Papers by Simone Chaudhary
Expert Review of Anticancer Therapy
Arterial spin labeling is a completely non-invasive method for blood-flow measurement techniques.... more Arterial spin labeling is a completely non-invasive method for blood-flow measurement techniques. Alzheimer's disease pathology includes microvascular abnormalities in addition to practically all risk factors having a vascular component that reduces cerebral perfusion. Hemodynamic parameters of cerebral blood flow and arterial transit time were estimated via single-compartment modeling of pseudo continuous arterial spin labeling data and neurocognitive test scores (Alzheimer's disease assessment scale and mini-mental state examination) were compared between a group of healthy (N=20) and early Alzheimer's disease (N=25) subjects before and six months after the Alzheimer's subjects began treatment with cholinesterase inhibitors. The early Alzheimer's group showed improved CBF after 6 months' treatment in every Alzheimer's-prone region except the medial and lateral temporal lobes. No difference in arterial transit time was found between groups, indicating th...
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2016
Despite the growing recognition of the significance of cerebrovascular impairment in the etiology... more Despite the growing recognition of the significance of cerebrovascular impairment in the etiology and progression of Alzheimer's disease (AD), the early stage brain vascular dysfunction and its sensitivity to pharmacological interventions is still not fully characterized. Due to the early and aggressive treatment of probable AD with cholinesterase inhibitors (ChEI), which in and of themselves have direct effects on brain vasculature, the vast majority of hemodynamic measurements in early AD subjects reported hitherto have consequently been made only after the start of treatment, complicating the disentanglement of disease-vs. treatment-related effects on the cerebral vasculature. To address this gap, we used pseudo continuous arterial spin labeling MRI to measure resting perfusion and visual stimulation elicited changes in cerebral blood flow (CBF) and blood oxygenation dependent (BOLD) fMRI signal in a cohort of mild AD patients immediately prior to, 6 months post, and 12 months post commencement of open label cholinesterase inhibitor treatment. Although patients exhibited no gray matter atrophy prior to treatment and their resting perfusion was not distinguishable from that in age, education and gendermatched controls, the patients' visual stimulation-elicited changes in BOLD fMRI and blood flow were decreased by 10 ± 4% (BOLD) and 23 ± 2% (CBF), relative to those in controls. Induction of cholinesterase inhibition treatment was associated with a further, 7 ± 2% reduction in patients' CBF response to visual stimulation, but it stabilized, at this new lower level, over the follow-up period. Likewise, MMSE scores remained stable during the treatment; furthermore, higher MMSE scores were associated with higher perfusion responses to visual stimulation. This study represents the initial step in disentangling the effects of AD pathology from those of the first line treatment with cholinesterase inhibitors on cerebral hemodynamics and supports the use of arterial spin labeling MRI for quantitative evaluation of the brain vascular function in mild Alzheimer's disease. The findings provide evidence of a pronounced deficit in the visual cortex hyperemia despite the relative sparing of visual function in early stage AD, its reduction with ChEI treatment induction, and its stabilization in the first year of cholinesterase inhibition treatment. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M.
Journal of Magnetic Resonance Imaging, 2012
Purpose: To evaluate the spatiotemporal progression of perfusion changes in early stages of Alzhe... more Purpose: To evaluate the spatiotemporal progression of perfusion changes in early stages of Alzheimer's disease (AD), we imaged the perfusion response to pharmacological treatment in a group of mild AD patients and contrasted it to the perfusion of age-, sex-, and educationmatched healthy volunteers over the same time interval. Materials and Methods: We used pseudo continuous arterial spin labeling (PCASL) MRI for quantitative threedimensional mapping of perfusion immediately before and 6 months after cholinesterase inhibitor treatment. Results: Before treatment, patients were found hypoperfused relative to their healthy counterparts in the gray matter of lateral temporal lobe, posterior cingulate, and anterior cingulate as well as in the white matter of the posterior cingulate. Most of the cortical regions investigated and the white matter of posterior cingulate and prefrontal regions showed treatment-elicited increases in perfusion, which were not secondary to changes in regional tissue volume nor were they associated with improvement in either MMSE or ADAS-Cog scores, although lack of deterioration suggested a cognitive benefit. Conclusion: This study provides a hemodynamic profile of mild AD and sheds light on the perfusion changes related to prolonged cholinesterase inhibition in this early disease stage.
Cerebral Cortex, 2012
Default-mode network (DMN) connectivity at rest is disrupted in Alzheimer's Disease (AD), but it ... more Default-mode network (DMN) connectivity at rest is disrupted in Alzheimer's Disease (AD), but it is unknown whether this abnormality is a static feature, or if it varies across cognitive states. We measured DMN integrity in 16 patients with mild AD and 18 controls during resting state and a simple visual task. Patients showed resting-state deficits in the parahippocampal gyrus and posterior cingulate. No group differences were found during the task. Controls exhibited higher DMN connectivity of multiple regions during rest than task, while the patient group showed no modulation of the DMN between states. However, the relative degree of increased resting-versus task-state co-activation in the posterior cingulate and precuneus was predictive of mini-mental status exam (MMSE) scores in AD patients, while measures at rest or task alone were not associated with MMSE. These findings suggest that a resting state may be more suited to detecting DMN abnormalities in AD than a simple task. However, the degree of state-dependent modulation in the DMN may be a better predictor of the individual cognitive status than a single-state acquisition. This study demonstrates an apparent reduction in the capacity for DMN modulation in individuals with mild AD, the degree of which uniquely predicted cognitive status.
Alzheimer's & Dementia, 2011
Radiotherapy and Oncology, 2019
Purpose: Several fractionation schedules exist to treat localized prostate cancer. Some clinician... more Purpose: Several fractionation schedules exist to treat localized prostate cancer. Some clinicians are hesitant to prescribe moderate hypofractionation while waiting for clinical trial data to mature due to late toxicity concerns, and no phase III trials comparing stereotactic ablative radiotherapy (RT) to conventionally fractionated RT have been published. If the trade-off men are willing to make for treatment convenience at the expense of toxicity was quantified, then when the trial data are available clinicians will be better able to counsel localized prostate cancer patients regarding their external beam radiotherapy (EBRT) options. The purpose of this study was to pilot a Discrete Choice Experiment (DCE), a type of hypothetical conjoint analysis, as a method to elicit how patients weigh these different attributes of treatment choice. A pilot study was completed to determine; 1) the feasibility of conducting a DCE in this patient population; 2) test if the attributes and levels are appropriate; and 3) calculate parameter estimates and the minimum sample size required to design an efficient DCE.
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Papers by Simone Chaudhary