms And Management Of Autonomic Dysfunction In Parkinsons Disease Orthostatic Hypotension

A significant drop in systolic blood pressure when moving from sitting or lying to the standing position is undoubtedly one of the most important symptoms of autonomic failure seen in PD. Orthostatism can be either symptomatic, in which patients complain of lightheadedness, dizziness or actual syncope, or asymptomatic in spite of Estimates of the frequency of orthostatic hypotension vary. A community-based study conducted in U.K. found that 47 of a group of 89 patients enrolled had orthostatic hypotension, as defined by a drop of 20 mmHg when standing from a supine position or to a systolic pressure of less than 90 mmHg (19). They did not find an association between PD severity and the presence of orthostatic hypotension. In a study of early, untreated PD 14 of 51 patients met similar criteria for orthostatic hypotension (20). The strength of this study is that all patients were followed for at least seven years, and 9 of 60 patients were excluded from the analysis due to the...

Familial Parkinsonism

While most parkinsonian disorders are sporadic, rare familial forms have been described and mutations have been found or genetic linkage analyses have suggested a strong genetic factor in their etiology (58). Perhaps the most common cause of early onset familial PD is autosomal recessive juvenile PD (ARJP). The clinical features are somewhat atypical in that dystonia is common in ARJP (59). The pathology of ARJP is based upon only a few autopsy reports. Initial studies emphasized severe neuronal loss in the substantia nigra with no Lewy bodies, but a more recent report of an individual who died prematurely of an automobile accident had Lewy bodies in the substantia nigra and other vulnerable regions (60,61). Even in sporadic PD there is an inverse relationship between the disease duration and the number of Lewy bodies in the sub-stantia nigra. When the disease is very severe, there are very few residual neurons. Since Lewy bodies are intraneuronal inclusions that are phagocytosed...

Resonance Problems in Parkinsons Disease

Resonance problems are not common in PD, but when they are present, the voice often sounds like a foghorn. The acoustic and physiologic nature of this phenomenon is not clear, and perceptually, it is difficult to determine whether the voice is hypernasal or hyponasal. Aerodynamic and kinematic studies suggest that velopharyngeal movements may be reduced in some of these individuals (22,52,56). Abnormal tongue posture may also contribute to the resonance in parkinsonian speech. The abnormal resonance may also reflect motor symptoms not directly caused by PD such as pharmacologically induced dystonic or dyskinetic movements of the velopharyngeal and or tongue muscles.

Parkinsons Disease

The clinical features of Parkinson's disease (PD) include bradykinesia, rigidity, tremor, postural instability, autonomic dysfunction, and bradyphrenia. The most frequent pathologic substrate for PD is Lewy body disease (2). Some cases of otherwise clinically typical PD have other disorders, such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA) or vascular disease, but these are uncommon, especially when the clinical diagnosis is made after several years of clinical follow-up (3,4). The diagnostic accuracy rate has approached 90 in some series (5). The brain is usually grossly normal when viewed from the outer surface. There may be mild frontal atrophy is some cases, but this is variable. The most obvious morphologic change in PD is only visible after the brainstem is sectioned. The loss of neu-romelanin pigmentation in the substantia nigra and locus ceruleus is usually grossly apparent and may be associated with a rust color in the pars reticulata, which...

Is Levodopa Toxic

The notion that levodopa may be toxic to dopaminergic neurons leading to more rapid nigral degeneration has been a controversy for 25 years. It is based on a body of evidence that suggests that oxyradicals play an important role in the pathogenesis of cell death in PD (87). Evidence includes decreased glutathione, increased Fe2+, increased malondialdehyde, and decreased mitochondrial complex I activity in the substantia nigra (SN) (77). These changes appear to lead to apoptotic mechanisms of cell death (88). Dopamine, when metabolized by monoamine oxidase (MAO) or auto-oxidized, forms H2O2, a precursor to the toxic hydroxyl radical. In PD, after loss of a substantial number of nigral cells, those surviving neurons increase their dopamine metabolism, thus possibly increasing the risk of further free radical formation and neurodegeneration, especially in an environment where protective mechanisms such as glutathione are diminished and iron has accumulated. The use of levodopa may lead...

Isnt PD a disease of old people

For every person diagnosed with PD, at least two more have PD but have not been diagnosed. There are about 1.2 million people with PD in North America, and because the development of symptoms is slow and insidious, the time between onset and diagnosis may be between 2 to 5 years (some say PD may start 10 years before it's diagnosed). Given the long latency between the onset of the disease (which is virtually unnoticeable) and the diagnosis, it is estimated that for every person diagnosed with PD, at least two more have PD but have not been diagnosed. About 50,000 people are diagnosed with PD each year. PD affects slightly more men than women (approximately 55 men to 45 women). PD occurs evenly across different occupational and socioeconomic groups, and the rate of incidence has not changed since doctors have been keeping records. substantia nigra Figure 1 Diagram of the brain, showing the substantia nigra substantia nigra Figure 1 Diagram of the brain, showing the substantia nigra

Autonomic Dysfunction and Management

Although Parkinson's disease (PD) is commonly regarded as a disorder of dopamine deficiency, it is actually a multisystem degenerative disorder. As nondopaminergic brain pathways are involved in the genesis of many symptoms, these cannot be successfully treated by merely increasing brain dopaminergic stimulation. The auto-nomic symptoms fall into this category, and thus management is often challenging. The autonomic features of PD affect cardiovascular function, gastrointestinal (GI) motility, urinary bladder function, sexual ability, and thermal regulation. A list of the common symptoms and signs of autonomic dysfunction is shown in Table 1. Although symptoms of autonomic failure typically present later in the course of the disease, rare case reports exist of autonomic abnormalities as the presenting feature (1). This chapter will outline the common autonomic features of PD and discuss treatment approaches for each.

[123IMetaiodobenzylguanidine Scintigraphy

123I Metaiodobenzylguanidine (MIBG) is a norepinephrine analog, which is transported into and stored in the terminals of sympathetic nerve endings. MIBG uptake is expressed as a ratio of single photon emission computed tomography signal in heart to that of the upper mediastinum. The lower the ratio, the fewer are the functioning sympathetic nerve terminals in the heart. A number of studies have looked at the sympathetic innervation of cardiac muscle in PD patients using this technique, and all have shown that MIBG uptake in myocardium is significantly less in PD than in matched controls (4). Courbon et al. (5) compared MIBG uptake in two groups of patients with PD those with normal autonomic function tests and those with overt dysautonomia. They found that patients without dysautonomia had impaired MIBG uptake, just like patients with overt autonomic symptoms. They concluded that MIBG scintigraphy is a sensitive marker of PD, even in patients without autonomic symptoms. Orimo et al....

If a relative and I have PD does this mean PD is inherited

Heredity or genetic predisposition may play a role. Between 15 and 25 of people with PD report that another relative also has PD. In about 1 of families in whom PD is known to occur in many members over several generations. Studies of the genetics of these families have identified specific, mutated genes that are linked to PD. However, the results cannot be generalized to all people with PD. Genes are the basis for heredity. A gene consists of a long strand of four molecules arranged like beads on the 23 pairs of chromosomes found in each of us. Each chromosome carries thousands of genes, each gene consists of millions of molecules of the four chemicals that compose DNA. Genes determine the way in which proteins are made. If a gene is abnormal, the protein it determines will also be abnormal, and these abnormal proteins may cause PD. Scientists studying genetics have, so far, identified 3 mutations and 6 different locations in humans that are involved in PD. But there is much more to...

Urinary Bladder Dysfunction

The most frequent urinary complaints in PD patients are frequency, urgency, urge incontinence, and nocturia. Hobson et al. (58) performed a community-based questionnaire survey in Wales, U.K., and found that bladder problems were reported in 51 of 123 PD patients returning the survey compared to 31 of 92 controls. The calculated relative risk of developing bladder symptoms in PD patients compared to controls was 2.4. Lemack et al. (59) performed a similar questionnaire-based assessment of bladder problems in PD patients, but selected early-stage patients (Hoehn and Yahr stage 2.5 or lower) to determine if bladder problems occur early in the disease. Men with early PD assessed using the American Urological Association Symptom Index had a mean score of 12 compared to the community sample of normal male volunteers whose mean score was 4.8. Significant differences were seen on questions for frequency, urgency, and weak urinary stream. Women completed the Urogenital Distress Inventory-6...

Measuring Sleep Disorders

Until 2002, there were no specific instruments to clinically assess sleep problems of PD in a comprehensive and holistic fashion. Existing sleep scales for other disorders, such as the Pittsburgh Sleep Quality Index (PSQI), Stanford Sleepiness Scale, or the Karolinska Sleepiness Scale, are not specific for PD and have problems related to scale clinimetrics in relation to complexity and face validity when these are used in PD (66, 71-73). For instance, the PSQI, although quantifiable, does not specifically address sleep disturbances of PD, such as restlessness of legs, painful posturing of arms or legs, tremors, or fidgeting. The Stanford Sleepiness Scale and the Karolinska Sleepiness Scale appear too short for a comprehensive assessment of sleep problems. The gold standards for measurement of physiological aspects of sleep architecture are PSG and MSLT. However, these are tests of sleep structure, need specialized sleep laboratories, and can be expensive. In the United Kingdom, for...

Excessive Daytime Sleepiness

In PD, severe EDS needs treatment, and first concurrent medications that may be sedating should be eliminated or reduced (Table 5). Modafinil (100-400 mg day), a nonaddictive sleep-wake cycle activator, is nonstimulating and the only drug that has shown efficacy in improving EDS in double-blind, placebo-controlled trials (87,88). A seven-week, double-blind, placebo-crossover study of modafinil (200 mg) followed by a four-week open-label extension (200 and 400 mg) study by Adler et al. (88) showed significant improvement in ESS with modafinil and improvement in clinical global impression scores for wakefulness in the open-label arm. Those with high ESS scores and a history of sudden onset of sleep should be advised not to drive alone or long distances. Dopamine agonists when initiated should be titrated up slowly, especially in older patients.

Rapid Eye Movement Behavior Disorder and Restless Legs Syndrome

The treatment of choice for RBD is clonazepam, a benzodiazepine, although the mechanism is unknown and there are no controlled trials (13). Other drugs thought to be helpful for RBD include pramipexole, levodopa, carbamazepine, donepezil, and melatonin (64,89-91). Caution needs to be exercised with the use of clonazepam, as in some cases, RBD may be confused with sleep apnea, which can be worsened by clonazepam. Nighttime dosing with drugs such as selegiline may aggravate RBD. Others have reported a paradoxical worsening of RBD with deep brain stimulation (DBS) of the subthalamic nucleus (STN) (92). RLS may complicate PD and cause significant sleep disruption, and there are no trials investigating treatment of RLS in PD. In some cases, targeted treatment with a long-acting dopamine agonist such as cabergoline, given at nighttime, may be effective (84,85). The role of drugs, such as the rotigotine transdermal patch or the

Neuropsychology Behavioral Neurology And Neuropsychiatry

Sir William Osler first used the term neuropsychology in 1913 however, neuropsychology, at least as a clinical endeavor, did not emerge as a subdiscipline of psychology until the 1940s, largely in response to demands for the assessment and rehabilitation of brain-injured soldiers in World War II (1). The likely first published use of a clinical neuropsychological test with persons having parkinsonian syndrome is Shaskin et al.'s (2) administration of the Wechsler Bellevue Scale, an intelligence scale, to postencephalitic parkinsonians. Neuropsychology shares with behavioral neurology and neuropsychiatry the goal of relating behavior to underlying brain structure and function (3). However, neuropsychology's principal clinical method, namely its standardized, quantitative, norm-referenced approach to the evaluation

Attention and Executive Functions

Attention and executive deficits in PD are most often ascribed to frontal lobe dysfunction secondary to striatofrontal deafferentation and, in particular, pathophysio-logical alterations in the basal ganglionic-dorsolateral frontal loops with medial nigral dopamine depletion impacting the caudate and its frontal projections (31). Performance on simple tasks of attention, for example, forward digit span, is most often preserved in patients with PD (32). On the other hand, deficits on tasks, requiring complex attention, planning, reasoning, abstraction, conceptualization, and cognitive flexibility, are more readily identified in PD. Deficits are most apparent on tasks that require spontaneous, self-directed information, processing strategy formulation and deployment (33). Executive dysfunction may account for some of the deficits observed on recall, verbal fluency, and visuoperceptual tasks (34), but it is unlikely that executive deficits alone can explain the range of cognitive changes...

Visuospatial Perception

Visuoperceptual impairments are thought to occur in early PD, even when motoric task demands are minimized (62,63) however, some argue that visuoperceptual impairments are secondary to deficits in set-shifting, spatial memory, bradyphrenia, and dexterity (34,64). Visuospatial impairments do not appear to improve with dopamine replacement and do not reliably vary with motor on and off periods. Thus, if dopamine impacts visuoperceptual abnormalities in PD, it is probably in conjunction with other neurochemical or pathophysiological processes (65).

Anticholinergics and Cholinesterase Inhibitors

Anticholinergic medications used to treat motor symptoms in PD potentially produce adverse effects on memory, executive functions, and global cognitive abilities. In placebo-controlled studies, Bedard et al. (114,115) found anticholinergics to induce executive deficits in PD, but not in control participants. Although anticholinergic-induced memory decrements are observable even in patients without preexisting cognitive impairments (116), Saint-Cyr (117) found that confusional states are more likely to be induced by anticholinergics in patients with preexisting cognitive impairment. Thus, anticholinergics should be avoided in elderly patients who are susceptible to developing confusional states (118). Cholinesterase inhibitors were initially used sparingly and rarely in PDD and LBD. There is increasing recognition that cholinesterase inhibitors such as rivastig-mine, donepezil, and galantamine may improve not only cognition, but also neu-ropsychiatric symptoms in both conditions, and...

Preface to the Second Edition

Glenna had Parkinson's for about twenty years but never gave up living. A year after her diagnosis, she retired from teaching so that we could do some of the things we had planned for later in life. As you will see, she didn't let Parkinson's get her down. In fact, we worked on the book's revision in a campground in Florida. She and I still ran the Parkinson's support group that we started more than eighteen years ago. She remained busy on committees, in church, and by planning special events with her grandchildren. They were her pride and joy. It wasn't Parkinson's but other health problems that limited Glenna at the end. In fact, she died of a heart attack.

Selegiline and Rasagiline

Selegiline and rasagiline, selective monoamine oxidase-B (MAO-B) inhibitors, have been hypothesized to exert a neuroprotective effect in PD by way of reducing physiologic stress associated with MAO-B oxidation of dopamine. Along with improvement in motor functions, several small, uncontrolled studies have found selegiline to be associated with improved global cognitive functioning, P300 latencies, and or memory in patients with PD (137-140). In contrast, selegiline was reported not to significantly impact cognition in a large sample of untreated patients with early PD (141). The potential cognitive effects of rasagiline in PD patients have not been evaluated.

Are there tests for PD

No specific test is currently available to determine whether PD is the cause of your symptoms. A disease-specific biological marker for PD has not been found. The only conclusive test for PD is a postmortem examination of the brain. Taking a history of your symptoms, their relationship to one another, their evolution, and performing a neurological examination is, at present, the best way of making a diagnosis. Magnetic resonance imaging (MRI) will not make a diagnosis of PD. It may reveal disorders such as multiple strokes, hydro-cephalus (a fluid build-up in the brain) or a tumor that can mimic the symptoms of PD. PET and SPECT scans are relatively new and have provided much heretofore unavailable information about the state of the substantia nigra in living people. However, they are not readily available and require experts to interpret them. In time, PET and SPECT scans may become major adjuncts to the neurological examination. Parkinsonism a class of movement disorders with...

Deep Brain Stimulation

Nonablative surgical procedures for treatment of PD involve either unilateral or bilateral implantation of high-frequency stimulation electrodes into deep brain nuclei. Studies detailing neuropsychological outcomes after unilateral globus pallidus (GPi) deep brain stimulation (DBS) have supported the neurobehavioral safety of this technique (113,157), although a few studies have demonstrated minor postoperative declines in verbal fluency (158-160). The majority of studies indicate that even bilateral GPi stimulation is cognitively well tolerated (161-163), although in isolated cases, cognitive declines can occur (152,164).

Progressive Supranuclear Palsy

Prevalence rates of dementia in PSP range from 50 to 80 , but some authors contend that these numbers reflect over-diagnosis due to bradyphrenia, emotional problems, and visual dysfunction that accompany PSP. Cognitive deficits are seen in approximately 50 of patients with PSP (172), with the neuropsychological profile being typical of diseases with subcortical involvement, including slowed information processing, executive dysfunction, and information retrieval deficits (173). As compared to patients with PD, cognitive slowing and executive dysfunction in PSP emerges earlier in the disease course, is more severe, and progresses more rapidly (174-177), and this differential executive dysfunction may reflect radiographically demonstrated differences in frontal atrophy between the two conditions (178). Executive dysfunction in PSP may also differ qualitatively from that in PD (179). Memory and attention are relatively intact in PSP, although retrieval deficits and accelerated rates of...

Do these symptoms mean PD Can they mean something else

The symptoms of PD are called parkinsonism, but not all people with parkinsonism have PD. In fact, some of the symptoms of PD may be present in other diseases, the pathology and causes of which are different from PD. These PD-like disorders initially may be difficulty to distinguish from PD. In time, over several years, the differences become apparent. Occasionally, when doubt persists, a trial of levodopa may be given. Improvement occurs in PD improvement is less consistent, or not present in the PD-like disorders (Figure 2). Magnetic resonance imaging (MRI) is not helpful in diagnosing PD, the PD-like disorders, or in distinguishing PD from the PD-like disorders. Positron emission tomography (PET scans) or single photon Years of Levodopa Rx Figure 2 Curves showing how levodopa therapy affects PD patients over time, with 85 of patients having an improvement of symptoms in the first two years. Over time, about 1 3 of these responsive patients show a marked decline, 1 3 return to near...

Have PD What do I do

If you have been diagnosed with PD, you may feel many conflicting emotions. You may fear becoming physically, emotionally, and economically dependent on others, or you may worry because the money that you've saved for retirement may have to go toward paying medical expenses. You may think that you no longer control your future or that you're alone and isolated. All of these concerns are normal however, there are things you can and should do to take control of PD. your job, your friends, and most of all, your independence. These are honest reasons for being fearful or anxious however, an excellent way to master fear is to learn as much as you can about PD. Talk with people who have PD and who have gone through similar experiences. They can tell you what worked or what didn't. Find resources, information, workshops, and support groups that can help you to understand PD. For example, the National Parkinson Foundation has more than 1,000 support groups throughout the United States and has...

Detection and Recognition

No standardized tool or method has been specifically developed to detect and assess anxiety in the PD population. Detection may be problematic, because several symptoms of anxiety overlap with mental and somatic symptoms commonly associated with PD. The Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for GAD in the general population includes a period of at least six months with prominent tension, worry, and feelings of apprehension about everyday events and problems, along with the presence of at least four of 22 accompanying autonomic, psychic, and somatic symptoms (36). However, several of these accompanying symptoms, such as tremor, concentration difficulties, dizziness, muscle aches, and numbness or tingling, are also commonly attributed to PD and may not be recognized as components of an anxiety disorder. Given that anxiety appears to be common over the course of PD, periodic assessment would significantly enhance detection. In the absence...

Why is PD called a movement disorder

PD, PSP, and MSA, described in Question 17 earlier, fall into a category of disorders in which movement is either slowed or absent. Although the tremor in PD may resemble a hyperkinetic disorder, the fact that it occurs when the limb is at rest places it in the hypoki-netic category.

Preface to the First Edition

This is the book that I wish I could have found when my Parkinson's was diagnosed in 1981. At the time, very little information was available for the layperson, and the little that existed was very depressing. What I wanted to find was a source of information that would help me understand Parkinson's, that would give me an opportunity to relate to someone who has managed well in the same situation, and that would leave me with reasons to maintain a positive attitude. This is my personal story how I have coped and how I continue to cope positively as a person living with Parkinson's. It is interwoven with facts about managing Parkinson's as I have learned them since my diagnosis, through Talking with other people who have Parkinson's My Parkinson's specialist, Dr. Robert G. Feldman, and his knowledgeable team in the Parkinson's Program at Boston Medical In this book, I attempt to present the facts while, at the same time, sharing the ups and downs of my daily life as someone who has...

Depression Epidemiology

In a community-based study, the prevalence of depressive symptomatology in PD patients was six times that of healthy age- and sex-matched controls (2). In a registry-based study of 211,245 patients, Nilsson et al. (65) compared the incidence of depression in PD patients (n 11,698) with non-PD patients with diabetes (n 91,318) and non-PD patients with osteoarthritis (n 10,822) who were matched for degree of disability. An increased probability of developing a depressive episode was found for patients with PD when compared with the diabetes and osteoarthritis groups. Nilsson et al. (66) also showed that patients with an affective disorder (depression or mania) had an increased risk of being diagnosed with PD (odds ratio 2.2) when compared to patients with osteoarthritis or diabetes. In an analysis of 10 studies that used DSM-III criteria to define depression, an aggregate prevalence of 42 was reported for depressive disorders in PD (67). The prevalence rates...

Detection and Assessment

There are no reliable and empirically derived criteria for recognition of depression in PD. Therefore, it is not surprising that depression remains under-detected and under-treated in the PD population (15,71). In a clinic-based study, nearly two-thirds of patients with clinically significant depressive symptomatology were not receiving antidepressant therapy (11). Older individuals often underreport depressive symptoms and are likely to focus on somatic or vegetative complaints (e.g., fatigue or loss of energy, reduced sexual desire or functioning, pain, sleep changes, or appetite changes), which are the prominent features of mood disorders as well as PD (102). Patients may simply attribute any mood symptoms to their PD, even when their PD has been relatively stable and the mood changes are relatively acute. In one study, over half the patients who had clinically significant depressive symptoms did not consider themselves depressed (11). In a clinic-based study, the detection of...

Assessment of Efficacy

Overall, based on clinical experience and the available scientific data, SSRIs and TCAs may be considered useful for the treatment of depression in PD, and the agent that provides the best overall clinical benefit-to-risk profile should be selected (168). Amoxapine and lithium should be avoided, given the propensity of these agents to worsen motor symptoms and the availability of safer agents (169,170). Additionally, the nonselective MAO inhibitors (e.g., isocarboxazid, phenelzine, and tranylcypromine) should be avoided in levodopa-treated patients due to the risk of hypertensive crisis. Several antidepressants, such as bupropion, fluoxetine, fluvoxamine, nefa-zodone, and paroxetine, are potent in vivo inhibitors of various cytochrome P450 (CYP450) drug-metabolizing isoenzymes (171,172). These antidepressants may increase the risk for drug interactions.

PD is progressive What does this mean

Example, the stooped posture of PD may be taken as bad posture, or the softening of the voice may be taken as hoarseness. When PD begins, usually only one side is affected, such as stiffness in a leg when you're walking or holding an arm flexed at your elbow and close to your body. As PD progresses, the other side becomes involved. Often you are not aware of the changes and don't think anything is wrong It is your spouse or partner who insists there has been a change. Changes are not rapid in PD in fact, if a change does appear suddenly, then it is time to check for something else.

What is the goal of treatment

Because there is no cure, the goal of treatment in PD, as in all incurable diseases, is to provide you with the best quality of life that is possible. Successful treatment starts by establishing good working relationships between you, your doctor, and your family. It requires working together to find not only the best drugs but also the best ways to live with PD. To accomplish this, it is important that you know as much as you can about PD and how your drugs work. It is not enough just to take your drugs. You must be willing to change your life to make the most of living with PD.

Pathophysiology of Psychosis and Risk Factors

The pathophysiology of psychosis in PD is poorly understood, but dopaminergic and serotonergic mechanisms have been proposed. One theory is that chronic excessive stimulation of dopamine receptors, particularly in the mesolimbic mesocorti-cal pathways, causes hypersensitization, resulting in psychosis when patients are treated with dopaminergic agents (36). However, exogenous dopamine supplementation by itself is not the only factor in the development of psychosis since all PD medications (anticholinergics, dopaminergics, and amantadine) can induce similar hallucinations despite their different mechanisms of action (25), and PD psychosis was described prior to the use of levodopa (37). Serotonin has been implicated because the atypical antipsychotic drugs are purported to work through their high affinity for 5-HT2 compared to D2 receptors. However, PD patients with psychosis have decreased serotonin content in the brainstem at autopsy (38). Potential explanations for this finding...

Atypical Antipsychotics

Atypical antipsychotics are typically used to treat psychosis in PD. Table 1 provides a summary of atypical antipsychotic studies in PD. The United States Food and Drug Administration (FDA) recently asked all atypical antipsychotic manufacturers to add a boxed warning to their product labels, saying that atypical antipsychotics, when used in elderly patients with dementia, were associated with a higher risk of mortality (54). However, since the deaths were primarily due to cardiovascular or infectious causes, it is unclear how the atypical antipsychotics cause increased mortality. Since psychosis can be difficult to treat in PD, it is likely that these agents will continue to be utilized until a direct cause and effect relationship is uncovered. Parkinson Study Abbreviations-. BPRS, Brief Psychosis Rating Scale CGIS, Clinical Global Impression of Severity NPI, Neuropsychiatrie Inventory PANSS, Positive and Negative Syndrome Scale PD, Parkinson's disease UPDRS, Unified Parkinson's...

Cholinesterase Inhibitors

Fabbrini et al. (104) administered donepezil (5 mg qhs) to eight nondemented PD patients with visual hallucinations, with or without delusions. At the end of two months, subjects had decreased PPRS scores with hallucinations and paranoid ideation, being the most responsive. However, two patients experienced clinically significant motor decline. Another small open-label study enrolled six patients with PD, dementia, and psychotic symptoms and treated them with 10 mg d of donepezil (105). Five patients showed moderate-to-significant improvement in psychosis and one showed minimal improvement. None had worsening of motor symptoms. Finally, Kurita et al. (106) reported three PD patients who had improvement of visual hallucinations with 5 mg d of donepezil without worsening of motor function, but one patient had treatment emergent delusions that resolved, after donepezil was discontinued. Only one placebo-controlled trial of donepezil has been reported for PD psychosis (107). This was a...

Electroconvulsive Therapy

Electroconvulsive therapy (ECT) is an effective treatment for primary psychiatric disorders, especially treatment-resistant depression. Experience with ECT for PD psychosis, however, is limited to case studies. ECT has been demonstrated to be beneficial in PD patients with psychosis (112-114), and can transiently improve parkinsonian motor symptoms, but may require a period of hospitalization, and result in significant confusion. ECT should only be considered when patients are resistant to pharmacological therapies.

Long Term Outcome of Treatment for Psychosis

Goetz and Stebbins (5) described 11 PD patients in a nursing home with hallucinations, all of whom were never discharged from the nursing home and died within two years. In an open-label extension of the U.S. double-blind clozapine trial, only 25 of completers died over a 26-month observational period. Forty-two percent were in nursing homes, 68 were demented, and 69 were still psychotic (4). A separate study of 39 parkinsonian patients, treated with clozapine for psychosis, found that only 15 had died over a span of five years and 33 had been admitted to nursing homes (115).

Incidence Prevalence and Risk Factors

Estimates of incidence and prevalence of dementia in PD vary widely because of different definitions, methods of ascertainment, and study designs. Prevalence rates of dementia in hospital- or clinic-based cohort studies range from 11 to 22 (123-125), whereas population-based estimates are somewhat higher, ranging from 18 to 44 (9,126-129), perhaps reflecting referral bias. A recent systematic review of the literature estimated that the prevalence of dementia in PD ranges from 25 to 31 (130). This review also found that dementia in PD accounted for 3 to 4 of the total dementia population. Incidence rates for PD dementia range from 4 to 11 per year, with a relative risk for the development of dementia in PD of 2 to 6 (12,129,131-133). Age and severity of extrapyramidal symptoms were associated with an overall risk of developing dementia. One study demonstrated that age and severity of disease by themselves were not associated with a greater risk of dementia, but the combination of these...

Pathophysiology of Dementia

There is controversy regarding which features are the primary contributors to dementia in PD. PD is characterized by cell loss in the substantia nigra pars compacta (SNc), resulting in loss of dopaminergic input into the striatum. Several pathological and functional imaging studies have shown that in PD, there is greater depletion in the lateral compartment of the SNc, which projects to the putamen, than in the medial compartment, which projects to the caudate (139-141). Cognitive impairment is associated with loss of dopaminergic projections to the caudate (142). This functional division of the striatum is, perhaps, the main reason for the predominance of motor, over cognitive symptoms in PD and is likely why dopaminergic agents do not markedly improve cognition in PD (143). A relationship between cholinergic deficiency and dementia in PD has also been reported (144). Striking cell loss is seen in the nucleus basalis of Meynert, which provides projections to the amygdala and...

Other Pharmacologic Agents

Few other pharmacologic strategies for specifically treating dementia in PD have even been reported. Because noradrenergic depletion could contribute to executive dysfunction in PD, Bedard et al. (170) conducted a trial of naphtoxazine (SDZ-NVI-085), a selective noradrenergic alpha 1 agonist, versus placebo in nondemented patients with PD. The results of the study demonstrated improved performance on tasks of set-shifting and cognitive flexibility, such as the Stroop and Odd-Man-Out tests. Furthermore, specific evoked potentials (Nd1 and Nd2 curves), thought to reflect attentional processes and known to be affected in PD, were improved with naphtoxazine. Memantine, an N-methyl-D-aspartate antagonist, has been approved for AD but to date there are no published studies of memantine for PD dementia. Estrogen replacement therapy (ERT) may be a reasonable protective strategy for the development of dementia in women who have PD. The effect of ERT on the risk of development of dementia was...

Why should I take Sinemet

Carbidopa levodopa (Sinemet) helps reverse most of the symptoms of PD in most people but will not delay the rate of progression of PD. There are, however, concerns about how long the action of Sinemet will last. The levodopa in Sinemet is changed by cells in the substantia nigra into dopamine. As PD progresses, there is a continual loss of cells in the substantia nigra and the remaining cells become less efficient in changing levodopa to dopamine. There is no evidence that levodopa increases the rate of progression of PD, but as the cells die because of PD, the remaining cells are not as effective as they were originally. The early use of Sinemet, especially at doses of 600 mg a day or more of levodopa, is more likely to result in the appearance of changes such as wearing off and dyskinesia after 2 Sinemet comes in two forms immediate or regular-release and a controlled or extended release, with varying doses of each, giving you and your doctor more possibilities to adjust the dosage...

Multiple System Atrophy

MSA refers to a neurodegenerative disease characterized by parkinsonism, cerebellar ataxia, and orthostatic hypotension (31). There is no known genetic risk factor or genetic locus in MSA. The MSA brain shows varying degrees of atrophy of the cerebellum, cerebellar peduncles, pons and medulla, as well as atrophy and discoloration of the posterolateral putamen and pigment loss in the substantia nigra. The histopathological findings include neuronal loss, gliosis, and microvacuolation, involving the putamen, substantia nigra, cerebellum, olivary nucleus, pontine base, and intermediolateral cell column of the spinal cord. White matter inevitably shows demyelination, with the brunt of the changes affecting white matter tracts in the cerebellum and pons (Fig. 3). FIGURE 3 Multiple system atrophy (MSA) Substantia nigra neuronal loss in MSA is obvious in the cluster of pigment-laden macrophages (arrow in A), but neuronal inclusions are not present. Synuclein immunostaining of the substantia...

Midbrain Dopamine Neurons That Express Calcium Binding Proteins

CR is closely related to CB and has significant similarities in the homology of the amino acid sequence (32,33). CR-immunoreactive neurons are much less frequently observed in the entire brain. Approximately 50 of CR-immunoreactive cells in the SN VTA complex also display TH-immunoreactivity (34,35). Within the midbrain, CR-immunoreactive cell bodies are more numerous in all the subdivisions of dopamine neurons of the VTA than in the SNpc. Within the SNpc, the CR-positive cells are more abundant in the dorsal tier of the SNpc than substantia nigra pars reticulate (SNpr) or substantia nigra pars lateralis (SNpl).

Transcription Factor Pitx3

Yet another clue to the factor(s) that render the dopamine neurons of the SNpc vulnerable to neurodegeneration in PD is obtained from the studies on the role of the transcription factor Pitx3 in aphakic mice. Aphakic mice have small eyes with no lens and a loss of development of the anterior chamber of the eye (57,58). The clinical features of the aphakic mice result from a deletion of a large segment of the promotor region, exon 1, and intron regions of the Pitx3 gene (58). In addition to the ophthalmic dysgenesis, aphakic mice exhibit degeneration of dopamine neurons of the SNpc cells during development. Pitx3 expression is localized to TH-immunoreactivity. Pitx3 is necessary for the expression of TH as well as continued maintenance of TH expression, even during the rest of the life of midbrain dopamine neurons. Accordingly, Pitx3 is expressed during ontogenesis of dopamine neurons as well as throughout the rest of the life of the midbrain dopamine neurons in rodents and humans...

Anatomy The Basics For Circuitry

The major sources of input to the striatum are glutaminergic projections from the cerebral cortex and thalamus. Virtually, the entire cortex projects to the striatum in a topographic fashion. The frontal cortex projects to the head of the caudate and anterior putamen, the motor and somatosensory cortices project to the postcommissural putamen, and the temporal cortex projects to the tail of the caudate. The cortex also projects directly to the STN. Inputs from the thalamus include projections from the centromedian, parafascicular, and VL thalamus. The substantia nigra pars compacta (SNpc) sends dopaminergic projections to the striatum. The striatum projects to the globus pallidus external segment (GPe), Gpi, and substantia nigra pars reticulata (SNr). There appears to be two separate groups of striatal neurons based on projection targets and neurotransmitters. All outputs from the striatum utilize gamma amino butyric acid (GABA) but differ in the polypeptide cotransmitter. Striatal...

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