1. PSYC4080 6.0D Dementias 1 Dementias

2. Dementias 2 Neurodegenerative Disorders A varied assortment of central nervous system disorders characterized by gradual and progressive loss of neural tissue. 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 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 Disorders can affect anyone at any age, not just a disease in the elderly Can even strike during infancyCan even strike during infancy

3. PSYC4080 6.0D Dementias 3 Incidence, Prevalence Usually a disease of aging populations Usually a disease of aging populations Highest prevalence over age 85. Highest prevalence over age 85. Can occur in children and adolescents, and shown as a deterioration in function. Can occur in children and adolescents, and 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, 1995) 10% genetic concordance (Sherrington, 1995)

4. PSYC4080 6.0D Dementias 4 Prevalence Parkinson’s: 8-15 in 100,000 (0.00008- 0.00015%) Parkinson’s: 8-15 in 100,000 (0.00008- 0.00015%) Alzheimer’s: 435,000 persons over 65 years (0.01%) Alzheimer’s: 435,000 persons over 65 years (0.01%)

5. PSYC4080 6.0D Dementias 5 Neuropathology Protein Degeneration (Cummings, 2003) Abnormalities in the metabolism of three proteins account for more than 90% of all neurodegenerative dementias 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 misfolded proteins that cannot be properly degraded within affected cells Amyloid-beta, alpha-synuclein, and tau Amyloid-beta, alpha-synuclein, and tau 1.Binding along the membrane 2.Accumulation of these proteins 3.Abnormal cellular maintenance

6. PSYC4080 6.0D Dementias 6 Protein Degeneration All of these proteins are involved with maintaining the structure and integrity of neurons 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 DA neurons may be selectively vulnerable to toxic effects 3.Tau: microtubule assembly and stabilization Dysregulation contributes to cell death Dysregulation contributes to cell death

7. PSYC4080 6.0D Dementias 7 Protein Degeneration Accumulation of these proteins often begins in brainstem (substantia nigra, locus coeruleus) Accumulation of these proteins often begins in brainstem (substantia nigra, locus coeruleus) Work their way to limbic and (frontal, temporal) cortical areas Work their way to limbic and (frontal, temporal) cortical areas Producing characteristic cell death and subsequent affects and memory and executive functioning. Producing characteristic cell death and subsequent affects and memory and executive functioning.

8. PSYC4080 6.0D Dementias 8 Protein Degeneration www.alzheimer.ca

9. PSYC4080 6.0D Dementias 9 Neuropathology A. Frontal lobe dysfunction/dementias Degeneration of neurons in the frontal lobe, basal ganglia Degeneration of neurons in the frontal lobe, basal ganglia Interruption of frontal-subcortical pathways Interruption of frontal-subcortical pathways Deficits similar to those of frontal lobe lesion patients. Deficits similar to those of frontal lobe lesion patients.

10. PSYC4080 6.0D Dementias 10 Neuropathology Symptoms of dementia (DSM-IV) 1.Aphasia (language disturbance). 2.Apraxia (impaired ability to carry out motor activities despite intact motor function). 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). 3.Agnosia (failure to recognize or identify objects despite intact sensory function).

11. PSYC4080 6.0D Dementias 11 Neuropathology Symptoms of dementia (DSM-IV) 4.Executive functioning  Planning, organizing, sequencing, abstracting  Working memory  Encoding new memories  Episodic memories 5.Delusions or hallucinations

12. PSYC4080 6.0D Dementias 12 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

13. PSYC4080 6.0D Dementias 13 Parkinson’s Disease Assessment by a neuropsychologist is always undertaken in these cases 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

14. PSYC4080 6.0D Dementias 14 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.

15. PSYC4080 6.0D Dementias 15 Parkinson’s Disease Cognitive Deficits 2. Visuospatial difficulties: line orientation, block design, and picture arrangement, non–familiar- face discrimination (IQ subtests).  present even when motor impairment is absent.

16. PSYC4080 6.0D Dementias 16 Parkinson’s Disease Cognitive Deficits 3. Memory deficits: retrieval deficits in immediate- and long-term memory impairment, abnormalities in procedural memory, (includes anterograde and retrograde amnesias) Providing patients with retrieval cues can improve memory performance Providing patients with retrieval cues can improve memory performance Disproportionately impaired in their ability to temporally order or sequence new information Disproportionately impaired in their ability to temporally order or sequence new information

17. PSYC4080 6.0D Dementias 17 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.

18. PSYC4080 6.0D Dementias 18 Parkinson’s Disease A neuropsychiatrist need only be involved when: 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

19. PSYC4080 6.0D Dementias 19 Alzheimer’s Dementia Confirmed only though postmortem studies Confirmed only though postmortem studies Poor relation between neurobiological changes and clinical symptoms Poor relation between neurobiological changes and clinical symptoms Diagnosis is based on the general symptoms of dementia, not on imaging data. Diagnosis is based on the general symptoms of dementia, not on imaging data. Scale of Behavioural Change used to determine stages (Reisburg, 1983) Scale of Behavioural Change used to determine stages (Reisburg, 1983) From Very Mild to Very SevereFrom Very Mild to Very Severe

20. PSYC4080 6.0D Dementias 20 Alzheimer’s Dementia

21. PSYC4080 6.0D Dementias 21 Alzheimer’s Dementia

22. PSYC4080 6.0D Dementias 22 Alzheimer’s Neuropathology Still mainly confirmed through postmortem findings (S elkoe, 1992; Brun, 1983) Still mainly confirmed through postmortem findings (S elkoe, 1992; Brun, 1983) neuropathology non-specific to Alzheimer’sneuropathology non-specific to Alzheimer’s Neuritic plaques - found in cerebral cortex, and correlated with degree of cognitive dysfunction (amyloid-beta peptide) 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) Neurofibrillary tangles in the neurons, especially hippocampus (helical fragments) Loss of cortical volume typically in temporal areas, limbic cortex, posterior parietal areas. Loss of cortical volume typically in temporal areas, limbic cortex, posterior parietal areas.

23. PSYC4080 6.0D Dementias 23 Alzheimer’s Neurobiology Loss of cells in entorhinal cortex (main input into the hippocampus) Loss of cells in entorhinal cortex (main input into the hippocampus) Loss of dendrites Loss of dendrites General decrease in neurotransmitters: NA, DA, 5HT, glutamate General decrease in neurotransmitters: NA, DA, 5HT, glutamate Similar findings have been suggested for other types of dementias Similar findings have been suggested for other types of dementias

24. PSYC4080 6.0D Dementias 24 Lewy Bodies Dementia Neurodegenerative disorder associated with abnormal structures (Lewy bodies) found in certain areas of the brain. Neurodegenerative disorder associated with abnormal structures (Lewy bodies) found in certain areas of the brain. Associated with Parkinson's and Alzheimer's diseases 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. 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 Quite common: 10-25% of all dementia cases

25. PSYC4080 6.0D Dementias 25 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

26. PSYC4080 6.0D Dementias 26 Other Information Generally speaking, the severity of neuropsychological dysfunction (dementia and mood) is correlated to the extent of brain atrophy 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.More related to brain volume than to effects on a particular brain area. The cause of neurodegenerative disorders is unknown The cause of neurodegenerative disorders is unknown Still some debate as to whether Alzheimer’s is a disease at all Still some debate as to whether Alzheimer’s is a disease at all

27. PSYC4080 6.0D Dementias 27 Other Information Typically dementias are not reversible but follow a progressive or static course 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) Reversible only if caused by a treatable general medical condition (e.g. hypoglycemia) Ultimately, dementias lead to death (related to mobility) Ultimately, dementias lead to death (related to mobility) 1.increased incidence of accidents 2.increased susceptibility to infections

28. PSYC4080 6.0D Dementias 28 The problem of treatment Antiparkinsonian (DA) medication may actually worsen such symptoms as hallucinations and delusions. 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). 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? Which symptoms to treat, or can both movement and psychiatric conditions be addressed?