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During the early development of medicine, clinical diagnosis relied on symptoms, history, as well as the visual, auditory, tactile, and olfactory skills of the physician. More recently, advances of technology led to the development of the stethoscope, EKG machine, X-ray, etc. Another line of technology involved measurements of electrolytes and other substances in blood, urine and other body fluids. Most areas of medicine have greatly benefited from these advances especially and the diagnosis of Alzheimer's disease primarily uses clinical information. Fortunately, this situation is now undergoing rapid evolution. There are a number of candidate biomarkers which can be used for diagnosis, early detection, or monitoring progression of Alzheimer's disease. Structural MRI demonstrates hippocampal atrophy in demented and mildly impaired subjects.. Flurodeoxyglucose PET shows reduced glucose metabolism in the posterior cingulate gyrus and hippocampal regions. Recent studies with C-11 PIB and F18 amyloid ligands suggest that the brain amyloid load may be quantified. As expected, subjects with Alzheimer's almost all have high amyloid loads detected by such imaging techniques. A high fraction of MCI and a lower fraction of normal elderly also have high brain amyloid. Measurements of CSF obtained by lumbar puncture show that patient's with Alzheimer's disease have low CSF amyloid and elevated tau and phosphotau. A variety of proteins and other substances in blood also appear to change in Alzheimer's disease. For many years its been known that many elderly subjects who appear cognitively normal for age, have evidence of Alzheimer's pathology at autopsy. An important question is: do normal elderly subjects with evidence for Alzheimer's pathology (e.g. small hippocampus, reduced posterior cingulate glucose metabolism, reduced CSF amyloid and elevated tau etc) have a higher risk for cognitive decline and ultimate conversion to dementia? Similarly, do subjects with MCI who have biomarker/imaging evidence for Alzheimer's pathology have a higher risk for future converstion to dementia? This special (1-17) issue focuses on the use of various imaging techniques and biomarkers for Alzheimer's disease clinical trials. In this setting imaging/biomarkers have at least 4 uses:

Imaging and biomarkers will be used for detection and monitoring progression of early Alzheimer’s disease