BACKGROUND– Alzheimer's disease (AD) is a progressive dementia associated with distinct neuropathologic changes and characterized by memory loss and impairment in at least one other area of cognition. The underlying neuropathologic substrate for cognitive and noncognitive behavioral disturbances in AD is uncertain, but likely includes deficiencies of cholinergic and other transmitters in addition to plaques and tangles.
REVIEW– Therapies based on cholinergic hypotheses have lead to two approved drugs, tacrine and donepezil; other cholinergic drugs, including cholinesterase inhibitors, muscarinic agonists, and nicotinic agonists, are under development. Other therapies have been devised based on presumed risk and protective factors, such as aging, APO E genotype, head trauma, menopause/estrogen deficiency, the effect of education on the brain, anti-inflammatory drugs, and anti-oxidants. Recently, numerous basic studies have demonstrated the significance of amyloid protein, τ protein, and apolipoprotein E in the pathogenesis of plaques and tangles.
SUMMARY– Treatment of the cognitive disturbances in AD will likely use multiple approaches to improve symptoms and to slow progression. Therapy for the noncognitive disturbances involves communication between the clinician and the caregiver, as well as pharmacologic and nonpharmacologic treatments.
CONCLUSIONS– AD is a heterogeneous disorder. Treatment must be individualized and must address both cognitive and noncognitive disturbances. Future therapies may also take various genetic risk factors and gender into account.
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