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Year 2 Medicine > Dementia - The Grand 21st Century Challenge > Flashcards

Dementia - The Grand 21st Century Challenge Flashcards

1
Q

The beginning - Dementia

  • Senile p..
  • … tangles (tau)
  • … disease
A
  • Senile plaques
  • Neurofibrillary tangles (tau)
  • Alzheimer’s disease
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2
Q

Currently - Dementia

  • No cure, no disease … treatment
  • Current treatment/medication is …, at best
  • BPSD a significant treatment challenge
    • BPSD - … and … symptoms of dementia
A
  • No cure, no disease modifying treatment
  • Current treatment/medication is symptomatic, at best
  • BPSD a significant treatment challenge
    • BPSD - behavioural and psychological symptoms of dementia
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3
Q

So not too good news - Dementia

  • Dementia is only diagnosed in about … of those who have it
  • No disease … treatment
  • No Tx licensed for DLB, VaD, FTD
  • Dozens of phase II and III clinical trials have failed
  • 25-30% of … cases may be misdiagnosed
  • Misdiagnosis/underdiagnosing DLB
A
  • Dementia is only diagnosed in about half of those who have it
  • No disease modifying treatment
  • No Tx licensed for DLB, VaD, FTD
  • Dozens of phase II and III clinical trials have failed
  • 25-30% of AD cases may be misdiagnosed
  • Misdiagnosis/underdiagnosing DLB
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4
Q

So not too good news - Dementia

  • Dementia is only diagnosed in about half of those who have it
  • No disease modifying treatment
  • No Tx licensed for DLB, VaD, FTD
  • Dozens of phase II and III clinical trials have failed
  • …-…% of AD cases may be misdiagnosed
  • Misdiagnosis/underdiagnosing DLB
A
  • Dementia is only diagnosed in about half of those who have it
  • No disease modifying treatment
  • No Tx licensed for DLB, VaD, FTD
  • Dozens of phase II and III clinical trials have failed
  • 25-30% of AD cases may be misdiagnosed
  • Misdiagnosis/underdiagnosing DLB
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5
Q

Dementia - good things

  • Increased … of dementias
  • Increased ability to … correctly
  • Recent significant advances in … investigations
  • Even without disease modifying treatment many advantages to diagnose correctly
  • … factors identified
  • … may work
  • Disease modifying TX need not be a …!
A
  • Increased understanding of dementias
  • Increased ability to diagnose correctly
  • Recent significant advances in diagnostic investigations
  • Even without disease modifying treatment many advantages to diagnose correctly
  • Risk factors identified
  • Prevention may work
  • Disease modifying TX need not be a cure!
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6
Q

Some facts - Dementia

  • Over past century: >65y.o. increased from …% to …%
  • 6-8% of those >65 years old have dementia
  • Over …. in UK have dementia
  • Half a million people have AD
A
  • Over past century: >65y.o. increased from 5% to 16%
  • 6-8% of those >65 years old have dementia
  • Over 800,000 in UK have dementia
  • Half a million people have AD
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7
Q

Some facts - Dementia

  • Over past century: >65y.o. increased from 5% to 16%
  • …-…% of those >65 years old have dementia
  • Over 800,000 in UK have dementia
  • … a million people have AD
A
  • Over past century: >65y.o. increased from 5% to 16%
  • 6-8% of those >65 years old have dementia
  • Over 800,000 in UK have dementia
  • Half a million people have AD
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8
Q

Beyond clinical - Dementia

  • Ageing population - worldwide
  • … constraints
  • Competitions with other … conditions
  • Dementia has not always won
A
  • Ageing population - worldwide
  • Financial constraints
  • Competitions with other chronic conditions
  • Dementia has not always won
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9
Q

Future management strategies for dementia

  • First strategy is …
  • Second strategy is to … down … of disease with what we have got
  • Third strategy is to introduce disease … treatment
  • Fourth strategy is …
  • Support patients to live well with dementia
A
  • First strategy is prevention
  • Second strategy is to slow down progression of disease with what we have got
  • Third strategy is to introduce disease modifying treatment
  • Fourth strategy is cure
  • Support patients to live well with dementia
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10
Q

Prevention - can we prevent Alzheimer’s disease?

A
  • Currently no prophylactic treatment/cure
  • Epidemiological data point to Alzheimer’s disease being a preventable condition
  • Must identify manageable risk factors
  • Develop health programmes or treatments to at least mitigate their effects
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11
Q

Risk Factors for Dementia

  • Fixed
    • Age
    • Genetics
    • Brain …
    • … level
    • A…
  • Can change
    • D…
    • H…
    • Brain injury
    • … disorders
    • Depression
    • Obesity
    • Physical health
A
  • Fixed
    • Age
    • Genetics
    • Brain injury
    • Educational level
    • Alcoholism
  • Can change
    • Diabetics
    • Hypertension
    • Brain injury
    • Sleep disorders
    • Depression
    • Obesity
    • Physical health
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12
Q

Risk Factors for Dementia

  • Fixed
    • …
    • …
    • Brain injury
    • Educational level
    • Alcoholism
  • Can change
    • Diabetics
    • Hypertension
    • Brain injury
    • Sleep …
    • D…
    • O…
    • … health
A
  • Fixed
    • Age
    • Genetics
    • Brain injury
    • Educational level
    • Alcoholism
  • Can change
    • Diabetics
    • Hypertension
    • Brain injury
    • Sleep disorders
    • Depression
    • Obesity
    • Physical health
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13
Q

Prevention steps - Dementia

  • E…
  • Dietary …
  • E…
  • … stimulation
  • Look after physical and mental health:
    • Hypertension, s…, vitamin D, d…, blood …, depression, hypothyroidism, infections, no smoking/…, head injuries
    • (… changes)
A
  • Education
  • Dietary interventions
  • Exercise
  • Cognitive stimulation
  • Look after physical and mental health:
    • Hypertension, sleep, vitamin D, diabetes, blood cholesterol, depression, hypothyroidism, infections, no smoking/drinking, head injuries
    • (Lifestyle changes)
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14
Q

Can we slow down progression? - Dementia

  • Clever use of all current available approaches
  • Optimal use of available drugs
    • D…, Rivastigmine, Galantamine, Memantine, Huperzine A
  • Psychosocial support
  • Lifestyle changes. Never too late…
    • Identify vitamin … and manage accordingly (vitamin B12/folate & D)
    • …
    • Exercise
    • … stimulation
    • Timely diagnosis and treatment of physical and … health conditions
A
  • Clever use of all current available approaches
  • Optimal use of available drugs
    • Donepezil, Rivastigmine, Galantamine, Memantine, Huperzine A
  • Psychosocial support
  • Lifestyle changes. Never too late…
    • Identify vitamin deficiencies and manage accordingly (vitamin B12/folate & D)
    • Diet
    • Exercise
    • Cognitive stimulation
    • Timely diagnosis and treatment of physical and mental health conditions
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15
Q

Can we slow down progression? - Dementia

  • Clever use of all current available approaches
  • Optimal use of available drugs
    • Donepezil, R…, Galantamine, Memantine, Huperzine A
  • … support
    • Lifestyle changes. Never too late…
    • Identify vitamin deficiencies and manage accordingly (vitamin …/… & D)
    • Diet
    • Exercise
    • … stimulation
    • … diagnosis and … of physical and mental health conditions
A
  • Clever use of all current available approaches
  • Optimal use of available drugs
    • Donepezil, Rivastigmine, Galantamine, Memantine, Huperzine A
  • Psychosocial support
    • Lifestyle changes. Never too late…
    • Identify vitamin deficiencies and manage accordingly (vitamin B12/folate & D)
    • Diet
    • Exercise
    • Cognitive stimulation
    • Timely diagnosis and treatment of physical and mental health conditions
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16
Q

Vitamin E - Dementia

A
  • “there is sufficient evidence of possible benefit to justify further studies” - Tabel et al. 2000 (Cochrane)
  • “there is no evidence of efficacy of Vitamin E in the prevention or treatment of people with AD or MCI” - Isaac et al., 2008 (Cochrane)
  • “no convincing evidence that vitamin E is of benefit in the treatment of AD or MCI. Future trials assessing vitamin E treatment in AD should not be restricted to alpha-tocopherol”.
  • Alpha, beta, gamma, and delta tocopherol and alpha, beta, gamma, and delta tocotrienol - Farina et al. 2012
17
Q

NSAIDs - Dementia

  • Strong epidemiological evidence
  • “NSAIDs are associated with severe side-effects and their use… can only be justified if the benefits clearly outweigh the … To date no evidence exists to support the use of NSAIDs… either prophylactically or therapeutically, and as such these drugs cannot be recommended” - Tabet 2003 (Evidence-based Healthcare)
  • “Based on the studies carried out so far, the efficacy of aspirin, steroid and NSAIDs (traditional NSAIDs and COX-2 inhibitors) is not proven. Therefore, these drugs cannot be recommended for the treatment of AD”. - Jaturapatporn et al., 2012 (Cochrane)
A
  • Strong epidemiological evidence
  • “NSAIDs are associated with severe side-effects and their use… can only be justified if the benefits clearly outweigh the risks. To date no evidence exists to support the use of NSAIDs… either prophylactically or therapeutically, and as such these drugs cannot be recommended” - Tabet 2003 (Evidence-based Healthcare)
  • “Based on the studies carried out so far, the efficacy of aspirin, steroid and NSAIDs (traditional NSAIDs and COX-2 inhibitors) is not proven. Therefore, these drugs cannot be recommended for the treatment of AD”. - Jaturapatporn et al., 2012 (Cochrane)
18
Q

Ginkgo Biloba - dementia

A
  • Extract EGB 761
  • 17 active metabolites: 3 antioxidants
  • Dose - 120-140 mg
  • SE - allergy, bleeding, skin reactions, GIT, drug interaction
  • Weak evidence
19
Q

Individual variability in rate of decline: accelerators of decline (Dementia)

  • Psychosis
  • Anti-psychotic …
  • D…
  • D..
  • I..
  • Anaesthesia
  • Decreased … reserve
  • Physical inactivity
  • … status
  • Age
  • Polypharmacy
  • …/vitamins deficiency
A
  • Psychosis
  • Anti-psychotic treatment
  • Depression
  • Delirium
  • Infections
  • Anaesthesia
  • Decreased cognitive reserve
  • Physical inactivity
  • Genetic status
  • Age
  • Polypharmacy
  • Hypothyroidism/vitamins deficiency
20
Q

Disease modifying treatment - Dementia

  • Currently targeting 2 proteins that misfold and accumulate in the brains in patients with AD
    • …
    • …
  • But role of these is still being debated
  • Itzhaki et al. 2016. Microbes and Alzheimer’s disease. J Alzheimers Dis.
  • Kumar et al. 2016. Amyloid-B peptide protects against microbial infection in mouse and warm models of Alzheimer’s disease. Sci Transl Med.
A
  • Currently targeting 2 proteins that misfold and accumulate in the brains in patients with AD
    • Amyloid
    • Tau
  • But role of these is still being debated
  • Itzhaki et al. 2016. Microbes and Alzheimer’s disease. J Alzheimers Dis.
  • Kumar et al. 2016. Amyloid-B peptide protects against microbial infection in mouse and warm models of Alzheimer’s disease. Sci Transl Med.
21
Q

Disease modifying treatment - Dementia

  • Currently targeting 2 proteins that … and … in the brains in patients with …
    • Amyloid
    • Tau
  • But role of these is still being debated
  • Itzhaki et al. 2016. Microbes and Alzheimer’s disease. J Alzheimers Dis.
  • Kumar et al. 2016. Amyloid-B peptide protects against microbial infection in mouse and warm models of Alzheimer’s disease. Sci Transl Med.
A
  • Currently targeting 2 proteins that misfold and accumulate in the brains in patients with AD
    • Amyloid
    • Tau
  • But role of these is still being debated
  • Itzhaki et al. 2016. Microbes and Alzheimer’s disease. J Alzheimers Dis.
  • Kumar et al. 2016. Amyloid-B peptide protects against microbial infection in mouse and warm models of Alzheimer’s disease. Sci Transl Med.
22
Q

Anti-amyloid treatment strategies

  • Destroy existing amyloid …
  • Stop …
  • Best, both
A
  • Destroy existing amyloid plaques
  • Stop aggregation
  • Best, both
23
Q

Targeting existing amyloid aggregates

  • …
    • Bapineuzumab, Solanezumab, Crenezumab & Gantenerumab
  • … are ongoing
    • CNS clearance hypothesis
    • Peripheral sink hypothesis
A
  • MABs
  • Bapineuzumab, Solanezumab, Crenezumab & Gantenerumab
  • RCTs are ongoing
  • CNS clearance hypothesis
  • Peripheral sink hypothesis
24
Q

Need to know that there are … … developed - target amyloid … in brain - under clinical trials

A

Need to know that there are monoclonal antibodies developed - target amyloid aggregates in brain - under clinical trials

25
Q

Stopping new amyloid aggregation

  • Through agents blocking or modulating beta and gamma secretases
  • Phase I-III … are ongoing
A
  • Through agents blocking or modulating beta and gamma secretases
  • Phase I-III RCTs are ongoing
26
Q

Anti-Tau medication

  • LMTX:
    • Reformulated methylene blue
    • Acts by reducing levels of … or … Tau proteins
    • In … phase clinical trial
A
  • LMTX:
    • Reformulated methylene blue
    • Acts by reducing levels of aggregated or misfolded Tau proteins
    • In final phase clinical trial
27
Q

Cure - Dementia

A

Hope for a better treatment one day

28
Q

Support patients to live with dementia

  • … - patients/carers, doctors/nurses
  • Increase clinical and social care …
  • … - care, research
  • Highlight dementia
A
  • Education - patients/carers, doctors/nurses
  • Increase clinical and social care interaction
  • Funding - care, research
  • Highlight dementia
29
Q

Research activities - Dementia

  • … reviews
  • … trials
  • Research into …, physical health/illness as they relate to disease …
A
  • Systematic reviews
  • Clinical trials
  • Research into lifestyles, physical health/illness as they relate to disease progression
30
Q

Conclusion - Dementia (21st century challenge)

  • … away from a cure
  • P..
  • Use current … to best effect
  • Help patients live … with dementia
  • Research & … trials
  • National & world …
A
  • Years away from a cure
  • Prevent
  • Use current treatment to best effect
  • Help patients live well with dementia
  • Research & clinical trials
  • National & world policy

Year 2 Medicine (162 decks)

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