Normal Versus Pathological Aging of the Brain

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The line between normal and abnormal cognitive changes with age remains indistinct. Normal aging is due to physiological processes over a person’s lifetime, in which the biological clock controls development and survival of nerve cells. That does not exclude a spectrum of variable levels of health or a continuum within normal aging, as well as between normal and pathological aging. At one end there are individuals with “successful aging” [34]. At the other end, we find frail, easily incompensated people. According to the “threshold hypothesis” of normal aging, the reserve slowly diminishes and a critical level may be reached. Alternatively, someone may start with a low reserve and more easily reach the threshold for the clinical manifestation of dementia as they age [35,36]. Concepts such as “benign senescent forgetfulness” [37,38], “age associated mental impairment” (AAMI) [39–41] and “mild cognitive impairment” (MCI) have been adopted to indicate alternative interpretations of cognitive decline with increasing age. The criteria for AAMI, developed by a National Institute of Mental Health work group [39], were at least 50 years of age, complaints of memory loss in everyday life, memory performance on standardized tests at least one standard deviation below the average for young adults, and the absence of dementia. AAMI is not a widely accepted diagnostic entity [38,41], while MCI has become the most widely used concept in research on early cognitive deficits indicating an illness that leads to dementia [42]. AAMI is similar to the concept of age-related cognitive decline (ARCD) presented by DSM-IV (1994). MCI patients perform memory tasks at 1.5 standard deviations below age-matched controls that cover the spectrum between normal aging and dementia. Of the elderly population 5–10% develops dementia, and 4–12% of MCI patients are expected to develop AD each year [43–45]. An alternative to the MCI concept is that of “age-associated cognitive decline” (AACD)...
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