NLP SNP

Report for Mutation V66M

Developed by Shray Alag, 2020.

SNP Clinical Trial Gene

There are 44 clinical trials

Clinical Trials

1 Combined Exposure Therapy and D-Cycloserine vs. Placebo for Posttraumatic Stress Disorder

This study proposes to evaluate the effects of D-cycloserine (DCS) combined with Virtual Reality exposure therapy in a sample of patients who developed posttraumatic stress disorder (PTSD) following either the events of September 11, 2001, or military service in the war in Iraq. In addition, this study hopes to determine whether a common human genetic single nucleotide polymorphism (SNP) in a growth factor, brain derived neurotrophic factor, BDNF (Val66Met), predicts treatment response to PTSD. Overall, this study aims 1) to determine if subjects administered DCS show a significantly larger decrease in symptoms of PTSD as compared to those administered a placebo, 2) to determine if subjects administered DCS show a decrease in PTSD symptomatology significantly earlier (as measured by weeks) than those administered a placebo, 3) to determine if differences in symptomatology are evident at a 6-month follow-up and indicate long-term differences between groups, and 4) to determine if the BDNF SNP predicts treatment response.

NCT00632632 Posttraumatic Stress Disorder Drug: D-Cycloserine Other: Placebo

MeSH:Stress Disorders, Traumatic Stress Disorders, Post-Traumatic

In addition, this study hopes to determine whether a common human genetic single nucleotide polymorphism (SNP) in a growth factor, brain derived neurotrophic factor, BDNF (Val66Met), predicts treatment response to PTSD. --- Val66Met ---

Primary Outcomes

Description: Total CAPS severity score range is 0-136. Higher values represent a worse outcome (i.e. greater severity of posttraumatic symptoms). CAPS consists of 3 subscales, which are combined to form a total severity score. Subscales: CAPS cluster B (reexperiencing symptoms, range 0-40) CAPS cluster C (avoidance and numbing symptoms, range 0-56) CAPS cluster D (hyperarousal symptoms, range 0-40)

Measure: Clinician Administered PTSD Scale(CAPS)

Time: Immediately following treatment

Measure: Clinician Administered PTSD Scale(CAPS)

Time: 6-months follow-up

Secondary Outcomes

Description: Structured Clinical Interview for DSM-IV - Major Depressive Disorder is a clinical interview to assess presence/absence of Major Depressive Disorder.

Measure: Structured Clinical Interview for DSM-IV - Major Depressive Disorder (SCID-MDD)

Time: Immediately following treatment

2 D-cycloserine Enhanced Imaginal ExposureTherapy for Posttraumatic Stress Disorder (PTSD)

This study proposes to evaluate the effects of D-cycloserine (DCS) combined with cognitive-behavioral treatment with exposure therapy in a sample of patients who developed posttraumatic stress disorder (PTSD) as a consequence of various traumas (e.g., motor vehicle and accidents, burns and other injuries, combat, World Trade Center attack, etc.). In addition, this study hopes to determine whether a common human genetic single nucleotide polymorphism (SNP) in a growth factor, brain derived neurotrophic factor, BDNF SNP (Val66Met), predicts treatment response to PTSD. Patients living in areas that are not geographically proximal to the Weill-Cornell Medical Center New York City campus will receive cognitive behavioral therapy using telemedicine (videoconferencing technology). Overall, this study aims 1) to determine if subjects administered DCS show a significantly larger decrease in symptoms of PTSD as compared to those administered a placebo, 2) to determine if subjects administered DCS show a decrease in PTSD symptomatology significantly earlier (as measured by weeks) than those administered a placebo, 3) to determine if differences in symptomatology are evident at a 6-month follow-up and indicate long-term differences between groups, 4) to determine if the BDNF SNP predicts treatment response, 5)to determine if it is feasible and acceptable to provide imaginal exposure (IE) therapy for PTSD using videoconferencing technology.

NCT00875342 Posttraumatic Stress Disorder Drug: DCS Other: Placebo

MeSH:Stress Disorders, Traumatic Stress Disorders, Post-Traumatic

In addition, this study hopes to determine whether a common human genetic single nucleotide polymorphism (SNP) in a growth factor, brain derived neurotrophic factor, BDNF SNP (Val66Met), predicts treatment response to PTSD. --- Val66Met ---

In addition, all participants will be genotyped once for the BDNF SNP (Val66Met) using a non-invasive saliva sample. --- Val66Met ---

Primary Outcomes

Measure: symptoms of Posttraumatic Stress Disorder-Clinician Administered PTSD Scale(CAPS) and PCL

Time: At initial assessment, during treatment, immediately following treatment, and 6 months after completion of treatment

Secondary Outcomes

Measure: Other measures include BDI, BSI, STAXI-2, Expectancy of Therapeutic Outcomes

Time: At initial assessment, during treatment, immediately following treatment, and 6 months after completion of treatment

3 Brain Derived Neurotrophic Factor as a Predictor of Response to Treatment in Bipolar Depression and Mania: 16-weeks Follow-up With Quetiapine XR

There is sound evidence that quetiapine is effective in the treatment of manic and depressive episodes associated with Bipolar Disorder (BD) (Yatham et al 2006). However, even with the development of effective new treatment options, not all patients respond to treatments available. Biological markers have been investigated as predictors of response to treatment and of remission of symptoms. This would explain in part the individual's differences in the response to treatment, taking into account the genetic variability plus environmental factors influencing specific biological markers. A potential biological marker of response to treatment in BD would be the levels of neurotrophins, as they are, in fact, altered during acute mood episodes (Cunha et al 2006). Among neurotrophins, the Brain-Derived Neurotrophic Factor (BDNF) has been repeatedly and consistently reported to be associated with BD physiopathology (Post 2007). Furthermore, medications that are known to be effective in BD, like lithium and divalproex, increase BDNF levels.

NCT00879307 BIPOLAR DISORDER Drug: quetiapine

MeSH:Depression Bipolar Disorder

HPO:Bipolar affective disorder Mania

Interestingly, a single nucleotide polymorphism at nucleotide196 (G/A) in the human BDNF gene at codon 66 (Val66Met) have been reported to be associated with a predisposition to BD in family-based studies (Rybakowski et al 2006, Green et al 2006). --- Val66Met ---

Furthermore, there are consistent findings in BD regarding the association of Val66Met polymorphism of BDNF gene with prefrontal cognitive impairment, which was recently confirmed in a large sample of bipolar subjects (Rybakowski et al 2006). --- Val66Met ---

In addition, crosssectional studies showed that the polymorphism of BDNF gene (Val66Met) was associated with response to lithium prophylaxis, but findings were not universal (Rybakowski et al 2005, Masui et al 2006). --- Val66Met ---

We also aim to investigate the polymorphism of BDNF gene (Val66Met) and its correlation with BDNF serum levels and treatment response. --- Val66Met ---

Primary Outcomes

Measure: Efficacy of quetiapine as a treatment for acute mania and depression, and of as a manutence treatment.

Time: 16 weeks

Secondary Outcomes

Measure: Assess the pharmacodynamics of quetiapine by neurotrophins in blood samples.

Time: 16 weeks

4 Brain Derived Neurotrophic Factor as a Predictor of Response to Treatment in Bipolar Depression and Mania: 16-weeks Follow-up Study

NCT00879632 BIPOLAR DISORDER

MeSH:Depression Bipolar Disorder

HPO:Bipolar affective disorder Mania

We also aim to investigate the polymorphism of BDNF gene (Val66Met) and its correlation with BDNF serum levels and treatment response. --- Val66Met ---

Primary Outcomes

Measure: Hamilton depression raing scale and young mania rating scale

Time: 16 weeks

Secondary Outcomes

Measure: Serum BDNF levels as predictor of response to treatment

Time: 16 weeks

5 Genetic Association Study Between Single Nucleotide Polymorphisms (SNPs) and Cognitive Performance in Young Bipolar Type I Patients: LICAVALGENE

This is a genetic association study of cognitive impairment in young bipolar disease type I patients without medications in mania, depression, hypomania or mixed states.

NCT00969930 Bipolar

Methods: 80 patients with BD type I (SCID DSM-IV), age from 18 to 35 years old, currently on mania, depression, hypomania or mixed state after medication wash out will be submitted to complete neuropsychological evaluation and genotyped for COMT (val158met, rs165599, -287, rs737865), ApoE (epsilon 4) and BDNF (val66met)and 80 healthy controls. --- val158met --- --- val66met ---

Primary Outcomes

Measure: Cognitive deficits in BD patients are associated with COMT, ApoE and BDNF polymorphisms

Time: 18 months

6 Transcranial Magnetic Stimulation (TMS) Measures of Plasticity and Excitatory/Inhibitory Ratio as Biomarkers for R-baclofen Effects in Normal Volunteers

Our overall objective is to apply Transcranial Magnetic Stimulation (TMS) to develop measures of human synaptic plasticity and of brain excitatory:inhibitory ratio (E:I ratio), which we propose as novel biomarkers and outcome measures that will expedite clinical trials of treatments for Autism Spectrum Disorder (ASD). One potential therapeutic agent, R-baclofen will be investigated under this protocol. TMS is a safe, inexpensive and noninvasive means to focally stimulate the human brain. Presently, TMS is in extensive use as a means to measure regional brain excitability, which is dependent on local synaptic strength. TMS can be used to temporarily alter synaptic strength as well as to acutely measure levels of cortical excitability and short and long interval inhibition. Since altered synaptic plasticity and an imbalanced inhibitory:excitatory ratio are cited as fundamental abnormalities in ASD, we hypothesize that both severity of ASD-related learning deficits and their improvement after therapy will correlate with TMS measures of synaptic plasticity and E:I ratio. We propose to embed TMS measures of synaptic plasticity and E:I ratio in a 'Proof of Principal' trial of R-baclofen and to examine: Aim 1: Whether R-baclofen (a potential therapeutic agent for ASD) predictably alters TMS measures of synaptic plasticity and E:I ratio as a function of plasma concentration in adult volunteers. We will test the following hypotheses: 1. R-baclofen produces a significant change in TMS measures of LTD and E:I ratio; and 2. R-baclofen plasma levels and TMS measures of LTD and E:I ratio show a predictable exposure-response relationship. Exploratory Aim 1: Whether the presence of genetic polymorphisms of the BDNF and GABA-B receptor genes has a moderating effect on TMS measures and on R-baclofen effects. We will test the following hypotheses: 1. Presence of the BDNF val66met allele will be associated with decreased long-term depression (LTD) of cortical excitability 2. Polymorphisms of GABA-B receptor genes will be associated with altered magnitude of response to R-baclofen as measured by TMS

NCT01172509 Autism Drug: R-baclofen

We will test the following hypotheses: 1. Presence of the BDNF val66met allele will be associated with decreased long-term depression (LTD) of cortical excitability 2. Polymorphisms of GABA-B receptor genes will be associated with altered magnitude of response to R-baclofen as measured by TMS percent of baseline TMS-induced measures of (1) human synaptic plasticity (LTD). --- val66met ---

Primary Outcomes

Description: Synaptic plasticity or LTD will be measured using the MEP in response to stimulation set at 80% of the active motor threshold. This MEP will be measured at 90 minutes after study drug dose to establish baseline MEP amplitude then LTD will be induced with the cTBS procedure. The amount of LTD remaining at the different time points, post-cTBS will be quantified by measuring the MEPs and dividing it by the baseline MEP. This will yield a percent of baseline MEP at the various time points.

Measure: percent of baseline TMS-induced measures of (1) human synaptic plasticity (LTD)

Time: at 90 minutes after study drug dose

7 Enhancing Exposure Therapy for PTSD: Virtual Reality and Imaginal Exposure With a Cognitive Enhancer

The purpose of this study is to test the differences between four active treatment conditions for combat-related Post Traumatic Stress Disorder (PTSD): virtual reality exposure therapy (VRE) or prolonged imaginal exposure therapy (PE), both with DCS or placebo, as well as to examine predictors for PTSD and response to treatment in active duty military personnel, veterans, and civilians who served in Iraq and Afghanistan.

NCT01352637 Post Traumatic Stress Disorder Drug: DCS (D-Cycloserine ) + Prolonged Imaginal Exposure Drug: DCS (D-Cycloserine ) + Virtual Reality Exposure Drug: Placebo + Prolonged Imaginal Exposure Drug: Placebo (sugar pill) + Virtual Reality Exposure

MeSH:Stress Disorders, Traumatic Stress Disorders, Post-Traumatic

heart rate, blood pressure) and/or a genetic polymorphism (BDNF Val66Met) obtained from a saliva sample will be examined. --- Val66Met ---

Primary Outcomes

Description: Clinician Administered PTSD Scale (CAPS) for the DSM-IV [34]. The CAPS-IV is a structured clinical interview designed to assess the 17 DSM-IV PTSD symptoms. CAPS-IV provides categorical ratings of diagnostic status as well as a quantitative index of symptom severity. The CAPS total severity score is based on response to the 17 items that assess the frequency and intensity of current PTSD symptoms. Symptom severity is assessed separately for past month and past week time frames. CAPS-IV range is 0-136, higher scores mean a worse outcome.

Measure: CAPS-IV at the End of Treatment

Time: after weekly treatment session 9 (at posttreatment assessment)

8 Motor Outcomes and Neural Correlates of Asymmetrical Gait Training in Children With Acquired Hemiplegia

The purposes of this pilot research study are 1. To begin to test if two different types of physical therapy might have different results in children and adolescents who have had a prior stroke, and 2. To determine if either type of physical therapy causes changes in the brain signals that control leg muscles. All participants will receive physical therapy 3 times per week for 8 weeks. Half of the participants will receive typical physical therapy, such as walking practice, muscle strengthening, and balance training. Half of the participants will receive asymmetrical gait training physical therapy, which uses new technology to train each leg differently during walking practice. After enrolling, participants will be randomly assigned to the type of therapy. Measurements will be taken before, during, and after the 8 weeks of physical therapy. These include walking tests to measure symmetry, walking speed and daily step activity, and brain tests to measure the strength of the signals from the brain to the leg muscles. One blood test is also taken to identify if certain genetic factors affect how each child responds to the physical therapy.

NCT01827436 Stroke Hemiplegia Behavioral: Conventional physical therapy Behavioral: Asymmetrical gait training

MeSH:Stroke Hemiplegia

HPO:Hemiplegia Spastic hemiparesis Stroke

We will also establish a genetic database to identify the presence or absence of two genetic variants [Apolipoprotein E (ApoE Є4) and val66met Brain-derived neurotropic factor (BDNF) polymorphisms] associated with decreased potential for neuroplasticity for planning future investigations. --- val66met ---

Primary Outcomes

Measure: Change in walking symmetry

Time: before and after 8 weeks of therapy

Secondary Outcomes

Measure: Change in walking speed

Time: before and after 8 weeks of therapy

Measure: Change in excitability of neural motor pathways

Time: before and after 8 weeks of therapy

Measure: Change in patient/parent satisfaction rating

Time: before and after 8 weeks of therapy

Measure: Change in community step activity

Time: before and after 8 weeks of therapy

Other Outcomes

Measure: Changes in walking ability and cortical excitability measures (detailed above)

Time: before and after a 4 week baseline phase; before and after a 4 week withdraw phase

9 Investigating the Plastic Effects of Repetitive Paired Associative Stimulation (rPAS) in Dystonia

Background: - People with dystonia have serious muscle contractions that cause abnormal movements or postures. This significantly affects their daily lives. The common type is called organic. The other type is psychogenic. People with this type have typical symptoms plus some psychological effects. Researchers will look at how rapid transcranial magnetic stimulation (rTMS) of the brain combined with stimulation of a nerve affects the ability to detect sensations. They will compare the responses of people with different types of dystonia. They will also compare the responses of people with dystonia to responses of people without it. This study may help us learn more about the nature of different types of dystonia. Objectives: - To see whether TMS combined with nerve stimulation affects the brain differently in people with different types of dystonia and those without dystonia. Eligibility: - Individuals at least 18 years old, who are right-handed and have dystonia. - Healthy volunteers at least 18 years old. Design: - Participants will have two clinical visits. Each visit will be a few hours long. They can be done on the same day. - Participants will be screened with a medical history and physical exam. - Participants will take several sensory tests. For these tests, electrodes will be placed on their skin. The participants will feel small electric shocks during some of the tests. - Participants will undergo TMS. For 2 minutes, quick electrical currents will pass through a wire coil placed on their head. As this happens, researchers will ask the participants to move certain muscles.

NCT01888926 Dystonia

MeSH:Dystonia Dystonic Disorders

HPO:Dystonia Focal dystonia Limb dystonia Paroxysmal dystonia Writer's cramp

Outcome Measures Primary outcome variable: Change in MEP amplitudes at T30 from baseline Secondary outcome variables: - Input-output curve parameters (measured at baseline, T0, T30, and T60) - Temporal discrimination threshold (TDT) Exploratory Measures - Short interval intracortical inhibition (SICI), a measure of inhibition in the motor cortex - Influence of Val66Met BDNF polymorphism on the output variables Repeated measures analyses of variance (ANOVA) will be used to investigate the following three factors on the outcome variables: time (four levels: baseline, T0, T30 and T60) and muscle (two levels: APB and FDI) as within-subject factor and group (three levels: organic dystonia, psychogenic dystonia, and healthy controls) as between-subjects factor. --- Val66Met ---

Primary Outcomes

Measure: Change from baseline in the motor evoked potential (MEP) amplitude at S50 after 30 minutes from rPAS (T30).

Time: 30 minutes from rPAS

10 Neuroimaging Predictors of Antidepressant Treatment Outcome

Current medical therapies for depression take weeks to achieve full efficacy, and are ineffective in many patients or cause intolerable side effects, emphasizing the need for a deeper understanding of depression and its treatment. Identifying early brain biomarkers of treatments responses seems necessary to improve antidepressant treatment outcome. In this study we aim to detect early brain responses to a fast acting antidepressant-like treatment administered intravenously during a Real-Time Neurofeedback functional magnetic resonance imaging (MRI) Task to predict antidepressant treatment outcome in depression. At completion of the neuroimaging task, participants will enter a placebo-controlled clinical trial with a selective serotonin reuptake inhibitor (SSRI).

NCT02000726 Depression Drug: Placebo Drug: Citalopram Drug: Fast acting antidepressant-like treatment. administered i.v. during the fMRI scanning session

MeSH:Depression

Inferential Reasoning (including cost-benefit analysis): Delayed Discounting of Money Rewards, Iowa Gambling Task, Common Difference effect gambling task and the WCST.. BDNF Val66Met single nucleotide polymorphism(SNP)genotyping. --- Val66Met ---

Primary Outcomes

Measure: Blood-oxygen-level dependent (BOLD) responses during the Real-Time Neurofeedback Task.

Time: BOLD responses will be assessed at baseline and depression severity will be assessed at baseline

Secondary Outcomes

Measure: Depression severity assessed with several depressive questionnaires.

Time: Every two weeks until the end of the trial (16 weeks total), or until the participants leave the study.

Other Outcomes

Description: Affect processing: Emotional Words Task and Facial Emotion Perception test. Attention and Inhibitory Control: Parametric Go/NoGo, Trail Making test and the Stroop Color Word test . Inferential Reasoning (including cost-benefit analysis): Delayed Discounting of Money Rewards, Iowa Gambling Task, Common Difference effect gambling task and the WCST.

Measure: Neuropsychological functioning of patients with depression

Time: At baseline

Description: 5ml of blood drawn per participants will be used for genotyping

Measure: BDNF Val66Met single nucleotide polymorphism(SNP)genotyping

Time: At baseline

11 The Effect of BDNF on Motor Learning

The purpose of the study is to assess the status of brain-derived neurotrophic factor brain (BDNF) and how the brain behaves in response to skill acquisition. Specifically we will investigate the relationship of the status of BDNF with cortical excitability changes and learning that occur during a motor training paradigm. We aim to 1) determine cortical excitability changes by using transcranial magnetic stimulation (TMS) before and after training; 2) to determine finger tracking accuracy before and after training; and 3) determine the presence of BDNF polymorphism in each participant. We are testing healthy adults in this study, and eventually would like to apply to persons who have neurologic disorders such as stroke or dystonia. By applying a magnetic field to the outside of the head, electrical currents are produced within the brain that can stimulate brain tissue. Using TMS, the brain can be studied to gain a greater understanding of the mechanisms associated with cortical excitability in healthy and patient populations. There is limited knowledge of what influence genetic biomarkers such as BDNF have on cortical excitability changes within the cortex following learning. Studies have indicated that people without this certain gene are less likely to show changes in brain excitability during TMS and during motor learning than people with this gene

NCT02074696 BDNF Polymorphism, Genetic

We will screen for the Val66met polymorphism.. Inclusion Criteria: - 18-45 years - no past history of psychiatric or neurologic disease. --- Val66met ---

Primary Outcomes

Description: A computer quantified tracking performance measure in each test. This is a calculation of accuracy by using the equation: AI = 100(P-E)/P. Where E is the root mean square (r.m.s.) error between the target line and the response line, and P is the size of the individual's target pattern, calculated as the r.m.s. difference between the sine wave and the midline separating the upper and lower phases of the sine wave. The magnitude of P is determined by the scale of the vertical axis, which is the subject's range of finger motion. Therefore, the AI is normalized to each subject's own range of motion and takes into account any differences between subjects in the excursion of the tracking target. The maximum possible score is 100%. Negative scores occur when the response line is so distant from the target that it falls on the opposite side of the midline.

Measure: Accuracy Index

Time: Day 1: posttest after training

Secondary Outcomes

Description: Cortical excitability will be measured with transcranial magnetic stimulation (TMS) single and paired pulse stimulation to measure short-interval intracortical inhibition (SICI), cortical silent period (CSP) and motor evoked potential (MEP) amplitude.

Measure: Cortical Excitability

Time: Day 1: baseline

Measure: Cortical Excitability

Time: Day 1: posttest

Other Outcomes

Description: BDNF genetic variant screening will be conducted via saliva sample collected at the end of the session on day 1. We will screen for the Val66met polymorphism.

Measure: BDNF genetic status

Time: Day 1

12 Mechanism of tDCS-induced Learning Enhancement - the Role of Serotonin

The aim of this study is to assess whether the application of a selective serotonin reuptake inhibitor (SSRI) enhances and prolongs the learning enhancement achieved by anodal transcranial direct current stimulation (atDCS). For this, young and older healthy subjects will be tested with a well established learning paradigm. Results of this study may help to support the application of atDCS also in patients, e.g. with dementia or mild cognitive impairment.

NCT02092974 Healthy Young and Older Adults Procedure: tDCS Drug: Citalopram Other: sham-tDCS + placebo

To assess predictors of SSRI-enhanced brain stimulation, genotyping of several learning related polymorphisms will be performed (i.e., APOE, BDNF, Val66Met, COMT, Val158Met, KIBRA, rs17070145, 5-Hydroxytryptamine transporter).. Inclusion Criteria: - right handedness - unobtrusive neuropsychological screening - ability to provide written informed consent - no pathological findings in head MRI - age: 18 to 35 years (young adults) or 50-80 years (older adults) - Highly effective contraception (Pearl Index < 1) or reliable abstinence from any heterosexual relationships in women of childbearing potential Exclusion Criteria: - severe internal or psychiatric disease (especially depression or suicidal thoughts) - epilepsy - cognitive impairment (< SD under age adjusted norm in neuropsychological testing) - concurrent taking of serotonin precursors (tryptophan, 5-HTP) or MAO inhibitors - concurrent taking of tramadol or triptans - concurrent taking of pimozide or linezolid - concurrent taking of other drugs prolonging the QT-interval - long-QT-syndrome - hypokalemia or hypomagnesemia - known intolerance of the study medication - claustrophobia or metallic implants, tattoos (MRI exclusion criteria) - pregnancy or lactation - participation in another drug-interventional clinical trial within the last month or during the entire study - probands that are placed in an institution due to official or judicial order - non-agreement to save and transmit pseudonymised study data within the clinical trial Inclusion Criteria: - right handedness - unobtrusive neuropsychological screening - ability to provide written informed consent - no pathological findings in head MRI - age: 18 to 35 years (young adults) or 50-80 years (older adults) - Highly effective contraception (Pearl Index < 1) or reliable abstinence from any heterosexual relationships in women of childbearing potential Exclusion Criteria: - severe internal or psychiatric disease (especially depression or suicidal thoughts) - epilepsy - cognitive impairment (< SD under age adjusted norm in neuropsychological testing) - concurrent taking of serotonin precursors (tryptophan, 5-HTP) or MAO inhibitors - concurrent taking of tramadol or triptans - concurrent taking of pimozide or linezolid - concurrent taking of other drugs prolonging the QT-interval - long-QT-syndrome - hypokalemia or hypomagnesemia - known intolerance of the study medication - claustrophobia or metallic implants, tattoos (MRI exclusion criteria) - pregnancy or lactation - participation in another drug-interventional clinical trial within the last month or during the entire study - probands that are placed in an institution due to official or judicial order - non-agreement to save and transmit pseudonymised study data within the clinical trial Healthy Young and Older Adults null --- Val66Met ---

Primary Outcomes

Description: Recall score immediately after learning phase (=training of visual-spatial abilities) under tDC stimulation + SSRI application compared to learning under tDC stimulation + placebo.

Measure: Recall score after learning under tDC stimulation + SSRI compared to learning under tDC stimulation + placebo.

Time: immediately after end of learning phase (approx. 1 hour)

Secondary Outcomes

Description: Measurement of recall scores on the evening of the same day after the learning phase (+tDCS + SSRI), the morning of the day after and 1 week later in order to assess the prolongation of atDCS induced learning enhancement by the SSRI.

Measure: prolongation of the atDCS induced learning enhancement by SSRI

Time: 1 week

Description: Measurement of recall scores directly after learning phase after application of atDCS + placebo or sham-tDCS + SSRI vs. sham-tDCS + placebo.

Measure: Increase of learning enhancement by atDCS + placebo or sham-tDCS + SSRI vs. sham-tDCS + placebo

Time: immediately after learning phase (approx. 1 hour)

Description: Measurement of recall scores on the evening of the same day of learning phase, the morning of the day after and 1 week later under application of atDCS + placebo or sham-tDCS + SSRI vs. sham-tDCS + placebo, in order to assess prolongation of learning enhancement by SSRI.

Measure: prolongation of learning enhancement by atDCS + placebo or sham-tDCS + SSRI vs. sham-tDCS + placebo

Time: 1 week

Description: To assess predictors of SSRI-enhanced brain stimulation, genotyping of several learning related polymorphisms will be performed (i.e., APOE, BDNF, Val66Met, COMT, Val158Met, KIBRA, rs17070145, 5-Hydroxytryptamine transporter).

Measure: genotyping of learning related polymorphisms

Time: once

13 Modulation of Visual-Spatial Learning in Patients With Mild Cognitive Impairment (MCI) by Transcranial Direct Current Stimulation - Proof of Principle and Mechanisms

The aim of this study is to investigate whether a combination of intensive training of visual-spatial abilities (LOCATO task) with anodal transcranial direct current stimulation (tDCS) leads to an improvement in learning and memory in patients with mild cognitive impairment (MCI) and to examine the underlying neuronal mechanism.

NCT02110043 Mild Cognitive Impairment (MCI) Device: tDCS Behavioral: training

MeSH:Cognitive Dysfunction

HPO:Cognitive impairment Mental deterioration

To assess predictors of positive reaction to brain stimulation, genotyping of several learning related polymorphisms will be performed (i.e., APOE, BDNF Val66Met, COMT Val158Met).. Inclusion Criteria (MCI patients): - right handedness - amnestic and amnestic plus MCI with: 1. subjective memory impairment; 2. objective memory difficulties, at least 1 SD below gender, age and education adjusted standard values; 3. relatively normal performance in other cognitive domains; 4. no constraints in activities of daily livings 5. age: 50-90 years Exclusion Criteria: - severe internal or psychiatric disease - epilepsy - other severe neurological diseases, e.g. --- Val66Met ---

Primary Outcomes

Description: Investigation whether the combination of intensive visual-spatial training (LOCATO task) and tDCS leads to improvement of visual-spatial learning and memory measured by performance in LOCATO task after end of a 3 day period of training compared to sham stimulation.

Measure: Performance in LOCATO task (Visual-spatial learning and memory) after a combination of intensive visual-spatial training and tDCS

Time: immediately after end of a 3-day period of training in tDCS condition vs sham condition

Secondary Outcomes

Description: long term effects measured by performance in LOCATO task in tDCS condition after end of cognitve training and after 1 month compared to control conditions

Measure: long term effects

Time: after 1 month vs baseline

Description: Connectivity (measured by resting-state fMRT and correlation analysis) at baseline compared to end of 3 day period of training

Measure: functional changes: Connectivity

Time: end of 3-day cognitive training vs baseline

Description: cortical excitability measured by transcranial magnetic stimulation (TMS)

Measure: cortical excitability

Time: at baseline

Description: quality of life as measured by standardized questionaire at baseline compared to quality of life measured 1 month after intervention (training and stimulation vs. training and sham-stimualtion)

Measure: Quality of Life

Time: after 1 month vs baseline

Description: memory performance tested at baseline compared to memory performance after the end of a 3-day cognitive training period and after 1 month (posttraining) in training and stimulation vs. training and sham stimulation

Measure: memory

Time: immediately after end of 3-day of cognitive training, after 1 month vs. baseline

Description: affective state measured at baseline compared to affective state measured after the end of a 3-day cognitve training period and after 1 month (posttraining) in training and stimulation vs. training and sham stimulation

Measure: affective state

Time: immediately after the end of 3-day cognitive training, after 1 month vs. baseline

Description: To assess predictors of positive reaction to brain stimulation, genotyping of several learning related polymorphisms will be performed (i.e., APOE, BDNF Val66Met, COMT Val158Met).

Measure: genotyping of learning related polymorphisms

Time: once

14 Modulation of Visual-Spatial Learning in Healthy Older Adults by Transcranial Direct Current Stimulation - Proof of Principle and Mechanisms

The aim of this study is to investigate whether a combination of intensive training of visual-spatial abilities (LOCATO task) with anodal transcranial direct current stimulation (tDCS) leads to an improvement of learning and memory in healthy older adults and to examine the underlying neuronal mechanism.

NCT02110056 Healthy Older Adults Device: tDCS Behavioral: training

To assess predictors of positive reaction to brain stimulation, genotyping of several learning related polymorphisms will be performed (i.e., APOE, BDNF Val66Met, COMT Val158Met).. Inclusion Criteria (old healthy controls): - right handedness - unobtrusive neuropsychological screening - age: 50-90 years Exclusion Criteria: - severe internal or psychiatric disease - epilepsy - other severe neurological diseases, e.g. --- Val66Met ---

Primary Outcomes

Description: Investigation whether the combination of intensive visual-spatial training (LOCATO task) and tDCS leads to an improvement of visual-spatial learning and memory measured by performance in LOCATO task after end of a 3 day training period compared to sham stimulation.

Measure: Performance in LOCATO task (Visual-Spatial learning and memory) after a combination of intensive visual-spatial training and tDCS

Time: immediately after the end of a 3 day training period in tDCS condition compared to sham condition

Secondary Outcomes

Description: long term effects measured by performance in LOCATO task after end of training and after 1 month compared to control condition

Measure: long term effects

Time: after 1 month vs baseline

Description: Connectivity (measured by resting-state fMRT and correlation analysis) at baseline compared to end of 3 day period of training

Measure: functional changes: Connectivity

Time: after end of 3-day period of training vs baseline

Description: measured by transcranial magnetic stimulation (TMS) at baseline

Measure: cortical excitability

Time: at baseline

Measure: Quality of life

Time: after 1 month vs baseline

Measure: memory

Time: immediately after end of 3-day of cognitive training, after 1 month vs. baseline

Measure: affective state

Time: immediately after the end of 3-day cognitive training, after 1 month vs. baseline

Description: To assess predictors of positive reaction to brain stimulation, genotyping of several learning related polymorphisms will be performed (i.e., APOE, BDNF Val66Met, COMT Val158Met).

Measure: genotyping of learning related polymorphisms

Time: once

15 Modulation of Visual-Spatial Learning in Healthy Young Adults by Transcranial Direct Current Stimulation - Proof of Principle and Mechanisms

The aim of this study is to investigate whether a combination of intensive training of visual-spatial abilities (LOCATO task) with anodal transcranial direct current stimulation (tDCS) leads to an improvement of learning and memory in healthy young adults and to examine the underlying neuronal mechanism.

NCT02110407 Healthy Young Adults Device: tDCS Behavioral: training

To assess predictors of positive reaction to brain stimulation, genotyping of several learning related polymorphisms will be performed (i.e., APOE, BDNF Val66Met, COMT Val158Met).. Inclusion Criteria: - right handednesss - unobtrusive neuropsychological screening - age: 18-35 years Exclusion Criteria: - severe internal or psychiatric disease - epilepsy - other severe neurological disease, e.g. --- Val66Met ---

Primary Outcomes

Description: Investigation whether the combination of intensive visual-spatial training (LOCATO task) and tDCS leads to improvement of visual-spatial learning and memory measured by the performance in LOCATO task after end of a 3 day period of training compared to sham stimulation.

Measure: performance in LOCATO task (visual-spatial learning and memory) after a combination of intensive visual-spatial training and tDCS

Time: immediately after end of a 3 day period of training in tDCS condition vs sham condition

Secondary Outcomes

Description: long term effetcs measured by performance in LOCATO task after end of training and after 1 month compared to control conditions

Measure: long term effects

Time: after 1 month vs baseline

Description: Connectivity (measured by resting-state fMRT and correlation analysis) at baseline compared to end of training

Measure: functional changes: Connectivity

Time: after end of 3-day cognitive training vs baseline

Description: cortical excitability measured by transcranial magnetic stimulation (TMS)

Measure: cortical excitability

Time: at baseline

Measure: Quality of Life

Time: after 1 month vs baseline

Measure: memory

Time: immediately after end of 3-day of cognitive training, after 1 month vs. baseline

Description: To assess predictors of positive reaction to brain stimulation, genotyping of several learning related polymorphisms will be performed (i.e., APOE, BDNF Val66Met, COMT Val158Met).

Measure: genotyping of learning related polymorphisms

Time: once

16 Study of the BDNF- Val66Met Polymorphism in Alcohol-dependent Subjects in Relation to Abstinence After Withdrawal

This study is complementary to the main study "Brain Derived Neurotrophic Factor Serum Levels Evolution During the Six Months After Alcohol Withdrawal " NCT01491347. The purpose of this study is to evaluate the Bdnf gene - Val66Met polymorphism in subjects with alcohol dependence according to their alcohol consumption status 6 months after withdrawal (relapse or abstinence), in relation to the presence of psychiatric co-morbidities.

NCT02146963 Alcohol Dependence

MeSH:Alcoholism

Study of the BDNF- Val66Met Polymorphism in Alcohol-dependent Subjects in Relation to Abstinence After Withdrawal. --- Val66Met ---

Study of the BDNF-Val66Met Polymorphism in Alcohol-dependent Subjects in Relation to Abstinence After Withdrawal This study is complementary to the main study "Brain Derived Neurotrophic Factor Serum Levels Evolution During the Six Months After Alcohol Withdrawal " NCT01491347. --- Val66Met ---

The purpose of this study is to evaluate the Bdnf gene - Val66Met polymorphism in subjects with alcohol dependence according to their alcohol consumption status 6 months after withdrawal (relapse or abstinence), in relation to the presence of psychiatric co-morbidities. --- Val66Met ---

Primary Outcomes

Measure: Frequency of the Bdnf gene Val/Val, Val/Met and Met/Met phenotypes as a function of relapse

Time: at the time of inclusion

Secondary Outcomes

Measure: serum BDNF levels variations between inclusion and 6 months later (or 4 months if the participants does not come for the 4 months-follow-up).

Time: 6 months after alcohol withdrawal

Measure: existence of a psychiatric co-morbidity at the inclusion (major depression, schizophrenia, anxiety disorder)

Time: at the time of inclusion

Measure: presence of a psychiatric co-morbidity at 6 months after withdrawal (major depression, schizophrenia, anxiety disorder)

Time: 6 month after alcohol withdrawal

17 High-intensity Exercise and Fall Prevention Boot Camp for Parkinson's Disease

Several animal and human epidemiologic studies have provided evidence that exercise may be neuroprotective in Parkinson's disease (PD). Exercise may forestall diagnosis and, in the case of those who have already been diagnosed with PD, it may slow the observed neurodegeneration. Unfortunately, because this line of research is in early stages, there is little evidence to indicate what biological mechanisms underlie the neuroprotection that is conferred with exercise. Toward this end, it is possible that an interaction between endogenous antioxidant enzymes, inflammatory processes, and reactive oxygen species may be associated with exercise improvements in PD. One of the most common reasons for premature death in PD is falls. Several meta-analyses have concluded that exercise training programs focused on balance and/or strength training are effective at improving aspects of balance. Taken together, the current body of evidence suggests that exercise may be neuroprotective and balance/strength training may decrease the likelihood of a fall. The combination of these efficacious treatment modalities (exercise and balance/strength training) in a comprehensive treatment approach to improve PD symptoms and balance has been previously reported at relatively mild or moderate exercise intensities. Because recent research has suggested that patients with PD may benefit more from more physically intense programs, we are proposing a more aggressive approach with regard to exercise intensity and frequency in the present trial. The primary purpose of this study is to determine the feasibility and safety of a high intensity exercise approach to PD. A secondary purpose is to determine the trajectory of change in outcomes over the duration of the trial from a high intensity fall prevention program. It is hoped that a signal of efficacy will allow this trial to progress to a comparative effectiveness trial. An important innovative design element is collecting biological assays to better understand the mechanism underlying the anticipated clinical improvements. Aim 1 is to test the feasibility of a high-intensity exercise and fall prevention boot camp (HIBC) in patients with PD by analyzing adherence and whether they achieve minimum Centers for Disease Control exercise standards (150 min/wk moderate level aerobic exercise; strengthening at least two times per week) for the duration of the trial. Aim 2 is to determine if participation in an 8-week HIBC under the direction of a physical therapist is safe for individuals with PD. Secondary Aim 3 is to determine if participation in an 8-week HIBC will produce a signal of efficacy for several physical outcomes: falls per physical activity ratio, balance efficacy, motor activity, fatigue, muscle strength, bone health, cognition/mood, and quality of life. Secondary Aim 4 is to determine if participation in an 8-week HIBC will produce a signal of efficacy for biological outcomes, anti-inflammatory cytokines and anti-oxidant enzymes. An additional exploratory aim will be an analysis of BDNF val66val, val66met, met66met polymorphisms to determine if there is a differential response to exercise. This trial is innovative because it utilizes a high intensity comprehensive exercise treatment approach (aerobic exercise, strengthening, and balance training). To our knowledge, there have been no trials of individuals with PD who have participated in a trial of this intensity in a group "boot camp" setting. Another innovative design element is the use of three novel assessments: biological assays of pro- and anti-inflammatory cytokines, endogenous anti-oxidant enzymes and a novel assessment of falls (falls per physical activity ratio). Participants will be randomly assigned into either an 8-week HIBC group or an 8-week usual care control group (standard, low intensity group therapy class) under the direction of physical therapists. Each group will have 15 participants with a 1:5 patient-to-therapist ratio. The HIBC will be 1.5 hours daily, Monday through Friday. Participants will be required to attend 3 out of the 5 days. The protocol of the HIBC will include the following exercise components: A. 30 minutes of moderate-high intensity aerobic exercise; B. 15 minutes of strengthening the major muscle groups; C. 15 minutes of balance training; and, D. 15 minutes of interspersed rest and stretching. Participants will rotate through these four exercise components. Participants will have one baseline test and assessments at the 2-week, 4 week, 8-week, and 6-month points. Outcomes of the primary aims (Aim 1 and Aim 2) will be frequency counts of participation, adverse events, and compliance with exercise. The outcomes for the secondary aims will include measures of balance and falls, physical capacity, fatigue, exercise/physical activity behavior, and biological assays.

NCT02230267 Parkinson's Disease Other: High intensity exercise and balance training Other: Usual care arm exercise

MeSH:Parkinson Disease

An additional exploratory aim will be an analysis of BDNF val66val, val66met, met66met polymorphisms to determine if there is a differential response to exercise. --- val66met ---

Primary Outcomes

Description: The number of participants that attend and participate in the treatment at least 3 times per week for 8 weeks.

Measure: Frequency feasibility

Time: After completion of the 8 week trial

Description: The number of participants that complete at least 150 minutes per week of moderate intensity exercise (70%+ of their estimated HR maximum). This will be ascertained using heart rate monitors.

Measure: Aerobic feasibility

Time: At the end of the 8 week trial

Description: The number of participants that participate in strengthening exercises that incorporates all the major muscle groups at least two days per week.

Measure: Strength feasibility

Time: At the end of the 8 week trial

Description: Drop-out rate and reason for drop-out will be tracked.

Measure: Compliance

Time: At the end of the 8 week trial

Description: Exercise-related adverse events (e.g., strains/sprains, cardiovascular events).

Measure: Safety

Time: Ongoing throughout the 8 week trial

Description: The Intrinsic Motivation Inventory (IMI) will be used to gather information about motivation.

Measure: Motivation

Time: At 8 weeks

Description: Falls and fall injuries in and out of boot camp will be collected.

Measure: Falls

Time: At the end of the 8 week trial

Secondary Outcomes

Description: Falls will be tracked for 6 months after the boot camp using a falls diary. A member of the research team will call each month to interview participants about their falls. We will assess falls/fall injuries per physical activity ratio during the 6 month period following the trial and time to a fall/fall injury after the trial.

Measure: Falls

Time: up to 6 months

Description: Physical activity will be assessed using the Physical Activity Monitoring System (PAMsys).

Measure: Motor activity

Time: up to 6 months

Description: Fatigue will be assessed using the Parkinson Fatigue Scale (PFS).

Measure: Fatigue

Time: up to 6 months

Description: This will be assessed functionally using the 30 second Sit-To-Stand Test (30STS) for muscle strength.

Measure: Strength

Time: up to 6 months

Description: Cognition will be assessed using the Montreal Cognitive Assessment (MoCA).

Measure: Cognition

Time: up to 6 months

Description: This will be assessed by using a measure of disease-specific quality of life (Parkinson's Disease Questionnaire-39 (PDQ39)).

Measure: Quality of life

Time: up to 6 months

Description: All participants will track their participation in exercise and physical activity using an exercise diary for 6 months following the boot camp. Participants will be called monthly to reinforce completion of the exercise diary.

Measure: Long term behavioral change

Time: up to 6 months

Description: Performance-based balance tasks.

Measure: mini-Balance Evaluation Systems Test (mini-BESTest)

Time: up to 6 months

Description: Activities Specific Balance Confidence Scale (ABC)

Measure: Falls self-efficacy

Time: up to 6 months

Description: Self-report measurement tool: Falls Efficacy Scale (FES)

Measure: Fall Efficacy

Time: Up to 6 months

Description: Self-report of fall catastrophization: Catastrophization about Falls Questionnaire (CAFS)

Measure: Fall catastrophization

Time: Up to 6 months

Description: Self-report measure physical activity: International Physical Activity Questionnaire (IPAQ)

Measure: Physical activity

Time: Up to 6 months

Description: Unified Parkinson's Disease Rating Scale motor subscale (UDPRS III)

Measure: Motor symptoms

Time: Up to 6 months

Description: Self-report scale of avoidance behavior due to a fear of falling: Fear of Falls Avoidance Behavior Questionnaire (FFABQ)

Measure: Fear of falling

Time: Up to 6 months

Description: Endurance will be assessed using the 6 Minute Walk Test (6MWT).

Measure: Endurance

Time: Up to 6 months

Description: Bone health will be measured using bone mineral densiometry (BMD).

Measure: bone health

Time: up to 6 months

Description: Mood will be measured using the Beck Depression Inventory.

Measure: Mood

Time: up to 6 months

Description: Catalase concentrations from blood will be quantified utilizing enzyme-linked immunosorbent assays.

Measure: Catalase

Time: Up to 6 months

Description: Cytokine (TNFα, IL-6, IL-10) concentrations from blood will be quantified utilizing enzyme-linked immunosorbent assays.

Measure: Cytokines

Time: Up to 6 months

Other Outcomes

Description: Circulating BDNF concentrations from blood will be quantified utilizing enzyme-linked immunosorbent assays.

Measure: BDNF

Time: up to 6 months

18 BDNF as a Potential Biomarker for Cognitive Remediation Therapy in Schizophrenia

The main objective of the study is to analyse the role of a neurotrophic factor (BDNF) as a putative biological marker of the cognitive recovery in schizophrenia following a Cognitive Remediation Therapy (CRT). Additionally, the role as outcome predictors of BDNF serum levels and the Val66met polymorphism and data from functional and structural neuroimaging will be studied.

NCT02341131 Schizophrenia Behavioral: Cognitive Remediation Therapy Behavioral: Psychoeducation

MeSH:Schizophrenia

HPO:Schizophrenia

Additionally, the role as outcome predictors of BDNF serum levels and the Val66met polymorphism and data from functional and structural neuroimaging will be studied. --- Val66met ---

Primary Outcomes

Description: Change Measurements of serum BDNF levels will be carried out by personnel blind to subjects' group assignment. Platelet and serum samples will be diluted with diluent included in the R&D Human BDNF Quantikine Enzym Linked Immunosorbent Assay (ELISA) kit (Yasuhito et al. 1987).

Measure: BDNF (change from baseline serum BDNF levels)

Time: Baseline, 1 month and 4 months

Secondary Outcomes

Description: Change from baseline in Positive and Negative Syndrome Scale (PANSS) scores at time 16 weeks

Measure: Symptoms (Change from baseline in Positive and Negative Syndrome Scale (PANSS) scores)

Time: Baseline and 4 months

19 Does the Brain-derived Neurotrophic Factor Val66Met Gene Polymorphism Predict Inter-individual Variation in Responsiveness Following Lumbar Radiofrequency Denervation? A Single-centre, Prospective, Exploratory Study in Subjects Diagnosed With Zygapophysial Joint Pain

The Investigators have designed this exploratory study in patients suffering from zygapophysial joint mediated pain to investigate if a correlation exists between inter-individual genetic variability (genotype) with treatment response (phenotype). More specifically, the investigators aim to identify any form of correlation between a specific SNP of the BDNF gene (Val66Met) and the effectiveness and/or duration of radiofrequency facet joint neurotomy. The study population is patients suffering from chronic low back pain who have been scheduled for radiofrequency neurotomy following the diagnosis of facet joint mediated pain (using medial branch block test). The investigators will evaluate if a common variant of BDNF gene (Val66Met) can be directly correlated to a significant degree of pain relief following RF treatment, and whether the result of such a procedure can be predicted from a specific genetic profile.

NCT02383524 Chronic Low Back Pain Procedure: Lumbar Radiofrequency Medial Branch Neurolysis

MeSH:Back Pain Low Back Pain

HPO:Back pain Low back pain

Does the Brain-derived Neurotrophic Factor Val66Met Gene Polymorphism Predict Inter-individual Variation in Responsiveness Following Lumbar Radiofrequency Denervation? --- Val66Met ---

More specifically, the investigators aim to identify any form of correlation between a specific SNP of the BDNF gene (Val66Met) and the effectiveness and/or duration of radiofrequency facet joint neurotomy. --- Val66Met ---

The investigators will evaluate if a common variant of BDNF gene (Val66Met) can be directly correlated to a significant degree of pain relief following RF treatment, and whether the result of such a procedure can be predicted from a specific genetic profile. --- Val66Met ---

Primary Outcomes

Description: Number of patients in each group who report 50% reduction in pain on the visual analogue scale 3 months after radiofrequency denervation for lumbar zygapophysial (facet) joint mediated pain

Measure: Responder Rate

Time: 3 months

Secondary Outcomes

Measure: Medication intake, Functional status, Ability to work and Quality of life

Time: 3 months

Other Outcomes

Description: To evaluate whether any specific and/or combination of SNPs observed could be related with the clinical outcomes measured in this study

Measure: Pre-specified Single Nucleotide Polymorphism (SNP) analysis

Time: 3 months

20 Evolving Methods to Combine Cognitive and Physical Training for Individuals With Mild Cognitive Impairment: An Efficacy Study

This study aims to investigate and compare the intervention effects of combining exercise and cognitive training (either sequentially or simultaneously in a dual-task paradigm) in elderly with mild cognitive impairment. The investigators hypothesize that (1) both sequential and dual-task training can induce greater improvements in the outcome measures than single mode of training; (2) the improvement in cognitive functions and other outcomes may differ between the groups.

NCT02512627 Mild Cognitive Impairment Behavioral: Cognitive training Behavioral: Physical exercise

MeSH:Cognitive Dysfunction

HPO:Cognitive impairment Mental deterioration

The raw score of each subtest will also be transferred to standardized Z scores and summed to represent an index of general cognitive function.. BDNF val66met genotype. --- val66met ---

Saliva samples will be collected at baseline to determine the Brain-Derived Neurotrophic Factor (BDNF) val66met genotype.. Inclusion Criteria: 1. able to follow instruction, 2. clinical dementia rating (CDR) = 0.5 or 1, 3. self- or informant-reported memory or cognitive complaint, and 4. able to perform activities of daily living (Barthel Index ≥ 70). --- val66met ---

Primary Outcomes

Description: The MoCA will be used to assess general cognitive functions. It examines several cognitive domains with a total score of 30.

Measure: Change scores of Montreal Cognitive Assessment (MoCA)

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The Stroop test will be used to assess the processing speed, inhibition, set-shifting, and selective attention abilities. The participants will be tested under 2 conditions: congruent and incongruent conditions. In the congruent condition, the color ink of a word is consistent with the written color name; while the color ink differs from the written color name under the incongruent condition.

Measure: Change scores of Stroop test

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The dual-task tests will be assessed to determine the ability for an individual to perform 2 tasks simultaneously. The investigators will assess the dual-task performance during walking and performing box and block test. The results of the dual-task tests will provide information regarding to whether the 2 tasks compete for the same class of neural resources or one of the tasks can be carried out automatically.

Measure: Change scores of Dual-task test

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The TUG test will be used to assess the mobility and dynamic balance ability. The participants will be required to stand up from a chair, walk 3 meters, turn around, then walk back to the chair, and sit down. The time to complete the TUG test has been shown to be a good indicator to detect potential fallers and frail elderly (Podsiadlo & Richardson, 1991). The test-retest reliability of TUG on individuals with cognitive impairment was excellent (Blankevoort, van Heuvelen, & Scherder, 2013).

Measure: Change scores of Timed up and go (TUG) test

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Secondary Outcomes

Description: Verbal fluency tests will be used to evaluate the semantic memory of the participants. The participants will be instructed to say as many words as possible from a given category (i.e., fruit or animal) in 1 minute. The validity, reliability, and normative performance of verbal fluency tests have been well-established (Harrison, Buxton, Husain, & Wise, 2000).

Measure: Change scores of the Verbal Fluency Test

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: Useful field of view (UFOV) is the visual area over which useful information could be obtained at a quick glance without eye or head movements. This UFOV will be assessed with the BrainHQ program. The UFOV will assess the abilities of visuomotor processing speed, divided attention, and selective attention (Ball, Edwards, & Ross, 2007).

Measure: Change scores of the Useful Field of View (UFOV)

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The 30 second chair stand test (CST) will be assessed to indicate the strength and endurance level of the lower extremities. The participants will be asked to stand up from a standardized chair and then sit down as many times as possible within 30 seconds. The feasibility and reliability of using CST in people with cognitive impairment have been established to be good (Blankevoort et al., 2013).

Measure: Change scores of the 30 second chair stand test (CST)

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The Chinese version of the International Physical Activity Questionnaires (IPAQ) is an international measure for health-related physical activity. A short form of IPAQ will be used to assess changes in physical activity before and after intervention in this study. The reliability and validity of IPAQ has been established across 12 countries (Craig et al., 2003).

Measure: Change scores of the Chinese version of the International Physical Activity Questionnaires (IPAQ)

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: Assess activities of daily living

Measure: Change scores of the Barthel Index (BI)

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: Assess activities of daily living.

Measure: Change scores of the Lawton Instrumental Activities of Daily Living Scale

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: Assess activities of daily living.

Measure: Change scores of the Disability Assessment for Dementia (DAD)

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The Chinese version of QoLAD will be used.

Measure: Change scores of the Quality of Life in Alzheimer's Disease Instrument (QoLAD)

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The Chinese version of CBI will be used.

Measure: Change scores of the Caregiver Burden Inventory (CBI)

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The Chinese version of short form GDS will be used.

Measure: Change scores of the Geriatric Depression Scale (GDS)

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The CIQ measures items relevant to home integration, social integration, and productive activities.

Measure: Change scores of the Community Integration Questionnaire (CIQ)

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The actigraphy will be placed on the waist for a 3-day period immediately before and after the intervention. The participants will wear the actigraphy during all daily activities except for those that involve water (i.e., showering or swimming).

Measure: Change scores of the ActiGraph GX3 accelerometers Change scores of the ActiGraph

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The participant will be seated upright in a chair with back support, the knee will be placed in 90-degree flexion and the evaluator will stabilize the thing to eliminate synergistic movements. Participants will be asked to perform a maximal isometric contraction of knee flexion and extension with both lower extremities. The investigators will record the mean value of 3 attempts.

Measure: Change scores of evaluating isometric knee flexors and extensors muscle strength

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The participant is seated, with the elbow at 90-degree flexion. The investigators will record the mean value of 3 attempts.

Measure: Change scores of using hand dynamometer to measure grip strength of both hand

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The investigators will use the WMS-III subtests, including Faces Recognition (score range 0-48), Verbal Paired Associates (score range 0-32), Word Lists (0-48), and Spatial Span (0-32) to assess the immediate, delayed, and working memory tests. Higher scores indicated better performance for each subtest. The raw score of each subtest will also be transferred to standardized Z scores and summed to represent an index of general memory function.

Measure: Change scores of Wechsler Memory Scale - Third Edition (WMS-III)

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The WAIS-III includes tests that evaluate cognitive functions in verbal comprehension, working memory, perceptual organization, and processing speed. The subtests that the investigators will use are the Digit Symbol-Coding (scores range 0-133) and Matrix Reasoning tests (0-26). The raw score of each subtest will also be transferred to standardized Z scores and summed to represent an index of general cognitive function.

Measure: Change scores of Wechsler Adult Intelligence Scale - Third Edition (WAIS-III)

Time: baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: Saliva samples will be collected at baseline to determine the Brain-Derived Neurotrophic Factor (BDNF) val66met genotype.

Measure: BDNF val66met genotype

Time: baseline

21 Synergistic Effects of Aerobic Exercise and Cognitive Training on Cognition, Physiological Markers, Daily Function and Quality of Life in Stroke Patients With Cognitive Decline

The purpose of this study is to determine the treatment effects of sequential combination of aerobic exercise and cognitive training on cognitive function, physiological markers, daily function, physical function, social participation and quality of life in stroke patients with cognitive decline. The investigators hypothesized that: (1) sequential training protocol can improve outcome measures compared to single mode of training; (2) these treatment effects will retain at 6-month follow-up.

NCT02550990 Stroke Patients With Cognitive Decline Behavioral: Cognitive training Behavioral: Aerobic exercise training Behavioral: Sequential combination of aerobic exercise and cognitive training

MeSH:Stroke Cognitive Dysfunction

HPO:Cognitive impairment Mental deterioration Stroke

Genotyping of the BDNF val66met polymorphism. --- val66met ---

Primary Outcomes

Measure: Change scores of Montreal Cognitive Assessment (MoCA)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Wechsler Memory Scale - Third Edition (WMS-III)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Wechsler Adult Intelligence Scale - Third Edition (WAIS-III)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Useful Field of View (UFOV)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Stroop Color-Word test

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Dual-task test

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Secondary Outcomes

Measure: Change scores of serum BDNF level

Time: Baseline, posttest (an expected average of 3 months)

Description: Antioxidative markers will be used to reflect the changes on oxidative stress. In particular, we will be analyzing the total antioxidant capacity (TAC).

Measure: Change scores of Antioxidative marker

Time: Baseline, posttest (an expected average of 3 months)

Description: HbA1C level will be tested to investigate the relationships between blood glucose level and aerobic exercise.

Measure: Change scores of Glucose indicator

Time: Baseline, posttest (an expected average of 3 months)

Description: The cholesterol ratio (total cholesterol divided by high-density lipid) will be evaluated to reflect the lipid level in the blood.

Measure: Change scores of Plasma lipid level

Time: Baseline, posttest (an expected average of 3 months)

Measure: Change scores of Functional Independence Measure (FIM)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Lawton Instrumental Activities of Daily Living Scale (Lawton IADL)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Stroke Impact Scale (SIS)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Caregiver Burden (CB) scale

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of EuroQol (EQ)-5D questionnaire

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Timed up and go test (TUG)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Six-minute walk test (6MWT)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Mobility level

Time: Baseline, posttest (an expected average of 3 months)

Measure: Change scores of International Physical Activity Questionnaires (IPAQ)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Fugl-Meyer Assessment (FMA)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Rivermead Mobility Index (RMI)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: We will evaluate isometric knee flexors and extensors muscle strength using handheld dynamometer. Also, we will use hand dynamometer to measure grip strength of the affected and less affected hand while the participant is seated, with the elbow at 90-degree flexion. We will record the mean value of 3 attempts.

Measure: Change scores of muscle strength

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Community Integration Questionnaire (CIQ)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Geriatric Depression Scale (GDS)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Genotyping of the BDNF val66met polymorphism

Time: Between baseline and posttest (an expected average of 3 months)

22 Secondary Prevention of Depression Applying an Experimental Attentional Bias Modification Procedure

Depression (Major Depressive Disorder; MDD) has been dubbed "the common cold among the mental illnesses" and it is also a highly recurrent disorder. Secondary prevention has been identified as a key goal in the long-term management of depression. High recurrence rate suggests that there are specific vulnerability factors that increase people's risk for developing repeated episodes of the disorder. Preventive strategies should identify and ameliorate these factors to reduce the individual's risk of subsequent episodes. Biased attention for emotional stimuli is central to the cognitive model where increased sensitivity to negative cues is believed to fuel the negative thoughts and feelings in depression and play a key role in maintaining the illness. Selective biases in attention can be modified by a simple computerized technique; The Attention Bias Modification Task (ABM). This project aims to investigate whether ABM can reduce surrogate and clinical markers of relapse in a large group highly vulnerable to depressive episodes. The effects of ABM, immediately after the two weeks intervention, on three key risk factors for depression will be studied: Residual symptoms, cortisol awakening response and emotion regulation strategies. The participants will be followed up after 1 month, 6 months and 12 months. The hypothesis that ABM will reduce subsequent episodes of low mood over the following 12 months in this group in a manner predicted by early changes in these risk factors will be investigated. It will also be tested if such effects in the lab may be dependent on candidate genes which affect serotonin reuptake and which have been implicated in malleability and emotional learning. Effects on underlying neural correlates of emotion regulation will be studied in an fMRI experiment in a sub-sample and which will also be stratified by serotonin transporter genotype (see also NCT02931487). The predictive value of meta cognitions related to rumination and the possible mediating effects of automatic thoughts and perceived stress will also be investigated in a sub group (see also NCT02648165). The characterization of the cognitive, genetic and neural mechanisms underlying the ABM effect will have key implications for future treatment development and combination with other treatment modalities like pharmacotherapy.

NCT02658682 Major Depression Behavioral: Attention Bias Modification Behavioral: Sham Attention Bias Modification

MeSH:Depression Depressive Disorder

HPO:Depressivity

Brain Derived Neurotrophic Factor (BDNF) val66met polymorphic variation linked to Brian Derived Neurotrophic Factor (BDNF) variation will moderate the effect of ABM on residual symptoms compared to neutral ABM placebo condition. --- val66met ---

Primary Outcomes

Description: Beck Depression Inventory

Measure: Change in residual symptoms of depression. Self report.

Time: At baseline and immediately after ABM intervention (during first week after ABM).

Description: Hamilton Depression Rating Scale

Measure: Change in residual symptoms of depression. Clinician rating

Time: At baseline and immediately after ABM intervention (during first week after ABM).

Secondary Outcomes

Description: Measured by the MINI structured interview

Measure: Recurrence of major depressive episodes

Time: Will be measured 12 month after baseline

Description: Emotion Regulation Questionnaire (ERQ).

Measure: Changes in Emotion Regulation

Time: At baseline.

Description: The Rumination Response Scale

Measure: Changes in Rumination

Time: At baseline and 12 months after intervention

Description: Cortisol samples from saliva measured by diural variation (6 samples).

Measure: Changes in cortisol response.

Time: At baseline, immediately after ABM intervention and one month after intervention.

Description: Beck Anxiety Inventory

Measure: Changes in symptoms of anxiety

Time: At baseline, immediately after ABM intervention (during first week after ABM intervention), 1 month after intervention, 6 months after intervention and 12 months after intervention

Other Outcomes

Description: Automatic Thought Questionnaire (ATQ)

Measure: Automatic thoughts

Time: At baseline, immediately after ABM intervention (average one day), 1 month after intervention, 6 months after intervention and 12 months after intervention

Description: Perceived Stress Scale (PSS).

Measure: Changes in perceived stress

Time: At baseline, immediately after ABM intervention (average one day), , 1 month after intervention, 6 months after intervention and 12 months after intervention

Description: Positive and Negative Beliefs about Rumination scale (PBRS and NBRS)

Measure: Meta cognitions

Time: At baseline and 12 months after intervention

Measure: 5-HTTLPR+A>G polymorphic variation divided by the triallelic functional "high expressive" versus "low expressive" genotype will moderat the effect of ABM on residual symptoms compared to neutral ABM placebo condition

Time: Immediately after ABM intervention.

Measure: Brain Derived Neurotrophic Factor (BDNF) val66met polymorphic variation linked to Brian Derived Neurotrophic Factor (BDNF) variation will moderate the effect of ABM on residual symptoms compared to neutral ABM placebo condition

Time: Immediately after ABM intervention.

Measure: A serotonergic cumulative Genetic score, including (5-HHTLPR, HTR1A 8rs6295) and HTR 2A (rs 6311) polymorphisms will moderate the effects of ABM on residual symptoms compared to neutral placebo condition

Time: Immediately after ABM intervention.

Description: Beck Depression Inventory

Measure: Change in residual symptoms of depression. Self report

Time: One month after intervention, 6 months after intervention and 12 months after intervention

Description: Hamilton Depression Rating Scale

Measure: Change in residual symptoms of depression. Clinical rating

Time: One month after intervention, 6 month after intervention and 12 month after intervention

Measure: Primary outcome measures will be modified by the degree of attentional change during the ABM intervention.

Time: Immediately after the ABM intervention

Measure: Primary outcome measures will be modified by executive functioning

Time: At baseline

23 The Development of Skin Adhesive Patches for the Monitoring and Prediction of Mental Disorders

development of skin adhesive patches for the monitoring and prediction of mental disorders

NCT02690324 Major Depressive Disorder, Anxiety Disorder Behavioral: cognitive stress (serial 7)

MeSH:Depressive Disorder Depressive Disorder, Major Anxiety Disorders

HPO:Depressivity

Brain-derived neurotrophic factor(BDNF) genotyping: Val66Met. --- Val66Met ---

Primary Outcomes

Description: changes of skin conductane level(SCL) and skin conductance response(SCR)

Measure: Electrodermal activity(EDA)

Time: baseline, 0.5, 1,2,3 months

Description: changes of SDNN, RMSSD and LF/HF ratio

Measure: Heart rate variability

Time: baseline, 0.5, 1,2,3 months

Secondary Outcomes

Measure: Brain-derived neurotrophic factor(BDNF) genotyping: Val66Met

Time: baseline, 0.5, 1,2,3 months

Description: IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12(p70), IFN-γ, TNF-α

Measure: Cytokines

Time: baseline, 0.5, 1,2,3 months

Measure: Leptin

Time: baseline, 0.5, 1,2,3 months

Measure: Adiponectin

Time: baseline, 0.5, 1,2,3 months

Measure: Epinephrine

Time: baseline, 0.5, 1,2,3 months

Measure: Norepinephrine

Time: baseline, 0.5, 1,2,3 months

Measure: C reactive protein

Time: baseline, 0.5, 1,2,3 months

Description: serum, plasma, platelet BDNF

Measure: BDNF

Time: baseline, 0.5, 1,2,3 months

Description: structured interview assessing for DSM-IV Axis I disorders with strong reliability and validity in relation to the Structured Clinical Interview for DSM-IV (SCID-IV)

Measure: MINI plus

Time: Baseline

Description: assess current and past Axis I diagnoses

Measure: MINI Suicidality Module

Time: baseline, 0.5, 1,2,3 months

Description: changes of HAMD-17 total socres

Measure: Hamilton Depression Rating Scale-17(HAMD-17)

Time: baseline, 0.5, 1,2,3 months

Description: changes of HAMA total scores

Measure: Hamilton Anxiety Rating Scale(HAMA)

Time: baseline, 0.5, 1,2,3 months

Description: ASI-3 to measure the three most supported AS domains: social (i.e., fear of exhibiting symptoms in public that may elicit embarrassment), cognitive (i.e., fear of losing cognitive control or experiencing concentration difficulties), and physical (i.e., fear that physical sensations are a sign of an immediate physical problem).

Measure: Anxiety Sensitivity Index(ASI)

Time: baseline, 0.5, 1,2,3 months

Description: The APPQ (Rapee et al., 1995) is a 27-item instrument that is designed to measure interoceptive, agoraphobic, and social situational fear. Subjects respond to each item on a 9-point Likert scale from 0 to 8, according to how much fear they think they would experience in a given situation so that total scores range from 0 to 216.

Measure: APPQ(Albany Panic and Phobia Questionnaire)

Time: baseline, 0.5, 1,2,3 months

Description: 16-item questionnaire that aims to measure the trait of worry, using Likert rating from 1 (not at all typical of me) to 5 (very typical of me)

Measure: PSWQ(Penn state worry questionnaire)

Time: baseline, 0.5, 1,2,3 months

Description: emotional, somatic, cognitive, and behavioral stress responses.

Measure: SRI(Stress response Inventory)

Time: baseline, 0.5, 1,2,3 months

Description: The Perceived Stress Scale (PSS) is the most widely used psychological instrument for measuring the perception of stress. It is a measure of the degree to which situations in one's life are appraised as stressful.

Measure: Perceived Stress Scale(PSS)

Time: baseline, 0.5, 1,2,3 months

Description: The Barratt Impulsiveness Scale (BIS) is a widely used measure of impulsiveness. It includes 30 items that are scored to yield six first-order factors (attention, motor, self-control, cognitive complexity, perseverance, and cognitive instability impulsiveness) and three second-order factors (attentional, motor, and non-planning impulsiveness).The BIS-11 is a 30-item self-report questionnaire, that is scored to yield a total score, three second-order factors, and six first-order factors.

Measure: Barratt Impulsivity Scale

Time: baseline, 0.5, 1,2,3 months

Description: The items assess panic frequency, distress during panic, panic-focused anticipatory anxiety, phobic avoidance of situations, phobic avoidance of physical sensations, impairment in work functioning, and impairment in social functioning. The overall assessment is made by a total score, which is calculated by summing the scores for all seven items. The total scores range from 0 to 28.

Measure: Panic disorder severity scale(PDSS)

Time: baseline, 0.5, 1,2,3 months

24 Restoring Emotion Regulation Networks in Depression Vulnerability: An Experimental Study Applying an Attention Bias Modification Procedure

Selective biases in attention can be modified by a simple computerized technique: The Attention Bias Modification Task (ABM) pioneered by MacLeod et al. Cognitive biases may be one reason depression recurs, and altering these biases should reduce risk of recurrence. Recently, evidence has supported this hypothesis . The mechanisms by which ABM works are not well understood. More research is needed to explore how altering an implicit attentional bias can lead to changes in subjective mood. One possible explanation is that positive attentional biases are an important component of explicit methods of emotion regulation. The ability to effectively regulate one's emotions is a fundamental component of mental health and this ability is impaired in depression. It has also been shown that recovered depressed people spontaneously show a more dysfunctional pattern of emotion regulation as compared to never depressed controls. Supporting this, growing evidence implicates dysregulation of a medial/orbitofrontal circuit in mood disorders. This circuit includes the orbitofrontal cortex and anterior cingulate cortex, the ventral striatum, the ventral pallidum and medial thalamus. Components of this circuit are reciprocally connected with the amygdala, which is implicated in emotional processing in the healthy brain and dysregulated in depression. Negative emotion processing biases depend on both enhanced "bottom-up" responses to emotionally salient stimuli and reduces "top-down" cognitive control mechanisms, required to suppress responses to emotionally salient but task irrelevant information. Cognitive reappraisal and distancing are common strategies to down- or upregulate emotional responses. Reappraisal is an emotion regulation strategy that involves reinterpretation and changing the way one thinks about an event or stimulus with the goal of changing its affective impact. Distancing is a type of reappraisal that involves creating mental space between oneself and the emotional event in order to see things from a different, less self-focused perspective. It has been shown that distancing is a strategy that people can improve at over time compared to reinterpretation. The neural systems which support the explicit regulation of emotion have previously been characterized and include both lateral- and prefrontal cortex. This frontal activity is predicted to downregulate limbic circuitry involving the amygdala during passive viewing of emotional salient stimuli.

NCT02931487 Major Depression Behavioral: Attentional Bias Modification Behavioral: Sham Comparator

MeSH:Depression Depressive Disorder

HPO:Depressivity

Brain Derived Neurotropic Factor (BDNF) val66met polymorphic variation linked to Brain Derived Neurotropic Factor (BDNF) variation will differentiate between ABMT and neutral AMB placebo as measured by fMRI whole brain BOLD responses.. Serotonergic cumulative genetic score and fMRI. --- val66met ---

Primary Outcomes

Description: Stronger fMRI BOLD response in prefrontal cortical regions in ABMT compared to neutral AMB placebo condition.

Measure: BOLD response in prefrontal cortical regions

Time: Two weeks after after ABM-training

Secondary Outcomes

Description: Lower ABM fMRI BOLD response within the amygdala in ABMT compared to neutral ABM placebo condition.

Measure: BOLD response within the amygdala

Time: Two weeks after ABM-training

Description: Increased neural integrity as measured by fractional anisotropy values in the uncinate fasciculi (UF) in the active AMBT compared to neutral ABM placebo condition.

Measure: DTI

Time: Two weeks after ABM-training

Description: Increased integrity within the attentional networks at rest as measured by independent component analysis (ICA) in ABMT compared to neutral ABM training.

Measure: RSFC

Time: Two weeks after ABM-training

Description: The low expressive variant will be associated with more frontal BOLD activation and lower amygdala activation after ABMT

Measure: 5-HTTLPR + A>G polymorphic variation divided by the triallelic functional "high expressive" versus "low expressive" genotype will moderate the impact from ABMT as measured by whole brain BOLD responses.

Time: Two weeks after ABM-training

Description: Brain Derived Neurotropic Factor (BDNF) val66met polymorphic variation linked to Brain Derived Neurotropic Factor (BDNF) variation will differentiate between ABMT and neutral AMB placebo as measured by fMRI whole brain BOLD responses.

Measure: BDNF

Time: Two week after ABM-training

Description: A serotonergic cumulative Genetic score, including (5-HHTLPR, HTR1A 8rs6295) and HTR 2A (rs 6311) polymorphisms will moderate the effects of ABM on fMRI BOLD signal compared to a neutral placebo condition.

Measure: Serotonergic cumulative genetic score and fMRI

Time: Two weeks after ABM-training

Description: A serotonergic cumulative Genetic score, including (5-HHTLPR, HTR1A 8rs6295) and HTR 2A (rs 6311) polymorphisms will moderate the effects of ABM on structural MRI as measured by total grey matter volume compared to a neutral placebo condition.

Measure: Serotonergic cumulative genetic score and morphompetry

Time: Two weeks after ABM-training

Description: A serotonergic cumulative Genetic score, including (5-HHTLPR, HTR1A 8rs6295) and HTR 2A (rs 6311) polymorphisms will moderate the effects of ABM on DTI MRI as measured by fractional anisotropy compared to a neutral placebo condition.

Measure: Serotonergic cumulative genetic score and fMRI and DTI

Time: Two weeks after ABM-training

25 The Effects and Mechanism of the Sequential Combination of Exercise and Cognitive Training on Cognitive Function in Stroke Patients With Cognitive Decline: A Randomized Controlled Trial

NCT03045991 Stroke Patients With Cognitive Decline Behavioral: aerobic exercise training Behavioral: control training Behavioral: cognitive training

MeSH:Stroke Cognitive Dysfunction

HPO:Cognitive impairment Mental deterioration Stroke

The Chinese version of short form GDS will be used.. Genotyping of the BDNF val66met polymorphism. --- val66met ---

Primary Outcomes

Description: The MoCA will be used to assess general cognitive functions. It examines several cognitive domains with a total score of 30

Measure: Change scores of Montreal Cognitive Assessment (MoCA)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The WMS-III is a standardized and reliable neuropsychological examination tool designed to evaluate visuospatial and memory functions

Measure: Change scores of Wechsler Memory Scale - Third Edition (WMS-III)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The WAIS-III is developed to measure an individual's intelligence level. It includes tests that evaluate cognitive functions in verbal comprehension, working memory, perceptual organization, and processing speed

Measure: Change scores of Wechsler Adult Intelligence Scale - Third Edition (WAIS-III)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The UFOV assessment is a computer-based visual test containing three subtests: visuomotor processing speed, divided attention, and selective attention.

Measure: Change scores of Useful Field of View (UFOV)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The Stroop Color-Word assesses the abilities of selective attention, inhibition and executive function. The participants will be tested under congruent and incongruent conditions.

Measure: Change scores of Stroop Color-Word test

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The dual-task test evaluates the ability to shift attention between one task and another. Participants will perform the box and block test (BBT) while doing secondary cognitive tasks while sitting. Participants will perform BBT by affected and less affected hand.

Measure: Change scores of Dual-task test

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Secondary Outcomes

Description: Up-regulation of neurotrophic and vascular growth factors

Measure: Change scores of serum BDNF level

Time: Baseline, posttest (an expected average of 3 months)

Description: Antioxidative markers will be used to reflect the changes on oxidative stress. In particular, we will be analyzing the total antioxidant capacity (TAC).

Measure: Change scores of Antioxidative marker

Time: Baseline, posttest (an expected average of 3 months)

Description: HbA1C level will be tested to investigate the relationships between blood glucose level and aerobic exercise

Measure: Change scores of Glucose indicator

Time: Baseline, posttest (an expected average of 3 months)

Description: The cholesterol ratio (total cholesterol divided by high-density lipid) will be evaluated to reflect the lipid level in the blood.

Measure: Change scores of Plasma lipid level

Time: Baseline, posttest (an expected average of 3 months)

Measure: Change scores of Functional Independence Measure (FIM)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The Lawton IADL scale assesses independent living skills, such as shopping or managing finances.

Measure: Change scores of Lawton Instrumental Activities of Daily Living Scale (Lawton IADL)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The SIS 3.0 will be used to evaluate health-related quality of life for patients with stroke. The SIS assesses eight domains (strength, hand function, ADL/IADL, mobility, communication, emotion, memory and thinking, and participation/role function) with 59 test items.

Measure: Change scores of Stroke Impact Scale (SIS)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: CB scale evaluates the burden of the primary caregiver of the participants. Lessening the burden of caregivers after the intervention may significantly improve the quality of life for patients with stroke and their family.

Measure: Change scores of Caregiver Burden (CB) scale

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of EuroQol (EQ)-5D questionnaire

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Timed up and go test (TUG)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Six-minute walk test (6MWT)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Measure: Change scores of Mobility level

Time: Baseline, posttest (an expected average of 3 months)

Description: The IPAQ is an international measure of health-related physical activity.

Measure: Change scores of International Physical Activity Questionnaires (IPAQ)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The UE-FMA subscale will be used to assess the sensorimotor impairment level of UE in patients after stroke. The UE-FMA contains 33 movements with a score range from 0 to 66. A higher UE-FMA score indicates less impairment of the paretic limb. The validity and reliability of FMA is good to excellent.

Measure: Change scores of Fugl-Meyer Assessment (FMA)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: The RMI evaluates the participant's bed mobility, postural transfers and walking ability. It contains a 15-item scale which includes 14 questions and one direct observation, with a total of score of 15.

Measure: Change scores of Rivermead Mobility Index (RMI)

Time: Baseline, posttest (an expected average of 3 months), follow-up (up to 9 months)

Description: Accelerometers will be used to provide an objective measure of the amount of arm movements in real-life situations. The participants will be asked to wear an Actigraphy activity monitor. We will evaluate isometric knee flexors and extensors muscle strength using handheld dynamometer. Also, we will use hand dynamometer to measure grip strength of the affected and less affected hand while the participant is seated, with the elbow at 90-degree flexion. We will record the mean value of 3 attempts.