Transcript 19Dementias

Dementias
PSYC4080 6.0D
Dementias
1
Neurodegenerative Disorders
 A varied assortment of central nervous system
disorders characterized by gradual and
progressive loss of neural tissue.
 Examples: Alzheimer’s, Parkinson’s, Multiple
Sclerosis, dementia with Lewy bodies, multiple
system atrophy
 Disorders can affect anyone at any age, not just
a disease in the elderly
• Can even strike during infancy
PSYC4080 6.0D
Dementias
2
Incidence, Prevalence
 Usually a disease of aging populations
 Highest prevalence over age 85.
 Can occur in children and adolescents, and shown
as a deterioration in function.
 Estimates (Census, 2001)
• 3% in adults 20-70
• 10% 70-85
• 20% over 85 years
 10% genetic concordance (Sherrington, 1995)
PSYC4080 6.0D
Dementias
3
Prevalence
 Parkinson’s: 8-15 in 100,000 (0.000080.00015%)
 Alzheimer’s: 435,000 persons over 65 years
(0.01%)
PSYC4080 6.0D
Dementias
4
Neuropathology
Protein Degeneration (Cummings, 2003)
 Abnormalities in the metabolism of three
proteins account for more than 90% of all
neurodegenerative dementias
 misfolded proteins that cannot be properly
degraded within affected cells
 Amyloid-beta, alpha-synuclein, and tau
1. Binding along the membrane
2. Accumulation of these proteins
3. Abnormal cellular maintenance
PSYC4080 6.0D
Dementias
5
Protein Degeneration
 All of these proteins are involved with
maintaining the structure and integrity of
neurons
1. Amyloid-beta: regulation of synaptic strength
2. Alpha-synuclein: integrity of vesicles containing
neurotransmitter
•
DA neurons may be selectively vulnerable to toxic
effects
3. Tau: microtubule assembly and stabilization
 Dysregulation contributes to cell death
PSYC4080 6.0D
Dementias
6
Protein Degeneration
 Accumulation of these proteins often begins in
brainstem (substantia nigra, locus coeruleus)
 Work their way to limbic and (frontal, temporal)
cortical areas
 Producing characteristic cell death and
subsequent affects and memory and executive
functioning.
PSYC4080 6.0D
Dementias
7
Protein Degeneration
www.alzheimer.ca
PSYC4080 6.0D
Dementias
8
Neuropathology
A. Frontal lobe dysfunction/dementias
 Degeneration of neurons in the frontal lobe,
basal ganglia
 Interruption of frontal-subcortical pathways
 Deficits similar to those of frontal lobe lesion
patients.
PSYC4080 6.0D
Dementias
9
Neuropathology
Symptoms of dementia (DSM-IV)
1. Aphasia (language disturbance).
2. Apraxia (impaired ability to carry out motor activities despite intact
motor function).
3. Agnosia (failure to recognize or identify objects despite intact
sensory function).
PSYC4080 6.0D
Dementias
10
Neuropathology
Symptoms of dementia (DSM-IV)
4. Executive functioning




Planning, organizing, sequencing, abstracting
Working memory
Encoding new memories
Episodic memories
5. Delusions or hallucinations
PSYC4080 6.0D
Dementias
11
Neuropathology
B. Mood disturbances
 Major depressive disorder common
 Correlated to executive functioning deficits, implying
further frontal lobe effects

Evidence that the severity of executive and mood
disorders directly related to the volume of cortex
destroyed
PSYC4080 6.0D
Dementias
12
Parkinson’s Disease
 Assessment by a neuropsychologist is always
undertaken in these cases
1. assessment of recall and recognition memory
2. assessment of long term memories
3. short-term memory
4. cued versus uncued recall
5. word naming for language function
6. testing for apraxia
7. visuospatial functioning
8. executive functioning
PSYC4080 6.0D
Dementias
13
Parkinson’s Disease
Cognitive Deficits
1. Disorders of executive function: generating,
maintaining, shifting, and blending of sets
characterize executive-function disorders,
(mental inflexibility)
 decreased generation and maintenance of sets
and slowness in shifting sets in new situations.
 no impairment when performing overlearned
tasks
 benefit from external cues and structure.
 difficulty with novel stimuli.
PSYC4080 6.0D
Dementias
14
Parkinson’s Disease
Cognitive Deficits
2. Visuospatial difficulties: line orientation, block
design, and picture arrangement, non–familiarface discrimination (IQ subtests).
 present even when motor impairment is absent.
PSYC4080 6.0D
Dementias
15
Parkinson’s Disease
Cognitive Deficits
3. Memory deficits: retrieval deficits in immediateand long-term memory impairment,
abnormalities in procedural memory, (includes
anterograde and retrograde amnesias)
 Providing patients with retrieval cues can
improve memory performance
 Disproportionately impaired in their ability to
temporally order or sequence new information
PSYC4080 6.0D
Dementias
16
Parkinson’s Disease
Cognitive Deficits
4. Language abnormalities: naming and fluency,
comprehending syntactically embedded
questions. Their sentences tend to be
grammatically simple. Deficits in speech
production.
5. Full blown dementia: Disturbance in executive
function is the most common; apraxia and
agnosia rarely occur.
PSYC4080 6.0D
Dementias
17
Parkinson’s Disease
 A neuropsychiatrist need only be involved when:
1. risk-taking behaviours increase as disease
progresses.
2. violent behaviour
3. disinhibited behaviours
4. delusions of persecution
5. hallucinations
6. exaggerated responses to stress
PSYC4080 6.0D
Dementias
18
Alzheimer’s Dementia
 Confirmed only though postmortem studies
 Poor relation between neurobiological changes
and clinical symptoms
 Diagnosis is based on the general symptoms of
dementia, not on imaging data.
 Scale of Behavioural Change used to determine
stages (Reisburg, 1983)
• From Very Mild to Very Severe
PSYC4080 6.0D
Dementias
19
Alzheimer’s Dementia
Degree of Cognitive
Decline
None
Very mild
PSYC4080 6.0D
Symptoms
 No subjective complaints of memory
deficits.
 No memory deficits noted on testing
 Complaints of memory deficit: 1)
forgetting where one has placed familiar
objects, or 2) forgetting names that once
knew well
 No objective evidence of memory
problem on interview
 No objective deficits in employment or
social situations
 Appropriate concern with respect to
symptomatology
Dementias
20
Alzheimer’s Dementia
Degree of Cognitive
Decline
Very severe
PSYC4080 6.0D
Symptoms






All verbal abilities are lost.
Often no speech at all, only grunting.
Incontinent of urine
Require assitance in toileting and feeding.
Losses basic motor skills (ability to walk)
Brain and body are disconnected.
Dementias
21
Alzheimer’s Neuropathology
 Still mainly confirmed through postmortem
findings (Selkoe, 1992; Brun, 1983)
• neuropathology non-specific to Alzheimer’s
 Neuritic plaques - found in cerebral cortex, and
correlated with degree of cognitive dysfunction
(amyloid-beta peptide)
 Neurofibrillary tangles in the neurons,
especially hippocampus (helical fragments)
 Loss of cortical volume typically in temporal
areas, limbic cortex, posterior parietal areas.
PSYC4080 6.0D
Dementias
22
Alzheimer’s Neurobiology
 Loss of cells in entorhinal cortex (main input into
the hippocampus)
 Loss of dendrites
 General decrease in neurotransmitters: NA, DA,
5HT, glutamate
 Similar findings have been suggested for other
types of dementias
PSYC4080 6.0D
Dementias
23
Lewy Bodies Dementia
 Neurodegenerative disorder associated with abnormal
structures (Lewy bodies) found in certain areas of the
brain.
 Associated with Parkinson's and Alzheimer's diseases
 Researchers not sure whether it’s a distinct clinical entity
or a variant of Alzheimer's or Parkinson's disease.
 Quite common: 10-25% of all dementia cases
PSYC4080 6.0D
Dementias
24
Lewy Bodies Dementia



Appear as toxic dark
red or brown spots in
the cytoplasm of the
neuron, typically in
substantia nigra.
DA neurons may be
selectively vulnerable
to toxic effects
Contain the protein
alpha-synuclein, which
normally maintains
integrity of vesicles
containing
neurotransmitter
PSYC4080 6.0D
Dementias
25
Other Information
 Generally speaking, the severity of
neuropsychological dysfunction (dementia and mood)
is correlated to the extent of brain atrophy
• More related to brain volume than to effects on a
particular brain area.
 The cause of neurodegenerative disorders is
unknown
 Still some debate as to whether Alzheimer’s is a
disease at all
PSYC4080 6.0D
Dementias
26
Other Information
 Typically dementias are not reversible but follow
a progressive or static course
 Reversible only if caused by a treatable general
medical condition (e.g. hypoglycemia)
 Ultimately, dementias lead to death (related to
mobility)
1. increased incidence of accidents
2. increased susceptibility to infections
PSYC4080 6.0D
Dementias
27
The problem of treatment
 Antiparkinsonian (DA) medication may actually worsen
such symptoms as hallucinations and delusions.
 Neuroleptic (antipsychotic) drugs prescribed for
psychiatric symptoms may markedly worsen the
movement symptoms (DA antagonist, among other
things).
 Which symptoms to treat, or can both movement and
psychiatric conditions be addressed?
PSYC4080 6.0D
Dementias
28