The STRENGTH Project is a prospective randomised controlled trial for the assessment of the effects of a multimodal intervention (i.e., adapted tango, music therapy, engagement in social activities, cognitive stimulation, and psycho-education for 6 months) in subjects with MCI. The study uses a multidisciplinary approach, has a 3-year duration and includes 3 follow-up phases, as indicated in Fig. 1.
Specific aim 1
To study the effect of the multimodal intervention on cognitive performances, functional status, and mobility in MCI subjects by objectively measured parameters (baseline vs. follow-up 1, follow-up 2 and follow-up 3). Mobility (i.e., the ability of a subject to move in his/her environment) is often compromised in elderly people as a consequence of falls and other injuries and this could cause disability and reduced social engagement. The identification of approaches that might prevent motor–cognitive impairment would be a pivotal advancement in the correct management of aging people. Mobility will be evaluated by means of balance, walking test and gait speed; motor–cognitive function, defined as a process of coordination of movements finalized to a particular motor goal, will be measured by means of visual–spatial memory task.
The longitudinal monitoring of cognitive decline and dementia onset will also be implemented (follow-up 2 and follow-up 3).
Specific aim 2
To study the effect of the intervention on psycho-social aspects (e.g., psychological well-being, perceived stress, quality of life, metacognition and mood status), lifestyle characteristics and social network (baseline vs. follow-up 1, follow-up 2 and follow-up 3).
Specific aim 3
To study the effect of the intervention on specific biomarkers (baseline vs. follow-up 1, follow-up 2 and follow-up 3).
Experimental design aim 1
Neuropsychological as well as cognitive and clinical assessment, including cardiovascular, anthropometric, and functional evaluation (e.g., blood pressure, body mass index, ultrasound heart examination through standard echocardiogram, 6-min walk test, gait speed, Berg Balance Scale, handgrip strength, Physical Activity Scale for the Elderly, basic activities of daily living and instrumental activities of daily living) will be carried out (Table 1).
Experimental design aim 2
Enrolled subjects will undergo a detailed protocol of tests and questionnaires to evaluate the following aspects: psychological well-being, perceived stress, quality of life, metacognition, mood status, lifestyle characteristics and social network (Table 1) [20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39].
Experimental design aim 3
The following parameters will be evaluated (details are reported in Fig. 2):
BDNF and ceruloplasmin protein amounts in plasma and their mRNA expression in peripheral blood monuclear cells (PBMC), as the role of peripheral leukocyte dysfunctions in Alzheimer’s disease (AD) development [40, 41] is well known;
mRNA expression in PBMC of 84 key genes involved in AD physiopathology (i.e., beta-amyloid generation, oligomerization, clearance, and degradation; cytoskeleton regulators; synaptic formation; lipid metabolism; apoptosis; cell cycle; cell signalling molecules; transcriptional regulation; oxidative stress; proteases and protease inhibitors);
plasma copper, zinc, and other important micronutrients;
a panel of the most common laboratory parameters.
Recruitment and screening phase
The project started on 1 August 2019 and will last until 31 July 2022. The protocol was approved by the local ethics committee (Bioethics Advisory Committee of IRCCS INRCA, Ancona, Italy; code no. 18006). Three hundred community-dwelling older adults (age ≥ 60 years) with diagnosis of MCI will be enrolled in the Evaluation of dementia’s disease Unit of IRCCS INRCA Hospital in Fermo. MCI will be diagnosed by an extended neuropsychological, clinical and functional evaluation, as well as by neuroimaging and laboratory tests according to diagnostic guidelines . The subjects’ screening will be performed during routine clinical visits applying specific inclusion/exclusion criteria as explicated below. Written informed consent will be obtained from all subjects.
The selected subjects will be randomly allocated to the experimental group (EG, n = 150) or to the control group (CG, n = 150) using a randomisation list.
Inclusion and exclusion criteria
The inclusion criteria comprise: (a) diagnosis of MCI according to the guidelines of the National Institute of Aging ; (b) age 60 years or older, (c) availability during the intervention and testing phases, (d) presence of a caregiver; (e) capability to sign the informed consent.
Exclusion criteria include: (a) presence of sensory-physical deficits that would prevent participation in the study; (b) diagnosis of dementia; (c) presence of serious medical and/or psychiatric conditions.
Sample size calculation
It was based on the null hypothesis that proportion of “success” and “failure” of the intervention is equal in the two groups (i.e., EG and CG), such as OR = 1.
Success and failure were defined on the basis of significant variation in the primary outcomes. Considering an OR = 1.5 indicative of an effect of the intervention, a total sample of 300 subjects allows us to reach a 90% of statistical power using logistic regression at the 5% level (two tailed). Drop-out rate was set at 20%.
A group approach will be used. The intervention will be focused not only on cognitive enhancement, but also on several other aspects, such as advice and psycho-education about healthy lifestyle strategies as well as engagement in leisure activities. EG will be followed by a multidisciplinary team (i.e., psychologists, physicians, nurses, tango instructors and music therapist).
Multimodal intervention will consist in a 20-class syllabus of 180-min session, once a week, including 90 min of adapted tango in accordance to guidelines for physical activity in aging and literature , and, in the same session, further 90 min of comprehensive cognitive intervention for 6 months. The intervention will maximize social participation. Tango will be adapted for older adults with mild cognitive decline and possible mild balance and musculoskeletal impairment. Tango classes will be carried out in a ballroom dancing, led by two experienced and qualified Argentine instructors, with years of certified proficiency and experience in teaching adapted tango methods to elderly people. Classes will take into account the engagement of participants and feasibility. Each class will include about 25 subjects who will dance in pairs with other participants, including instructors, relatives and caregivers. Classes will begin with a phase of warm-up consisting of postural alignment and breathing. The main phase of dance will include enhancement exercises and addition of novel simple steps at each class with varied speeds and rhythms, individually and in pairs, focused on body awareness to educate subjects on prevention of falls, improving mobility, foot placement, whole body coordination, postural control, balance, self-confidence and attention to dance partner. In the last phase, participants can share their experience or ask questions. Possible adverse events will be tracked.
Cognitive intervention will include restorative and compensatory cognitive stimulation, learning mnemonics strategies and music therapy, and will be carried out by two trained psychologists and a music therapist. Intervention will use a metacognitive and a motivational approach applied to subjects with MCI, as described in previous studies [43, 44]. Participants will be also required to perform home exercises, which will include some cognitive stimulation exercises, assigned at the end of each class. Homework will be reviewed by the psychologist during the next class.
An example syllabus of classes is reported in Table 2.
Possible adverse events, adherence to the study and participants’ attrition will be monitored by the principal investigator, adapted tango teachers and other staff members involved in the intervention.
To avoid bias effect of the intervention, GC will receive psycho-education and advice for healthy lifestyle as well as suggestions about the prevention of dementia once a month for 6 months. This group will receive the same clinical monitoring of the general health status, neuropsychological assessment, and cardiovascular parameters of EG. Moreover, they will be informed about the results and possible benefits of intervention, so they could have the possibility to start classes of tango therapy at the end of the study, if they so wish. Indeed, at the end of the study, we expect that this type of program will become a new service offered by IRCCS INRCA to elderly persons with an increased risk of cognitive decline.
Primary outcome: success of the intervention
The response to the intervention will be evaluated using performance in the Corsi test : an increase of at least 1 point will indicate a success based on the enhancement of the spatial learning processes.
the assessment of the intervention effects on lifestyle characteristics as well as psychological, functional and health status;
the assessment of the intervention effects on mobility;
the investigation of the conversion rate from MCI to dementia;
the identification of biomarkers able to mirror the intervention effects.
All data will be collected in a database. A descriptive analysis will be performed to assess the distribution of variables and the presence of possible outliers. The latter will be checked and identified separately and then excluded from the analysis. For normally distributed variables, the comparisons between EG and CG at baseline will be carried out by t Student test or Chi-square test, while those between baseline and follow-up phases by paired sample t test. For non-normally distributed variables, non-parametric tests will be used. Correlation analysis will be performed to evaluate the relationships among variables and general linear models and repeated measures ANOVA will be used to assess the intervention effects adjusted for confounding variables (e.g., gender, age classes, marital status, schooling, drugs, and other variables that will emerge after analysis of secondary outcomes). The SPSS software will be employed.