1 Generalized Cognitive Disorders Lecture 10 June 21 st, 2006

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Generalized Cognitive Disorders

Lecture 10

June 21st, 2006

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Up until today we talked about specific deficits (e.g., prosopagnosia, aprosidia, dyslexia, etc.) that were associated with specific brain damage (more or less)

Today we will talk about generalized disorders – syndromes in which the loss of function is not restricted to one cognitive domain but affects multiple cognitive abilities simultaneously

Various causes Traumatic brain injury Dementing disorders (e.g., Alzheimer’s disease) Exposure to toxins

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Traumatic Brain Injury (TBI)

Closed head injury occurs when the brain sustains damage because the head forcefully comes into contact with another object (e.g., a car windshield, the ground, or a blunt instrument such as a baseball bat), but no object penetrates the brain

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TBI

U.S. – 1.5 million new cases annually

300-400 per 100,000 in industrialized countries

TBI cases outnumber all other generalized cognitive disorders (combined)

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200000

400000

600000

800000

1000000

1200000

1400000

1600000

TBI Breast Cancer HIV/AIDS

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TBI Population

Falls

Firearms

Other

Transportation

age

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TBI and Focal Brain Injury

Orbitofrontal cortex and anterior temporal lobes are the most likely to sustain focal injury

03-09

W. W. Norton

Frontal Lobes

Temporal Lobes

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TBI and Focal Brain Injury

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TBI and Diffuse Axonal Injury

Acceleration-deceleration injury Neurons with long axons (white matter tracts) Usually no focal injury Difficult to observe with imaging One sign of injury is endema (i.e., swelling) With time reduced white matter can be observed

(DTI)

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TBI and Diffuse Axonal Injury

Corpus Callosaum

Central White Matter

Midbrain

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TBI – Assessment of Consciousness

Glasgow Coma Score (GCS)

Eye Opening (E) Verbal Response (V) Motor Response (M)

4=Spontaneous3=To voice2=To pain1=None

5=Normal conversation4=Disoriented conversation3=Words, but not coherent2=No words......only sounds1=None

6=Normal5=Localizes to pain4=Withdraws to pain3=Decorticate posture2=Decerebrate1=None

Total = E+V+M

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TBI and GCS

GCS scores are divided into 3 categories: Severe injury (a score of 8 or less) Moderate injury (a score of 9-12) Mild injury (a score of 13-15)

GCS scores have prognostic value for survival rates

E.g., GCS score of 8 or less (6 hours after injury) 35-50% chance of dying within next 6

months 1-5% chance of remaining in persistent vegetative

state20-30% chance of being disabled25% recovery that allows independent living

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TBI and Recovery

Commonly observed cognitive deficitsMemory (posttraumatic amnesia; possibly due

to damage to the cholinergic system)Attention (e.g., selective and divided attention)Executive function deficits (e.g., planning,

inhibition)Affective deficits (e.g., experiencing, detecting

and interpreting emotions)

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Mild Head Injury - Concussion

Mild head injury or concussion occurs when individuals have a change in consciousness (but not necessarily unconsciousness) for 2-30 minutes and do not have any other gross signs of neurological damage

Long lasting effects and increase likelihood of another head injury

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Traumatic Brain Injury and Sports

E.g., head trauma associated with boxing – dementia pugilistica or chronic posttraumatic encephalophahy Tremors Difficulty speaking Abnormal reflexes Disordered thinking Changes in emotion

Other sports are also associated with closed brain injuries (e.g., football, skiing, horseback riding)

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Dementing Diseases

Dementia – refers to an acquired and persistent syndrome of intellectual impairment

DSM-IV defines the two essential diagnostic features of dementia:

1. Memory and other cognitive deficits2. Impairment in social and occupational functioning

• Typically progresses in stages: mild, moderate and severe (eventually leads to death)

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Dementias

Dementias can be divided based on the region of the brain most affected:Subcortical (Parkinson’s disease,

Huntington’s chorea)Cortical (Alzheimer’s disease, Pick’s

disease and Creutzfeldt-Jacob disease)Mixed (vascular dementia a.k.a. multi-

infarct dementia; AIDS dementia

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Cortical Dementia – Alzheimer’s disease

Alzheimer’s disease or dementia of Alzheimer’s type (DAT)

Decline of memory, language, visuospatial skills, abstract thinking, motor performance and judgment

Later on emotional changes and changes in personality

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Two subsyndromes: Early onset Alzheimer’s (onset before 65; rapid

progress) Late onset Alzheimer’s (after 65; slower progression)

No physiological test Probable diagnosis is based on neuropsych profile Confirmation of disease can be made at postmortem

autopsy


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MemoryGlobal anterograde amnesiaRetrograde amnesia (temporally graded)Deficits in short-term memory Procedural memory is not spared

How are Alzheimer’s disease patients similar and different from medial-temporal-lobe amnesia patients?


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Language Aphasia Semantics are more affected than syntax and phonology

• Name as many animals as possible • Name as many words that begin with letter ‘F’

Emotional functioning Neurotic Anxious Introverted Passive Less agreeable


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Neurophysiological BasisNeurofibrillary tangles

(twisted pairs of helical filament within neurons) disruption of normal neuronal functioning

• They can be found in normal aged individuals as well

• Down syndrome etc.• Neurofibliary tangles are not

equally distributed across the cortex


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Amyloid plaques – deposits consisting of aluminum silicate and amyloid peptides (essentially protein buildup)


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NeurotransmittersCholinergic system is most

affected90% of cells in the nucleus

basalis of Meynert are destroyed

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Genetic bases and risk factors Genes associated with increased amyloid beta protein and

early onset Alzheimer’s Smoking ↑ Cardiovascular disease ↑ Diabetes mellitus ↑ Head injury ↑

Non-steroidal anti-inflammatory drugs ↓ Higher education ↓ Mentally challenging work and activity ↓ Estrogen replacement therapy (women) ↓

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Therapeutic Interventions Drugs targeting the cholinergic system Drugs that block acetylcholine (e.g., scopolamine) cause memory

impairments In Alzheimer’s disease an attempt is made to increase the amount

acetylcholine Boosting the levels of acetycholine precursors does not work Drugs that block acetylcholinestarase (the enzyme that breaks

down acetycholine) have been somewhat successful (e.g., tacrine) Many side effects of tacrine Recently used donepezil, rivastigmine, metrifonte, eptastigmine

and galanthamine

These drugs just slow the progression of the disease

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Other therapeutic treatmentsEstrogenNon-steroidal anti-inflamatory drugsAntioxidants (free radical inhibitors)

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Cortical Dementias – Frontotemporal Dementia

Frontotemporal dementia – cortical dementia characterized by poor social-emotional functioning, poor language skills, and motor difficulties

Pick’s disease (type of frontotemporal dementia) 15-20% of dementias Changes in social-emotional functioning

• Lack of inhibition• Impulsivity• Shoplifting• Lack of concern for social norms• Perseveration• Lack of insight• Obsessed with food

Language• Poor naming• Difficulties in reading and writing

No deficits in spatial processing and memory (at least early on)

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Cortical Dementias – Frontotemporal Dementia

Physiological characteristics Atrophy of frontal and

temporal lobesNeurons are pale and

swollenPick’s bodies in the

cytoplasm

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Cortical Dementias – Creutzfeldt-Jacob Disease

CJD is rare (1 in every 1 million people) Caused by prions (proteinaceus infectious particles) Prion proteins can not be broken down, they accumulate

and lead to cell death Incubation period is quite long Prions are highly transmittable (e.g., corneal transplants) Eating cattle with spongiform encephalopathy (mad cow

disease) Behavioural decline is much quicker than Alzheimer’s or

frontotemporal dementia Individuals live about a year after dementia diagnosis

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Subcortical Dementias – Huntington’s Disease

GABAergic neurons in the striatum are destroyed leading to excess movement

Leads to dementia Deficits in

Executive function• Switching mental sets, inhibition (WCST), planning

Spatial processingMemory

• Much better at recognition than recall (unlike DAT)• No temporal gradient (unlike DAT)

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Subcortical Dementias – Parkinson’s Disease

Loss of DA neurons in substantia nigra Dementia occurs in about 30% of individuals Deficits

Impoverishment of feeling, motive and attentionSpeed of thinking - thinking is slowed down -

bradyphreniaexecutive functions (WCST)Spatial memory

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Mixed Varieties Dementias – Vascular Dementias

Caused by many small strokes (obstruction of blood flow) that create both cortical and subcortical lesions

2nd most common type of dementia When restricted to the subcortical white matter,

dementia is referred to as Binswanger’s disease In contrast to other dementias, the onset is quite

rapid (following stroke) There can be an improvement in cognitive

functioning

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Mixed Varieties Dementias – AIDS Dementia

AIDS deficits in the immune system that lead to death

HIV produces neuronal death Both cortical and subcortical areas can

be affected but white matter is particularly susceptible

AIDS dementia affects 6-30% of all adult AIDS patients

Deficits Slowing of mental functions Slowing of motor functions Attention Memory Executive functions Changes in affect

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Demyelinating Diseases – Multiple Sclerosis (MS)

Characterized by loss of myelin, inflammation of neurons and neuronal degeneration

MS is believed to be caused by immunological disruption (body mistakenly identifies it’s own parts as foreign and attacks it – autoimmune disorder)

Pariventricular areas of the brain are most affected Behavioural effects are highly variable and

unpredictable

Documents

1 Generalized Cognitive Disorders Lecture 10 June 21 st, 2006