Dementias PSY 350 Spr 09 97 03

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DEMENTIA

A general descriptive term for a brain disorder

that produces widespread deterioration of

mental functions and social capabilities.


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Types of Dementia

Cortical Dementias Primarily affect the cerebral cortex or gray matter

Alzheimers Disease (AD) (most common form of dementia-50%)

Picks Disease (type of FTD frontotemporal dementia)

Subcortical Dementias Primarily affect the white matter

Acquired Immune Deficiency Syndrome (AIDS)

Huntingtons Disease (HD)

Creutzfeldt-Jakob Disease (CJD)

Parkinsons Disease (PD)

Mixed Dementias Affect both the gray and white matter

Lewy Body Disease (LBD) (2nd most common form of dementia-25%)

Vascular Dementia (3rd most common form of dementia-15%)


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Types of Dementia


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Alzheimers Disease (AD)

Statistics

Symptoms

Brain Pathology

Potential Causes

Diagnosis and Treatment

Neuropsychological Function

Alois Alzheimer

(1864 1915)


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Statistics

The first case of AD was reported in 1901 by a German Psychiatrist namedAlois Alzheimer.

AD affects approximately 4.5 millionAmericans. By the year 2050, this numbercould increase to 11.3 - 16 million.

Increasing age is the greatest risk factor forAD. Approximately 10% of individuals overthe age of 65 and 50% of those over the ageof 85 are affected. First Alzheimers Disease

patient

Auguste Deter

(Dx at 51 yrs. Old)


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Statistics

It is estimated that after the onset of symptoms, individuals with AD livean average of 8 years, but the duration of the disease can range anywherefrom 3 to 20 years.

AD represents more than 50% ofdiagnosed dementia cases.


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Senile Plaques


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Senile Plaques


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Neurofibrillary Tangles


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NFT


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Plaques and Tangles


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Brain Pathology


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Cortical Atrophy and Enlarged Ventricles


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Brain Pathology

Cortical atrophy will be observed in

most areas of the brain, especially

the temporal, parietal, and frontal

lobes. Atrophy results from the

accumulation of amyloid plaques

and neurofibrillary tangles (NFTs).

Enlarged ventricles (from atrophy)

Changes in neurotransmitter systems most notably,

decreases in acetylcholine (ACh), which directly affects

memory.


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Cerebral Atrophy - Narrowed Gyri and

Widened Sulci


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Symptoms


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DSM-IV-TR criteria (294.1x)

A. The development of multiple cognitive deficits manifested by both:

Memory impairment

One or more of the following cognitivedisturbances:

Aphasia (language disturbance)

Apraxia (impaired ability to carry out motor activities)

Agnosia (impaired object recognition)

Executive disturbance (planning, organizing, etc.)


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Potential Causes

Genetics Presenile AD (40-65 yrs)

chromosomes 1, 14, 21

Late-onset AD (65 + yrs) chromosome 19 (APOE gene) APOE-e2, APOE-e3, APOE-e4

Each person has two copies of theAPOE gene (one from each parent).Greatest risk is associated with the

e4 variant.


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Potential Causes

Education Level (cognitive ability)

Previous Head Injury


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Diagnosis is by the process of elimination blood work, physical, brain

scans, neuropsychological assessment, examination of medications, etc.

Given Probable AD diagnosis.

Confirmation of disorder is made at autopsy or brain biopsy (which israrely chosen).

There is no cure for AD one can only treat some of the symptoms. Drugs

that inhibit the breakdown of ACh are commonly given - Aricept, Tacrine,

Exelon, Reminyl, etc. to aid with memory difficulties. Results aretemporary. Other drugs can be given to aid with symptoms (e.g.,

depression, anxiety).


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Korsakoffs dementia


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Koraskoffs Dememntia

Cause lack of Thiamine (B1)

Secondary to alcoholism


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Korsakoffs Dementia

Major symptoms

Anterograde amnesia - mamillary bodies

Confabulation prefrontal cortex

Lack of content in conversation Wernickesarea

Lack of insight prefrontal cortex

Apathy limbic system


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Korsakoffs Dementia


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Parkinsons Disease

Who Gets Parkinson's Disease? Average age of onset is 60

years, but about 5 to 10 percent of people with PD have "early-

onset" disease that begins before the age of 50.

http://www.ninds.nih.gov/disorders/


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Statistics Originally described in 1817 by an English physician, Dr. James

Parkinson, who called it "Shaking Palsy."

Affects 1% of the population over age50 years.

Mean age of onset is mid-50s

40% develop the disease between 50and 60.

Approximately 10-15% ofpatients show signs of dementia.

Men and women equally affected;no social, ethnic, economic orgeographic boundaries.


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Motor Symptoms Initial symptom: mild tremor and weakness of one hand. The

disease progresses to involve other limbs, posture becomes lesserect, and general slowness develops. The patient has difficulty

initiating voluntary movement. The clinical symptoms of PD

progressively worsen over a period of 20 years before

individuals become severely disabled.

PD is most commonly recognized by its motor disturbances

which will undoubtedly appear at some point during the disease

progression. These motor symptoms fall into two groups:

positive and negative.

The positive symptoms indicate an excess of motor behavior,

orabnormal motor reactivity, whereas the negative symptoms

indicate a reduction in orloss of motor functioning.


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Positive Negative

Resting Tremor (70% of PD)

Essential Tremor

Poor balance

Cogwheel rigidity

Pill rolling

Bradykinesia (slowness of movement)

Hypokinesia (reduced motor initiation)

Rapid small steps (fenestrating gait);freezing

Reduced facial expression (masked facies)

Slowed speech (dysarthria)

Decreased voice amplitude (hypophonia)

Micrographia (small writing)


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Non-Motor Signs:

1) Cognitive problems (executive, spatial, working memory) ordementia

2) Emotional changes (depression, anxiety, apathy, irritability)

3) Sleep dysfunction (restless sleep, daytime drowsiness)

4) Fatigue and loss of energy


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Brain Pathology

PD selectively destroys dopaminergic neurons in the

substantia nigra.

Approximately 50% to 80% of these neurons must bedestroyed before symptoms become apparent.

The disease is also characterized by Lewy bodies.


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Substantia Nigra and Parkinsons Diseasehttp://health.allrefer.com/health/


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Basal ganglia: Caudate (blue) and

putamen (green)http://www9.biostr.washington.edu/cgi-bin/DA/imageform


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Dopaminergic pathways


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Lewy Bodies

These are small, tightlypacked granular

structures with ring-like

filaments found within

dying neurons.

Lewy bodies are NOT

specific to PD, but they

must be there in order to

receive a diagnosis of PD.


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RPD: Right Side Motor

Symptom Onset

Left Hemisphere

LPD: Left Side Motor

Symptom Onset

Right Hemisphere

Side of Motor Symptom Onset

T f PD


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Types of PD

Idiopathic (unknown cause; describes most cases of PD)

Postencephalitic parkinsonism (encephalitis lethargica, sleepingsickness)

Drug-induced (reversible; from use of certain psychiatric drugs, such

as chlorpromazine and haloperidol, which decrease dopamine)

Arteriosclerotic parkinsonism (vascular)

Parkinsonism-dementia complex of Guam/Chamorro (with motor

neuron disease resembling amyotrophic lateral sclerosis)

Post-traumatic parkinsonism ("punch-drunk syndrome, dementia

pugilistica)

Toxin-induced parkinsonism (e.g., MPTP)

http://www.ninds.nih.gov/disorders/parkinsons_disease/detail_parkinsons_disease.htm


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The Case of the Frozen Addicts:

How the solution of an extraordinary

medical mystery spawned a revolution inthe understanding and treatment of

Parkinson's disease

J. William Langston and Jon Palfreman, 1996


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Pethidine: Ethyl-1-methyl-4-phenylpiperidine-4-carboxylate (aka

Meperidine; Demerol). Opiate analgesic used as arecreational drug.

MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Selectivelytargets neurons of the substantia nigra, producingirreversible PD.

(Structures from Wikipedia)

What they wanted to make: Pethidine

What they made: MPTP

(neurotoxic when it metabolizes to MPP+)

P t ti l C
http://www.answers.com/main/ntquery;jsessionid=1pixvr4x82twm?method=4&dsname=Wikipedia+Images&dekey=MPTP.png&sbid=lc02a


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Potential Causes

Rural living and drinking well water are associated with anincreased risk of PD.

Exposure to pesticides and herbicides environmental toxin

hypothesis.

PD has an inverse relationship with smoking. PD patients are

nonsmokers. Individuals diagnosed with PD tend to be low

alcohol consumers.

Research suggests that genetics play a limited role in the

development of PD. Only about 10-15% of individuals with PD

have relatives with PD.


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Treatments

L Dopa DA agonist

Sinimet (CR)

Behavioral Deep Brain Stimulation (GP)

Stem Cells

GDNF


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Deep Brain Stimulation

GDNF


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Lewy Body Disease

Statistics

Symptoms

Brain Pathology

Potential Causes


Neuropsychological Function

Statistics
http://images.google.com/imgres?imgurl=http://www.jhsph.edu/bin/p/o/31parkinson_disease.jpg&imgrefurl=http://www.jhsph.edu/publichealthnews/magazine/archive/Mag_Fall04/microcosmos/enemy_within.html&h=240&w=300&sz=55&tbnid=eNDySUPU350V0M:&tbnh=88&tbnw=111&hl=en&start=39&prev=/images%3Fq%3Dlewy%2Bbody%2Bdisease%26start%3D20%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DN


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Statistics

The disease was discovered in 1912 by Friedrich Lewy (1885-1950)

LBD occurs in approximately 20-35% of demented patients.(2nd most common dementia)

Onset is typically between 75-80 years; average duration is 6years (range 1-20)

Slight male predominance

Symptoms


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Symptoms

Dementia plus two of the following three symptoms indicates a

probable diagnosis of LBD:

1) Extrapyramidal (Parkinsonian) signs such asbradykinesia, rigidity and postural instability, but not

always a tremor.

2) Fluctuating cognitive ability. Sometimes there willbe daily shifts in lucidity or mood exhibited.

3) Visual and other sensory hallucinations. Forexample, a patient may repeatedly experience asingle identical odor that cant be explained.

Other features include falling, loss of balance, fainting spells,

transient loss of consciousness, and delusions.

B i P th l


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Brain Pathology

Typical distribution of senile plaques andNFTs of AD.

Typical subcortical changes (i.e., Lewy bodiesand cell loss) in the substantia nigra of PD.

Lewy bodies that are diffusely distributedthroughout the neocortex.


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Causes

Cause is currently unknown, although having

a family member with LBD may increase

ones risk.

There is also no information about potential

environmental risk factors.


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There is no cure for LBD; diagnosis is made

by the process of elimination. Confirmation is

made upon autopsy.

As with other types of dementia, medications

can be given to help with some of the

symptoms (e.g., memory loss andhallucinations).


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Overlap between LBD, PD, and AD


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Creutzfeldt-Jakob Diseasehttp://health.allrefer.com/health/

C t f ldt J k b Di


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Creutzfeldt-Jakob Disease

CJD is a rare, degenerative, invariably fatal brain disorder. Typical onset ofsymptoms occurs about age 60. It is one of the Transmissible Spongiform

Encephalopathies (TSEs). TSEs are caused by a type of protein called aprion. The harmless and the infectious forms of the prion protein are nearlyidentical, but the infectious form takes a different folded shape than thenormal protein.

Course and treatment. Early stages: poor memory, behavioral changes, lackof coordination and visual disturbances. Later stages:, pronounced mental

deterioration, involuntary movements, blindness, weakness of extremities,coma. There is no cure or treatment. 90 percent die within 1 year.

Types of CJD: sporadic, hereditary, and acquired

Related conditions:1) Kuru: epidemic in the1950s-60s among the Fore of New Guinea. Resultof the practice of ritualistic cannibalism (eating brain tissue).

2) TSEs in animals: bovine spongiform encephalopathy (mad cowdisease), scrapie in sheep and goats; chronic wasting disease in deer andelk; others

http://www.ninds.nih.gov/disorders/


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Mad Squirrels and Kentuckians

In Which Neither Changing Custom, Nor PublicOpprobrium, Nor Learned Medical Opinion Can Dissuade

Some People From Eating a Small Rodents Brain

(From: Noodling for Flatheads, Burkhard Bilger, 2000)

Possible association of eating squirrel brains with CJD in


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Possible association of eating squirrel brains with CJD inrural Kentucky, where eating squirrel and other small gameis not uncommon

A history of eating squirrel brains was obtained from familymembers of all five patients with probable or definite CJDseen over 3.5 years in a neurocognitive clinic in westernKentucky. None were related and each lived in a differenttown. Eating squirrel brains was reported among 12 of 42

patients with Parkinson's disease seen in the same clinicand 27 of 100 age-matched controls without neurologicaldisease living in western Kentucky

Culinary preparations include scrambling the brains with

eggs or putting them in a meat and vegetable stew referredto as "burgoo".

Documents

Dementias PSY 350 Spr 09 97 03