Alex Hishaw

Interests

Research

Behavioral Neurology, Neuropsychiatry, Head Injury, Dementia

Courses

Scholarly Contributions

Journals/Publications

• Hardcastle, C., Hausman, H. K., Kraft, J. N., Albizu, A., Evangelista, N. D., Boutzoukas, E. M., O'Shea, A., Langer, K., Van Van Etten, E., Bharadwaj, P. K., Song, H., Smith, S. G., Porges, E., DeKosky, S. T., Hishaw, G. A., Wu, S. S., Marsiske, M., Cohen, R., Alexander, G. E., & Woods, A. J. (2022). Higher-order resting state network association with the useful field of view task in older adults. GeroScience, 44(1), 131-145.
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  Speed-of-processing abilities decline with age yet are important in performing instrumental activities of daily living. The useful field of view, or Double Decision task, assesses speed-of-processing and divided attention. Performance on this task is related to attention, executive functioning, and visual processing abilities in older adults, and poorer performance predicts more motor vehicle accidents in the elderly. Cognitive training in this task reduces risk of dementia. Structural and functional neural correlates of this task suggest that higher-order resting state networks may be associated with performance on the Double Decision task, although this has never been explored. This study aimed to assess the association of within-network connectivity of the default mode network, dorsal attention network, frontoparietal control network, and cingulo-opercular network with Double Decision task performance, and subcomponents of this task in a sample of 267 healthy older adults. Multiple linear regressions showed that connectivity of the cingulo-opercular network is associated with visual speed-of-processing and divided attention subcomponents of the Double Decision task. Cingulo-opercular network and frontoparietal control network connectivity is associated with Double Decision task performance. Stronger connectivity is related to better performance in all cases. These findings confirm the unique role of the cingulo-opercular network in visual attention and sustained divided attention. Frontoparietal control network connectivity, in addition to cingulo-opercular network connectivity, is related to Double Decision task performance, a task implicated in reduced dementia risk. Future research should explore the role these higher-order networks play in reduced dementia risk after cognitive intervention using the Double Decision task.
• Boutzoukas, E. M., O'Shea, A., Albizu, A., Evangelista, N. D., Hausman, H. K., Kraft, J. N., Van Etten, E. J., Bharadwaj, P. K., Smith, S. G., Song, H., Porges, E. C., Hishaw, A., DeKosky, S. T., Wu, S. S., Marsiske, M., Alexander, G. E., Cohen, R., & Woods, A. J. (2021). Frontal White Matter Hyperintensities and Executive Functioning Performance in Older Adults. Frontiers in aging neuroscience, 13, 672535.
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  Frontal lobe structures decline faster than most other brain regions in older adults. Age-related change in the frontal lobe is associated with poorer executive function (e.g., working memory, switching/set-shifting, and inhibitory control). The effects and presence of frontal lobe white matter hyperintensities (WMH) on executive function in normal aging is relatively unknown. The current study assessed relationships between region-specific frontal WMH load and cognitive performance in healthy older adults using three executive function tasks from the NIH Toolbox (NIHTB) Cognition Battery. A cohort of 279 healthy older adults ages 65-88 completed NIHTB and 3T T1-weighted and FLAIR MRI. Lesion Segmentation Toolbox quantified WMH volume and generated lesion probability maps. Individual lesion maps were registered to the Desikan-Killiany atlas in FreeSurfer 6.0 to define regions of interest (ROI). Independent linear regressions assessed relationships between executive function performance and region-specific WMH in frontal lobe ROIs. All models included age, sex, education, estimated total intracranial volume, multi-site scanner differences, and cardiovascular disease risk using Framingham criteria as covariates. Poorer set-shifting performance was associated with greater WMH load in three frontal ROIs including bilateral superior frontal (left β = -0.18, FDR- = 0.02; right β = -0.20, FDR- = 0.01) and right medial orbitofrontal (β = -0.17, FDR- = 0.02). Poorer inhibitory performance associated with higher WMH load in one frontal ROI, the right superior frontal (right β = -0.21, FDR- = 0.01). There were no significant associations between working memory and WMH in frontal ROIs. Our study demonstrates that location and pattern of frontal WMH may be important to assess when examining age-related differences in cognitive functions involving switching/set-shifting and inhibition. On the other hand, working memory performance was not related to presence of frontal WMH in this sample. These data suggest that WMH may contribute selectively to age-related declines in executive function. Findings emerged beyond predictors known to be associated with WMH presence, including age and cardiovascular disease risk. The spread of WMH within the frontal lobes may play a key role in the neuropsychological profile of cognitive aging. Further research should explore whether early intervention on modifiable vascular factors or cognitive interventions targeted for executive abilities may help mitigate the effect of frontal WMH on executive function.
• Hausman, H. K., Hardcastle, C., Albizu, A., Kraft, J. N., Evangelista, N. D., Boutzoukas, E. M., Langer, K., O'Shea, A., Van Etten, E. J., Bharadwaj, P. K., Song, H., Smith, S. G., Porges, E., DeKosky, S. T., Hishaw, G. A., Wu, S., Marsiske, M., Cohen, R., Alexander, G. E., & Woods, A. J. (2021). Cingulo-opercular and frontoparietal control network connectivity and executive functioning in older adults. GeroScience.
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  Executive function is a cognitive domain that typically declines in non-pathological aging. Two cognitive control networks that are vulnerable to aging-the cingulo-opercular (CON) and fronto-parietal control (FPCN) networks-play a role in various aspects of executive functioning. However, it is unclear how communication within these networks at rest relates to executive function subcomponents in older adults. This study examines the associations between CON and FPCN connectivity and executive function performance in 274 older adults across working memory, inhibition, and set-shifting tasks. Average CON connectivity was associated with better working memory, inhibition, and set-shifting performance, while average FPCN connectivity was associated solely with working memory. CON region of interest analyses revealed significant connections with classical hub regions (i.e., anterior cingulate and anterior insula) for each task, language regions for verbal working memory, right hemisphere dominance for inhibitory control, and widespread network connections for set-shifting. FPCN region of interest analyses revealed largely right hemisphere fronto-parietal connections important for working memory and a few temporal lobe connections for set-shifting. These findings characterize differential brain-behavior relationships between cognitive control networks and executive function in aging. Future research should target these networks for intervention to potentially attenuate executive function decline in older adults.
• Kraft, J. N., Albizu, A., O'Shea, A., Hausman, H. K., Evangelista, N. D., Boutzoukas, E., Hardcastle, C., Van Etten, E. J., Bharadwaj, P. K., Song, H., Smith, S. G., DeKosky, S., Hishaw, G. A., Wu, S., Marsiske, M., Cohen, R., Alexander, G. E., Porges, E., & Woods, A. J. (2021). Functional Neural Correlates of a Useful Field of View (UFOV)-Based fMRI Task in Older Adults. Cerebral cortex (New York, N.Y. : 1991).
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  Declines in processing speed performance occur in aging and are a critical marker of functional independence in older adults. Studies suggest that Useful Field of View (UFOV) training may ameliorate cognitive decline. Despite its efficacy, little is known about the neural correlates of this task. Within the current study, 233 healthy older adults completed a UFOV-based task while undergoing functional magnetic resonance imaging (fMRI). During the "stimulus" portion of this task, participants must identify a target in the center of the screen and the location of a target in the periphery, among distractors. During the "probe" portion, participants must decide if the object in the center and the location of the target in the periphery were identical to the "stimulus" screen. Widespread bilateral whole-brain activation was observed when activation patterns of the "probe" contrast were subtracted from the "stimulus" contrast. Conversely, the subtraction of "stimulus" from "probe" was associated with discrete activation patterns consisting of 13 clusters. Additionally, when evaluating the variance associated with task accuracy, specific subregions were identified that may be critical for task performance. Our data elucidate the functional neural correlates of a UFOV-based task, a task used in both cognitive training paradigms and assessment of function.
• Lane, R. D., Solms, M., Weihs, K. L., Hishaw, A., & Smith, R. (2021). Is the concept of affective agnosia a useful addition to the alexithymia literature?. Neuroscience and biobehavioral reviews, 127, 747-748.
• Van Etten, E. J., Bharadwaj, P. K., Hishaw, G. A., Huentelman, M. J., Trouard, T. P., Grilli, M. D., & Alexander, G. E. (2021). Influence of regional white matter hyperintensity volume and apolipoprotein E ε4 status on hippocampal volume in healthy older adults. Hippocampus, 31(5), 469-480.
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  While total white matter hyperintensity (WMH) volume on magnetic resonance imaging (MRI) has been associated with hippocampal atrophy, less is known about how the regional distribution of WMH volume may differentially affect the hippocampus in healthy aging. Additionally, apolipoprotein E (APOE) ε4 carriers may be at an increased risk for greater WMH volumes and hippocampal atrophy in aging. The present study sought to investigate whether regional WMH volume mediates the relationship between age and hippocampal volume and if this association is moderated by APOE ε4 status in a group of 190 cognitively healthy adults (APOE ε4 status [carrier/non-carrier] = 59/131), ages 50-89. Analyses revealed that temporal lobe WMH volume significantly mediated the relationship between age and average bilateral hippocampal volume, and this effect was moderated by APOE ε4 status (-0.020 (SE = 0.009), 95% CI, [-0.039, -0.003]). APOE ε4 carriers, but not non-carriers, showed negative indirect effects of age on hippocampal volume through temporal lobe WMH volume (APOE ε4 carriers: -0.016 (SE = 0.007), 95% CI, [-0.030, -0.003]; APOE ε4 non-carriers: .005 (SE = 0.006), 95% CI, [-0.006, 0.017]). These findings remained significant after additionally adjusting for sex, years of education, hypertension status and duration, cholesterol status, diabetes status, Body Mass Index, history of smoking, and the Wechsler Adult Intelligence Scale-IV Full Scale IQ. There were no significant moderated mediation effects for frontal, parietal, and occipital lobe WMH volumes, with or without covariates. Our findings indicate that in cognitively healthy older adults, elevated WMH volume regionally localized to the temporal lobes in APOE ε4 carriers is associated with reduced hippocampal volume, suggesting greater vulnerability to brain aging and the risk for Alzheimer's disease.
• Evangelista, N. D., O'Shea, A., Kraft, J. N., Hausman, H. K., Boutzoukas, E. M., Nissim, N. R., Albizu, A., Hardcastle, C., Van Etten, E. J., Bharadwaj, P. K., Smith, S. G., Song, H., Hishaw, G. A., DeKosky, S., Wu, S., Porges, E., Alexander, G. E., Marsiske, M., Cohen, R., & Woods, A. J. (2020). Independent Contributions of Dorsolateral Prefrontal Structure and Function to Working Memory in Healthy Older Adults. Cerebral cortex (New York, N.Y. : 1991).
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  Age-related differences in dorsolateral prefrontal cortex (DLPFC) structure and function have each been linked to working memory. However, few studies have integrated multimodal imaging to simultaneously investigate relationships among structure, function, and cognition. We aimed to clarify how specifically DLPFC structure and function contribute to working memory in healthy older adults. In total, 138 participants aged 65-88 underwent 3 T neuroimaging and were divided into higher and lower groups based on a median split of in-scanner n-back task performance. Three a priori spherical DLPFC regions of interest (ROIs) were used to quantify blood-oxygen-level-dependent (BOLD) signal and FreeSurfer-derived surface area, cortical thickness, and white matter volume. Binary logistic regressions adjusting for age, sex, education, and scanner type revealed that greater left and right DLPFC BOLD signal predicted the probability of higher performing group membership (P values.05). Importantly, this suggests BOLD signal and surface area may independently contribute to working memory performance in healthy older adults.
• Franchetti, M. K., Bharadwaj, P. K., Nguyen, L. A., Van Etten, E. J., Klimentidis, Y. C., Hishaw, G. A., Trouard, T. P., Raichlen, D. A., & Alexander, G. E. (2020). Interaction of Age and Self-reported Physical Sports Activity on White Matter Hyperintensity Volume in Healthy Older Adults. Frontiers in aging neuroscience, 12, 576025.
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  Cerebral white matter (WM) lesion load, as measured by white matter hyperintensity (WMH) volume with magnetic resonance imaging (MRI), has been associated with increasing age and cardiovascular risk factors, like hypertension. Physical sports activity (PSA) may play an important role in maintaining WM in the context of healthy aging. In 196 healthy older adults, we investigated whether participants reporting high levels of PSA ( = 36) had reduced total and regional WMH volumes compared to those reporting low levels of PSA ( = 160). Age group [young-old (YO) = 50-69 years; old-old (OO) = 70-89 years], PSA group, and age by PSA group interaction effects were tested, with sex, hypertension, and body mass index (BMI) as covariates. We found significant main effects for age group and age by PSA group interactions for total, frontal, temporal, and parietal WMH volumes. There were no main effects of PSA group on WMH volumes. The OO group with low PSA had greater total, frontal, temporal, and parietal WMH volumes than the YO with low PSA and OO with high PSA groups. WMH volumes for the YO and OO groups with high PSA were comparable. These findings indicate an age group difference in those with low PSA, with greater WMH volumes in older adults, which was not observed in those with high PSA. The results suggest that engaging in high levels of PSA may be an important lifestyle factor that can help to diminish WMH lesion load in old age, potentially reducing the impact of brain aging.
• Hardcastle, C., O'Shea, A., Kraft, J. N., Albizu, A., Evangelista, N. D., Hausman, H. K., Boutzoukas, E. M., Van Etten, E. J., Bharadwaj, P. K., Song, H., Smith, S. G., Porges, E. C., Dekosky, S., Hishaw, G. A., Wu, S. S., Marsiske, M., Cohen, R., Alexander, G. E., & Woods, A. J. (2020). Contributions of Hippocampal Volume to Cognition in Healthy Older Adults. Frontiers in aging neuroscience, 12, 593833.
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  : The association between hippocampal volume and memory is continuing to be characterized in healthy older adults. Prior research suggests smaller hippocampal volume in healthy older adults is associated with poorer episodic memory and processing speed, as well as working memory, verbal learning, and executive functioning as measured by the NIH Toolbox Fluid (Fluid Cognition Composite, FCC) and Crystalized Cognition Composites (CCC). This study aimed to replicate these findings and to evaluate the association between: (1) hippocampal asymmetry index and cognition; and (2) independent contributions of the left and right hippocampal volume and cognition in a large sample of healthy older adults. : One-hundred and eighty-three healthy older adults (M age = 71.72, SD = 5.3) received a T1-weighted sequence on a 3T scanner. Hippocampal subfields were extracted using FreeSurfer 6.0 and combined to provide left, right, and total hippocampal volumes. FCC subtests include Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, List Sorting, Picture Sequence Memory, and Pattern Comparison. CCC subtests include Picture Vocabulary and Oral Reading Recognition. Multiple linear regressions were performed predicting cognition composites from the total, left and right, and asymmetry of hippocampal volume, controlling for sex, education, scanner, and total intracranial volume. Multiple comparisons in primary analyses were corrected using a false discovery rate (FDR) of < 0.05. : FCC scores were positively associated with total ( = 0.226, FDR = 0.044) and left ( = 0.257, FDR = 0.024) hippocampal volume. Within FCC, Picture Sequence Memory scores positively associated with total ( = 0.284, = 0.001) and left ( = 0.98, = 0.001) hippocampal volume. List Sorting scores were also positively associated with left hippocampal volume ( = 0.189, = 0.029). : These results confirm previous research suggesting that bilateral hippocampal volume is associated with FCC, namely episodic memory. The present study also suggests the left hippocampal volume may be more broadly associated with both episodic and working memory. Studies should continue to investigate lateralized hippocampal contributions to aging processes to better identify predictors of cognitive decline.
• Hausman, H. K., O'Shea, A., Kraft, J. N., Boutzoukas, E. M., Evangelista, N. D., Van Etten, E. J., Bharadwaj, P. K., Smith, S. G., Porges, E., Hishaw, G. A., Wu, S., DeKosky, S., Alexander, G. E., Marsiske, M., Cohen, R., & Woods, A. J. (2020). The Role of Resting-State Network Functional Connectivity in Cognitive Aging. Frontiers in aging neuroscience, 12, 177.
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  Aging is associated with disruptions in the resting-state functional architecture of the brain. Previous studies have primarily focused on age-related declines in the default mode network (DMN) and its implications in Alzheimer's disease. However, due to mixed findings, it is unclear if changes in resting-state network functional connectivity are linked to cognitive decline in healthy older adults. In the present study, we evaluated the influence of intra-network coherence for four higher-order cognitive resting-state networks on a sensitive measure of cognitive aging (i.e., NIH Toolbox Fluid Cognition Battery) in 154 healthy older adults with a mean age of 71 and education ranging between 12 years and 21 years (mean = 16). Only coherence within the cingulo-opercular network (CON) was significantly related to Fluid Cognition Composite scores, explaining more variance in scores than age and education. Furthermore, we mapped CON connectivity onto fluid cognitive subdomains that typically decline in advanced age. Greater CON connectivity was associated with better performance on episodic memory, attention, and executive function tasks. Overall, the present study provides evidence to propose CON coherence as a potential novel neural marker for nonpathological cognitive aging.
• Kraft, J. N., O'Shea, A., Albizu, A., Evangelista, N. D., Hausman, H. K., Boutzoukas, E., Nissim, N. R., Van Etten, E. J., Bharadwaj, P. K., Song, H., Smith, S. G., Porges, E., DeKosky, S., Hishaw, G. A., Wu, S., Marsiske, M., Cohen, R., Alexander, G. E., & Woods, A. J. (2020). Structural Neural Correlates of Double Decision Performance in Older Adults. Frontiers in aging neuroscience, 12, 278.
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  Speed of processing is a cognitive domain that encompasses the speed at which an individual can perceive a given stimulus, interpret the information, and produce a correct response. Speed of processing has been shown to decline more rapidly than other cognitive domains in an aging population, suggesting that this domain is particularly vulnerable to cognitive aging (Chee et al., 2009). However, given the heterogeneity of neuropsychological measures used to assess the domains underpinning speed of processing, a diffuse pattern of brain regions has been implicated. The current study aims to investigate the structural neural correlates of speed of processing by assessing cortical volume and speed of processing scores on the POSIT Double Decision task within a healthy older adult population ( = 186; mean age = 71.70 ± 5.32 years). T1-weighted structural images were collected via a 3T Siemens scanner. The current study shows that less cortical thickness in right temporal, posterior frontal, parietal and occipital lobe structures were significantly associated with poorer Double Decision scores. Notably, these include the lateral orbitofrontal gyrus, precentral gyrus, superior, transverse, and inferior temporal gyrus, temporal pole, insula, parahippocampal gyrus, fusiform gyrus, lingual gyrus, superior and inferior parietal gyrus and lateral occipital gyrus. Such findings suggest that speed of processing performance is associated with a wide array of cortical regions that provide unique contributions to performance on the Double Decision task.
• Mendoza, N. S., Moreno, F. A., Hishaw, G. A., Gaw, A. C., Fortuna, L. R., Skubel, A., Porche, M. V., Roessel, M. H., Shore, J., & Gallegos, A. (2020). Affirmative Care Across Cultures: Broadening Application. Focus (American Psychiatric Publishing), 18(1), 31-39.
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  Affirmative practice is an approach to health and behavioral health care that validates and supports the identities stated or expressed by those served. Affirmative care requires the practitioner to actively honor and celebrate identity while at the same time validating the oppression felt by individuals seeking services. Validation and empathy fundamentally result from increased understanding of individuals' history, cultural context, and lived experiences. Origins of the approach honored the experience of those in LGBTQ+ communities; however, affirmative care should be valued across cultures, systems, and settings in which health and behavioral health care are offered. Affirmative care principles should be applied across cultures and communities while recognizing the worth of the individual and avoiding stereotyping. Along with delineating historical and demographic contexts, the authors offer recommendations for affirmative care in practice with African American, Asian, Indigenous, and Latinx individuals, as well as those living in rural communities.
• Mendoza, N. S., Moreno, F. A., Hishaw, G. A., Saw, A. C., Fortuna, L. R., Skubel, A., Porche, M. V., Roessel, M. H., Shore, J., & Gallegos, A. (2020). Affirmative Care Across Cultures: Broadening Application. FOCUS, 18(1), 31-39.
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  Affirmative practice is an approach to health and behavioral health care that validates and supports the identities stated or expressed by those served. Affirmative care requires the practitioner to actively honor and celebrate identity while at the same time validating the oppression felt by individuals seeking services. Validation and empathy fundamentally result from increased understanding of individuals’ history, cultural context, and lived experiences. Origins of the approach honored the experience of those in LGBTQ+ communities; however, affirmative care should be valued across cultures, systems, and settings in which health and behavioral health care are offered. Affirmative care principles should be applied across cultures and communities while recognizing the worth of the individual and avoiding stereotyping. Along with delineating historical and demographic contexts, the authors offer recommendations for affirmative care in practice with African American, Asian, Indigenous, and Latinx individuals, as well as those living in rural communities.
• Van Etten, E. J., Bharadwaj, P. K., Nguyen, L. A., Hishaw, G. A., Trouard, T. P., & Alexander, G. E. (2020). Right hippocampal volume mediation of subjective memory complaints differs by hypertension status in healthy aging. Neurobiology of aging, 94, 271-280.
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  Subjective memory complaints (SMCs) may be an important early indicator of cognitive aging and preclinical Alzheimer's disease risk. This study investigated whether age-related differences in right or left hippocampal volume underlie SMCs, if these relationships differ by hypertension status, and how they are related to objective memory performance in a group of 190 healthy older adults, 50-89 years of age. Analyses revealed a significant mediation of the relationship between age and mild SMCs by right hippocampal volume that was moderated by hypertension status. This moderated mediation effect was not observed with left hippocampal volume. Additionally, a moderated serial mediation model showed that age predicted right hippocampal volume, which predicted SMCs, and in turn predicted objective memory performance on several measures of verbal selective reminding in individuals with hypertension, but not in non-hypertensives. Together, these findings suggest that even mild SMCs, in the context of hypertension, provide an early indicator of cognitive aging, reflecting a potential link among vascular risk, SMCs, and the preclinical risk for Alzheimer's disease.
• Nguyen, L. A., Haws, K. A., Fitzhugh, M. C., Torre, G. A., Hishaw, G. A., & Alexander, G. E. (2016). Interactive effects of subjective memory complaints and hypertension on learning and memory performance in the elderly. Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition, 23(2), 154-70.
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  This study evaluated whether the relation between subjective memory complaints and cognitive performance is influenced by the presence of hypertension in the elderly. One hundred and five healthy older adults, 70-89 years of age, with and without hypertension treatment or diagnosis, completed a scale of subjective memory complaints. Participants were divided into those with mild memory concerns and those with minimal or no complaints. All participants completed a battery of neuropsychological tests including measures of verbal and nonverbal memory. After controlling for differences in age, gender, education, and overall intellectual ability, there were significant main effects for memory concerns and significant interactions for memory complaints and hypertension on several measures of memory performance. There were no main effects for hypertension on memory performance. Simple effects analyses of the interactions showed that the hypertensive complainers demonstrated poorer performance on measures of long-term memory and greater reliance on short-term recall than the hypertensive non-complainers. There were no differences in memory performance for the non-hypertensive groups. Among healthy elderly community-dwelling adults, those with mild subjective memory complaints in the context of hypertension demonstrated greater objective cognitive difficulties than those without hypertension as well as a greater reliance on a less efficient learning strategy. These findings suggest that memory concerns in the presence of hypertension may be important when evaluating treatment efficacy in these individuals and for identifying differences in cognitive aging.
• Lane, R. D., Weihs, K. L., Herring, A., Hishaw, A., & Smith, R. (2015). Affective agnosia: Expansion of the alexithymia construct and a new opportunity to integrate and extend Freud's legacy. Neuroscience and biobehavioral reviews, 55, 594-611.
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  We describe a new type of agnosia consisting of an impairment in the ability to mentally represent or know what one is feeling. Freud the neurologist coined the term "agnosia" in 1891 before creating psychoanalysis in 1895 but the term has not been previously applied to the domain of affective processing. We propose that the concept of "affective agnosia" advances the theory, measurement and treatment of what is now called "alexithymia," meaning "lack of words for emotion." We trace the origin of the alexithymia construct and discuss the strengths and limitations of extant research. We review evidence that the ability to represent and put emotions into words is a developmental achievement that strongly influences one's ability to experience, recognize, understand and use one's own emotional responses. We describe the neural substrates of emotional awareness and affective agnosia and compare and contrast these with related conditions. We then describe how this expansion of the conceptualization and measurement of affective processing deficits has important implications for basic emotion research and clinical practice.
• Salloway, S., Sperling, R., Fox, N. C., Blennow, K., Klunk, W., Raskind, M., Sabbagh, M., Honig, L. S., Porsteinsson, A. P., Ferris, S., Reichert, M., Ketter, N., Nejadnik, B., Guenzler, V., Miloslavsky, M., Wang, D., Lu, Y., Lull, J., Tudor, I. C., , Liu, E., et al. (2014). Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. The New England journal of medicine, 370(4), 322-33.
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  Bapineuzumab, a humanized anti-amyloid-beta monoclonal antibody, is in clinical development for the treatment of Alzheimer's disease.