Neuropsychological and neuroimaging changes in preclinical Alzheimer's disease
Alzheimer's disease (AD) is a common, devastating form of dementia. With the advent of promising symptomatic treatment, the importance of recognizing AD at its very earliest stages has increased. We review the extant neuropsychological and neuroimaging literature on preclinical AD, focusing on longitudinal studies of initially nondemented individuals and cross-sectional investigations comparing at-risk with normal individuals. We systematically reviewed 91 studies of neuropsychological functioning, structural neuroimaging, or functional neuroimaging in preclinical AD. The neuropsychological studies indicated that preclinical AD might be characterized by subtle deficits in a broad range of neuropsychological domains, particularly in attention, learning and memory, executive functioning, processing speed, and language. Recent findings from neuroimaging research suggest that volume loss and cerebral blood flow or metabolic changes, particularly in the temporal lobe, may be detected before the onset of dementia. There exist several markers of a preclinical period of AD, in which specific cognitive and biochemical changes precede the clinical manifestations. The preclinical indicators of AD reflect early compromise of generalized brain integrity and temporal lobe functioning in particular. (JINS, 2006, 12, 707–735.)(Received November 15 2005)
(Revised March 13 2006)
(Accepted March 21 2006)
Key Words: Dementia; Neuropsychology; Magnetic resonance imaging; Positron emission tomography; Cognition disorders; Memory disorders.
c1 Correspondence and reprint requests to: Elizabeth W. Twamley, Ph.D., University of California, San Diego, Department of Psychiatry, 9500 Gilman Drive (0851), La Jolla, CA 92093. E-mail: [email protected]