Down syndrome and Alzheimer's disease: a link between development and aging

A subset of aged individuals with Down syndrome (DS) exhibits the clinical features of Alzheimer's disease (AD) but our ability to detect dementia in this population is hampered by developmental differences as well as the sensitivity of existing test tools. Despite the apparent clinical heterogeneity in aged individuals with DS, age-associated neuropathology is a consistent feature. This is due to the fact that trisomy 21 leads to a dose-dependent increase in the production of the amyloid precursor protein and subsequently the production of the amyloidogenic fragments leading to early and predominant senile plaque formation. A review of the existing literature indicates that oxidative damage and neuroinflammation may interact to accelerate the disease process particularly in individuals with DS over the age of 40 years. By combining clinical information with measures of brain-region specific neuropathology we can "work backwards" and identify the earliest and most sensitive clinical change that may signal the onset of AD. For the past 50 years, investigators in the fields of mental retardation, developmental disabilities, and aging have been interested in the curious link between AD and DS. The morphologic and biochemical origins of AD are seen in the early years of the lifespan for individuals with DS. Study of the process by which AD evolves in DS affords an opportunity to understand an important link between development and aging. This review will focus on advances in the molecular and clinical basis of this association.     

Gray matter correlates of fluid,crystallized, and spatial intelligence: Testing the P-FIT model

The parieto-frontal integration theory (P-FIT) nominates several areas distributed throughout the brain as relevant for intelligence. This theory was derived from previously published studies using a variety of both imaging methods and tests of cognitive ability. Here we test this theory in a new sample of young healthy adults (N = 100) using a psychometric battery tapping fluid, crystallized, and spatial intelligence factors. High resolution structural MRI scans (3T) were obtained and analyzed with Voxel-based Morphometry (VBM). The main findings are consistent with the P-FIT, supporting the view that general intelligence (g) involves multiple cortical areas throughout the brain. Key regions include the dorsolateral prefrontal cortex, Broca's and Wernicke's areas, the somato-sensory association cortex, and the visual association cortex. Further, estimates of crystallized and spatial intelligence with g statistically removed, still share several brain areas with general intelligence, but also show some degree of uniqueness.     

The Conceptual Project in Child Variance

This report covers highlights from a survey of the literature on emotional disturbance. The survey was begun in 1970 by the Conceptual Project in Child Variance at the University of Michigan. The Project has developed the survey to serve both as a model for graduate student training and as a source of materials for graduate level programs across the United States. Results are being published in a four-volume work, A Study of Child Variance,which examines theories, intervention practices, and service delivery systems, and presents an overview with a look toward the future. The activities of the graduate students and of professional workshop groups are described, and a summary of Project materials is also reported.This study was prepared under grants 0EG-0-70-4806(603), 0EG-0-71-3680(603), and 0EG-0-72-3680(603) from the Bureau for Education of the Handicapped, U.S. Office of Education. The project is located in the Institute for the Study of Mental Retardation and Related Disabilities at the University of Michigan, Ann Arbor. This support is gratefully acknowledged.     

Landmark Discrimination Learning in the Dog

Allocentric spatial memory was studied in dogs of varying ages and sources using a landmark discrimination task. The primary goal of this study was to develop a protocol to test landmark discrimination learning in the dog. Using a modified version of a landmark test developed for use in monkeys, we successfully trained dogs to make a spatial discrimination on the basis of the position of a visual landmark relative to two identical discriminanda. Task performance decreased, however, as the distance between the landmark and the “discriminandum” was increased. A subgroup of these dogs was also tested on a delayed nonmatching to position spatial memory task (DNMP), which relies on egocentric spatial cues. These findings suggest that dogs can acquire both allocentric and egocentric spatial tasks. These data provide a useful tool for evaluating the ability of canines to use allocentric cues in spatial learning.     

Size and reversal learning in the beagle dog as a measure of executive function and inhibitory control in aging

Several studies converge on the idea that executive processes age earlier than other cognitive processes. As part of a larger effort to investigate age-related changes in executive processes in the dog, inhibitory control was measured in young, middle-aged, old, and senior dogs using size discrimination learning and reversal procedures. Compared to young and middle-aged dogs, old and senior dogs were impaired on both the initial learning of the size task and the reversal of original reward contingencies. Impaired performance in the two aged groups was characterized as a delay in learning the correct stimulus-reward contingencies and, among the senior dogs in particular, an increase in perseverative responding. These separate patterns of reversal impairments in the old and senior dogs may reflect different rates of aging in subregions of the frontal cortex.     

Evidence for a detrimental relationship between hypertension history, prospective memory, and prefrontal cortex white matter in cognitively normal older adults

Hypertension affects many older adults and is associated with impaired neural and cognitive functioning. We investigated whether a history of hypertension was associated with impairments to prospective memory, which refers to the ability to remember to perform delayed intentions, such as remembering to take medication. Thirty-two cognitively normal older adult participants with or without a history of hypertension (self-reported) performed two laboratory prospective memory tasks, one that relied more strongly on executive control (nonfocal prospective memory) and one that relied more strongly on spontaneous memory retrieval processes (focal prospective memory). We observed hypertension-related impairments for nonfocal, but not focal, prospective memory. To complement our behavioral approach, we conducted a retrospective analysis of available structural magnetic resonance imaging data. Lower white matter volume estimates in the anterior prefrontal cortex were associated with lower nonfocal prospective memory and with a history of hypertension. A history of hypertension may be associated with worsened executive control and lower prefrontal white matter volume. The translational implication is that individuals who must remember to take antihypertensive medications and to monitor their blood pressure at home may be impaired in the executive control process that helps to support these prospective memory behaviors.     

A Comparison of Simultaneous Prompting and Constant Time Delay Procedures in Teaching State Capitals

This investigation compared the effectiveness and efficiency of constant time delay (CTD) and simultaneous prompting (SP) procedures in teaching discrete social studies facts to 4 high school students with learning and behavior disorders using an adapted alternating treatments design nested within a multiple probe design. The results indicated that both procedures were effective, with the simultaneous prompting procedure being slightly more efficient in terms of errors during instructional and maintenance phases. In addition, when interviewed about their preferences, both the instructor and participants preferred the simultaneous prompting procedure. This investigation extends current research as there are small numbers of studies comparing SP to other response prompting strategies, and to date, SP and CTD have not been compared with high school students with high-incidence disabilities. Future research issues are discussed.