Several studies have demonstrated that Alzheimer?s disease is characterised by a long preclinical period during which cognitive deficits are already detectable. Retrospective analysis comparing cognitive performance of persons that develop Alzheimer disease compared to those that remain free of dementia, indicates preclinical deficits in Alzheimer disease in global indicators of cognitive functioning such as the Mini-Mental State Examination (MMSE), as well as for specific tasks assessing psychomotor functioning, perceptual speed, attention, verbal ability, reasoning, and visuospatial skill. Several studies indicate that the most pronounced deficit occurs in episodic memory, especially where a longer interval is examined between cognitive assessment and AD diagnosis. Figure 4 shows the difference in performance on episodic memory tasks (word recall, face recognition) in persons that go on to develop AD compared to persons that remain nondemented. Both three and six years before diagnosis AD subjects perform significantly worse than nondemented controls on tasks of episodic memory. These findings raise questions concerning whether and how it is possible to identify subjects in a preclinical phase of AD with high positive predictivity.

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