Alzheimer's disease is the most common form of dementing illness, affecting nearly 4.5 million Americans according to current estimates. The disease exhibits a strong association with old age, and is not commonly observed in individuals <65 years of age. Among individuals >65 years of age, the prevalence of Alzheimer's disease is ∼10%, and nearly half of all persons >85 years of age are affected by this condition. Given the apparent link between Alzheimer's risk and increasing age, as well as expected changes in the demographic structure of the United States population, it has been projected that the number of Americans with Alzheimer's disease will reach unprecedented levels in the coming years. In fact, it has been predicted that, barring the development of novel preventive therapies, the number of US residents with Alzheimer's will increase to 11–16 million by the year 2050.

The expected rise in the number of Alzheimer's disease cases represents a daunting challenge, due to the far-reaching negative impact of the disease. Alzheimer's disease is a condition that not only has profound effects on the affected patient but also takes a dramatic toll on the patient's primary caregiver, who is in many cases the spouse or an adult child of the patient. Patients with Alzheimer's experience cognitive and functional declines, often in association with behavioral disturbances, while caregivers frequently suffer reductions in quality of life attributable to the immense emotional, physical, and financial burdens associated with the task of providing care.

Evidence exists for both cholinergic and glutamatergic involvement in the etiology of Alzheimer's disease. Acetylcholine (ACh), a neurotransmitter essential for processing memory and learning, is decreased in both concentration and function in patients with Alzheimer's disease. This deficit and other presynaptic cholinergic deficits, including loss of cholinergic neurons and decreased acetylcholinesterase activity, underscore the cholinergic hypothesis of Alzheimer's disease. The glutamatergic hypothesis links cognitive decline in patients with Alzheimer's to neuronal damage resulting from overactivation of N-methyl-D-aspartate (NMDA) receptors by glutamate. The sustained low-level activation of NMDA receptors, which are pivotal in learning and memory, may result from deficiencies in glutamate reuptake by astroglial cells in the synaptic cleft. This article reviews the roles of ACh and glutamate in Alzheimer's disease, with particular attention given to the overlap between cholinergic and glutamatergic pathways. In addition, the potential synergy between cholinesterase inhibitors and the NMDA receptor antagonist memantine in correcting neurologic abnormalities associated with Alzheimer's disease is addressed.

Alzheimer's disease is a devastating neurological disorder characterized by cognitive deficits, functional impairment, and often troublesome behavioral symptoms. Unfortunately, Alzheimer's disease can be difficult to diagnose at early and even moderate stages of the disease. This article outlines simple, efficient strategies for identifying patients with potential dementia. The discussion focuses on the key components of a comprehensive assessment plan, which typically involves taking the patient's history, as well as conducting cognitive testing, laboratory testing, neurologic examination, and neuroimaging to evaluate patients for Alzheimer's disease. Finally, opportunities for the improvement of care are discussed, with an emphasis on overcoming barriers to diagnosis such as time limitations and reimbursement issues.

Alzheimer's disease is a degenerative neurological condition characterized by the presence of β-amyloid plaques and neurofibrillary tangles in the limbic and neocortical regions of the brain. Pittsburgh Compound-B (PIB), a benzothiazole analog, has recently been found to specifically label amyloid deposits in positron emission tomography (PET) studies of the brain, opening the door for a wide range of applications related to Alzheimer's disease. In this article, data demonstrating the specificity of PIB as a PET tracer for β-amyloid lesions are reviewed, and the potential clinical applications of PIB PET imaging is discussed. Because amyloid plaques are common even in elderly individuals who are not suffering from dementia, the primary diagnostic function of PIB PET imaging presumably would be to rule out, rather than definitively confirm, Alzheimer's diagnoses in elderly patients. Other possible uses include monitoring plaque loads in patients receiving anti-amyloid therapy for Alzheimer's disease, as well as assessing plaque formation in unaffected individuals as a means of evaluating future Alzheimer's disease.

Deficits in cholinergic and glutamatergic neurotransmission have been linked to the symptomatology of Alzheimer's disease, and current therapies for Alzheimer's, including cholinesterase inhibitors (ChEIs) and the N-methyl-D-aspartate receptor antagonist memantine, have been developed to compensate for these deficits. This article reviews the results of clinical trials involving agents approved by the United States Food and Drug Administration for use in the treatment of Alzheimer's disease (namely, ChEIs for mild to moderate Alzheimer's and memantine for moderate to severe Alzheimer's). In particular, the efficacy of current monotherapy strategies in the treatment of cognitive and functional symptoms of Alzheimer's disease will be addressed. In addition, data from a clinical trial examining the use of a ChEI in combination with memantine will also be discussed, as it has been hypothesized that ChEIs and memantine may offer synergistic benefits due to their distinct mechanisms of action.

Behavioral and psychological symptoms of dementia pose significant challenges in the management of patients with Alzheimer's disease. Neuropsychiatric symptoms are associated with cognitive decline, highly impaired activities of daily living, and frontal lobe pathology. Moreover, behavioral and psychological symptoms can diminish patient quality of life, increase caregiver distress, and accelerate nursing home placement. Although these symptoms are often associated with the later stages of Alzheimer's disease, a high percentage of individuals with mild cognitive impairment or mild Alzheimer's report symptoms as well. This article provides an overview of behavioral and neuropsychiatric symptoms associated with Alzheimer's disease and discusses nonpharmacologic and pharmacologic approaches to the management of such symptoms. For patients with severe behavioral and psychological symptoms of dementia, pychotropic agents may be warranted, whereas approved therapies for Alzheimer's, including cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist memantine, may be appropriate in less severe cases.