Dementias

1. Dementias Dementias

2. 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 Dementias

3. 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) Dementias

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

5. 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 • Binding along the membrane • Accumulation of these proteins • Abnormal cellular maintenance Dementias

6. Protein Degeneration • All of these proteins are involved with maintaining the structure and integrity of neurons • Amyloid-beta: regulation of synaptic strength • Alpha-synuclein: integrity of vesicles containing neurotransmitter • DA neurons may be selectively vulnerable to toxic effects • Tau: microtubule assembly and stabilization • Dysregulation contributes to cell death Dementias

7. 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. Dementias

8. Protein Degeneration www.alzheimer.ca Dementias

9. 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. Dementias

10. Neuropathology Symptoms of dementia (DSM-IV) • Aphasia (language disturbance). • Apraxia (impaired ability to carry out motor activities despite intact motor function).

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

 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 Dementias

12. Neuropathology • 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 Dementias

13. Parkinson’s Disease • Assessment by a neuropsychologist is always undertaken in these cases • assessment of recall and recognition memory • assessment of long term memories • short-term memory • cued versus uncued recall • word naming for language function • testing for apraxia • visuospatial functioning • executive functioning Dementias

14. Parkinson’s Disease Cognitive Deficits • 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. 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. 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 • Disproportionately impaired in their ability to temporally order or sequence new information Dementias

17. Parkinson’s Disease Cognitive Deficits • 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. Dementias

18. Parkinson’s Disease • A neuropsychiatrist need only be involved when: • risk-taking behaviours increase as disease progresses. • violent behaviour • disinhibited behaviours • delusions of persecution • hallucinations • exaggerated responses to stress Dementias

19. 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 Dementias

20. Alzheimer’s Dementia Dementias

21. Alzheimer’s Dementia Dementias

22. 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. Dementias

23. 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 Dementias

24. 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 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 Dementias

26. 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 Dementias

27. 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) • increased incidence of accidents • increased susceptibility to infections Dementias

28. 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? Dementias