Global demographic changes and the challenge of dementia Marc I combrinck



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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 of Ageing,

  • University of Cape Town


Aspects

  • world demographic trends

  • dementia

  • Alzheimer’s disease

  • projected prevalence rates

  • costs

  • treatment, prevention

  • Sub-Saharan Africa & HIV/AIDS dementia











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



Medical consequences II

  • multi-morbidity

  • polypharmacy



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



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.



Alzheimer-type pathology



Amyloid hypothesis



Pathogenesis of amyloidosis in AD



Brain atrophy in Alzheimer’s disease





Risk factors for AD

  • Age



AD prevalence rates

  • US General Accounting Office (1998)

  • % prevalence rate – all severity levels

  • Age males females

  • 65 0.6 0.8

  • 70 1.3 1.7

  • 75 2.7 3.5

  • 80 5.6 7.1

  • 85 11.1 13.8

  • 90 20.8 25.2

  • 95 35.6 41.5







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



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)



AD risk factors II

  • Probable

  • depression

  • hypertension

  • head injury

  • homocysteine



AD: risk factors III

  • Possible

  • gender (F>M)

  • education / neuro-cognitive reserve

  • diabetes

  • smoking

  • cholesterol

  • herpes simplex virus-I?



Possible protective factors

  • anti-inflammatory drugs

  • oestrogen

  • apolipoprotein e2 allele

  • high neurocognitive reserve & ­ cognitively stimulating activities

  • cholesterol lowering drugs (statins)

  • alcohol



AD & vascular disease



AD: cholinergic hypothesis



drug treatment

  • centrally acting acetylcholinesterase inhibitors e.g. donepezil, rivastigmine, galantamine

  • NMDA receptor antagonist: memantine

  • symptomatic treatment in early disease, only 30-40% respond



new drugs?

  • -secretase inhibitors

  • ß-secretase inhibitors

  • ß-amyloid immunisation

  • anti- ß-amyloid monoclonal antibodies

  • mitochondrial stabilisers



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













Alzheimer’s disease in Africa?



Alzheimer’s disease in Africa II

  • Nigeria: Ibadan vs. African Americans in Indianapolis

  • no other good studies

  • few pathological reports

  • clinical anecdotal evidence



Life expectancy at birth: Sub-Saharan Africa



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%





HIV/AIDS South Africa



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



HIV encephalopathy II





HIV dementia / HIVassociated neuro-cognitive disorders III

  • prevalence? 20-30% Uganda, South Africa

  • risk factors: high initial viral load, low CD4 counts, age, anaemia, systemic symptoms

  • APOE ε4 allele

  • anti-retroviral drug therapy   incidence & often reverses deficits



HIV encephalopathy IV

  • HAART   HIV dementia but  minor cognitive-motor disorders (MCMD)

  • CNS sanctuary for latent or slowly replicating virus?

  • slow neurodegeneration



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)



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?



Impact of HIV/AIDS on elderly

  • Care of ill children

  • Care of AIDS orphaned grand-children



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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