Selected publications

A sample of some recently-published articles based on our research.

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Temporospatial components of brain ERPs as biomarkers for Alzheimer’s disease

Published in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, 2018

In this paper, we combined ERPs from multiple different scalp locations (electrodes) through two-step temporospatial Principal Components Analysis (PCA). Our goal was to determine if we could achieve increased accuracy in detecting early-stage Alzheimer’s disease with enhanced brain spatial information. We found this approach did significantly improve upon results using only one electrode. This paper provides insight into not only what is different in the brain with the onset of AD but also where these changes are occuring.

Chapman, Robert M., Gardner, Margaret N., Klorman, Rafael, Mapstone, Mark, Porsteinsson, Anton P., Antonsdottir, Inga M., & Kamalyan, Lily. (2018). Temporospatial components of brain ERPs as biomarkers for Alzheimer’s disease. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, 10, 604-614.

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ERP C250 shows the elderly (cognitively normal, Alzheimer’s disease) store more stimuli in short-term memory than Young Adults do

Published in Clinical Neurophysiology, 2016

We continued our analysis of ERP component C250 as a measure of short-term memory storage by extending our investigation to elderly with healthy cognition and those with Alzheimer’s Disease. Here we found large changes between young adults and healthy elderly such that healthy elderly individuals ended up storing more information in short-term memory as indexed by C250 amplitudes than young adults did. There was also a marked decrease in C250 activity to stimuli that should be stored in short-term memory in individuals with AD, suggesting C250 might be a useful indicator of cognitive decline.

Chapman, Robert M., Gardner, Margaret N., Mapstone, Mark, Klorman, Rafael, Porsteinsson, Anton, Dupree, Haley M., . . . Kamalyan, Lily. (2016). ERP C250 shows the elderly (cognitively normal, Alzheimer's disease) store more stimuli in short-term memory than young adults do. Clinical Neurophysiology, 127, 2423-2435.

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Memory timeline: Brain ERP C250 (not P300) is an early biomarker of short-term storage

Published in Brain Research, 2015

In this paper, we investigated ERP component C250 as a marker of short-term memory storage. This work was principally focused on young individuals. We found this ERP component produces larger amplitudes for stimuli that are stored in short-term memory than for stimuli that are not. C250 is distinct from other ERP components typically involved in memory operations, most notably P300, and it occurs earlier in the sequence of ERP components related to information processing. This could prove a valuable tool in studying how aging and dementia affect the key act of storing important information in memory.

Chapman, Robert M., Gardner, Margaret N., Mapstone, Mark, Dupree, Haley M. & Antonsdottir, Inga M.. (2013). Memory timeline: Brain ERP C250 (not P300) is an early biomarker of short-term storage. Brain Research 10(7), 732-741.

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The impact of AD drug treatments on event-related potentials as markers of disease conversion

Published in Current Alzheimer Research, 2013

This paper investigates how commonly prescribed pharmacologic treatments for Alzheimer’s disease (AD) affect Event-Related Potential (ERP) biomarkers as tools for predicting AD conversion in individuals with Mild Cognitive Impairment (MCI). We gathered baseline ERP data from two MCI groups (those taking AD medications and those not) and later determined which subjects developed AD (Convert->AD) and which subjects remained cognitively stable (Stable). We utilized a previously developed and validated multivariate system of ERP components to measure medication effects among these four subgroups. Discriminant analysis produced classification scores for each individual as a measure of similarity to each clinical group (Convert->AD, Stable), and we found a large significant main Group effect but no main AD Medications effect and no Group by Medications interaction. This suggested AD medications have negligible influence on this set of ERP components as weighted markers of disease progression. These results provide practical information to those using ERP measures as a biomarker to identify and track AD in individuals in a clinical or research setting.

Chapman, Robert M., P Porsteinsson, Anton P., Gardner, Margaret N., Mapstone, Mark, McCrary, John W., Sandoval, Tiffany C., Guillily, Maria D., Reilly, Lindsey A. & DeGrush, Elizabeth. (2013). The Impact of AD Drug Treatments on Event-Related Potentials as Markers of Disease Conversion. Current Alzheimer Research, 10(7), 732-741.

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C145 as a short-latency electrophysiological index of cognitive compensation in Alzheimer's disease

Published in Journal of Alzheimer's Disease, 2013

Brain plasticity and cognitive compensation in the elderly are of increasing interest, and Alzheimer's disease (AD) offers an opportunity to elucidate how the brain may overcome damage. We provide neurophysiological evidence of a short-latency ERP component (C145) linked to stimulus relevancy that may reflect cognitive compensation in early-stage Alzheimer's disease (AD). Thirty-six subjects with early-stage, mild AD and 36 like-aged normal elderly (Controls) had their EEG recorded while performing our Number-Letter task, a cognitive/perceptual paradigm that manipulates stimulus relevancies. ERP components, including C145, were extracted from ERPs using Principal Components Analysis. C145 amplitudes and spatial distributions were compared among Controls, AD subjects with high performance on the Number-Letter task, and AD subjects with low performance. Compared to AD subjects, Control subjects showed enhanced C145 processing of visual stimuli in the occipital region where differential processing of relevant stimuli occurred. AD high performers recruited central brain areas in processing task relevancy. Controls and AD low performers did not show a significant task relevancy effect in these areas. We conclude that short-latency ERP components can detect electrophysiological differences in early-stage AD that reflect altered cognition. Differences in C145 amplitudes between AD and normal elderly groups regarding brain locations and types of task effects suggest compensatory mechanisms can occur in the AD brain to overcome loss of normal functionality, and this early compensation may have a profound effect on the cognitive efficiency of AD individuals.

Chapman, Robert M., Porsteinsson, Anton P., Gardner, Margaret N., Mapstone, Mark, McCrary, John W., Sandoval, Tiffany C., Guillily, Maria D., DeGrush, Elizabeth & Reilly, Lindsey A. (2013). C145 as a short-latency electrophysiological index of cognitive compensation in Alzheimer's disease. Journal of Alzheimer's Disease, 33(1), 55-68.

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Women have farther to fall: Gender differences between normal elderly and Alzheimer's disease in verbal memory engender better detection of AD in women

Published in Journal of the International Neuropsychological Society, 2011

We analyzed verbal episodic memory learning and recall using the Logical Memory (LM) subtest of the Wechsler Memory Scale-III to determine how gender differences in AD compare to those seen in normal elderly and whether or not these differences impact assessment of AD. We administered the LM to both an AD and a Control group, each comprised of 21 men and 21 women, and found a large drop in performance from normal elders to AD. Of interest was a gender interaction whereby the women’s scores dropped 1.6 times more than the men’s did. Control women on average outperformed Control men on every aspect of the test, including immediate recall, delayed recall, and learning. Conversely, AD women tended to perform worse than AD men. Additionally, the LM achieved perfect diagnostic accuracy in discriminant analysis of AD versus Control women, a statistically significantly higher result than for men. The results indicate the LM is a more powerful and reliable tool in detecting AD in women than in men.

Chapman, Robert M., Mapstone, Mark, Gardner, Margaret N., Sandoval, Tiffany C., McCrary, John W., Guillily, Maria D., Reilly, Lindsey A. & DeGrush, Elizabeth. (2011). Women have farther to fall: Gender differences between normal elderly and Alzheimer's disease in verbal memory engender better detection of AD in women. Journal of the International Neuropsychological Society, 17, 654-662.

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Brain ERP components predict which individuals progress to Alzheimer’s disease and which do not

Published in Neurobiology of Aging, 2011

Predicting which individuals will progress to Alzheimer’s disease (AD) is important in both clinical and research settings. We used brain Event-Related Potentials (ERPs) obtained in a perceptual/cognitive paradigm with various processing demands to predict which individual Mild Cognitive Impairment (MCI) subjects will develop AD versus which will not. ERP components, including P3, memory “storage” component, and other earlier and later components, were identified and measured by Principal Components Analysis. When measured for particular task conditions, a weighted set of eight ERP component conditions performed well in discriminant analysis at predicting later AD progression with good accuracy, sensitivity, and specificity. The predictions for most individuals (79%) had high posterior probabilities and were accurate (88%). This method, supported by a cross-validation where the prediction accuracy was 70–78%, features the posterior probability for each individual as a method of determining the likelihood of progression to AD. Empirically obtained prediction accuracies rose to 94% when the computed posterior probabilities for individuals were 0.90 or higher (which was found for 40% of our MCI sample).

Chapman, Robert M., McCrary, John W., Gardner, Margaret N., Sandoval, Tiffany C., Guillily, Maria D., Reilly, Lindsey A. & DeGrush, Elizabeth. (2011). Brain ERP components predict which individuals progress to Alzheimer's disease and which do not. Neurobiology of Aging, 32, 1742-1755.

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Predicting conversion from mild cognitive impairment to Alzheimer's disease using neuropsychological tests and multivariate methods

Published in Journal of Clinical and Experimental Neuropsychology, 2011

Behavioral markers measured through neuropsychological testing in mild cognitive impairment (MCI) were analyzed and combined in multivariate ways to predict conversion to Alzheimer’s disease (AD) in a longitudinal study of 43 MCI patients. The test measures taken at a baseline evaluation were first reduced to underlying components (principal component analysis, PCA), and then the component scores were used in discriminant analysis to classify MCI individuals as likely to convert or not. When empirically weighted and combined, episodic memory, speeded executive functioning, recognition memory (false and true positives), visuospatial memory processing speed, and visuospatial episodic memory were together strong predictors of conversion to AD. These multivariate combinations of the test measures achieved through the PCA were good, statistically significant predictors of MCI conversion to AD (84% accuracy, 86% sensitivity, and 83% specificity). Importantly, the posterior probabilities of group membership that accompanied the binary prediction for each participant indicated the confidence of the prediction. Most of the participants (81%) were in the highly confident probability bins (.70–1.00), where the obtained prediction accuracy was more than 90%. The strength and reliability of this multivariate prediction method were tested by cross-validation and randomized resampling.

Chapman, Robert M., Mapstone, Mark, McCrary, John W., Gardner, Margaret N., Porsteinsson, Anton, DeGrush, Elizabeth, Reilly, Lindsey A., Sandoval, Tiffany C., & Guillily, Maria D. (2011). Predicting conversion from mild cognitive impairment to Alzheimer's disease using neuropsychological tests and multivariate methods. Journal of Clinical and Experimental Neuropsychology, 33(2), 187-199.

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