Appraisal of cognition in preclinical Alzheimer's disease: a conceptual review.

Biomarker evidence and clinical observations support the hypothesis that there is a diagnosable condition termed preclinical Alzheimer's disease (AD). Recently, a workgroup convened under the auspices of the National Institute on Aging and the Alzheimer's Association proposed a framework for defining preclinical AD. The definition was based on the presence of biomarkers that are indicative of the AD pathophysiological process. In the context of abnormal AD biomarkers, the workgroup postulated that 'subtle cognitive changes' occurred as well. Based on studies of genetically at-risk individuals and those destined to become demented, who were observed while still cognitively normal, low performance on learning and memory functions may be the earliest cognitive manifestations of preclinical AD, at the group level at least. It is not clear whether subtle cognitive decline can be detected reliably on an individual basis. Preclinical AD cognitive changes could be diagnosed by traditional neuropsychological testing, computerized testing, assessments of subjective memory loss, assessments of levels of participation in cognitively stimulating activities and direct measurement of activity using recently developed monitoring technology. Confounding effects of normal aging, test-retest variability, variations in educational attainment, as well as the presence of other brain diseases make diagnosing cognitive decline due to preclinical AD challenging.