Alzheimer disease, in living color.
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Alzheimer Disease↗
Biomedical subjects
Scott A Small
Publications and source records attributed to Scott A Small.
Imaging correlates of brain function in monkeys and rats isolates a hippocampal subregion differentially vulnerable to aging.
The hippocampal formation contains a distinct population of neurons organized into separate anatomical subregions. Each hippocampal subregion expresses a unique molecular profile accounting for their differential vulnerability to mechanisms of memory dysfunction. Nevertheless, it remains unclear which hippocampal subregion is most sensitive to the effects of advancing age. Here we investigate this question by using separate imaging techniques, each assessing different correlates of neuronal function. First, we used MRI to map cerebral blood volume, an established correlate of basal metabolism, in the hippocampal subregions of young and old rhesus monkeys. Second, we used in situ hybridization to map Arc expression in the hippocampal subregions of young and old rats. Arc is an immediate early gene that is activated in a behavior-dependent manner and is correlated with spike activity. Results show that the dentate gyrus is the hippocampal subregion most sensitive to the effects of advancing age, which together with prior studies establishes a cross-species consensus. This pattern isolates the locus of age-related hippocampal dysfunction and differentiates normal aging from Alzheimer's disease.
Aging↗
Combining brain imaging with microarray: isolating molecules underlying the physiologic disorders of the brain.
Many diseases of the nervous system cause dysfunction by impairing neuronal physiology more than by altering brain anatomy--including age-related cognitive decline, most psychiatric disorders, and even the earliest stages of Alzheimer's disease. The absence of clear anatomical markers makes it difficult to identify targeted cells, which in turn impedes attempts to isolate the pathogenic molecules that cause physiologic disruption. Here we show how brain imaging and microarray can be used as complimentary techniques that together can characterize the cellular and molecular aspects of this class of diseases.
Adult↗
Quantifying cerebral blood flow: regional regulation with global implications.
In 1948, Seymour S. Kety and Carl F. Schmidt published back-to-back papers in the JCI that are widely acknowledged as landmarks. Upon publication, the studies resolved a century-old debate, irrefutably demonstrating that cerebral blood flow is regionally regulated. The reported findings turned out to be so powerful in their implications that they provided the inspirational spark that illuminated a brand-new field: functional brain imaging. Thus these papers are landmarks of the rarest kind, not only ending a controversy, but also giving birth to one of the most exciting fields within modern day neuroscience.
Carbon Dioxide↗
Imaging Alzheimer's disease.
Prior reviews on the topic of imaging and Alzheimer's disease have focused predominately on the technical features of imaging modalities or have summarized the results of epidemiologic studies. As brain scientists and brain practitioners, our main focus should be on the neurobiologic correlates of imaging, so we can intertwine this knowledge with our understanding of disease pathophysiology. A focus on these two features--the neurobiologic correlates of imaging and the pathophysiology of Alzheimer's disease--has provided the organizing principle of this review.
Alzheimer Disease↗
Imaging hippocampal function across the human life span: is memory decline normal or not?
Memory function commonly declines in later life. Whether memory decline represents a disease process or whether it is part of normal aging remains unknown. Here we answer this question by assessing the function of multiple subregions that make up the hippocampal circuit across the human life span. A newly developed MRI approach--designed to detect functional changes in individual hippocampal subregions--was used to assess the hippocampal circuit in 70 subjects between 20 and 88 years of age. Using strict parametric criteria, analysis revealed that function in two hippocampal subregions--the subiculum and the dentate gyrus--decline normally with age. In contrast, function in the entorhinal cortex declines pathologically. Single-subject analysis revealed that hippocampal dysfunction, found in 60% of elders was selectively correlated with memory decline. These results show that memory decline is caused by different mechanisms and suggests how memory decline should be approached clinically.
Adult↗
Reading level attenuates differences in neuropsychological test performance between African American and White elders.
The current study sought to determine if discrepancies in quality of education could explain differences in cognitive test scores between African American and White elders matched on years of education. A comprehensive neuropsychological battery was administered to a sample of African American and non-Hispanic White participants in an epidemiological study of normal aging and dementia in the Northern Manhattan community. All participants were diagnosed as nondemented by a neurologist, and had no history of Parkinson's disease, stroke, mental illness, or head injury. The Reading Recognition subtest from the Wide Range Achievement Test-Version 3 was used as an estimate of quality of education. A MANOVA revealed that African American elders obtained significantly lower scores than Whites on measures of word list learning and memory, figure memory, abstract reasoning, fluency, and visuospatial skill even though the groups were matched on years of education. However, after adjusting the scores for WRAT-3 reading score, the overall effect of race was greatly reduced and racial differences on all tests (except category fluency and a drawing measure) became nonsignificant. These findings suggest that years of education is an inadequate measure of the educational experience among multicultural elders, and that adjusting for quality of education may improve the specificity of certain neuropsychological measures.
Black or African American↗
The longitudinal axis of the hippocampal formation: its anatomy, circuitry, and role in cognitive function.
The ability to learn and access new memories requires an intact hippocampal formation, a complex three-dimensional structure that spans the anterior-posterior aspect of the temporal lobe. Historically, the transverse axis has dominated studies exploring mnemonic properties of the hippocampus, but in the last decade the importance of the long axis has been coming into focus. Anatomical and physiological findings are reviewed suggesting that the long axis functions as a circuit. Recent imaging studies investigating the long axis as a circuit are summarized, pointing to specific mechanisms that can account for how the hippocampus associates separate sensory input during memory acquisition and recall.
Animals↗
Acquisition, recall, and forgetting of verbal information in long-term memory by young, middle-aged, and elderly individuals.
Memory performance by four age groups (30-45 years, 46-60 years, 61-75 years, and 76-90 years) was compared on a multi-trial verbal recall task with 20-minute and 1-day delay free recall and recognition trials. The rate of acquisition across 5 learning trials was similar for all ages except the youngest group whose performance was constrained by a ceiling effect. The level of acquisition achieved was less in the two oldest groups. Words gained across trials and words lost across trials made similar contributions to the shape of the learning curve for the acquisition trials. Subjective organization decreased with age, but remained strongly related to the number of words recalled during acquisition for all age groups. The two oldest age groups demonstrated significant declines in words recalled on the 20-minute and 1-day delay trials. A subset of the oldest group demonstrated more rapid forgetting at the 1-day delay when participants from all age conditions were matched on acquisition. Thus, many aspects of free recall were impaired with age, and variance measurement of recall showed greater inter-individual differences with increasing age. This increase in individual differences could reflect a single form of age-related memory impairment, or it could indicate that memory impairment in the elderly is due to multiple processes. The importance of testing across the life span and using tests that examine a variety of memory components and processes for establishing norms and clarifying age-related deficits are discussed.
Adult↗
Measuring correlates of brain metabolism with high-resolution MRI: a promising approach for diagnosing Alzheimer disease and mapping its course.
As we enter the pharmacological era for the treatment of Alzheimer disease (AD), there is a growing urgency to diagnosis AD as early as possible. The ability to visualize the living brain with imaging techniques holds great promise in detecting the first lesions caused by AD and, because mapping the course of the disease over time is important for testing drug efficacy, imaging is potentially useful in drug development. In the last few years, we have been exploring imaging approaches designed to map AD's effect on the living brain. Here, these attempts will be reviewed, highlighting the advantages but also the potential pitfalls of imaging a dysfunctional brain.
Alzheimer Disease↗