Parkinson Disease: New England

Fregni F, Pascual-Leone A. · Harvard Medical School and the Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. · Nat Clin Pract Neurol. · Pubmed #17611487 No free full text.

Abstract: In neurology, as in all branches of medicine, symptoms of disease and the resulting burden of illness and disability are not simply the consequence of the injury, inflammation or dysfunction of a given organ; they also reflect the consequences of the nervous system's attempt to adapt to the insult. This plastic response includes compensatory changes that prove adaptive for the individual, as well as changes that contribute to functional disability and are, therefore, maladaptive. In this context, brain stimulation techniques tailored to modulate individual plastic changes associated with neurological diseases might enhance clinical benefits and minimize adverse effects. In this Review, we discuss the use of two noninvasive brain stimulation techniques--repetitive transcranial magnetic stimulation and transcranial direct current stimulation--to modulate activity in the targeted cortex or in a dysfunctional network, to restore an adaptive equilibrium in a disrupted network for best behavioral outcome, and to suppress plastic changes for functional advantage. We review randomized controlled studies, in focal epilepsy, Parkinson's disease, recovery from stroke, and chronic pain, to illustrate these principles, and we present evidence for the clinical effects of these two techniques.

Cohen PD, Herman L, Jedlinski S, Willocks P, Wittekind P. · Parkinson Pipeline Project, Washington, DC 20015, USA. · Neurotherapeutics. · Pubmed #17599719 No free full text.

Abstract: A patient-centered paradigm for clinical research and medical care is presented as a solution to the problem of declining innovation and increasing costs and development time in the pipeline for new therapies. Fundamental differences in values and motivations among scientists, clinicians, industry sponsor, and patients in neurotherapeutics provide a framework for analysis of ethical conflicts and the loss of public confidence in medical research. Parkinson advocates' views on clinical trial participation, perceived risks and benefits, placebo controls, and sham surgery are presented. These views reflect the sense of urgency and the unique perspective that comes from living with this progressive, debilitating condition full time. A patient-centered paradigm that includes authentic voices of patients as collaborators at every stage of development will help to resolve conflicts, build trust, recruit trial participants, and accelerate new therapies. Key elements are adaptive clinical trial methods and the development of information technology for the assessment of outcomes and surveillance of safety over the life cycle of a medical product. Supported by the Parkinson's Disease Foundation, the Parkinson Pipeline Project is a grassroots group of Parkinson's patients whose goal is to represent an authentic voice for patients in the treatment development process. This group promotes education and communication between members of the Parkinson's community and active stakeholders in medical research, industry, and regulatory agencies. Its members are an example of a new breed of knowledgeable consumers, armed with first-hand access to research findings and reinforced by on-line connections to like-minded peers throughout the world.

Walsh EP. · Electrophysiology Division, Department of Cardiology, Children's Hospital Boston, 300 Longwood Ave, Boston, MA 02115, USA. · Circulation. · Pubmed #17592091 links to  free full text

This publication has no abstract.

Borek LL, Chou KL, Friedman JH. · Neurohealth Alzheimer's Disease and Movement Disorders Center, and Department of Geriatric Psychiatry, Butler Hospital, Warren Alpert Medical School of Brown University, RI, USA. · Expert Rev Neurother. · Pubmed #17563253 No free full text.

Abstract: Parkinson's disease is a progressive and debilitating movement disorder that is diagnosed by its motor signs. The behavioral manifestations of Parkinson's disease are prevalent and frequently complicate the course of the disease. These may be due to the illness itself or its treatment and are often more disabling than the motor symptoms. This review focuses on the management of the most common behavioral symptoms of Parkinson's disease, including depression, anxiety, psychosis, dementia, delirium, sleep disorders, fatigue, apathy, emotionalism and compulsive behaviors.

Seltzer B. · V.A. Boston Healthcare System, Department of Neurology, Harvard Medical School, Geriatric Research Center, Boston, MA 02130, USA. · Expert Opin Pharmacother. · Pubmed #17472546 No free full text.

Abstract: Donepezil hydrochloride is the most widely prescribed drug for Alzheimer's disease (AD). The main mechanism of action through which it influences cognition and function is presumed to be the inhibition of acetylcholinesterase enzyme in the brain; however, donepezil may also impact the pathophysiology of AD at several other points. Officially approved for mild-to-moderate and severe AD, donepezil has also been shown to be effective in early-stage AD, vascular dementia, Parkinson's disease dementia/Lewy body disease and cognitive symptoms associated with multiple sclerosis. In addition, one study suggested that donepezil may delay the onset of AD in subjects with mild cognitive impairment, a prodrome to AD. The pharmacokinetics, pharmacodynamics, safety/tolerability profile and drug interaction properties of donepezil make it an easy and safe agent to use. However, in general, the efficacy of donepezil is limited, and ongoing studies are investigating other agents that may ultimately overtake its present position as the mainstay of anti-AD therapy.

Chou KL, Borek LL, Friedman JH. · Department of Clinical Neurosciences, Warren Alpert Medical School of Brown University, Providence, RI, USA. · Expert Opin Pharmacother. · Pubmed #17472539 No free full text.

Abstract: Psychosis may be seen with several movement disorders. As pharmacological treatments can sometimes worsen movement disorders, psychosis in these situations can be complex for clinicians to manage. This review covers the management of psychosis in three different movement disorders: Parkinson's disease, dementia with Lewy bodies and Huntington's disease.

Gale JT, Amirnovin R, Williams ZM, Flaherty AW, Eskandar EN. · Department of Neurosurgery, Massachusetts General Hospital, Boston, MA 02114, USA. · Neurosci Biobehav Rev. · Pubmed #17466375 No free full text.

Abstract: Despite remarkable advances, the relationship between abnormal neuronal activity and the clinical manifestations of Parkinson disease (PD) remains unclear. Numerous hypotheses have emerged to explain the relationship between neuronal activity and symptoms such as tremor, rigidity and akinesia. Among these are the antagonist balance hypothesis wherein increased firing rates in the indirect pathway inhibits movement; the selectivity hypothesis wherein loss of neuronal selectivity leads to an inability to select or initiate movements; the firing pattern hypothesis wherein increased oscillation and synchronization contribute to tremor and disrupt information flow; and the learning hypothesis, wherein the basal ganglia are conceived as playing an important role in learning sensory-motor associations which is disrupted by the loss of dopamine. Deep brain stimulation (DBS) surgery provides a unique opportunity to assess these different ideas since neuronal activity can be directly recorded from PD patients. The emerging data suggest that the pathophysiologic changes include derangements in the overall firing rates, decreased neuronal selectivity, and increased neuronal oscillation and synchronization. Thus, elements of all hypotheses are present, emphasizing that the loss of dopamine results in a profound and multifaceted disruption of normal information flow through the basal ganglia that ultimately leads to the signs and symptoms of PD.

Horvitz JC, Choi WY, Morvan C, Eyny Y, Balsam PD. · Department of Psychology, Boston College, Chestnut Hill, MA 02467, USA. · Ann N Y Acad Sci. · Pubmed #17360799 No free full text.

Abstract: While extracellular dopamine (DA) concentrations are increased by a wide category of salient stimuli, there is evidence to suggest that DA responses to primary and conditioned rewards may be distinct from those elicited by other types of salient events. A reward-specific mode of neuronal responding would be necessary if DA acts to strengthen behavioral response tendencies under particular environmental conditions or to set current environmental inputs as goals that direct approach responses. As described in this review, DA critically mediates both the acquisition and expression of learned behaviors during early stages of training, however, during later stages, at least some forms of learned behavior become independent of (or less dependent upon) DA transmission for their expression.

Brass SD, Chen NK, Mulkern RV, Bakshi R. · Center for Neurological Imaging, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. · Top Magn Reson Imaging. · Pubmed #17179895 No free full text.

Abstract: Deposition of iron in the brain is proposed to play a role in the pathophysiology of the normal aging process and neurodegenerative diseases. Whereas iron is required for normal neuronal metabolism, excessive levels can contribute to the formation of free radicals, leading to lipid peroxidation and neurotoxicity. Magnetic resonance imaging (MRI) is a powerful tool to detect excessive iron in the brain and longitudinally monitor changes in iron levels. Iron deposition is associated with a reduction in the T2 relaxation time, leading to hypointensity on spin-echo and gradient-echo T2-weighted images. The MRI changes associated with iron deposition have been observed both in normal aging and in various chronic neurological diseases, including multiple sclerosis, Alzheimer disease, and Parkinson disease. Magnetic resonance imaging metrics providing information about iron concentrations include R2, R2', and R2*. The purpose of this review is to discuss the role of iron and its detection by MRI in various neurological disorders. We will review the basic biochemical properties of iron and its influence on MRI signal. We will also summarize the sensitivity and specificity of MRI techniques in detecting iron. The MRI and pathological findings pertaining to brain iron will be reviewed with respect to normal aging and a variety of neurological disorders. Finally, the biochemistry and pathophysiology surrounding iron, oxidative stress, free radicals, and lipid peroxidation in the brain will be discussed, including therapeutic implications. The potential role of iron deposition and its assessment by MRI provides exciting potential applications to the diagnosis, longitudinal monitoring, and therapeutic development for disorders of the brain.

Friedman JH, Brown RG, Comella C, Garber CE, Krupp LB, Lou JS, Marsh L, Nail L, Shulman L, Taylor CB, Anonymous00113. · NeuroHealth, Warwick, Rhode Island 02886, USA. · Mov Disord. · Pubmed #17133511 No free full text.

Abstract: Fatigue is a common problem in Parkinson's disease (PD), often the most troubling of all symptoms. It is poorly understood, generally under-recognized, and has no known treatment. This article reviews what is known about the symptom, putting it into the context of fatigue in other disorders, and outlines a program for developing better understanding and therapy.

Friedl KE, Grate SJ, Proctor SP, Ness JW, Lukey BJ, Kane RL. · U.S. Army Research Institute of Environmental Medicine, Natick, MA 01760-5007, United States. · Arch Clin Neuropsychol. · Pubmed #17127031 No free full text.

Abstract: Information on the mental status of soldiers operating at the limits of human tolerance will be vital to their management in future deployments; it may also allow earlier intervention for conditions such as undiagnosed Gulf War illnesses and Parkinson's Disease. The Army needs a parsimonious set of neuropsychological tests that reliably identify subtle changes for: (1) early detection of individual health and military performance impairments and (2) management of occupational and deployment health risks. Testing must characterize cognitive lapses in healthy individuals faced with relevant operational stressors (i.e., anxiety, information overload, thermal strain, hypoxia, fatigue, head impact, chemical or radiation exposures, metabolic challenges). This effort must also explore the neuropsychological methods in militarily relevant conditions to extend our understanding of relevant functional domains and how well they correspond to modes of testing. The ultimate objective is unobtrusive real-time mental status monitoring.

Schwarzschild MA, Agnati L, Fuxe K, Chen JF, Morelli M. · MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Boston, MA 02129, USA. · Trends Neurosci. · Pubmed #17030429 No free full text.

Abstract: The adenosine A2A receptor has emerged as an attractive non-dopaminergic target in the pursuit of improved therapy for Parkinson's disease (PD), based in part on its unique CNS distribution. It is highly enriched in striatopallidal neurons and can form functional heteromeric complexes with other G-protein-coupled receptors, including dopamine D2, metabotropic glutamate mGlu5 and adenosine A1 receptors. Blockade of the adenosine A2A receptor in striatopallidal neurons reduces postsynaptic effects of dopamine depletion, and in turn lessens the motor deficits of PD. A2A antagonists might partially improve not only the symptoms of PD but also its course, by slowing the underlying neurodegeneration and reducing the maladaptive neuroplasticity that complicates standard 'dopamine replacement' treatments. Thus, we review here a prime example of translational neuroscience, through which antagonism of A2A receptors has now entered the arena of clinical trials with realistic prospects for advancing PD therapeutics.

Wurtman RJ. · Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. · Metabolism. · Pubmed #16979425 No free full text.

Abstract: Narcolepsy is a chronic neurologic disease characterized by excessive daytime sleepiness and one or more of three additional symptoms (cataplexy, or sudden loss of muscle tone; vivid hallucinations; and brief periods of total paralysis) related to the occurrence of rapid eye movement (REM) sleep at inappropriate times. The daytime sleepiness typically presents as a sudden overwhelming urge to sleep, followed by periods of sleep that last for seconds or minutes, or even longer. During daytime sleep episodes, patients may exhibit "automatic behavior," performing conventionalized functions (eg, taking notes), but not remembering having done so once they are awake. About 10% of narcoleptics are members of familial clusters; however, genetic factors alone are apparently insufficient to cause the disease, inasmuch as the most common genetic disorder, a mutation in chromosome 6 controlling the HLA antigen immune complex, although seen in 90% to 100% of patients, also occurs in as many as 50% of people without narcolepsy. A dog model of narcolepsy exhibits a mutation on chromosome 12 that disrupts the processing of the peptide neurotransmitter hypocretin. No such mutation characterizes human narcolepsy; however, cerebrospinal fluid (CSF) hypocretin levels are profoundly depressed in narcoleptic patients, and a specific reduction in hypocretin-containing neurons has been described. One hypothesis concerning the pathophysiology of narcolepsy proposes that the HLA subtype resulting from the mutation on chromosome 6 increases the susceptibility of hypocretin-containing brain neurons to immune attack. Because hypocretin may normally participate in the maintenance of wakefulness, the loss of neurons that release this peptide might allow REM sleep to occur at inappropriate times, ie, while the patient is awake, in contrast to its normal cyclic appearance after a period of slow-wave sleep. The cataplexy, hallucinations, and/or paralysis associated with REM episodes normally are unnoticed-or, at least, not remembered-when the transition to REM follows slow wave sleep, as is normally the case; however, they are remembered when, in people with narcolepsy, the REM episode starts during a period of wakefulness. The association of narcolepsy with a deficiency in a specific neurotransmitter, in this case, hypocretin, is reminiscent of the associations between Parkinson disease and dopamine, or early Alzheimer disease and acetylcholine.

Anderson WS, Lenz FA. · Johns Hopkins University School of Medicine, Baltimore, MA 21287, USA. · Nat Clin Pract Neurol. · Pubmed #16932575 No free full text.

Abstract: Over the past two decades, deep brain stimulation (DBS) has supplanted lesioning techniques for the treatment of movement disorders, and has been shown to be safe and efficacious. The primary therapeutic indications for DBS are essential tremor, dystonia and Parkinson's disease. In the case of Parkinson's disease, DBS is effective for treating the primary symptoms--tremor, bradykinesia and rigidity--as well as the motor complications of drug treatment. Progress has been made in understanding the effects of stimulation at the neuronal level, and this knowledge should eventually improve the effectiveness of this therapy. Preliminary studies also indicate that DBS might be used to treat Tourette's syndrome, obsessive-compulsive disorder, depression and epilepsy. As we will discuss in this review, the success of DBS depends on an appropriate rationale for the procedure, and on collaborations between neurologists and neurosurgeons in defining outcomes.

Outeiro TF, Giorgini F. · Whitehead Institute for Biomedical Research, MIT, Cambridge, MA, USA. · Biotechnol J. · Pubmed #16897706 No free full text.

Abstract: The high degree of conservation of cellular and molecular processes between the budding yeast Saccharomyces cerevisiae and higher eukaryotes have made it a valuable system for numerous studies of the basic mechanisms behind devastating illnesses such as cancer, infectious disease, and neurodegenerative disorders. Several studies in yeast have already contributed to our basic understanding of cellular dysfunction in both Huntington's and Parkinson's disease. Functional genomics approaches currently being undertaken in yeast may lead to novel insights into the genes and pathways that modulate neuronal cell dysfunction and death in these diseases. In addition, the budding yeast constitutes a valuable system for identification of new drug targets, both via target-based and non-target-based drug screening. Importantly, yeast can be used as a cellular platform to analyze the cellular effects of candidate compounds, which is critical for the development of effective therapeutics. While the molecular mechanisms that underlie neurodegeneration will ultimately have to be tested in neuronal and animal models, there are several distinct advantages to using simple model organisms to elucidate fundamental aspects of protein aggregation, amyloid toxicity, and cellular dysfunction. Here, we review recent studies that have shown that amyloid formation by disease-causing proteins and many of the resulting cellular deficits can be faithfully recapitulated in yeast. In addition, we discuss new yeast-based techniques for screening candidate therapeutic compounds for Huntington's and Parkinson's diseases.

Borek LL, Amick MM, Friedman JH. · Department of Geriatric Psychiatry, Brown University School of Medicine, Providence, RI, USA. · CNS Spectr. · Pubmed #16816793 links to  free full text

Abstract: Parkinson's disease is primarily considered to be a movement disorder and is defined by its motor signs. Yet, the behavioral manifestations of the disease are often more debilitating than its motor complications. This review will focus on the non-motor aspects of Parkinson's disease, including mood, psychosis, cognitive, sleep, fatigue, apathy, delirium, and repetitive disorders, that may occur. The phenomenology, pathology, and treatment of the behavioral symptoms of Parkinson's disease will be discussed.

Kalda A, Yu L, Oztas E, Chen JF. · Molecular Neuropharmacology Lab, Department of Neurology, Boston University Medical Center, Boston, MA 02118, USA. · J Neurol Sci. · Pubmed #16806272 No free full text.

Abstract: The adenosine A(2A) receptor has recently emerged as a leading non-dopaminergic therapeutic target for Parkinson's disease, largely due to the restricted distribution of the receptor in the striatum and the profound interaction between adenosine and dopamine receptors in brain. Two lines of research in particular have demonstrated the promise of the A(2A) receptor antagonists as novel anti-parkinsonian drugs. First, building on extensive preclinical animal studies, the A(2A) receptor antagonist KW6002 has demonstrated its potential to increase motor activity in PD patients of the advanced stage in a recent clinical phase IIB trial. Second, recently two prospective epidemiological studies of large cohorts have firmly established the inverse relationship between the consumption of caffeine (a non-specific adenosine antagonist) and the risk of developing PD. The potential neuroprotective effect of caffeine and A(2A) receptor antagonists in PD is further substantiated by the demonstration that pharmacological blockade (by caffeine or specific A(2A) antagonists) or genetic depletion of the A(2A) receptor attenuated dopaminergic neurotoxicity and neurodegeneration in animal models of PD. Moreover, A(2A) receptor antagonism-mediated neuroprotection goes beyond PD models and can be extended to a variety of other brain injuries induced by stroke, excitotoxicity and mitochondrial toxins. Intensive investigations are under way to dissect out common cellular mechanisms (such as A(2A) receptor modulation of neuroinflammation) which may underlie the broad spectrum of neuroprotection by A(2A) receptor inactivation in brain.

Shirzadi AA, Ghaemi SN. · Harvard South Shore Psychiatry Program, Brockton, MA, USA. · Harv Rev Psychiatry. · Pubmed #16787887 No free full text.

Abstract: In this article we examine the two major classes of side effects with atypical antipsychotics: extrapyramidal symptoms (EPS) and the metabolic syndrome (the triad of diabetes, dyslipidemia, and hypertension, with associated obesity). We conclude that atypical antipsychotics continue to have notable risks of EPS, particularly akathisia, and that these agents also appear to increase the risk of the metabolic syndrome, though this effect seems most marked with clozapine and olanzapine. Novel conclusions based on this review are as follows: we provide a classification scheme based on low versus high D2 binding affinity (which is, to our knowledge, a new means of classifying atypical antipsychotics); we emphasize that the akathisia risk is likely equal among agents and that tardive dyskinesia is an early, and not late, risk in treatment (a common misconception); we make the methodological point that in randomized clinical trials, there is a high risk of false-negatives regarding side effects; we raise the issue of confounding bias in epidemiological studies of metabolic syndrome; and we stress the need to compare side effects in the same studies and not different studies. Future prospective observational cohort studies must target side effects and be designed to collect and analyze data on confounding factors.

McNamara P, Durso R. · Department of Neurology, Boston University School of Medicine, Boston VA Healthcare System, Boston, MA 02130, USA. · Behav Neurol. · Pubmed #16720959 No free full text.

Abstract: Many patients with Parkinson's Disease (PD) experience significant cognitive and mood impairment -even early in the course of the disease. These mental impairments are only partially responsive to levodopa treatment and are often as disabling as the motor impairment, particularly in mid and late stages of the disease. Investigators have recently begun a search for new agents that can effectively treat mental dysfunction of PD. Although there have been only a handful of properly controlled clinical trials of interventions targeted at amelioration of mental dysfunction in PD, progress has been made. Based on the available evidence, targeting catecholaminergic and cholinergic function may be an effective strategy for amelioration of cognitve, mood and psychiatric disturbances in PD.

Chang VC, Chou KL. · Rhode Island Hospital, USA. · Med Health R I. · Pubmed #16676911 No free full text.

Abstract: DBS is a safe and effective option for the treatment of patients with advanced PD. To ensure a successful outcome, however, it is important to select the appropriate candidates. The ideal candidate has idiopathic PD, suffers from complications of chronic levodopa therapy despite optimal medical management, and has no cognitive impairment or active psychiatric issues. Although the exact mechanism of how DBS exerts its effects remains under investigation, it is clearly apparent that bilateral stimulation of either the GPi or STN effectively helps the motor symptoms of PD. While many surgical centers favor stimulation of the STN over the GPi, there is accumulating evidence that STN stimulation may result in adverse non-motor outcomes such as depression. Future studies will be needed in order to determine the best site of stimulation, the exact mechanisms of DBS, and the long-term outcomes of both motor and non-motor symptoms. As our understanding of these components becomes clearer, we will be able to optimize the treatment and management for those whose lives are affected by Parkinson's disease.

Amick MM, Grace J. · Memorial Hospital of Rhode Island, Department of Medical Rehabilitation, 111 Brewster Street, Pawtucket, RI 02860, USA. · Med Health R I. · Pubmed #16676908 No free full text.

Abstract: Neuropsychological assessment has two primary roles in the DBS process. First, assessment of cognitive and emotional functioning ensures that only appropriate candidates undergo this surgical procedure. Patients with dementia, cognitive performance suggestive of an additional neuropathological process, or significant psychiatric impairments should not undergo DBS. Second, neuropsychological assessment is essential to determine the cognitive and emotional outcomes following surgery. At the present time, a disruption in verbal fluency is the only consistent cognitive decline associated with DBS. While worsening of depression and the development of symptoms of mania are potential side effects from DBS, more studies find that DBS is associated with improvements in emotional functioning. Based on the growing understanding of the risk factors and potential side effects to DBS, neuropsychological assessment is necessary to ensure that patients selected to undergo this surgical intervention will likely have positive cognitive and emotional outcomes, in addition to the expected benefits in motor functioning.

Schernhammer E, Chen H, Ritz B. · Department of Medicine, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. · Cancer Causes Control. · Pubmed #16596313 No free full text.

Abstract: Lower rates of cancer mortality/incidence in patients with Parkinson's disease (PD) have given rise to speculations about risk or preventative factors common to both diseases, including life-style factors (such as smoking) and genetic susceptibility. Melatonin, a hormone known for its sleep regulatory effects, may play an important role in carcinogenesis as suggested by substantial laboratory and less direct epidemiologic evidence. Particularly, a reduction in melatonin, such as experienced by persons who are exposed to light at night, appears to increase cancer risk. Variations in melatonin levels have been linked to PD in several different ways. Some studies show higher morning melatonin levels in PD patients than in healthy controls. One could speculate that the sleep disorders that affect almost two thirds of those suffering from PD and can precede PD motor symptoms by several years may be associated with variations in melatonin levels. Moreover, in animal models, interventions that increase the bioavailability of melatonin appears to increase the severity of parkinsonian symptoms, whereas reduction in melatonin by pinealectomy or exposure to bright light can enhance recovery from parkinsonisms symptoms. Finally, preliminary epidemiological evidence suggests that longer years of working night shifts is associated with a reduced risk of PD among participants of the Nurses' Health Study (NHS), whereas longer hours of sleep appear to increase their risk. In sum, while lower melatonin concentrations may predict a higher cancer risk, there is also some evidence that they may be associated with a lower risk of PD. We therefore hypothesize that elevated circulating melatonin levels in PD patients may contribute to their lower cancer rates.

Chou KL, Fernandez HH. · Department of Clinical Neurosciences, Brown Medical School, Providence, Rhode Island, USA. · Expert Opin Investig Drugs. · Pubmed #16548784 No free full text.

Abstract: Parkinson's disease (PD) patients commonly experience psychotic symptoms, with the most frequent manifestation being visual hallucinations. In PD, psychosis is predominantly drug induced and an important issue for clinicians to address as it increases the risk of nursing home placement as well as mortality. This review summarises the current knowledge regarding the clinical manifestations, pathophysiology and risk factors for drug-induced psychosis in patients with PD and focuses on treatment, especially with regard to the atypical antipsychotics.

Bertram L, Hsiao M, McQueen MB, Parkinson M, Mullin K, Blacker D, Tanzi RE. · Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. · Neurobiol Aging. · Pubmed #16378661 No free full text.

Abstract: Genetic linkage studies suggest the presence of an Alzheimer's disease (AD) risk gene on chromosome 19, acting independently of apolipoprotein E (apoE), a known AD risk factor on 19q13. The low density lipoprotein receptor (LDLR) is an interesting candidate because it maps within the linked interval, and is intimately involved in cholesterol homeostasis and the function of apoE. We tested three previously reported single nucleotide polymorphisms (SNPs) within LDLR in a large sample of discordant sibships from multiplex AD families, and failed to find evidence for genetic association with disease risk. In addition, we performed meta-analyses for SNP rs5925 on published data from five independent case control samples, but did not detect any significant summary odds ratios. Based on our data, it seems unlikely that these genetic variants in LDLR make a significant contribution to AD risk in the general population.

Fregni F, Simon DK, Wu A, Pascual-Leone A. · Harvard Center for Noninvasive Brain Stimulation, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA. · J Neurol Neurosurg Psychiatry. · Pubmed #16291882 links to  free full text

Abstract: A systematic review and meta-analysis were conducted to quantify the efficacy of transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT) for the treatment of motor dysfunction in patients with Parkinson's disease (PD). Prospective studies which evaluated the effects of either TMS (12 studies) or ECT (five studies) on motor function in PD using the motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRS) for TMS studies and any continuous measures of motor function in PD for ECT studies were included. The pooled effect size (standardised mean difference between pre-treatment versus post-treatment means) from a random effects model was 0.62 (95% confidence interval: 0.38, 0.85) for TMS treatment and 1.68 (0.79, 2.56) for ECT treatment, and from a fixed effects model was 0.59 (0.39, 0.78) for TMS treatment and 1.55 (1.07, 2.03) for ECT treatment. TMS, across applied stimulation sites and parameters, can exert a significant, albeit modest, positive effect on the motor function of patients with PD. ECT also may exert a significant effect on motor function in PD patients.