HS 350 Exam 2

Why Parkinson's Disease and Alzheimer's Disease

Incidence of both increases with age

Population is aging (2030, proportion of the population >65, 20%)

Huge impact on health care (NIA projecting 14 million with AD by 2040)

Alzheimer's disesae

Most common cause of dementia (65%)

Begins after 60, risk goes up with age

PROGRESSIVE loss of cognitive function

---memory

---judgement and reasoning

---movement coordination

Central Nervous System Involvement

Alzheimers disease begins in the hippocampus, spreads to cerebral cortex

--Neuritic plaque

--Neurofibrillary tangles

--Cell loss

---Loss of Acetylcholine

Develops slowly over time

Neuritic plaques

abnormal clumps of protein (amyloid) outside the neuron

Neurofibrillary tangles

twisted proteins (tau) inside the neuron

Mild Alzheimers signs and symptoms

mild forgetfullness

Moderate Alzheimers signs and symptoms

Severe memory loss

Can't do simple tasks

Speaking, writing

Personality change

Severe Alzheimers signs and symptoms

Unable to take care of themselves

Wandering

Gait/balance disturbances (falls)

Causes/Risk Factors of Alzheimer's Disease

Age (older)

Female

Genetic Link

HBP, High cholesterol

Sedentary lifestyle

Education

Genetic link with AD

ApOE4 (double allele)

Risk increases 4-fold if first degree relative has AD; risk increases 40 fold if 2 or more first degree relatives have AD

Sedentary lifestyle AD

Survey of people with AD and healthy family control of midlife activities

--Persons with AD, greater time spent watching TV

--Each additional hour of TV watching increased risk of AD by a factor of 1.3

Education with AD

109 pairs of twins one had AD and other had no AD

Treatment of AD

No cure

Medications - Aricept, Exelon

Keep as physically and mentally active as possible

New findings in mice: hope for a cure

Prevention (delay) Stay active!

Exercise (large prospective studies)

--increased exercise showed a decrease in cognitive decline

--Engaged 4 or more physical activities, half risk of dementia compared to those in one or none (not absolute energy expenditure, but number of activities)

--What's good for the heart is good for the mind

How does exercise impact cognition?

Increased blood flow

Brain derived neurotrophic factor

Work in conjunction with estrogen

Parkinson's Disease

-Disease of the ganglia

-Primarily older adults

-More common in men than women

-Most common among Hispanics followed by non-Hispanic Whites, Asians, and Blacks

-Affects movement primarily, but can eventually affect cognition and emotion

Basal ganglia

substantia nigra

Substantia nigra

produces dopamine (neurotransmitter)

Parkinson's disease where and why

With age: death of cells 70-80% Parkinson's Disease symptoms

Cause of additional cell death? Unknown

PD Cause idiopathic

Genetics: positive family history

Environmental: herbicides, pesticides, heavy metals, proximity to industry, rural residence, well water, welders have higher incidence

Head trauma

Drugs

Cardinal Characteristics of PD

-Resting tremor

-Bradykinesia: slow movement

-Akinesia: slowness to initiate movement

-Rigidity (cogwheel movement)

-Movement sequencing

-Postural instability

-Fatigue

Bradykinesia

slow movement

Akinesia

slowness to initiate movement

Additional signs and symptoms of PD

-Masked face

-Stooped, shuffling gait (festination)

-Decreased arm swing when walking

-Difficulty initiating movement

-Microphagia

-Soft speech

-Slow to initiate speech

-Loss of the sense of smell

Non-motor symptoms of PD

Sleep disorders

Cognitive impairment

Depression

- 40-90% patients

-Endogenous depression (chemical changes, not stressful life event)

-Reduction in QOL

-Depression and panic attacks precede motor symptoms in 30%

PD Basal Ganglia

less activation which, in turn, results in less activation of the planning areas of the motor cortex

Basic principles of medical treatment for PD

Current therapies/drugs treat symptoms

Treat according to functional deficit

-varies with the individual

Long term planning

-now live only 1-1.5 years less than if no disease

-chronic illness

-QOL issues

PD Treatment

Drugs: Levodopa and carbidopa (Sinemet)

Surgery

-lesion areas or insert simulators

Deep Brain Stimulation

Therapeutic intervention for PD

Encouraged to stay active

Flexibility, strength

Research in MC/L Lab: coordination

-learning complex movements more slowly

-need more augmented feedback

-once learned, retained (possible exception, memory driven skills)

-memory driven movements more difficult

BIG and LOUD speech therapy

Hunington's Disease

Disease of basal ganglia

Genetic (cell death) - chromosome 4

Age: 30-40s that already have children

Both motor and cognitive symptoms

Too much movement - writing, tics

Ultimately fatal

Those on PD meds too long have HD motor symptoms

Multiple sclerosis

Primarily young adults

-onset in 20 to 40 years olds

More common in

-women

-caucasians (northern European ancestry)

-areas farther away from equator

Multiple sclerosis CNS involvement

Progressive demyelination of axons

-Myelin around axons degenerates (white matter)

-Axon degeneration

Can occur in CNS or PNS

-Any area in the brain

-Motor or sensory neurons

Short circuits and slow signals

Etiology of multiple sclerosis

Believed to be an auto immune disease

-Immune system attacks itself

Causes inflammation, which breaks down myelin

Scarring (sclerosis) forms plaques

Causes of multiple scleorsis

Unknown

Genetics contribute

Vitamin D deficiency

Viruses that infect nervous system

May be stress related

Early symptoms of multiple sclerosis

Wide variation

-(affects different parts of CNS and/or PNS)

Sensory numbness or tingling

Muscular weakness or incoordination

Visual difficulties (one eye affected)

Vertigo

Fatigue

Decreased memory, poor reasoning

Depression

Progression of multiple sclerosis

Remission, re-occur

Gait affected (use of wheel chair)

Rigidity, spasticity

Poor speech

Any early symptoms with greater severity

Multiple sclerosis treatment

Corticosteroids (to reduce inflammation)

Exercise (try to stay active as possible, yoga, tai chi)

Avoid stress and fatigue (avoid increasing core temperature)

Amyotrophic Lateral Sclerosis (ALS) (Lou Gehrig Disease)

Cause: genetic

Attacks cell bodies in motor areas of cerebral cortex and corticospinal tract axons

Motor symptoms, disabling, usually dying from respiratory failure

Degenerative diseases cerebral cortex

Alzheimer's disease

Degenerative diseases basal ganglia

Parkinson's disease

Huntington's disease

Degenerative diseases white matter

Multiple sclerosis

Degenerative diseases gray matter

Amyotrophic Lateral Sclerosis

Cerebral Palsy

Disorder of posture and movement that is non-progressive/non-hereditary

Prevalence: 1-2 per 1000 children

More in low birth weight infants (50% of cases)

More in caucasians and in males

More prevalent in premature births

Etiology of Cerebral Palsy

Damage to CNS prior to, during or soon after birth

Insult while brain is rapidly developing

Note: hypoxia is not a primary contributor (human error)

Severity dependent upon degree damage

Characteristics of Cerebral Palsy

Spastic (motor cortex)

-sudden muscle contractions

-tense/contracted muscles

Athetoid (basal ganglia)

-writhing, uncontrolled movements of the limbs, head, and eyes

Ataxic (cerebellum)

-poor coordination, timing

-poor balance

Can involve upper or lower limbs, trunk, neck, speech

Scoliosis

Associated involvement: cognition, language and vision

Treatment of Cerebral Palsy

Medication for rigidity (baclofen pump)

Rehabilitation therapy

-increase strength and range of motion

-improve coordination

Rhizotomy

-severing some sensory neurons to reduce spasticity in legs

Orthopedic

-tendon lengthening

-rods in backs

Assistive technologies

-wheelchair, communication

Stroke: Cerebrovascular Accident (CVA)

Any sudden spontaneous vascular event in the brain

Not a neurological disease

Disease that affects blood flow, which in turn damages the brain

Stroke statistics

-750,000 people/yr, 66% survival rate

-Third leading cause of death in the US

-The leading cause of diability

-Most frequent reasons for admission to nursing home

-Costs $30 billion annually

-More common in elderly >60 year old

-20% occur in persons

Non-modifiable risk factors for stroke

Age >60 (20%

Modifiable risk factors for stroke

-HBP: single most important modifiable risk factor

-coronary artery disease

-high cholesterol

-diabetes

-smoking

-alcohol abuse

-obesity

-lack of physical activity

-use of oral contraception

-sleep apnea

Subarachnoid space

is the space which normally exists between the arachnoid and the pia mater, which is filled with cerebrospinal fluid

Types of stroke

Epidural hematoma

Subdural hematoma

Subarachnoid hemorrhage

Hemorrhagic stroke

Ischemic stroke

Epidural hematoma

Beneath skull, but outside dura mater

Skull fracture arterial, so fast blood loss; lucid interval

Subdural hematoma

Beneath dura mater

Abrupt motion of head leads to venous, so slow blood loss

Subarachnoid hemorrhage

Subarachnoid space

Spontaneous is arterial, so fast

Hemorrhagic stroke

"Red stroke" bleeding in the brain

Chronic hypertension causing aneurysms; fatal

Ischemic stroke

"White stroke" lack of oxygen to brain typically due to blood clot - kills brain cells

85% OF ALL STROKES

Treatment: anticoagulant therapy (heparin)

Impairment post stroke depends on

Condition of person prior to stroke

Where in the brain, and size of damaged area

Type of stroke

Ischemic stroke sides

Left hemispheric damage: right side of body

Right hemisphere damage: left side of body

Common stroke impairments cognitive

Confusion

Personality changes

Apraxia

Neglect

Receptive aphasia

Common stroke impairments motor

Weakness

Spasticity

Balance of difficulties

Loss of sensation, or hypersensitivity

Expressive aphasia

Stroke treatment: role of exercise

Rehabilitative/Recovery of Function

Acute: basic functions

-Goals: go home, be safe, decrease fall risk

-Physical, occupational, and speech therapy

Chronic: conditioning/fitness

-Goals: increased fitness levels, reducing risk factor to prevent second stroke, help with depression

Stroke prevention: role of exercise

Prospective Studies examining LTPA and PA

-Followed 22,000 men, asked about their PA, relative risk for stroke decreased as PA increased, dose-response manner

-Followed 72,000 women since 1986, again found that increased PA DECREASED RISK FOR STROKE

Bone-related conditions

Osteoporosis

Osteoarthritis

Neuromuscular conditions

Fibromyalgia

Muscular Dystrophy

Musculoskeletal health

65+ Population is aging

-31 million in 2000

-40 million in 2010

-72 million projected in 2030

-88.5 million by 2050

1 in 5 over 65 years by 2030

Biology of bone mechanical

Structural support for heart, lungs and marrow

Protection for brain, uterus, and other internal organs

Attachment sites for muscles allowing limb movement

Biology of bone metabolic

Mineral reservoir for 99% of the body's calcium, 85% of phosphorous and 65% of the sodium

Biology of bone hematopoietic

Bone marrow makes red and white blood cells and platelets

Biology of bone architecture

Cancellous (trabecular or spongy)

Cortical (compact or solid)

CTM

Cortical bone

Trabecular bone

Marrow tissue

Cancellous (trabecular or spongy)

supporting strength to ends of weight-bearing bone

Cortical (compact or solid)

forms shaft of long bone, on the outside

Osteoblasts

bone formation and lining cells (cover surface of bone)

B in blast B for BUILD

Osteoclasts

resorb/dissolve bone

release calcium to blood

Osteocytes

Maintenance

Transport metabolites

Cell communication

Regulate mineral balance

Remodeling regulated by

Parathyroid hormone (stimulates osteoclasts)

Thyroid hormone (stimulates osteoblasts)

Sex hormones (estrogen: suppresses activity of osteoclasts)

Vitamin D

Wolf's Law

Bone is laid down where it is needed (in response to stress) and resorbed where it is not needed

Minimal essential strain

-Threshold signal is sent to osteoblasts; if threshold signal is not met, osteoclasts are produced to resorb bone

Factors that determine peak bone mass

Genetic factors

Hormonal milieu

Mechanical loading

Nutritional factors

Other factors

Late 20/early 30s

typical peak bone mass

Etiology of osteoporosis

Characterized by decreased bone mass and structural deterioration of bone tissue, leading to bone fragility and increased susceptibility to fractures

Metabolic bone disorder resulting from resorption of calcium from bone

Osteo means

bone

Porous means

full of holes

Diagnosis of osteoporosis

1. Bone mineral density (BMD)

2. Laboratory biochemical markers

3. Bone biopsy with pathologic

Bone mineral density (BMD)

is the weight of mineral per unit volume of bone (how many minerals are deposited in the bone or how porous the bone is)

-DEXA (Dual energy x-ray absorptiometry)

-Quantitative CT Scan

-Quantitative Ultrasound

Laboratory biochemical markers

Circulating calcium, vitamin D, and estrogen levels

WHO definitions of osteoporosis

T-Score -1.0 and above = normal BMD

T-Score -1.0-2.5 = low bone mass (osteopenia)

T-Score -2.5 and below = osteoporosis

T-Score -2.5 and fragility fracture present = severe osteoporosis

Prevalence of osteoporsis

-44 million Americans potentially affected

-10 million individuals have osteoporosis; 34 million have low bone mass = increased risk

-Gender

--80% affected are women

--Loss of bone mass with aging, perhaps 0.7% per year in adults

--Women may lose 20% bone density in 5-7 years after menopause

-Fracture risk

--1 in 2 women and 1 in 4 men over 50 will have an osteoporosis related fracture in their lifetime

-Caucasian women have 2x fracture incidence as African-American women

-Race/Ethnicity

--20% caucasian and Asian women, 7% men

--10% Hispanic women 3% men

--5% African American women, 4% men

--Risk is increasing most rapidly in hispanic women

Osteoporosis risk factors

Gender

Age >70 years

Caucasian or Asian race

Small frame/low weight

Heritability (40-70% BMD)

Nutritional issues

Sedentary lifestyle

Low vitamin D levels

Smoking!

Medications

Inadequate estrogen/testosterone

Importance of vitamin D

Lowest fracture risk when vitamin D serum between 24-32 mg/dl

May be associated with mortality, morbidity, cancer, multiple sclerosis, diabetes, osteoarthritis, fibromyalgia

Consequences of osteoporosis

Compression fracture

Kyphosis

-shortening of the spine

Falls

-femur (hip) 24% over age 50 die in 1st year

-6 months post-fracture, only 15% walk across room without aid

-spine

-wrist

Preventing osteoporosis

Athletic youngsters or individuals active in sport during youth possess greater BMD than non-athletic persons ("bank account" during youth) site specific formation of bone: sport related

Physical activity: walking 4 hrs/week = 40% reduction in hip fractures

Nutrition (supplements)

-Total calcium: 1,200 mg/day

-Vitamin D: 800-1000 IU/day supplement

Fall prevention for older adults

1. keep bathroom lights on

2. install grab bars

3. avoid loose rugs

4. remove clutter

5. keep wires behind furniture

Treatment of osteoporosis

Dietary calcium

Vitamin D supplements

Physical activity

Hormone replacement therapy (estrogen)

Pharmacologic Intervention

-Biphosphonates (reclast, fosamax, Actonel) stimulates apoptosis of osteoclasts

-Estrogen receptor agonists (Evista/Tamoxifen) protects osteoblasts from apoptosis

-Parathyroid hormone (Forteo) stimulates osteoblast activity

Exercising with osteoporosis

Weight bearing aerobic activities (3-5 days/wk) and resistance exercises (2-3 d/wk)

-stair climbing, walking, weight lifting

-moderate intensity: 40-60% VO2R or HRR $ 8-12 repetitions

Balance training

Avoid explosive movements or high impact loading

Avoid exercise causing twisting, bending, or compression of the spine (sit ups, hypertension)

Osteoarthritis

There are more than 100 different types of arthritis

Osteoarthritis is the most common

Etiology of osteoarthritis

Primary: typically due to heredity and mechanical factors with overuse; aging

-unknown etiology

-affects spine, hip, or knee (weight bearing joints)

Secondary: history of injury or trauma

-associated obesity

-congential abnormality

-diabetes, gout, etc

-often lower extremity affected

Background osteoarthritis

Chronic, progressive disorder causing deterioration of joint cartilage and bone

Cartilage

-becomes rigid and thin

-easily damaged by use or injury

Bone

-thickening bone

-bone spurs

Fragment of bone or cartilage may float in joint space

Joint lining becomes inflamed ("joint inflammation)

Not systematic - localized

Osteoarthritis symptoms

Pain

Crepitus (grinding)

Swelling leads to cartilage deterioration

Lose motion leading to joint deformity

Diagnosis of osteoarthritis

Diagnosis based on

-Physical exam

-Symptom history

-X-rays (advanced disease)

--loss of cartilage

--joint space narrowing

--spur formation

-No current blood test for OA