1 Neurocognitive Aging Katherine M. Krpan PSY 393 March 27 th, 2007.

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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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IMPLICIT MEMORY

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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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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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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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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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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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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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EXPLICIT MEMORY

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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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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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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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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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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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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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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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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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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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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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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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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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Visuospatial Memory Take Home Message

Older adults show visuospatial memory decline

BUT Visually distinctive contexts reduce

or eliminate this effect

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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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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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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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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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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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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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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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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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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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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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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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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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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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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

1 Neurocognitive Aging Katherine M. Krpan PSY 393 March 27 th, 2007.

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Transcript of 1 Neurocognitive Aging Katherine M. Krpan PSY 393 March 27 th, 2007.