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Despite the exponential growth of knowledge about late-onset sporadic Alzheimer disease (AD), the factors that promote its development remain largely elusive. Drachman stresses the importance of considering sporadic AD in the context of its most potent risk factor, advancing age. In this vein, he reviews age-related changes (ARCs) and their impact on neuronal vulnerability, brain structure, and cognition.
Drachman divides ARCs into intrinsic and extrinsic forms. Intrinsic ARCs are programmed, predictable declines in neuronal function and other biologic processes, including telomeric shortening, which leads to a reduced supply of neural stem cells and to neuronal apoptosis. Extrinsic ARCs are the less predictable results of “wear and tear” or…