Alzheimer's disease (AD) is a debilitating condition currently affecting 4.5 million elderly citizens in the United States alone. It is the most common form of dementia and is associated with significant disability. For many years the prognosis of the disease has remained largely unchanged. Those patients who develop AD face progressive cognitive and functional decline that ultimately shortens their life expectancy and destroys their quality of life. At the same time, the disease has a significant adverse impact on the lives of those family members who serve as caregivers. With the aging of the baby-boomer generation and the expected associated increase in the number of patients with AD, clinicians who treat the elderly will clearly be in need of some new answers. Recent advances in assessment, diagnosis, and treatment offer some hope for relief from this bleak prognosis.

Advances in AD include the establishment of clear diagnostic criteria, the validation of disease-specific assessment instruments, and pharmacologic and behavioral therapies for management of symptoms. A handful of medications that enhance cognition have obtained the approval of the Food and Drug Administration, and more are currently in development. Trials of existing medications have demonstrated benefit in the management of the psychiatric symptoms (eg, psychosis and agitation) typically associated with the disease. But much still remains to be done.

In the first article in this supplement, Michael A. Rogawski, MD, PhD, explains what is known about the pathogenesis and the behavioral and psychological symptoms of AD. He discusses the scientific basis for empirical therapies currently being used to relieve the symptoms of this disease, focusing on drug therapies approved by the FDA, including the newest AD medication to market memantine.

Alzheimer's disease (AD) is characterized by the abnormal extracellular accumulation of amyloid β-peptide (Aβ) into neuritic plaques and the intraneuronal aggregation of the microtubule-associated protein tau to form neurofibrillary tangles. These molecular events are implicated in the selective damage to neural systems critical for the brain functions that are impaired in AD. Impairment of cholinergic neurotransmission may be an important factor underlying the defects in cognition and memory that characterize AD. Cholinesterase (ChE) inhibitors, such as donepezil, rivastigmine, and galantamine, cause symptomatic improvement by inhibiting the breakdown of the neurotransmitter acetylcholine to increase its synaptic availability and, in the case of galantamine, by also allosterically potentiating nicotinic cholinergic receptors. Other agents, including vitamin E, monoamine oxidase inhibitors, and statins, have shown some benefit in epidemiological studies and clinical trials although compelling evidence of their efficacy is lacking. Memantine, shown to cause cognitive and functional improvement, is not an ChE inhibitor and does not interact with marketed ChE inhibitors. While the mechanism of action of memantine in AD is not known, the principal pharmacologic actions at therapeutic dose are inhibition of ionotropic neurotransmitter receptors, specifically N-methyl-D-aspartate (NMDA), 5-HT3, and nicotinic receptors. Like other NMDA antagonists, memantine causes behavioral activation associated with enhanced cerebral glucose utilization. Studies have shown that memantine can reverse the decreased metabolic activity associated with AD, possibly accounting for its beneficial effects on cognition and global functioning. Memantine also has neuroprotective properties and can inhibit Aβ-induced neurodegeneration.

Alzheimer's disease (AD) is a debilitating condition affecting millions of elderly citizens. The quality of life for AD patients significantly deteriorates in the face of worsening cognitive deficits and disabling functional declines, both contributing to manifestations of difficult behaviors. Of the estimated 4 million individuals with AD, only 60% of probable AD cases are diagnosed, with little more than half of those receiving treatment. One of the possible reasons for this problem is the large role primary care physicians (PCPs) have in diagnosing and treating AD. The barriers that PCPs confront to adequately manage these patients will be discussed. Finally, the specific challenges that geriatric psychiatrists will face in addressing these issues in an environment where there is only a limited number of trained geriatric psychiatrists will be discussed, as well as the possible role that new technology could have in finding the solution to this difficult problem.

A major challenge in the management of Alzheimer's disease (AD) is accurate diagnosis of the condition. Aging itself is associated with cognitive change, and physicians must first distinguish between age-associated complaints and true memory impairment as in AD before optimal management can begin. This article reviews tools used to assess and diagnose AD patients in both the primary care and clinical trial setting. AD assessment instruments commonly used in research may be too cumbersome for use in primary care. Tools specifically designed to meet the needs of busy practitioners that can accurately assess function, cognition, and global change will be reviewed. The issues of cognitive screening in old age and age-associated memory impairment will be discussed. Similarly, the pitfalls and advantages of routine cognitive screening in daily practice will be addressed.

The prevalence of Alzheimer's disease (AD) and dementia continues to rise. However, a significant number of patients are undiagnosed or untreated. Given the complexities of detecting cognitive impairment and the early signs of AD, this review discusses how advances in brain imaging can help assist in improving overall management. Imaging techniques and surrogate markers may provide unique opportunities to diagnose accurately AD in presymptomatic stages with practical consequences for patients, caregivers, and physicians. The possible outcomes for using imaging and surrogate markers as adjuncts to clinical examination and as screening tools for AD, as well as tangible and intangible advantages to early diagnosis and treatment, will be discussed. The specific value of using advanced serial imaging in patients with a genetic disposition to AD will be evaluated. If neurons can be protected from neurodegenerative damage in early stages, this may preserve patient cognition, function, and quality of life, and may confer considerable societal healthcare benefits.

Alzheimer's disease (AD) is a complex medical condition involving abnormalities in multiple biological and environmental domains. Current knowledge suggests that simultaneous intervention in these domains may be the most effective way to help AD patients and their families. Treatments for AD are centered on the inhibition of enzymes responsible for the degradation of acetylcholine—a neurotransmitter that is reduced in AD patients. Four cholinesterase inhibitors have been approved by the United States Food and Drug Administration, three of which are routinely used for the symptomatic treatment of mild-to-moderate AD. Strategies will be reviewed with regard to cognitive, functional, and behavioral domains. Providing a different treatment option for patients with AD, memantine is a low-to-moderate affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that has been approved for the treatment of moderate-to-severe AD. The clinical efficacy and tolerability of memantine monotherapy and combination therapy in patients with AD will be presented. Finally, the role of non-pharmacologic intervention will be discussed.