Auguste D Dementia update Historical context Early diagnosis MCI Medication issues current and future Driving Any questions Auguste Deter Dr Alzheimer Auguste D 1901 Paper 1907 Alzheimers ID: 1034932
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1. Alzheimers disease111 years on from Auguste D
2. Dementia updateHistorical contextEarly diagnosisMCIMedication issues, current and futureDrivingAny questions?
3. Auguste Deter
4. Dr Alzheimer
5. Auguste D 1901Paper 1907Alzheimers disease Kraplein 1910 (rare presenile dementia)Alzheimers Disease 1977, amyloid plaquesNFT 19841993 Choline esterase inhibitors2000 memantine
6. MCITransition healthy ageing to clinical dementiaDriven by need for early recognitionBroadening of initial construct away from prodromal AD
7. Mild Cognitive ImpairmentConcept developed in late 1980s2003 symposium DSM V
8. MCI criteriaSubjective concerns from patient, informant or clinicianEvidence of impairment in one or more domainsPreservation of function
9. MCI sub typesaMCI (single)aMCI (multiple)naMCI (single)naMCI (multiple)
10. MCI as a prodrome of AD……Uncertain: clinical MCI, no biomarkersIntermediate: MCI plus evidence of increased amyloid or neurodegeneration High Probability: MCI plus amyloid plus neurodegeneration
11. Biomarkers (Increased Beta-amyloid burden) PET studies (Pittsburgh compound)CSF AB42 levels
12. Biomarkers (neurodegeneration)CSF TauHippocampal/ medial temporal lobe volume MRIFDG-PET (hypoperfusion)SPECT perfusion
13. Clinically useful?Prevalence rates ( >65) ~ 20%Conversion to clinical dementia ~ 10% (20% in Memory Clinic) per yearNo evidence of benefit from treatment with Cognitive Enhancers, no alteration of conversion rate
14. Identification of presymptomatic ADNot possible currentlyPeripheral biomarkersPathology developing for 10 – 20 yrs before symptoms
15. So………MCI useful in identifying those at higher risk of subsequently developing ADUse of biomarkers limited to researchImportant group to monitor
16. Screening toolsOver estimation of valueMust always be seen in context of underlying prevalence
17. medicationCholine esterase InhibitorsMemantineAnti depressantsMood stabilisersAnti psychoticsbenzodiazepines
18. Choline Esterase InhibitorsDonepezil, Galantamine, RivastigmineNo difference in efficacyDonepezil easy to use, cheapTransdermal Rivastigmine, PD dementia
19. Choline Esterase InhibitorsMild – moderate ADModest effect on cognition, care giver burden, delay need for institutional careCan be helpful in non cognitive symptoms, particularly agitation and psychosis
20. MemantineMod- severe ADIntolerant of AchEI’sModest effect on cognitive symptoms/functionHelpful with non cognitive symptoms, particularly those with a significant affective component
21. Memantine & AchEI’s in combinationComplimentary actionsGood evidence baseSABP reviewing guidanceCognitive & non cognitive symptoms
22. Anti depressantsGenerally safeConflicting evidence from studiesUseful in affective lability, irritability, emotional incontinence Best evidence for Sertraline & citalopram, increasing for Mirtazepine
23. Anti psychoticsHave been over usedNot the work of SatanBut increase all cause mortality, increase incidence of cerebrovascular events, impair cognitionHelpful in florid psychotic symptoms, aggression & agitationBest evidence for risperidone, then Olanzapine
24. Mood stabilisersCarbemazepine & gabapentin can be helpful in challenging behavioursPoorly toleratedSignificant side effectsValproate not helpful
25. BenzodiazepinesNO
26. The future…………No drugs since memantineFrom 2002 to 2014:244 compounds413 clinical trials99.6% failure rate
27. bapineuzumabAmyloid antibodyPfizer, J&J, Elan+ve mouse studiesReduces amyloid burden on PETDoesn’t workX2 phase 3 trials“Hundreds of Millions of dollars”
28. CREAD crenezumab, amyloid AB, phase 3SYMBAD, BPSD, mirtazepine & carbemazepineMasitinib tyrosine kinase inhibitor, phase 3 , AD and ALSELAN liraglutide, long acting glucagon like agonist, phase 32017 - SABP
29. driving
30. Driving Individuals must inform DVLADecision made on individual basisMay issue driving licence for 12 monthsDVLA approved assessment centres
31. drivingX 3 – 8 risk of RTARisk linked to duration of symptoms and disease severity3 years symptoms = 16 – 24 yr old male
32. Driving - factors to considerSubj reports unhelpfulPoor correlation between informant & riskMMSETests of visuospatial function +/- executive function better predictive value
33. drivingModerate – severe : stopMild: consider referral to driving centre if any concerns