Early Markers Of Alzheimer Disease

Aging

Investigators

Linked publications & trials

Abstract

Summary of work: Alzheimer's disease (AD) is the most widespread among several neurological degenerative diseases (dementias) that occur principally at later ages, occasionally before 60, but more frequently after age 70. This study examines prospective psychological, neurological, and neuropsychological changes in participants from the Baltimore Longitudinal Study of Aging (BLSA). Neurological and neuropsychological examinations are administered to participants aged 60 and older, repeating many of the tests that were administered to these subjects at earlier ages. Diagnoses of probable Alzheimer's disease follow the NINCDS-ADRDA criteria. In a follow-up to previous findings on a small sample, Section investigators examined premorbid neuropsychological test scores in order to determine whether long term deficits in the Benton Visual Retention Test predicted the development of Alzheimer?s disease decades later in participants from the Baltimore Longitudinal Study of Aging. The relative risks for Alzheimer?s disease associated with making 6 or more visual memory errors versus less than 6 errors at 1 to 3, 3 to 5, 5 to 10, and 10 to 15 years before the diagnosis of AD were 5.69, 2.11, 1.76, and 1.83 respectively (p<0.05). The relative risk for 15 or more years before diagnosis was not significant (p>0.10). A greater number of visual memory errors are associated with an increased risk of AD up to 15 years later. These findings suggest that poor visual memory performance may represent an early expression of AD years before diagnosis and point to the possibility of an increased window of opportunity for preventive treatment before definitive diagnosis. We also investigated executive function measures emphasizing Alpha Span to understand relationships among executive and non-executive tasks. Non-demented elderly participants (N=417) received a comprehensive cognitive battery. Partial correlations adjusting for age and vocabulary revealed associations among Alpha Span, WAIS-R Digit Span subtests, and fluency tasks. Component analysis with orthogonal rotation revealed a 4 component solution (86% of the variance) with executive variables contributing to all loadings. We performed regression analyses with calculated component indices predicting ASp performance. After accounting for age (6% of the variance), a component reflecting brief attention and mental manipulation accounted for 13% of variance in Alpha Span; other components accounted for small proportions of variance, 11% for verbal language ability, 2% for sustained attention/mental tracking, and <1% for visuo-perceptual spatial organization and planning. Results emphasize the importance of considering executive and non-executive aspects of cognition in understanding executive functioning.