What are we getting right and what are we getting wrong?

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Silvester Campbell
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1 What are we getting right and what are we getting wrong? GERARD BYRNE BSc (Med), MBBS (Hons), PhD, FRANZCP School of Medicine University of Queensland

2 Some Important Goals Understanding the causes of dementia Developing primary prevention strategies Developing disease modifying treatments Developing better symptomatic treatments Developing better programs of care Combating the stigma associated with dementia

3 Underlying Causes of Dementia Genetic factors Probabilistic genes (APOE) Deterministic genes (e.g. PS1) Environmental factors (largely unknown) Brain ageing Brain reserve

4 Underlying Causes of Dementia Genetic factors Probabilistic genes (APOE) Deterministic genes (e.g. PS1) Environmental factors (largely unknown) Brain ageing Brain reserve

5 Apolipoprotein E (APOE) Margaret Pericak Vance

6 Underlying Causes of Dementia Genetic factors Probabilistic genes (APOE) Deterministic genes (e.g. PS1) Environmental factors (largely unknown) Brain ageing Brain reserve

7 Underlying Causes of Dementia Genetic factors Probabilistic genes (APOE) Deterministic genes (e.g. PS1) Environmental factors (largely unknown) Brain ageing Brain reserve

8 Underlying Causes of Dementia Genetic factors Probabilistic genes (APOE) Deterministic genes (e.g. PS1) Environmental factors (largely unknown) Brain ageing Brain reserve

9 Telomeres (in red) Elizabeth Blackburn

10 Sally Temple Neural Stem Cells (photo from Zhang lab)

11 Underlying Causes of Dementia Genetic factors Probabilistic genes (APOE) Deterministic genes (e.g. PS1) Environmental factors (largely unknown) Brain ageing Brain reserve

12 The Nun Study

13 Are There Two Types of Alzheimer s Disease? Type 1 Early onset familial Type 2 Late onset sporadic

15 Primary Prevention Decreased Risk of AD (low quality evidence) Mediterranean diet Folic acid Light to moderate alcohol intake Cognitive activities Physical activity Increased Risk of AD (low quality evidence) Diabetes mellitus Hyperlipidaemia in midlife Current tobacco use Because the quality of the evidence is low, more research is needed.

16 Primary Prevention Not Associated with Risk of AD (high quality evidence) Vitamin E Ginkgo biloba Not Associated with Risk of AD (low quality evidence) Hypertension Omega 3 fatty acids Vitamin B12 Beta carotene Because the quality of the evidence is low, more research is needed.

17 Primary Prevention Insufficient Evidence to Comment Saturated fats in diet Fruit & vegetable intake in diet Because there is insufficient evidence to comment, more research is needed.

18 Preventive Activities with General Health Benefits Stop smoking Regular physical exercise Regular cognitive activities Prudent diet (perhaps the diet espoused by Willett) Treat hypertension in mid life Treat hyperlipidaemia in mid life None of these things have been proven to prevent AD but all are likely to improve general health in most people.

19 Disease Modifying Treatment AN 1792 Gamma secretase inhibitors Bapineuzumab Intravenous immunoglobulin Tarenflurbil Tramiposate Methylene blue

20 Better Symptomatic Treatment Cognitive Function Donepezil, Rivastigmine, Galantamine, Memantine Rivastigmine transdermal patch Higher dose slow release Donepezil Dimebon 292 clinical trials currently recruiting in the US, most of which are testing symptomatic treatments

21 Better Symptomatic Treatment Challenging Behaviour Antidepressants Antipsychotics Anticonvulsants Non pharmacological interventions

22 Better Programs of Care Humane care at home Hospital care Nursing home care Management of challenging behaviours Palliative care There is a need for more humane care delivered by people who know what they are doing and have the time to do it.

23 Combating Stigma Raising awareness Educating the general public Educating politicians & health bureaucrats Educating health professionals Combating therapeutic nihilism Changing the name Major Neurocognitive Disorder Minor Neurocognitive Disorder

24 Report Card Prevention Early detection Symptomatic treatment Disease modifying treatment Humane care at home Nursing home care Hospital care End of life care

25 Report Card: Satisfactory Progress Research into the underlying mechanisms of Alzheimer s disease Epidemiological research into patterns of dementia in populations Support for carers of people with dementia

26 Report Card: Could Do Better Symptomatic treatments for Alzheimer s disease Disease modifying treatments for Alzheimer s disease Management of challenging behaviour in people with dementia (with or without drugs) Dementia research funding

27 Report Card: Insufficient Effort! Prevention of dementia Treatment of dementias other than Alzheimer s disease Appropriate care for younger people with dementia Appropriate care for people with dementia in hospital Palliative care for people with dementia at the end of life

Appendix K: Evidence review flow charts

Appendix K: Evidence review flow charts K.1 Dementia diagnosis K.1.1 Dementia diagnosis What are the most effective methods of primary assessment to decide whether a person with suspected dementia should be referred to a dementia service? What