Exercises for Rehabilitation of COgnition and Lifestyle Enhancement in Patients With Mild Cognitive Impairment

Официальное название

Sviluppo di un Intervento di Riabilitazione Cognitiva Applicabile e Sostenibile Nella Pratica Clinica Per i Pazienti Con Mild Cognitive Impairment

Обзор

Mild Cognitive Impairment (MCI) is a clinical condition with a heterogeneous etiology and clinical course characterized by objective cognitive deficits not severe enough to cause clear functional limitations or to warrant a diagnosis of dementia. Since MCI represents a risk factor for progression to various forms of dementia, timely preventive intervention is essential, although outpatient cognitive rehabilitation for this population is still limited by issues related to service accessibility. This study aims to investigate the effectiveness of a multimodal group cognitive rehabilitation intevention designed to be accessible for patients with MCI and sustainable in clinical practice. The primary objective of the study is to evaluate the effects of the intervention on cognitive, behavioural, and functional profile of patients with MCI, compared with an active control group. Outcome measures will be collected for all participants at T0 (baseline), T1 (after 12 weeks of intervention), and T2 (3 months after the end of the intervention and approximately 6 months from baseline), in order to assess both short-term and long-term effects of the intervention. The secondary objective is to explore the relationship between changes in outcome measures in the experimental group following the intervention and patients' demographic and clinical characteristics, with the aim of identifying potential predictors of a greater response to the intervention. Treatment accessibility, which guided the study design, will be evaluated though dropout and attendance rates, use of the provided tools and responses to the final satisfaction questionnaire. The experimental group will receive a multimodal cognitive rehabilitation intervention, including (a) a multi-domain cognitive training and (b) a lifestyle intervention, consisting of psychoeducational sessions on neuroprotective factors and supported by the use of a web-based application accessible via computer and tablet. The intervention program will be delivered in small groups, with two 60-minute sessions per week over 12 weeks. The intervention was designed to enhance accessibility and sustainability by limiting intervention intensity and duration, using technology, and delivering group-based rehabilitation in groups that are not highly homogeneous. This approach is expected to result in a better cost-benefit balance and greater transferability to clinical practice. The control group will receive an informational booklet on neuroprotective factors, including practical daily-life recommendations to reduce risk profiles. Forty patients with MCI and their informants will be recruited and randomly assigned to the experimental or control group. Participants in the experimental group will be further divided into small subgroups based on the presence of memory impairment.

Подробное описание

Mild Cognitive Impairment (MCI) is a clinical condition with a heterogeneous etiology and clinical course, characterized by objective cognitive deficits that are not severe enough to cause clear functional limitations or to warrant a diagnosis of dementia. MCI represents a risk factor for progression to dementia: annual conversion rates vary widely across studies, ranging from 2% to 31%, with an average of around 10%. In addition to patients with MCI who progress to dementia, some may show persistent but non-progressive cognitive deficits, while others may even return to normal cognitive functioning, while remaining at higher risk of future cognitive decline. In this context, early diagnosis and timely interventions to reduce the risk of dementia are crucial.

Various interventions have been proposed for the non-pharmacological management of MCI. A review of 14 studies on cognitive rehabilitation in MCI indicated that multimodal interventions and lifestyle-based approaches are the most promising in terms of improving objective cognitive performance (Huckans et al., 2013). Another meta-analysis on 26 studies confirmed the effectiveness of multimodal interventions, as well as multi-domain and memory-specific approaches (Sherman et al., 2017). Other factors, such as MCI subtype, intervention format (individual, group, or computerized), type of control (passive vs. active), follow-up duration (less or more than two weeks), and adjustment for repeated testing showed no appreciable effects on the outcomes. Regarding the dose-response effect of treatment, there is no consensus on the amount of training required for significant benefits. A review and meta-analysis on the relationship between treatment dose (defined by frequency, intensity, and duration) and outcomes found the most robust effects for multi-component approaches delivered 1-2 times per week, 30-60 minutes per session, over a total duration of 8-16 weeks (Shao et al., 2022). Finally, given the increasing role of information and communication technologies in healthcare, cognitive rehabilitation has started to include eHealth tools, which are also suitable for older adults and patients with MCI. Despite the encouraging results reported in the literature, outpatient cognitive rehabilitation for MCI is still limited by issues related to service accessibility.

This study aims to investigate the effectiveness of a multimodal group cognitive rehabilitation intevention designed to be accessible for patients with MCI and sustainable in clinical practice.

The primary objective of the study is to evaluate the effects of the intervention on cognitive, behavioural, and functional profile of patients with MCI, compared with an active control group. Outcome measures will be collected for all participants at T0 (baseline), T1 (after 12 weeks of intervention), and T2 (3 months after the end of the intervention and approximately 6 months from baseline), in order to assess both short-term and long-term effects of the intervention. The secondary objective is to explore the relationship between changes in outcome measures in the experimental group following the intervention and patients' demographic and clinical characteristics, including age, sex, cognitive reserve, MCI subtype, and time since diagnosis, with the aim of identifying potential predictors of a stronger response to the treatment. Treatment accessibility, which guided the study design, will be evaluated though dropout and attendance rates, use of the provided tools and responses to the final satisfaction questionnaire.

The experimental group will receive a multimodal cognitive rehabilitation intervention, including (a) a multi-domain cognitive training and (b) a lifestyle intervention, consisting of psychoeducational sessions on neuroprotective factors and supported by the use of a web-based application accessible via computer and tablet. The intervention program will be delivered in small groups formed according to the presence of memory impairment, with two 60-minute sessions per week for a total of 12 weeks. The multimodal approach, including multi-domain cognitive rehabilitation and lifestyle interventions, was selected based on the best available evidence in the literature. A multi-domain format also makes the program well-suited for group delivery, where some heterogeneity in cognitive profiles can still be expected among participants within each subgroup. The limited intervention intensity and duration, the use of technology, and the use of groups not highly homogeneous aimed to enhance accessibility, sustainability and transferability in clinical practice.

The control group will receive an informational booklet on the 14 protective factors for dementia described by the Lancet Commission, including practical daily-life recommendations to reduce risk.

This study has a mixed design consisting of a between-subjects factor ("Group," with two levels: experimental and control) and a within-subjects factor ("Assessment Time," with three levels: T0, T1, and T2).

To evaluate the effect of the treatment on outcome measures assessing the cognitive, behavioral, and functional profile of patients with MCI, compared with an active control group, a series of repeated-measures analyses of variance (ANOVA) will be performed. In the event of a violation of the assumption of normality, assessed using the Kolmogorov-Smirnov test, either data normalization procedures (e.g., logarithmic transformation) or non-parametric tests (e.g., Kruskal-Wallis) will be adopted.

To explore the relationship between changes in outcome measures in the experimental group and patients' demographic and clinical data, correlations will be conducted between the difference in scores obtained at T0 and T1 and the variables age, cognitive reserve, and time since diagnosis; an independent-samples t-test will be performed for the variable gender; and a one-way ANOVA will be conducted to evaluate the MCI subtype effect.

Sample size was determined through a power analysis conducted with the G\*Power software, with a 10% oversampling to compensate for potential dropouts. Forty patients with MCI and their informants will be recruited and randomly assigned to the experimental or control group using stratified randomization based on memory impairment. Participants in the experimental group will be further divided into small subgroups according to the stratification factor.

Вмешательства

• Поведенческое Multimodal Group Cognitive Rehabilitation Intervention
  The multimodal Group Cognitive Rehabilitation Intervention included a multi-domain cognitive training and a lifestyle intervention. The exercise package adopted in the multi-domain cognitive training will be adapted from that used in a previous cognitive enhancement study by Tagliabue and colleagues (2018) conducted in neurologically healthy adults over 60. The lifestyle intervention will consist of psychoeducational sessions on neuroprotective factor and supported by the use of a web-based appl
• Поведенческое Active Control
  The control group will receive an informational booklet on the 14 protective factors for dementia described by the Lancet Commission in 2024, including practical daily-life recommendations to reduce risk. An ad hoc questionnaire will be administered to the patients assigned to the control condition and to one of their family members every two weeks for a period of 12 weeks, in order to monitor patients' efforts and progress in following the recommendations provided.

Первичные конечные точки

• Montreal Cognitive Assessment (MoCA) score [Срок оценки: Data will be collected at T0 (baseline), T1 (upon completion of the 12-week treatment), and T2 (six months after baseline).]
• Forward Digit span [Срок оценки: Data will be collected at T0 (baseline), T1 (upon completion of the 12-week treatment), and T2 (six months after baseline).]
• Copy of the Modified Taylor Complex Figure [Срок оценки: Data will be collected at T0 (baseline), T1 (upon completion of the 12-week treatment), and T2 (six months after baseline).]
• Rey Auditory Verbal Learning Test (RAVLT) [Срок оценки: Data will be collected at T0 (baseline), T1 (upon completion of the 12-week treatment), and T2 (six months after baseline).]
• Boston Naming Test (BNT) [Срок оценки: Data will be collected at T0 (baseline), T1 (upon completion of the 12-week treatment), and T2 (six months after baseline).]
• Multiple Features Target Cancellation (MFTC) [Срок оценки: Data will be collected at T0 (baseline), T1 (upon completion of the 12-week treatment), and T2 (six months after baseline).]
• Raven's Colored Progressive Matrices (CPM) [Срок оценки: Data will be collected at T0 (baseline), T1 (upon completion of the 12-week treatment), and T2 (six months after baseline).]
• Semantic and phonemic fluency [Срок оценки: Data will be collected at T0 (baseline), T1 (upon completion of the 12-week treatment), and T2 (six months after baseline).]
• Trail Making Test (TMT) [Срок оценки: Data will be collected at T0 (baseline), T1 (upon completion of the 12-week treatment), and T2 (six months after baseline).]
• Weigl sorting test (WST) [Срок оценки: Data will be collected at T0 (baseline), T1 (upon completion of the 12-week treatment), and T2 (six months after baseline).]

Вторичные конечные точки (4)

• Functional Activities Questionnaire (FAQ) [Срок оценки: Data will be collected at T0 (baseline), T1 (upon completion of the 12-week treatment), and T2 (six months after baseline).]
• Neuropsychiatric Inventory Questionnaire (NPI-q) [Срок оценки: Data will be collected at T0 (baseline), T1 (upon completion of the 12-week treatment), and T2 (six months after baseline).]
• Geriatric Depression Scale (GDS) [Срок оценки: Data will be collected at T0 (baseline), T1 (upon completion of the 12-week treatment), and T2 (six months after baseline).]
• Self-reported 12-item Short Form questionnaire (SF-12) [Срок оценки: Data will be collected at T0 (baseline), T1 (upon completion of the 12-week treatment), and T2 (six months after baseline).]

Критерии участия

Критерии включения

• Diagnosis of MCI according to the diagnostic criteria of Petersen (2004) and Winblad et al. (2004) and, if applicable (i.e., MCI due to AD), according to those of Albert and colleagues (2011).
• Self-reported basic skills in using technological devices, or access to a close person able to provide assistance.
• Willingness of the patient to report, during the study period, any changes in the dosage of psychotropic drugs or other medications that may affect cognition, such as anticholinergics, opioids, benzodiazepines, antidepressants, muscle relaxants, and antiepileptics.

Критерии исключения

• Parkinson's disease.
• Linguistic single-domain MCI (suspected onset of primary progressive aphasia).
• Other neurological conditions potentially associated with cognitive impairment (e.g., previous stroke or traumatic brain injury).
• Significant laboratory abnormalities potentially associated with cognitive impairment (e.g., low levels of vitamin B12 or folate, or values indicative of thyroid disorders).
• Primary psychiatric disorders.
• Alcohol or substance use disorder in the previous 10 years.
• Severe behavioral disturbances limiting group participation.
• Hearing or visual impairments that may interfere with assessment or treatment.
• Medical conditions that may interfere with completion of the study.
• Exposure, during the study period, to other neuropsychological rehabilitation interventions.
• Patient's refusal to sign the informed consent.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Италия · 2 центра

• Casa di Cura Igea — Milan
• Casa di Cura Igea — Milan

Публикации

• Canevelli M, Di Pucchio A, Marzolini F, Mayer F, Massari M, Salvi E, Palazzesi I, Lacorte E, Bacigalupo I, Di Fiandra T, Vanacore N. A National Survey of Centers for Cognitive Disorders and Dementias in Italy. J Alzheimers Dis. 2021;83(4):1849-1857. doi: 10.3233/JAD-210634. PMID 34459403
• Bruscoli M, Lovestone S. Is MCI really just early dementia? A systematic review of conversion studies. Int Psychogeriatr. 2004 Jun;16(2):129-40. doi: 10.1017/s1041610204000092. PMID 15318760
• Huckans M, Hutson L, Twamley E, Jak A, Kaye J, Storzbach D. Efficacy of cognitive rehabilitation therapies for mild cognitive impairment (MCI) in older adults: working toward a theoretical model and evidence-based interventions. Neuropsychol Rev. 2013 Mar;23(1):63-80. doi: 10.1007/s11065-013-9230-9. Epub 2013 Mar 8. PMID 23471631
• Sherman DS, Mauser J, Nuno M, Sherzai D. The Efficacy of Cognitive Intervention in Mild Cognitive Impairment (MCI): a Meta-Analysis of Outcomes on Neuropsychological Measures. Neuropsychol Rev. 2017 Dec;27(4):440-484. doi: 10.1007/s11065-017-9363-3. Epub 2017 Dec 27. PMID 29282641
• Shao Z, Hu M, Zhang D, Zeng X, Shu X, Wu X, Kwok TCY, Feng H. Dose-response relationship in non-pharmacological interventions for individuals with mild cognitive impairment: A systematic review and meta-analysis of randomised controlled trials. J Clin Nurs. 2022 Dec;31(23-24):3390-3401. doi: 10.1111/jocn.16240. Epub 2022 Jan 30. PMID 35098610
• Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004 Sep;256(3):183-94. doi: 10.1111/j.1365-2796.2004.01388.x. PMID 15324362
• Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, Nordberg A, Backman L, Albert M, Almkvist O, Arai H, Basun H, Blennow K, de Leon M, DeCarli C, Erkinjuntti T, Giacobini E, Graff C, Hardy J, Jack C, Jorm A, Ritchie K, van Duijn C, Visser P, Petersen RC. Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognit PMID 15324367
• Livingston G, Huntley J, Liu KY, Costafreda SG, Selbaek G, Alladi S, Ames D, Banerjee S, Burns A, Brayne C, Fox NC, Ferri CP, Gitlin LN, Howard R, Kales HC, Kivimaki M, Larson EB, Nakasujja N, Rockwood K, Samus Q, Shirai K, Singh-Manoux A, Schneider LS, Walsh S, Yao Y, Sommerlad A, Mukadam N. Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. Lancet. 2024 A PMID 39096926

Идентификаторы

NCT: NCT07517380 · CasaCura

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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