Authors: Charil, Arnaud | Shcherbinin, Sergey | Southekal, Sudeepti | Devous, Michael D. | Mintun, Mark | Murray, Melissa E. | Miller, Bradley B. | Schwarz, Adam J.
Article Type: Research Article
Abstract: At autopsy, individuals with Alzheimer’s disease (AD) exhibit heterogeneity in the distribution of neurofibrillary tangles in neocortical and hippocampal regions. Subtypes of AD, defined using an algorithm based on the relative number of tangle counts in these regions, have been proposed—hippocampal sparing (relative sparing of the hippocampus but high cortical load), limbic predominant (high hippocampal load but lower load in association cortices), and typical (balanced neurofibrillary tangles counts in the hippocampus and association cortices) AD—and shown to be associated with distinct antemortem clinical phenotypes. The ability to distinguish these AD subtypes from the more typical tau signature in vivo could …have important implications for clinical research. Flortaucipir positron emission tomography (PET) images acquired from 45 amyloid-positive participants, defined clinically as mild cognitive impairment or AD, aged 50–92 years, 56% female, and estimated to be Braak V-VI based on their PET pattern of tau pathology, were studied. By translating the neuropathologic algorithm to flortaucipir PET scans, patterns of tau pathology consistent with autopsy findings, and with a similar prevalence, were identified in vivo . 6/45 (13%) participants were identified as hippocampal sparing and 6/45 (13%) as limbic predominant AD subtypes. Hippocampal sparing participants were significantly younger than those assigned to the other two subtypes. Worse performance on delayed recall was associated with increased hippocampal tau signal, and worse performance on the trail making test B-A was associated with lower values of the hippocampus to cortex ratio. Prospective studies can further validate the flortaucipir SUVR cut-points and the phenotype of the corresponding AD subtypes. Show more
Keywords: Hippocampal sparing, limbic predominant, subtype, tau
DOI: 10.3233/JAD-190264
Citation: Journal of Alzheimer's Disease, vol. 71, no. 3, pp. 1037-1048, 2019
Authors: Samudra, Niyatee | Motes, Michael | Lu, Hanzhang | Sheng, Min | Diaz-Arrastia, Ramon | Devous, Michael | Hart, John | Womack, Kyle B.
Article Type: Research Article
Abstract: Alzheimer’s disease (AD) is the most common cause of neurodegenerative cognitive impairment, defined by abnormal accumulations of amyloid-β and tau. Approaches directly targeting these proteins have not resulted in a disease modifying therapy. Neurovascular unit dysfunction is a feature of AD offering an alternative target for intervention. Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, improves cognitive functioning in mouse models of AD. Recent work in AD patients has demonstrated increased cerebral blood flow, as well as brain oxygen utilization after a single dose of sildenafil. Its effect on nitric oxide-cGMP signaling may have downstream effects on neuroplasticity, amyloid-β processing, and improved …neurovascular unit function. Fractional amplitude of low frequency fluctuations (fALFF) assesses spontaneous neural activity via resting state fMRI BOLD signal (0.01–0.08 or 0.10 Hz). In AD, other assessments have revealed increased fALFF in hippocampi and parahippocampal gyri. Here, we examined the effects of a single dose of sildenafil on fALFF in a cohort of 10 AD patients. We found a decrease (p < 0.03, α = 0.05) in fALFF an hour after sildenafil administration in the right hippocampus. Additionally, cerebral vascular reactivity in response to carbon dioxide inhalation, a measure of neural vascular reserve previously collected on most of these participants, was not significantly correlated with this decrease, implying that change in fALFF may not have been solely due to altered vascular reactivity to CO2 . We demonstrate that in patients with AD, hippocampal fALFF decreases in response to sildenafil, suggesting a normalization. These findings support further investigation into the effects of sildenafil in AD. Show more
Keywords: Alzheimer’s disease, cognitive impairment, fractional amplitude of low frequency fluctuations, functional magnetic resonance imaging, sildenafil.
DOI: 10.3233/JAD-190128
Citation: Journal of Alzheimer's Disease, vol. 70, no. 1, pp. 163-170, 2019
Authors: Walker-Batson, Delaina | Unwin, Hal | Curtis, Sandra | Allen, Elizabeth | Wood, Midge | Smith, Patricia | Devous, Michael D. | Reynolds, Sharon | Greenlee, Ralph G.
Article Type: Short Communication
Abstract: The effects of d-amphetamine on the recovery of aphasia following stroke was examined in 6 patients. Patients entered the study between 10 and 30 days post onset and were followed for 3 months. The Porch Index of Communicative Ability was used to project a 6 month recovery score. By 3 months post onset, 5 of the 6 patients obtained scores in excess of 100% of the 6 month projections.
Keywords: Aphasia, Recovery, Amphetamine, Norepinephrine, Stroke, Cardiovascular accident
DOI: 10.3233/RNN-1992-4106
Citation: Restorative Neurology and Neuroscience, vol. 4, no. 1, pp. 47-50, 1992
Authors: O'Bryant, Sid E. | Xiao, Guanghua | Edwards, Melissa | Devous, Michael | Gupta, Veer Bala | Martins, Ralph | Zhang, Fan | Barber, Robert | for the Texas Alzheimer's Research and Care Consortium (TARCC)
Article Type: Research Article
Abstract: Background: Mexican Americans are the fastest aging segment of the U.S. population, yet little scientific literature exists regarding the Alzheimer’s disease (AD) among this segment of the population. The extant literature suggests that biomarkers of AD will vary according to race/ethnicity though no prior work has explicitly studied this possibility. The aim of this study was to create a serum-based biomarker profile of AD among Mexican American. Methods: Data were analyzed from 363 Mexican American participants (49 AD and 314 normal controls) enrolled in the Texas Alzheimer’s Research & Care Consortium (TARCC). Non-fasting serum samples were analyzed using a luminex-based multi-plex …platform. A biomarker profile was generated using random forest analyses. Results: The biomarker profile of AD among Mexican Americans was different from prior work from non-Hispanic populations with regards to the variable importance plots. In fact, many of the top markers were related to metabolic factors (e.g., FABP, GLP-1, CD40, pancreatic polypeptide, insulin-like-growth factor, and insulin). The biomarker profile was a significant classifier of AD status yielding an area under the receiver operating characteristic curve, sensitivity, and specificity of 0.77, 0.92, and 0.64, respectively. Combining biomarkers with clinical variables yielded a better balance of sensitivity and specificity. Conclusion: The biomarker profile for AD among Mexican American cases is significantly different from that previously identified among non-Hispanic cases from many large-scale studies. This is the first study to explicitly examine and provide support for blood-based biomarkers of AD among Mexican Americans. Areas for future research are highlighted. Show more
Keywords: Alzheimer's disease, biomarkers, Mexican American, neuropsychology
DOI: 10.3233/JAD-122074
Citation: Journal of Alzheimer's Disease, vol. 34, no. 4, pp. 841-849, 2013
Authors: O'Bryant, Sid E. | Johnson, Leigh | Balldin, Valerie | Edwards, Melissa | Barber, Robert | Williams, Benjamin | Devous, Michael | Cushings, Blair | Knebl, Janice | Hall, James
Article Type: Research Article
Abstract: The purpose of the study was to provide characterization of Mexican Americans who meet criteria for Alzheimer's disease (AD) and mild cognitive impairment (MCI). For the study, 1,069 participants ages 40 and above who self-identified as either non-Hispanic white (n = 633) or Mexican American (n = 436) were recruited using a community-based participatory research approach. Global cognition was assessed via the Mini-Mental State Examination (MMSE), dementia severity by the Clinical Dementia Rating Scale, and depression via the Geriatric Depression Scale 30-item version. Age, gender, education, ApoE ε4 allele frequency, and diabetic diagnoses were also analyzed. The findings showed that …Mexican Americans (normal controls, MCI, and AD) were younger, less highly educated, performed more poorly on the MMSE, endorsed more symptoms of depression, were more likely to be diagnosed with diabetes, and possessed the ApoE ε4 allele less frequently. Age was the only significant risk factor for cognitive dysfunction (AD/MCI) among Mexican Americans (OR = 1.06, 95% CI = 1.03–1.09). Age (B = 0.07, std = 0.02, p < 0.001) and ApoE ε4 presence (B = 0.9, std = 0.4, p = 0.02) were significantly related to increased disease severity. Given the rapidly growing and aging Mexican American population, there is a substantial need for research into cognitive aging, MCI, and AD among this ethnic group. The current findings hold important implications for both clinic and research settings and point to additional research needs. Show more
Keywords: Alzheimer's disease, cognition, depression, diabetes, Hispanic, Mexican American, mild cognitive impairment
DOI: 10.3233/JAD-2012-121420
Citation: Journal of Alzheimer's Disease, vol. 33, no. 2, pp. 373-379, 2013
Authors: Sheng, Min | Lu, Hanzhang | Liu, Peiying | Li, Yang | Ravi, Harshan | Peng, Shin-Lei | Diaz-Arrastia, Ramon | Devous, Michael D. | Womack, Kyle B.
Article Type: Research Article
Abstract: Background: Alzheimer’s disease (AD) is the leading cause of degenerative dementia in the aging population. Patients with AD have alterations in cerebral hemodynamic function including reduced cerebral blood flow (CBF) and cerebral metabolic rate. Therefore, improved cerebrovascular function may be an attractive goal for pharmaceutical intervention in AD. Objective: We wished to observe the acute effects of sildenafil on cerebrovascular function and brain metabolism in patients with AD. Methods: We used several novel non-invasive MRI techniques to investigate the alterations of CBF, cerebral metabolic rate of oxygen (CMRO2 ), and cerebrovascular reactivity (CVR) after a single dose of sildenafil administration …in order to assess its physiological effects in patients with AD. CBF, CMRO2 , and CVR measurements using MRI were performed before and one hour after the oral administration of 50 mg sildenafil. Baseline Montreal Cognitive Assessment score was also obtained. Results: Complete CBF and CMRO2 data were obtained in twelve patients. Complete CVR data were obtained in eight patients. Global CBF and CMRO2 significantly increased (p = 0.03, p = 0.05, respectively) following sildenafil administration. Voxel-wise analyses of CBF maps showed that increased CBF was most pronounced in the bilateral medial temporal lobes. CVR significantly decreased after administration of sildenafil. Conclusion: Our data suggest that a single dose of sildenafil improves cerebral hemodynamic function and increases cerebral oxygen metabolism in patients with AD. Show more
Keywords: Cerebral blood flow, cerebral metabolic rate of oxygen, cerebrovascular reactivity, magnetic resonance imaging, Montreal Cognitive Assessment, sildenafil
DOI: 10.3233/JAD-161006
Citation: Journal of Alzheimer's Disease, vol. 60, no. 4, pp. 1351-1364, 2017
Authors: O'Bryant, Sid E. | Johnson, Leigh | Edwards, Melissa | Soares, Holly | Devous, Michael D. | Ross, Sarah | Rohlfing, Geoffrey | Hall, James | for the Texas Alzheimer's Research & Care Consortium
Article Type: Research Article
Abstract: Background: The aim of this study is to evaluate the link between C-reactive protein (CRP) and Alzheimer’s disease (AD) and mild cognitive impairment (MCI) among Mexican Americans. Methods: Non-fasting serum CRP levels, Mini-Mental State Examination scores, and Clinical Dementia Rating scale (CDR) scores were analyzed from 1,066 participants (Mexican American n = 471; non-Hispanic n = 595) of the Texas Alzheimer’s Research & Care Consortium. Results: Among the total cohort, CRP levels among AD cases were significantly decreased as compared to normal controls (p < 0.001) and MCI cases (p = 0.002). CRP levels among MCI cases were decreased relative to …controls (p = 0.03). Among Mexican American and non-Hispanic AD cases, CRP levels were significantly decreased among AD cases as compared to controls. CRP levels were only associated with disease severity (CDR scores) among non-Hispanics (p = 0.03) AD cases. Conclusions: These results show that while CRP levels are decreased among Mexican American AD cases, CRP does not appear to be related to clinical variables as it is among non-Hispanic whites. Show more
Keywords: Alzheimer's disease, C-reactive protein, Mexican American, neuropsychology
DOI: 10.3233/JAD-122071
Citation: Journal of Alzheimer's Disease, vol. 34, no. 3, pp. 701-706, 2013