The effect of physical exercise on cerebral blood flow in Alzheimer's disease.
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ABSTRACT:
SUBMITTER: van der Kleij LA
PROVIDER: S-EPMC6129739 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
Publications
The effect of physical exercise on cerebral blood flow in Alzheimer's disease.
van der Kleij Lisa A LA Petersen Esben T ET Siebner Hartwig R HR Hendrikse Jeroen J Frederiksen Kristian S KS Sobol Nanna A NA Hasselbalch Steen G SG Garde Ellen E
NeuroImage. Clinical 20180904
In recent years there has been an increasing focus on the relation between cerebrovascular health, physical exercise and Alzheimer's disease. The aim of the current study was to determine the effect of moderate-to-high-intensity aerobic exercise on cerebral blood flow in patients with mild to moderate Alzheimer's disease. Fifty-one patients were randomized to either usual care or moderate-to-high intensity aerobic exercise for 16 weeks. Exercise had no consistent effect on whole brain or regiona ...[more]
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Project description:Background: Depression is common in Alzheimer's disease (AD) with an unclear neural mechanism. This study aimed to investigate the underlying cerebral perfusion associated with depression in AD and evaluate its clinical significance. Method: Twenty-one AD patients and 21 healthy controls (HCs) were enrolled in this study. The depressive symptom was defined according to the Hamilton Depression Rating Scale (HAMD). Nine patients were diagnosed as AD with depression symptoms (HAMD >7). Three-dimensional pseudocontinuous arterial spin labeling MR imaging was conducted to measure regional cerebral blood flow (CBF). Neuropsychological tests covered cognition and depressive scores. Between-group comparisons on clinical variables and regional CBFs, relationship between regional CBF and depressive score, and identification of AD patients with depression were performed using covariance analysis, linear regression, and receiver operating characteristic (ROC) analysis, respectively. Results: Compared with HCs, AD patients without depression exhibited lower gray matter CBF (p = 0.016); compared with AD patients without depression, AD patients with depression had higher CBF in the right supplementary motor area (39.23 vs. 47.91 ml/100 g/min, p = 0.017) and right supramarginal gyrus (35.54 vs. 43.85 ml/100 g/min, p = 0.034). CBF in the right supplementary motor area was correlated with depressive score (β = 0.46, p = 0.025). The combination of CBF in the right supplementary motor area and supramarginal gyrus and age could identify AD patients with depression from those without depression with a specificity of 100%, sensitivity of 66.67%, accuracy of 85.71%, and area under the curve of 0.87. Conclusions: Our findings suggested that hyperperfusion of the right supplementary motor area and right supramarginal gyrus were associated with depression syndrome in AD, which could provide a potential neuroimaging marker to evaluate the depression state in AD.
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Project description:Background and objectivesVascular disease is a known risk factor for Alzheimer's disease (AD). Endothelial dysfunction has been linked to reduced cerebral blood flow. Endothelial nitric oxide synthase pathway (eNOS) upregulation is known to support endothelial health. This single-center, proof-of-concept study tested whether the use of three medications known to augment the eNOS pathway activity improves cognition and cerebral blood flow (CBF).MethodsSubjects with mild AD or mild cognitive impairment (MCI) were sequentially treated with the HMG-CoA reductase synthesis inhibitor simvastatin (weeks 0-16), L-arginine (weeks 4-16), and tetrahydrobiopterin (weeks 8-16). The primary outcome of interest was the change in CBF as measured by MRI from baseline to week 16. Secondary outcomes included standard assessments of cognition.ResultsA total of 11 subjects were deemed eligible and enrolled. One subject withdrew from the study after enrollment, leaving 10 subjects for data analysis. There was a significant increase in CBF from baseline to week 8 by ~13% in the limbic and ~15% in the cerebral cortex. Secondary outcomes indicated a modest but significant increase in the MMSE from baseline (24.2±3.2) to week 16 (26.0±2.7). Exploratory analysis indicated that subjects with cognitive improvement (reduction of the ADAS-cog 13) had a significant increase in their respective limbic and cortical CBF.ConclusionsTreatment of mild AD/MCI subjects with medications shown to augment the eNOS pathway was well tolerated and associated with modestly increased cerebral blood flow and cognitive improvement.Trial registrationThis study is registered in https://www.Clinicaltrialsgov ; registration identifier: NCT01439555; date of registration submitted to registry: 09/23/2011; date of first subject enrollment: 11/2011.
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Project description:Studies in transgenic mice overexpressing amyloid precursor protein (APP) demonstrate impaired autoregulation of cerebral blood flow (CBF) to changes in arterial pressure and suggest that cerebrovascular dysfunction may be critically important in the development of pathological Alzheimer's disease (AD). Given the relevance of such a finding for guiding hypertension treatment in the elderly, we assessed autoregulation in individuals with AD. Twenty persons aged 75±6 years with very mild or mild symptomatic AD (Clinical Dementia Rating 0.5 or 1.0) underwent (15)O-positron emission tomography (PET) CBF measurements before and after mean arterial pressure (MAP) was lowered from 107±13 to 92±9 mm Hg with intravenous nicardipine; (11)C-PIB-PET imaging and magnetic resonance imaging (MRI) were also obtained. There were no significant differences in mean CBF before and after MAP reduction in the bilateral hemispheres (-0.9±5.2 mL per 100 g per minute, P=0.4, 95% confidence interval (CI)=-3.4 to 1.5), cortical borderzones (-1.9±5.0 mL per 100 g per minute, P=0.10, 95% CI=-4.3 to 0.4), regions of T2W-MRI-defined leukoaraiosis (-0.3±4.4 mL per 100 g per minute, P=0.85, 95% CI=-3.3 to 3.9), or regions of peak (11)C-PIB uptake (-2.5±7.7 mL per 100 g per minute, P=0.30, 95% CI=-7.7 to 2.7). The absence of significant change in CBF with a 10 to 15 mm Hg reduction in MAP within the normal autoregulatory range demonstrates that there is neither a generalized nor local defect of autoregulation in AD.
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Project description:Cerebrovascular adaptation to pregnancy is poorly understood. We sought to assess cerebrovascular regulation in response to visual stimulation, hypercapnia and exercise across the three trimesters of pregnancy. Using transcranial Doppler (TCD) ultrasound, middle and posterior cerebral artery mean blood velocities (MCAvmean and PCAvmean) were measured continuously at rest and in response to (1) visual stimulation to assess neurovascular coupling (NVC); (2) a modified Duffin hyperoxic CO2 rebreathe test, and (3) an incremental cycling exercise test to volitional fatigue in non-pregnant (n = 26; NP) and pregnant women (first trimester [n = 13; TM1], second trimester [n = 21; TM2], and third trimester [n = 20; TM3]) in total 47 women. At rest, MCAvmean and PETCO2 were lower in TM2 compared to NP. PCAvmean was lower in TM2 but not TM1 or TM3 compared to NP. Cerebrovascular reactivity in MCAvmean and PCAvmean during the hypercapnic rebreathing test was not different between pregnant and non-pregnant women. MCAvmean continued to increase over the second half of the exercise test in TM2 and TM3, while it decreased in NP due to differences in ΔPETCO2 between groups. Pregnant women experienced a delayed decrease in MCAvmean in response to maximal exercise compared to non-pregnant controls which was explained by CO2 reactivity and PETCO2 level.
| S-EPMC7585927 | biostudies-literature
Project description:BACKGROUND:In clinical practice, visual assessment of glucose metabolism images is often used for the diagnosis of Alzheimer's disease (AD) through 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scans. However, visual assessment of the characteristic AD hypometabolic pattern relies on the expertise of the reader. Therefore, user-independent pipelines are preferred to evaluate the images and to classify the subjects. Moreover, glucose consumption is highly correlated with cerebral perfusion. Regional cerebral blood flow (rCBF) images can be derived from dynamic 11C-labelled Pittsburgh Compound B PET scans, which are also used for the assessment of the deposition of amyloid-? plaques on the brain, a fundamental characteristic of AD. The aim of this study was to explore whether these rCBF PIB images could be used for diagnostic purposes through the PMOD Alzheimer's Discrimination Tool. RESULTS:Both tracer relative cerebral flow (R1) and early PIB (ePIB) (20-130?s) uptake presented a good correlation when compared to FDG standardized uptake value ratio (SUVR), while ePIB (1-8?min) showed a worse correlation. All receiver operating characteristic curves exhibited a similar shape, with high area under the curve values, and no statistically significant differences were found between curves. However, R1 and ePIB (1-8?min) had the highest sensitivity, while FDG SUVR had the highest specificity. CONCLUSION:rCBF images were suggested to be a good surrogate for FDG scans for diagnostic purposes considering an adjusted threshold value.
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