A wealth of evidence demonstrates that a prodromal period of Alzheimer's disease (AD) exists for some years prior to the appearance of significant cognitive and functional declines required for the clinical diagnosis. This prodromal period of decline is characterized by a number of different neuropsychological and brain changes, and reliable identification of individuals prior to the development of significant clinical symptoms remains a top priority of research. In this review we provide an overview of those neuropsychological changes. In particular, we examine specific domains of cognition that appear to be negatively affected during the prodromal period of AD, and we review newer analytic strategies designed to examine cognitive asymmetries or discrepancies between higher-order cognitive functions versus fundamental skills. Finally, we provide a critical examination of the clinical concept of Mild Cognitive Impairment and offer suggestions for an increased focus on the impact of cerebrovascular disease (CVD) and CVD risk during the prodromal period of AD.

For nearly a century, the primary method employed by psychologists to define and test the validity of constructs evaluated by assessment instruments has been shared-variance techniques such as intervariable correlations or factor analysis with large normative or mixed clinical samples. To illustrate the shortcomings of this approach, we conducted (1) correlational analyses of immediate- and delayed-memory measures separately in normal participants and in homogeneous samples of patients with either Alzheimer's disease or Huntington's disease; and (2) factor analysis of immediate and delayed-recall and recognition measures in a large, homogeneous sample of patients with Alzheimer's disease. The findings revealed that cognitive measures that share variance in the intact brain-thereby giving the facade of assessing a unitary construct-can dissociate and contribute to unique variance in the damaged brain, but only if the pathology occurs in brain regions known to disrupt vital cognitive processes tapped by those measures. The results illustrate that shared-variance procedures applied to normal or mixed clinical populations can mask some of the most vital cognitive constructs, such as the classic distinction between short- and long-term memory. Implications of these findings for research and clinical practice are discussed.

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