Anatomical changes underlying dementia in Alzheimers disease

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Bradley T. Hyman1

The severity of the clinical problem of Alzheimer's disease (AD) is astounding: the Alzheimer's Association estimates that 1 in 10 Americans is affected by someone with AD in their family. Despite decades of research and advances in the cell biology and genetics of AD, current medications provide only subtle symptomatic benefits. Studies of the natural history of the illness present an even more worrisome image: the pathologic changes of AD begin years prior to the emergence of overt clinical symptoms. New imaging modalities (PIB amyloid PET scans, quantitative MRI scans, etc.) and more sensitive clinical instruments are pushing the diagnosis of AD earlier in the course, leading to an explosion of recognition of the illness in its earliest stages that makes the need for disease-modifying interventions even more pressing. The key to successful prevention and treatment is understanding what causes dementia. The major theme of this chapter is to examine ideas about the pathological substrates of impaired brain function in AD, with special emphasis on those issues that may well prove amenable to therapeutic intervention.

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