Post on 26-Dec-2015
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Neurocognitive Aging
Katherine M. KrpanPSY 393
March 27th, 2007
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Outline The Healthy Aging Brain
What declines and what doesn't Theories on neurocognitive aging Laterality in the aging brain
Dedifferentiation and Compensation
Disorders of the Aging Brain Dementias
Cortical Subcortical Mixed
Aging Gracefully: Strategies to slow the process of aging and risk factors for dementia
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What’s Hot and What’s Not
As we age, certain aspects of cognition decline, while others are maintained, or even improved!
One of the most common complaints of older adults is a decline in memory function… so that will be our focus today
We will now examine a variety of implicit and explicit memory tasks to illustrate the neurocognitive profile (of memory) in healthy older adults
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What’s Hot and What’s Not
IMPLICIT MEMORY
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What’s Hot and What’s Not
Motor Learning Pursuit Rotor Task
Must keep the tip of a stylus in continuous contact with a moving target
Motor skill = time spent on target Motor Learning = increased time-on-
target across repeated trials Older adults show slower learning
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What’s Hot and What’s Not
Motor Learning
Confound of slowed motor speed
Age differences have not been found on tasks where the task is subject paced (e.g., learning a sequence of motor responses)
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What’s Hot and What’s Not
Motor Learning Take Home Message
Older adults are not as adept as younger adults at performing motor tasks
BUT
They are equally skilled in learning, retaining, and transferring motor skills IF they are allowed to pace themselves during learning
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What’s Hot and What’s Not
Priming Word stem completion older adults
show priming similar to young
BUT, when asked to recall the word list, older adults were impaired (just like the amnesic patients…think back to the memory lecture!)
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What’s Hot and What’s Not
Priming Presented with inverted words (450 ms) Asked to say words out-loud Repeated words on some trials (prime)
Older adults showed priming like young Older adults were less skilled at learning the
task Task was slowed to 900 ms
Age related deficits were abolished
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What’s Hot and What’s Not
Take Home Message on Priming
Older adults show priming (perceptual, conceptual and associative)
Are less skilled at learning tasks BUT This effect can be abolished if
presentation time is slowed
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What’s Hot and What’s Not
EXPLICIT MEMORY
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What’s Hot and What’s Not
Semantic Memory
Older adults show minimal declines in vocabulary, knowledge of historical facts, and knowledge of concepts
Older adults can retrieve already learned semantic information, and can learn new semantic information
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What’s Hot and What’s Not
Semantic Memory There is an exception to preserved semantic
memory with age Older adults show difficulty retrieving
familiar words Tip of the Tongue States inability to recall
a sought-after word, combined with a strong feeling that the word is, in fact, known
Suggests selective failure in accessing phonological info (cues fix the problem)
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What’s Hot and What’s Not
Take Home Message for Semantic Memory
Older adults show preserved semantic memory
BUT Have difficulty with word finding,
and are more susceptible to the ‘Tip of the Tongue’ state
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What’s Hot and What’s Not
Personal Episodic Memory Asked participants to generate
memories in response to cue words Distribution of memories from most
recent (10-20 yrs) did not differ in relation to age
Recent memories were most available Retention decreased with increasing time
since the event occurred
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What’s Hot and What’s Not
Personal Episodic Memory Reminiscence Bump a
disproportionate number of memories from early adulthood
WHY??? Peak in cognitive performance? Greater number of significant life events? Bump overshadowed (in middle-age) by
recent events in middle adulthood?
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What’s Hot and What’s Not
Take Home Message for Personal Episodic Memory
Older adults show a profile similar to young adults
BUT
Older adults show a ‘reminiscence bump’
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What’s Hot and What’s Not
Episodic Memory (text and words)
Marked declines in recall for text and words in participants 55+ (16yr longitudinal study)
No deficits in recognition
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What’s Hot and What’s Not
Episodic Memory (text and words)
It is well established that older adults show deficits in recall, but NOT recognition
WHY??? More attentional demand for recall (drain
resources)? More environmental support in recognition?
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What’s Hot and What’s Not
Take Home Message for Episodic Memory (text and words)
Recall for words declines fastest Recall for text and words is
markedly lower in those +55BUT
Recognition is spared
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What’s Hot and What’s Not
Visuospatial Memory Viewed 20 common objects in one of 4
rooms
Later asked to place the object in the room it was observed (3, 15, and 30 min delays)
Older adults were less accurate on the 30min delay condition (not on others)
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What’s Hot and What’s Not
Visuospatial Memory Subjects followed the experimenter
along a novel route
Older adults were impaired at retracing the route and ordering landmarks
Unimpaired at recognizing landmarks
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What’s Hot and What’s Not
Visuospatial Memory
Age-related deficits CAN be reduced, or even eliminated, but HOW??
Visually distinctive context greatly reduces visuospatial memory deficits
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What’s Hot and What’s Not
Visuospatial Memory Take Home Message
Older adults show visuospatial memory decline
BUT Visually distinctive contexts reduce
or eliminate this effect
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What’s Hot and What’s Not
Working Memory Reading Span Paradigm
Read a list of two, three or four sentences and then recall the last 2 words of the sentences
Age related declines in span Can reduce deficit by giving breaks
between trials
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What’s Hot and What’s Not
Working Memory
Younger adults perform like older adults when to be remember stimuli is presented in a noisy environment
Do older adults have a greater vulnerability to interference from irrelevant or distracting info?
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What’s Hot and What’s Not
Take Home Message For WM
Older adults show a decline in working memory (storage and manipulation)
This may be due to increased susceptibility to environmental distractors
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What’s Hot and What’s NotProspective Memory (form the intention to carry out an act in
the future)
100 participants, 10 age cohorts (35-80)
Task to remind experimenter that a form must be signed at the end of testing
61% of subjects aged 35-45yrs remembered
25% of subjects aged 70-80yrs remembered
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What’s Hot and What’s NotProspective Memory
Older adults perform more poorly than young on laboratory prospective memory tests
Older adults OUTPERFORM younger adults (20’s) on prospective memory tasks in the real world!!
Superiority reflects more structured daily lives in older adults??
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What’s Hot and What’s Not
Take Home Message for Prospective Memory
Older adults show declines in prospective memory in the laboratory
BUT
Outperform young adults in real-world memory tasks
They are just more variable…have more momentary lapses of intention
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What’s Hot and What’s Not
Source Memory (capacity to remember the origin of our knowledge)
Participants listen to a series of words read aloud by either male or female voices
Older adults have more difficulty recalling the sex of the voice (even when memory performance for the words is controlled)
Perceptual deficits??
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What’s Hot and What’s Not
Source Memory Source memory deficits are evident
even when sources are not primarily perceptual in origin Older adults do have intact perceptual
functions, but require more effort?
Can reduce or eliminate source memory deficits Highly perceptually distinct stimuli Consider facts not emotions Personal rather than general relevance
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What’s Hot and What’s Not
Take Home Message for Source Memory
Source memory deficits in older adults are reliable
BUT Numerous manipulations can attenuate
or eliminate deficits Suggests source memory in not a separate
and impaired system These results may reflect different ways in
which older adults use strategies
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What’s Hot and What’s NotFalse Memory
Older adults are more susceptible to misleading post-event suggestion
For young adults, multiple study-list exposures results in increased true memory
For older adults, multiple study-list exposures results in increased true and false memory
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What’s Hot and What’s Not
Take Home Message forFalse Memory
Older adults are more susceptible to false memories A deficit in source memory? Can’t
remember where info came from? A deficit of reality monitoring?
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What’s Hot and What’s Not
Meta-Memory (memory beliefs)
Older adults report deteriorating faculties regardless of whether they show an increase in self-reported memory decline
Suggests memory complaints are based on stereotype rather than evaluation of the self
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What’s Hot and What’s Not
Meta-Memory Programs aimed to increase memory self-
efficacy improve memory performance
De-emphasizing the ‘memory’ component and emphasizing ‘knowledge’ component of memory tasks eliminates age differences on some memory tasks
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What’s Hot and What’s Not
Take Home Message for Meta-Memory
It’s a matter of mind over matter!!
Memory performance can be improved by increasing self-efficacy beliefs and placing emphasis on ‘knowledge’
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What’s Hot and What’s Not: Summary Page
INTACT Motor learning Priming Semantic memory
(not word finding) Episodic Memory for
well-learned life events
Passive short-term storage of information
Recognition memory Prospective memory
in the real-world
DECLINES WM– especially with
interference Encoding new
information in deep elaborative way (less strategic)
Retrieval (particularly when effortful)
Uncued recall, prospective memory, recovery of specific details, source memory
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What’s Hot and What’s Not We see that different memory systems are
affected differently by age (more evidence for multiple memory systems?!)
Why are some functions impaired, while others are intact?
It seems that functions that are contingent on frontal integrity are most impaired
We will now briefly touch upon more general deficits experienced by older adults
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The Frontal Lobes As we age, the frontal lobes:
1. Are the last to mature (into our 20’s)2. Show the greatest reduction in blood flow
(later in life) 3. Show the greatest amount of tissue loss
(later in life)
Not surprisingly, older adults often show deficits on neuropsychological tests that are considered ‘frontal’
(think back to the executive functions lecture…and about strategies used to remember things)
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The Frontal Lobes Older adults show deficits on task
like: Self-ordered pointing Wisconsin Card Sorting Test Verbal Fluency (FAS) Stroop Task Working Memory Tasks Prospective-memory tasks Source Memory Tasks
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Parietal Lobes
The parietal lobes are also susceptible to the effects of aging, though not to the extent of the frontal lobes
Right hemisphere constructional and visuomotor tasks
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Temporal Lobes As discussed, older adults show deficits on
declarative memory tasks
Problems on recall (not so much recognition)
Problems strategically searching through memory to retrieve memory (frontal too??)
Related to loss of hippocampal tissue (extreme cases of Alzheimer’s Disease)
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Theoretical Frameworks: Memory Decline in Older Adults
Decline in Processing Speed Decreased processing speed
underlies many of the cognitive deficits noted in older adults
Memory is not impaired, per se, but is due to slow mental processing or difficulties with timing of complex mental functions
Evidence: experimenter paced motor learning tasks
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Theoretical Frameworks: Memory Decline in Older Adults
Depletion of Attentional Resources Reduced attentional resources to carry
out mental functions Observe differences between
performance of simple (stable) and complex (decline) tasks
Evidence: tasks requiring more effort (e.g., free recall, prospective and source memory)
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Theoretical Frameworks: Memory Decline in Older Adults
Age-Related Inhibitory Deficits Older adults are less efficient at inhibiting
partially activated representations Inhibitory functions play three important
roles in memory:1. Provides control over access to WM (i.e., restrict
access to task relevant info)2. Supports deletion of irrelevant information from
WM3. Provides restraint of pre-potent responding
Evidence: age-differences in WM tasks interference???
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Theoretical Frameworks: Memory Decline in Older Adults
Decreased Cognitive Control Older adults suffer from an impairment in
executive control of cognitive processing Relies on distinction between automatic
(unconscious) and controlled (effortful) processes
Automatic processes are immune to the effects of aging while controlled processes demonstrate decline (combo of reduced resources & inhibitory deficit theories)
Evidence: can account for WM, episodic, source prospective, false….maybe too much? Need to understand more about executive functions
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Laterality in Older Adults Think back to the hemispheric specialization
lecture……
Recall that certain functions are lateralized within the brain…can you think of some examples?
HAROLDHemispheric Asymmetry Reduction in Old Adults
Episodic memory retrieval, episodic encoding/semantic retrieval, working memory, perception, and inhibitory control
Evidence using both functional neuroimaging and electrophysiological methodologies
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Dedifferentiation Hypothesis Reduced hemispheric asymmetry in old
adults may reflect and age-related difficulty in recruiting specialized neural mechanisms
asymmetries are just another example of the deleterious effects of aging on the brain
Evidence: correlations among different cognitive measures increase with age
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Compensation Hypothesis Increased bilaterality in old adults could help
counteract age-related neurocognitive deficits
asymmetries are an example of the brain reorganizing to compensate for the effects of aging
Evidence: as a result of contralateral recruitment, cognitive functions that are strongly lateralized in the healthy brain may become more bilateral following brain damage
Evidence: Following L hem stroke, better language recovery is observed in aphasic patients with bilateral activation (fMRI)
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Evidence for the compensation hypothesis
High performing older adults show bilateral activation
Low performing older adults show lateralized activation
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DEMENTIAS
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Dementias Recent medical and technological advances have
increased the average life expectancy of Canadians
Consequence aging population that is plagued with neurodegenerative disease = poor quality of life and lost productivity
Estimated 280,000 Canadians have Alzheimer’s Disease (5.5 billion $/year)
By 2031, an estimated 3-4 million Canadians will have Alzheimer’s Disease
Economic impact is large long disease duration, high cost of healthcare, lack of effective treatments
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Dementias Dementia 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: Three Broad Categories
1. Cortical Alzheimer’s disease, Pick’s disease and
Creutzfeldt-Jacob disease
2. Subcortical Parkinson’s disease, Huntington’s chorea
3. Mixed Vascular dementia a.k.a. multi-infarct
dementia
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Alzheimer’s Disease: History First recognized 100 years ago by Alois Alzheimer
1906 presented data on patient ‘Auguste D’, a 51-year-old woman with “delerium and frenzied jealousy of her husband”
Alzheimer claimed that her dementia was caused by gross neuroanatomical lesions identified in her brain post-mortem
Observed “milliary bodies” and nerve cells that were choked by “dense bundles of fibrils”
“Clinicopathological era” scientists began to investigate the correlates of clinical symptoms and pathology (something that was not accepted until that time)
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Alzheimer’s Disease: History 1960’s autopsies of patients with ‘senility’ confirmed
what Alzheimer had claimed
In most cases there were clearly visible deposits of beta-amyloid plaques (“milliary bodies”) and intracellular deposits of neurofibrillary tangles (“dense bundles of fibrils”)
Today, AD can only be definitively diagnosed post-mortem
Characterized by the accumulation of neuritic plaques composed of amyloid-beta peptide fibrils, and neurofibrillary tangles of hyperphosphorylated tau within the limbic and neocortical areas of the brain
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Alzheimer’s Disease: Pathology Healthy individuals
produce beta-amyloids (protein fragments) that are quickly broken down and removed by the body
In AD, these proteins accumulate between neurons and form hard, insoluble plaques
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Alzheimer’s Disease: Pathology
Neurofibrillary tangles composed of twisted fibres inside the neuron consisting of the protein tau, which form microtubles, which are responsible for the transport of nutrients in and out of the cell
In AD the tau protein is abnormal and causes neurofibrillary tangles which in turn cause the microtubule structure to collapse
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Cortical Dementia:Alzheimer’s Disease AD is also characterized by a severe loss
of cholinergic innervations in the cerebral cortex, an overall decrease in brain volume, and enlargement of ventricles
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Alzheimer’s Disease: DSM-IV The DSM-IV lists four separate diagnostic
criteria for Alzheimer’s disease dependent on:1. the time of onset (earl versus late) 2. the presence of delirium, delusions, or depressed
mood
In simple terms late onset uncomplicated AD = gradual development of multiple cognitive and memory deficits including aphasia, apraxia, agnosia, and executive dysfunction
Disturbance of everyday function, must progress steadily, and must not be attributable to some other Axis I disorder, caused by systemic conditions (e.g., vitamin deficiency), or substance abuse
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Alzheimer’s Disease: Progression Early stages memory deficits caused by
degeneration of neurons in the hippocampus During this initial stage of the disease, there are no motor,
sensory and co-ordination deficits
As progresses extends to the cerebral cortex affecting the frontal lobes, deficits in judgement, decision making, inhibition, personality, mood, language and communication are observed
Final stages the ability to recognize faces and communicate is completely abolished, followed by loss of bladder and bowel control, and finally death
The average time from diagnosis to death is approximately 10 years
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Memory Global anterograde amnesia Retrograde 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 (FAS)
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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Cortical Dementia: Alzheimer’s Disease
Therapeutic Interventions Drugs targeting the cholinergic system
Drugs that block acetylcholine (e.g., scopolamine) cause memory impairments in healthy individuals
Increase the amount acetylcholine facilitates memory Drugs that block acetylcholinestarase (the enzyme that
breaks down acetycholine) have been somewhat successful (e.g., tacrine)
Many side effects
These drugs just slow the progression of the disease
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Cortical Dementias: Frontotemporal Dementia
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 lobes
Neurons are pale and swollen ‘ballooned’
Pick’s bodies in the cytoplasm (rather than neurofibrillary tangles)
Presents primarily in the realm of social-emotional functioning (think of the OFC patients)
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Cortical Dementias:Creutzfeldt-Jacob Disease
1 in a million = RARE!
Caused by prions (proteinaceus infectious particles)
Prions are normal proteins found in the brain, but they can undergo a change of shape and become insoluble
Thus, cannot be broken down, they accumulate and lead to cell death
Incubation period is quite long
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Cortical Dementias:Creutzfeldt-Jacob Disease Prions are highly transmittable (e.g., corneal
transplants, contact with infected brain tissue)
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 (caudate, putamen, globus
pallidus) are destroyed leading to excess movement Jerky, rapid, uncontrolled movement
Almost always leads to dementia
Deficits in: Executive function
Switching mental sets, inhibition (WCST), planning Spatial processing Memory
Much better at recognition than recall (unlike AD) No temporal gradient equal memory impairment
across time (unlike AD)
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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 (emotion,
desire or physiological need) and attention Slowing of motor and thought bradyphrenia Executive functions (WCST, Tower of London) Spatial memory
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Mixed Varieties Dementias: Vascular Dementias AKA: Multi-Infarct Dementia
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) abrupt onset vs insidious onset in AD
There can be fluctuations in symptoms
Display predominantly problems with executive function ,verbal fluency and attention (FRONTAL LOBES)
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Risk Factors and Strategies for Aging Gracefully
Protective Factors
Non-steroidal anti-inflammatory drugs ↓
Higher education ↓
Mentally challenging work and activity ↓
Estrogen replacement therapy (women) ↓↑???
Risk Factors
APOE-4 allele =
↓ cholinergic activity ↑ density of senile plaques
Smoking ↑
Cardiovascular disease ↑
Diabetes ↑
Head injury ↑
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What you should know… Describe the deficits and spared functions
observed in healthy older adults, and provide evidence to support your statement (implicit, explicit)
Describe the theories of cognitive decline and provide one piece of evidence for each theory
Describe the dedifferentiation and compensation hypothesis of delateralization and supporting evidence
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What you should know… Describe the cortical, subcortial and
mixed dementias Know cognitive profile of each, be able to
compare and contrast dementias
Be aware of the risk factors associated with dementia, and strategies for improving/maintaining function later in life