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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
Cortical Dementia – Alzheimer’s disease
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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?
Cortical Dementia – Alzheimer’s disease
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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
Cortical Dementia – Alzheimer’s disease
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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
Cortical Dementia – Alzheimer’s disease
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Amyloid plaques – deposits consisting of aluminum silicate and amyloid peptides (essentially protein buildup)
Cortical Dementia – Alzheimer’s disease
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Cortical Dementia – Alzheimer’s disease
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Cortical Dementia – Alzheimer’s disease
NeurotransmittersCholinergic system is most
affected90% of cells in the nucleus
basalis of Meynert are destroyed
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Cortical Dementia – Alzheimer’s disease
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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Cortical Dementia – Alzheimer’s disease
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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Cortical Dementia – Alzheimer’s disease
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
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