cognitive disorders Flashcards
specific disorders
result from focal damage to the brain
ie/ injuries caused strokes, bullet wounds
generalized disorders
more distributed effects on brain tissue
breakdown is not restricted to one cognitive domain, but multiple cognitive abilities are effected simultaneously
ie/ closed head injuries, demetias and demyelinating diseases
closed head injuries
brain sustains damage when the head forcefully comes into contact with another object (but object does not actually penetrate brain
lead cause of traumatic brain injury (TBI)
TBI
traumatic brain injury
general term for referring to a sudden external trauma interfering with brain functioning
significant source of neuropsychological dysfunction
- more than 69 million cases each year worldwide
causes of closed head injury
adolescents and young adults = vehicle bicycle and other similar accidents
young children and older adults = falling causing injury
sports-related and combat related
alcohol is involved in about 1/2 of TBI
focal damage
due to the impact of the brain on the skull
diffuse damage
due to twisting and shearing of neurons
acceleration-deceleration injury
primary mechanism of damage in closed head injury
energy imparted to brain causes it to move within the skull
damage from rapid acceleration of the head followed by sudden deceleration
could be focal or diffuse damage
neurons most vulnerable to twisting are those in white-matter tracts, which have long axons and connect distinct brain regions
closed head injury results in neuronal loss in white matter, especially the corpus callosum
can be detected by edema (swelling)
consequences of acceleration-deacceleration injury
secondary biochemical effects include glutamate excitotoxicity (overproduction of glutamate) which can cause cell death
disease state lasts beyond initial accident. can appear as: enlargement of the ventricles, loss of volume in large myelinated tracts
longitudinal studies indicate white-matter deterioration continues for several years following TBI
what areas are most likely to sustain a head injury
orbitalfrontal and temporal regions
bones at these points are rough and potrude through cavity
coup injury
focal damage at the site of impact
contrecoup injury
focal damage opposite the site of impact
glasgow coma scale
one prominent sign of closed head injury is a significant alteration in consciousness
basic aspects of wakefulness and consciousness are controlled by the brainstem
assesses the level of consciousness - used in ER rooms around the world
provides a method for classifying the severity of damage in someone who has sustained head injury
evaluates three realms of functioning
1. visual responsiveness
2. motor capabilities
3. verbal responsiveness
3-8 severe head injury
9-12 moderate injury
13 or greater mild head injury
score has prognostic value for survival rates and fture level of functioning
not a perfect predictor of outcomes
concussion
mild traumatic brain inries
head injury consequences
vary in severity, but all can impact mental functioning
attention and executive functioning (memory) often affected by head injury
difficulty in selected and divided attention, response inhibition and cognitive flexibilty
lack of motivation (due to emotions)
lack of understanding deficits
poor behavioural control
post traumatic amnesia
varies from inability to learn new info to an inability to report basic information
initial presentation of these memory problems tend to predict the severity of injury
long term consequences of sustaining a closed head injury
raises risk for sustaining another injury (by 4-6 times) could be due to poor attention and judgement
risk factor for longer-term neurological problems
associated with post traumatic epilepsy, which may begin more than a year after the head injury
may put an individual at higher risk for dementias
if occurs in early adulthood, significant increase in drepression
interventions for closed head injury
preventions: safety protections, violence prevention (seat belts, helmets)
pharmacological treatments to lessen effects of biochemical cascades including excitotoxicity and inflammation
interventions can be specifically targeted at the cognitive level
cortical dementia: alzheimer’s disease (AD)
brain damage is diffuse
defined by a decline in memory and other aspects of cognitive functioning, including at least one of the following: language , visuospatial skills, abstract thinking, motor performance, and judgement
- at first subtle and then became profound
also see emotional dysfunction and personality changes, which tend to worsen over time
what are the two types subtypes of cortical dementia: AD
early-onset AD: onset occurs before the age of 65; progresses rapidly
late-onset AD: onset after the age of 65; slower cognitive decline
how is alzheimer’s disease diagnosed?
based on behaviour and cognition
the defining biological characteristic can only be determined by post-mortem examination of brain
a probable diagnosis is made when other causes of dementia are ruled out and the person’s behavioural pattern i consistent with the disease
research has focused on potential biomarkers o serve as additional indicators of disease presence
alzheimer’s disease symtoms
AD have an inability to acquire new info as a result of severe, global anterograde amnesia
people with this remain in familiar environments and routines, reducing the need to acquire new information
widespread amnesia impacts procedural knowledge and implicit learning as well as working memory
more aspects of memory are affected because more brain regions are affected, including cortical regions
struggle with:
language: verbal fluency, semantic aspects of language
visuospatial processing
conceptual aspect of motor behaviour
executive functioning
changes in emotional functioning and personality
neurofibrillary tangles
twisted pairs of helical filaments found within the neuron
found in normal functioning brain, but increases in AD
disrupt neurons functional matrix
not equally disributed throughout the brain
amyloid plaques
deposits consisting of aluminium silicate and amyloid peptides that create a conglomeration of proteins
amyloid plaques and AD
observed in normal brain too - just concentrates in the hippocampus and cortex with AD
typically surrounded by neurons containing neurofibrillary tangles, and believed to cause vascular damage and neuronal cell loss
PET methods (involving a ligand that binds to amyloid) have made it possible to assess the presence of amyloid plaque for a living person
progressive accumulation of amyloid plaques is correlated with cognitive decline in living AD patients
Advanced AD and neuron loss
accumulating tangles and amyloid plaques result in loss of synapses and cells
in later stages, cell loss is viable on anatomical brain images; cortex is atrophied, ventricles enlarged
distributed across frontal, anterior temporal, and parietal cortex
subcortical structures affected include hippocampus, amygdala, and olfactory system
Genetic bases and risk factors
typically associated with one of three gene mutations which all involve the increase of production of amylad beta protein
APP mutation
presenilin one or presenilin 2
Apolipoprotein E (ApoE)
APP mutation
located on chromosome 21, codes for amyloid precursor protein and results in amyloid deposits
presenilin 1 or presenilin 2 mutation
affects the presenilin protein and results in accumulation or amyloid plaques
Apolipoprotein E
most closely associated with alzheimers
thought to play a role in clearing amyloid plaques
ApoE-4 allele associated with an increased risk of AD
present in 15% of general population but 40% in AD patients
AD patients with ApoE-4 allele show faster rates of hippocampal atrophy
AD patients with ApoE-4 allele have greater levels of amyloid plaque accumulation
the alone will not cause alzheimers - also genetic and environmental factors
increased risk factors for AD
smoking
cardiovascular disease
diabetes
head injury
decreased risk factors for AD
increase amount of education
mentally challenging activities
social engagement
physical activity
diet
AD treatment
no cure: ; treatment focuses on slowing cognitive decline
treatments attempt to influence the cholinergic system (b/c acetylcholine levels are linked to severity of memory loss and dementia)
neurofibrillary tangles lead to cell death (starved acetylcholine) in the nucleus basalis of meynert and starves (located at the base of the brain route to hippocampus and cortex) the rest of the brain of acetylcholine
drugs given to AD patients attempt to increase availability of acetylcholine - slow AD, but do not stop int
Two main subtypes of FTD
behavioural-varient FTD
primary progressive aphasia (semantic aphasia)
cortical dementia: frontotemporal dementia (FTD)
differs from AD in age of onset, symptom profile, and the brain regions most affected
average age of onset approx 56-58
- FTD accounts for about 10% of dementia cases under the age of 65, but only about 3% over 65
behavioural-variant FTD subtype
characterized by anterior temporal as well as orbitofrontal damage
behavioural-variant FTD subtype symptoms
lack of inhibitatory control, especially social-emotional functioning
impulsiveness
swearing at inappropriate times, outbursts of frusteration and inappropriate sexual behaviour
preoccupation with repetitive or routinized behaviour. ie/ going to the same appointment over and over again
mood changes (especially depression and anxiety)
primary progressive aphasia FTD subtype
progressive decline in language (breakdown in vocab knowledge)
involves more specific left-sided anterior temporal deterioration
primary progressive aphasia FTD subtype symptoms
patients mainly exhibit difficulties in the domain of language
difficulty in verbal expression
over time, speech has less and less content, and eventually patients become practically mute
difficulties in reading and writing also develop
later may develop parkinson-like motor functioning
frontotemporal dementia vs. alzheimer’s disease
patients with AD have thinning across all major cortical regions
patients with FTD have characteristics thinning in frontal and anterior temporal regions
patients with FTD have greater loss of white matter in the frontal lobes than do AD patients
neurological characteristics of FTD
FTD also differs from AD in the abnormal cellular characteristics within damaged regions
abnormal protein deposits within the neurons
pale neurons swollen as if they had “ballooned”
clumps of fibers in the cytoplasm known as Pick’s bodies
risk factors and treatment for FTD
the greatest risk is the presence of FTD in a closely related family member - strong genetic component
genes linked to this include a gene coding for the tau protein, and other genes coding for pathological proteins
no cure, treatment is targeted at managing symptoms. Pharmacological approaches seem to have little benefit
subcortical dementia: Parkinson’s disease (PD)
specific cell loss in the substantia nigra region of the basal ganglia (primary source of dopaminergic neurons)
along with the motor symptoms that accompany the disease, dementia is evident in approximately 30% of PD patients, and others exhibit mild cognitive impairment that may develop into dementia during the course of the disease
parkinson’s disease: cognitive symptoms
difficulties with executive function
deficits in memory encoding and retrieval processes
bradyphrenia (general slowing of motor processes
emotional changes, including depression
parkinson mask - expressionless face
general slowing of motor and thought processes
parkinson’s disease and dopamine
deficient dopamine in the dopaminergic path from the midbrain to subcortical and cortical regions of the frontal lobe
dopamine in the prefrontal cortex facilitates executive function
deficient dopamine may not explain all cognitive symptoms seen in PD
not everyone with parkinson’s disease develops dementiaa, even though they all have insufficient dopamine
dopamine agonist drugs do not appear to improve memory deficits seen in some PD patients
cognitive decline in PD patients
some researchers argue that dementia occurs when the typical dopamine deficits of parkinson’s are combined with pathology typical of alzheimer’s disease, ie/ amyloid plaqyes and neurofibrillary tangles
others argue that the presense in the cortex of “Lewy bodies” - clumps of abnormal porteins inside cells - can account for cognitive decline
could be a combination of both
PD and dopamine treatments
Ldopa is a precursor to dopamine can cross the blood brain barrier
unfortunately associated with dyskinesia in about 35% of patients with hallucinations in other patients
it loses drug efficacy over time
levadopa (ldopa) can improve some aspects of executive function, but also impair other functions (inhibitory cointrol of behaviour is impaired resulting in impulsiveness)
PD and other treatments
over time, ldopa resistance builds so more invasive treatment options may be considered:
deep brain stimulation or ablation of the thalamus or the internal portion of the globus pallidus
subcortical dementia: Huntington’s disease
causes by a genetic mutation, abnormal protein folding destroys GABAergic (and cholinergic) neurons in the striatum (caudate nucleus and putamen) and to some degree in the globus pallidus
this destruction produces a movement disorder characterized by jerky , rapid and uncontrollable movements
neurological degeneration in HD
smaller caudate
enlarge ventricles because of lost tissue in basal ganglia
chorea
jerky movements
HD cognitive symptoms
specific difficulties in intiating behaviour, selecting a response, selecting a stimulus on the basis of particular attributes, and switching mental sets
difficulty planning and scheduling
reduced verbal fluency, perseverative tendencies and a loss of cognitive flexibility
deficits in memory recal
difficulty making the kind of self-guided search through memory that is required to recal info
HD changes in emotional functioning
half of the patients have major depressive episodes , which precedes motor symptoms
common: irritable, apathetic, impulsive, aggressive and emotionally labile
might exhibit psychotic symptoms (delusions)
often act in socially inappropriate ways and have difficulting recognizing emotions in others
HD diagnosis
possible to identify people that will develop this disorder
people who carry HD gene but are asymptomatic with regard to motor signs, exhibit poorer performance than noncarriers on tasks of memory and executive functioning
mixed variety dementias
characterized by a substantial degree of both cortical and subcortical damage, which makes the clinical profile of these disorders an mixture of the cortical and subcortical dementias
HD treatment
no cure
aim is to address motor and psychiatric symptoms
vascular dementia
also known as multi-infarct dementia
common form of mixed-variety dementia; second most common type of dementia overall
results from the cumlative effects of many small strokes that tend to create both cortical and subcortical lesions
affects multiple areas over time as the consequence of multiple small strokes accumulate
the brain and vascular dementia
various brain areas affected
some cases the vascular damage is cortical, more often in the frontal lobes than any other
other cases especially people in with arterial, lesions occur in small blood vessels supplying subcortical area
evidence for vascular dementia
long standing medical history of arterial hypertension
focal neurological signs that suggest a stroke
MRI scans revealing specific and multiple infarcts of the cortex in either the white or grey matter
vascular dementia vs AD
similar neuropsychological profile
vascular dementia occurs with a relatively abrupt onset, is accompanied by a stepwise rather than gradual course, and is not restricted to onset in the later years
the pattern of impairment in vascular dementia can fluctuate, being worse initially and then improving
multiple sclerosis (MS)
One of the most common neurological diseases of non-traumatic origin
- affects cognitive function of young and middle ages adults
Cause is unknown; evidence suggests environmental and genetic contributions
One in five MS patients has a family member with MS
MS affects women about twice as often as men
Characterized by multiple discrete areas of scarring (sclerosis), ranging in size, in which neurons have absent or damaged myelin
The destruction of myelin in MS is thought to result from an immunological disruption
- autoimmune disorder (body identifies a part of its own system for foreign matter)
- or death of ogliodendrocytes
- either way may interfere with neural transmission because of axonal degration
MS symptoms
MS symptoms depend on location of myelin damage in the nervous system
- commonly starts as blurred/lost vision, vision, muscle weakness/tingling, coordination difficulty
Symptoms get progressively worse and can come and go (appear/dissapear)
Cognitive deficits occur in 40–60 percent of patients
Variable, but difficulties may involve slowed information processing and difficulty in memory (affecting recall more than recognition), conceptual reasoning, and visuospatial cognition
Usually accompanied by changes in mood and personality
General sparing of language and knowledge systems
MS functional connectivity
MS affects myelination of axons, which impacts communication between brain regions
Especially the frontal lobes and connections with subcortical structures
Research has found both increased and decreased functional connectivity
Researchers speculate that the increase in connectivity between brain regions reflects a compensatory process of some sort in order to maintain functionality
MS treatment
No cure exists; treatments attempt to curtail symptoms and delay relapses
Main treatment: The drug “interferon beta-1b”
- interferons
Future treatment: Promoting axonal regeneration and myelin repair
- Stem cells may prove to be especially beneficial in repairing myelin
interferons
are proteins produced by the body that have antiviral characteristics and modulate the immune response.
classes of epilepsy
- generalized onset seizure
- focal onset seizure
epilepsy
diagnosis based on 2 or more seizure
A disease with recurrent but intermittent seizure activity
Epileptic seizures are episodes with extreme hyperpolarization of neurons that spreads over a large area in an atypical and abnormal manner.
generalized onset seizure
abnormal activation in large networks on both sides of the brain
focal onset seizure
abnormal activity starts on one side of the brain
- fairly localized, may then spread to other regions
tonic-clonic seizures
convulsive behavior due to changes in muscle activity, such as stiffness (tonic) and jerkiness (clonic)
absence seizures
brief periods of altered awareness or “blacking out”
Other seizures can involve changes in breathing, thinking, speech, emotions, or sensations
Seizure types identifiable by characteristic EEG abnormalities
symptomatic
when the cause of the seizure is known
idiopathic
seizure disorders with no known cause
seizure causes
Typical causes: head trauma, metabolic disorders, infection, toxins, and tumors.
Seizure episodes can be triggered by a variety of stimuli, with the likely trigger varying from person to person.
epilepsy: cognitive symptoms
Impaired cognitive and psychosocial functioning
- Disrupted sustained attention and executive function
Consciousness is disrupted during the seizure
Interictal (between-seizure) consequences occur as well:
- Connectivity between brain regions and networks is altered
- Cognitive disruption reflect dysfunction of the area where the seizure originates (focal onset seizures)
Epilepsy treatment options
Treatment option #1 – drug therapy:
- Anticonvulsant medication – 3 major classes of drugs:
- Barbiturates mimic neurotransmitter GABA
- Hydantoins block the influx of sodium into the neuron
- More recent anti-epileptic drugs attenuate the release of glutamate
Drug treatment effective for about 70–80% of patients
epilepsy treatment options
Treatment option #2 – surgery:
Drug-resistant epilepsy is much more difficult to treat
If a focal origin can be identified, surgery might be an option
Removing the tissue source of the seizure activity helps preclude healthy areas from becoming compromised.
Researchers continue the search for new treatments as medication is not always effective and surgery is invasive
