Alzheimer's disease

Alzheimer's disease (AD), a neurodegenerative disorder, is the most common cause of dementia and characterised clinically by progressive intellectual deterioration together with declining activities of daily living and neuropsychiatric symptoms or behavioral changes. The most striking early symptom is memory loss (amnesia), usually manifest as minor forgetfulness that becomes steadily more dense with illness progression, with relative preservation of older memories. As the disorder progresses, cognitive (intellectual) impairment extends to the domains of language (aphasia), coordinated movement (apraxia), recognition (agnosia) and those functions (such as decision-making and planning) closely related to the frontal lobe of the brain, reflecting extension of the underlying pathological process. This consists principally of neuronal (cell) loss (or atrophy), together with deposition of amyloid plaques and neurofibrillary tangles. Genetic factors are known to be important, and polymorphisms (variations) in three different autosomal dominant genes - Presenilin 1, Presenilin 2, and A-Beta - have been identified that account for a small number of cases of familial, early-onset AD. For late onset AD (LOAD), only one susceptibility gene has so far been identitified - the epsilon 4 allele of the APOE gene. Age of onset itself has a heritability of around 40%.

References

• Areosa SA, McShane R, Sherriff F. Memantine for dementia. Cochrane Database Syst Rev 2004(4);CD003154.pub2. PMID 15495043
• Courtney C, Farrell D, Gray R, Hills R, Lynch L, Sellwood E, Edwards S, Hardyman W, Raftery J, Crome P, Lendon C, Shaw H, Bentham P; AD2000 Collaborative Group. Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial. Lancet 2004;363:2105-15. PMID 15220031.