What are the boundary zones between normal aging and Alzheimer's disease (AD)? Are many elderly people whom we regard as normal actually in the early stages of AD? Alzheimer's disease does not develop overnight; the early phases may last for years or even decades. Recently, clinical investigators have identified a transitional condition between normal aging and and very early Alzheimer's disease that they have called mild cognitive impairment, or MCI. This term typically refers to memory impairment beyond what one would expect in individuals of a given age whose other abilities to function in daily life are well preserved. Persons who meet the criteria for mild cognitive impairment have an increased risk of progressing to Alzheimer's disease in the near future. Though many questions about this condition and its underlying neuropathology remain open, full clinical trials are currently underway worldwide aimed at preventing the progression from MCI to Alzheimer's disease. This book addresses the spectrum of issues involved in mild cognitive impairment, and includes chapters on clinical studies, neuropsychology, neuroimaging, neuropathology, biological markers, diagnostic approaches, and treatment. It is intended for clinicians, researchers, and students interested in aging and cognition, among them neurologists, psychiatrists, geriatricians, clinical psychologists, and neuropsychologists.
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Ronald C. Peterson is at Mayo Clinic and Medical School.From The New England Journal of Medicine:
During the past two decades, the diagnosis of Alzheimer's disease and the characterization of patients with this disease have progressed to the point where we now feel capable of identifying and describing the presymptomatic stage of the disease and distinguishing persons with it from elderly persons who are healthy and cognitively unaffected. Mild Cognitive Impairment, a compendium of 12 well-indexed chapters written by leading clinicians and neuropsychologists in the fields of human aging and dementia, provides the latest data and informed commentary on how to make this distinction. In 1962, V.A. Kral classified certain elderly persons with subtle changes in memory as having "benign senescent forgetfulness." Such changes are now seen in a more sinister light and are considered to represent "mild cognitive impairment." Most of the authors of this book believe that mild cognitive impairment is often pathologic and is likely to be a prodrome of Alzheimer's disease. One problem with this, however, is that there is no consensus on the definition of mild cognitive impairment. A group from the Mayo Clinic focuses on problems with memory, but Peterson indicates that the condition can also affect multiple cognitive domains or even a single nonmemory domain. Cummings adds changes in mood, personality, and emotion as potential markers of mild cognitive impairment. Another problem concerns the unaffected population from which persons with mild cognitive impairment are to be distinguished. Confusion is introduced in this regard by Smith and Ivnik, as well as other contributors to the book, who consider "normal" or "representative" elderly persons as a potential comparison group for persons with mild cognitive impairment, although these "normal" persons may have diabetes, hypertension, or other diseases that can affect cognitive ability. It would have been more useful if the authors had agreed to use as a comparison group only "healthy" elderly persons who are free of such diseases. A third problem follows from the use of different criteria in the cognitive tests for dementia that have been used to identify mild cognitive impairment. Because of these limitations, the success rates in identifying mild cognitive impairment as a prodrome of Alzheimer's disease on the basis of follow-up data vary widely among institutions. A Mayo Clinic study reported that dementia developed in 80 percent of their study cohort with mild cognitive impairment within six years after the initial diagnosis, whereas a study in Bordeaux, France, showed a 60 percent rate of conversion to Alzheimer's disease within five years after diagnosis. In other studies with average follow-up periods of two to two and a half years, as Johnson and Albert note, the conversion rate was only 24 to 41 percent. Clearly, the diagnostic criteria for distinguishing mild cognitive impairment as a presymptomatic stage of Alzheimer's disease are evolving; this evolution and its likely directions are elaborated in this book. Other markers, in addition to cognitive tests, that might be used in discriminant-function analysis to identify the condition include elevated brain myo-inositol levels on magnetic resonance spectroscopy, brain atrophy on magnetic resonance imaging, reduced blood flow in the brain and reduced metabolism on positron-emission tomography or single-photon-emission computed tomography, altered cerebrospinal fluid concentrations of tau and phosphorylated tau proteins and of beta-amyloid peptide, and (as a risk factor) the presence of the (epsilon)4 allele of the gene encoding apolipoprotein E. Future studies with longitudinal follow-up should clarify which markers will be the most useful. Stanley I. Rapoport, M.D.
Copyright © 2003 Massachusetts Medical Society. All rights reserved. The New England Journal of Medicine is a registered trademark of the MMS.
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