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Early Markers Of Alzheimer Disease

$0Z01FY2005AGNIH

Aging

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Abstract

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. Section investigators examined the increased risk for dementia and Alzheimer's disease (AD) associated with symptoms of depression, although it is unclear whether depression represents an actual risk factor or a prodrome. To determine the relative hazard of premorbid depressive symptomatology for development of dementia and AD, we studied risk for incident dementia and AD over a 14-year period in 1,357 community-dwelling men and women participating in the 40-year prospective Baltimore Longitudinal Study of Aging. Screening for depressive symptoms, comprehensive medical and neuropsychological evaluations were prospectively collected every 2 years. Time-dependent proportional hazards of development of AD or dementia were calculated separately for men and women, with symptoms of depression detected at 2-, 4-, and 6-year intervals before onset of dementia symptoms. Vascular risk factors were analyzed as covariates. Premorbid depressive symptoms significantly increased risk for dementia, particularly AD in men but not in women. Hazard ratios were approximately two times greater than for individuals without history of depressive symptoms, an effect independent of vascular disease. We concluded that the impact of depressive symptoms on risk for dementia and AD may vary with sex. Section investigators developed a computerized method to help predict individuals at risk for developing Alzheimer's disease (AD). This method would be a valuable tool for clinicians in developing treatment plans for potential AD patients. Using the initial level and rates of change in visual memory performance, such a method could predict potential AD patients in a fast and inexpensive manner. A longitudinal case-control study of 52 female and 145 male participants was performed in a gerontology research center using premorbid tests of visual memory and neurologic examinations to identify individuals with and without dementia and AD. The classification method for each individual starts on the second examination and proceeds to compute that person's risk of AD one examination at a time based on all the follow-up information of the remaining individuals. By performing a crossvalidation study, the optimal combination of sensitivity and specificity derived from a receiver operating characteristic (ROC) curve showed 65% of the Alzheimer cases and 75% of the noncases were correctly classified for females, while 65 and 60% of cases and noncases, respectively, were correctly classified for males. Longitudinal measurements of cognition can be useful in detecting the presence of AD.

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