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PARKINSON’S DISEASE SYMPTOMS PowerPoint Presentation
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PARKINSON’S DISEASE SYMPTOMS

PARKINSON’S DISEASE SYMPTOMS

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PARKINSON’S DISEASE SYMPTOMS

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  1. Bradykinesia Tremor Rigidity Postural instability Gait disturbance Other features: Dementia Psychiatric disturbance Autonomic dysfunction Dystonia Eye movement abnormalities PARKINSON’S DISEASE SYMPTOMS

  2. PD EPIDEMIOLOGY • ~ 1,000,000 patients in the United States • Annual incidence of about 50,000 – 60,000 • Net prevalence increase of 15,000 patients annually • Average age of onset: 50 – 65 years old • 85% of patients over age 65

  3. FACTORS ASSOCIATED WITH INCREASED RISK FOR PD • Age • Gender (males > females) • Race (whites) • Life experiences: • Trauma • Emotional stressors • Personality (shyness, depressiveness)

  4. FACTORS ASSOCIATED WITH INCREASED RISK FOR PD • Environmental Exposure: • Metals (manganese, iron) • Drinking well water • Farming • Rural residence • Wood pulp mills • Steel alloy industries • Herbicide and pesticide exposure • MPTP and MPTP-like compounds • Infectious agents

  5. FACTORS ASSOCIATED WITH DECREASED RISK FOR PD • Diet: • Vitamin E use • Supplemental multivitamins • Life Experiences: • Cigarette smoking • Alcohol use • Caffeine use

  6. COGNITIVE CHANGES IN PARKINSON’S DISEASE • Estimates range from 30% - 90% • Important to distinguish “dementia” from specific cognitive changes: • Dementia: global deterioration of intellect – occurs in about 10% - 20% of PD patients • Specific pattern of cognitive impairment seen in a majority of PD patients

  7. COGNITIVE CHANGES IN PD • General findings: • Slowed information processing • Difficulty starting or stopping mental activity • Delayed response times • Memory impairment: • Reduced attention span • Impaired spontaneous recall of information • Relatively preserved recognition memory • Impairment of “working memory” • Capacity to hold information in brief, short-term storage in order to perform a mental manipulation

  8. COGNITIVE CHANGES IN PD • Other Cognitive Findings: • Mental Inflexibility • Tendency to get “stuck” on a thought or action • Inability to shift attention or thought process • Decreased planning/organizational ability • Tendency to repeat things over and over • Visuospatial impairment • Independent of motor component • Deficits in visual analysis and integration • Difficulty with visual discrimination and matching • Intact abilities: perceptual orientation, mental rotation

  9. DEPRESSION IN PD • Can occur in 20% to 40% of PD patients • Major reactive depression (initial diagnosis) • Adjustment disorder (physical/cognitive limitations) • May be part of the clinical spectrum of PD

  10. ANXIETY IN PD ANXIETY:A state characterized by a vague and unpleasant sense of apprehension, often accompanied by physical symptoms such as sweating and dry mouth IN PD: Anxiety is often caused by lack of effectiveness of PD medications, dyskinesias, motor fluctuations, fear of freezing/falling. Panic attacks are common

  11. ANXIETY DISORDERS IN PD • Generalized anxiety disorder • Panic Attacks/Disorder – tend to occur when PD medications become less effective or patients experience various motor fluctuations • Social Phobias – fear of an inability to function in social settings • Obsessive-Compulsive Disorder (fear of disabling physical capacity, excessive worry about taking medication, fear of freezing or falling, repetitive checking (e.g., pill box, clock)

  12. PSYCHOSIS IN PD • Relatively uncommon in PD • Occurs in about 20% of patients with advanced PD and on chronic anti-PD medications • Almost always drug-induced (e.g., Sinemet) • Often characterized by visual hallucinations, vivid dreams or nightmares • Usually accompanied by a clear sensorium (e.g., the patient is alert and not delirious) • Older patients with cognitive impairment at higher risk • Most common reason for nursing home placement

  13. HUNTINGTON’S DISEASE • Named for Long Island, NY physician who described disorder in 1872 • Autosomal dominant neurodegenerative disorder • Determined by genetic mutation on short arm of chromosome 4 • Mutation is an expanded and unstable trinucleotide repeat of cytosine-adenosine-guanine (CAG); •  34 Normal Range •  39 Positive Inheritance • 35–38 Indeterminate

  14. Age of Onset and CAG Repeat Length CAG repeat length on normal and HD chromosomes and age at onset in HD. The CAG repeat length distribution of alleles found on normal (blue line) and HD (red line) The mean age at onset associated with each CAG repeat length is plotted as a red square (against the left axis). The pink area surrounding the mean age at onset denotes the range of ages at onset associated with any given repeat length, with deviations presumably being due to the effects of genetic or environmental modifiers.

  15. HUNTINGTON’S DISEASE • Estimated 30,000 Americans with HD • 200,000 individuals at-risk • Onset is usually between ages 30-45 although there is a juvenile variant • Progressive loss of functional ability and death within 10-30 yrs from onset • Key clinical features: • Motor impairment • Cognitive impairment • Psychiatric manifestations • Decline in ADL’s

  16. HUNTINGTON’S DISEASECognitive Changes • 100% of patients experience progressive cognitive decline • Pattern of cognitive decline: • “Subcortical” - slowed information processing, encoding and retrieval deficits (intact recognition memory) • Anterior cortical – mental inflexibility, impaired planning, organization, sequencing and decreased judgement, reasoning and problem-solving • Late Stage HD – global dementia

  17. HUNTINGTON’S DISEASEBehavioral and Psychiatric Features • Can be initial presenting symptom in HD • Prevalence of psychiatric symptoms ranges from 35% - 75% • Most common psychiatric disorder is depression (30% - 50% prevalence) • Modestly increased suicide rate in HD • No increased risk in presymptomatic individuals who test gene positive

  18. HUNTINGTON’S DISEASEBehavioral and Psychiatric Features • Psychosis • Paranoid ideation and persecutory delusions most common • Auditory and visual hallucinations commonly reported in patients with psychosis • Anxiety and OCD • Shared pathophysiology between HD and OCD • Anxiety symptoms typically secondary to worry and concern about financial difficulty, guilt about passing gene to offspring

  19. HUNTINGTON’S DISEASEBehavioral and Psychiatric Features • Other Psychiatric/Behavioral Problems • Changes in personality (irritability, apathy, antisocial, intermittent explosive) • Change in sexual behavior (hypo- and hyper-sexuality) • Restlessness and agitation • Apathy (? link to frontal dysfunction) • Increased risk for alcohol and drug dependency • Bipolar disorder and/or manic episodes reported but less common

  20. HD Treatment • Currently no pharmacological treatment available • Can treat psychiatric manifestations • Use of DA blocking agents will  chorea • NMDA receptor antagonists (data disappointing thus far) • Free Radical Scavengers • Coenzyme Q10 • Creatine • Caspase Inhibition – Minocycline • Inhibition of acetyltransferases – HDAC inhibitors reverse neuronal degeneration in drosophila model of HD • Ongoing investigation of huntingtin • Agents that prevent nuclear aggregation • Agents that “cleave” protein rendering non-toxic