Early Markers Of Alzheimer Disease

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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. To characterize the relationship between age-related memory change and repeat testing, we investigated longitudinal change and the effects of age, sex, education, and repeat testing on new learning and recall by analyzing measures of verbal learning and interference, short and long-delay free and cued recall and recognition hits in separate mixed-effects regressions. We found cross-sectional effects of age (p<0.001) and sex (p<0.05) on learning and interference, regardless of baseline performance. Younger adults outperformed older adults, and women outperformed men. There were longitudinal age changes across total learning, long-delay free and cued recall regardless of baseline scores (p<0.05). In addition, controlling for baseline scores enhanced the sensitivity for detection of longitudinal age changes on short-delay cued recall and recognition hits (p<0.05). The influence of repeated administrations changed with advancing baseline age for total learning and short and long-delay recall such that younger baseline age was associated with improvement over time while older baseline age was associated with decline over time. There are declines in verbal learning performance associated with normal aging that are influenced by baseline age. Failing to account for the influence of repeat testing with aging may decrease sensitivity to detect pathological decline. Section investigators developed a computerized method to help predict individuals at risk for developing Alzheimer's disease based on longitudinal changes in memory as tool for clinicians in managing treatment plans for potential dementia AD patients. Using the initial level and rates of change in visual memory performance, we performed longitudinal case-control study of 52 women and 145 men using pre-morbid tests of visual memory and neurological 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 cross-validation study and using the optimal combination of sensitivity and specificity derived from a receiver operating characteristic (ROC) curve, 65% of the Alzheimer cases and 75% of the non-cases were correctly classified for females, while 65% and 60% of cases and non-cases, respectively, were correctly classified for males. Section investigators used virtual environment (VE) technology to assess spatial navigation in humans to quantify age-related deficits in human spatial navigation and to promote a comparative approach to the neuroscience of cognitive aging. We assessed age differences in navigational behavior in a VE and examined the relationship between this navigational measure and other more traditional measures of cognitive aging. Following pre-training, participants were confronted with a VE spatial learning task and completed a battery of cognitive tests. The VE consisted of a richly textured series of interconnected hallways, some leading to dead ends and others leading to a designated goal location in the environment. Compared to younger participants, older volunteers took longer to solve each trial, traversed a longer distance, and made significantly more spatial memory errors. After 5 learning trials, 86% of young and 24% of elderly volunteers were able to locate the goal without error. Performance on the VE navigation task was positively correlated with measures of mental rotation and verbal and visual memory.