PARKINSON’S DISEASE SYMPTOMS

Bradykinesia Tremor Rigidity Postural instability Gait disturbance

Other features: Dementia Psychiatric disturbance

Autonomic dysfunction Dystonia Eye movement

abnormalities

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

FACTORS ASSOCIATED WITH INCREASED RISK FOR PD

Age Gender (males > females) Race (whites) Life experiences:

Trauma Emotional stressorsPersonality (shyness, depressiveness)

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

FACTORS ASSOCIATED WITH DECREASED RISK FOR PD

Diet:Vitamin E useSupplemental multivitamins

Life Experiences:Cigarette smokingAlcohol useCaffeine use

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

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

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

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

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

ANXIETY DISORDERS IN PD

1. Generalized anxiety disorder2. Panic Attacks/Disorder – tend to occur when PD

medications become less effective or patients experience various motor fluctuations

3. Social Phobias – fear of an inability to function in social settings

4. 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)

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

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

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.

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 impairmentCognitive impairmentPsychiatric manifestationsDecline in ADL’s

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

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 HDNo increased risk in presymptomatic

individuals who test gene positive

HUNTINGTON’S DISEASEBehavioral and Psychiatric Features

PsychosisParanoid ideation and persecutory delusions

most commonAuditory 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

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

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