Cardiovascular Metrics Associated With Prevention of Aging-Related Parkinsonian Signs Following Exercise Intervention in Sedentary Older Rats.
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ABSTRACT:
SUBMITTER: Kasanga EA
PROVIDER: S-EPMC8714671 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveMild parkinsonian signs (MPS) are an underappreciated neurologic condition in older adults; we assessed associations of MPS with measures of dopaminergic (catechol-O-methyltransferase [COMT] genotype, an indicator of synaptic dopamine levels) and vascular (white matter hyperintensities [WMH], an indicator of cerebral small vessel disease) factors.MethodsIn a cohort of older adults (mean age 82.6 years [SD 2.6]; 58.0% female; 38.8% black), we assessed cross-sectional associations of WMH volume and COMT Val158Met (rs4680) genotype (n = 35 Met/Met, n = 180 Val carriers) with MPS by regression models adjusted for demographic and health characteristics. Interactions between WMH and COMT were assessed and analyses were repeated stratified by COMT genotype (Met/Met related to higher synaptic dopamine vs Val carriers related to lower synaptic dopamine).ResultsMPS was present in 42.3% of our sample. WMH (odds ratio [OR] 1.16, confidence interval [CI] 1.05-1.27) but not COMT (Met/Met compared to Val carrier: OR 0.62, CI 0.27-1.42) was related to MPS. There was a significant interaction between WMH and COMT (p = 0.03). Stratified analyses reveled a strong association between WMH and MPS among COMT Val carriers (OR 1.23, CI 1.09-1.38), but not for Met/Met (OR 0.68, CI 0.45-1.02), independent of covariates.ConclusionsWMH had a direct relation with MPS. In contrast, COMT was not associated with MPS, but it did modify the effect of WMH on MPS. The dopaminergic system may provide compensation for the effects of WMH on MPS. These findings suggest that MPS has a vascular rather than dopaminergic origin in older adults, but both factors are important in MPS manifestation.
| S-EPMC5772161 | biostudies-literature
Project description:Background and Objective: Progressive loss of motor function including parkinsonian signs is common in older adults. As diet may contribute to the motor decline, we tested the hypothesis that dietary intake of antioxidant nutrients (carotenoids, vitamin E and vitamin C) is related to the progression of parkinsonian signs in older adults.Research Design and Methods: A total of 682 participants without a clinical diagnosis of Parkinson's Disease from the Rush Memory and Aging Project, were assessed annually over an average of 5.7 (±3.0) years using a 26-item modified version of the United Parkinson's Disease Rating Scale. The scale assesses the severity of four parkinsonian signs (bradykinesia, gait, tremors, and rigidity) that were averaged to construct a global parkinsonian sign score. Nutrient intakes were assessed at baseline using a validated food frequency questionnaire. The associations between quintiles of antioxidant nutrient intakes and progression of parkinsonian signs were assessed using mixed effects models adjusted for age, sex, education, smoking.Results: In separate adjusted models, a slower rate of progressive parkinsonian signs was observed among those in the highest intake quintiles of total carotenoids (β= -0.06, 95%CI: -0.10 to -0.02,), beta-carotene from foods (β= -0.04, 95% CI:-0.08 to -0.0021), lutein-zeaxanthin (β= -0.05, 95%CI:-0.09 to -0.02), vitamin E from foods (β= -0.04, 95%CI:-0.08 to -0.01,) and vitamin C from foods (β= -0.06, 95%CI:-0.10 to -0.02), when compared to those in the lowest quintiles of intake.Conclusion: A higher level of dietary antioxidant nutrients may slow the rate of parkinsonian sign progression in older adults.
| S-EPMC7680274 | biostudies-literature
Project description:ImportanceParkinsonian motor signs are common in the aging population and are associated with adverse health outcomes. Compared with Parkinson disease (PD), potential genetic risk factors for mild parkinsonian signs have been largely unexplored.ObjectiveTo determine whether PD susceptibility loci are associated with parkinsonism or substantia nigra pathology in a large community-based cohort of older persons.Design, setting, and participantsEighteen candidate single-nucleotide polymorphisms from PD genome-wide association studies were evaluated in a joint clinicopathologic cohort. Participants included 1698 individuals and a nested autopsy collection of 821 brains from the Religious Orders Study and the Rush Memory and Aging Project, 2 prospective community-based studies.Main outcomes and measuresThe primary outcomes were a quantitative measure of global parkinsonism or component measures of bradykinesia, rigidity, tremor, and gait impairment that were based on the motor Unified Parkinson's Disease Rating Scale. In secondary analyses, we examined associations with additional quantitative motor traits and postmortem indices, including substantia nigra Lewy bodies and neuronal loss.ResultsParkinson disease risk alleles in the MAPT (rs2942168; P = .0006) and CCDC62 (rs12817488; P = .004) loci were associated with global parkinsonism, and these associations remained after exclusion of patients with a PD diagnosis. Based on motor Unified Parkinson's Disease Rating Scale subscores, MAPT (P = .0002) and CCDC62 (P = .003) were predominantly associated with bradykinesia, and we further discovered associations between SREBF1 (rs11868035; P = .005) and gait impairment, SNCA (rs356220; P = .04) and rigidity, and GAK (rs1564282; P = .03) and tremor. In the autopsy cohort, only NMD3 (rs34016896; P = .03) was related to nigral neuronal loss, and no associations were detected with Lewy bodies.Conclusions and relevanceIn addition to the established link to PD susceptibility, our results support a broader role for several loci in the development of parkinsonian motor signs and nigral pathology in older persons.
| S-EPMC4039209 | biostudies-literature
Project description:IntroductionMild parkinsonian signs (MPS) are associated with morbidity. Identification of MPS progression markers may be vital for preventive management, yet has not been pursued. This study aimed to ascertain clinical/neuroimaging features predictive of MPS progression.Methods205 participants in the Health ABC Study were included. MPS was defined using published guidelines. MPS progression was evaluated by determining UPDRS-III change between baseline and follow-up ≥2 years later. Standard brain MRI and DTI were obtained at baseline. Correlation coefficients between demographics, vascular risk factors, imaging markers, and UPDRS-III change were adjusted for follow-up time. Linear regression was used to adjust for possible confounders in the relationship between imaging markers and MPS progression.Results30% of participants had baseline MPS. Demographics and risk factors did not differ significantly between participants with MPS (MPS+) and without MPS (MPS-). Mean follow-up time was 3.8±0.8 years. Older age, male gender, diabetes were associated with faster rate of UPDRS-III change in MPS- but not MPS+ participants. Among MPS- participants, the only imaging marker associated with faster UPDRS-III progression was higher gray matter mean diffusivity (MD), widespread in various cortico-subcortical bihemispheric regions, independent of age, gender, diabetes. No imaging features were associated with UPDRS-III change among MPS+ participants.ConclusionsLower gray matter integrity predicted MPS progression in those who did not have baseline MPS. Microstructural imaging may capture early changes related to MPS development, prior to macrostructural change. Any future management promoting gray matter preservation may inhibit MPS development.
| S-EPMC7415586 | biostudies-literature
Project description:Based upon a prior cross-sectional study, we hypothesized that an aerobic exercise intervention in sedentary older adults would improve a primary T cell-dependent immune response. Participants were a subset of older subjects from a large, ongoing exercise intervention study who were randomly assigned to either an aerobic exercise (Cardio, n=30, 68.9+0.8 years) or flexibility/balance (Flex, n=20, 69.9+1.2 years) intervention. The intervention consisted of either three aerobic sessions for 30-60 min at 55-70% VO(2 max) or two 60 min flexibility/balance sessions weekly for 10 months. Eight months into the intervention, samples were collected before intramuscular administration of KLH (125 microg), followed by sampling at 2, 3, and 6 weeks post-KLH. Serum anti-KLH IgM, IgG1, and IgG2 was measured by ELISA. Physiological and psychosocial measures were also assessed pre- and post-intervention. While there was no difference in the anti-KLH IgG2 response between groups, Cardio displayed significantly (p<0.05) higher anti-KLH IgG1 (at weeks 2, 3, and 6 post) and IgM responses when compared to Flex. Despite cardiovascular intervention-induced improvement in physical fitness (approximately 11% vs. 1% change in VO(2 peak) in Cardio vs. Flex, respectively), we found no relationship between improved fitness and enhanced anti-KLH antibody responses. Optimism, perceived stress, and affect were all associated with enhanced immune response. We have shown for the first time that cardiovascular training in previously sedentary elderly results in significantly higher primary IgG1 and IgM antibody responses, while having no effect on IgG2 production.
| S-EPMC2576741 | biostudies-literature
Project description:BackgroundThe recurrent hemizygous 22q11.2 deletion associated with 22q11.2 deletion syndrome has been identified as a genetic risk factor for early-onset PD. However, little is known about early motor signs in this condition.ObjectivesWe examined the presence, severity and possible factors associated with parkinsonism in adults with 22q11.2 deletion syndrome and without PD.MethodsWe compared motor signs between 82 adults with 22q11.2 deletion syndrome and 25 healthy controls, using the MDS-UPDRS part III, and three-dimensional motion-tracker technology to quantify components of bradykinesia.ResultsMedian MDS-UPDRS part III total and bradykinesia subscores were significantly higher in 22q11.2 deletion syndrome (median age: 26 years; range, 17-65) than in controls (P = 0.000; P = 0.000, respectively). Age was a significant contributor to bradykinesia subscore (B = 0.06; P = 0.01) and to the electronic bradykinesia component, velocity (B = -0.02; P = 0.000); psychotic illness did not significantly impact these analyses. In 22q11.2 deletion syndrome, MDS-UPDRS-defined bradykinesia was present in 18.3%, rigidity in 14.6%, and rest tremor in 12.2%.ConclusionsParkinsonian motor signs appear to be common and age related in 22q11.2 deletion syndrome. Longitudinal studies are needed to investigate possible symptom progression to PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
| S-EPMC7497092 | biostudies-literature
Project description:Age-related declines in cardiorespiratory fitness and physical function are mitigated by regular endurance exercise in older adults. This may be due, in part, to changes in the transcriptional program of skeletal muscle following repeated bouts of exercise. However, the impact of chronic exercise training on the transcriptional response to an acute bout of endurance exercise has not been clearly determined. Here, we characterized baseline differences in muscle transcriptome and exercise-induced response in older adults who were active/endurance trained or sedentary. RNA-sequencing was performed on vastus lateralis biopsy specimens obtained before, immediately after, and 3 h following a bout of endurance exercise (40 min of cycling at 60%–70% of heart rate reserve). Using a recently developed bioinformatics approach, we found that transcript signatures related to type I myofibers, mitochondria, and endothelial cells were higher in active/endurance-trained adults and were associated with key phenotypic features including V̇o2peak, ATPmax, and muscle fiber proportion. Immune cell signatures were elevated in the sedentary group and linked to visceral and intermuscular adipose tissue mass. Following acute exercise, we observed distinct temporal transcriptional signatures that were largely similar among groups. Enrichment analysis revealed catabolic processes were uniquely enriched in the sedentary group at the 3-h postexercise timepoint. In summary, this study revealed key transcriptional signatures that distinguished active and sedentary adults, which were associated with difference in oxidative capacity and depot-specific adiposity. The acute response signatures were consistent with beneficial effects of endurance exercise to improve muscle health in older adults irrespective of exercise history and adiposity.
2022-03-01 | GSE151066 | GEO
Project description:Older adults have low rates meeting the physical activity (PA) guidelines and high sedentary time. Low PA and excessive sedentary time have been linked to adverse health outcomes. Less is known about whether exercise training influences sedentary time and PA in various intensities.PurposeThis study aimed to examine the effects of a 16-wk aerobic exercise training on time spent being sedentary and on light-intensity PA (LPA) and moderate- to vigorous-intensity PA (MVPA) and step numbers in older women.MethodsInactive women (n = 61; age = 65.5 ± 4.3 yr) participated in moderate-intensity walking of either a low or a moderate dose (33.6 and 58.8 kJ·kg body weight per week, respectively). They wore a SenseWear Mini Armband at baseline and at end intervention to determine sedentary, LPA, and MVPA time and step numbers.ResultsTime being sedentary, or spent on LPA and MVPA, did not change differently by exercise groups with different doses (all P values for group-time interaction >0.580). Overall, time being sedentary reduced from baseline to end intervention by approximately 39 min·d (P < 0.001), and LPA increased by 19 min·d (P = 0.003). MVPA time increased (P < 0.001), which was primarily accounted for by the supervised exercise. Interestingly, daily steps increased more in the moderate-dose than the low-dose group (P = 0.023 for group-time interaction; 33.6% and 19.8% median increase in moderate- and low-dose groups, respectively). Also, there were individual differences in these changes.ConclusionResults indicated that, on average, older women did not reduce time of LPA or MVPA outside the exercise program or increase sedentary time as a result of participating in the exercise program.
| S-EPMC7944948 | biostudies-literature
Project description:Healthy but sedentary aging leads to cardiovascular stiffening, whereas life-long endurance training preserves left ventricular (LV) compliance. However, it is unknown whether exercise training started later in life can reverse the effects of sedentary behavior on the heart.Twelve sedentary seniors and 12 Masters athletes were thoroughly screened for comorbidities. Subjects underwent invasive hemodynamic measurements with pulmonary artery catheterization to define Starling and LV pressure-volume curves; secondary functional outcomes included Doppler echocardiography, magnetic resonance imaging assessment of cardiac morphology, arterial stiffness (total aortic compliance and arterial elastance), and maximal exercise testing. Nine of 12 sedentary seniors (70.6±3 years; 6 male, 3 female) completed 1 year of endurance training followed by repeat measurements. Pulmonary capillary wedge pressures and LV end-diastolic volumes were measured at baseline, during decreased cardiac filling with lower-body negative pressure, and increased filling with saline infusion. LV compliance was assessed by the slope of the pressure-volume curve. Before training, Vo(2)max, LV mass, LV end-diastolic volume, and stroke volume were significantly smaller and the LV was less compliant in sedentary seniors than Masters athletes. One year of exercise training had little effect on cardiac compliance. However, it reduced arterial elastance and improved Vo(2)max by 19% (22.8±3.4 versus 27.2±4.3 mL/kg/mL; P<0.001). LV mass increased (10%, 64.5±7.9 versus 71.2±12.3 g/m(2); P=0.037) with no change in the mass-volume ratio.Although 1 year of vigorous exercise training did not appear to favorably reverse cardiac stiffening in sedentary seniors, it nonetheless induced physiological LV remodeling and imparted favorable effects on arterial function and aerobic exercise capacity.
| S-EPMC3730488 | biostudies-literature
Project description:Mild motor symptoms including parkinsonian signs are common in old age, but their underlying neuropathology is unclear. We tested the hypothesis that cerebrovascular pathologies are related to parkinsonian signs.We studied brain autopsies from 418 deceased participants from the Religious Order Study, who underwent evaluation of parkinsonian signs with a modified version of the motor section of the Unified Parkinson's Disease Rating Scale. Brains were evaluated for macroscopic and microinfarcts and the severity of arteriolosclerosis. Regression analyses were used to examine the association of cerebrovascular pathologies with parkinsonian signs.More than 35% of cases (N=149) showed macroscopic infarcts. Almost 30% of cases without macroscopic infarcts showed pathologies not detected by conventional brain imaging: microinfarcts (N=33 [7.9%]), arteriolosclerosis (N=62 [14.8%]), or both (N=24 [5.7%]). Macroscopic infarcts, specifically multiple cortical and ?1 subcortical macroscopic infarcts, were related to higher global parkinsonian scores. The presence of multiple and cortical microinfarcts was associated with global parkinsonian score. Arteriolosclerosis was associated with global parkinsonian score, but this effect was attenuated and no longer significant after accounting for infarcts. Each of the 3 pathologies was separately associated with parkinsonian gait (macroscopic infarcts [estimate, 0.552; SE, 0.210; P=0.009]; microinfarcts [estimate, 0.424; SE, 0.213; P=0.047]; arteriolosclerosis [estimate, 0.191; SE, 0.056; P<0.001]). Further analyses showed that subcortical macroscopic and microinfarcts were specifically associated with the severity of parkinsonian gait.Cerebrovascular pathologies, including macroscopic infarcts, microinfarcts, and arteriolosclerosis, are common in older persons and may be unrecognized common etiologies of mild parkinsonian signs, especially parkinsonian gait, in old age.
| S-EPMC3202031 | biostudies-literature