Clinical trial NCT02033850: Rehabilitation of Attention in Patients With MCI and Brain Subcortical Vascular Changes Using the APT-II
Official title: The Rehabilitation of Attention in Patients With Mild Cognitive Impairment and Brain Subcortical Vascular Changes Using the Attention Process Training-II
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mild Cognitive Impairment
Keywords: small vessel disease
cognition
treatment
rehabilitation
attention
fMRI
vascular dementia
Lead sponsor: Azienda Ospedaliero-Universitaria Careggi
Sponsor class: OTHER
Collaborators: name: Ministero della Salute, Italy
First posted: 2014-01-13
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Functionality in Activities of Daily Living (Changes in Scores Approach)
timeFrame: Baseline, 6 months and 12 months
measure: Quality of Life (Changes in Scores Approach)
timeFrame: Baseline, 6 months and 12 months
measure: Quality of Life (Clinically Significance Approach)
timeFrame: Baseline, 6 months and 12 months
Secondary outcomes:
measure: Cognitive Performance (Changes in Scores Approach)
timeFrame: Baseline, 6 months and 12 months
measure: Cognitive Performance TMT-A, TMT-B, Stroop (Changes in Scores Approach)
timeFrame: Baseline, 6 months and 12 months
measure: Cognitive Performance Verbal Fluency (Changes in Scores Approach)
timeFrame: Baseline, 6 months and 12 months
measure: Cognitive Performance (Clinically Significance Approach)
timeFrame: Baseline, 6 months and 12 months
measure: Transition to Dementia
timeFrame: 12 months
measure: Cognitive Plasticity
timeFrame: Baseline, 12 months
Other outcomes:
Locations:
city: Firenze
country: Italy
facility: Stroke Unit and Neurology, VAS-COG clinic
Study officials:
affiliation: University of Milan
name: Leonardo Pantoni, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.