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DEMENTIA

DEMENTIA. FM Brett MD., FRCPath. DEMENTIA. Acquired global impairment of intellect memory and personality Impairment of intellectual function in the presence of normal consciousness affecting Language Visuospatial skills Emotion or personality Cognition. Dementia

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DEMENTIA

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  1. DEMENTIA FM Brett MD., FRCPath

  2. DEMENTIA • Acquired global impairment of intellect memory and personality • Impairment of intellectual function in the presence of normal consciousness affecting • Language • Visuospatial skills • Emotion or personality • Cognition

  3. Dementia Distinguished from mental retardation on the basis of having attained an appropriate degree of occupational and social functioning Presence of multiple cortical defects implies involvement of multiple cortical areas

  4. Prevalence • at least 2% at age 65-70 • 20 % at age 80

  5. Exclude Temporary confusion Primary memory loss

  6. Pathological basis

  7. Two main clinical patterns of Dementia Temporoparietal dementias- begin with impairment of memory and dysfunction of the temporal lobes. Patients later develop parietal lobe dysfunction – dysphasias and dyspraxias Frontotemporal dementias – behavioural disturbances of frontal lobe type. Patients later develop temporal lobe dysfunction. Typically parietal lobe function is preserved

  8. Common causes of dementia Neurodegenerative – common – AD DLBD CVS - multi-infarct dementia Hydrocephalus Toxic and metabolic Drugs Alcohol Mitochondrial encephalopathy Demyelinating disease Head injury Prion diseases Infective – HIV, neurosyphylis Neoplasia – paraneoplastic syndromes

  9. Specific cell systems Neurone Transmitter loss depletion

  10. Alzheimer’s Disease ~ Commonest cause of dementia ~ 50-75% of all cases of dementia ~ 5 groups ~ Sporadic late onset (commonest) ~ Familial late onset (uncommon) ~ Familial early onset (rare) ~ Associated with Down’s syndrome ~ Associated other degenerative disease

  11. ATROPHY PARTICULARLY TEMPORAL LOBES

  12. Pathological features of AD ~ Deposition of amyloid in the brain as plaques ~ Intraneuronal filamentous inclusions NFT ~ Dystrophic neurites ~ Loss of synapses and later neurones

  13. Associated pathologic changes include: Amyloid angiopathy Granulovacuolar degeneration Hirano bodies Increased lipofuscin in neurones Corpora amylacea

  14. TRANSMEMBRANE RECEPTOR AMYLOID PRECURSOR PROTEIN Abnormal proteolytic clevage Amyloidogenic fragments released

  15. Plaques DIFFUSE PRIMITIVE CLASSICAL BURNT-OUT ? progression

  16. SENILE PLAQUES PHF Amyloid fibrils Degenerate neurites Glial cell processes

  17. PAIRED HELICAL FILAMENTS NOT DERIVED FROM NEURONE CYTOSKELETON Antigenic similarity with a protein in normal neurones ? PHF – ALTERED NEURAL PROTEIN

  18. TAU Microtubular associated protein Controls MICROTUBULE FORMATION NERVE CELL SKELETON

  19. TANGLE ACCUMULATION NEURONE OF PHF DEATH

  20. Molecular pathology of AD AD1 mutations in the APP on Ch21 AD2 ass with the APOE4 allele on Ch 19 AD3 associated with the presenilin 1 gene on Ch 14 AD4 mutation in the presenilin 2 gene on Ch 1

  21. CAUSES OF PARKINSONISMCOMMON – PD LESS COMMON – Drug induced, MSA, PSP, vascular RARE - CBD, AD, MSD, hydrocephalus, FTD, HC, Dementia pugilistica, toxins, WD

  22. Parkinson’s Disease Clinical diagnosis REQUIRE 2 of the 3 cardinal features Bradykinesia Resting tremor Rigidity Associated features: Autonomic dysfunction Cognitive disturbance Dysphagia

  23. Manifestations of PD largely attributable to reduced dopaminergic input into the striatum due to degeneration of neurones in the pars compacta of the SN Genetic Free radical damage Environmental agents

  24. DLBD Progressive cognitive decline • + two of the following • Fluctating cognition • Recurrent visual hallucinations • Spontaneous motor features of Parkinsonism

  25. DLBD Supportive features – Repeated falls Syncope Neuroleptic sensitivity Systematised delusions Hallucinations

  26. Frontotemporal dementia Patients presenting with progressive frontal lobe dysfunction (that may later be followed by evidence of temporal lobe dysfunction) Accounts for 10% of all cases of dementia

  27. Vascular Dementia ~ Cumulative cognitive decline caused by effects of multiple episodes of cerebral ischaemia ~ Excludes cases caused by diffuse cerebral cortical damage due to a single episode of severe hypoxia or global cerebral hypoperfusion

  28. Vascular Dementia ~ arteriolosclerosis ~ Small vessel disease causing granular cortical atrophy ~ Large regional infarct ~ Critically sited infarcts e.g hippocampal region may cause hippocampal sclerosis

  29. Spongiform encephalopathies

  30. CJD historical aspects 1920-21 Jacob and Creutzfeldt – fatal brain disease 1950 - Kuru – New Guinea 1958 – Gajdusek – arrives New Guinea 1959 - Wm Hadlow- Uk to study scrapie 1976 - Gadjusek nobel prize for CJD research

  31. CJD historical aspects 1982 - Pruisner – prion disease 1985 – BSE- cows, Pt dies CJD post GH 1987 – CJD post dura mater graft 1996 – nvCJD 1998 – Pruisner Nobel prize

  32. CJD classification Definite sporadic Probable sporadic Iatrogenic Familial GSS

  33. Epidemiology of CJD Annual worldwide incidence of 1-2 cases per million Higher rates in Libyan Jews, Slovakia, Hungary and eastern England (families with mutations) M=F; Onset 55-75 (peak 7th decade) 10% FAMILIAL

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