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Alzheimer's Disease: Current Concepts & Future Directions

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Neurodegenerative Disorders of Aging: The Down Side of Rising Longevity

The exact causes of neurodegeneration remain the focus of much investigation, but as nerve cells have some of the highest metabolic rates in the human body, one possibility links the lifetime "wear and tear" on these cells

by John C. Morris, MD

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The United States (U.S.) population is undergoing a demographic revolution, with ever-growing numbers of adults living to age 65 and beyond such that the proportion of older adults in our society will increase from 13% in 2010 to 20% by 2040. All-race U.S. life expectancies, also increasing, already are 81 years for women and 76 years for men. There thus not only are many more older adults, they are living longer. Longevity brings increasing risk for neurodegenerative disorders, in which nerve cells (neurons) deteriorate and die.

The exact causes of neurodegeneration remain the focus of much investigation, but as nerve cells have some of the highest metabolic rates in the human body, one possibility links the lifetime “wear and tear” on these cells to a failure to produce sufficient bioenergetics and to successfully neutralize byproducts of metabolism, such as free radicals, necessary to maintain neuronal health. Such a notion is consistent with the marked association with increasing age of the most common (and most feared) neurodegenerative disorder, Alzheimer's disease (AD).

AD already is a public health menace of the highest order, as the disease costs over $200 billion a year in the U.S. to care for its victims. It is by far the most common cause of dementia and, alone among the leading causes of death, lacks any effective therapy to materially slow or halt its course or to prevent its occurrence. It is a disorder unique to humans, as the most highly developed brain cells in higher order association cortex are most vulnerable to the disease process. As synapses and neurons gradually degenerate and die, their brain functions become gradually impaired and eventually lost.

Hence, the clinical presentation of the illness is reflected in the gradual onset and inevitable progression of the clinical manifestations of the deteriorating function of higher order association cortex: impaired memory, insight, attention, reasoning, language, and personality. As the disease progresses over the typical seven to ten years from onset to death (AD is universally fatal), eventually other brain areas are affected and the individual loses the ability to control sphincters, swallow, talk, or walk. It is so feared because the affected individual gradually but steadily loses their autonomy and their very personhood, becoming ever more dependent and disabled.

Alzheimer's disease currently is diagnosed based on its dementia syndrome: the gradual onset and progression of memory and other cognitive impairment, representing a decline for that individual from previously attained abilities, which is sufficient to interfere with the performance of accustomed activities. However, this diagnostic process is time-consuming and inexact; it is estimated that 50% of all individuals with AD dementia remain to be diagnosed by their physicians.

The Knight Alzheimer's Disease Research Center (ADRC) at Washington University in St. Louis is working to improve dementia diagnosis and management and to translate these improvements to our clinician colleagues. This work focuses on enhancing the tools needed to accurately identify persons with AD and in developing and evaluating mechanism-based therapies that one day may provide truly effective therapy for this disorder. This model of better recognition of neurodegenerative dementing disorders and related diseases ultimately will result in better management, and better management will lead to better understanding of the responsible etiologies. In this way, we ultimately can develop drugs that offer meaningful benefit and perhaps even may prevent these devastating diseases.

 

Published October 29, 2013

 

John C. Morris, MD, MSMA member since 2007, is the Friedman Distinguished Professor of Neurology and the Director of the Knight Alzheimer’s Disease Research Center at Washington University School of Medicine.

 

Editor's note: This article is part of a special series brought to you by Missouri Medicine, the Journal of the Missouri State Medical Association (MSMA). MedHelp, Missouri Medicine, and MSMA are collaborating to educate and empower health consumers by making the latest scientific studies and medical research available to the public. Learn more about MSMA and see more from Missouri Medicine.

These articles originally appeared in the September/October 2013 issue of Missouri Medicine and are reprinted with permission.

 

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