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Benefits of Early Pharmacological Treatment in Alzheimer Disease

Benefits of Early Pharmacological Treatment in Alzheimer Disease

As the aging of the world population continues, the number of people affected by dementia is likely to steadily increase. It is estimated that there are 4.5 million affected people in United States alone and that this number will triple in the first half of this century. Alzheimer disease (AD), the most common form of dementia, remains a major public health challenge internationally. This disease not only exacts a heavy toll on patients but also causes anguish to millions of caregivers and costs society more than $100 billion annually in the United States alone.1

Dementia refers to a generally chronic syndrome characterized by a decline in intellectual functioning that is substantial enough to interfere with a person's ability to perform usual and daily activities. Depending on the underlying cause, the clinical course can be static or progressive. AD is clinically characterized by an insidious onset and progressive decline. The identified neuropathological hallmarks of this disease include extracellular amyloid plaques, intracellular neurofibrillary tangles, and an associated loss of neurons. Eventually all aspects of the affected individual's life are involved to the extent that he or she becomes dependent on care providers for the most basic activities of daily life (Table 1). The psychiatric symptoms of a patient with AD often result in caregiver burnout and may lead to the patient's placement in a supervised living facility.2

Early treatment begins with early detection
Successful intervention requires an early and timely diagnosis. Caregivers of persons with AD often state that an average of 2 years passes from the onset of symptoms to a formal diagnosis.3 Similarly, it is recognized that pathological changes of AD begin to appear years or decades before a clinical diagnosis is made.4 Thus, early diagnosis remains a challenge.5 Clinicians may fail to recognize the earliest signs of AD or may feel uncomfortable diagnosing AD because of a lack of standard assessment tools, time and reimbursement constraints, and fears that a diagnosis of dementia may open a Pandora's box. Alternatively, patients and families may not report cognitive problems, either because they are in denial or they fear stigmatization.

We do not know what causes AD, but the past 2 decades have seen remarkable progress in our understanding of its origin and treatment. A major focus of research is to refine our ability to identify the illness at the earliest point by using biological and imaging markers. In terms of treatment, the ideal solution is to effectively prevent the disease and limit the number of new cases. Although some risk factors have been identified,6 we may not yet have the ability to prevent the disease before it develops (primary prevention); the focus, therefore, is on maximizing the effectiveness of available treatments for symptomatic patients and identifying those in transition to or at risk for progression to AD (secondary prevention). Current available treatments (cholinesterase inhibitors and memantine) limit the devastation that is unleashed by this disease (tertiary prevention). Mild cognitive impairment (MCI) is increasingly being recognized as a prodrome to dementia but is not an FDA-approved indication for treatment with the above agents. In addition to symptomatic treatments, several disease modification strategies are under clinical investigation.

Defining success
AD is not merely a cognitive disorder (Table 1). The data from regulatory trials of antidementia agents may not look impressive unless success is defined in broader terms. In the absence of a cure, both improvement and slower rate of decline over time are positive therapeutic outcomes (Figure). Recent studies of antidementia agents have addressed some of the limitations of regulatory trials in an effort to enhance their clinical relevance. Inclusion of broader patient populations,7,8 extended period of observation,9,10 and use of behavioral, caregiver, and economic outcomes11-13 have helped redefine "success." On average, untreated patients decline relentlessly, whereas treated patients tend to show a less progressive deterioration. We now have the ability to stabilize cognitive function in a substantial percentage of patients and limit long-term disability for at least 1 year. Put simply, these treatments work reasonably well.14-16

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