PSYC4080 6.0D Dementias 1 Dementias. Dementias 2 Neurodegenerative Disorders A varied assortment of central nervous system disorders characterized by

PSYC4080 6.0DPSYC4080 6.0D DementiasDementias 11

DementiasDementias


Neurodegenerative DisordersNeurodegenerative Disorders

A varied assortment of central nervous A varied assortment of central nervous system disorders characterized by gradual system disorders characterized by gradual and progressive loss of neural tissue. and progressive loss of neural tissue.

Examples: Alzheimer’s, Parkinson’s, Examples: Alzheimer’s, Parkinson’s, Multiple Sclerosis, dementia with Lewy Multiple Sclerosis, dementia with Lewy bodies, multiple system atrophy bodies, multiple system atrophy

Disorders can affect anyone at any age, Disorders can affect anyone at any age, not just a disease in the elderlynot just a disease in the elderly• Can even strike during infancyCan even strike during infancy


Incidence, PrevalenceIncidence, Prevalence

Usually a disease of aging populationsUsually a disease of aging populations Highest prevalence over age 85.Highest prevalence over age 85. Can occur in children and adolescents, and Can occur in children and adolescents, and shown as a deterioration in function.shown as a deterioration in function.

Estimates (Census, 2001)Estimates (Census, 2001)• 3% in adults 20-703% in adults 20-70• 10% 70-8510% 70-85• 20% over 85 years20% over 85 years

10% genetic concordance (Sherrington, 10% genetic concordance (Sherrington, 1995)1995)


PrevalencePrevalence

Parkinson’s: 8-15 in 100,000 (0.00008-Parkinson’s: 8-15 in 100,000 (0.00008-0.00015%)0.00015%)

Alzheimer’s: 435,000 persons over 65 years Alzheimer’s: 435,000 persons over 65 years (0.01%)(0.01%)


NeuropathologyNeuropathology

Protein Degeneration (Cummings, 2003)Protein Degeneration (Cummings, 2003) Abnormalities in the metabolism of three Abnormalities in the metabolism of three

proteins account for more than 90% of all proteins account for more than 90% of all neurodegenerative dementiasneurodegenerative dementias

misfolded proteins that cannot be misfolded proteins that cannot be properly degraded within affected cells properly degraded within affected cells

Amyloid-betaAmyloid-beta, , alpha-synucleinalpha-synuclein, and , and tautau1.1. Binding along the membraneBinding along the membrane2.2. Accumulation of these proteinsAccumulation of these proteins3.3. Abnormal cellular maintenanceAbnormal cellular maintenance


Protein DegenerationProtein Degeneration

All of these proteins are involved with All of these proteins are involved with maintaining the structure and integrity of maintaining the structure and integrity of neuronsneurons

1.1. Amyloid-beta: regulation of synaptic Amyloid-beta: regulation of synaptic strengthstrength

2.2. Alpha-synuclein: integrity of vesicles Alpha-synuclein: integrity of vesicles containing neurotransmittercontaining neurotransmitter• DA neurons may be selectively vulnerable to DA neurons may be selectively vulnerable to

toxic effects toxic effects

3.3. Tau: microtubule assembly and Tau: microtubule assembly and stabilizationstabilization

Dysregulation contributes to cell deathDysregulation contributes to cell death



Accumulation of these proteins often Accumulation of these proteins often begins in brainstem (substantia nigra, begins in brainstem (substantia nigra, locus coeruleus)locus coeruleus)

Work their way to limbic and (frontal, Work their way to limbic and (frontal, temporal) cortical areastemporal) cortical areas

Producing characteristic cell death and Producing characteristic cell death and subsequent affects and memory and subsequent affects and memory and executive functioning.executive functioning.



www.alzheimer.ca



A. A. Frontal lobe dysfunction/dementias Frontal lobe dysfunction/dementias Degeneration of neurons in the frontal Degeneration of neurons in the frontal

lobe, basal ganglialobe, basal ganglia Interruption of frontal-subcortical Interruption of frontal-subcortical

pathwayspathways Deficits similar to those of frontal lobe Deficits similar to those of frontal lobe

lesion patients.lesion patients.



Symptoms of dementia (DSM-IV)Symptoms of dementia (DSM-IV)1.1. Aphasia Aphasia (language disturbance).(language disturbance).

2.2. Apraxia Apraxia (impaired ability to carry out motor activities despite intact (impaired ability to carry out motor activities despite intact motor function).motor function).

3.3. Agnosia Agnosia (failure to recognize or identify objects despite intact (failure to recognize or identify objects despite intact sensory function).sensory function).



Symptoms of dementia (DSM-IV)Symptoms of dementia (DSM-IV)

4.4. Executive functioning Executive functioning Planning, organizing, sequencing, abstractingPlanning, organizing, sequencing, abstracting Working memoryWorking memory Encoding new memoriesEncoding new memories Episodic memoriesEpisodic memories

5.5. Delusions or hallucinationsDelusions or hallucinations



B.B. Mood disturbancesMood disturbances Major depressive disorder common Major depressive disorder common Correlated to executive functioning deficits, implying Correlated to executive functioning deficits, implying

further frontal lobe effectsfurther frontal lobe effects

Evidence that the severity of executive and mood Evidence that the severity of executive and mood disorders directly related to the volume of cortex disorders directly related to the volume of cortex destroyeddestroyed


Parkinson’s DiseaseParkinson’s Disease

Assessment by a neuropsychologist is Assessment by a neuropsychologist is always undertaken in these casesalways undertaken in these cases

1.1. assessment of recall and recognition assessment of recall and recognition memorymemory

2.2. assessment of long term memoriesassessment of long term memories

3.3. short-term memoryshort-term memory

4.4. cued versus uncued recallcued versus uncued recall

5.5. word naming for language functionword naming for language function

6.6. testing for apraxiatesting for apraxia

7.7. visuospatial functioningvisuospatial functioning

8.8. executive functioningexecutive functioning



Cognitive DeficitsCognitive Deficits1.1.Disorders of executive function: Disorders of executive function:

generating, maintaining, shifting, and generating, maintaining, shifting, and blending of sets characterize executive-blending of sets characterize executive-function disorders, (mental inflexibility)function disorders, (mental inflexibility)

decreased generation and maintenance of decreased generation and maintenance of sets and slowness in shifting sets in new sets and slowness in shifting sets in new situations. situations.

no impairment when performing overlearned no impairment when performing overlearned tasks tasks

benefit from external cues and structure. benefit from external cues and structure. difficulty with novel stimuli.difficulty with novel stimuli.



Cognitive DeficitsCognitive Deficits

2. Visuospatial difficulties: line 2. Visuospatial difficulties: line orientation, block design, and picture orientation, block design, and picture arrangement, non–familiar-face arrangement, non–familiar-face discrimination (IQ subtests). discrimination (IQ subtests).

present even when motor impairment is present even when motor impairment is absent.absent.




3. Memory deficits: retrieval deficits in 3. Memory deficits: retrieval deficits in immediate- and long-term memory immediate- and long-term memory impairment, abnormalities in procedural impairment, abnormalities in procedural memory, (includes anterograde and memory, (includes anterograde and retrograde amnesias)retrograde amnesias)

Providing patients with retrieval cues can Providing patients with retrieval cues can improve memory performanceimprove memory performance

Disproportionately impaired in their Disproportionately impaired in their ability to temporally order or sequence ability to temporally order or sequence new informationnew information




4.4. Language abnormalities: naming and Language abnormalities: naming and fluency, comprehending syntactically fluency, comprehending syntactically embedded questions. Their sentences tend embedded questions. Their sentences tend to be grammatically simple. Deficits in to be grammatically simple. Deficits in speech production.speech production.

5. 5. Full blown dementia: Disturbance in Full blown dementia: Disturbance in executive function is the most common; executive function is the most common; apraxia and agnosia rarely occur. apraxia and agnosia rarely occur.



A neuropsychiatrist need only be involved A neuropsychiatrist need only be involved when:when:

1.1. risk-taking behaviours increase as risk-taking behaviours increase as disease progresses.disease progresses.

2.2. violent behaviourviolent behaviour

3.3. disinhibited behaviours disinhibited behaviours

4.4. delusions of persecutiondelusions of persecution

5.5. hallucinationshallucinations

6.6. exaggerated responses to stressexaggerated responses to stress


Alzheimer’s DementiaAlzheimer’s Dementia

Confirmed only though postmortem studiesConfirmed only though postmortem studies Poor relation between neurobiological Poor relation between neurobiological changes and clinical symptomschanges and clinical symptoms

Diagnosis is based on the general symptoms Diagnosis is based on the general symptoms of dementia, not on imaging data.of dementia, not on imaging data.

Scale of Behavioural Change used to Scale of Behavioural Change used to determine stages (Reisburg, 1983)determine stages (Reisburg, 1983)• From Very Mild to Very SevereFrom Very Mild to Very Severe


Alzheimer’s DementiaAlzheimer’s DementiaDegree of Cognitive Decline

Symptoms

None • No subjective complaints of memory deficits.

• No memory deficits noted on testing Very mild • 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


Alzheimer’s DementiaAlzheimer’s Dementia

Degree of Cognitive Decline

Symptoms

Very severe • 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.


Alzheimer’s NeuropathologyAlzheimer’s Neuropathology

Still mainly confirmed through postmortem Still mainly confirmed through postmortem findings (Sfindings (Selkoe, 1992; Brun, 1983)elkoe, 1992; Brun, 1983)

• neuropathology non-specific to Alzheimer’sneuropathology non-specific to Alzheimer’s

Neuritic plaquesNeuritic plaques - found in cerebral - found in cerebral cortex, and correlated with degree of cortex, and correlated with degree of cognitive dysfunction (amyloid-beta cognitive dysfunction (amyloid-beta peptide)peptide)

Neurofibrillary tanglesNeurofibrillary tangles in the neurons, in the neurons, especially hippocampus (helical fragments)especially hippocampus (helical fragments)

Loss of cortical volume typically in Loss of cortical volume typically in temporal areas, limbic cortex, posterior temporal areas, limbic cortex, posterior parietal areas.parietal areas.


Alzheimer’s NeurobiologyAlzheimer’s Neurobiology

Loss of cells in entorhinal cortex (main Loss of cells in entorhinal cortex (main input into the hippocampus)input into the hippocampus)

Loss of dendritesLoss of dendrites General decrease in neurotransmitters: NA, General decrease in neurotransmitters: NA, DA, 5HT, glutamateDA, 5HT, glutamate

Similar findings have been suggested for Similar findings have been suggested for other types of dementiasother types of dementias


Lewy Bodies DementiaLewy Bodies Dementia

Neurodegenerative disorder associated with abnormal Neurodegenerative disorder associated with abnormal structures (Lewy bodies) found in certain areas of the structures (Lewy bodies) found in certain areas of the brain.brain.

Associated with Parkinson's and Alzheimer's diseasesAssociated with Parkinson's and Alzheimer's diseases Researchers not sure whether it’s a distinct clinical entity Researchers not sure whether it’s a distinct clinical entity

or a variant of Alzheimer's or Parkinson's disease.or a variant of Alzheimer's or Parkinson's disease. Quite common: 10-25% of all dementia casesQuite common: 10-25% of all dementia cases


Lewy Bodies DementiaLewy Bodies Dementia Appear as toxic dark Appear as toxic dark

red or brown spots red or brown spots in the cytoplasm of in the cytoplasm of the neuron, the neuron, typically in typically in substantia nigra.substantia nigra.

DA neurons may be DA neurons may be selectively selectively vulnerable to toxic vulnerable to toxic effects effects

Contain the protein Contain the protein alpha-synucleinalpha-synuclein, , which normally which normally maintains integrity maintains integrity of vesicles of vesicles containing containing neurotransmitterneurotransmitter


Other InformationOther Information

Generally speaking, the severity of Generally speaking, the severity of neuropsychological dysfunction neuropsychological dysfunction (dementia and (dementia and

mood)mood) is correlated to the extent of brain is correlated to the extent of brain atrophyatrophy• More related to brain volume than to effects on More related to brain volume than to effects on a particular brain area.a particular brain area.

The cause of neurodegenerative disorders The cause of neurodegenerative disorders is unknownis unknown

Still some debate as to whether Still some debate as to whether Alzheimer’s is a disease at allAlzheimer’s is a disease at all


Other InformationOther Information

Typically dementias are not reversible Typically dementias are not reversible but follow a progressive or static coursebut follow a progressive or static course

Reversible only if caused by a treatable Reversible only if caused by a treatable general medical condition (e.g. general medical condition (e.g. hypoglycemia)hypoglycemia)

Ultimately, dementias lead to death Ultimately, dementias lead to death (related to mobility)(related to mobility)

1.1. increased incidence of accidentsincreased incidence of accidents

2.2. increased susceptibility to infectionsincreased susceptibility to infections


The problem of treatmentThe problem of treatment

Antiparkinsonian (DA) medication may actually worsen Antiparkinsonian (DA) medication may actually worsen such symptoms as hallucinations and delusions. such symptoms as hallucinations and delusions.

Neuroleptic (antipsychotic) drugs prescribed for Neuroleptic (antipsychotic) drugs prescribed for psychiatric symptoms may markedly worsen the psychiatric symptoms may markedly worsen the movement symptoms (DA antagonist, among other movement symptoms (DA antagonist, among other things). things).

Which symptoms to treat, or can both movement and Which symptoms to treat, or can both movement and psychiatric conditions be addressed?psychiatric conditions be addressed?

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PSYC4080 6.0D Dementias 1 Dementias. Dementias 2 Neurodegenerative Disorders A varied assortment of central nervous system disorders characterized by