Met Carriers Research Articles

Association Between BDNF Val66Met Polymorphism and Mild Behavioral Impairment in Patients With Parkinson's Disease.

Neuropsychiatric symptoms (NPS) are common in Parkinson's disease (PD) and have demonstrated an association with the p. Val66Met, a polymorphism in the BDNF gene. Mild behavioral impairment (MBI) is a validated syndrome describing emergent and persistent NPS in older adults as a marker of potential cognitive decline and dementia. This study investigated if PD patients with the Met allele were more likely to have MBI and whether they had impairments in specific domains of MBI using the Mild Behavioral Impairment Checklist (MBI-C) as the MBI ascertainment tool. One hundred forty-six PD patients were screened for neuropsychiatric and cognitive impairments with the MBI-C and the Montreal Cognitive Assessment (MoCA). All participants were genotyped for the BDNF p.Val66Met single-nucleotide polymorphism (SNP) using TaqMan Genotyping Assay. Statistical analysis was performed using multiple linear and logistic regression models. Met carriers had a 2 times higher likelihood of being MBI positive (MBI-C total score ≥8) than Val carriers. Met carriers had significantly higher MBI-C total scores and significantly greater impairments in the mood/anxiety and the psychotic domains of MBI-C compared to Val carriers. These findings indicate that the BDNF Met allele is associated with a higher neuropsychiatric burden in PD.

In search of positive mental health: Personality profiles and genetic polymorphisms.

Individuals vary greatly in their mental health and these differences may play a critical role in stress resistance, risk reduction and illness recovery. Here we ask how these differences may be related to normal variation in personality and genotype. One hundred healthy college students completed measures of mental health (Mental Health Continuum-Short Form [MHC-SF]), personality (NEO Five Factor Inventory) and adverse childhood experiences. Participants also provided saliva samples, genotyped for both the serotonin transporter (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF), each assayed for naturally occurring polymorphisms, 5-HTTLPR (short/long) and BDNF (valine/methionine). Mental health correlated strongly with the NEO triad of conscientiousness-extraversion-neuroticism, with largest contributions to MHC-SF scores for conscientiousness, followed by extraversion and then neuroticism. The personality trait interaction of extraversion × conscientiousness uniquely accounted for approximately 44.22% 44.62% of the variance in MHC-SF scores. Polygenic comparisons showed a significant gene × gene interaction, with highest mental health for 5-HTTLPR-S, Met carriers. Together these results provided support for distinct yet interacting roles of personality and genetics in the phenotypical expression of mental health.

Gamma-transcranial alternating current stimulation and theta-burst stimulation: inter-subject variability and the role of BDNF

ObjectiveThe main limitation of neuromodulation techniques is inter-subject variability. Combining theta-burst stimulation (TBS) with gamma-transcranial alternating current stimulation (γ-tACS) allows to shape cortical plasticity. However, it is unknown whether γ-tACS modifies TBS-induced response variability. In this study, we measured the inter-subject variability of TBS-γ tACS and controlled the effect of the Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism. MethodsIntermittent TBS (iTBS)-sham tACS, iTBS-γ tACS, continuous TBS (cTBS)-sham tACS, and cTBS-γ tACS were applied in randomised sessions. Inter-subject variability was measured using grand average and clustering methods. TBS-γ tACS effects on motor evoked potentials (MEP) were compared between Val/Val and Met carriers. ResultsWe found that γ-tACS boosted iTBS-induced MEP facilitation and cancelled cTBS-induced MEP depression. Grand average analysis showed that γ-tACS prominently increased the percentage of iTBS responders and cTBS non-responders. The clustering method demonstrated that TBS-γ tACS response varied between subjects, a phenomenon unrelated to the BDNF genotype. ConclusionsEnhancing γ oscillations through tACS boosts iTBS-induced LTP-like plasticity and suppresses cTBS-induced LTD-like plasticity of the primary motor cortex in a reliable manner. The BDNF Val66Met polymorphism does not influence these effects. SignificanceSince γ-tACS significantly increases the number of iTBS responders, it may be used in clinical settings.

The BDNF Val66Met polymorphism impacts victim's moral emotions following interpersonal transgression.

Immoral behaviors make individuals abominate and punish transgressors. Inspired by the associations between the Val66Met polymorphism of brain-derived neurotropic factor (BDNF) gene and emotional responses following negative events, we investigated whether this polymorphism was also associated moral emotions such as punishment and forgiveness following interpersonal transgression. To do so, we categorized 340 individuals according to the BDNF Val66Met and assessed moral emotions by using 12 hypothetic scenarios in different conditions of intention and interpersonal consequence. The results indicated that this polymorphism was significantly associated with moral aversion and punishment towards transgressors. Victims with the Val/Val genotype expressed less aversion and punishment than the Met carriers, regardless of intention and interpersonal consequence. Moreover, this polymorphism was associated with forgiveness. Victims with the Val/Val genotype expressed more forgiveness than the Met carriers. Taken together, these findings highlight the importance of the BDNF Val66Met to moral emotions.

Effect of BDNF Val66Met on hippocampal subfields volumes and compensatory interaction with APOE-\u03b54 in middle-age cognitively unimpaired individuals from the ALFA study

BackgroundCurrent evidence supports the involvement of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, and the ε4 allele of APOE gene in hippocampal-dependent functions. Previous studies on the association of Val66Met with whole hippocampal volume included patients of a variety of disorders. However, it remains to be elucidated whether there is an impact of BDNF Val66Met polymorphism on the volumes of the hippocampal subfield volumes (HSv) in cognitively unimpaired (CU) individuals, and the interactive effect with the APOE-ε4 status.MethodsBDNF Val66Met and APOE genotypes were determined in a sample of 430 CU late/middle-aged participants from the ALFA study (ALzheimer and FAmilies). Participants underwent a brain 3D-T1-weighted MRI scan, and volumes of the HSv were determined using Freesurfer (v6.0). The effects of the BDNF Val66Met genotype on the HSv were assessed using general linear models corrected by age, gender, education, number of APOE-ε4 alleles and total intracranial volume. We also investigated whether the association between APOE-ε4 allele and HSv were modified by BDNF Val66Met genotypes.ResultsBDNF Val66Met carriers showed larger bilateral volumes of the subiculum subfield. In addition, HSv reductions associated with APOE-ε4 allele were significantly moderated by BDNF Val66Met status. BDNF Met carriers who were also APOE-ε4 homozygous showed patterns of higher HSv than BDNF Val carriers.ConclusionTo our knowledge, the present study is the first to show that carrying the BDNF Val66Met polymorphisms partially compensates the decreased on HSv associated with APOE-ε4 in middle-age cognitively unimpaired individuals.

0043 BDNF Genotype Modulates Circadian Response to Simulated Nightwork in IL-6

Abstract Introduction Brain Derived Neurotrophic Factor (BDNF) is involved in synaptic plasticity and may be involved in sleep and circadian regulation. The BDNF gene has a single nucleotide polymorphism (Val66Met) resulting in decreased BDNF secretion. The Met allele is associated with reduced nocturnal slow wave activity following sleep loss, and may also enable more flexible adaptation to circadian misalignment. We used IL-6, a pleiotropic cytokine with biphasic circadian secretion, to compare the response of Val and Met carriers to circadian misalignment. Methods 15 healthy men (26.7±4.9y) participated in a 16-day laboratory study of simulated nightwork with two nighttime duty cycles and an intervening 58h restart break. The study began with two baseline 10h time in bed (TIB) nighttime sleep opportunities (22:00-08:00) and a 5h TIB afternoon nap (15:00-20:00). Each duty cycle consisted of five nighttime waking periods and four 10h TIB daytime sleeps (10:00-20:00). The restart break began with a 5h TIB morning nap (10:00-15:00), followed by two 10h TIB nighttime sleeps (22:00-08:00). The middle two daytime sleep periods from each duty cycle were monitored polysomnographically and visually scored. During the baseline and restart periods, blood samples were collected at 08:25 and then at 2h intervals until 20:00. Plasma IL-6 was measured by means of ELISA. BDNF Val66Met genotype was determined from whole blood. Results The genotype distribution was in Hardy-Weinberg equilibrium (Val/Val:5; Val/Met:10; Met/Met:0). On average, Met carriers slept 52.2min longer (p=0.052) and displayed 27.7min more REM (p=0.013) than Val/Val subjects during the 10h TIB daytime sleeps. Baseline IL-6 concentrations were similar between genotypes. However, during the restart break, Val/Met subjects showed reduced IL-6 compared to baseline and to Val/Val subjects (p=0.022). Conclusion BDNF Val66Met heterozygotes exhibited blunted IL-6 levels following simulated nightwork, suggesting this genotype experienced a substantial circadian shift and/or altered response to sleep loss associated with daytime sleep. Support FMCSA award DTMC75-07-D-00006; Elliot D. Weitzman, M.D. Research Grant from the Sleep Research Society Foundation.

The BDNF Val66Met Polymorphism, Regular Exercise, and Cognition: A Systematic Review.

The purpose of this study was to synthesize research evidence from studies on the relationships among the BDNF Val66Met polymorphism, regular exercise, and cognition in human subjects. PubMed, CINAHL, and Web of Science were searched systematically. Search limiters applied in these databases included humans, English language, time limits from 2009 to 2019, and peer-reviewed journal articles. Eight studies were included in the current review. While there was some evidence to tentatively suggest that greater levels of exercise were associated with certain forms of memory in Val/Val homozygotes than Met carriers, more research is needed to corroborate these findings. Regarding attention/information processing speed, executive function as well as global cognition, the evidence is either inconsistent or sparse and does not allow for tentative conclusions. Compelling evidence from high-quality clinical trials is needed to re-examine the relationship between the BDNF Val66Met polymorphism, exercise, and cognition.

Impact of APOE and BDNF Val66Met Gene Polymorphisms on Cognitive Functions in Patients with Amnestic Mild Cognitive Impairment.

Apolipoprotein (APOE) ɛ4 is a well-known risk factor for late-onset Alzheimer's disease (AD), but other AD-related gene polymorphisms might also be important, such as the polymorphism within the brain-derived neurotrophic factor (BDNF) gene. Carriage of BDNF Val66Met has been associated with faster cognitive decline and greater hippocampal atrophy in cognitively normal elderly. Thus, we examined the effects of the concurrent presence of APOE and BDNF polymorphisms on cognitive functions and brain morphometry in amnestic mild cognitive impairment (aMCI) patients. 107 aMCI patients (mean age = 72.2) were recruited from the Czech Brain Aging Study and, based on APOE and BDNF genes polymorphisms, were divided into four groups: ɛ4-BDNFVal/Val (n = 37), ɛ4-BDNFMet (n = 19), ɛ4+BDNFVal/Val (n = 35), and ɛ4+BDNFMet (n = 16). All patients underwent clinical examination, magnetic resonance imaging, and complex neuropsychological battery. The combination of APOEɛ4+ and BDNF Met was associated with significantly worse memory performance in immediate and delayed recall compared to other polymorphism groups. We did not observe increased atrophy in areas related to memory function in the ɛ4+BDNFMet group. Our findings suggest that carriage of ɛ4+BDNFMet is associated with more pronounced memory dysfunction, a typical feature of early AD, but not with structural brain changes in aMCI patients. These findings suggest that in APOEɛ4/BDNF Met carriers, synaptic dysfunction affecting memory may precede pronounced structural changes.

The BDNF Val66Met Polymorphism Has No Effect on Encoding-Related Hippocampal Response But Influences Recall in Remitted Patients With Bipolar Disorder.

Background: Cognitive impairments in bipolar disorder (BD) such as memory deficits are associated with poor functional outcomes and it has been suggested that the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism contributes to individual variability in memory function in BD. The current study investigated the relationship between the BDNF Val66Met polymorphism, neural activity during a picture-encoding task, and subsequent memory recall.Methods: A total of 70 patients with BD grouped according to genotype [ValVal or Met carriers (MetVal/MetMet)] underwent fMRI while performing a picture-encoding task. Memory for the encoded pictures was tested with a subsequent free recall memory task.Results: There was no difference between the ValVal homozygotes and Met carriers in the involvement of hypothesized memory encoding regions i.e. hippocampus and dorsal prefrontal cortex (dPFC). However, an exploratory whole-brain analysis showed greater encoding-related lateral occipital cortex activity in Met carriers. Behaviorally, Met carriers also showed better free recall of the encoded pictures.Conclusions: We found no effect of the BDNF genotype on encoding-related hippocampal and dPFC activity in BD, although Met carriers showed superior memory performance after the scan, which could be related to more efficient perceptual processing during encoding.

Association Between BDNF Val66Met Polymorphism and Optic Neuritis Damage in Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system (CNS). The purpose of the study was to examine the association between the brain-derived neurotrophic factor (BDNF) Val66Met genotype and structural and functional optic nerve damage in the eyes of NMOSD patients. A total of 17 NMOSD subjects (34 eyes) were included in the study and were divided into subgroups based on optic neuritis (ON) history and BDNF Val66Met polymorphisms. The mean (range) age was 47.8 (23–78) years, and the mean (SD) disease duration was 7.4 (2–39) years. All participants had undergone optical coherence tomography (OCT) scans for global retinal nerve fiber layer (gRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness and multifocal visual evoked potential (mfVEP) test for amplitude and latency. BDNF Val66Met polymorphisms were genotyped in all participants. OCT and mfVEP changes were compared between two genotype groups (Met carriers vs. Val homozygotes) by using the generalised estimating equation (GEE) models. The BDNF Val66Met polymorphism was significantly associated with more severe nerve fiber layer damage and axonal loss in ON eyes of NMOSD subjects. Met carriers had more significantly reduced GCIPL (P = 0.002) and gRNFL (P < 0.001) thickness as well as more delayed mfVEP latency (P = 0.008) in ON eyes. No association was found between Val66Met variants and non-ON (NON)-eye of the participants. These findings suggest that the BDNF Val66Met polymorphism may be associated with optic nerve damage caused by acute ON attacks in NMOSD patients.

MARKERS AND BIOMARKERS OF DEMENTIA BDNF GENOTYPE AND CHANGES IN WHITE MATTER HYPERINTENSITIES AND HIPPOCAMPAL MICROSTRUCTURE IN OLDER MEN AND WOMEN

Brain-derived neurotrophic factor (BDNF) may protect against cerebral gray and white matter impairments in older age. The val66met genetic polymorphism of BDNF is recently emerging as an early marker of brain structural integrity. However, evidence is sparse, cross-sectional, and mostly in men. In a longitudinal cohort study of community-dwelling older adults (N=139, mean age=81.6, 58% female, 58% white, mean follow-up=3.4 years), we estimated the overall and sex-stratified effects of BDNF val66met polymorphism on changes in cognition and gray and white matter macro- and micro-structure. Annualized percent change was computed for volume of white matter (WM) hyperintensities and gray matter (GM), fractional anisotropy of normal appearing WM, and mean diffusivity (MD) of GM in whole brain and memory and executive control function networks. Significant associations were adjusted for variables differing by genotype (race, APOE4, diabetes, triglycerides, smoking). Compared to met carriers, val homozygotes had slower annual whole brain WMH accrual (median (IQR) 31.4% (61.7) vs. 60.7% (92.4)), stronger in women. Met carriers had slower annual accrual of hippocampal MD (median (IQR) 1.26% (0.92) vs. 1.85% (1.09) for right hippocampus, stronger for women, and 1.45% (1.06) vs. 1.97% (1.22) for left hippocampus, stronger for men) compared to val homozygotes. Associations were robust to covariates’ adjustment. BDNF polymorphism was not associated with cognitive changes. BDNF polymorphism may help in early identification of those more likely to resist accrual of WMH and loss of hippocampal microstructural integrity, with effects varying by sex.

BDNF Val66Met Genetic Polymorphism Results in Poor Recovery Following Repeated Mild Traumatic Brain Injury in a Mouse Model and Treatment With AAV-BDNF Improves Outcomes.

Clinicians have long noticed that some Traumatic Brain Injury (TBI) patients have worse symptoms and take a longer time to recover than others, for reasons unexplained by known factors. Identifying what makes some individuals more susceptible is critical to understanding the underlying mechanisms through which TBI causes deleterious effects. We have sought to determine the effect of a single nucleotide polymorphism (SNP) in Brain-derived neurotrophic factor (BDNF) at amino acid 66 (rs6265) on recovery after TBI. There is controversy from human studies as to whether the BDNF Val66Val or Val66Met allele is the risk factor for worse outcomes after brain trauma. We therefore investigated cellular and behavioral outcomes in genetically engineered mice following repeated mild TBI (rmTBI) using a lateral fluid percussion (LFP) injury model. We found that relative to injured Val66Val carriers, injured Val66Met carriers had a larger inflammation volume and increased levels of neurodegeneration, apoptosis, p-tau, activated microglia, and gliosis in the cortex and/or hippocampus at 1 and/or 21 days post-injury (DPI). We therefore concluded that the Val66Met genetic polymorphism is a risk factor for poor outcomes after rmTBI. In order to determine the mechanism for these differences, we investigated levels of the apoptotic-inducing pro BDNF and survival-inducing mature BDNF isoforms and found that Met carriers had less total BDNF in the cortex and a higher pro/mature ratio of BDNF in the hippocampus. We then developed a personalized approach to treating genetically susceptible individuals by overexpressing wildtype BDNF in injured Val66Met mice using an AAV-BDNF virus. This intervention improved cellular, motor, and cognitive behavior outcomes at 21 DPI and increased levels of mature BDNF and phosphorylation of mature BDNF's receptor trkB. This study lays the groundwork for further investigation into the genetics that play a role in the extent of injury after rmTBI and highlights how personalized therapeutics may be targeted for recovery in susceptible individuals.

Self-Reported Mild Traumatic Brain Injuries in Relation to Rumination and Depressive Symptoms: Moderating Role of Sex Differences and a Brain-Derived Neurotrophic Factor Gene Polymorphism.

Mild traumatic brain injuries (mTBIs) have frequently been associated with the emergence and persistence of depressive symptoms. However, the factors which contribute to the increased risk for depression after these head injuries remain unclear. Accordingly, we examined the relationship between frequency of self-reported mTBIs and current symptoms of depression and the mediating role of rumination and cognitive flexibility. We also examined whether these relations were moderated by sex differences and the presence of the Val66Met polymorphism in a gene coding for brain-derived neurotrophic factor (BDNF). Retrospective, cross-sectional. Carleton University. Two hundred nineteen Carleton University undergraduate students. Cognitive flexibility as assessed by the Wisconsin Card Sorting Task (WCST); subtypes of rumination (Ruminative Response Scale; Treynor, Gonzalez, and Nolen-Hoeksema, 2003); depressive symptoms (Beck Depression Inventory; Beck, Ward, and Mendelson, 1961). Greater frequency of self-reported mTBIs was associated with more frequent depressive rumination among women, but not men, which was accompanied by elevated current depressive symptoms. In addition, among Met allele carriers of the BDNF polymorphism, but not those who were Val homozygotes, greater frequency of mTBIs was related to higher levels of brooding, which was accompanied by heightened depressive symptoms. Brain-derived neurotrophic factor genotype also moderated the relationship between self-reported mTBIs and cognitive flexibility in that more frequent mTBIs were associated with more perseverative errors on the WCST among Met carriers, but not Val homozygotes. The present findings raise the possibility that the evolution of depression after mTBIs may be dependant on a BDNF polymorphism and sex differences.

Brain-Derived Neurotrophic Factor Val66Met Polymorphism Is Associated With a Reduced ERP Component Indexing Emotional Recollection.

The Met allele of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with reduced functioning of the amygdala and hippocampus. It has been linked to major psychiatric conditions, including depression and post-traumatic stress disorder, and is associated with deficits in episodic memory. The precise mechanisms of the BDNF gene’s influence on emotional memory are not well characterized, especially its impact on recognition. Two electrophysiological experiments of emotional memory were run on two independent samples genotyped for BDNF Val66Met. Event-related potentials (ERPs) corresponding to the recognition of negative and neutral words (Experiment 1, N = 37) and negative and positive words (Experiment 2, N = 23) were recorded, and the late parietal component (LPC), typically associated with conscious recollection, was analyzed. In Experiment 1, a reduced LPC was observed in Met carriers (N = 12) compared to Val homozygotes (N = 25) in the negative condition, but the group difference was not present in the neutral condition. In Experiment 2, the reduced LPC was seen in Met carriers (N = 12) compared to Val homozygotes (N = 11) across both conditions. This study provides the first evidence of an association between the BDNF Val66Met genotype and the late parietal electrophysiological component, suggesting that the conscious experience of emotional recollection may differ according to BDNF Val66Met genotype. Further, these results suggest that this effect is likely due to emotional arousal rather than valence polarity. Results were discussed with reference to the possible mechanisms by which emotional recollection deficits may contribute to psychopathology.

BDNF Val66Met polymorphism moderates the association between sleep spindles and overnight visual recognition

A common single nucleotide polymorphism (SNP) of the brain-derived neurotrophic factor (BDNF) gene, Val66Met, has been reported to impair BDNF secretion and memory function. However, few studies have investigated the interaction of BDNF genotype and sleep characteristics, such as sleep spindles, that promote long-term potentiation during sleep. In this study we compared overnight visual memory between the carriers of BDNF Met and non-carriers (Val homozygotes), and examined how sleep spindle density associated with memory performance.The sample constituted of 151 adolescents (mean age 16.9 years; 69% Val homozygotes, 31% Met carriers). The learning task contained high and low arousal pictures from Interactive Affective Picture System. The learning task and all-night polysomnography were conducted at the homes of the adolescents. Slow (10–13 Hz) and fast (13–16 Hz) spindles were detected with automated algorithm.Neither post-sleep recognition accuracy nor spindle density differed between Val homozygotes and Met carriers. While frontal slow and fast spindle densities associated with better recognition accuracy in the entire sample, examining the allelic groups separately indicated paralleling associations in Val homozygotes only. Interaction analyses revealed a significant genotype-moderated difference in the associations between frontal fast sleep spindles and high arousal pictures.In sum, sleep spindles promote or indicate visual learning in Val homozygote adolescents but not in Met carriers. The result suggests that the role of sleep spindles in visual recognition memory is not equal across individuals but moderated by a common gene variant.

Social support and unsupportive interactions in relation to depressive symptoms: Implication of gender and the BDNF polymorphism

ABSTRACTReduced levels of brain derived neurotrophic factor (BDNF), through its role in neurogenesis and neuroplasticity, may be involved in the evolution and maintenance of depression. Depression has also been tied to fewer social relationships, which can vary by gender. Thus, we assessed whether the functional single nucleotide polymorphism (SNP) on the BDNF gene, Val66Met, moderated the relationship between depressive symptoms and perceived social support and unsupportive relationships, and whether these associations differed by gender. Among 945 students, (n = 667 females; n= 278 males), depressive scores were inversely related to social support, and positively related with unsupportive relations. Females reported greater social support and depressive scores compared to males. A3-way interaction was found between unsupportive relations, the Val66Met SNP, and gender, such that irrespective of genotype, females displayed astrong relationship between unsupport and depressive scores. Male Met carriers displayed this relationship, but this was less apparent among males with the Val/Val genotype. The Val66Met SNP did not moderate the link between support and depressive scores. This BDNF SNP may serve to moderate the links between psychosocial factors and depressive symptoms, but such links are nuanced, being gender-dependent and varying with the nature of the social interactions experienced.

THE RELATIONSHIP BETWEEN BRAIN-DERIVED NEUROTROPHIC GROWTH FACTOR (BDNF) AND ALZHEIMER'S DISEASE: IS THIS A BIOMARKER FOR THE DISEASE?

There are even a few potential candidate genes that convey the risk of developing AD. A promising gene has been identified as Brain-derived Neurotrophic Factor (BDNF). (Kao 2012). The relationship between BDNF and AD is still being determined, but multiple studies have found that there is some form of link between the two. In fact, significant evidence suggests that BDNF is associated with AD. (Sen 2017). This is because neurotrophic factors are proteins that regulate several aspects of cognitive operations. They are essential in memory formation and cognition, atonal guidance, cell morphology and neuronal survival. Neurotrophic factors have received a great deal of attention in Alzheimer's research because of these roles. (O'Bryant 2011). The purpose is to compare multiple BDNF genotypes and memory loss and/or diagnosis in humans who have shown early signs of decline. The genotypes of BDNF include Val/Val, Val/Met, and Met/Met. Currently, the appearance of the Met trait will diagnose the potential development of AD. This hypothesis has not been proven to date and that is the main goal of this project. One hundred and fifty subjects aged 50+, 100 with impaired memory and 50 with normal memory, participated in this study. Demography and history, cognitive assessments, and biospecimen collection – buccal/saliva swab were collected. Samples were redacted. The results were not disclosed to the subjects. Memory Impaired subjects did not show a statistical difference among the VAL/VAL, VAL/MET, and MET/MET genotypes. There was a trend in low MMSE and MET carriers. 92 patients with memory impairment and 50 subjects with normal memory were included. memory impaired 62 VAL/VAL, 25 VAL/MET, and 5 MET/MET normal memory 31 VAL/VAL, 17 VAL/MET, and 2 MET/MET Chi Square 0.62654. - the sample size was small but the statistics offered evidence that BDNF alleles are not different in the memory impaired or normal people - the research is centered around AD which is only one of many cognitive diseases - it is possible that other illnesses could potentially use BDNF as a possible biomarker - BDNF alone may not be a marker but due to the complexity of these type of diseases a combination of other proteins along with BDNF could actually be used as a biomarker - Further investigation is needed in order to find an accurate marker for AD.

Appetite effects of prefrontal stimulation depend on COMT Val158Met polymorphism: A randomized clinical trial

The regulation of appetite is supported by dopamine-modulated brain circuits. Recent studies have shown that transcranial direct current stimulation (tDCS) aimed at increasing the excitability of the dorsolateral prefrontal cortex can reduce appetite, but the underlying mechanisms remain unknown, and response variability is large. The aim of this study was to determine whether individual differences in Catechol-O-methyl transferase (COMT) Val158Met polymorphism can influence tDCS effects on appetite. Thirty-eight adult women with obesity, classified as carriers or non-carriers of the Met allele, underwent a randomized, double-blind, sham-controlled tDCS intervention involving three phases: Phase I, target engagement (immediate effects of tDCS on working memory performance), Phase II, tDCS only (10 sessions, two weeks), and Phase III, tDCS + hypocaloric diet: (6 sessions, two weeks, 30% energy intake reduction, inpatient). Data were analyzed using linear mixed-effects models and mixed ANCOVA. Appetite was evaluated using visual analogue scales. We found that Met-carriers receiving active tDCS were the only participants who experienced a significant reduction of appetite over time. Conversely, Met non-carriers maintained high levels of appetite during the intervention; this effect was driven by a delayed paradoxical rise in appetite after stimulation. Working memory task performance at phase I correlated with subsequent appetite change in a COMT-dependent manner: speed improvements during the task predicted appetite increase in Met carriers and appetite reduction in Met non-carriers. Our findings suggest that genotype differences impacting dopamine levels influence prefrontal tDCS effects on appetite. This source of variability should be considered in the design of future studies.

Sex-Specific Effect of BDNF Val66Met Genotypes on the Progression of Open-Angle Glaucoma.

To investigate whether the brain-derived neurotrophic factor (BDNF) Val66Met genotype is associated with the rate of progression of open-angle glaucoma (OAG). In this retrospective cohort study, 148 OAG patients (292 eyes) were enrolled with a median follow-up period of 5.3 (range, 1.1-8.6) years. All participants had undergone regular clinical examinations by using spectral-domain optical coherence tomography (SD-OCT) scans and Humphrey (SITA) visual field tests. BDNF Val66Met polymorphisms were genotyped in all participants. Longitudinal visual field and retinal nerve fiber layer (RNFL) changes were compared between Met carriers (n = 68, 135 eyes) and Val homozygotes (n = 80, 157 eyes) by using the generalized estimating equations (GEE) model and Kaplan-Meier survival analysis. There was no significant difference in mean rates of progression for the two genotypes. However, there was a significant association between the Val66Met genotypes and slower OAG progression, as suggested by a higher rate of global RNFL loss in Val/Val homozygotes (P = 0.008) in the long-term survival analysis. The effect demonstrated a degree of sex specificity, with the significant difference present only in females (P = 0.016) but not males. Similar sexual dimorphism was presented in superior (P = 0.005 in females, P = 0.38 in males) and inferior (P = 0.004 in females, P = 0.41 in males) RNFL loss. No significant difference was observed in visual field parameters. Our results suggested that carriage of Met allele reduces the rate of long-term OAG progression. However, the fact that this effect is observed only in females indicates BDNF Val66Met influences the progression rate of OAG in a sex-specific manner.

Associations of Later-Life Education, the BDNF Val66Met Polymorphism and Cognitive Change in Older Adults.

In 358 participants of the Tasmanian Healthy Brain Project, we quantified the cognitive consequences of engaging in varying loads of university-level education in later life, and investigated whether or not BDNF Val66Met affected outcomes. Assessment of neuropsychological, health, and psychosocial function was undertaken at baseline, 12-month, and 24-month follow-up. Education load was positively associated with change in language processing performance, but this effect did not reach statistical significance (P = 0.064). The BDNF Val66Met polymorphism significantly moderated the extent to which education load was associated with improved language processing (P = 0.026), with education load having a significant positive relationship with cognitive change in BDNF Met carriers but not in BDNF Val homozygotes. In older adults who carry BDNF Met, engaging in university-level education improves language processing performance in a load-dependent manner.