The Mind Tl 1

Front 1

Define delirium.

Back 1

1. acute onset of fluctuating confusion & disorientation
2. usually limited duration
3. disrubance of attention, sleep/wake pattern, perception, activity
4. secondary to one or more medical disorders

Front 2

Where is delirium found?

Back 2

usually elderly
ED, medical ward, ICU, CABG pts;

Front 3

Discuss morbidity with delirium.

Back 3

more likely to
1. get nosocomial infections
2. experience functional decline
3. go to a nursing home
4. have residual cognitive impairment
5. die within a year of discharge

Front 4

Discuss mortality with delirium.

Back 4

In-hospital:
Acute MI: 9%
On admission: 10-26%
Develop in hospital: 22-76%
Post-op: 4-13%

Front 5

What are some DSM IV TR symptoms of delirium?

Back 5

confusion
disorganized thinking
restlessness
hallucinations
delusions
pulling IVs
sudden onset
inattention
resisting care
aggressiveness
fluctuation course
lethargy

Front 6

What is the confusion assessment method (CAM)?

Back 6

simple standardized tool used by non-psychiatrically trained physicians & nurses.
*Diagnosis requires 1+2;3 or 4
1. acute onset & fluctuating course of mental status change
2. inattention
3. disorganized thinking
4. altered level of consciousness

Front 7

What are some common causes of delirium? Which is most common?

Back 7

1. drugs MOST COMMON CAUSE(sedatives/hypnotics, benzodiazepines, anticholinergics, antidepressants, fluoroquinolones, LOTS)
2. Alcohol withdrawal or intoxication
3. infections (pneumonia, UTI, septic, systemic viruses)
4. metabolic disorders
5. CV disorders (MI, stroke, TIA, cerebral vasculitis, subdural hamatoma, SBE...)

Front 8

What are less common causes of delirium?

Back 8

1. neoplasms
2. trauma (injury, surgery, burns)
3. environmental (deprivation, overstimulation)

Front 9

Delirium mnemonic:

Back 9

Dementia
Electrolytes
Lungs,liver,heart,kidney,brain
Infection
Rx (espec. anticholinergics)
Injury: pain, stress, head
Unfavorable environment
Metabolic

Front 10

What are normal cognitive changes associated with aging?

Back 10

1. slower learning
2. learning & encoding vulnerable to distraction
3. classification & storage less efficient
4. crystallized intelligence increases; fluid intelligence decreases

Front 11

What is the DSM-IV definition of dementia?

Back 11

1. Memory impairment AND
2. Other cognitive disturbances:
*aphasia
*apraxia
*agnosia
*disturbances of planning, organizing, sequencing, abstraction

Front 12

Clinical key to differentiate delirium & dementia?

Back 12

delirium: attention & wakefulness ALWAYS disturbed.
dementia: attention & wakefulness preserved.

Front 13

How to differentiate between depression & dementia?

Back 13

depression/dementia
1. clear onset, rapid progression/insidious onset, slow progress
2. exaggerated deficits/minimize deficits
3. variable performance/consistent performance
4. little effort/struggle to perform

Front 14

NINCDS-ADRDA criteria for PROBABLY Alzheimer disease? (6)

Back 14

1. dementia established by clinical criteria
2. deficits in at least 2 areas of cognition
3. progressive worsening of cognitive function
4. no disturbance of consciousness
5. onset between 40-90 yrs, usually after 65
6. absence of other diseases that could account for progressive deficits

Front 15

What are the 7 stages of Alzheimer's Disease?

Back 15

1. No cognitive decline
2. Very mild (minimal memory & cognitive impairment)
3. Mild/Early confusional (anxiety or denial, other may notice)
4. Moderate/Late confusional
5. Moderately severe/Early dementia (needs assistance; marked deficits)
6. Severe/Middle dementia
7. Very severe/Late dementia

Front 16

What abnormal proteins are found in Alzheimer's disease?

Back 16

1. Beta amyloid [in plaques; mutation of APP gene on chromosome 21]
2. Tau [hyperphosphorylated; high in CSF]

Front 17

What are neuritic plaques?

Back 17

focal, spherical, collections of dilated, tortuous, silver-staining dystrophic neurite (dendrites) process often around a central amyloid core
microglial cells & reactive astrocytes at periphery
AzD: found in hippocampus > amygdala > neocortex > deep gray matter
Core stains Congo red; A-beta 42 (beta amyloid)
Looks like burnt-out campfire

Front 18

What are diffuse plaques?

Back 18

beta-amyloid depositing lacking the surrounding neuritic reaction.
Found in superficial cerebral cortex, BG, & cerebellar cortex.
Early stage of plaque development

Front 19

What are neurofibrillary tangles?

Back 19

bundles of filaments in cytoplams of neurons; displace or encircle nucleus.
Flame shape in pyramidal neurons.
cortical neurons (entorhinal), hippocampus, amygdala, basal forebrain, raphe nuclei
hyperphosphrylated TAU PROTEIN
also contains MAP2, ubiquitin
NOT SPECIFIC TO AzD.

Front 20

What are normal physiological age-related changes?

Back 20

1. decreased brain weight
2. cortical atrophy (fewer neurons, more astrocytes; affects females more & earlier)
3. ventricular enlargement
4. vascular: amyloid deposits, arteriosclerosis, atherosclerosis
5. Neurons: fewer, smaller; fewer dendrites; accumulation of NF tangles, neuritic plaques, Lewy bodies; change in NT distribution & number

Front 21

What are Lewy bodies?

Back 21

cytoplasmic, round eosinophilic inclusions
midbrain & pons > cerebral cortex > deep gray matter
contains alpha-synuclein (fine filament)
NF antigens, parkin, & ubiquitin also present

Front 22

Gross morphology of Alzhemier's Disease?

Back 22

brain weight < 1000g
frontal & temporal cortical atrophy
loss of gray & white matter
hydrocephalus ex vauco
BS & SC normal

Front 23

What are histologic changes in Alzheimer's disease?

Back 23

in cerebral cortex & hippocampus:
1. neuritic plaques
2. neurofibrillary tangles - correlate most w/degree of dementia
3. granulovacuolar degeneration - Hirano bodies
4. congophilic angiopathy (beta-amyloid)
*distribution similar to normal aging, but far more extensive*

Front 24

Discuss cerebral amyloid in Alzheimer's disease.

Back 24

AB40 present in normal neurons
Encoded on chrom.21
APP (amyloid precursor protein) normally cleaved by alpha-secretase then gamma-secretase (GACE) to soluble form.
AD: APP cleaved by beta-secratase (BACE) then GACE -> abnormal, toxic, insoluble AB-42

Front 25

What is the most common form of Alzheimer's?

Back 25

sporadic

Front 26

Familial Alzheimer's chart

Back 26

Front 27

Why are anticholinergics contraindicated in Alzhermier's & other dementias?

Back 27

Choline acetyl transferase (CAT) activity is is significantly lower than in control group. Synapses can't work!
Can give AChE inhibitors to treat/slow the dementia.

Front 28

What are comon AChE inhibitors (also in textbook notes)?

Back 28

Donepezil = Aricept
Galantamine = Razadyne
Rivastigmine = Exelon*
Tacrine = Cognex
*Rivastigmine also comes in a patch for easy administration.

Front 29

What is a NMDA receptor antagonist?

Back 29

memantine = Namenda
non-competitive
blocks glu-induced activation of Ca channels
protects against neuron death.

Front 30

What are indications for cognitive enhancement therapy?

Back 30

probably Alzheimer's
mild to moderate

Front 31

What are goals of cognitive enhancement therapy?

Back 31

1. early recovery of cognitive function (not dramatic)
2. retard deterioration
3. preserve function
4. delay placement outside home
*DOESN'T REVERSE EFFECTS OF AzD*

Front 32

Criteria for vascular dementia?

Back 32

1. dementia criteria AND
2. focal neurological signs indicative of cerebrovascular etiology (reflexes, paresis, ataxia) OR
3. lab or radiologic evidence indicative of cerebrovascular etiology

Front 33

Clinical features of vascular dementia?

Back 33

1. abrupt onset
2. stepwise deterioration
3. fluctuating course
4. spotty or patchy deficits
5. depression or emotional incontinence
6. relative preservation of personality

Front 34

Risk factors for vascular dementia?

Back 34

1. HTN
2. smoking
3. diabetes
4. hypercholesterolemia
5. other signs & symptoms of vascular disease
[strokes]
men > women
earlier onset than AD

Front 35

Alcohol-Induced Persistent Dementia: how much do you need to drink to make it likely?

Back 35

>5 oz absolute EtOH/day for 10+ years
(12-pk beer, 2 bottles wine, 1/2 fifth)

Front 36

Describe alcohol amnestic disorder.

Back 36

Korsakoff's psychosis or
Wernicke-Korsakoff syndrome
-specific short-term memory impairment
-no general loss of intellectual function

Front 37

Discuss dementia associated with alcoholism.

Back 37

1. global loss of intellectual abilities
2. memory impairment
3. disturbances of at least one of the following:
*abstract thinking
*judgment
*higher cortical function
*personality
4. NO disturbance in level of consciousness

Front 38

What is the most common infectious cause of dementia in the US?

Back 38

HIV

Front 39

ID. Disease? Stain? Where found?

Back 39

1. Neuritic plaque
2. Associated w/normal aging, but many more with Alzheimer's Disease
3. Congo red stain; also can be seen in silver stain or polarized CR stain.
4. hippocampus > cerebral cortex > deep GM

Front 40

ID. Disease? Where found? composition?

Back 40

1. Neurofibrillary tangle
2. normal aging, but more in AD.
3. hippocampus > cerebral cortex > deep gray matter > brain stem
4. hyperphosphorylated tau proteins

Front 41

ID. Disease? Where found? Composition?

Back 41

Lewy Body.
normal aging. Increased in Parkinsons, Lewy Body Dementia.
fine filament alpha-synuclein (also NF antigens, parkin, & ubiquitin)

Front 42

Compare cerebral amyloid to its normal counterpart.

Back 42

derived from amyloid precursor protein; Chr 21
Found in normal neurons (soluble).
Cleavage by alpha secretase + gamma secretase -> normal.
Cleavage by beta-secretase + gamma-secretase -> toxic AB.

Front 43

Discuss characteristics of AB.

Back 43

aggregates readily
B-pleated sheets
binds Congo red
resistant to degradation
elicits response from astrocytes & microglia
can be directly neurotoxic.

Front 44

What are degenerative diseases affecting the cerebral cortex?

Back 44

1. Alzheimer's Disease
2. Frontotemporal Dementia/Picks Disease
3. Frontotemporal Dementia w/Parkinsonism linked to Chromosome 17
4. Progressive Supranuclear Palsy (PSP)
5. Corticobasal Degeneration (CBD)
6. motor neuron disease inclusion dementia
7. dementia lacking distinctive histology
2.

Front 45

Which frontotemporal dementias have tau pathology?

Back 45

1. FTD w/Parkonsonism - chr17
2. FTD/Pick Disease
3. PSP
4. CBD

Front 46

Which frontotemporal dementias lack tau pathology?

Back 46

1. motor neuron disease inclusion dementia
2. dementia lacking distinctive histology

Front 47

Describe Pick's Disease.

Back 47

rare
peak ~ 60yrs
sporadic, sometimes AD inher.
2-5 yr course
extreme "kinfe-edge" frontotemporal atrophy
brain wt <1000g
compensatory hydrocephalus
Pick bodies in surviving neurons

Front 48

What are in Pick bodies?

Back 48

neurofilaments
microtubules
vesiculated ER
paired helical filaments w/3-repeat tau.
do not survive after death.

Front 49

What are the most important degenerative diseases of the basal ganglia & brainstem?

Back 49

parkinsonism
Huntington chorea

Front 50

What are examples of Parkinsonism?

Back 50

1. Parkinson disease
2. Multiple System Atrophy
3. Postencephalitic parkinsonism
4. PSP (movt+cognitive)
5. CBD (movt + cognitive)

Front 51

Describe Parkinson Disease.

Back 51

diminished facial expression, stooped posture, slow voluntary movt, festinating gait, rigidity, tremor at rest
+ dementia (10-15%)
fluctuating course
hallucinations
frontal signs.
Lewy bodies in cerebral cortex, amygdala, & BS

Front 52

Describe Multiple System Atrophy.

Back 52

glial cytoplasmic inclusions w/in oligo cytoplams [contain α-synuclein]
Atrophy of cerebellum, peduncles, pons, medulla, SN, striatum
1. striatonigral degeneration,
2. Shy-Drager Syndrome,
3. olivopontocerebellar atrophy

Front 53

Describe the onset of Huntington's Disease.

Back 53

Rare, inherited AD (HD gene on 4p16.3 tri-NT repeat expansion).
30s-40s

Front 54

What are early symptoms of Huntington's Disease? Late symptoms?

Back 54

Early: personality change & depression
Late: choreiform movts, jerking, & dementia

Front 55

Cause of Freidrich Ataxia?
Age of Onset?

Back 55

1. AR: Chr 9q13 (usually GAA repeat expansion: frataxin) → generalized mito dysfunction.
2. 5-15 yrs old.

Front 56

Degenerative symptoms of Freidrich's Ataxia?

Back 56

Begins w/difficulty walking (gait ataxia).
Worsens, spreads to arms, then trunk (wheelchair w/in 5 yrs of onset).
Loss of tendon reflexes, impaired joint position & vibraion, dysarthria.
Foot deformities.
Nystagmus common.
Scoliosis.

Front 57

Other symptoms of Friedrich Ataxia?
Diseases?

Back 57

1.chest pain, SOB, heart palps
2. cardiomyopathy, myocardial fibrosis, cardiac failure
3. CHO intolerance, DM

Front 58

What is the cause of Ataxia-Telangiectasia?

Back 58

AR: Chr 11q22-23
can't repair dsDNA breaks

Front 59

Age of onset of AT?
Clinical Course?

Back 59

1. early childhood.
2. death in early 2nd decade.
ataxia, telangiectasias in conjunctiva & skin; Immunodeficiencies (hypoplastic lymph nodes, thymus, & gonads)
3. often die from cancer

Front 60

What are different ways that degenerative diseases affecting motor neurons affect the motor neurons?

Back 60

1. LNNs in anterior horns of SC
2. LMNs in certain cranial nerve motor nuclei (V, VII, IX, XII), but not those that control eye move (III, IV, VI)
3. UMNs (Betz cells) in motor cortex

Front 61

What are causes of ALS?
Onset?
Who is affected?

Back 61

1. 90% sporadic, 10% chr 21 [no single cause explains all the pathology]
2. >40yrs
3. men slightly more than women

Front 62

Where is the damage in ALS?

Back 62

UMN damage in prefrontal cortex. LMN damage in cranial nerve nuclei & anterior horn cells

Front 63

Describe symptoms of ALS.

Back 63

neuronal muscle atrophy d/t LMN damage; hyperreflexia d/t UMN damage.
Early: weakness of hands & spasticity of arms & legs.
Later: ↓ muscle strength & bulk, fasciculations.

Front 64

Describe bulbospinal atrophy (Kennedy Syndrome)

Back 64

X-linked. Adult onset.
Distal limb amyotrophy & blublar signs (atrophy, fasciculations of tongue & dysphasia). androgen insensitivity.
defect in androgen receptor.

Front 65

What are the three variants of ALS?

Back 65

1. progressive bulbar palsy: predominant cranial nerve involvement
2. progressive Muscular atrophy:predominant LMN involvement
3. primary lateral sclerosis:predominant UMN/ corticospinal tract involvement

Front 66

Disease? Why?

Back 66

ALS
bulbar palsy
mild demyelination of anterior & lateral tracts d/t UMN disease

Front 67

Disease? Why?

Back 67

ALS
demyelination of lateral & anterior corticospinal tracts due to UMN disease
Lack of neurons in anteior horn w/reactive gliosis (LMN disease)
Atrophy of anterior spinal roots

Front 68

Disease? Why?

Back 68

ALS
demyelination of lateral & anterior corticospinal tracts due to UMN disease
Lack of neurons in anteior horn w/reactive gliosis (LMN disease)
Atrophy of anterior spinal roots

Front 69

ID. Diseases?

Back 69

Hirano Body. In AD, CJD.

Front 70

What disease is represented on the left?

Back 70

Huntingtons

Front 71

ID.

Back 71

Neuritic plaque silver stain

Front 72

What disease?

Back 72

Parkinson's Disease

Front 73

ID. Disease?

Back 73

Perivascular neuritic plaque.
Amyloid angiopathy & perivascular plaques often in AD.

Front 74

What disease?

Back 74

Pick's Disease.

Front 75

Disease?

Back 75

Alzheimers

Front 76

Disease?

Back 76

None. Normal Brain!

Front 77

Disease?

Back 77

Alzheimers

Front 78

Disease?

Back 78

Huntington's

Front 79

Normal Nissl Stain

Back 79

ALS Nissl Stain

Front 80

Normal myelin stain

Back 80

ALS myelin stain

Front 81

Disease?

Back 81

Friedrich's Ataxia:
degeneration of
1. posterior columns
2. corticospinal tracts
3. dorsal spinocerebellar tracts
4. ventral spinocerebellar tracts
Dorsal roots & peripheral nerves also shrunken when advanced.