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| Name | Class |
|---|---|
| Ministero della Salute, Italy | OTHER |
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Background: Subcortical Vascular Dementia (VaD), consequent to deep brain small vessel disease (SVD), is the most frequent form of VaD. The term vascular mild cognitive impairment (VMCI) defines a transitional state between normal ageing and VaD. Attentional deficits are a common finding in patients affected by VMCI or subcortical VaD. At present, no drug treatment is available to prevent vascular dementia in patients with VMCI or to improve cognitive performances of this large group of patients. Cognitive rehabilitation is directed to achieve functional changes by reinforcing, strengthening, or reestablishing previously learned patterns of behavior, or establishing new patterns of cognitive activity or compensatory mechanisms.
A hierarchical model of attention has been used to build the Attention Process Training-II (APT-II) programme.
The APT-II programme effectiveness have been demonstrated in traumatic brain injury and post-stroke rehabilitation, but there is an increasing interest in the study of cognitive rehabilitation in pathological processes that evolve over time, such as chronic cerebrovascular diseases (CVD).
Aims: The purpose of this study is to investigate whether the APT-II programme could be a useful tool in the rehabilitation of attention in individuals affected by VMCI with SVD, and if so, whether the improvement in performance is generalized to functionality in daily activities and quality of life.
Main Expected Results and Impact: Considering that the APT-II contains specific exercises to facilitate generalization to daily life, the skills that are learned by each patient during the rehabilitation programme should be generalized to daily activities.
Furthermore, the improvement of cognitive skills should also improve patient's overall quality of life because these learned skills are applicable to real-life situations. The main expected results are: 1) an impact of APT-II on disability, everyday cognition, quality of life, and performance on attention tests at short and long term after rehabilitation programme ending as compared with standard care; 2) a reduction of the risk of transition to dementia at 1 year follow-up as compared with control group.
Study design
The present study is a 3-year prospective, single-blinded, randomized clinical trial. The enrolment will be carried out at the Stroke Unit and the VASCOG clinic of the Careggi University Hospital. Forty patients will be enrolled according to the following criteria: 1) MCI defined according to Winblad et al. criteria (19); 2) Evidence of impairment across attention neuropsychological tests; 3) Evidence on MRI of subcortical vascular lesions:
moderate to severe age-related white matter changes (WMC) according to a modified version of the Fazekas scale (20). Exclusion criteria: age<18 years. All enrolled patients will be evaluated at baseline according to the study protocol, that includes: 1) Clinical assessment; 2) Functional, quality of life and mood assessment; 3) Extensive neuropsychological assessment; 4) MRI protocol. After baseline assessment, participants will be randomly assigned to attention training or standard care. Stratified minimization randomization will be used to ensure the balance for possible prognostic factors (i.e., age, gender, MMSE total score, extension and localization of WMC) across the groups. All APT-II sessions will be administered by a clinical neuropsychologist, or an appositely trained graduate student in medicine. The student clinicians will receive a minimum of 30 hours of training with adult rehabilitation patients, and will be closely supervised by the neuropsychologist. Participants in the APT-II group will receive overall up to 40 hours of individual attention process training. Therapy will be administered in one two-hour session each week over a total of 20 weeks. Participants in the standard care group will not receive cognitive training or rehabilitation interventions, will be instructed to have an usual lifestyle, and will be conventionally provided of medication and clinic consultations. Each patient will be followed-up at 6 and 12 months after baseline assessment. During the follow-up visits clinical assessment, an extensive neuropsychological evaluation, and mood, functional, and quality of life assessments will be performed according to the baseline protocol. The MRI protocol will be repeated at 1-year follow-up.
Work Methodology
Baseline and follow-up clinical, neuropsychological, functional, and MRI data will be collected in a dedicated database. Data will be checked and controlled for consistency in real time during collection. At the end of the enrolment, a first exploratory data analysis will be carried out. Postprocessing of neuroimaging acquired at baseline will be performed by an experienced radiologist. At the end of each follow-up (6 and 12 months after enrollment), analysis of data (uni- and multivariate models and effect size measures) will be carried out. All analyses will be performed using SPSS 18 and will be mainly directed to: 1) evaluate the short and long-term effectiveness of the rehabilitation program, using cognitive performance and functional and quality of life measures as dependents variables (within and between groups analyses); 2) identify potential predictors of effectiveness of the rehabilitation program (multivariate model). The variables included in the model will be: demographic and vascular risk factors, baseline cognitive profile and functional status, and preexisting brain structural changes; 3) evaluate the potential protective effect of the rehabilitation program on the increase of cognitive impairment or transition to dementia at 1 year follow-up; 4) evaluate the long-term effect of rehabilitation on brain activation, using f-MRI data, whole-brain histograms, and voxel-based analyses as dependents variables (within and between groups analyses).
Milestones
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| APT-II group | Experimental | Intervention: rehabilitation of attention using the Attention Process Training-II. Participants in the APT-II group will receive overall up to 40 hours of individual attention process training. Therapy will be administered in one two-hour session each week over a total of 20 weeks. |
|
| standard care group | No Intervention | Participants in the standard care group will not receive cognitive training or rehabilitation interventions, will be instructed to have an usual lifestyle, and will be conventionally provided of medication and clinic consultations |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Attention Process Training-II | Behavioral | Rehabilitation of attention using the Attention Process Training-II |
|
| Measure | Description | Time Frame |
|---|---|---|
| Functionality in Activities of Daily Living (Changes in Scores Approach) | Changes in scores (Δ) approach. Delta scores (Δs) were calculated by computing the difference between the scores obtained in 2 evaluations (baseline vs. 6 months; 6 vs. 12 months; baseline vs. 12 months) for each patient. All Δs were calculated in order that a positive score indicates an improvement, while a negative score indicates a worsening. Δs were analyzed using independent sample t tests with treatment as the only independent variable. Scales:
| Baseline, 6 months and 12 months |
| Quality of Life (Changes in Scores Approach) | Changes in scores (Δ) approach. Delta scores (Δs) were calculated by computing the difference between the scores obtained in 2 evaluations (baseline vs. 6 months; 6 vs. 12 months; baseline vs. 12 months) for each patient. All Δs were calculated in order that a positive score indicates an improvement, while a negative score indicates a worsening. Δs were analyzed using independent sample t tests with treatment as the only independent variable. Scales:
| Baseline, 6 months and 12 months |
| Quality of Life (Clinically Significance Approach) | Clinically significance approach. The availability of t scores for the Short Form Health Survey (SF-36) Physical and Mental Component Summary scores (MCS, PCS) allowed us to classify each patient evaluation as 'normal well-being' (t score >40) or 'reduced well-being' (t score ≤40) at each visit (higher scores mean a better outcome). Variations in performance categories over time (baseline vs. 6 month; 6 vs. 12 month; baseline vs. 12 month) were evaluated for each patient and dichotomized as: 'stable or better evaluation' or 'worst evaluation'. Variations in performance categories were analyzed using chi square tests. |
| Measure | Description | Time Frame |
|---|---|---|
| Cognitive Performance (Changes in Scores Approach) | Delta (Δ) scores were calculated by computing the difference between the scores obtained in 2 evaluations (baseline vs. 6 months; 6 vs. 12 months; baseline vs. 12 months) for each patient. A positive Δ score indicates an improvement, while a negative Δ score indicates a worsening. Delta scores were analyzed using independent sample t tests with treatment as the only independent variable. Test battery: Montreal Cognitive Assessment MoCA (minimum and maximum values 0-30); Mini Mental Status Examination MMSE (minimum and maximum values 0-30), Rey Auditory-Verbal Learning RAVL immediate (minimum and maximum values 0-75) and recall (minimum and maximum values 0-15), Short story (minimum and maximum values 0-28), Rey-Osterrieth Complex Figure ROCF copy and recall (minimum and maximum values 0-36), Visual search (minimum and maximum values 0-50), Symbol Digit Modalities Test SDMT (minimum and maximum values 0-110). Higher scores mean better outcome for all tests. |
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Inclusion Criteria:
Patients will be enrolled according to the following criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Leonardo Pantoni, MD, PhD | University of Milan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stroke Unit and Neurology, VAS-COG clinic | Florence | 50134 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27371187 | Background | Salvadori E, Poggesi A, Valenti R, Della Rocca E, Diciotti S, Mascalchi M, Inzitari D, Pantoni L. The rehabilitation of attention in patients with mild cognitive impairment and brain subcortical vascular changes using the Attention Process Training-II. The RehAtt Study: rationale, design and methodology. Neurol Sci. 2016 Oct;37(10):1653-62. doi: 10.1007/s10072-016-2649-z. Epub 2016 Jul 1. | |
| 28869475 |
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| ID | Title | Description |
|---|---|---|
| FG000 | APT-II Group | Intervention: rehabilitation of attention using the Attention Process Training-II. Participants in the APT-II group received overall up to 40 hours of individual training administered in one 2-hour session each week over a total of 20 weeks. |
| FG001 | Standard Care Group | Participants in the standard care group did not received cognitive training or rehabilitation interventions, were instructed to have an usual lifestyle, and conventionally provided of medication and clinic consultations |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | APT-II Group | Intervention: rehabilitation of attention using the Attention Process Training-II. Participants in the APT-II group received overall up to 40 hours of individual training administered in one 2-hour session each week over a total of 20 weeks. |
| BG001 | Standard Care Group |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Functionality in Activities of Daily Living (Changes in Scores Approach) | Changes in scores (Δ) approach. Delta scores (Δs) were calculated by computing the difference between the scores obtained in 2 evaluations (baseline vs. 6 months; 6 vs. 12 months; baseline vs. 12 months) for each patient. All Δs were calculated in order that a positive score indicates an improvement, while a negative score indicates a worsening. Δs were analyzed using independent sample t tests with treatment as the only independent variable. Scales:
| Posted | Mean | Standard Deviation | units on a scale | Baseline, 6 months and 12 months |
|
12 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | APT-II Group | Intervention: rehabilitation of attention using the Attention Process Training-II. Participants in the APT-II group will receive overall up to 40 hours of individual attention process training. Therapy will be administered in one two-hour session each week over a total of 20 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cerebral haemorrhage | Vascular disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Leonardo Pantoni, Principal Investigator | 'L. Sacco' Department of Biomedical and Clinical Sciences University of Milan | 0039-02-50319865 | leonardo.pantoni@unimi.it |
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D015140 | Dementia, Vascular |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D002561 | Cerebrovascular Disorders |
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| Baseline, 6 months and 12 months |
| Baseline, 6 months and 12 months |
| Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Delta (Δ) scores were calculated by computing the difference between the scores obtained in 2 evaluations (baseline vs. 6 months; 6 vs. 12 months; baseline vs. 12 months) for each patient. A positive Δ score indicates an improvement, while a negative Δ score indicates a worsening. Delta scores were analyzed using independent sample t tests with treatment as the only independent variable. Cognitive tests based on execution time in seconds: Trail Making Test TMT part A (minimum and maximum values 0-300), TMT part B (minimum and maximum values 0-300), and Stroop Test (minimum and maximum values 0-300). Higher scores mean worse outcome. | Baseline, 6 months and 12 months |
| Cognitive Performance Verbal Fluency (Changes in Scores Approach) | Delta (Δ) scores were calculated by computing the difference between the scores obtained in 2 evaluations (baseline vs. 6 months; 6 vs. 12 months; baseline vs. 12 months) for each patient. A positive Δ score indicates an improvement, while a negative Δ score indicates a worsening. Delta scores were analyzed using independent sample t tests with treatment as the only independent variable. Cognitive tests based on the total number of words produced: phonemic (minimum and maximum values not applicable) and semantic verbal fluency (minimum and maximum values not applicable). Higher scores mean better outcome for both tests. | Baseline, 6 months and 12 months |
| Cognitive Performance (Clinically Significance Approach) | Clinically significance approach. The availability of national norms for the cognitive variables allowed us to classify each patient's performance as 'normal', 'borderline' or 'abnormal' at each visit. Variations in performance categories over time (baseline vs. 6 month; 6 vs. 12 month; baseline vs. 12 month) were evaluated for each patient and dichotomized as: 'stable or better evaluation' or 'worst evaluation'. Variations in performance categories were analyzed using chi square tests. Test battery:
| Baseline, 6 months and 12 months |
| Transition to Dementia | Data collected during the 1-year follow-up visit were used to evaluate the occurrence of a transition from MCI to dementia according to DSM-V criteria. Chi square test for a 2x2 contingency table was used to compare patients who became demented at 1-year follow-up visit with those who did not, in the two treatment groups. | 12 months |
| Cognitive Plasticity | Improvement in long-term brain activity was measured by means of regional homogeneity (ReHo) of resting state functional MRI (rsfMRI) data. Statistical analysis of rsfMRI data was carried out by feeding Z-transformed ReHo data into voxel-wise inter-subject statistics using permutation-based nonparametric inference within the general linear model framework. P-values were calculated employing permutation-based statistics and corrected for multiple comparisons using the 3D parameter settings with threshold-free cluster enhancement, and a p-value <0.05 was considered statistically significant. Z-transformed ReHo differences (12 months-baseline) were computed separately for treated and non-treated patients, and a voxel-wise between-group comparison was used to evaluate the treatment effect . A positive mean of the Z-transformed ReHo differences represents an increase in activation over time (better outcome), and a negative mean represents a decrease in activation over time (worse outcome). | Baseline, 12 months |
| Result |
| Pantoni L, Poggesi A, Diciotti S, Valenti R, Orsolini S, Della Rocca E, Inzitari D, Mascalchi M, Salvadori E. Effect of Attention Training in Mild Cognitive Impairment Patients with Subcortical Vascular Changes: The RehAtt Study. J Alzheimers Dis. 2017;60(2):615-624. doi: 10.3233/JAD-170428. |
| 26960231 | Derived | Ciulli S, Citi L, Salvadori E, Valenti R, Poggesi A, Inzitari D, Mascalchi M, Toschi N, Pantoni L, Diciotti S. Prediction of Impaired Performance in Trail Making Test in MCI Patients With Small Vessel Disease Using DTI Data. IEEE J Biomed Health Inform. 2016 Jul;20(4):1026-33. doi: 10.1109/JBHI.2016.2537808. Epub 2016 Mar 3. |
| 26079418 | Derived | Salvadori E, Poggesi A, Valenti R, Pracucci G, Pescini F, Pasi M, Nannucci S, Marini S, Del Bene A, Ciolli L, Ginestroni A, Diciotti S, Orlandi G, Di Donato I, De Stefano N, Cosottini M, Chiti A, Federico A, Dotti MT, Bonuccelli U, Inzitari D, Pantoni L; VMCI-Tuscany Study Group. Operationalizing mild cognitive impairment criteria in small vessel disease: the VMCI-Tuscany Study. Alzheimers Dement. 2016 Apr;12(4):407-18. doi: 10.1016/j.jalz.2015.02.010. Epub 2015 Jun 13. |
Participants in the standard care group did not received cognitive training or rehabilitation interventions, were instructed to have an usual lifestyle, and conventionally provided of medication and clinic consultations |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Education | Mean | Standard Deviation | years |
|
| Hypertension | Count of Participants | Participants |
|
| Hypercholesterolemia | Count of Participants | Participants |
|
| Diabetes | Count of Participants | Participants |
|
| Smoking habits | Anamnestic data: current and former smokers were included among smokers. | Count of Participants | Participants |
|
| History of stroke | Count of Participants | Participants |
|
| Alcohol consumption | Current alcohol consumption considering the following three beverages: beer, wine, and liquor. | Count of Participants | Participants |
|
| Mini Mental State Examination | Total score ranging from 0 to 30: higher scores represent better performance. | Mean | Standard Deviation | units on a scale |
|
| Montreal Cognitive Assessment | Total score ranging from 0 to 30: higher scores represent better performance. | Mean | Standard Deviation | units on a scale |
|
| Activities of Daily Living (preserved items) | Preserved items were summed into a global score ranging from 0 (completely dependent) to 6 (completely autonomous). | Mean | Standard Deviation | units on a scale |
|
| Instrumental Activities of Daily Living (impaired items) | Impaired items were summed into a global score ranging from 0 (completely autonomous) to 8 (completely dependent). | Mean | Standard Deviation | units on a scale |
|
| Disability Assessment in Dementia | Forty dichotomous items summed into a total score and converted into a percentage ranging from 0 to 100 (higher scores represent less disability). | Mean | Standard Deviation | units on a scale |
|
| Attention Questionnaire | Total score ranging from 0 (absence of attention problems) to 36 (highest presence of attention problems) | Mean | Standard Deviation | units on a scale |
|
| EuroQol (summary index) | Single summary index ranging from 0 to 1 (higher scores represent better health status) | Mean | Standard Deviation | units on a scale |
|
| EuroQol (visual scale) | Visual analogue scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state) | Mean | Standard Deviation | units on a scale |
|
| Geriatric Depression Scale | Total score ranging from 0 (absence of depressive symptoms) to 15 (severe depressive symptoms) | Mean | Standard Deviation | units on a scale |
|
| OG000 |
| APT-II Group |
Intervention: rehabilitation of attention using the Attention Process Training-II. Participants in the APT-II group received overall up to 40 hours of individual training administered in one 2-hour session each week over a total of 20 weeks. |
| OG001 | Standard Care Group | Participants in the standard care group did not received cognitive training or rehabilitation interventions, were instructed to have an usual lifestyle, and conventionally provided of medication and clinic consultations |
|
|
|
| Primary | Quality of Life (Changes in Scores Approach) | Changes in scores (Δ) approach. Delta scores (Δs) were calculated by computing the difference between the scores obtained in 2 evaluations (baseline vs. 6 months; 6 vs. 12 months; baseline vs. 12 months) for each patient. All Δs were calculated in order that a positive score indicates an improvement, while a negative score indicates a worsening. Δs were analyzed using independent sample t tests with treatment as the only independent variable. Scales:
| Posted | Mean | Standard Deviation | units on a scale | Baseline, 6 months and 12 months |
|
|
|
|
| Primary | Quality of Life (Clinically Significance Approach) | Clinically significance approach. The availability of t scores for the Short Form Health Survey (SF-36) Physical and Mental Component Summary scores (MCS, PCS) allowed us to classify each patient evaluation as 'normal well-being' (t score >40) or 'reduced well-being' (t score ≤40) at each visit (higher scores mean a better outcome). Variations in performance categories over time (baseline vs. 6 month; 6 vs. 12 month; baseline vs. 12 month) were evaluated for each patient and dichotomized as: 'stable or better evaluation' or 'worst evaluation'. Variations in performance categories were analyzed using chi square tests. | Posted | Count of Participants | Participants | Baseline, 6 months and 12 months |
|
|
|
|
| Secondary | Cognitive Performance (Changes in Scores Approach) | Delta (Δ) scores were calculated by computing the difference between the scores obtained in 2 evaluations (baseline vs. 6 months; 6 vs. 12 months; baseline vs. 12 months) for each patient. A positive Δ score indicates an improvement, while a negative Δ score indicates a worsening. Delta scores were analyzed using independent sample t tests with treatment as the only independent variable. Test battery: Montreal Cognitive Assessment MoCA (minimum and maximum values 0-30); Mini Mental Status Examination MMSE (minimum and maximum values 0-30), Rey Auditory-Verbal Learning RAVL immediate (minimum and maximum values 0-75) and recall (minimum and maximum values 0-15), Short story (minimum and maximum values 0-28), Rey-Osterrieth Complex Figure ROCF copy and recall (minimum and maximum values 0-36), Visual search (minimum and maximum values 0-50), Symbol Digit Modalities Test SDMT (minimum and maximum values 0-110). Higher scores mean better outcome for all tests. | Not all the participants completed the entire neuropsychological evaluation during the follow-up visits due to refuse or failure to learn or remember the instructions, or to perform the task until the end | Posted | Mean | Standard Deviation | units on a scale | Baseline, 6 months and 12 months |
|
|
|
|
| Secondary | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Delta (Δ) scores were calculated by computing the difference between the scores obtained in 2 evaluations (baseline vs. 6 months; 6 vs. 12 months; baseline vs. 12 months) for each patient. A positive Δ score indicates an improvement, while a negative Δ score indicates a worsening. Delta scores were analyzed using independent sample t tests with treatment as the only independent variable. Cognitive tests based on execution time in seconds: Trail Making Test TMT part A (minimum and maximum values 0-300), TMT part B (minimum and maximum values 0-300), and Stroop Test (minimum and maximum values 0-300). Higher scores mean worse outcome. | Not all the participants completed the entire neuropsychological evaluation during the follow-up visits due to refuse or failure to learn or remember the instructions, or to perform the task until the end | Posted | Mean | Standard Deviation | seconds | Baseline, 6 months and 12 months |
|
|
|
|
| Secondary | Cognitive Performance Verbal Fluency (Changes in Scores Approach) | Delta (Δ) scores were calculated by computing the difference between the scores obtained in 2 evaluations (baseline vs. 6 months; 6 vs. 12 months; baseline vs. 12 months) for each patient. A positive Δ score indicates an improvement, while a negative Δ score indicates a worsening. Delta scores were analyzed using independent sample t tests with treatment as the only independent variable. Cognitive tests based on the total number of words produced: phonemic (minimum and maximum values not applicable) and semantic verbal fluency (minimum and maximum values not applicable). Higher scores mean better outcome for both tests. | Not all the participants completed the entire neuropsychological evaluation during the follow-up visits due to refuse or failure to learn or remember the instructions, or to perform the task until the end | Posted | Mean | Standard Deviation | words | Baseline, 6 months and 12 months |
|
|
|
|
| Secondary | Cognitive Performance (Clinically Significance Approach) | Clinically significance approach. The availability of national norms for the cognitive variables allowed us to classify each patient's performance as 'normal', 'borderline' or 'abnormal' at each visit. Variations in performance categories over time (baseline vs. 6 month; 6 vs. 12 month; baseline vs. 12 month) were evaluated for each patient and dichotomized as: 'stable or better evaluation' or 'worst evaluation'. Variations in performance categories were analyzed using chi square tests. Test battery:
| Not all the participants completed the entire neuropsychological evaluation during the follow-up visits due to refuse or failure to learn or remember the instructions, or to perform the task until the end | Posted | Count of Participants | Participants | Baseline, 6 months and 12 months |
|
|
|
|
| Secondary | Transition to Dementia | Data collected during the 1-year follow-up visit were used to evaluate the occurrence of a transition from MCI to dementia according to DSM-V criteria. Chi square test for a 2x2 contingency table was used to compare patients who became demented at 1-year follow-up visit with those who did not, in the two treatment groups. | Posted | Count of Participants | Participants | 12 months |
|
|
|
|
| Secondary | Cognitive Plasticity | Improvement in long-term brain activity was measured by means of regional homogeneity (ReHo) of resting state functional MRI (rsfMRI) data. Statistical analysis of rsfMRI data was carried out by feeding Z-transformed ReHo data into voxel-wise inter-subject statistics using permutation-based nonparametric inference within the general linear model framework. P-values were calculated employing permutation-based statistics and corrected for multiple comparisons using the 3D parameter settings with threshold-free cluster enhancement, and a p-value <0.05 was considered statistically significant. Z-transformed ReHo differences (12 months-baseline) were computed separately for treated and non-treated patients, and a voxel-wise between-group comparison was used to evaluate the treatment effect . A positive mean of the Z-transformed ReHo differences represents an increase in activation over time (better outcome), and a negative mean represents a decrease in activation over time (worse outcome). | RsfMRI data were available in in 22 patients (12 treated and 10 non-treated) after the exclusion of patients for technical reasons or head movement greater than 2 mm, and patients with incidental non-lacunar infarcts in the cerebral cortex, cerebellum, or brainstem to avoid a possible confounding effect on rsfMRI analysis. | Posted | Median | Inter-Quartile Range | standard Z-values | Baseline, 12 months |
|
|
|
|
| 1 |
| 23 |
| 1 |
| 23 |
| 0 |
| 23 |
| EG001 | Standard Care Group | Participants in the standard care group will not receive cognitive training or rehabilitation interventions, will be instructed to have an usual lifestyle, and will be conventionally provided of medication and clinic consultations | 0 | 23 | 1 | 23 | 0 | 23 |
| Gastrointestinal perforation | Gastrointestinal disorders | Non-systematic Assessment |
|
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| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D002537 | Intracranial Arteriosclerosis |
| D020765 | Intracranial Arterial Diseases |
| D003704 | Dementia |
| D056784 | Leukoencephalopathies |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| Δs on AQ (baseline vs 12 months) |
|
| Δs on EQ index (baseline vs 6 months) |
|
| Δs on EQ index (6 vs 12 months) |
|
| Δs on EQ index (baseline vs 12 months) |
|
| Δs on EQ visual (baseline vs 6 months) |
|
| Δs on EQ visual (6 vs 12 months) |
|
| Δs on EQ visual (baseline vs 12 months) |
|
| Δs on GDS (baseline vs 6 months) |
|
| Δs on GDS (6 vs 12 months) |
|
| Δs on GDS (baseline vs 12 months) |
|
| Δs on MCS (baseline vs 6 months) |
|
| Δs on MCS (6 vs 12 months) |
|
| Δs on MCS (baseline vs 12 months) |
|
| Δs on PCS (baseline vs 6 months) |
|
| Δs on PCS (6 vs 12 months) |
|
| Δs on PCS (baseline vs 12 months) |
|
| .810 |
| Superiority |
| Δs on AQ (baseline vs 12 months) | t-test, 2 sided | .193 | Superiority |
| Δs on EQ index (baseline vs 6 months) | t-test, 2 sided | .698 | Superiority |
| Δs on EQ index (6 vs 12 months) | t-test, 2 sided | .283 | Superiority |
| Δs on EQ index (baseline vs 12 months) | t-test, 2 sided | .647 | Superiority |
| Δs on EQ visual (baseline vs 6 months) | t-test, 2 sided | .057 | Superiority |
| Δs on EQ visual (6 vs 12 months) | t-test, 2 sided | .685 | Superiority |
| Δs on EQ visual (baseline vs 12 months) | t-test, 2 sided | .056 | Superiority |
| Δs on GDS (baseline vs 6 months) | t-test, 2 sided | .393 | Superiority |
| Δs on GDS (6 vs 12 months) | t-test, 2 sided | .958 | Superiority |
| Δs on GDS (baseline vs 12 months) | t-test, 2 sided | .448 | Superiority |
| Δs on MCS (baseline vs 6 months) | t-test, 2 sided | .567 | Superiority |
| Δs on MCS (6 vs 12 months) | t-test, 2 sided | .274 | Superiority |
| Δs on MCS (baseline vs 12 months) | t-test, 2 sided | .668 | Superiority |
| Δs on PCS (baseline vs 6 months) | t-test, 2 sided | .709 | Superiority |
| Δs on PCS (6 vs 12 months) | t-test, 2 sided | .567 | Superiority |
| Δs on PCS (baseline vs 12 months) | t-test, 2 sided | .867 | Superiority |
| MCS outcome (6 vs 12 months) |
|
| MCS outcome (baseline vs 12 months) |
|
| PCS outcome (baseline vs 6 months) |
|
| PCS outcome (6 vs 12 months) |
|
| PCS outcome (baseline vs 12 months) |
|
| .729 |
| Superiority |
| MCS outcome (baseline vs 12 months) | Chi-squared | .115 | Superiority |
| PCS outcome (baseline vs 6 months) | Chi-squared | .576 | Superiority |
| PCS outcome (6 vs 12 months) | Chi-squared | .191 | Superiority |
| PCS outcome (baseline vs 12 months) | Chi-squared | .790 | Superiority |
| Δs on MoCA (6 vs 12 months) |
|
|
| Δs on MoCA (baseline vs 12 months) |
|
|
| Δs on MMSE (baseline vs 6 months) |
|
|
| Δs on MMSE (6 vs 12 months) |
|
|
| Δs on MMSE (baseline vs 12 months) |
|
|
| Δs on RAVL immediate (baseline vs 6 months) |
|
|
| Δs on RAVL immediate (6 vs 12 months) |
|
|
| Δs on RAVL immediate (baseline vs 12 months) |
|
|
| Δs on RAVL recall (baseline vs 6 months) |
|
|
| Δs on RAVL recall (6 vs 12 months) |
|
|
| Δs on RAVL recall (baseline vs 12 months) |
|
|
| Δs on ROCF recall (baseline vs 6 months) |
|
|
| Δs on ROCF recall (6 vs 12 months) |
|
|
| Δs on ROCF recall (baseline vs 12 months) |
|
|
| Δs on short story (baseline vs 6 months) |
|
|
| Δs on short story (6 vs 12 months) |
|
|
| Δs on short story (baseline vs 12 months) |
|
|
| Δs on visual search (baseline vs 6 months) |
|
|
| Δs on visual search (6 vs 12 months) |
|
|
| Δs on visual search (baseline vs 12 months) |
|
|
| Δs on SDMT (baseline vs 6 months) |
|
|
| Δs on SDMT (6 vs 12 months) |
|
|
| Δs on SDMT (baseline vs 12 months) |
|
|
| Δs on ROCF copy (baseline vs 6 months) |
|
|
| Δs on ROCF copy (6 vs 12 months) |
|
|
| Δs on ROCF copy (baseline vs 12 months) |
|
|
| .188 |
| Superiority |
| Δs on MoCA (baseline vs 12 months) | t-test, 2 sided | .381 | Superiority |
| Δs on MMSE (baseline vs 6 months) | t-test, 2 sided | .458 | Superiority |
| Δs on MMSE (6 vs 12 months) | t-test, 2 sided | .236 | Superiority |
| Δs on MMSE (baseline vs 12 months) | t-test, 2 sided | .601 | Superiority |
| Δs on RAVL immediate (baseline vs 6 months) | t-test, 2 sided | .839 | Superiority |
| Δs on RAVL immediate (6 vs 12 months) | t-test, 2 sided | .021 | Superiority |
| Δs on RAVL immediate (baseline vs 12 months) | t-test, 2 sided | .032 | Superiority |
| Δs on RAVL recall (baseline vs 6 months) | t-test, 2 sided | .858 | Superiority |
| Δs on RAVL recall (6 vs 12 months) | t-test, 2 sided | .212 | Superiority |
| Δs on RAVL recall (baseline vs 12 months) | t-test, 2 sided | .268 | Superiority |
| Δs on ROCF recall (baseline vs 6 months) | t-test, 2 sided | .184 | Superiority |
| Δs on ROCF recall (6 vs 12 months) | t-test, 2 sided | .358 | Superiority |
| Δs on ROCF recall (baseline vs 12 months) | t-test, 2 sided | .768 | Superiority |
| Δs on short story (baseline vs 6 months) | t-test, 2 sided | .164 | Superiority |
| Δs on short story (6 vs 12 months) | t-test, 2 sided | .420 | Superiority |
| Δs on short story (baseline vs 12 months) | t-test, 2 sided | .527 | Superiority |
| Δs on visual search (baseline vs 6 months) | t-test, 2 sided | .762 | Superiority |
| Δs on visual search (6 vs 12 months) | t-test, 2 sided | .405 | Superiority |
| Δs on visual search (baseline vs 12 months) | t-test, 2 sided | .674 | Superiority |
| Δs on SDMT (baseline vs 6 months) | t-test, 2 sided | .328 | Superiority |
| Δs on SDMT (6 vs 12 months) | t-test, 2 sided | .198 | Superiority |
| Δs on SDMT (baseline vs 12 months) | t-test, 2 sided | .639 | Superiority |
| Δs on ROCF copy (baseline vs 6 months) | t-test, 2 sided | .098 | Superiority |
| Δs on ROCF copy (6 vs 12 months) | t-test, 2 sided | .235 | Superiority |
| Δs on ROCF copy (baseline vs 12 months) | t-test, 2 sided | .789 | Superiority |
| Δs on Stroop test (baseline vs 12 months) |
|
| Δs on TMT-A (baseline vs 6 months) |
|
| Δs on TMT-A (6 vs 12 months) |
|
| Δs on TMT-A (baseline vs 12 months) |
|
| Δs on TMT-B (baseline vs 6 months) |
|
| Δs on TMT-B (6 vs 12 months) |
|
| Δs on TMT-B (baseline vs 12 months) |
|
| .428 |
| Superiority |
| Δs on Stroop test (baseline vs 12 months) | t-test, 2 sided | .294 | Superiority |
| Δs on TMT-A (baseline vs 6 months) | t-test, 2 sided | .157 | Superiority |
| Δs on TMT-A (6 vs 12 months) | t-test, 2 sided | .094 | Superiority |
| Δs on TMT-A (baseline vs 12 months) | t-test, 2 sided | .476 | Superiority |
| Δs on TMT-B (baseline vs 6 months) | t-test, 2 sided | .142 | Superiority |
| Δs on TMT-B (6 vs 12 months) | t-test, 2 sided | .651 | Superiority |
| Δs on TMT-B (baseline vs 12 months) | t-test, 2 sided | .534 | Superiority |
| Δs on phonemic fluency (baseline vs 12 months) |
|
| Δs on semantic fluency (baseline vs 6 months) |
|
| Δs on semantic fluency (6 vs 12 months) |
|
| Δs on semantic fluency (baseline vs 12 months) |
|
| .835 |
| Superiority |
| Δs on phonemic fluency (baseline vs 12 months) | t-test, 2 sided | .951 | Superiority |
| Δs on semantic fluency (baseline vs 6 months) | t-test, 2 sided | .392 | Superiority |
| Δs on semantic fluency (6 vs 12 months) | t-test, 2 sided | .973 | Superiority |
| Δs on semantic fluency (baseline vs 12 months) | t-test, 2 sided | .486 | Superiority |
| Worst |
|
| MoCA variations (6 vs 12 months) |
|
|
| MoCA variations (baseline vs 12 months) |
|
|
| MMSE variations (baseline vs 6 months) |
|
|
| MMSE variations (6 vs 12 months) |
|
|
| MMSE variations (baseline vs 12 months) |
|
|
| RAVL immed. variations (baseline vs 6 months) |
|
|
| RAVL immed. variations (6 vs 12 months) |
|
|
| RAVL immed. variations (baseline vs 12 months) |
|
|
| RAVL recall variations (baseline vs 6 months) |
|
|
| RAVL recall variations (6 vs 12 months) |
|
|
| RAVL recall variations (baseline vs 12 months) |
|
|
| ROCF recall variations (baseline vs 6 months) |
|
|
| ROCF recall variations (6 vs 12 months) |
|
|
| ROCF recall variations (baseline vs 12 months) |
|
|
| Short story variations (baseline vs 6 months) |
|
|
| Short story variations (6 vs 12 months) |
|
|
| Short story variations (baseline vs 12 months) |
|
|
| Visual search variations (baseline vs 6 months) |
|
|
| Visual search variations (6 vs 12 months) |
|
|
| Visual search variations (baseline vs 12 months) |
|
|
| SDMT variations (baseline vs 6 months) |
|
|
| SDMT variations (6 vs 12 months) |
|
|
| SDMT variations (baseline vs 12 months) |
|
|
| Stroop test variations (baseline vs 6 months) |
|
|
| Stroop test variations (6 vs 12 months) |
|
|
| Stroop test variations (baseline vs 12 months) |
|
|
| TMT-A variations (baseline vs 6 months) |
|
|
| TMT-A variations (6 vs 12 months) |
|
|
| TMT-A variations (baseline vs 12 months) |
|
|
| TMT-B variations (baseline vs 6 months) |
|
|
| TMT-B variations (6 vs 12 months) |
|
|
| TMT-B variations (baseline vs 12 months) |
|
|
| Phonemic fluency variations (baseline vs 6 months) |
|
|
| Phonemic fluency variations (6 vs 12 months) |
|
|
| Phonemic fluency variation (baseline vs 12 months) |
|
|
| Semantic fluency variations (baseline vs 6 months) |
|
|
| Semantic fluency variations (6 vs 12 months) |
|
|
| Semantic fluency variation (baseline vs 12 months) |
|
|
| ROCF copy variations (baseline vs 6 months) |
|
|
| ROCF copy variations (6 vs 12 months) |
|
|
| ROCF copy variations (baseline vs 12 months) |
|
|
| .170 |
| Superiority |
| MoCA variations (baseline vs 12 months) | Chi-squared | .716 | Superiority |
| MMSE variations (baseline vs 6 months) | Chi-squared | .973 | Superiority |
| MMSE variations (6 vs 12 months) | Chi-squared | .973 | Superiority |
| MMSE variations (baseline vs 12 months) | Chi-squared | .300 | Superiority |
| RAVL immed. variations (baseline vs 6 months) | Chi-squared | .068 | Superiority |
| RAVL immed. variations (6 vs 12 months) | Chi-squared | .089 | Superiority |
| RAVL immed. variations (baseline vs 12 months) | Chi-squared | .241 | Superiority |
| RAVL recall variations (baseline vs 6 months) | Chi-squared | .089 | Superiority |
| RAVL recall variations (6 vs 12 months) | Chi-squared | .170 | Superiority |
| RAVL recall variations (baseline vs 12 months) | Chi-squared | .413 | Superiority |
| ROCF recall variations (baseline vs 6 months) | Chi-squared | .777 | Superiority |
| ROCF recall variations (6 vs 12 months) | Chi-squared | .134 | Superiority |
| ROCF recall variations (baseline vs 12 months) | Chi-squared | .498 | Superiority |
| Short story variations (baseline vs 6 months) | Chi-squared | .942 | Superiority |
| Short story variations (6 vs 12 months) | Chi-squared | .578 | Superiority |
| Short story variations (baseline vs 12 months) | Chi-squared | .413 | Superiority |
| Visual search variations (baseline vs 6 months) | Chi-squared | 1 | Superiority |
| Visual search variations (6 vs 12 months) | Chi-squared | .038 | Superiority |
| Visual search variations (baseline vs 12 months) | Chi-squared | .658 | Superiority |
| SDMT variations (baseline vs 6 months) | Chi-squared | .522 | Superiority |
| SDMT variations (6 vs 12 months) | Chi-squared | .674 | Superiority |
| SDMT variations (baseline vs 12 months) | Chi-squared | .170 | Superiority |
| Stroop test variations (baseline vs 6 months) | Chi-squared | .961 | Superiority |
| Stroop test variations (6 vs 12 months) | Chi-squared | .413 | Superiority |
| Stroop test variations (baseline vs 12 months) | Chi-squared | .477 | Superiority |
| TMT-A variations (baseline vs 6 months) | Chi-squared | .420 | Superiority |
| TMT-A variations (6 vs 12 months) | Chi-squared | .241 | Superiority |
| TMT-A variations (baseline vs 12 months) | Chi-squared | .295 | Superiority |
| TMT-B variations (baseline vs 6 months) | Chi-squared | .453 | Superiority |
| TMT-B variations (6 vs 12 months) | Chi-squared | .952 | Superiority |
| TMT-B variations (baseline vs 12 months) | Chi-squared | .881 | Superiority |
| Phonemic fluency variations (baseline vs 6 months) | Chi-squared | .413 | Superiority |
| Phonemic fluency variations (6 vs 12 months) | Chi-squared | .961 | Superiority |
| Phonemic fluency variation (baseline vs 12 months) | Chi-squared | .951 | Superiority |
| Semantic fluency variations (baseline vs 6 months) | Chi-squared | .951 | Superiority |
| Semantic fluency variations (6 vs 12 months) | Chi-squared | .674 | Superiority |
| Semantic fluency variation (baseline vs 12 months) | Chi-squared | .951 | Superiority |
| ROCF copy variations (baseline vs 6 months) | Chi-squared | 1 | Superiority |
| ROCF copy variations (6 vs 12 months) | Chi-squared | .027 | Superiority |
| ROCF copy variations (baseline vs 12 months) | Chi-squared | .169 | Superiority |
| reverted to normal cognitive function |
|
| Z-transformed ReHo difference in left VIIb lobule |
|
Z-transformed ReHo difference in right VIIb lobule
| General linear model voxel-wise |
| 0.04 |
Corrected for multiple comparisons using the "3D" parameter settings with threshold-free cluster enhancement. A priori threshold for statistical significance 0.05 |
| Superiority |
| Z-transformed ReHo difference in left VIIb lobule | General linear model voxel-wise | 0.039 | Corrected for multiple comparisons using the "3D" parameter settings with threshold-free cluster enhancement. A priori threshold for statistical significance 0.05 | Superiority |