Parkinson Disease: US Central Zone

Pahwa R, Factor SA, Lyons KE, Ondo WG, Gronseth G, Bronte-Stewart H, Hallett M, Miyasaki J, Stevens J, Weiner WJ, Anonymous00045. · University of Kansas Medical Center, Kansas City, USA. · Neurology. · Pubmed #16606909 No free full text.

Abstract: OBJECTIVE: To make evidence-based treatment recommendations for the medical and surgical treatment of patients with Parkinson disease (PD) with levodopa-induced motor fluctuations and dyskinesia. To that end, five questions were addressed. 1. Which medications reduce off time? 2. What is the relative efficacy of medications in reducing off time? 3. Which medications reduce dyskinesia? 4. Does deep brain stimulation (DBS) of the subthalamic nucleus (STN), globus pallidus interna (GPi), or ventral intermediate (VIM) nucleus of the thalamus reduce off time, dyskinesia, and antiparkinsonian medication usage and improve motor function? 5. Which factors predict improvement after DBS? METHODS: A 10-member committee including movement disorder specialists and general neurologists evaluated the available evidence based on a structured literature review including MEDLINE, EMBASE, and Ovid databases from 1965 through June 2004. RESULTS, CONCLUSIONS, AND RECOMMENDATIONS: 1. Entacapone and rasagiline should be offered to reduce off time (Level A). Pergolide, pramipexole, ropinirole, and tolcapone should be considered to reduce off time (Level B). Apomorphine, cabergoline, and selegiline may be considered to reduce off time (Level C). 2. The available evidence does not establish superiority of one medicine over another in reducing off time (Level B). Sustained release carbidopa/levodopa and bromocriptine may be disregarded to reduce off time (Level C). 3. Amantadine may be considered to reduce dyskinesia (Level C). 4. Deep brain stimulation of the STN may be considered to improve motor function and reduce off time, dyskinesia, and medication usage (Level C). There is insufficient evidence to support or refute the efficacy of DBS of the GPi or VIM nucleus of the thalamus in reducing off time, dyskinesia, or medication usage, or to improve motor function. 5. Preoperative response to levodopa predicts better outcome after DBS of the STN (Level B).

Goetz CG, Poewe W, Rascol O, Sampaio C, Stebbins GT, Counsell C, Giladi N, Holloway RG, Moore CG, Wenning GK, Yahr MD, Seidl L, Anonymous00253. · Rush University Medical Center, 1725 W. Harrison Street, Chicago, IL 60612, USA. · Mov Disord. · Pubmed #15372591 links to  free full text

Abstract: The Movement Disorder Society Task Force for Rating Scales for Parkinson's disease (PD) prepared a critique of the Hoehn and Yahr scale (HY). Strengths of the HY scale include its wide utilization and acceptance. Progressively higher stages correlate with neuroimaging studies of dopaminergic loss, and high correlations exist between the HY scale and some standardized scales of motor impairment, disability, and quality of life. Weaknesses include the scale's mixing of impairment and disability and its non-linearity. Because the HY scale is weighted heavily toward postural instability as the primary index of disease severity, it does not capture completely impairments or disability from other motor features of PD and gives no information on nonmotor problems. Direct clinimetric testing of the HY scale has been very limited, but the scale fulfills at least some criteria for reliability and validity, especially for the midranges of the scale (Stages 2-4). Although a "modified HY scale" that includes 0.5 increments has been adopted widely, no clinimetric data are available on this adaptation. The Task Force recommends that: (1) the HY scale be used in its original form for demographic presentation of patient groups; (2) when the HY scale is used for group description, medians and ranges should be reported and analysis of changes should use nonparametric methods; (3) in research settings, the HY scale is useful primarily for defining inclusion/exclusion criteria; (4) to retain simplicity, clinicians should "rate what you see" and therefore incorporate comorbidities when assigning a HY stage; and (5) because of the wide usage of the modified HY scale with 0.5 increments, this adaptation warrants clinimetric testing. Without such testing, however, the original five-point scales should be maintained.

Maricich SM, Zoghbi HY. · Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA. · Cell. · Pubmed #16839867 No free full text.

Abstract: Advances in understanding basic developmental and physiological processes often have direct relevance to human disease. They provide insights into pathogenic mechanisms and reveal new pathways that can be exploited in diagnosis and the development of therapeutics.

Prodoehl J, Corcos DM, Vaillancourt DE. · Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612, USA. · Neurosci Biobehav Rev. · Pubmed #19428499 No free full text.

Abstract: The classic grasping network has been well studied but thus far the focus has been on cortical regions in the control of grasping. Sub-cortically, specific nuclei of the basal ganglia have been shown to be important in different aspects of precision grip force control but these findings have not been well integrated. In this review, we outline the evidence to support the hypothesis that key basal ganglia nuclei are involved in parameterizing specific properties of precision grip force. We review literature from different areas of human and animal work that converges to build a case for basal ganglia involvement in the control of precision gripping. Following on from literature showing anatomical connectivity between the basal ganglia nuclei and key nodes in the cortical grasping network, we suggest a conceptual framework for how the basal ganglia could function within the grasping network, particularly as it relates to the control of precision grip force.

Jeitner TM, Pinto JT, Krasnikov BF, Horswill M, Cooper AJ. · Red Anvil, LLC, Milwaukee, Wisconsin, USA. · J Neurochem. · Pubmed #19393023 No free full text.

Abstract: Transglutaminases (TGs) are Ca2+-dependent enzymes that catalyze a variety of modifications of glutaminyl (Q) residues. In the brain, these modifications include the covalent attachment of a number of amine-bearing compounds, including lysyl (K) residues and polyamines, which serve to either regulate enzyme activity or attach the TG substrates to biological matrices. Aberrant TG activity is thought to contribute to Alzheimer disease, Parkinson disease, Huntington disease, and supranuclear palsy. Strategies designed to interfere with TG activity have some benefit in animal models of Huntington and Parkinson diseases. The following review summarizes the involvement of TGs in neurodegenerative diseases and discusses the possible use of selective inhibitors as therapeutic agents in these diseases.

Chan CS, Gertler TS, Surmeier DJ. · Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. · Trends Neurosci. · Pubmed #19307031 No free full text.

Abstract: Parkinson's disease (PD) is a common neurodegenerative disorder of which the core motor symptoms are attributable to the degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Recent work has revealed that the engagement of L-type Ca(2+) channels during autonomous pacemaking renders SNc DA neurons susceptible to mitochondrial toxins used to create animal models of PD, indicating that homeostatic Ca(2+) stress could be a determinant of their selective vulnerability. This view is buttressed by the central role of mitochondria and the endoplasmic reticulum (linchpins of current theories about the origins of PD) in Ca(2+) homeostasis. Here, we summarize this evidence and suggest the dual roles had by these organelles could compromise their function, leading to accelerated aging of SNc DA neurons, particularly in the face of genetic or environmental stress. We conclude with a discussion of potential therapeutic strategies for slowing the progression of PD.

Swanson CR, Sesso SL, Emborg ME. · Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center;, University of Wisconsin-Madison, Madison, WI, USA. · Front Biosci. · Pubmed #19273153 No free full text.

Abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects 1 million people in the United States. Although the cause of PD remains unknown, a number of factors that increase the risk of developing this disease have been identified. Other factors that may prevent or slow down PD development and progression have also been found. In this review, we describe current basic, clinical and epidemiological findings on risk and neuroprotective factors and discuss how they can affect PD.

Harris MK, Shneyder N, Borazanci A, Korniychuk E, Kelley RE, Minagar A. · Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. · Med Clin North Am. · Pubmed #19272514 No free full text.

Abstract: Abnormal involuntary movements are major features of a large group of neurologic disorders, some of which are neurodegenerative and pose a significant diagnostic and treatment challenge to treating physicians. This article presents a concise review of clinical features, pathogenesis, epidemiology, and management of seven of the most common movement disorders encountered in a primary care clinic routinely. The disorders discussed are Parkinson disease, essential tremor, restless legs syndrome, Huntington disease, drug-induced movement disorder, Wilson disease, and Tourette syndrome.

Simuni T, Lyons KE, Pahwa R, Hauser RA, Comella C, Elmer L, Weintraub D. · Department of Neurology, Northwestern University, Parkinson's Disease and Movement Disorders Center, Chicago, Ill, USA. · Eur Neurol. · Pubmed #19176961 links to  free full text

Abstract: The management of early Parkinson's disease (PD) involves the treatment of motor symptoms, and, increasingly, non-motor symptoms. Given the fast pace of clinical research in PD, clinicians are faced with the challenge of integrating the latest findings into the ongoing care of individual PD patients. Part 1 of this 2-part article reviews efficacy and safety data for the newest PD treatment options, as well as for established therapies. Part 2 of the article, presented here, reviews key data relevant to the assessment of potential neuroprotective therapies and the treatment of non-motor symptoms.

Simuni T, Lyons KE, Pahwa R, Hauser RA, Comella C, Elmer L, Weintraub D. · Department of Neurology, Northwestern University, Parkinson's Disease and Movement Disorders Center, Chicago, Ill 60611, USA. · Eur Neurol. · Pubmed #19176960 links to  free full text

Abstract: The management of early Parkinson's disease (PD) involves the treatment of motor symptoms and, increasingly, non-motor symptoms. Given the fast pace of clinical research in PD, clinicians are faced with the challenge of integrating the latest findings into the ongoing care of individual PD patients. Part 1 of this 2-part article reviews motor symptom efficacy data for the newest PD treatment options, as well as for established therapies. Safety and tolerability data are also reviewed. Part 2 of the article reviews key findings relevant to the assessment of potential neuroprotective therapies and the treatment of non-motor symptoms.

Nass R, Merchant KM, Ryan T. · Department of Pharmacology and Toxicology, Center for Environmental Health, and Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. · Mol Interv. · Pubmed #19144901 No free full text.

Abstract: It has been over forty years since dopamine neuron degeneration in the substantia nigra and Lewy body formation within surviving cells were described as the pathological hallmarks of Parkinson's disease (PD). Although research in the intervening decades particularly in the last twenty-five years has yielded a variety of robust animal models and invaluable mechanistic insights into PD-associated neuronal dysfunction and cell death, therapeutic agents have not been forthcoming to alter the course of PD. Recently, the screening of experimental therapeutics for PD has been pursued through the use of genetically tractable models, such as the nematode Caenorhabditis elegans. This simple worm remarkably recapitulates the basic cellular and molecular pathways associated with PD, is amenable to facile genetic methods, and through the use of high-throughput screening technologies, provides powerful new opportunities for the in vivo identification of therapeutic targets. In this review we briefly describe the utility that the C. elegans model system may have for PD drug discovery.

Simuni T, Sethi K. · Department of Neurology, Northwestern University, Chicago, IL, USA. · Ann Neurol. · Pubmed #19127582 No free full text.

Abstract: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Traditionally, attention has focused on the motor symptomatology of PD, but it is now appreciated that the nonmotor symptoms affecting neuropsychiatric, sleep, autonomic, and sensory domains occur in up to 88% of PD patients and can be an important source of disability. Nonmotor manifestations of PD play a significant role in the impairment of disease-related quality of life. The cause of nonmotor manifestations of PD is multifactorial, but to a large extent, these manifestations are related to the nature of the neurodegenerative process and the widespread nondopaminergic neuropathological changes associated with the disease. Recognition of nonmotor disability is essential not only for ascertaining the functional status of patients but also for better appreciating the nature of the neurodegenerative process in PD. In addition, a number of nonmotor manifestations can precede the onset of motor symptoms in PD and can be used as screening tools allowing for early disease identification and for trials of possible disease-modifying interventions. This article reviews depression, sleep, and autonomic dysfunction in PD.

Narayana S, Jacks A, Robin DA, Poizner H, Zhang W, Franklin C, Liotti M, Vogel D, Fox PT. · Research Imaging Center, Honors College, The University of Texas Health Science Center, San Antonio, 7703 Floyd Curl Drive MSC 6240, San Antonio, TX 78229-3900, USA. · Am J Speech Lang Pathol. · Pubmed #19029533 No free full text.

Abstract: PURPOSE: To explore the use of noninvasive functional imaging and "virtual" lesion techniques to study the neural mechanisms underlying motor speech disorders in Parkinson's disease. Here, we report the use of positron emission tomography (PET) and transcranial magnetic stimulation (TMS) to explain exacerbated speech impairment following subthalamic nucleus deep brain stimulation (STN-DBS) in a patient with Parkinson's disease. METHOD: Perceptual and acoustic speech measures, as well as cerebral blood flow during speech as measured by PET, were obtained with STN-DBS on and off. TMS was applied to a region in the speech motor network found to be abnormally active during DBS. Speech disruption by TMS was compared both perceptually and acoustically with speech produced with DBS on. RESULTS: Speech production was perceptually inferior and acoustically less contrastive during left STN stimulation compared to no stimulation. Increased neural activity in left dorsal premotor cortex (PMd) was observed during DBS on. "Virtual" lesioning of this region resulted in speech characterized by decreased speech segment duration, increased pause duration, and decreased intelligibility. CONCLUSIONS: This case report provides evidence that impaired speech production accompanying STN-DBS may result from unintended activation of PMd. Clinical application of functional imaging and TMS may lead to optimizing the delivery of STN-DBS to improve outcomes for speech production as well as general motor abilities.

Reilly JL, Lencer R, Bishop JR, Keedy S, Sweeney JA. · Center for Cognitive Medicine, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA. · Brain Cogn. · Pubmed #19028266 No free full text.

Abstract: The increasing use of eye movement paradigms to assess the functional integrity of brain systems involved in sensorimotor and cognitive processing in clinical disorders requires greater attention to effects of pharmacological treatments on these systems. This is needed to better differentiate disease and medication effects in clinical samples, to learn about neurochemical systems relevant for identified disturbances, and to facilitate identification of oculomotor biomarkers of pharmacological effects. In this review, studies of pharmacologic treatment effects on eye movements in healthy individuals are summarized and the sensitivity of eye movements to a variety of pharmacological manipulations is established. Primary findings from these studies of healthy individuals involving mainly acute effects indicate that: (i) the most consistent finding across several classes of drugs, including benzodiazepines, first- and second- generation antipsychotics, anticholinergic agents, and anticonvulsant/mood stabilizing medications is a decrease in saccade and smooth pursuit velocity (or increase in saccades during pursuit); (ii) these oculomotor effects largely reflect the general sedating effects of these medications on central nervous system functioning and are often dose-dependent; (iii) in many cases changes in oculomotor functioning are more sensitive indicators of pharmacological effects than other measures; and (iv) other agents, including the antidepressant class of serotonergic reuptake inhibitors, direct serotonergic agonists, and stimulants including amphetamine and nicotine, do not appear to adversely impact oculomotor functions in healthy individuals and may well enhance aspects of saccade and pursuit performance. Pharmacological treatment effects on eye movements across several clinical disorders including schizophrenia, affective disorders, attention deficit hyperactivity disorder, Parkinson's disease, and Huntington's disease are also reviewed. While greater recognition and investigation into pharmacological treatment effects in these disorders is needed, both beneficial and adverse drug effects are identified. This raises the important caveat for oculomotor studies of neuropsychiatric disorders that performance differences from healthy individuals cannot be attributed to illness effects alone. In final sections of this review, studies are presented that illustrate the utility of eye movements for use as potential biomarkers in pharmacodynamic and pharmacogenetic studies. While more systematic studies are needed, we conclude that eye movement measurements hold significant promise as tools to investigate treatment effects on cognitive and sensorimotor processes in clinical populations and that their use may be helpful in speeding the drug development pathway for drugs targeting specific neural systems and in individualizing pharmacological treatments.

Weidong Le, Shen Chen, Jankovic J. · Department of Neurology, Baylor College of Medicine, Houston, Texas, USA. · Neuroscientist. · Pubmed #19008336 No free full text.

Abstract: Parkinson disease (PD) probably represents a syndrome of different disorders and origins converging into a relatively uniform neurodegenerative process. Although clinical-pathological studies have suggested that the presymptomatic phase of PD may be relatively short, perhaps less than a decade, the authors postulate that the pathogenic mechanisms may begin much earlier, possibly even in the prenatal period. Thus, some patients with PD may be born with a fewer than normal number of dopaminergic (and nondopaminergic) neurons as a result of genetic or other abnormalities sustained during the prenatal or perinatal period; as a result of normal age-related neuronal attrition, they eventually reach the critical threshold (60% or more) of neuronal loss needed for onset of PD to become clinically manifest. The authors review the emerging evidence that genetic disruption of normal development, coupled with subsequent environmental factors (the so called multiple-hit hypothesis), plays an important role in the etiopathogenesis of PD.

Kamat CD, Gadal S, Mhatre M, Williamson KS, Pye QN, Hensley K. · Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. · J Alzheimers Dis. · Pubmed #18997301 links to  free full text

Abstract: Oxidative damage is strongly implicated in the pathogenesis of neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and stroke (brain ischemia/reperfusion injury). The availability of transgenic and toxin-inducible models of these conditions has facilitated the preclinical evaluation of putative antioxidant agents ranging from prototypic natural antioxidants such as vitamin E (alpha-tocopherol) to sophisticated synthetic free radical traps and catalytic oxidants. Literature review shows that antioxidant therapies have enjoyed general success in preclinical studies across disparate animal models, but little benefit in human intervention studies or clinical trials. Recent high-profile failures of vitamin E trials in Parkinson's disease, and nitrone therapies in stroke, have diminished enthusiasm to pursue antioxidant neuroprotectants in the clinic. The translational disappointment of antioxidants likely arises from a combination of factors including failure to understand the drug candidate's mechanism of action in relationship to human disease, and failure to conduct preclinical studies using concentration and time parameters relevant to the clinical setting. This review discusses the rationale for using antioxidants in the prophylaxis or mitigation of human neurodiseases, with a critical discussion regarding ways in which future preclinical studies may be adjusted to offer more predictive value in selecting agents for translation into human trials.

Hermanns M. · American Parkinon's Disease Association, East Texas Chapter, USA. · RN. · Pubmed #18942321 No free full text.

This publication has no abstract.

Dowling J. · Washington University School of Medicine, USA. · Mo Med. · Pubmed #18807366 No free full text.

Abstract: Deep brain stimulation (DBS) has been used to treat a number of neurological and psychiatric diseases. Initially applied to chronic pain, DBS today is routinely used to treat movement disorders, predominantly Parkinson's Disease, essential tremor, and dystonia. Recent studies have demonstrated potential for treating depression and obsessive-compulsive disorder.

Floyd RA, Kopke RD, Choi CH, Foster SB, Doblas S, Towner RA. · Experimental Therapeutics Research Program, Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. · Free Radic Biol Med. · Pubmed #18793715 No free full text.

Abstract: Nitrones have the general chemical formula X-CH=NO-Y. They were first used to trap free radicals in chemical systems and then subsequently in biochemical systems. More recently several nitrones, including alpha-phenyl-tert-butylnitrone (PBN), have been shown to have potent biological activity in many experimental animal models. Many diseases of aging, including stroke, cancer development, Parkinson disease, and Alzheimer disease, are known to have enhanced levels of free radicals and oxidative stress. Some derivatives of PBN are significantly more potent than PBN and have undergone extensive commercial development for stroke. Recent research has shown that PBN-related nitrones also have anti-cancer activity in several experimental cancer models and have potential as therapeutics in some cancers. Also, in recent observations nitrones have been shown to act synergistically in combination with antioxidants in the prevention of acute acoustic-noise-induced hearing loss. The mechanistic basis of the potent biological activity of PBN-related nitrones is not known. Even though PBN-related nitrones do decrease oxidative stress and oxidative damage, their potent biological anti-inflammatory activity and their ability to alter cellular signaling processes cannot readily be explained by conventional notions of free radical trapping biochemistry. This review is focused on our studies and others in which the use of selected nitrones as novel therapeutics has been evaluated in experimental models in the context of free radical biochemical and cellular processes considered important in pathologic conditions and age-related diseases.

Chitnis S. · Clinical Center for Movement Disorders, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9036, USA. · Neurol Clin. · Pubmed #18774441 No free full text.

Abstract: Parkinsonism is a syndrome characterized by a combination of cardinal features including resting tremor, bradykinesia, rigidity, and loss of postural reflexes. The most common presentation of parkinsonism is the idiopathic variety first described by James Parkinson in 1817 now known as Parkinson's disease (PD). This article focuses on identifying the different subtypes of PD, with the recognition that treatment approaches may differ depending on the initial presenting feature. It also addresses issues related to the recognition and treatment of nonmotor comorbidities of PD, such as autonomic dysfunction and neuropsychiatric problems including depression and dementia.

Dewey RB. · University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9036, USA. · Neurol Clin. · Pubmed #18774440 No free full text.

Abstract: Given the magnitude of the problem of motor fluctuations in patients who have Parkinson's disease treated with levodopa, a significant effort has been expended by physicians, researchers, and pharmaceutical manufacturers over the years to find effective treatments. This article briefly reviews the medical options for managing motor fluctuations that are in common use in the United States or that are expected to be available soon.

Adibhatla RM, Hatcher JF. · Department of Neurological Surgery, Cardiovascular Research Center, Neuroscience Training Program, University of Wisconsin School of Medicine and Public Health, Madison, WI., William S. Middleton Veterans Affairs Hospital, Madison, WI 53792, USA. · Subcell Biochem. · Pubmed #18751914 links to  free full text

Abstract: Deregulated lipid metabolism may be of particular importance for CNS injuries and disorders, as this organ has the highest lipid concentration next to adipose tissue. Atherosclerosis (a risk factor for ischemic stroke) results from accumulation of LDL-derived lipids in the arterial wall. Pro-inflammatory cytokines (TNF-alpha and IL-1), secretory phospholipase A2 IIA and lipoprotein-PLA2 are implicated in vascular inflammation. These inflammatory responses promote atherosclerotic plaques, formation and release of the blood clot that can induce ischemic stroke. TNF-alpha and IL-1 alter lipid metabolism and stimulate production of eicosanoids, ceramide, and reactive oxygen species that potentiate CNS injuries and certain neurological disorders. Cholesterol is an important regulator of lipid organization and the precursor for neurosteroid biosynthesis. Low levels of neurosteroids were related to poor outcome in many brain pathologies. Apolipoprotein E is the principal cholesterol carrier protein in the brain, and the gene encoding the variant Apolipoprotein E4 is a significant risk factor for Alzheimer's disease. Parkinson's disease is to some degree caused by lipid peroxidation due to phospholipases activation. Niemann-Pick diseases A and B are due to acidic sphingomyelinase deficiency, resulting in sphingomyelin accumulation, while Niemann-Pick disease C is due to mutations in either the NPC1 or NPC2 genes, resulting in defective cholesterol transport and cholesterol accumulation. Multiple sclerosis is an autoimmune inflammatory demyelinating condition of the CNS. Inhibiting phospholipase A2 attenuated the onset and progression of experimental autoimmune encephalomyelitis. The endocannabinoid system is hypoactive in Huntington's disease. Ethyl-eicosapetaenoate showed promise in clinical trials. Amyotrophic lateral sclerosis causes loss of motorneurons. Cyclooxygenase-2 inhibition reduced spinal neurodegeneration in amyotrophic lateral sclerosis transgenic mice. Eicosapentaenoic acid supplementation provided improvement in schizophrenia patients, while the combination of (eicosapentaenoic acid + docosahexaenoic acid) provided benefit in bipolar disorders. The ketogenic diet where >90% of calories are derived from fat is an effective treatment for epilepsy. Understanding cytokine-induced changes in lipid metabolism will promote novel concepts and steer towards bench-to-bedside transition for therapies.

Uc EY, Rizzo M. · Department of Neurology, University of Iowa, Carver College of Medicine, 200 Hawkins Drive-2RCP, Iowa City, IA 52242, USA. · Curr Neurol Neurosci Rep. · Pubmed #18713573 No free full text.

Abstract: The proportion of elderly people in the general population is rising, resulting in greater numbers of drivers with neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. These neurodegenerative disorders impair cognition, visual perception, and motor function, leading to reduced driver fitness and greater crash risk. Yet neither medical diagnosis nor age alone is reliable enough to predict driver safety or crashes or to revoke the driving privileges of these individuals. Driving research utilizes tools such as questionnaires about driving habits and history, driving simulators, standardized road tests utilizing instrumented vehicles, and state driving records. Research challenges include outlining the evolution of driving safety, understanding the mechanisms of driving impairment, and developing a reliable and efficient standardized test battery for prediction of driver safety in neurodegenerative disorders. This information will enable healthcare providers to advise their patients with neurodegenerative disorders with more certainty, affect policy, and help develop rehabilitative measures for driving.

Ferrara JM, Stacy M. · Baylor College of Medicine, Houston, TX, USA. · CNS Spectr. · Pubmed #18704024 links to  free full text

Abstract: Parkinson's disease is a neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, and resting tremor. Increasingly, Parkinson's disease has been associated with a broad spectrum of non-motor symptoms, such as olfactory loss, sleep disorders, autonomic dysfunction, cognitive impairment, psychosis, depression, anxiety, and apathy. In addition, a minority of Parkinson's disease patients develop compulsive behaviors while receiving dopamine-replacement therapy, including medication hoarding, pathological gambling, binge eating, hyperlibidinous behavior, compulsive shopping, and punding. These behaviors may result in psychosocial impairment for patients and therapeutic challenges for clinicians. This article reviews the anatomic substrates, behavioral spectrum, associated factors, and potential treatments for dopamine-replacement therapy-related compulsions in Parkinson's disease.

Sowell RA, Owen JB, Butterfield DA. · Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA. · Ageing Res Rev. · Pubmed #18703168 No free full text.

Abstract: The risk of developing neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) increases with age. AD and PD are the two most common neurodegenerative diseases that currently affect millions of persons within the United States population. While many clues about the mechanisms of these disorders have been uncovered, to date, the molecular mechanisms associated with the cause of these diseases are not completely understood. Furthermore, there are no available cures or preventive treatments for either disorder. Animal models of AD and PD, though not perfect, offer a means to gain knowledge of the basic biochemistry associated with these disorders and with drug efficacy. The field of proteomics which focuses on identifying the dynamic nature of the protein content expressed within a particular cell, tissue, or organism, has provided many insights into these disturbing disorders. Proteomic studies have revealed many pathways that are associated with disease pathogenesis and that may lead to the development of potential therapeutic targets. This review provides a discussion of key findings from AD and PD proteomics-based studies in various animal models of disease.