Reduced brain perfusion and cognitive performance due to constitutional hypotension.
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ABSTRACT:
SUBMITTER: Duschek S
PROVIDER: S-EPMC1858602 | biostudies-other | 2007 Apr
REPOSITORIES: biostudies-other
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Project description:BackgroundThe haemodynamic stress brought about by dialysis could justify the loss of structural and functional integrity of the central nervous system (CNS). The main objective of this study was to analyse the relationship between intradialytic hypotension (IDH) and cognitive function and brain morphometry.MethodsThe cross-sectional KIDBRAIN study (Cohort Study of Morphological Changes of the Brain by MRI in Chronic Kidney Disease Patients) included 68 prevalent patients with no history of neurological disorders (cerebrovascular disease and cognitive impairment) undergoing haemodialysis (HD). We analysed 18 non-consecutive dialysis sessions (first three of each month over a 6-month period) and various definitions of IDH were recorded. Global cognitive function (GCF) was assessed using the Mini-Mental State Examination (MMSE) and parameters of structural integrity of the CNS were obtained using volume morphometry magnetic resonance imaging analysis [grey matter (GM), white matter (WM) and hippocampus).ResultsA greater number of sessions with IDH were associated with less volume of WM (r = -0.359,P = 0.003) and hippocampus (r = -0.395, P = 0.001) independent of cardiovascular risk factors according to multivariable linear regression models (β = -0.198, P = 0.046 for WM; β = -0.253, P = 0.017 for hippocampus). The GCF by the MMSE was 27.3 ± 7.3.1 and was associated with WM volume (β = 0.403, P = 0.001) independent of GM and hippocampus volume. Symptomatic IDH was associated with GCF (r = -0.420, P < 0.001) in adjusted analysis (β = -0.339, P = 0.008).ConclusionsEven when asymptomatic, IDH is associated with a lower WM and hippocampus volume and reduced GCF in patients undergoing HD, thus suggesting greater vulnerability of the brain to the haemodynamic stress that may be generated by a dialysis session.
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Project description:We characterized the in vivo and in vitro consequences of reduced expression of Slc1a1 in mice. Heterozygous (HET) Slc1a1+/- mice, which model the hemi-deletion we found in human subjects with schizophrenia, were examined in a series of behavioral, anatomical and biochemical assays. Knockout (KO) mice were also included in the behavioral studies for comparative purposes. Both HET and KO mice exhibited evidence of increased anxiety-like behavior, impaired working memory, decreased exploratory activity and impaired sensorimotor gating, but no changes in overall locomotor activity compared to wildtype (WT) mice. The magnitude of changes was approximately equivalent in the HET and KO mice suggesting a dominant effect of the haploinsufficiency. Whole transcriptome RNA-Seq analysis detected expression changes of genes and pathways involved in cytokine signaling and synaptic functions in both brain and blood of the HET mice compared to WT mice.
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Project description:BackgroundThere is a range of factors that predict the development of Alzheimer's disease (AD) dementia among patients with amnestic mild cognitive impairment (MCI).ObjectivesTo identify the neuropsychological, genetic, and functional brain imaging data that best predict conversion to AD dementia in patients with amnestic MCI.MethodsFrom an initial group of 42 amnestic MCI patients assessed with neurological, neuropsychological, and brain SPECT, 39 (25 converters, 14 non-converters) were followed for 4 years, and 36 had APOE ε4 genotyping. Baseline neuropsychological data and brain SPECT data were used to predict which of the MCI patients would develop dementia by the end of the 4 years of observation.ResultsThe MCI patients who had converted to AD dementia had poorer performance on long-term visual memory and Semantic Fluency tests. The MCI subjects who developed dementia were more likely to carry at least one copy of the APOE ε4 allele (Hazard Risk = 4.22). There was lower brain perfusion in converters than non-converters, mainly in postcentral gyrus. An additional analysis of the SPECT data found differences between the MCI subjects and controls in the posterior cingulate gyrus and the basal forebrain. When the brain imaging and neuropsychological test data were combined in the same Cox regression model, only the neuropsychological test data were significantly associated with time to dementia.ConclusionAlthough the presence of reduced brain perfusion in postcentral gyrus and basal forebrain indicated an at-risk condition, it was the extent of memory impairment that was linked to the speed of decline from MCI to AD.
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Project description:The functional organization of the human brain adapts dynamically in response to a rapidly changing environment. However, the relation of these rapid changes in functional organization to cognitive functioning is not well understood. This study used a graph-based time-frame modularity analysis approach to identify temporally recurrent functional configuration patterns in neural responses to an n-back working memory task during fMRI. Working memory load was manipulated to investigate the functional relevance of the identified brain states. Four distinct brain states were defined by the predominant patterns of activation in the task-positive, default-mode, sensorimotor, and visual networks. Associated with escalating working memory load, the occurrence of the task-positive state and the probability of transitioning into this state increased. In contrast, the occurrence of the default-mode and sensorimotor states and the probability of these 2 states transitioning away from the task-positive state decreased. The task-positive state occurrence rate and the probability of transitioning from the default-mode state back to the task-positive state explained a significant and unique portion of the variance in task performance. The results demonstrate that dynamic brain activities support successful cognitive functioning and may have heuristic value for understanding abnormal cognitive functioning associated with multiple neuropsychiatric disorders.
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Project description:In a recent study of young mice, we showed that chronic mild hypoxia (CMH, 8% O2 ) triggers transient blood-brain barrier (BBB) disruption, and that microglia play an important vasculo-protective function in maintaining BBB integrity. As hypoxia is a common component of many age-related diseases, here we extended these studies to aged mice and found that hypoxia-induced vascular leak was greatly amplified (5-fold to 10-fold) in aged mice, being particularly high in the olfactory bulb and midbrain. While aged mice showed no obvious difference in the early stages of hypoxic angiogenic remodeling, the compensatory increase in vascularity and vessel maturation was significantly delayed. Compared with young brain, microglia in the normoxic aged brain were markedly activated, and this was further increased under hypoxic conditions, but paradoxically, this correlated with reduced vasculo-protection. Microglial depletion studies showed that microglial still play an important vasculo-protective role in aged brain, but interestingly, partial attenuation of microglial activation with minocycline resulted in fewer vascular leaks and reduced loss of endothelial tight junction proteins. Taken together, these findings suggest that increased BBB disruption in hypoxic aged mice can be explained both by a delayed vascular remodeling response and reduced microglial vasculo-protection. Importantly, they show that overly activated microglia in the aged brain are less effective at maintaining vascular integrity, though this can be improved by reducing microglial activation with minocycline, suggesting therapeutic potential for enhancing BBB integrity in the hypoxia-predisposed elderly population.
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Project description:The 15-Objects Test (15-OT) provides useful gradation of visuoperceptual impairment from normal aging through Alzheimer's disease (AD) and correlates with temporo-parietal perfusion. The objectives of this study were to analyze progression of 15-OT performance in mild cognitive impairment (MCI) and AD, and its correlates with cognition and single photon emission computerized tomography (SPECT), as well as to examine neuropsychological and SPECT differences between the MCI patients who developed AD and those who did not. From the initial 126 participants (42/group), 38 AD, 39 MCI, and 38 elderly controls (EC) were reassessed (SPECT: 35 AD, 33 MCI, 35 EC) after two years. The progression of cognitive and SPECT scores during this period was compared between groups, and baseline data between converters and non-converters. The 15-OT was the only measure of progression that differed between the three groups; worsening scores on 15-OT were associated with worsening in verbal and visual retention, and decreased perfusion on left postsubicular area. In the MCI patients, cerebral perfusion fell over the two years in medial-posterior cingulate and fronto-temporo-parietal regions; AD showed extensive changes involving almost all cerebral regions. No SPECT changes were detected in controls. At baseline, the MCI patients who developed AD differed from non-converters in verbal recognition memory, but not in SPECT perfusion. In conclusion, SPECT and 15-OT appear to provide a potential measure to differentiate between normal aging, MCI, and AD. Worsening on 15-OT was related to decreased perfusion in postsubicular area; but further longitudinal studies are needed to determine the contribution of 15-OT as a predictor of AD from MCI.
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Project description:Background: Reports suggest presence of cerebral hypoperfusion in multiple sclerosis (MS). Currently there are no studies that examine if the cerebral MS perfusion is affected by presence of cardiovascular comorbidities. Objective: To investigate associations between cerebral perfusion and disease outcomes in MS patients with and without comorbid cardiovascular diseases (CVD). Materials: One hundred three MS patients (75.7% female) with average age of 54.4 years and 21.1 years of disease duration underwent 3T MRI dynamic susceptibility contrast (DSC) imaging and were tested with Expanded Disability Status Scale, Multiple Sclerosis Severity Score (MSSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT) and Symbol Digit Modalities Test (SDMT). Structural and perfusion-based normalized measures of cerebral blood flow (nCBF), cerebral blood volume (nCBV) and mean transit time (MTT) of global, tissue-specific and deep gray matter (DGM) areas were derived. CBV and CBF were normalized by the normal-appearing white matter counterpart. Results: In linear step-wise regression analysis, age- and sex-adjusted, MSSS (R 2 = 0.186) was associated with whole brain volume (WBV) (? = -0.244, p = 0.046) and gray matter (GM) nCBF (? = -0.22, p = 0.035). T25FW (R 2 = 0.278) was associated with WBV (? = -0.289, p = 0.012) and hippocampus nCBV (? = -0.225, p = 0.03). 9HPT (R 2 = 0.401) was associated with WBV (? = 0.195, p = 0.049) and thalamus MTT (? = -0.198, p=0.032). After adjustment for years of education, SDMT (R 2 = 0.412) was explained by T2-lesion volume (? = -0.305, p = 0.001), and GM nCBV (? = 0.236, p = 0.013). No differences in MTT, nCBF nor nCBV measures between patients with (n = 42) and without CVD (n = 61) were found. Perfusion-measures were also not able to distinguish CVD status in a logistic regression model. Conclusion: Decreased GM and deep GM perfusion is associated with poorer MS outcomes, but not with presence of CVD.
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