Dataset Information

Cerebrovascular Resistance in Healthy Aging and Mild Cognitive Impairment.

ABSTRACT: Measures of cerebrovascular reactivity (CVR) are used to judge the health of the brain vasculature. In this study, we report the use of several different analyses of blood oxygen dependent (BOLD) fMRI responses to CO₂ to provide a number of metrics of CVR based on the sigmoidal resistance response to CO₂. To assess possible differences in these metrics with age, we compiled atlases reflecting voxel-wise means and standard deviations for four different age ranges and for a group of patients with mild cognitive impairment (MCI) and compared them. Sixty-seven subjects were recruited for this study and scanned at 3T field strength. Of those, 51 healthy control volunteers between the ages of 18-83 were recruited, and 16 (MCI) subjects between the ages of 61-83 were recruited. Testing was carried out using an automated computer-controlled gas blender to induce hypercapnia in a step and ramp paradigm while monitoring end-tidal partial pressures of CO₂. Surprisingly, some resistance sigmoid parameters in the oldest control group were increased compared to the youngest control group. Resistance amplitude maps showed increases in clusters within the temporal cortex, thalamus, corpus callosum and brainstem, and resistance reserve maps showed increases in clusters within the cingulate cortex, frontal gyrus, and corpus callosum. These findings suggest that some aspects of vascular reactivity in parts of the brain are initially maintained with age but then may increase in later years. We found significant reductions in all resistance sigmoid parameters (amplitude, reserve, sensitivity, midpoint, and range) when comparing MCI patients to controls. Additionally, in controls and in MCI patients, amplitude, range, reserve, and sensitivity in white matter (WM) was significantly reduced compared to gray matter (GM). WM midpoints were significantly above those of GM. Our general conclusion is that vascular regulation in terms of cerebral blood flow (CBF) responsiveness to CO₂ is not significantly affected by age, but is reduced in MCI. These changes in cerebrovascular regulation demonstrate the value of resistance metrics for mapping areas of dysregulated blood flow in individuals with MCI. They may also be of value in the investigation of patients with vascular risk factors at risk for developing vascular dementia.

SUBMITTER: McKetton L

PROVIDER: S-EPMC6474328 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cerebrovascular Resistance in Healthy Aging and Mild Cognitive Impairment.

McKetton Larissa L Cohn Melanie M Tang-Wai David F DF Sobczyk Olivia O Duffin James J Holmes Kenneth R KR Poublanc Julien J Sam Kevin K Crawley Adrian P AP Venkatraghavan Lashmi L Fisher Joseph A JA Mikulis David J DJ

Frontiers in aging neuroscience 20190412

Measures of cerebrovascular reactivity (CVR) are used to judge the health of the brain vasculature. In this study, we report the use of several different analyses of blood oxygen dependent (BOLD) fMRI responses to CO<sub>2</sub> to provide a number of metrics of CVR based on the sigmoidal resistance response to CO<sub>2</sub>. To assess possible differences in these metrics with age, we compiled atlases reflecting voxel-wise means and standard deviations for four different age ranges and for a g ...[more]

PMID: 31031616

Similar Datasets

Project description:With increasing age, a subset of otherwise healthy individuals undergoes impairments in learning and memory that have been termed mild cognitive impairment (MCI). The enhanced neuronal activity associated with learning and memory requires increased cerebral blood flow (CBF) to specific brain regions. However, the interactions between cerebral blood flow and MCI remain unclear. In this study, we address whether baseline or hypercapnia-induced (increased blood CO(2) levels) changes in CBF are modified with age, and whether these measures are predictive of cognitive status in rodents. Adult and aged rats were evaluated using a hippocampally-dependent task in a water maze. Aged rats were classified as memory-impaired or memory-intact based on performance comparisons with adult rats. Cerebral blood flow was assessed using flow-alternating inversion recovery (FAIR) magnetic resonance imaging (MRI), before and after breathing 10% CO(2). The transition period between CO(2) concentrations was examined with blood oxygen level dependent (BOLD) MRI. Separation of aged animals into memory-intact and impaired categories revealed increased basal perfusion in the dorsal hippocampus of memory-impaired versus memory-intact aged animals. Linear regression revealed that higher hippocampal perfusion was correlated with impaired memory in aged animals, and a logistic regression indicated that hippocampal perfusion predicted spatial memory ability. Several brain regions of aged rats demonstrated an attenuation of the perfusion increase normally observed in adult rats under hypercapnia. Memory-impaired animals were the primary contributor to this effect, as their perfusion response to hypercapnia was significantly reduced compared to adult animals. Aged, memory-intact animals were not significantly different from adults. BOLD MRI demonstrated a reduced response in aged animals to hypercapnia, with impaired animals being the primary contributor to the effect. A logistic regression model based on basal and hypercapnia perfusion correctly predicted cognitive status in 83.3% of animals tested. Our results indicate that age-related changes in vascular reactivity and perfusion are important contributing factors in memory impairment.

Project description:Although subtle discourse declines in people with mild cognitive impairment (MCI) have been reported, heterogeneous measures and tasks among the MCI discourse studies have yielded widely varying outcomes. The present study aimed to first, identify discourse measures that aid the differentiation among people with amnestic MCI (aMCI), people with non-amnestic MCI (naMCI), and cognitively healthy control (HC) participants, and second, delineate the cognitive functions related to such discourse measures. Three discourse tasks (an episodic narrative, a planning task, and a picture description) were performed by 30 aMCI, 22 naMCI, and 21 HC participants. Samples were analyzed using six categories of 15 measures, namely coherence, cohesion, proposition, grammaticality, lexicality, and fluency. The statistical analyses included (1) a multivariate analysis of variance for group comparison; (2) binary simple logistic regression and receiver operating characteristic curve analysis for differentiation between two groups; (3) binary multiple logistic regression for being diagnosed with naMCI or aMCI with the minimum number of predictors; and (4) Pearson correlation analysis for identifying the cognitive functions associated with the discourse measures. The proportion of cohesive words and propositional density in aMCI participants were worse than those in naMCI participants. Global coherence, the proportion of cohesive words, and the proportion of dysfluencies and pauses in naMCI participants were lower than those in the HC participants. Global and local coherence and the proportion of cohesive words, cohesive ties per utterances, propositional density, and dysfluencies and pauses in aMCI participants were worse than those in the HC participants. The aforementioned measures were demonstrated to be effective predictors for classifying groups by receiver operating characteristic curve analysis. In addition, the proportions of cohesive words and pauses were common discourse measures for differentiation between naMCI and HC participants or between aMCI and HC participants using binary multiple logistic regression. According to the correlation analysis, memory and executive functions are needed for coherent, cohesive, and efficient discourse productions in MCI. The detailed description of discourse performances in this study will aid the characterization of the declined language abilities of MCI participants and also the understanding of the cognitive functions involved in discourse performance in MCI.

Project description:Growth hormone-releasing hormone (GHRH) has been previously shown to have cognition-enhancing effects. The role of neurotransmitter changes, measured by proton magnetic resonance spectroscopy, may inform the mechanisms for this response.To examine the neurochemical effects of GHRH in a subset of participants from the parent trial.Randomized, double-blind, placebo-controlled substudy of a larger trial.Clinical research unit at the University of Washington School of Medicine.Thirty adults (17 with mild cognitive impairment [MCI]), ranging in age from 55 to 87 years, were enrolled and successfully completed the study.Participants self-administered daily subcutaneous injections of tesamorelin (Theratechnologies Inc), a stabilized analogue of human GHRH (1 mg/d), or placebo 30 minutes before bedtime for 20 weeks. At baseline and weeks 10 and 20, participants underwent brain magnetic resonance imaging and spectroscopy protocols and cognitive testing and provided blood samples after fasting. Participants also underwent glucose tolerance tests before and after intervention.Brain levels of glutamate, inhibitory transmitters ?-aminobutyric acid (GABA) and N-acetylaspartylglutamate (NAAG), and myo-inositol (MI), an osmolyte linked to Alzheimer disease in humans, were measured in three 2?×?2?×?2-cm3 left-sided brain regions (dorsolateral frontal, posterior cingulate, and posterior parietal). Glutamate, GABA, and MI levels were expressed as ratios to creatine plus phosphocreatine, and NAAG was expressed as a ratio to N-acetylaspartate.After 20 weeks of GHRH administration, GABA levels were increased in all brain regions (P?<?.04), NAAG levels were increased (P?=?.03) in the dorsolateral frontal cortex, and MI levels were decreased in the posterior cingulate (P?=?.002). These effects were similar in adults with MCI and older adults with normal cognitive function. No changes in the brain levels of glutamate were observed. In the posterior cingulate, treatment-related changes in serum insulin-like growth factor 1 were positively correlated with changes in GABA (r?=?0.47; P?=?.001) and tended to be negatively correlated with MI (r?=?-0.34; P?=?.06). Consistent with the results of the parent trial, a favorable treatment effect on cognition was observed in substudy participants (P?=?.03). No significant associations were observed between treatment-related changes in neurochemical and cognitive outcomes. Glucose homeostasis in the periphery was not reliably affected by GHRH administration and did not account for treatment neurochemical effects.Twenty weeks of GHRH administration increased GABA levels in all 3 brain regions, increased NAAG levels in the frontal cortex, and decreased MI levels in the posterior cingulate. To our knowledge, this is the first evidence that 20 weeks of somatotropic supplementation modulates inhibitory neurotransmitter and brain metabolite levels in a clinical trial, and it provides preliminary support for one possible mechanism to explain favorable GHRH effects on cognition in adults with MCI and in healthy older adults. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00257712.

Dataset Information

Cerebrovascular Resistance in Healthy Aging and Mild Cognitive Impairment.

Publications

Cerebrovascular Resistance in Healthy Aging and Mild Cognitive Impairment.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets