Neurocognitive Aging

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Neurocognitive Aging

• Katherine M. Krpan
• PSY 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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Whats Hot and Whats 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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Whats Hot and Whats Not

• IMPLICIT MEMORY

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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats 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
  patientsthink back to the memory lecture!)

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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats Not

• EXPLICIT MEMORY

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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats 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 55
• BUT
• Recognition is spared

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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats Not

• Prospective 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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Whats Hot and Whats Not

• Prospective Memory
• Older adults perform more poorly than young on
  laboratory prospective memory tests
• Older adults OUTPERFORM younger adults (20s) on
  prospective memory tasks in the real world!!
• Superiority reflects more structured daily lives
  in older adults??

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Whats Hot and Whats 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 variablehave more momentary
  lapses of intention

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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats Not

• False 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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Whats Hot and Whats Not

• Take Home Message for
• False Memory
• Older adults are more susceptible to false
  memories
• A deficit in source memory? Cant remember where
  info came from?
• A deficit of reality monitoring?

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Whats Hot and Whats 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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Whats Hot and Whats 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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Whats Hot and Whats Not

• Take Home Message for
• Meta-Memory
• Its 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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Whats Hot and Whats 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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Whats Hot and Whats 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
• Are the last to mature (into our 20s)
• Show the greatest reduction in blood flow (later
  in life)
• 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
  lectureand 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 Alzheimers 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
• Provides control over access to WM (i.e.,
  restrict access to task relevant info)
• Supports deletion of irrelevant information from
  WM
• 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 braincan you think of some examples?
• HAROLD
• Hemispheric 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 Alzheimers
  Disease (5.5 billion /year)
• By 2031, an estimated 3-4 million Canadians will
  have Alzheimers 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
• Memory and other cognitive deficits
• 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

• Cortical
• Alzheimers disease, Picks disease and
  Creutzfeldt-Jacob disease
• Subcortical
• Parkinsons disease, Huntingtons chorea
• Mixed
• Vascular dementia a.k.a. multi-infarct dementia

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Alzheimers 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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Alzheimers Disease History

• 1960s ? 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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Alzheimers 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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Alzheimers 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 DementiaAlzheimers 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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Alzheimers Disease DSM-IV

• The DSM-IV lists four separate diagnostic
  criteria for Alzheimers disease dependent on
• the time of onset (earl versus late)
• 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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Alzheimers 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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Cortical DementiaAlzheimers Disease

• Memory
• Global anterograde amnesia
• Retrograde amnesia (temporally graded)
• Deficits in short-term memory
• Procedural memory is not spared
• How are Alzheimers disease patients similar and
  different from medial-temporal-lobe amnesia
  patients?

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Cortical DementiaAlzheimers Disease

• 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

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Cortical Dementia Alzheimers 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

• Picks 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 DementiasFrontotemporal Dementia

• Physiological characteristics
• Atrophy of frontal and temporal lobes
• Neurons are pale and swollen? ballooned
• Picks 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 DementiasCreutzfeldt-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 DementiasCreutzfeldt-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
  Alzheimers or frontotemporal dementia
• Individuals live about a year after dementia
  diagnosis

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Subcortical DementiasHuntingtons 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 Parkinsons 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 Binswangers 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