Genetic polymorphisms for BDNF, COMT, and APOE do not affect gait or ankle motor control in chronic stroke: A preliminary cross-sectional study.
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ABSTRACT:
SUBMITTER: Aljuhni R
PROVIDER: S-EPMC7647948 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Previous studies have demonstrated that post-stroke gait rehabilitation combining functional electrical stimulation (FES) applied to the ankle muscles during fast treadmill walking (FastFES) improves gait biomechanics and clinical walking function. However, there is considerable inter-individual variability in response to FastFES. Although FastFES aims to sculpt ankle muscle coordination, whether changes in ankle muscle activity underlie observed gait improvements is unknown. The aim of this study was to investigate three cases illustrating how FastFES modulates ankle muscle recruitment during walking. Methods: We conducted a preliminary case series study on three individuals (53-70 y; 2 M; 35-60 months post-stroke; 19-22 lower extremity Fugl-Meyer) who participated in 18 sessions of FastFES (3 sessions/week; ClinicalTrials.gov: NCT01668602). Clinical walking function (speed, 6-min walk test, and Timed-Up-and-Go test), gait biomechanics (paretic propulsion and ankle angle at initial-contact), and plantarflexor (soleus)/dorsiflexor (tibialis anterior) muscle recruitment were assessed pre- and post-FastFES while walking without stimulation. Results:Two participants (R1, R2) were categorized as responders based on improvements in clinical walking function. Consistent with heterogeneity of clinical and biomechanical changes commonly observed following gait rehabilitation, how muscle activity was altered with FastFES differed between responders. R1 exhibited improved plantarflexor recruitment during stance accompanied by increased paretic propulsion. R2 exhibited improved dorsiflexor recruitment during swing accompanied by improved paretic ankle angle at initial-contact. In contrast, the third participant (NR1), classified as a non-responder, demonstrated increased ankle muscle activity during inappropriate phases of the gait cycle. Across all participants, there was a positive relationship between increased walking speeds after FastFES and reduced SOL/TA muscle coactivation. Conclusion:Our preliminary case series study is the first to demonstrate that improvements in ankle plantarflexor and dorsiflexor muscle recruitment (muscles targeted by FastFES) accompanied improvements in gait biomechanics and walking function following FastFES in individuals post-stroke. Our results also suggest that inducing more appropriate (i.e., reduced) ankle plantar/dorsi-flexor muscle coactivation may be an important neuromuscular mechanism underlying improvements in gait function after FastFES training, suggesting that pre-treatment ankle muscle status could be used for inclusion into FastFES. The findings of this case-series study, albeit preliminary, provide the rationale and foundations for larger-sample studies using similar methodology.
| S-EPMC6306420 | biostudies-literature
Project description:ObjectiveThe objective of this study was to determine whether three common genetic polymorphisms [apolipoprotein (APOE) ε4 (rs42938 and rs7412), brain derived neurotrophic factor (BDNF) Met (rs6265), and catechol-O-methyltransferase (COMT) Val (rs4680)] are associated with increased psychiatric symptomatology in individuals with pharmacoresistant epilepsy.MethodsOne hundred forty-eight adults (Mage = 38 years; 53% female) with refractory epilepsy completed self-report measures of mood, anxiety, and/or personality/psychopathology. Mann-Whitney U, t-tests, and Fisher's exact tests were used to determine if APOE4, BDNF Val66Met, or COMT Val158Met are associated with increased psychiatric symptomatology in people with epilepsy.ResultsAs a group, BDNF Met carriers reported greater symptoms of depression on the Personality Assessment Inventory (PAI) than those without a Met allele (p = 0.004); COMT Val carriers reported greater symptoms on the PAI Schizophrenia (p = 0.007), Antisocial Features (p = 0.04), and Alcohol Problems (p = 0.03) scales than noncarriers. On the individual level, a significantly greater proportion of BDNF Met carriers demonstrated elevated PAI Depression scores compared to those without a Met allele (p = 0.046). There was also a larger proportion of COMT Val carriers with elevated PAI Anxiety scores as compared to those without a Val allele (p = 0.036).SignificanceThis retrospective cross-sectional study provides preliminary evidence for a genetic basis of psychiatric comorbidities in epilepsy and suggests that BDNF and COMT may play an important role in the pathophysiology of mental health problems in this vulnerable population.
| S-EPMC8299517 | biostudies-literature
Project description:ObjectivesStroke patients suffer from ankle joint deformities due to spastic ankle muscles. This study evaluated the viability of using 3D scanned surface images of the feet of stroke victims to visually assess the deformities of a hemiparetic foot and investigated the influences of deformed ankle joints on gait kinematics.MethodsA total of 30 subjects with stroke-induced hemiparesis and 11 age-matched healthy controls completed the clinical assessments. We analyzed their feet's morphometric characteristics using a 3D scanner, identified convenient anthropometric measurements, and conducted gait trials on even and uneven terrains. The 3D foot morphometric characteristics were evaluated using the geometric morphometrics method (GMM).ResultsResults showed that there were significant differences in bilateral foot shapes between the chronic stroke patients and healthy controls and between the paretic and non-paretic sides in the chronic stroke patients. In stroke patients, those with the smaller medial malleoli's vertical tilt angles showed significantly different ankle ranges of motion of dorsi-/plantar flexion during gaits on uneven terrains (p = 0.009). In addition, those with the greater medial malleoli's vertical tilt angles showed significantly different ankle ranges of motion of inversion/eversion during gaits on even and uneven terrains (p < 0.05).ConclusionUsing 3D scanning technology, bilateral morphometric changes in the feet of chronic stroke patients were shown by GMM and the simple anthropometric measurements identified its shape deformities in the feet. Their possible effects on gait kinematics while walking on uneven terrains were investigated. Current methodology can be potentially useful in applying conventional productions of clinically manufactured, patient-fitted ankle-foot-orthosis in orthotics and prosthetics, and in detecting various unidentified pathological deformities in the feet.
| S-EPMC9947404 | biostudies-literature
Project description:Several single nucleotide polymorphisms have been linked to neural and cognitive variation in healthy adults. We examined contribution of three polymorphisms frequently associated with individual differences in cognition (Catechol-O-Methyl-Transferase Val158Met, Brain-Derived-Neurotrophic-Factor Val66Met, and Apolipoprotein E epsilon4) and a vascular risk factor (hypertension) in a sample of 189 volunteers (age 18-82). Genotypes were determined from buccal culture samples, and cognitive performance was assessed in 4 age-sensitive domains?fluid intelligence, executive function (inhibition), associative memory, and processing speed. We found that younger age and COMT Met/Met genotype, associated with low COMT activity and higher prefrontal dopamine content, were independently linked to better performance in most of the tested domains. Homozygotes for Val allele of BDNF polymorphism exhibited better associative memory and faster speed of processing than the Met allele carriers, with greater effect for women and persons with hypertension. Carriers of ApoE epsilon4 allele evidenced steeper age-related increase in costs of Stroop color interference, but showed no negative effects on memory. The findings indicate that age-related cognitive performance is differentially affected by distinct genetic factors and their interactions with vascular health status.
| S-EPMC2729285 | biostudies-literature
Project description:Abnormal spasticity and associated synergistic patterns are the most common neuromuscular impairments affecting ankle-knee-hip interlimb coordinated gait kinematics and kinetics in patients with hemiparetic stroke. Although patients with hemiparetic stroke undergo various treatments to improve gait and movement, it remains unknown how spasticity and associated synergistic patterns change after robot-assisted and conventional treatment. We developed an innovative ankle-knee-hip interlimb coordinated humanoid robot (ICT) to mitigate abnormal spasticity and synergistic patterns. The objective of the preliminary clinical trial was to compare the effects of ICT combined with conventional physical therapy (ICT-C) and conventional physical therapy and gait training (CPT-G) on abnormal spasticity and synergistic gait patterns in 20 patients with acute hemiparesis. We performed secondary analyses aimed at elucidating the biomechanical effects of Walkbot ICT on kinematic (spatiotemporal parameters and angles) and kinetic (active force, resistive force, and stiffness) gait parameters before and after ICT in the ICT-C group. The intervention for this group comprised 60-min conventional physical therapy plus 30-min robot-assisted training, 7 days/week, for 2 weeks. Significant biomechanical effects in knee joint kinematics; hip, knee, and ankle active forces; hip, knee, and ankle resistive forces; and hip, knee, and ankle stiffness were associated with ICT-C. Our novel findings provide promising evidence for conventional therapy supplemented by robot-assisted therapy for abnormal spasticity, synergistic, and altered biomechanical gait impairments in patients in the acute post-stroke recovery phase.Trial Registration: Clinical Trials.gov identifier NCT03554642 (14/01/2020).
| S-EPMC8613200 | biostudies-literature
Project description:The common single-nucleotide polymorphism (SNP) brain-derived neurotrophic factor (BDNF) valine-to-methionine substitution at codon 66 (Val66Met) has been associated with differences in memory functions and cortical plasticity following brain stimulation. Other studies could not confirm these results, though, and potential interactions of BDNF carrier status with other learning-relevant SNPs are largely unknown. The present study aimed to evaluate the effects of BDNF Val66Met genotype on paired associative stimulation (PAS)-induced motor cortex plasticity, while additionally taking catechol-O-methyltransferase (COMT) Val158Met and kidney and brain (KIBRA) rs17070145 carrier status into account. Therefore, a cohort of 2 × 16 age- and education-matched healthy young females underwent transcranial magnetic stimulation using an excitatory PAS(25) protocol to induce cortical plasticity. Cognitive performance was assessed using implicit grammar- and motor-learning tasks and a detailed neuropsychological test battery. While BDNF carrier status alone did not significantly influence PAS-induced cortical plasticity, we found a significant BDNF × COMT interaction, showing higher plasticity immediately following the PAS(25) protocol for the BDNF Val/Val vs Met genotype in COMT Met homozygotes only (ANOVA, p = 0.027). A similar advantage for this group was noted for implicit grammar learning (ANOVA, p = 0.021). Accounting for KIBRA rs17070145 did not explain significant variance. Our findings for the first time demonstrate an interaction of BDNF by COMT on human cortical plasticity. Moreover, they show that genotype-related differences in neurophysiology translate into behavioral differences. These findings might contribute to a better understanding of the mechanisms of interindividual differences in cognition.
| S-EPMC6622078 | biostudies-literature
Project description:BackgroundCognitive dysfunction is common among patients with brain tumors and can be associated with the disease and treatment with radiotherapy and chemotherapy. However, little is known about genetic risk factors that may moderate the vulnerability for developing cognitive dysfunction. In this study, we examined the association of single nucleotide polymorphisms (SNPs) in the catechol-O-methyl transferase (COMT), brain-derived neurotrophic factor (BDNF), and dystrobrevin-binding protein 1 (DTNBP1) genes with cognitive functions and neuroimaging outcomes in patients with brain tumors.MethodsOne hundred and fifty patients with brain tumors completed neuropsychological tests of attention, executive functions, and memory and were genotyped for polymorphisms in the COMT, BDNF, and DTNBP1 genes. Ratings of white matter (WM) abnormalities on magnetic resonance imaging scans were performed.ResultsMultivariate regression shrinkage analyses, adjusted for age, education, treatment type, time since treatment completion, and tumor location, indicated a significant association between the COMT SNP rs4680 (Val158Met) and memory with lower scores in delayed recall (P < .01) among homozygotes (valine/valine). Additional COMT, BDNF and DTNBP1 SNPs were significantly associated with attention, executive functions, and memory scores.ConclusionThis is the first study to suggest that known and newly described polymorphisms in genes associated with executive and memory functions in healthy individuals and other clinical populations may modulate cognitive outcome in patients with brain tumors.
| S-EPMC5035520 | biostudies-literature
Project description:An unsettled question in the use of robotics for post-stroke gait rehabilitation is whether task-specific locomotor training is more effective than targeting individual joint impairments to improve walking function. The paretic ankle is implicated in gait instability and fall risk, but is difficult to therapeutically isolate and refractory to recovery. We hypothesize that in chronic stroke, treadmill-integrated ankle robotics training is more effective to improve gait function than robotics focused on paretic ankle impairments.Participants with chronic hemiparetic gait were randomized to either six weeks of treadmill-integrated ankle robotics (n?=?14) or dose-matched seated ankle robotics (n?=?12) videogame training. Selected gait measures were collected at baseline, post-training, and six-week retention. Friedman, and Wilcoxon Sign Rank and Fisher's exact tests evaluated within and between group differences across time, respectively. Six weeks post-training, treadmill robotics proved more effective than seated robotics to increase walking velocity, paretic single support, paretic push-off impulse, and active dorsiflexion range of motion. Treadmill robotics durably improved gait dorsiflexion swing angle leading 6/7 initially requiring ankle braces to self-discarded them, while their unassisted paretic heel-first contacts increased from 44 % to 99.6 %, versus no change in assistive device usage (0/9) following seated robotics.Treadmill-integrated, but not seated ankle robotics training, durably improves gait biomechanics, reversing foot drop, restoring walking propulsion, and establishing safer foot landing in chronic stroke that may reduce reliance on assistive devices. These findings support a task-specific approach integrating adaptive ankle robotics with locomotor training to optimize mobility recovery.NCT01337960. https://clinicaltrials.gov/ct2/show/NCT01337960?term=NCT01337960&rank=1.
| S-EPMC4890526 | biostudies-literature
Project description:The val(66)met polymorphism in brain-derived neurotrophic factor (BDNF) has been associated with poorer outcomes after stroke. The mechanism for this finding remains uncertain but might be related to the reduced motor system activation associated with this polymorphism in healthy people.The current study examined whether the presence of the BDNF val(66)met polymorphism is associated with reduced motor system activation after stroke.Forty-two patients with stroke who were enrolled in 1 of 2 studies of robot-assisted arm motor therapy participated in the study. All participants were tested for the BDNF val(66)met polymorphism followed by functional magnetic resonance imaging during affected hand movement.Participants averaged 12 months poststroke and had wide-ranging motor deficits (Fugl-Meyer scale scores=14-60). Brain activation in participants without the BDNF val(66)met polymorphism (n=26) spanned bilateral motor networks with a larger volume (total=334 cc) than that found in participants with this polymorphism (n=16) (97 cc). Regional analyses were consistent. Participants without this polymorphism showed larger ipsilesional primary sensorimotor cortex activation volume and magnitude compared with those in whom the polymorphism was present.The extent to which these findings generalize to other populations of people with stroke, such as those with stroke <7 days prior, remains uncertain.Functional magnetic resonance imaging during affected hand movement showed decreased brain activation among participants with the BDNF val(66)met polymorphism compared with those lacking this polymorphism, especially in the ipsilesional primary sensorimotor cortex contralateral to movement. These results echo findings in healthy people and suggest that genetic factors affecting the normal brain continue to be operative after stroke. The findings suggest a potential imaging-based endophenotype for the BDNF val(66)met polymorphism's effect on the motor system that may be useful in a clinical trial setting.
| S-EPMC4817211 | biostudies-other
Project description:Accumulation of ?-amyloid (A?) in the brain is associated with memory decline in healthy individuals as a prelude to Alzheimer's disease (AD). Genetic factors may moderate this decline. We examined the role of apolipoprotein E (?4 carrier[?4(+)], ?4 non-carrier[?4(-)]) and brain-derived neurotrophic factor (BDNF(Val/Val), BDNF(Met)) in the extent to which they moderate A?-related memory decline. Healthy adults (n=333, Mage=70 years) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent A? neuroimaging. Neuropsychological assessments were conducted at baseline, 18-, 36- and 54-month follow-ups. A? positron emission tomography neuroimaging was used to classify participants as A?(-) or A?(+). Relative to A?(-)?4(-), A?(+)?4(+) individuals showed significantly faster rates of cognitive decline over 54 months across all domains (d=0.40-1.22), while A?(+)?4(-) individuals showed significantly faster decline only on verbal episodic memory (EM). There were no differences in rates of cognitive change between A?(-)?4(-) and A?(-)?4(+) groups. Among A?(+) individuals, ?4(+)/BDNF(Met) participants showed a significantly faster rate of decline on verbal and visual EM, and language over 54 months compared with ?4(-)/BDNF(Val/Val) participants (d=0.90-1.02). At least two genetic loci affect the rate of A?-related cognitive decline. A?(+)?4(+)/BDNF(Met) individuals can expect to show clinically significant memory impairment after 3 years, whereas A?(+)?4(+)/BDNF(Val/Val) individuals can expect a similar degree of impairment after 10 years. Little decline over 54 months was observed in the A?(-) and A?(+) ?4(-) groups, irrespective of BDNF status. These data raise important prognostic issues in managing preclinical AD, and should be considered in designing secondary preventative clinical trials.
| S-EPMC4759101 | biostudies-literature