marker status over time can then be correlated with development of dementia. For example, it may be found that subjects who develop dementia will have had a combination of greater-than-average rate of progression of VBR as well as a 4-point worsening of ADAS score with scopolamine challenge. Or, more simply, those who develop dementia might be found to have a yearly 2-second worsening in trailmaking ability. For practical reasons, some studies, such as scopolamine challenge and CSF neuropeptide determination, will be difficult to obtain longitudinally in large numbers of subjects. Other markers, such as neurocognitive testing, can readily be followed longitudinally if an appropriate cohort can be recruited.
If a marker or combination of markers can be found that can predict development of dementia in a high-risk group, these would need to be studied in the elderly population in general to determine specificity for AD and possible utility as a general screening test. As presented here, the most robust or interesting markers for study include scopolamine sensitivity, cognitive measures including delayed recall and trailmaking, hypercortisolemia or dexamethasone resistance, rate of change of VBR, olfactory acuity, and immune factors including neural antibodies and ACT levels. These potential markers should be studied longitudinally in groups of first degree relatives of well-characterized AD patients, in multicenter trials.
Preparation of this manuscript was supported by NIH grants AG-02219 and AG-05138.
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