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:
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
Country Japan M F China M F India M F USA M F Europe M F France M F Life Expectancy at Birth
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 Silver stained plaques and tangles Thick arrow: senile (neuritic) plaque Small arrow: diffuse plaque Star: tangle
Amyloid hypothesis Secretase Secretase AA Aggregated A APP s NC Cell proliferation Calcium regulation Membrane KPI Secretase Secretase , 671 APP Reduced Ca ++ Neuroprotection Neuroplasticity Increased Ca ++ Neurotoxicity Abnormal outgrowth
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 Agemalesfemales
Ferri CP et al. Lancet 2005; 366:
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?
drug treatment centrally acting acetylcholinesterase inhibitors e.g. donepezil, rivastigmine, galantamine NMDA receptor antagonist: memantine symptomatic treatment in early disease, only 30-40% respond
HIV encephalopathy II macrophage, microglial and astrocyte activation multi-nucleated giant cells basal ganglia, deep white matter, brainstem especially affected
CT MRI-FLAIR HIV encephalopathy
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
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): 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