DEMENTIA

A general descriptive term for a brain disorder that produces widespread deterioration of mental functions and social capabilities.

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%)

Types of Dementia

Alzheimers Disease (AD)

Statistics Symptoms Brain Pathology Potential Causes Diagnosis and Treatment Neuropsychological Function

Alois Alzheimer (1864 1915)

Statistics
The first case of AD was reported in 1901 by a German Psychiatrist named Alois Alzheimer.

AD affects approximately 4.5 million Americans. By the year 2050, this number could increase to 11.3 - 16 million.

Increasing age is the greatest risk factor for AD. Approximately 10% of individuals over the age of 65 and 50% of those over the age of 85 are affected.

First Alzheimers Disease patient Auguste Deter (Dx at 51 yrs. Old)

Statistics
It is estimated that after the onset of symptoms, individuals with AD live an average of 8 years, but the duration of the disease can range anywhere from 3 to 20 years. AD represents more than 50% of diagnosed dementia cases.

Senile Plaques

Senile Plaques

Neurofibrillary Tangles

NFT

Plaques and Tangles

Brain Pathology

Cortical Atrophy and Enlarged Ventricles

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.

Cerebral Atrophy - Narrowed Gyri and Widened Sulci

Symptoms

Symptoms
Early Stages Forgetfulness (problems with memory) Memory problems lead to confusion and disorientation Inarticulate speech (problems staying on topic) Depression Middle Stages Poor judgment, impulse control, and disinhibition Problems with abstract thinking Personality changes including rapid changes in emotion Wandering Delusions and hallucinations Late Stages Bedridden totally dependent

DSM-IV-TR criteria (294.1x)

A. The development of multiple cognitive deficits manifested by both: Memory impairment One or more of the following cognitive disturbances:
Aphasia (language disturbance) Apraxia (impaired ability to carry out motor activities) Agnosia (impaired object recognition) Executive disturbance (planning, organizing, etc.)

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 the APOE gene (one from each parent). Greatest risk is associated with the e4 variant.

Potential Causes
Education Level (cognitive ability) Previous Head Injury

Diagnosis and Treatment

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 is rarely 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 are temporary. Other drugs can be given to aid with symptoms (e.g., depression, anxiety).

Korsakoffs dementia

Koraskoffs Dememntia
Cause lack of Thiamine (B1) Secondary to alcoholism

Korsakoffs Dementia
Major symptoms Anterograde amnesia - mamillary bodies Confabulation prefrontal cortex Lack of content in conversation Wernickes
area

Lack of insight prefrontal cortex Apathy limbic system

Korsakoffs Dementia

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 "earlyonset" disease that begins before the age of 50.
http://www.ninds.nih.gov/disorders/

Statistics
Originally described in 1817 by an English physician, Dr. James Parkinson, who called it "Shaking Palsy." Affects 1% of the population over age 50 years. Mean age of onset is mid-50s 40% develop the disease between 50 and 60. Approximately 10-15% of patients show signs of dementia. Men and women equally affected; no social, ethnic, economic or geographic boundaries.

Motor Symptoms
Initial symptom: mild tremor and weakness of one hand. The disease progresses to involve other limbs, posture becomes less erect, 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, or abnormal motor reactivity, whereas the negative symptoms indicate a reduction in or loss of motor functioning.

Positive
Resting Tremor (70% of PD) Essential Tremor Poor balance Cogwheel rigidity Pill rolling

Negative
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)

Non-Motor Signs:
1) Cognitive problems (executive, spatial, working memory) or dementia 2) Emotional changes (depression, anxiety, apathy, irritability) 3) Sleep dysfunction (restless sleep, daytime drowsiness) 4) Fatigue and loss of energy

Brain Pathology
PD selectively destroys dopaminergic neurons in the substantia nigra. Approximately 50% to 80% of these neurons must be destroyed before symptoms become apparent. The disease is also characterized by Lewy bodies.

Substantia Nigra and Parkinsons Disease

http://health.allrefer.com/health/

Basal ganglia: Caudate (blue) and putamen (green)

http://www9.biostr.washington.edu/cgi-bin/DA/imageform

Dopaminergic pathways

Lewy Bodies
These are small, tightly packed 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.

Side of Motor Symptom Onset

LPD: Left Side Motor Symptom Onset Right Hemisphere

RPD: Right Side Motor Symptom Onset Left Hemisphere

Types of PD
Idiopathic (unknown cause; describes most cases of PD) Postencephalitic parkinsonism (encephalitis lethargica, sleeping sickness) 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

The Case of the Frozen Addicts:

How the solution of an extraordinary medical mystery spawned a revolution in the understanding and treatment of Parkinson's disease
J. William Langston and Jon Palfreman, 1996

What they wanted to make: Pethidine

What they made: MPTP (neurotoxic when it metabolizes to MPP+)

Pethidine: Ethyl-1-methyl-4-phenylpiperidine-4-carboxylate (aka Meperidine; Demerol). Opiate analgesic used as a

recreational drug.

Selectively targets neurons of the substantia nigra, producing irreversible PD.

MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
(Structures from Wikipedia)

Potential Causes
Rural living and drinking well water are associated with an increased 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.

Treatments
L Dopa DA agonist Sinimet (CR) Behavioral Deep Brain Stimulation (GP) Stem Cells GDNF

 Deep Brain Stimulation GDNF

Lewy Body Disease

Statistics Symptoms Brain Pathology Potential Causes Diagnosis and Treatment Neuropsychological Function

Statistics
The disease was discovered in 1912 by Friedrich Lewy (18851950) LBD occurs in approximately 20-35% of demented patients. (2nd most common dementia) Onset is typically between 75-80 years; average duration is 6 years (range 1-20) Slight male predominance

Symptoms
Dementia plus two of the following three symptoms indicates a probable diagnosis of LBD: 1) Extrapyramidal (Parkinsonian) signs such as bradykinesia, rigidity and postural instability, but not always a tremor. Fluctuating cognitive ability. Sometimes there will be daily shifts in lucidity or mood exhibited. Visual and other sensory hallucinations. For example, a patient may repeatedly experience a single identical odor that cant be explained.

2) 3)

Other features include falling, loss of balance, fainting spells, transient loss of consciousness, and delusions.

Brain Pathology
Typical distribution of senile plaques and NFTs of AD. Typical subcortical changes (i.e., Lewy bodies and cell loss) in the substantia nigra of PD. Lewy bodies that are diffusely distributed throughout the neocortex.

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.

Diagnosis and Treatment

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 and hallucinations).

Overlap between LBD, PD, and AD

Creutzfeldt-Jakob Disease
http://health.allrefer.com/health/

Creutzfeldt-Jakob Disease
CJD is a rare, degenerative, invariably fatal brain disorder. Typical onset of symptoms occurs about age 60. It is one of the Transmissible Spongiform Encephalopathies (TSEs). TSEs are caused by a type of protein called a prion. The harmless and the infectious forms of the prion protein are nearly identical, but the infectious form takes a different folded shape than the normal protein. Course and treatment. Early stages: poor memory, behavioral changes, lack of 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. Result of the practice of ritualistic cannibalism (eating brain tissue). 2) TSEs in animals: bovine spongiform encephalopathy (mad cow disease), scrapie in sheep and goats; chronic wasting disease in deer and elk; others
http://www.ninds.nih.gov/disorders/

Mad Squirrels and Kentuckians

In Which Neither Changing Custom, Nor Public Opprobrium, 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 rural Kentucky, where eating squirrel and other small game is not uncommon A history of eating squirrel brains was obtained from family members of all five patients with probable or definite CJD seen over 3.5 years in a neurocognitive clinic in western Kentucky. None were related and each lived in a different town. Eating squirrel brains was reported among 12 of 42 patients with Parkinson's disease seen in the same clinic and 27 of 100 age-matched controls without neurological disease living in western Kentucky Culinary preparations include scrambling the brains with eggs or putting them in a meat and vegetable stew referred to as "burgoo".

(From: Berger, J.R., Weisman, E., Weisman, B (1997). Creutzfeldt-Jakob Disease and eating squirrel brains. Lancet 350, #9078.)