Mapping the transcriptomic changes of endothelial compartment in human hippocampus across aging and mild cognitive impairment.
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ABSTRACT:
SUBMITTER: Guebel DV
PROVIDER: S-EPMC8181899 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC6474328 | biostudies-literature
Project description:White matter lesions are highly prevalent in individuals with Alzheimer's disease (AD). Although these lesions are presumed to be of vascular origin and linked to small vessel disease in older adults, little information exists about their relationship to markers of classical AD neurodegeneration. Thus, we examined the link between these white matter changes (WMC) segmented on T1-weighted MRI and imaging markers presumed to be altered due to primary AD neurodegenerative processes. Tissue microstructure of WMC was quantified using diffusion tensor imaging and the relationship of WMC properties and volume to neuroimaging markers was examined in 219 cognitively healthy older adults and individuals with mild cognitive impairment and AD using data from the Alzheimer's Disease Neuroimaging Initiative. No significant group differences in WMC properties were found. However, there were strong associations between diffusivity of WMC and ventricular volume, volume of WMC and total WM volume. In comparison, group differences in parahippocampal white matter microstructure were found for all diffusion metrics and were largely explained by hippocampal volume. Factor analysis on neuroimaging markers suggested two independent sets of covarying degenerative changes, with potentially age- and vascular-mediated tissue damage contributing to one factor and classical neurodegenerative changes associated with AD contributing to a second factor. These data demonstrate two potentially distinct classes of degenerative change in AD, with one factor strongly linked to aging, ventricular expansion, and both volume and tissue properties of white matter lesions, while the other factor related to classical patterns of cortical and hippocampal neurodegeneration in AD.
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-08-05 | E-GEOD-63063 | biostudies-arrayexpress
Project description:Background: Effective treatment for Alzheimer’s disease (AD) remains an unmet need. Thus, identifying patients with mild cognitive impairment (MCI) who are at high-risk of progressing to AD is crucial for early intervention. Methods: Blood-based transcriptomics analyses were performed using a longitudinal study cohort to compare progressive MCI (P-MCI, n=28), stable MCI (S-MCI, n=39), and AD patients (n=49). Statistical DESeq2 analysis and machine learning methods were employed to identify differentially expressed genes (DEGs) and develop prediction models. Results: We discovered a remarkable gender-specific difference in DEGs that distinguish P-MCI from S-MCI. Machine learning models achieved high accuracy in distinguishing P-MCI from S-MCI (AUC 0.93), AD from S-MCI (AUC 0.94), and AD from P-MCI (AUC 0.92). An 8-gene signature was identified for distinguishing P-MCI from S-MCI.
2024-11-30 | GSE282742 | GEO
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.
| S-EPMC6714864 | biostudies-literature
Project description:BACKGROUND/OBJECTIVES:Behavioral problems in individuals with Alzheimer's disease (AD) impose major management challenges. Current prevention strategies are anchored to cognitive outcomes, but behavioral outcomes may provide another, clinically relevant opportunity for preemptive therapy. We sought to determine whether personality changes that predispose to behavioral disorders arise during the transition from preclinical AD to mild cognitive impairment (MCI). DESIGN:Longitudinal observational cohort study. SETTING:Academic medical center. PARTICIPANTS:Members of an apolipoprotein E (APOE) ɛ4 genetically enriched cohort of Maricopa County residents who were neuropsychiatrically healthy at entry (N = 277). Over a mean interval of 7 years, 25 who developed MCI and had the Neuroticism, Extraversion, and Openness Personality Inventory-Revised (NEO-PI-R) before and during the MCI transition epoch were compared with 252 nontransitioners also with serial NEO-PI-R administrations. INTERVENTION:Longitudinal administration of the NEO-PI-R and neuropsychological test battery. MEASUREMENTS:Change in NEO-PI-R factor scores (neuroticism, extraversion, openness, agreeableness, conscientiousness) from entry to the epoch of MCI diagnosis or an equivalent follow-up duration in nontransitioners. RESULTS:NEO-PI-R neuroticism T-scores increased significantly more in MCI transitioners than in nontransitioners (mean 2.9, 95% confidence interval (CI) = 0.9-4.9 vs 0, 95% CI = -0.7-0.7, P = .02), and openness decreased more in MCI transitioners than in nontransitioners (-4.8, 95% CI = -7.3 to -2.4 vs -1.0, 95% CI = -1.6 to -0.4, P < .001). Concurrent subclinical but statistically significant changes in behavioral scores worsened more in MCI transitioners than nontransitioners for measures of depression, somatization, irritability, anxiety, and aggressive attitude. CONCLUSION:Personality and subclinical behavioral changes begin during the transition from preclinical AD to incident MCI and qualitatively resemble the clinically manifest behavioral disorders that subsequently arise in individuals with frank dementia.
| S-EPMC5906173 | biostudies-literature
Project description:BackgroundLesbian and gay older adults have health disparities that are risk factors for Alzheimer's disease, yet little is known about the neurocognitive aging of sexual minority groups.ObjectiveTo explore cross-sectional and longitudinal dementia outcomes for adults in same-sex relationships (SSR) and those in mixed-sex relationships (MSR).MethodsThis prospective observational study utilized data from the National Alzheimer's Coordinating Center Uniform Data Set (NACC UDS) collected from contributing Alzheimer's Disease Research Centers. Participants were adults aged 55+ years at baseline with at least two visits in NACC UDS (from September 2005 to March 2021) who had a spouse, partner, or companion as a co-participant. Outcome measures included CDR® Dementia Staging Instrument, NACC UDS neuropsychological testing, and the Functional Activities Questionnaire. Multivariable linear mixed-effects models accounted for center clustering and repeated measures by individual.ResultsBoth MSR and SSR groups experienced cognitive decline regardless of baseline diagnosis. In general, MSR and SSR groups did not differ statistically on cross-sectional or longitudinal estimates of functioning, dementia severity, or neuropsychological testing, with two primary exceptions. People in SSR with mild cognitive impairment showed less functional impairment at baseline (FAQ M = 2.61, SD = 3.18 vs. M = 3.97, SD = 4.53, respectively; p < 0.01). The SSR group with dementia had less steep decline in attention/working memory (β estimates = -0.10 versus -0.18; p < 0.01).ConclusionParticipants in SSR did not show cognitive health disparities consistent with a minority stress model. Additional research into protective factors is warranted.
| S-EPMC10029351 | biostudies-literature
Project description:ObjectiveThis study evaluated longitudinal CSF biomarker measures collected when participants were cognitively normal to determine the magnitude and time course of biomarker changes before the onset of clinical symptoms in subjects with mild cognitive impairment (MCI).MethodsLongitudinal CSF collection and cognitive assessments were performed on a cohort of 265 participants who were cognitively normal at their baseline assessment and subsequently developed MCI or dementia. CSF ?-amyloid 1-42 (A?1-42), total tau (t-tau), and phosphorylated tau (p-tau) were determined longitudinally. Consensus diagnoses were completed annually. Cox regression analyses were performed, with baseline CSF values and time-dependent rate of change in CSF values as covariates (adjusted by baseline age, race, and education), in relation to time to onset of mild cognitive symptoms.ResultsThe mean time from baseline to onset of mild cognitive symptoms was 5.41 years. Increased risk of progressing from normal cognition to onset of clinical symptoms was associated with baseline values of A?1-42, p-tau, and the ratios of p-tau/A?1-42 and t-tau/A?1-42 (p < 0.002). Additionally, the rate of change in the ratios of t-tau/A?1-42 (p < 0.004) and p-tau/A?1-42 (p < 0.02) was greater among participants who were subsequently diagnosed with MCI.ConclusionsBaseline differences in CSF values were predictive of clinical symptoms that were a harbinger of a diagnosis of MCI more than 5 years before symptom onset, and continue to show longitudinal changes as cognitive symptoms develop, demonstrating that baseline and longitudinal changes in CSF biomarkers are evident during the preclinical phase of Alzheimer disease.
| S-EPMC3821715 | biostudies-literature
Project description:Amnestic MCI is often considered an early clinical stage of AD, but its subtle presentation leads to infrequent neurological evaluations. Early plasma biomarker screening during routine check-ups in community hospitals could enhance aMCI detection rates. Advances in proteomics, particularly mass spectrometry, have enabled the detection of low-abundance plasma proteins, opening new possibilities for aMCI biomarker identification. This study included 84 participants from the STAR cohort. We utilized deep plasma proteomics to detect low-abundance proteins, enriched with biofunctional magnetic beads. An early diagnostic model for aMCI was developed through bioinformatics and machine learning, with performance compared to the Simoa assay.
2024-09-26 | PXD056265 |
Project description:Alzheimer's disease (AD) patients suffer progressive cerebral atrophy before dementia onset. However, the region-specific atrophic processes and the influences of age and apolipoprotein E (APOE) on atrophic trajectory are still unclear. By mapping the region-specific nonlinear atrophic trajectory of whole cerebrum from amnestic mild cognitive impairment (aMCI) to AD based on longitudinal structural magnetic resonance imaging data from Alzheimer's disease Neuroimaging Initiative (ADNI) database, we unraveled a quadratic accelerated atrophic trajectory of 68 cerebral regions from aMCI to AD, especially in the superior temporal pole, caudate, and hippocampus. Besides, interaction analyses demonstrated that APOE ε4 carriers had faster atrophic rates than noncarriers in 8 regions, including the caudate, hippocampus, insula, etc.; younger patients progressed faster than older patients in 32 regions, especially for the superior temporal pole, hippocampus, and superior temporal gyrus; and 15 regions demonstrated complex interaction among age, APOE, and disease progression, including the caudate, hippocampus, etc. (P < 0.05/68, Bonferroni correction). Finally, Cox proportional hazards regression model based on the identified region-specific biomarkers could effectively predict the time to AD conversion within 10 years. In summary, cerebral atrophic trajectory mapping could help a comprehensive understanding of AD development and offer potential biomarkers for predicting AD conversion.
| S-EPMC9930625 | biostudies-literature