Cognitive ImpairmentNPT-CI2019NCT04118686
Non-Pharmacological Treatments and Cognitive Impairment (NPT-CI2019)
A study testing CoRe software training plus non-invasive brain stimulation techniques (anodical tDCS / rTMS) in people with Cognitive Impairment, run by IRCCS National Neurological Institute "C. Mondino" Foundation at 1 site in Italy.
Trial summary
The prevalence of neurodegenerative diseases is expected to increase over the next years, in parallel with the aging of the world population. Therefore, it is important to identify new methods to prevent, delay or stop the neurodegenerative waterfall responsible for dementia conversion. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Cognitive Impairment
- What is being tested?
- CoRe software training plus non-invasive brain stimulation techniques (anodical tDCS / rTMS)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteItaly
- Study dates
- 15 Mar 2017to 15 Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- presence of mild dementia or mild cognitive impairment;
- age between 50 and 85 years;
- educational level ≥ 5 years.
Who cannot join
- pre-existing cognitive impairment (e.g. aphasia, neglect);
- severe disturbances in consciousness;
- concomitant severe psychiatric disease or others neurological conditions (e.g. depression and behavioural disorders).
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Struttura Semplice Neuropsicologia Clinica/ Centro UVA
Pavia, 27100
Elena Sinforiani, MD, 0039 0382 380290, elena.sinforiani@mondino.it
sara bernini bernini, PhD, 0039 0382 380290, sara.bernini@mondino.it
About this study
Official title: New Approaches for the Treatment of Early Stages of Cognitive Impairment in Neurodegenerative Diseases
The prevalence of neurodegenerative diseases is expected to increase over the next years, in parallel with the aging of the world population. Therefore, it is important to identify new methods to prevent, delay or stop the neurodegenerative waterfall responsible for dementia conversion. To date, there is no fully proven pharmacological treatment for cognitive impairment and the available pharmacological armamentariums have limited efficacy because consist in symptomatic drugs with adverse side effects. On this point, non-pharmacological intervention may represent adjunctive therapy to medications in order to prevent or delay the onset of the cognitive deficits or dementia. This study aims to evaluate the effectiveness of a combined treatment protocol associating a Computerized cognitive training (CoRe) with non-invasive brain stimulation techniques: the transcranial Direct Current Stimulation (tDCS) or the repetitive Transcranial Magnetic Stimulation (rTMS). Patients with mild dementia or Mild Cognitive Impairment (MCI) are enrolled and randomly assigned to the experimental group (CoRe + anodic tDCS/rTMS) or control group (CoRe + sham tDCS/ sham rTMS). All patients are evaluated before (T0) and after (T1) treatment with an exhaustive neuropsychological assessment. Furthermore, follow-up visits are scheduled 6 months (T2) and 12 months (T3) after the end of the treatment.
Read the detailed description
Non-pharmacological intervention may represent adjunctive therapy to medications in order to delay the onset of the cognitive deficits or dementia. Moreover, increasing evidence suggests that environmental and lifestyle factors (education, cognitive engagement, experience..) impact on cognitive functions and brain plasticity during the lifetime and also during aging. These modifiable factors moderate differences in cognitive aging and are protective for the development of dementia.
Among non-pharmacological approaches, previous studies observed a positive effect of Cognitive Training (CT) both in healthy elderly people and patients in the early stage of neurodegenerative diseases. Moreover, the advances in the development of Information \& Communication Technologies has prompted the possibility to develop computer-based solution for the training of cognitive functions, being able to overcome traditional-training advantages. However, some issue remain unresolved and larger randomized controlled trials are necessary to examine long-term CT effects, due to the lack of longitudinal studies. Our previous data demonstrated that CT program with Computerized cognitive training (CoRe) software is safe and effective on cognition in patient with Parkinson Disease-Mild Cognitive Impairment, in the attempt of briefly stabilizing cognitive decline, delaying the downward trajectory.
Recently, different forms of non-invasive brain stimulation techniques have been applied to healthy older adults and patients with Alzheimer Disease (AD) in order to improve physiological and pathological aging-related cognitive impairments. Two main forms of non-invasive brain stimulation techniques are repetitive Transcranial Magnetic Stimulation (rTMS) and Transcranial Direct Current Stimulation (tDCS). rTMS is a painless, non-invasive method that modulates cortical activities by delivering strong magnetic pulses to the cortex through the scalp. Depending on stimulation parameters (e.g., duration, stimulus intensity, frequency), rTMS can enhance or suppress cortical excitability in targeted cortical regions. In general, high frequency rTMS facilitates cortical excitability whereas low frequency rTMS suppresses cortical excitability. tDCS delivers weak electrical currents to the scalp to modulate neuronal transmembrane potential towards hyperpolarization or depolarization, thereby altering plasticity in the stimulated brain regions. Depending on whether anodal or cathodal stimulation is applied, tDCS increases or decreases cortical excitability, respectively.These non-invasive brain stimulation techniques can be used alone or in combination with cognitive intervention programs. Some studies suggested that these non-invasive neurostimulation are able to enhance the effect of CT; however other studies yielded conflicting results, likely due to differences in stimulation parameters, experimental design and outcome measures. Thus, the overall efficacy of non-invasive neural stimulation as a therapeutic is still under debate.
In this frame, the primary goal of this double-blind randomized controlled trial is to assess whether the application of non-invasive brain stimulation techniques (tDCS or TMS) during the course of a computerized CT (on-line neurostimulation) enhances the effect on CT. Moreover, the follow-up visits allow to detect if the improvement are maintained over time and if this combined intervention affect the evolution of cognitive decline.
The treatment protocol consists of 12 sessions (4 session/week, 45 minutes/day) of CT with CoRe software (training memory and logical-executive functions) combined with on-line tDCS (anodic tDCS, 2mA for 20 minutes, versus sham tDCS applied to the cortical prefrontal cortex - DLPFC ) or rTMS (rTMS 20 Hz for 20 minutes versus sham TMS applied to DLPFC).
Patient with mild dementia or MCI are recruited from Neuropsychology/Alzheimer's Disease Assessment Unit and Neurorehabilitation Unit of IRCCS Mondino Foundation. The diagnosis of mild dementia or MCI is formulated on the basis of a comprehensive neuropsychological evaluation (baseline cognitive assessment - T0) according to the guidelines presented in the literature. The following standardized tests assessing different domains are used:
- global cognitive function: Mini-Mental State Examination (MMSE) and Montreal Montreal Overall Cognitive Assessment (MoCA);
- memory: verbal (Verbal Span; Digit Span) and spatial (Corsi's blocktapping test - CBTT) span; verbal long-term memory (Logical Memory Test immediate and delayed recall; Rey's 15-word test immediate and delayed recall); spatial long-term memory (Rey Complex Figure delayed recall - RCF-dr);
- logical-executive functions: non-verbal reasoning (Raven's Matrices 1947 - RM47); frontal functionality (Frontal Assessment Battery - FAB); semantic fluency (animals, fruits, car brands), phonological fluency (FAS);
- attention: visual selective attention (Attentive Matrices); simple speed processing and complex attention (Trail Making Test parts A - TMT A and part B - TMT B);
- visuospatial abilities: constructive apraxia Rey Complex Figure copy - RCF-copy.
The same battery is also used at follow-up visits; parallel versions are applied when available (verbal long-term memory tests), in order to avoid the learning effect. All the test scores are corrected for age, sex, and education and compared with the values available for the Italian population.
At the baseline, the cognitive reserve is assessed using Cognitive Reserve Index questionnaire (CRIq). The patients' functional status is assessed using Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) at the baseline and at the last follow-up visit after one year (T3). Moreover, mood is assessed using the Beck Depression Inventory (BDI) at the baseline and at the follow-up visits (T1, T2 and T3), while quality of life were assessed using the 36-Item Short Form Health Survey questionnaire (SF-36) at the baseline and at the follow-up visits six months (T2) and one year (T3) after training.
All the patients recruited undergo baseline cognitive assessment (T0). Patients who met the inclusion and exclusion criteria are enrolled and randomly assigned to the experimental group (CoRE + anodic tDCS/rTMS) or control group (CoRe + sham tDCS/rTMS).
- Conditions
- Cognitive Impairment
- Being tested
- CoRe software training plus non-invasive brain stimulation techniques (anodical tDCS / rTMS), CoRe software training plus sham non-invasive brain stimulation (sham tDCS/ sham rTMS)
- Keywords
- Neurodegenerative disease, Cognitive decline, Non-pharmacological treatments, Cognitive training, Non-invasive brain stimulation
- Medical subject headings
- Cognitive Dysfunction, Neurodegenerative Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CoRe software training plus non-invasive brain stimulation techniques (anodical tDCS / rTMS)Other
CT program with Computerized cognitive training (CoRe) plus stimulation that modulates cortical activities by delivering strong magnetic pulses to the cortex through the scalp (rTMS) and weak electrical currents to the scalp to modulate neuronal transmembrane potential towards hyperpolarization or depolarization (tDCS).
CoRe software training plus sham non-invasive brain stimulation (sham tDCS/ sham rTMS)Other
CT program with Computerized cognitive training (CoRe) plus sham stimulation
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | The group receives CoRe software training plus non-invasive brain stimulation techniques (anodical tDCS / rTMS) Receives: Other: CoRe software training plus non-invasive brain stimulation techniques (anodical tDCS / rTMS) |
| Control group | Sham comparator | The group receives CoRe software training plus sham non-invasive brain stimulation (sham tDCS/ sham rTMS) Receives: Other: CoRe software training plus sham non-invasive brain stimulation (sham tDCS/ sham rTMS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in global cognitive functioning measured by Mini-Mental State Examination (MMSE)
It is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. The score is between 0-30. Lower score is worse cognitive functioning.
Measured: After 3 -week intervention program (T1), 6 months (T2) and 1 year (T3) after the end of intervention program
Change in global cognitive functioning measured by Montreal Overall Cognitive Assessment (MoCA)
It is a widely used screening assessment for detecting cognitive impairment. It assesses several cognitive domains:
The short-term memory recall task (5 points). Visuospatial abilities a clock-drawing task (3 points) and a three-dimensional cube copy (1 point). Multiple aspects of executive functions are assessed using an alternation task adapted from the trail-making B task (1 point), a phonemic fluency task (1 point), and a two-item verbal abstraction task (2 points). Attention, concentration, and working memory are evaluated using a three-item confrontation naming task with low-familiarity animals (3 points), repetition of two syntactically complex sentences (2 points), and the aforementioned fluency task. Finally, orientation to time and place (6 points). Low score is worse outcome.
Measured: After 3 -week intervention program (T1), 6 months (T2) and 1 year (T3) after the end of intervention program
Secondary outcomes (5)
Change in memory
Verbal and spatial span; verbal long-ter memory; spatial long-term memory by using scales. Higher scores are better outcomes.
Measured: After 3 -week intervention program (T1), 6 months (T2) and 1 year (T3) after the end of intervention program
Change in executive functions
Logical-executive functions; attention; visuospatial abilities by using scale. Higher scorea are better outcomes.
Measured: After 3 -week intervention program (T1), 6 months (T2) and 1 year (T3) after the end of intervention program
Change in mood (assessed by Beck Depression Inventory - BDI)
Contains 21 questions. The items are rated on a 4-point severity scale (0-3) and are summed to give a total score (range 0-63). A higher score denotes more severe depression.
Measured: After 3 -week intervention program (T1), 6 months (T2) and 1 year (T3) after the end of intervention program
Change in Quality of Life (assessed by Short Form-36 Health Survey - SF - 36)
Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carriers equal weight. Low score is worse quality of life.
Measured: After 3 -week intervention program (T1), 6 months (T2) and 1 year (T3) after the end of intervention program
Change in the evolution of cognitive profile (assessed by Clinical Dementia Rating Scale - CDR)
CDR is a widely utilized clinical tool for grading the relative severity of dementia with scores that range from 0 (no impairment) to 3 (severe impairment)
Measured: After 3 -week intervention program (T1), 6 months (T2) and 1 year (T3) after the end of intervention program
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2019
- Study start15 Mar 2017
- Primary completion15 Dec 2020 (estimated)
- Study completion15 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Cognitive ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A prospective, double-blind, randomized, parallel, controlled study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 19 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS National Neurological Institute "C. Mondino" Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Elena Sinforiani, MD, Principal investigator, Struttura Semplice Neuropsicologia Clinica/Centro UVA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04118686
- Sponsor's protocol ID
- NPT-CI2019
- Acronym
- NPT-CI2019
- Status last verified
- Oct 2019
- First submitted
- 3 Oct 2019
- Last updated
- 8 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, Ballard C, Banerjee S, Burns A, Cohen-Mansfield J, Cooper C, Fox N, Gitlin LN, Howard R, Kales HC, Larson EB, Ritchie K, Rockwood K, Sampson EL, Samus Q, Schneider LS, Selbaek G, Teri L, Mukadam N. Dementia prevention, intervention, and care. Lancet. 2017 Dec 16;390(10113):2673-2734. doi: 10.1016/S0140-6736(17)31363-6. Epub 2017 Jul 20. No abstract available.
PubMed 28735855Lampit A, Hallock H, Valenzuela M. Computerized cognitive training in cognitively healthy older adults: a systematic review and meta-analysis of effect modifiers. PLoS Med. 2014 Nov 18;11(11):e1001756. doi: 10.1371/journal.pmed.1001756. eCollection 2014 Nov.
PubMed 25405755Coyle H, Traynor V, Solowij N. Computerized and virtual reality cognitive training for individuals at high risk of cognitive decline: systematic review of the literature. Am J Geriatr Psychiatry. 2015 Apr;23(4):335-359. doi: 10.1016/j.jagp.2014.04.009. Epub 2014 May 14.
PubMed 24998488Bernini S, Alloni A, Panzarasa S, Picascia M, Quaglini S, Tassorelli C, Sinforiani E. A computer-based cognitive training in Mild Cognitive Impairment in Parkinson's Disease. NeuroRehabilitation. 2019;44(4):555-567. doi: 10.3233/NRE-192714.
PubMed 31256092Prehn K, Floel A. Potentials and limits to enhance cognitive functions in healthy and pathological aging by tDCS. Front Cell Neurosci. 2015 Sep 14;9:355. doi: 10.3389/fncel.2015.00355. eCollection 2015.
PubMed 26441526Hsu WY, Ku Y, Zanto TP, Gazzaley A. Effects of noninvasive brain stimulation on cognitive function in healthy aging and Alzheimer's disease: a systematic review and meta-analysis. Neurobiol Aging. 2015 Aug;36(8):2348-59. doi: 10.1016/j.neurobiolaging.2015.04.016. Epub 2015 May 1.
PubMed 26022770Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21.
PubMed 21514249Litvan I, Goldman JG, Troster AI, Schmand BA, Weintraub D, Petersen RC, Mollenhauer B, Adler CH, Marder K, Williams-Gray CH, Aarsland D, Kulisevsky J, Rodriguez-Oroz MC, Burn DJ, Barker RA, Emre M. Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines. Mov Disord. 2012 Mar;27(3):349-56. doi: 10.1002/mds.24893. Epub 2012 Jan 24.
PubMed 22275317Rodella C, Bernini S, Panzarasa S, Sinforiani E, Picascia M, Quaglini S, Cavallini E, Vecchi T, Tassorelli C, Bottiroli S. A double-blind randomized controlled trial combining cognitive training (CoRe) and neurostimulation (tDCS) in the early stages of cognitive impairment. Aging Clin Exp Res. 2022 Jan;34(1):73-83. doi: 10.1007/s40520-021-01912-0. Epub 2021 Jun 22.
PubMed 34156651
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- New Approaches for the Treatment of Early Stages of Cognitive Impairment in Neurodegenerative Diseases
- ClinicalTrials.gov ID
- NCT04118686
- Acronym / sponsor ID
- NPT-CI2019 / NPT-CI2019
- Conditions
- Cognitive Impairment
- Keywords
- Neurodegenerative disease, Cognitive decline, Non-pharmacological treatments, Cognitive training, Non-invasive brain stimulation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 19 participants (estimated)
- Lead sponsor
- IRCCS National Neurological Institute "C. Mondino" FoundationUniversity, hospital or other
- Study start
- 15 Mar 2017 (actual)
- Primary completion
- 15 Dec 2020 (estimated)
- Study completion
- 15 Dec 2020 (estimated)
- First posted
- 8 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The prevalence of neurodegenerative diseases is expected to increase over the next years, in parallel with the aging of the world population. Therefore, it is important to identify new methods to prevent, delay or stop the neurodegenerative waterfall responsible for dementia conversion. To date, there is no fully proven pharmacological treatment for cognitive impairment and the available pharmacological armamentariums have limited efficacy because consist in symptomatic drugs with adverse side effects. On this point, non-pharmacological intervention may represent adjunctive therapy to medications in order to prevent or delay the onset of the cognitive deficits or dementia. This study aims to evaluate the effectiveness of a combined treatment protocol associating a Computerized cognitive training (CoRe) with non-invasive brain stimulation techniques: the transcranial Direct Current Stimulation (tDCS) or the repetitive Transcranial Magnetic Stimulation (rTMS). Patients with mild dementia or Mild Cognitive Impairment (MCI) are enrolled and randomly assigned to the experimental group (CoRe + anodic tDCS/rTMS) or control group (CoRe + sham tDCS/ sham rTMS). All patients are evaluated before (T0) and after (T1) treatment with an exhaustive neuropsychological assessment. Furthermore, follow-up visits are scheduled 6 months (T2) and 12 months (T3) after the end of the treatment.
Detailed description
Non-pharmacological intervention may represent adjunctive therapy to medications in order to delay the onset of the cognitive deficits or dementia. Moreover, increasing evidence suggests that environmental and lifestyle factors (education, cognitive engagement, experience..) impact on cognitive functions and brain plasticity during the lifetime and also during aging. These modifiable factors moderate differences in cognitive aging and are protective for the development of dementia.
Among non-pharmacological approaches, previous studies observed a positive effect of Cognitive Training (CT) both in healthy elderly people and patients in the early stage of neurodegenerative diseases. Moreover, the advances in the development of Information \& Communication Technologies has prompted the possibility to develop computer-based solution for the training of cognitive functions, being able to overcome traditional-training advantages. However, some issue remain unresolved and larger randomized controlled trials are necessary to examine long-term CT effects, due to the lack of longitudinal studies. Our previous data demonstrated that CT program with Computerized cognitive training (CoRe) software is safe and effective on cognition in patient with Parkinson Disease-Mild Cognitive Impairment, in the attempt of briefly stabilizing cognitive decline, delaying the downward trajectory.
Recently, different forms of non-invasive brain stimulation techniques have been applied to healthy older adults and patients with Alzheimer Disease (AD) in order to improve physiological and pathological aging-related cognitive impairments. Two main forms of non-invasive brain stimulation techniques are repetitive Transcranial Magnetic Stimulation (rTMS) and Transcranial Direct Current Stimulation (tDCS). rTMS is a painless, non-invasive method that modulates cortical activities by delivering strong magnetic pulses to the cortex through the scalp. Depending on stimulation parameters (e.g., duration, stimulus intensity, frequency), rTMS can enhance or suppress cortical excitability in targeted cortical regions. In general, high frequency rTMS facilitates cortical excitability whereas low frequency rTMS suppresses cortical excitability. tDCS delivers weak electrical currents to the scalp to modulate neuronal transmembrane potential towards hyperpolarization or depolarization, thereby altering plasticity in the stimulated brain regions. Depending on whether anodal or cathodal stimulation is applied, tDCS increases or decreases cortical excitability, respectively.These non-invasive brain stimulation techniques can be used alone or in combination with cognitive intervention programs. Some studies suggested that these non-invasive neurostimulation are able to enhance the effect of CT; however other studies yielded conflicting results, likely due to differences in stimulation parameters, experimental design and outcome measures. Thus, the overall efficacy of non-invasive neural stimulation as a therapeutic is still under debate.
In this frame, the primary goal of this double-blind randomized controlled trial is to assess whether the application of non-invasive brain stimulation techniques (tDCS or TMS) during the course of a computerized CT (on-line neurostimulation) enhances the effect on CT. Moreover, the follow-up visits allow to detect if the improvement are maintained over time and if this combined intervention affect the evolution of cognitive decline.
The treatment protocol consists of 12 sessions (4 session/week, 45 minutes/day) of CT with CoRe software (training memory and logical-executive functions) combined with on-line tDCS (anodic tDCS, 2mA for 20 minutes, versus sham tDCS applied to the cortical prefrontal cortex - DLPFC ) or rTMS (rTMS 20 Hz for 20 minutes versus sham TMS applied to DLPFC).
Patient with mild dementia or MCI are recruited from Neuropsychology/Alzheimer's Disease Assessment Unit and Neurorehabilitation Unit of IRCCS Mondino Foundation. The diagnosis of mild dementia or MCI is formulated on the basis of a comprehensive neuropsychological evaluation (baseline cognitive assessment - T0) according to the guidelines presented in the literature. The following standardized tests assessing different domains are used:
- global cognitive function: Mini-Mental State Examination (MMSE) and Montreal Montreal Overall Cognitive Assessment (MoCA);
- memory: verbal (Verbal Span; Digit Span) and spatial (Corsi's blocktapping test - CBTT) span; verbal long-term memory (Logical Memory Test immediate and delayed recall; Rey's 15-word test immediate and delayed recall); spatial long-term memory (Rey Complex Figure delayed recall - RCF-dr);
- logical-executive functions: non-verbal reasoning (Raven's Matrices 1947 - RM47); frontal functionality (Frontal Assessment Battery - FAB); semantic fluency (animals, fruits, car brands), phonological fluency (FAS);
- attention: visual selective attention (Attentive Matrices); simple speed processing and complex attention (Trail Making Test parts A - TMT A and part B - TMT B);
- visuospatial abilities: constructive apraxia Rey Complex Figure copy - RCF-copy.
The same battery is also used at follow-up visits; parallel versions are applied when available (verbal long-term memory tests), in order to avoid the learning effect. All the test scores are corrected for age, sex, and education and compared with the values available for the Italian population.
At the baseline, the cognitive reserve is assessed using Cognitive Reserve Index questionnaire (CRIq). The patients' functional status is assessed using Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) at the baseline and at the last follow-up visit after one year (T3). Moreover, mood is assessed using the Beck Depression Inventory (BDI) at the baseline and at the follow-up visits (T1, T2 and T3), while quality of life were assessed using the 36-Item Short Form Health Survey questionnaire (SF-36) at the baseline and at the follow-up visits six months (T2) and one year (T3) after training.
All the patients recruited undergo baseline cognitive assessment (T0). Patients who met the inclusion and exclusion criteria are enrolled and randomly assigned to the experimental group (CoRE + anodic tDCS/rTMS) or control group (CoRe + sham tDCS/rTMS).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- A prospective, double-blind, randomized, parallel, controlled study
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Other: CoRe software training plus non-invasive brain stimulation techniques (anodical tDCS / rTMS)The group receives CoRe software training plus non-invasive brain stimulation techniques (anodical tDCS / rTMS) |
| Control group | Sham comparator | Other: CoRe software training plus sham non-invasive brain stimulation (sham tDCS/ sham rTMS)The group receives CoRe software training plus sham non-invasive brain stimulation (sham tDCS/ sham rTMS) |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- presence of mild dementia or mild cognitive impairment;
- age between 50 and 85 years;
- educational level ≥ 5 years.
Key exclusion criteria (3 listed)
- pre-existing cognitive impairment (e.g. aphasia, neglect);
- severe disturbances in consciousness;
- concomitant severe psychiatric disease or others neurological conditions (e.g. depression and behavioural disorders).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CoRe software training plus non-invasive brain stimulation techniques (anodical tDCS / rTMS)CT program with Computerized cognitive training (CoRe) plus stimulation that modulates cortical activities by delivering strong magnetic pulses to the cortex through the scalp (rTMS) and weak electrical currents to the scalp to modulate neuronal transmembrane potential towards hyperpolarization or depolarization (tDCS). | Other | Experimental group |
| CoRe software training plus sham non-invasive brain stimulation (sham tDCS/ sham rTMS)CT program with Computerized cognitive training (CoRe) plus sham stimulation | Other | Control group |
Primary outcome
Change in global cognitive functioning measured by Mini-Mental State Examination (MMSE)
Time frame: After 3 -week intervention program (T1), 6 months (T2) and 1 year (T3) after the end of intervention program
It is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. The score is between 0-30. Lower score is worse cognitive functioning.
Change in global cognitive functioning measured by Montreal Overall Cognitive Assessment (MoCA)
Time frame: After 3 -week intervention program (T1), 6 months (T2) and 1 year (T3) after the end of intervention program
It is a widely used screening assessment for detecting cognitive impairment. It assesses several cognitive domains: The short-term memory recall task (5 points). Visuospatial abilities a clock-drawing task (3 points) and a three-dimensional cube copy (1 point). Multiple aspects of executive functions are assessed using an alternation task adapted from the trail-making B task (1 point), a phonemic fluency task (1 point), and a two-item verbal abstraction task (2 points). Attention, concentration, and working memory are evaluated using a three-item confrontation naming task with low-familiarity animals (3 points), repetition of two syntactically complex sentences (2 points), and the aforementioned fluency task. Finally, orientation to time and place (6 points). Low score is worse outcome.
5 secondary outcomes
Change in memory
Time frame: After 3 -week intervention program (T1), 6 months (T2) and 1 year (T3) after the end of intervention program
Change in executive functions
Time frame: After 3 -week intervention program (T1), 6 months (T2) and 1 year (T3) after the end of intervention program
Change in mood (assessed by Beck Depression Inventory - BDI)
Time frame: After 3 -week intervention program (T1), 6 months (T2) and 1 year (T3) after the end of intervention program
Change in Quality of Life (assessed by Short Form-36 Health Survey - SF - 36)
Time frame: After 3 -week intervention program (T1), 6 months (T2) and 1 year (T3) after the end of intervention program
Change in the evolution of cognitive profile (assessed by Clinical Dementia Rating Scale - CDR)
Time frame: After 3 -week intervention program (T1), 6 months (T2) and 1 year (T3) after the end of intervention program
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2019.
- Background: PubMed 28735855Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, Ballard C, Banerjee S, Burns A, Cohen-Mansfield J, Cooper C, Fox N, Gitlin LN, Howard R, Kales HC, Larson EB, Ritchie K, Rockwood K, Sampson EL, Samus Q, Schneider LS, Selbaek G, Teri L, Mukadam N. Dementia prevention, intervention, and care. Lancet. 2017 Dec 16;390(10113):2673-2734. doi: 10.1016/S0140-6736(17)31363-6. Epub 2017 Jul 20. No abstract available.
- Background: PubMed 25405755Lampit A, Hallock H, Valenzuela M. Computerized cognitive training in cognitively healthy older adults: a systematic review and meta-analysis of effect modifiers. PLoS Med. 2014 Nov 18;11(11):e1001756. doi: 10.1371/journal.pmed.1001756. eCollection 2014 Nov.
- Background: PubMed 24998488Coyle H, Traynor V, Solowij N. Computerized and virtual reality cognitive training for individuals at high risk of cognitive decline: systematic review of the literature. Am J Geriatr Psychiatry. 2015 Apr;23(4):335-359. doi: 10.1016/j.jagp.2014.04.009. Epub 2014 May 14.
- Background: PubMed 31256092Bernini S, Alloni A, Panzarasa S, Picascia M, Quaglini S, Tassorelli C, Sinforiani E. A computer-based cognitive training in Mild Cognitive Impairment in Parkinson's Disease. NeuroRehabilitation. 2019;44(4):555-567. doi: 10.3233/NRE-192714.
- Background: PubMed 26441526Prehn K, Floel A. Potentials and limits to enhance cognitive functions in healthy and pathological aging by tDCS. Front Cell Neurosci. 2015 Sep 14;9:355. doi: 10.3389/fncel.2015.00355. eCollection 2015.
- Background: PubMed 26022770Hsu WY, Ku Y, Zanto TP, Gazzaley A. Effects of noninvasive brain stimulation on cognitive function in healthy aging and Alzheimer's disease: a systematic review and meta-analysis. Neurobiol Aging. 2015 Aug;36(8):2348-59. doi: 10.1016/j.neurobiolaging.2015.04.016. Epub 2015 May 1.
- Background: PubMed 21514249Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21.
- Background: PubMed 22275317Litvan I, Goldman JG, Troster AI, Schmand BA, Weintraub D, Petersen RC, Mollenhauer B, Adler CH, Marder K, Williams-Gray CH, Aarsland D, Kulisevsky J, Rodriguez-Oroz MC, Burn DJ, Barker RA, Emre M. Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines. Mov Disord. 2012 Mar;27(3):349-56. doi: 10.1002/mds.24893. Epub 2012 Jan 24.
- Derived from this study: PubMed 34156651Rodella C, Bernini S, Panzarasa S, Sinforiani E, Picascia M, Quaglini S, Cavallini E, Vecchi T, Tassorelli C, Bottiroli S. A double-blind randomized controlled trial combining cognitive training (CoRe) and neurostimulation (tDCS) in the early stages of cognitive impairment. Aging Clin Exp Res. 2022 Jan;34(1):73-83. doi: 10.1007/s40520-021-01912-0. Epub 2021 Jun 22.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elena Sinforiani, MD principal investigator
Struttura Semplice Neuropsicologia Clinica/Centro UVA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CoRe software training plus non-invasive brain stimulation techniques (anodical tDCS / rTMS) in people with Cognitive Impairment, run by IRCCS National Neurological Institute "C. Mondino" Foundation at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Cinzia Fattore, MD (0039 0382 380385, cinzia.fattore@mondino.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in global cognitive functioning measured by Mini-Mental State Examination (MMSE) (time frame: After 3 -week intervention program (T1), 6 months (T2) and 1 year (T3) after the end of intervention program). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04118686, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2019.