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Global demographic changes and the challenge of dementia Marc I Combrinck Division of Neurology, Groote Schuur Hospital & Walter & Albertina Sisulu Institute.

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Presentation on theme: "Global demographic changes and the challenge of dementia Marc I Combrinck Division of Neurology, Groote Schuur Hospital & Walter & Albertina Sisulu Institute."— Presentation transcript:

1 Global demographic changes and the challenge of dementia Marc I Combrinck Division of Neurology, Groote Schuur Hospital & Walter & Albertina Sisulu Institute of Ageing, University of Cape Town

2 Aspects world demographic trends dementia Alzheimer’s disease projected prevalence rates costs treatment, prevention Sub-Saharan Africa & HIV/AIDS dementia

3 Country 1950 2000 2050 Japan M F 60.4 63.9 78.3 85.7 83.5 91 China M F 39.3 42.3 70.5 73.7 77.4 81.3 India M F 38.7 37.1 60.9 63.3 71.4 75.4 USA M F 66.1 72.0 75.8 80.6 80.8 85.8 Europe M F 63 68 69.6 78 78.5 84.5 France M F 64.1 69.9 75.8 83.1 88.9 Life Expectancy at Birth

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7 Medical consequences I an increase in age-related diseases dementia, depression stroke chronic musculo-skeletal disorders, arthritis, falls, hip fractures cardiovascular diseases cancers (prostate, colon) macular degeneration

8 Medical consequences II multi-morbidity polypharmacy

9 Dementia chronic progressive disorder deterioration in multiple aspects of cognitive function associated with behavioural & psychological symptoms severe impact on quality of life longest duration of burden on patient, family & society

10 Causes of dementia primary neurodegenerative diseases: Alzheimer’s, vascular disease, fronto- temporal dementia, Lewy body dementia secondary: hypothyroidism, CNS infections, vitamin B-12 deficiency, chronic subdural haematoma, tumour, etc.

11 Alzheimer-type pathology Silver stained plaques and tangles Thick arrow: senile (neuritic) plaque Small arrow: diffuse plaque Star: tangle

12 Amyloid hypothesis  Secretase  Secretase AA Aggregated A  APP s NC Cell proliferation Calcium regulation Membrane KPI  Secretase  Secretase 717670, 671  APP Reduced Ca ++ Neuroprotection Neuroplasticity Increased Ca ++ Neurotoxicity Abnormal outgrowth

13 Pathogenesis of amyloidosis in AD

14 Brain atrophy in Alzheimer’s disease

15 control   AD

16 Risk factors for AD Age

17 AD prevalence rates US General Accounting Office (1998) % prevalence rate – all severity levels Agemalesfemales 650.60.8 701.31.7 752.73.5 805.67.1 8511.113.8 9020.825.2 9535.641.5

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19 Ferri CP et al. Lancet 2005; 366: 2112 - 2117

20 In 2010, 57.7% of people with dementia live in low and middle income countries. By 2050, this will rise to 70.5%.

21 AD: risk factors I Established age family history Down’s syndrome apolipoprotein e4 allele autosomal dominant mutations: amyloid precursor protein gene (APP) chr 21, presenilin-1 gene chr 14, presenilin-2 gene chr 1. (<2% cases)

22 AD risk factors II Probable depression hypertension head injury homocysteine

23 AD: risk factors III Possible gender (F>M) education / neuro-cognitive reserve diabetes smoking cholesterol herpes simplex virus-I?

24 Possible protective factors anti-inflammatory drugs oestrogen apolipoprotein e2 allele high neurocognitive reserve & ­ cognitively stimulating activities cholesterol lowering drugs (statins) alcohol

25 AD & vascular disease

26 AD: cholinergic hypothesis

27 drug treatment centrally acting acetylcholinesterase inhibitors e.g. donepezil, rivastigmine, galantamine NMDA receptor antagonist: memantine symptomatic treatment in early disease, only 30-40% respond

28 new drugs?  -secretase inhibitors ß-secretase inhibitors ß-amyloid immunisation anti- ß-amyloid monoclonal antibodies mitochondrial stabilisers

29 Alzheimer’s prevention? treat vascular risk factors - dyslipidaemia, hypertension, diabetes mellitus lifestyle changes: improve diet, lose weight, exercise more, stop smoking keep mentally active vitamin D? anti-oxidants? statins? vitamin B group? non steroidal anti-inflammatory drugs? no proven interventions in randomised control trials

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35 Alzheimer’s disease in Africa?

36 Alzheimer’s disease in Africa II Nigeria: Ibadan vs. African Americans in Indianapolis no other good studies few pathological reports clinical anecdotal evidence

37 Life expectancy at birth: Sub- Saharan Africa 2008 South AfricaF 53 M 50 Malawi 53 Mozambique 51 Zimbabwe 42

38 South Africa 65+ population: 5% (Japan 23%) but marked socio-economic differences: “whites”: 13% “blacks” 4% 80+ population: 0.7% (Japan 5%) “whites” 2.4%, “blacks” 0.5%

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40 HIV/AIDS South Africa estimated 16.6% of population infected = 8 out of 48 x10 6 people

41 HIV-associated dementia/neuro- cognitive disorders a subcortical dementia progressive cognitive & behavioural decline memory deficits, psychomotor slowing, apathy slowed eye & limb movements hyper-reflexia, hypertonia, frontal lobe release signs

42 HIV encephalopathy II macrophage, microglial and astrocyte activation multi-nucleated giant cells basal ganglia, deep white matter, brainstem especially affected

43 CT MRI-FLAIR HIV encephalopathy

44 HIV dementia / HIVassociated neuro-cognitive disorders III prevalence? 20-30% Uganda, South Africa risk factors: high initial viral load, low CD 4 counts, age, anaemia, systemic symptoms APOE ε4 allele anti-retroviral drug therapy   incidence & often reverses deficits

45 HIV encephalopathy IV HAART   HIV dementia but  minor cognitive-motor disorders (MCMD) CNS sanctuary for latent or slowly replicating virus? slow neurodegeneration

46 APOE ε4 & HIV HIV-infected subjects with the E4 allele for APOE have excess dementia and peripheral neuropathy ELIZABETH H. CORDER, KEVIN ROBERTSON, LARS LANNFELT, NENAD BOGDANOVIC, GÖSTA EGGERTSEN, JEAN WILKINS, COLIN HALL Nature Medicine 1998;4(10):1182-4 E4 allele accelerates AIDS progression (Burt, PNAS 2008; 105: 8718)

47 HIV dementia & Alzheimer’s common pathological mechanisms? activation of microglial cells  release of inflammatory cytokines  damage to neurones & their synaptic connections  cognitive impairment  -amyloid found in both apolipoprotein E e4 a risk factor for both?

48 Impact of HIV/AIDS on elderly Care of ill children Care of AIDS orphaned grand-children

49 Summary increased life expectancy in industrialised countries and low to middle income countries of Asia, Latin America increased dementia prevalence increased dependent elderly population increased stress on social welfare systems & economies no good treatment available yet no proven preventative strategies additional problem of HIV dementia, especially in southern Africa


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