Mild Cognitive Impairment
Conditions
Keywords
small vessel disease, cognition, treatment, rehabilitation, attention, fMRI, vascular dementia
Brief summary
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.
Detailed description
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 * Phase 1 (4 months): 1) Project protocol establishment; 2) Dedicated database for data collection construction; 3) MRI protocol determination; 4) Training on cognitive rehabilitation * Phase 2 (24 months): 1) Baseline patients cohort enrolment and clinical, neuropsychological, functional, and MRI data collection; 2) Neuropsychological rehabilitation program administration; 3) Follow-up assessments (6 and 12 months after enrolment) * Phase 3 (8 months): 1) Post-processing of neuroimaging acquired at baseline and at 1-year follow-up; 2) Data completeness and consistency control; 3) Data analysis; 4) Dissemination of results
Interventions
BEHAVIORALAttention Process Training-II
Rehabilitation of attention using the Attention Process Training-II
Sponsors
Ministero della Salute, Italy
Azienda Ospedaliero-Universitaria Careggi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients will be enrolled according to the following criteria: * MCI defined according to Winblad et al. criteria; * Evidence of impairment across attention neuropsychological tests; * 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.
Exclusion criteria
* Age \< 18 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functionality in Activities of Daily Living (Changes in Scores Approach) | Baseline, 6 months and 12 months | 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: * Activities of Daily Living (ADL): preserved items summed into a global score (minimum and maximum values 0-6: higher scores mean a better outcome). * Instrumental Activities of Daily Living (IADL): impaired items summed into a global score (minimum and maximum values 0-8: higher scores mean a worse outcome). * Disability Assessment in Dementia (DAD): 40 dichotomous items summed into a total score and converted into a percentage (minimum and maximum values 0-100: higher scores mean a worse outcome). |
| Quality of Life (Changes in Scores Approach) | Baseline, 6 months and 12 months | 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: * Short Form Health Survey summary scores: Physical and Mental Component Summary (PCS, MCS) (minimum and maximum values 0-100: lower scores mean worse outcome). * EuroQol (EQ): summary index (min-max values 0-1) and visual analogue scale (minimum and maximum values 0-100: higher scores mean better outcome). * Attention Questionnaire (AQ) total score (minimum and maximum values 0-36: higher scores mean worse outcome). * Geriatric Depression Scale (GDS) total score (minimum and maximum values 0-15: higher scores mean worse outcome). |
| Quality of Life (Clinically Significance Approach) | Baseline, 6 months and 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Performance (Clinically Significance Approach) | Baseline, 6 months and 12 months | 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: * global cognitive functioning: Montreal Cognitive Assessment, MoCA; Mini Mental Status Examination, MMSE * memory: Rey Auditory-Verbal Learning (RAVL) immediate and recall, Short story, Rey-Osterrieth Complex Figure (ROCF) recall * attention/executive function: Trail Making Test part A and B (TMT-A and B), Visual search, Symbol Digit Modalities Test (SDMT), Stroop Test * language: phonemic and semantic verbal fluency * constructional praxis: ROCF copy |
| Cognitive Performance (Changes in Scores Approach) | Baseline, 6 months and 12 months | 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. |
| Cognitive Plasticity | Baseline, 12 months | 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). |
| Transition to Dementia | 12 months | 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. |
| Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Baseline, 6 months and 12 months | 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. |
| Cognitive Performance Verbal Fluency (Changes in Scores Approach) | Baseline, 6 months and 12 months | 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. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 21 |
| 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 | 22 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | unrelated medical reason | 1 | 1 |
Baseline characteristics
| Characteristic | APT-II Group | Standard Care Group | Total |
|---|---|---|---|
| Activities of Daily Living (preserved items) | 5.9 units on a scale STANDARD_DEVIATION 0.3 | 5.9 units on a scale STANDARD_DEVIATION 0.4 | 5.9 units on a scale STANDARD_DEVIATION 0.4 |
| Age, Continuous | 74.2 years STANDARD_DEVIATION 6 | 75.9 years STANDARD_DEVIATION 7.6 | 75.1 years STANDARD_DEVIATION 6.8 |
| Alcohol consumption | 9 Participants | 10 Participants | 19 Participants |
| Attention Questionnaire | 15.1 units on a scale STANDARD_DEVIATION 11.5 | 15.9 units on a scale STANDARD_DEVIATION 8.5 | 15.5 units on a scale STANDARD_DEVIATION 9.9 |
| Diabetes | 3 Participants | 4 Participants | 7 Participants |
| Disability Assessment in Dementia | 91.9 units on a scale STANDARD_DEVIATION 11.9 | 84.2 units on a scale STANDARD_DEVIATION 17.8 | 88 units on a scale STANDARD_DEVIATION 15.5 |
| Education | 9 years STANDARD_DEVIATION 5.3 | 7.4 years STANDARD_DEVIATION 3 | 8.2 years STANDARD_DEVIATION 4.3 |
| EuroQol (summary index) | 0.7 units on a scale STANDARD_DEVIATION 0.3 | 0.7 units on a scale STANDARD_DEVIATION 0.3 | 0.7 units on a scale STANDARD_DEVIATION 0.3 |
| EuroQol (visual scale) | 63.1 units on a scale STANDARD_DEVIATION 18.3 | 67.3 units on a scale STANDARD_DEVIATION 17.5 | 65.2 units on a scale STANDARD_DEVIATION 17.8 |
| Geriatric Depression Scale | 4.6 units on a scale STANDARD_DEVIATION 4 | 4.9 units on a scale STANDARD_DEVIATION 3.8 | 4.8 units on a scale STANDARD_DEVIATION 3.8 |
| History of stroke | 7 Participants | 10 Participants | 17 Participants |
| Hypercholesterolemia | 16 Participants | 15 Participants | 31 Participants |
| Hypertension | 18 Participants | 20 Participants | 38 Participants |
| Instrumental Activities of Daily Living (impaired items) | 1.9 units on a scale STANDARD_DEVIATION 2.1 | 2.2 units on a scale STANDARD_DEVIATION 2.4 | 2.1 units on a scale STANDARD_DEVIATION 2.2 |
| Mini Mental State Examination | 27.1 units on a scale STANDARD_DEVIATION 2.6 | 25.7 units on a scale STANDARD_DEVIATION 3.2 | 26.4 units on a scale STANDARD_DEVIATION 3 |
| Montreal Cognitive Assessment | 19.9 units on a scale STANDARD_DEVIATION 4.8 | 18.6 units on a scale STANDARD_DEVIATION 4.4 | 19.2 units on a scale STANDARD_DEVIATION 4.6 |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Male | 13 Participants | 15 Participants | 28 Participants |
| Smoking habits | 11 Participants | 7 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 23 | 0 / 23 |
| other Total, other adverse events | 0 / 23 | 0 / 23 |
| serious Total, serious adverse events | 1 / 23 | 1 / 23 |
Outcome results
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: * Activities of Daily Living (ADL): preserved items summed into a global score (minimum and maximum values 0-6: higher scores mean a better outcome). * Instrumental Activities of Daily Living (IADL): impaired items summed into a global score (minimum and maximum values 0-8: higher scores mean a worse outcome). * Disability Assessment in Dementia (DAD): 40 dichotomous items summed into a total score and converted into a percentage (minimum and maximum values 0-100: higher scores mean a worse outcome).
Time frame: Baseline, 6 months and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APT-II Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on DAD (baseline vs 6 months) | -2.2 units on a scale | Standard Deviation 10.3 |
| APT-II Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on ADL (baseline vs 6 months) | 0.1 units on a scale | Standard Deviation 0.3 |
| APT-II Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on ADL (6 vs 12 months) | -0.1 units on a scale | Standard Deviation 0.4 |
| APT-II Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on ADL (baseline vs 12 months) | 0 units on a scale | Standard Deviation 0.9 |
| APT-II Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on IADL (baseline vs 6 months) | -0.4 units on a scale | Standard Deviation 1.1 |
| APT-II Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on IADL (6 vs 12 months) | -0.3 units on a scale | Standard Deviation 1.3 |
| APT-II Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on IADL (baseline vs 12 months) | -0.7 units on a scale | Standard Deviation 1.1 |
| APT-II Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on DAD (6 vs 12 months) | -6.2 units on a scale | Standard Deviation 20.2 |
| APT-II Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on DAD (baseline vs 12 months) | -8.4 units on a scale | Standard Deviation 21.1 |
| Standard Care Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on IADL (baseline vs 6 months) | 0 units on a scale | Standard Deviation 0.9 |
| Standard Care Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on DAD (baseline vs 12 months) | -6.9 units on a scale | Standard Deviation 17.2 |
| Standard Care Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on DAD (baseline vs 6 months) | -3.9 units on a scale | Standard Deviation 11.3 |
| Standard Care Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on ADL (baseline vs 6 months) | 0 units on a scale | Standard Deviation 0 |
| Standard Care Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on IADL (6 vs 12 months) | -1 units on a scale | Standard Deviation 1.7 |
| Standard Care Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on ADL (6 vs 12 months) | -0.2 units on a scale | Standard Deviation 0.7 |
| Standard Care Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on DAD (6 vs 12 months) | -3 units on a scale | Standard Deviation 11.1 |
| Standard Care Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on ADL (baseline vs 12 months) | -0.2 units on a scale | Standard Deviation 0.7 |
| Standard Care Group | Functionality in Activities of Daily Living (Changes in Scores Approach) | Δs on IADL (baseline vs 12 months) | -1 units on a scale | Standard Deviation 1.7 |
Comparison: Δs on ADL (baseline vs 6 months)p-value: 0.145t-test, 2 sided
Comparison: Δs on ADL (6 vs 12 months)p-value: 0.618t-test, 2 sided
Comparison: Δs on ADL (baseline vs 12 months)p-value: 0.262t-test, 2 sided
Comparison: Δs on IADL (baseline vs 6 months)p-value: 0.24t-test, 2 sided
Comparison: Δs on IADL (6 vs 12 months)p-value: 0.134t-test, 2 sided
Comparison: Δs on IADL (baseline vs 12 months)p-value: 0.457t-test, 2 sided
Comparison: Δs on DAD (baseline vs 6 months)p-value: 0.612t-test, 2 sided
Comparison: Δs on DAD (6 vs 12 months)p-value: 0.522t-test, 2 sided
Comparison: Δs on DAD (baseline vs 12 months)p-value: 0.8t-test, 2 sided
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: * Short Form Health Survey summary scores: Physical and Mental Component Summary (PCS, MCS) (minimum and maximum values 0-100: lower scores mean worse outcome). * EuroQol (EQ): summary index (min-max values 0-1) and visual analogue scale (minimum and maximum values 0-100: higher scores mean better outcome). * Attention Questionnaire (AQ) total score (minimum and maximum values 0-36: higher scores mean worse outcome). * Geriatric Depression Scale (GDS) total score (minimum and maximum values 0-15: higher scores mean worse outcome).
Time frame: Baseline, 6 months and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on GDS (baseline vs 6 months) | -0.1 units on a scale | Standard Deviation 2.1 |
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on EQ index (6 vs 12 months) | -0.1 units on a scale | Standard Deviation 0.2 |
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on GDS (6 vs 12 months) | 0 units on a scale | Standard Deviation 2.7 |
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on AQ (baseline vs 12 months) | -5.1 units on a scale | Standard Deviation 8.4 |
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on GDS (baseline vs 12 months) | -0.1 units on a scale | Standard Deviation 2.9 |
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on EQ index (baseline vs 12 months) | 0 units on a scale | Standard Deviation 0.3 |
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on MCS (baseline vs 6 months) | 1.4 units on a scale | Standard Deviation 5.3 |
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on AQ (6 vs 12 months) | -3.8 units on a scale | Standard Deviation 7.9 |
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on MCS (6 vs 12 months) | -0.1 units on a scale | Standard Deviation 6.2 |
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on EQ visual (baseline vs 6 months) | 5.2 units on a scale | Standard Deviation 15.3 |
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on MCS (baseline vs 12 months) | 1.3 units on a scale | Standard Deviation 7 |
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on EQ index (baseline vs 6 months) | 0.1 units on a scale | Standard Deviation 0.2 |
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on PCS (baseline vs 6 months) | -1.1 units on a scale | Standard Deviation 6.5 |
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on EQ visual (6 vs 12 months) | -0.2 units on a scale | Standard Deviation 12.9 |
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on PCS (6 vs 12 months) | -0.9 units on a scale | Standard Deviation 6.6 |
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on AQ (baseline vs 6 months) | -1.3 units on a scale | Standard Deviation 7.8 |
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on PCS (baseline vs 12 months) | -2 units on a scale | Standard Deviation 8.1 |
| APT-II Group | Quality of Life (Changes in Scores Approach) | Δs on EQ visual (baseline vs 12 months) | 5 units on a scale | Standard Deviation 14.2 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on PCS (baseline vs 12 months) | -1.5 units on a scale | Standard Deviation 10.2 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on AQ (baseline vs 6 months) | 2.1 units on a scale | Standard Deviation 9.3 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on AQ (6 vs 12 months) | -3.3 units on a scale | Standard Deviation 5 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on AQ (baseline vs 12 months) | -1.2 units on a scale | Standard Deviation 10.6 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on EQ index (baseline vs 6 months) | 0.1 units on a scale | Standard Deviation 0.2 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on EQ index (6 vs 12 months) | 0 units on a scale | Standard Deviation 0.2 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on EQ index (baseline vs 12 months) | 0.1 units on a scale | Standard Deviation 0.3 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on EQ visual (baseline vs 6 months) | -2.3 units on a scale | Standard Deviation 9.2 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on EQ visual (6 vs 12 months) | -2 units on a scale | Standard Deviation 15.8 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on GDS (baseline vs 6 months) | -0.8 units on a scale | Standard Deviation 2.9 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on GDS (6 vs 12 months) | 0 units on a scale | Standard Deviation 2.9 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on GDS (baseline vs 12 months) | -0.7 units on a scale | Standard Deviation 2.5 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on MCS (baseline vs 6 months) | 3 units on a scale | Standard Deviation 11.4 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on MCS (6 vs 12 months) | -2.8 units on a scale | Standard Deviation 9.3 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on MCS (baseline vs 12 months) | 0.2 units on a scale | Standard Deviation 9.6 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on PCS (baseline vs 6 months) | -1.9 units on a scale | Standard Deviation 8.2 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on PCS (6 vs 12 months) | 0.5 units on a scale | Standard Deviation 8.3 |
| Standard Care Group | Quality of Life (Changes in Scores Approach) | Δs on EQ visual (baseline vs 12 months) | -4.3 units on a scale | Standard Deviation 16.6 |
Comparison: Δs on AQ (baseline vs 6 months)p-value: 0.204t-test, 2 sided
Comparison: Δs on AQ (6 vs 12 months)p-value: 0.81t-test, 2 sided
Comparison: Δs on AQ (baseline vs 12 months)p-value: 0.193t-test, 2 sided
Comparison: Δs on EQ index (baseline vs 6 months)p-value: 0.698t-test, 2 sided
Comparison: Δs on EQ index (6 vs 12 months)p-value: 0.283t-test, 2 sided
Comparison: Δs on EQ index (baseline vs 12 months)p-value: 0.647t-test, 2 sided
Comparison: Δs on EQ visual (baseline vs 6 months)p-value: 0.057t-test, 2 sided
Comparison: Δs on EQ visual (6 vs 12 months)p-value: 0.685t-test, 2 sided
Comparison: Δs on EQ visual (baseline vs 12 months)p-value: 0.056t-test, 2 sided
Comparison: Δs on GDS (baseline vs 6 months)p-value: 0.393t-test, 2 sided
Comparison: Δs on GDS (6 vs 12 months)p-value: 0.958t-test, 2 sided
Comparison: Δs on GDS (baseline vs 12 months)p-value: 0.448t-test, 2 sided
Comparison: Δs on MCS (baseline vs 6 months)p-value: 0.567t-test, 2 sided
Comparison: Δs on MCS (6 vs 12 months)p-value: 0.274t-test, 2 sided
Comparison: Δs on MCS (baseline vs 12 months)p-value: 0.668t-test, 2 sided
Comparison: Δs on PCS (baseline vs 6 months)p-value: 0.709t-test, 2 sided
Comparison: Δs on PCS (6 vs 12 months)p-value: 0.567t-test, 2 sided
Comparison: Δs on PCS (baseline vs 12 months)p-value: 0.867t-test, 2 sided
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.
Time frame: Baseline, 6 months and 12 months
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| APT-II Group | Quality of Life (Clinically Significance Approach) | PCS outcome (baseline vs 12 months) | Worse | 7 Participants |
| APT-II Group | Quality of Life (Clinically Significance Approach) | MCS outcome (baseline vs 6 months) | Stable/better | 19 Participants |
| APT-II Group | Quality of Life (Clinically Significance Approach) | MCS outcome (baseline vs 6 months) | Worse | 2 Participants |
| APT-II Group | Quality of Life (Clinically Significance Approach) | MCS outcome (6 vs 12 months) | Stable/better | 18 Participants |
| APT-II Group | Quality of Life (Clinically Significance Approach) | MCS outcome (6 vs 12 months) | Worse | 3 Participants |
| APT-II Group | Quality of Life (Clinically Significance Approach) | MCS outcome (baseline vs 12 months) | Stable/better | 18 Participants |
| APT-II Group | Quality of Life (Clinically Significance Approach) | MCS outcome (baseline vs 12 months) | Worse | 3 Participants |
| APT-II Group | Quality of Life (Clinically Significance Approach) | PCS outcome (baseline vs 6 months) | Stable/better | 16 Participants |
| APT-II Group | Quality of Life (Clinically Significance Approach) | PCS outcome (baseline vs 6 months) | Worse | 5 Participants |
| APT-II Group | Quality of Life (Clinically Significance Approach) | PCS outcome (6 vs 12 months) | Stable/better | 16 Participants |
| APT-II Group | Quality of Life (Clinically Significance Approach) | PCS outcome (6 vs 12 months) | Worse | 5 Participants |
| APT-II Group | Quality of Life (Clinically Significance Approach) | PCS outcome (baseline vs 12 months) | Stable/better | 14 Participants |
| Standard Care Group | Quality of Life (Clinically Significance Approach) | PCS outcome (6 vs 12 months) | Worse | 2 Participants |
| Standard Care Group | Quality of Life (Clinically Significance Approach) | MCS outcome (baseline vs 12 months) | Worse | 5 Participants |
| Standard Care Group | Quality of Life (Clinically Significance Approach) | MCS outcome (baseline vs 6 months) | Stable/better | 19 Participants |
| Standard Care Group | Quality of Life (Clinically Significance Approach) | PCS outcome (6 vs 12 months) | Stable/better | 20 Participants |
| Standard Care Group | Quality of Life (Clinically Significance Approach) | MCS outcome (baseline vs 6 months) | Worse | 3 Participants |
| Standard Care Group | Quality of Life (Clinically Significance Approach) | PCS outcome (baseline vs 6 months) | Stable/better | 17 Participants |
| Standard Care Group | Quality of Life (Clinically Significance Approach) | MCS outcome (6 vs 12 months) | Stable/better | 18 Participants |
| Standard Care Group | Quality of Life (Clinically Significance Approach) | PCS outcome (baseline vs 12 months) | Worse | 5 Participants |
| Standard Care Group | Quality of Life (Clinically Significance Approach) | PCS outcome (baseline vs 12 months) | Stable/better | 17 Participants |
| Standard Care Group | Quality of Life (Clinically Significance Approach) | MCS outcome (6 vs 12 months) | Worse | 4 Participants |
| Standard Care Group | Quality of Life (Clinically Significance Approach) | PCS outcome (baseline vs 6 months) | Worse | 5 Participants |
| Standard Care Group | Quality of Life (Clinically Significance Approach) | MCS outcome (baseline vs 12 months) | Stable/better | 17 Participants |
Comparison: MCS outcome (baseline vs 6 months)p-value: 0.095Chi-squared
Comparison: MCS outcome (6 vs 12 months)p-value: 0.729Chi-squared
Comparison: MCS outcome (baseline vs 12 months)p-value: 0.115Chi-squared
Comparison: PCS outcome (baseline vs 6 months)p-value: 0.576Chi-squared
Comparison: PCS outcome (6 vs 12 months)p-value: 0.191Chi-squared
Comparison: PCS outcome (baseline vs 12 months)p-value: 0.79Chi-squared
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.
Time frame: Baseline, 6 months and 12 months
Population: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on visual search (baseline vs 6 months) | -3.4 units on a scale | Standard Deviation 7.1 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on ROCF copy (6 vs 12 months) | -0.3 units on a scale | Standard Deviation 6.1 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on ROCF copy (baseline vs 12 months) | -1.6 units on a scale | Standard Deviation 8.8 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on MoCA (baseline vs 6 months) | 1.1 units on a scale | Standard Deviation 4.1 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on MoCA (6 vs 12 months) | 0.8 units on a scale | Standard Deviation 3 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on MoCA (baseline vs 12 months) | 2 units on a scale | Standard Deviation 3.9 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on MMSE (baseline vs 6 months) | -0.3 units on a scale | Standard Deviation 1.9 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on MMSE (6 vs 12 months) | -0.4 units on a scale | Standard Deviation 2.6 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on MMSE (baseline vs 12 months) | -0.7 units on a scale | Standard Deviation 2.8 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on RAVL immediate (baseline vs 6 months) | 2 units on a scale | Standard Deviation 7.6 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on RAVL immediate (6 vs 12 months) | 1.8 units on a scale | Standard Deviation 4.9 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on RAVL immediate (baseline vs 12 months) | 3.8 units on a scale | Standard Deviation 6.1 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on RAVL recall (baseline vs 6 months) | 0.3 units on a scale | Standard Deviation 2.2 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on RAVL recall (6 vs 12 months) | 0.5 units on a scale | Standard Deviation 2.5 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on RAVL recall (baseline vs 12 months) | 0.9 units on a scale | Standard Deviation 2.3 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on ROCF recall (baseline vs 6 months) | -0.4 units on a scale | Standard Deviation 7.4 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on ROCF recall (6 vs 12 months) | 0.6 units on a scale | Standard Deviation 6.5 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on ROCF recall (baseline vs 12 months) | 0.7 units on a scale | Standard Deviation 9.7 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on short story (baseline vs 6 months) | -1.3 units on a scale | Standard Deviation 3.1 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on short story (6 vs 12 months) | 0.7 units on a scale | Standard Deviation 2.2 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on short story (baseline vs 12 months) | -0.7 units on a scale | Standard Deviation 2.7 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on visual search (6 vs 12 months) | 0.3 units on a scale | Standard Deviation 6.9 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on visual search (baseline vs 12 months) | -3 units on a scale | Standard Deviation 8.2 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on SDMT (baseline vs 6 months) | 1.1 units on a scale | Standard Deviation 5.4 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on SDMT (6 vs 12 months) | -2 units on a scale | Standard Deviation 6.1 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on SDMT (baseline vs 12 months) | -0.9 units on a scale | Standard Deviation 4.6 |
| APT-II Group | Cognitive Performance (Changes in Scores Approach) | Δs on ROCF copy (baseline vs 6 months) | -1.5 units on a scale | Standard Deviation 7.9 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on SDMT (6 vs 12 months) | 0.3 units on a scale | Standard Deviation 5.8 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on RAVL recall (baseline vs 12 months) | 0.1 units on a scale | Standard Deviation 2 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on ROCF copy (6 vs 12 months) | -2.8 units on a scale | Standard Deviation 7.3 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on visual search (baseline vs 6 months) | -2.6 units on a scale | Standard Deviation 9.1 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on ROCF copy (baseline vs 12 months) | -0.9 units on a scale | Standard Deviation 7.8 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on ROCF recall (baseline vs 6 months) | 2.3 units on a scale | Standard Deviation 6.7 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on MoCA (baseline vs 6 months) | 1.1 units on a scale | Standard Deviation 3.4 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on SDMT (baseline vs 6 months) | -0.3 units on a scale | Standard Deviation 4.1 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on MoCA (6 vs 12 months) | -0.3 units on a scale | Standard Deviation 2.7 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on ROCF recall (6 vs 12 months) | -1 units on a scale | Standard Deviation 3.7 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on MoCA (baseline vs 12 months) | 0.8 units on a scale | Standard Deviation 4.5 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on visual search (6 vs 12 months) | -1.5 units on a scale | Standard Deviation 7.3 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on MMSE (baseline vs 6 months) | -0.8 units on a scale | Standard Deviation 1.9 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on ROCF recall (baseline vs 12 months) | 1.5 units on a scale | Standard Deviation 5.8 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on MMSE (6 vs 12 months) | 0.4 units on a scale | Standard Deviation 1.9 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on SDMT (baseline vs 12 months) | -0.1 units on a scale | Standard Deviation 7.8 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on MMSE (baseline vs 12 months) | -0.3 units on a scale | Standard Deviation 1.8 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on short story (baseline vs 6 months) | -0.1 units on a scale | Standard Deviation 2.5 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on RAVL immediate (baseline vs 6 months) | 1.6 units on a scale | Standard Deviation 4.9 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on visual search (baseline vs 12 months) | -4.2 units on a scale | Standard Deviation 9.7 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on RAVL immediate (6 vs 12 months) | -1.4 units on a scale | Standard Deviation 3.8 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on short story (6 vs 12 months) | 0 units on a scale | Standard Deviation 2.9 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on RAVL immediate (baseline vs 12 months) | 0.2 units on a scale | Standard Deviation 4.4 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on ROCF copy (baseline vs 6 months) | 2.3 units on a scale | Standard Deviation 6.7 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on RAVL recall (baseline vs 6 months) | 0.4 units on a scale | Standard Deviation 2.5 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on short story (baseline vs 12 months) | -0.1 units on a scale | Standard Deviation 3.2 |
| Standard Care Group | Cognitive Performance (Changes in Scores Approach) | Δs on RAVL recall (6 vs 12 months) | -0.3 units on a scale | Standard Deviation 2 |
Comparison: Δs on visual search (baseline vs 12 months)p-value: 0.674t-test, 2 sided
Comparison: Δs on MoCA (baseline vs 6 months)p-value: 0.936t-test, 2 sided
Comparison: Δs on MoCA (6 vs 12 months)p-value: 0.188t-test, 2 sided
Comparison: Δs on MoCA (baseline vs 12 months)p-value: 0.381t-test, 2 sided
Comparison: Δs on MMSE (baseline vs 6 months)p-value: 0.458t-test, 2 sided
Comparison: Δs on MMSE (6 vs 12 months)p-value: 0.236t-test, 2 sided
Comparison: Δs on MMSE (baseline vs 12 months)p-value: 0.601t-test, 2 sided
Comparison: Δs on RAVL immediate (baseline vs 6 months)p-value: 0.839t-test, 2 sided
Comparison: Δs on RAVL immediate (6 vs 12 months)p-value: 0.021t-test, 2 sided
Comparison: Δs on RAVL immediate (baseline vs 12 months)p-value: 0.032t-test, 2 sided
Comparison: Δs on RAVL recall (baseline vs 6 months)p-value: 0.858t-test, 2 sided
Comparison: Δs on RAVL recall (6 vs 12 months)p-value: 0.212t-test, 2 sided
Comparison: Δs on RAVL recall (baseline vs 12 months)p-value: 0.268t-test, 2 sided
Comparison: Δs on ROCF recall (baseline vs 6 months)p-value: 0.184t-test, 2 sided
Comparison: Δs on ROCF recall (6 vs 12 months)p-value: 0.358t-test, 2 sided
Comparison: Δs on ROCF recall (baseline vs 12 months)p-value: 0.768t-test, 2 sided
Comparison: Δs on short story (baseline vs 6 months)p-value: 0.164t-test, 2 sided
Comparison: Δs on short story (6 vs 12 months)p-value: 0.42t-test, 2 sided
Comparison: Δs on short story (baseline vs 12 months)p-value: 0.527t-test, 2 sided
Comparison: Δs on visual search (baseline vs 6 months)p-value: 0.762t-test, 2 sided
Comparison: Δs on visual search (6 vs 12 months)p-value: 0.405t-test, 2 sided
Comparison: Δs on SDMT (baseline vs 6 months)p-value: 0.328t-test, 2 sided
Comparison: Δs on SDMT (6 vs 12 months)p-value: 0.198t-test, 2 sided
Comparison: Δs on SDMT (baseline vs 12 months)p-value: 0.639t-test, 2 sided
Comparison: Δs on ROCF copy (baseline vs 6 months)p-value: 0.098t-test, 2 sided
Comparison: Δs on ROCF copy (6 vs 12 months)p-value: 0.235t-test, 2 sided
Comparison: Δs on ROCF copy (baseline vs 12 months)p-value: 0.789t-test, 2 sided
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: * global cognitive functioning: Montreal Cognitive Assessment, MoCA; Mini Mental Status Examination, MMSE * memory: Rey Auditory-Verbal Learning (RAVL) immediate and recall, Short story, Rey-Osterrieth Complex Figure (ROCF) recall * attention/executive function: Trail Making Test part A and B (TMT-A and B), Visual search, Symbol Digit Modalities Test (SDMT), Stroop Test * language: phonemic and semantic verbal fluency * constructional praxis: ROCF copy
Time frame: Baseline, 6 months and 12 months
Population: 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
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | RAVL immed. variations (baseline vs 6 months) | Stable/better | 16 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | ROCF recall variations (6 vs 12 months) | Worst | 1 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | RAVL immed. variations (baseline vs 6 months) | Worst | 5 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Short story variations (baseline vs 12 months) | Stable/better | 19 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | RAVL immed. variations (6 vs 12 months) | Stable/better | 20 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Stroop test variations (baseline vs 6 months) | Stable/better | 19 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | RAVL immed. variations (6 vs 12 months) | Worst | 1 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | RAVL immed. variations (baseline vs 12 months) | Worst | 2 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Stroop test variations (baseline vs 6 months) | Worst | 2 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Short story variations (baseline vs 12 months) | Worst | 2 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | RAVL recall variations (baseline vs 6 months) | Stable/better | 20 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Stroop test variations (6 vs 12 months) | Stable/better | 19 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | RAVL recall variations (baseline vs 6 months) | Worst | 1 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | ROCF recall variations (baseline vs 12 months) | Stable/better | 15 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | RAVL recall variations (6 vs 12 months) | Stable/better | 20 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Visual search variations (baseline vs 6 months) | Stable/better | 15 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | RAVL recall variations (6 vs 12 months) | Worst | 1 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Stroop test variations (baseline vs 12 months) | Stable/better | 18 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | RAVL recall variations (baseline vs 12 months) | Stable/better | 19 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Stroop test variations (baseline vs 12 months) | Worst | 3 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | RAVL recall variations (baseline vs 12 months) | Worst | 2 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | TMT-A variations (6 vs 12 months) | Worst | 2 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | ROCF recall variations (baseline vs 12 months) | Worst | 2 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | ROCF recall variations (baseline vs 6 months) | Worst | 5 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | TMT-A variations (baseline vs 6 months) | Stable/better | 15 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | TMT-A variations (baseline vs 12 months) | Stable/better | 18 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | SDMT variations (baseline vs 6 months) | Stable/better | 19 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Visual search variations (baseline vs 6 months) | Worst | 6 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | TMT-A variations (baseline vs 12 months) | Worst | 3 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | TMT-A variations (baseline vs 6 months) | Worst | 6 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | TMT-B variations (baseline vs 6 months) | Stable/better | 16 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Short story variations (baseline vs 6 months) | Stable/better | 17 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | TMT-B variations (baseline vs 6 months) | Worst | 2 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | TMT-A variations (6 vs 12 months) | Stable/better | 19 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | TMT-B variations (6 vs 12 months) | Stable/better | 16 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Visual search variations (6 vs 12 months) | Stable/better | 20 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | TMT-B variations (6 vs 12 months) | Worst | 2 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Visual search variations (6 vs 12 months) | Worst | 1 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | TMT-B variations (baseline vs 12 months) | Stable/better | 16 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | MoCA variations (baseline vs 6 months) | Stable/better | 18 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | TMT-B variations (baseline vs 12 months) | Worst | 3 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | RAVL immed. variations (baseline vs 12 months) | Stable/better | 19 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Phonemic fluency variations (baseline vs 6 months) | Stable/better | 19 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | MoCA variations (baseline vs 6 months) | Worst | 2 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Phonemic fluency variations (baseline vs 6 months) | Worst | 2 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Visual search variations (baseline vs 12 months) | Stable/better | 15 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Phonemic fluency variations (6 vs 12 months) | Stable/better | 19 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | MoCA variations (6 vs 12 months) | Stable/better | 20 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Short story variations (baseline vs 6 months) | Worst | 4 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Phonemic fluency variations (6 vs 12 months) | Worst | 2 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | MoCA variations (6 vs 12 months) | Worst | 1 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Phonemic fluency variation (baseline vs 12 months) | Stable/better | 18 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | SDMT variations (6 vs 12 months) | Stable/better | 19 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Visual search variations (baseline vs 12 months) | Worst | 6 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Phonemic fluency variation (baseline vs 12 months) | Worst | 3 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | MoCA variations (baseline vs 12 months) | Stable/better | 18 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | SDMT variations (baseline vs 12 months) | Stable/better | 20 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Semantic fluency variations (baseline vs 6 months) | Stable/better | 18 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | MoCA variations (baseline vs 12 months) | Worst | 2 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Semantic fluency variations (baseline vs 6 months) | Worst | 3 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | MMSE variations (baseline vs 6 months) | Stable/better | 20 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Semantic fluency variations (6 vs 12 months) | Stable/better | 19 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | ROCF recall variations (6 vs 12 months) | Stable/better | 15 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Semantic fluency variations (6 vs 12 months) | Worst | 2 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | MMSE variations (baseline vs 6 months) | Worst | 1 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Semantic fluency variation (baseline vs 12 months) | Stable/better | 18 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | SDMT variations (baseline vs 12 months) | Worst | 1 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Short story variations (6 vs 12 months) | Stable/better | 20 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Semantic fluency variation (baseline vs 12 months) | Worst | 3 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | MMSE variations (6 vs 12 months) | Stable/better | 20 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | ROCF copy variations (baseline vs 6 months) | Stable/better | 20 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | SDMT variations (baseline vs 6 months) | Worst | 2 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | ROCF copy variations (baseline vs 6 months) | Worst | 0 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | MMSE variations (6 vs 12 months) | Worst | 1 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | ROCF copy variations (6 vs 12 months) | Stable/better | 18 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | ROCF recall variations (baseline vs 6 months) | Stable/better | 13 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | ROCF copy variations (6 vs 12 months) | Worst | 1 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | MMSE variations (baseline vs 12 months) | Stable/better | 20 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | ROCF copy variations (baseline vs 12 months) | Stable/better | 19 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | SDMT variations (6 vs 12 months) | Worst | 2 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Stroop test variations (6 vs 12 months) | Worst | 2 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | MMSE variations (baseline vs 12 months) | Worst | 1 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | ROCF copy variations (baseline vs 12 months) | Worst | 1 Participants |
| APT-II Group | Cognitive Performance (Clinically Significance Approach) | Short story variations (6 vs 12 months) | Worst | 1 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | ROCF copy variations (baseline vs 12 months) | Worst | 4 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | MoCA variations (baseline vs 12 months) | Worst | 3 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | RAVL recall variations (baseline vs 12 months) | Worst | 4 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | ROCF recall variations (baseline vs 6 months) | Stable/better | 16 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | ROCF recall variations (baseline vs 6 months) | Worst | 5 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | ROCF recall variations (6 vs 12 months) | Stable/better | 15 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | ROCF recall variations (6 vs 12 months) | Worst | 5 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | ROCF recall variations (baseline vs 12 months) | Stable/better | 16 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Short story variations (baseline vs 6 months) | Stable/better | 18 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Short story variations (baseline vs 6 months) | Worst | 4 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Short story variations (6 vs 12 months) | Stable/better | 20 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Short story variations (6 vs 12 months) | Worst | 2 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Short story variations (baseline vs 12 months) | Stable/better | 18 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Short story variations (baseline vs 12 months) | Worst | 4 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Visual search variations (baseline vs 6 months) | Stable/better | 15 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Visual search variations (baseline vs 6 months) | Worst | 6 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Visual search variations (6 vs 12 months) | Worst | 6 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Visual search variations (baseline vs 12 months) | Stable/better | 13 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Visual search variations (baseline vs 12 months) | Worst | 7 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | SDMT variations (baseline vs 6 months) | Stable/better | 21 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | SDMT variations (6 vs 12 months) | Stable/better | 19 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | SDMT variations (6 vs 12 months) | Worst | 3 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | SDMT variations (baseline vs 12 months) | Stable/better | 18 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | SDMT variations (baseline vs 12 months) | Worst | 4 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Stroop test variations (baseline vs 6 months) | Stable/better | 20 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Stroop test variations (baseline vs 6 months) | Worst | 2 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Stroop test variations (6 vs 12 months) | Stable/better | 18 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Stroop test variations (6 vs 12 months) | Worst | 4 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Stroop test variations (baseline vs 12 months) | Worst | 5 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | TMT-A variations (baseline vs 6 months) | Stable/better | 18 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | TMT-A variations (baseline vs 6 months) | Worst | 4 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | TMT-A variations (6 vs 12 months) | Stable/better | 17 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | TMT-A variations (6 vs 12 months) | Worst | 5 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | MoCA variations (baseline vs 6 months) | Stable/better | 20 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | MoCA variations (baseline vs 6 months) | Worst | 2 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | MoCA variations (6 vs 12 months) | Stable/better | 18 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | MoCA variations (6 vs 12 months) | Worst | 4 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | MMSE variations (baseline vs 6 months) | Stable/better | 21 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | MMSE variations (baseline vs 6 months) | Worst | 1 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | MMSE variations (6 vs 12 months) | Stable/better | 21 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | MMSE variations (6 vs 12 months) | Worst | 1 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | MMSE variations (baseline vs 12 months) | Stable/better | 22 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | MMSE variations (baseline vs 12 months) | Worst | 0 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | RAVL immed. variations (baseline vs 6 months) | Stable/better | 21 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | RAVL immed. variations (baseline vs 6 months) | Worst | 1 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | RAVL immed. variations (6 vs 12 months) | Stable/better | 17 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | RAVL immed. variations (6 vs 12 months) | Worst | 5 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | RAVL immed. variations (baseline vs 12 months) | Stable/better | 17 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | RAVL immed. variations (baseline vs 12 months) | Worst | 5 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | RAVL recall variations (baseline vs 6 months) | Stable/better | 17 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | RAVL recall variations (baseline vs 6 months) | Worst | 5 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | RAVL recall variations (6 vs 12 months) | Stable/better | 18 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | RAVL recall variations (6 vs 12 months) | Worst | 4 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | RAVL recall variations (baseline vs 12 months) | Stable/better | 18 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | ROCF recall variations (baseline vs 12 months) | Worst | 4 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Visual search variations (6 vs 12 months) | Stable/better | 15 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | TMT-A variations (baseline vs 12 months) | Stable/better | 16 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | TMT-A variations (baseline vs 12 months) | Worst | 6 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | TMT-B variations (baseline vs 6 months) | Stable/better | 16 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | TMT-B variations (baseline vs 6 months) | Worst | 4 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | TMT-B variations (6 vs 12 months) | Stable/better | 15 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | TMT-B variations (6 vs 12 months) | Worst | 2 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | TMT-B variations (baseline vs 12 months) | Stable/better | 14 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | TMT-B variations (baseline vs 12 months) | Worst | 3 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Phonemic fluency variations (baseline vs 6 months) | Stable/better | 18 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Phonemic fluency variations (baseline vs 6 months) | Worst | 4 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | SDMT variations (baseline vs 6 months) | Worst | 1 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Phonemic fluency variations (6 vs 12 months) | Stable/better | 20 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Phonemic fluency variations (6 vs 12 months) | Worst | 2 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Phonemic fluency variation (baseline vs 12 months) | Stable/better | 19 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Phonemic fluency variation (baseline vs 12 months) | Worst | 3 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Semantic fluency variations (baseline vs 6 months) | Stable/better | 19 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Semantic fluency variations (baseline vs 6 months) | Worst | 3 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Semantic fluency variations (6 vs 12 months) | Stable/better | 19 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Semantic fluency variations (6 vs 12 months) | Worst | 3 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Semantic fluency variation (baseline vs 12 months) | Stable/better | 19 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Semantic fluency variation (baseline vs 12 months) | Worst | 3 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | ROCF copy variations (baseline vs 6 months) | Stable/better | 22 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | ROCF copy variations (baseline vs 6 months) | Worst | 0 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | ROCF copy variations (6 vs 12 months) | Stable/better | 14 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | ROCF copy variations (6 vs 12 months) | Worst | 7 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | ROCF copy variations (baseline vs 12 months) | Stable/better | 17 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | Stroop test variations (baseline vs 12 months) | Stable/better | 17 Participants |
| Standard Care Group | Cognitive Performance (Clinically Significance Approach) | MoCA variations (baseline vs 12 months) | Stable/better | 19 Participants |
Comparison: MoCA variations (baseline vs 6 months)p-value: 0.92Chi-squared
Comparison: MoCA variations (6 vs 12 months)p-value: 0.17Chi-squared
Comparison: MoCA variations (baseline vs 12 months)p-value: 0.716Chi-squared
Comparison: MMSE variations (baseline vs 6 months)p-value: 0.973Chi-squared
Comparison: MMSE variations (6 vs 12 months)p-value: 0.973Chi-squared
Comparison: MMSE variations (baseline vs 12 months)p-value: 0.3Chi-squared
Comparison: RAVL immed. variations (baseline vs 6 months)p-value: 0.068Chi-squared
Comparison: RAVL immed. variations (6 vs 12 months)p-value: 0.089Chi-squared
Comparison: RAVL immed. variations (baseline vs 12 months)p-value: 0.241Chi-squared
Comparison: RAVL recall variations (baseline vs 6 months)p-value: 0.089Chi-squared
Comparison: RAVL recall variations (6 vs 12 months)p-value: 0.17Chi-squared
Comparison: RAVL recall variations (baseline vs 12 months)p-value: 0.413Chi-squared
Comparison: ROCF recall variations (baseline vs 6 months)p-value: 0.777Chi-squared
Comparison: ROCF recall variations (6 vs 12 months)p-value: 0.134Chi-squared
Comparison: ROCF recall variations (baseline vs 12 months)p-value: 0.498Chi-squared
Comparison: Short story variations (baseline vs 6 months)p-value: 0.942Chi-squared
Comparison: Short story variations (6 vs 12 months)p-value: 0.578Chi-squared
Comparison: Short story variations (baseline vs 12 months)p-value: 0.413Chi-squared
Comparison: Visual search variations (baseline vs 6 months)p-value: 1Chi-squared
Comparison: Visual search variations (6 vs 12 months)p-value: 0.038Chi-squared
Comparison: Visual search variations (baseline vs 12 months)p-value: 0.658Chi-squared
Comparison: SDMT variations (baseline vs 6 months)p-value: 0.522Chi-squared
Comparison: SDMT variations (6 vs 12 months)p-value: 0.674Chi-squared
Comparison: SDMT variations (baseline vs 12 months)p-value: 0.17Chi-squared
Comparison: Stroop test variations (baseline vs 6 months)p-value: 0.961Chi-squared
Comparison: Stroop test variations (6 vs 12 months)p-value: 0.413Chi-squared
Comparison: Stroop test variations (baseline vs 12 months)p-value: 0.477Chi-squared
Comparison: TMT-A variations (baseline vs 6 months)p-value: 0.42Chi-squared
Comparison: TMT-A variations (6 vs 12 months)p-value: 0.241Chi-squared
Comparison: TMT-A variations (baseline vs 12 months)p-value: 0.295Chi-squared
Comparison: TMT-B variations (baseline vs 6 months)p-value: 0.453Chi-squared
Comparison: TMT-B variations (6 vs 12 months)p-value: 0.952Chi-squared
Comparison: TMT-B variations (baseline vs 12 months)p-value: 0.881Chi-squared
Comparison: Phonemic fluency variations (baseline vs 6 months)p-value: 0.413Chi-squared
Comparison: Phonemic fluency variations (6 vs 12 months)p-value: 0.961Chi-squared
Comparison: Phonemic fluency variation (baseline vs 12 months)p-value: 0.951Chi-squared
Comparison: Semantic fluency variations (baseline vs 6 months)p-value: 0.951Chi-squared
Comparison: Semantic fluency variations (6 vs 12 months)p-value: 0.674Chi-squared
Comparison: Semantic fluency variation (baseline vs 12 months)p-value: 0.951Chi-squared
Comparison: ROCF copy variations (baseline vs 6 months)p-value: 1Chi-squared
Comparison: ROCF copy variations (6 vs 12 months)p-value: 0.027Chi-squared
Comparison: ROCF copy variations (baseline vs 12 months)p-value: 0.169Chi-squared
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.
Time frame: Baseline, 6 months and 12 months
Population: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APT-II Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on TMT-B (baseline vs 6 months) | 24.5 seconds | Standard Deviation 55.9 |
| APT-II Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on TMT-A (6 vs 12 months) | 2.9 seconds | Standard Deviation 24.6 |
| APT-II Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on TMT-B (6 vs 12 months) | -13.2 seconds | Standard Deviation 51.4 |
| APT-II Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on TMT-A (baseline vs 12 months) | -4.8 seconds | Standard Deviation 29.6 |
| APT-II Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on Stroop test (baseline vs 12 months) | 2.2 seconds | Standard Deviation 18.4 |
| APT-II Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on Stroop test (baseline vs 6 months) | 0.4 seconds | Standard Deviation 16.4 |
| APT-II Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on TMT-A (baseline vs 6 months) | -7.7 seconds | Standard Deviation 23.8 |
| APT-II Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on TMT-B (baseline vs 12 months) | 10.7 seconds | Standard Deviation 45.3 |
| APT-II Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on Stroop test (6 vs 12 months) | 1.7 seconds | Standard Deviation 15.3 |
| Standard Care Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on TMT-B (baseline vs 12 months) | -4.6 seconds | Standard Deviation 53.8 |
| Standard Care Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on Stroop test (baseline vs 6 months) | -1.7 seconds | Standard Deviation 25.2 |
| Standard Care Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on Stroop test (6 vs 12 months) | -3.4 seconds | Standard Deviation 25.6 |
| Standard Care Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on Stroop test (baseline vs 12 months) | -5.1 seconds | Standard Deviation 26 |
| Standard Care Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on TMT-A (baseline vs 6 months) | 3.9 seconds | Standard Deviation 28.2 |
| Standard Care Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on TMT-A (6 vs 12 months) | -11.83 seconds | Standard Deviation 30.7 |
| Standard Care Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on TMT-A (baseline vs 12 months) | -13.2 seconds | Standard Deviation 44.9 |
| Standard Care Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on TMT-B (baseline vs 6 months) | -14.1 seconds | Standard Deviation 48.5 |
| Standard Care Group | Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach) | Δs on TMT-B (6 vs 12 months) | -4.2 seconds | Standard Deviation 21 |
Comparison: Δs on Stroop test (baseline vs 6 months)p-value: 0.743t-test, 2 sided
Comparison: Δs on Stroop test (6 vs 12 months)p-value: 0.428t-test, 2 sided
Comparison: Δs on Stroop test (baseline vs 12 months)p-value: 0.294t-test, 2 sided
Comparison: Δs on TMT-A (baseline vs 6 months)p-value: 0.157t-test, 2 sided
Comparison: Δs on TMT-A (6 vs 12 months)p-value: 0.094t-test, 2 sided
Comparison: Δs on TMT-A (baseline vs 12 months)p-value: 0.476t-test, 2 sided
Comparison: Δs on TMT-B (baseline vs 6 months)p-value: 0.142t-test, 2 sided
Comparison: Δs on TMT-B (6 vs 12 months)p-value: 0.651t-test, 2 sided
Comparison: Δs on TMT-B (baseline vs 12 months)p-value: 0.534t-test, 2 sided
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.
Time frame: Baseline, 6 months and 12 months
Population: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| APT-II Group | Cognitive Performance Verbal Fluency (Changes in Scores Approach) | Δs on phonemic fluency (baseline vs 6 months) | 0 words | Standard Deviation 6.7 |
| APT-II Group | Cognitive Performance Verbal Fluency (Changes in Scores Approach) | Δs on phonemic fluency (6 vs 12 months) | 0.1 words | Standard Deviation 6.4 |
| APT-II Group | Cognitive Performance Verbal Fluency (Changes in Scores Approach) | Δs on phonemic fluency (baseline vs 12 months) | 0.1 words | Standard Deviation 7.7 |
| APT-II Group | Cognitive Performance Verbal Fluency (Changes in Scores Approach) | Δs on semantic fluency (baseline vs 6 months) | -0.5 words | Standard Deviation 5.3 |
| APT-II Group | Cognitive Performance Verbal Fluency (Changes in Scores Approach) | Δs on semantic fluency (6 vs 12 months) | -0.1 words | Standard Deviation 5.9 |
| APT-II Group | Cognitive Performance Verbal Fluency (Changes in Scores Approach) | Δs on semantic fluency (baseline vs 12 months) | -0.6 words | Standard Deviation 7.2 |
| Standard Care Group | Cognitive Performance Verbal Fluency (Changes in Scores Approach) | Δs on semantic fluency (6 vs 12 months) | 0 words | Standard Deviation 5.6 |
| Standard Care Group | Cognitive Performance Verbal Fluency (Changes in Scores Approach) | Δs on phonemic fluency (baseline vs 6 months) | 0.3 words | Standard Deviation 5.4 |
| Standard Care Group | Cognitive Performance Verbal Fluency (Changes in Scores Approach) | Δs on semantic fluency (baseline vs 6 months) | 0.8 words | Standard Deviation 5 |
| Standard Care Group | Cognitive Performance Verbal Fluency (Changes in Scores Approach) | Δs on phonemic fluency (6 vs 12 months) | -0.3 words | Standard Deviation 6.5 |
| Standard Care Group | Cognitive Performance Verbal Fluency (Changes in Scores Approach) | Δs on semantic fluency (baseline vs 12 months) | 0.8 words | Standard Deviation 5.9 |
| Standard Care Group | Cognitive Performance Verbal Fluency (Changes in Scores Approach) | Δs on phonemic fluency (baseline vs 12 months) | 0 words | Standard Deviation 6.7 |
Comparison: Δs on phonemic fluency (baseline vs 6 months)p-value: 0.882t-test, 2 sided
Comparison: Δs on phonemic fluency (6 vs 12 months)p-value: 0.835t-test, 2 sided
Comparison: Δs on phonemic fluency (baseline vs 12 months)p-value: 0.951t-test, 2 sided
Comparison: Δs on semantic fluency (baseline vs 6 months)p-value: 0.392t-test, 2 sided
Comparison: Δs on semantic fluency (6 vs 12 months)p-value: 0.973t-test, 2 sided
Comparison: Δs on semantic fluency (baseline vs 12 months)p-value: 0.486t-test, 2 sided
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).
Time frame: Baseline, 12 months
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| APT-II Group | Cognitive Plasticity | Z-transformed ReHo difference in vermis VIIIb | 0.78 standard Z-values |
| APT-II Group | Cognitive Plasticity | Z-transformed ReHo difference in right VIIb lobule | 1.02 standard Z-values |
| APT-II Group | Cognitive Plasticity | Z-transformed ReHo difference in left VIIb lobule | 1.31 standard Z-values |
| Standard Care Group | Cognitive Plasticity | Z-transformed ReHo difference in vermis VIIIb | -0.66 standard Z-values |
| Standard Care Group | Cognitive Plasticity | Z-transformed ReHo difference in right VIIb lobule | -0.86 standard Z-values |
| Standard Care Group | Cognitive Plasticity | Z-transformed ReHo difference in left VIIb lobule | -1.27 standard Z-values |
Comparison: Z-transformed ReHo difference in vermis VIIIbp-value: 0.029General linear model voxel-wise
Comparison: Z-transformed ReHo difference in right VIIb lobulep-value: 0.04General linear model voxel-wise
Comparison: Z-transformed ReHo difference in left VIIb lobulep-value: 0.039General linear model voxel-wise
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.
Time frame: 12 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| APT-II Group | Transition to Dementia | demented at 1-year follow-up | 3 Participants |
| APT-II Group | Transition to Dementia | stable MCI | 17 Participants |
| APT-II Group | Transition to Dementia | reverted to normal cognitive function | 1 Participants |
| Standard Care Group | Transition to Dementia | reverted to normal cognitive function | 0 Participants |
| Standard Care Group | Transition to Dementia | demented at 1-year follow-up | 5 Participants |
| Standard Care Group | Transition to Dementia | stable MCI | 17 Participants |
p-value: 0.478Chi-squared