Age-related neuropathology, cognitive decline, and Alzheimer's disease

In the last 20 years, there have been tremendous strides made in the understanding of the molecular and cellular processes that occur during brain aging, as well as our understanding of age-related disorders of the central nervous system (CNS). Aging is associated with a decline in cognitive performance, and is the biggest risk factor for the development of Alzheimer's disease (AD), although the underlying basis for both of these observations is poorly defined. Both normal aging and AD are associated with overlapping and increased levels of pathology. Numerous reports have now linked elevations in pathology as potential mediators of cognitive decline in the elderly, with most studies focusing on the role of AD-related pathology. However, it is important to point out that there are numerous other pathological features observed in the aging brain including corpora amylacea, argyrophilic grains, neuromelanin, and lipofuscin. In this review, I discuss the decreased cognitive performance observed during normal aging, the potential for pathology to alter neuronal function and neuronal viability during normal brain aging, and the potential for common pathologies to either inhibit or promote the development of age-related disorders such as AD. (c) 2005 Elsevier Ireland Ltd. All rights reserved.