Falls prevention through physical and cognitive training (falls PACT) in older adults with mild cognitive impairment: a randomized controlled trial protocol

Physical exercise is one of the most common interventions used to prevent falls in the geriatric population [11, 12]. Exercise as a single intervention or as a component of a multifactorial intervention has been proven effective in reducing rate of falls and risk of falls among the general population of older adults living in the community [11, 12]. To successfully reduce falls incidence in older people, a minimum of three hours every week [11] for at least 40 h of exercise over the course of interventions is needed [13]. The optimal exercise frequency is purported to be three times per week [13]. Designing the program to comprehensively include balance, strength, endurance, and flexibility, but with at least one-third is focused on balance training, is recommended [11‐13].

For community-dwelling older adults with cognitive impairment, there is promising evidence that exercise as a standalone intervention may prevent the occurrence of falls, however, this entails confirmation with more trials [11]. Older adults with MCI, in particular, are faced with certain cognitive hindrances when engaging in exercise such as learning new routines and remembering how to perform them accurately [14]. These cognitive obstacles were observed in spite of previous involvement in similar exercise regimens [15].

In terms of the effect of exercise on cognitive function, contrasting findings were reported. One meta-analysis concluded that there is very limited evidence that exercise improves cognitive function in MCI [16]. A more recent systematic review, however, reported positive effects of exercise on global cognition, executive function, attention and delayed recall in older persons with MCI [17]. Specifically engaging in aerobic exercise (walking, dancing, jogging, Tai Chi) at 60–80% maximum heart rate or > 3 metabolic equivalents has resulted to improved cognitive ability of older adults with MCI [18]. On the other hand, doing functional tasks as a form of exercise has been found to provide cost-effective and sustainable improvements in global cognitive function, memory and executive function in community-dwelling older persons with MCI [19]. These benefits were obtained with the use of physical exercise alone and without formal cognitive training of the participants.

Cognitive training, which usually involves guided practice on a set of specific tasks designed to solicit targeted cognitive functions [20], has been proven effective in healthy older adults in improving cognitive functioning [21‐23] and may also be an effective preventive strategy in the onset of any cognitive decline among older persons [24]. Impairment in executive function is found to be independently associated with a heightened risk for falls and fall-related injuries in community-dwelling older adults [25, 26]. Executive function (EF) is a high-level subcomponent of cognition that regulates processes including working memory, inhibition and cognitive flexibility which are important in adapting efficiently to changing environment and task [27]. Targeting particularly executive dysfunction in cognitive training has been recommended to decrease the rate of falling in the geriatric population with cognitive impairment due to Alzheimer’s disease [28]. This strategy may help decrease falls rate in Alzheimer’s disease by addressing the perceptual-motor integration problem that causes instability in performing certain automatic tasks such as walking that eventually results in a fall [29].

In older adults with MCI, cognitive training has resulted in beneficial effects on cognitive function such as attention, orientation, perception, language, memory and executive function [23, 29]. However, there are a lot of inconsistencies in terms of the format (group versus individual), number and duration of treatment sessions in the previously implemented programs [23, 30]. It was found out that there is no dose-response relationship between the total training hours and the effectiveness of intervention on cognitive outcomes [23]. But, it seems that fewer sessions, about 6–20 sessions only, are considered more cost-effective [30]. Furthermore, cognitive training greater than 12 weeks duration did not show better outcomes compared to programs with ≤12 weeks duration, where the risk of attrition is also reduced [30].

A treatment paradigm that could potentially address both cognitive decline and risk of falls in MCI is to combine physical exercise and cognitive training. Neuroplastic changes in the brain may be more evident if these two interventions are integrated. In an animal study, it was suggested that physical activity and cognitive stimulus had a complementary effect on neurogenesis [31]. In humans, combined physical/cognitive training had an effect on brain functional plasticity. The Train the Brain Consortium (2017) reported that there were lesser neural resources utilized, which means better neural efficiency, for the same behavioral activities in older individuals with MCI on combined interventions training compared to those without training [32]. Aside from neural efficiency, increased cerebral blood flow in the parahippocampal area in the medial temporal lobe of the brain was more evident after combined interventions. This area of the brain subserves non-verbal spatial information processing [32].

Among healthy older adults, combined interventions in the form of stationary cycling with virtual reality [33], and integrated aerobic exercise and mental training [34] resulted in better effects in their cognitive performance compared when the interventions were delivered separately. Similarly, progressive balance training with dual and multi-task exercises lead to positive short and long-term benefits in gait, balance control and fear of falling among community-dwelling healthy older adults with increased risk of falling [35].

For older adults with cognitive impairment, the effect of combined physical and cognitive training is rather inconsistent. In older persons with Parkinson’s disease, the multimodal cognitive program, including cognition, transfer training, psychomotor and endurance, had superior effects in cognitive function compared to paper-and-pencil-based cognitive training only [36]. In older adults with MCI, cognitive status was significantly improved following a 7-month combined physical-cognitive training and music therapy compared to no training [32]. Simultaneous physical and cognitive training by dual-tasking in older persons with MCI also resulted in significantly better cognitive outcomes compared to a waitlist group [37] or an education control group [38].

On the contrary, a study that combined resistance training and cognitive training in older adults with MCI concluded that doing high-intensity resistive training alone for six months lead to significant increase in global cognitive function, memory and executive function while participating in combined training unexpectedly and significantly reduced the benefits of isolated progressive resistance training on executive and global cognitive function [39]. In another study also involving older persons with MCI, dual modality cognitive-physical training and single modality interventions of cognitive training alone or physical exercise alone resulted in no significant differences in cognitive outcome measures [40]. In a systematic review, both older adults with and without cognitive impairment gained improvements in cognitive functions and functional status from combined physical exercise and cognitive training interventions [41]. However, the evidence is lacking to ascertain the superiority of combined interventions when compared to active control groups. More studies with good methodological quality are warranted to explore the potential benefits of this new treatment approach [41].

The link connecting the improvements in cognitive function and physical factors after undergoing physical exercise and cognitive training, singly delivered or in combination, to the reduction of falls and the decrease in falls risk in the geriatric population, particularly to those with MCI, is yet to be established.

Thus, this study primarily aims to determine the effectiveness of combined physical and cognitive training on preventing falls and reducing the risk of falls among community-dwelling older adults with MCI. The hypothesis is that an intervention that incorporates elements of both physical exercise and cognitive training in one treatment program is more effective compared to physical exercise or cognitive training alone in preventing the occurrence of falls and in decreasing the risk of falls in older adults with MCI living in the community.

Community-dwelling older adults, both male and female, aged 60 or above with MCI will be included. They will be recruited from community sites in Manila, Philippines through the assistance of local coordinators of the Office of Senior Citizens Affairs (OSCA) of Manila. The presence of MCI will be established following the criteria of Winblad et al. (2004) [42]. A person is diagnosed to have MCI if 1) the cognitive function is not normal nor demented; 2) there is subjective report of the individual and/or informant on declining cognitive function compared to five years ago [5] on objective cognitive tasks; and 3) the performance of basic ADLs is preserved with only minor problems doing complex instrumental ADLs [42]. Not normal cognitive function or presence of mild impairment will be based on Montreal Cognitive Assessment (MoCA) score of < 26 [43]. Not demented will be based on not having a medical diagnosis of dementia or Alzheimer’s disease [5, 44]. Normal function in ADL and no or minimal impairment in instrumental ADL will be based on Katz ADL Scale [45] and Lawton Instrumental Activities of Daily Living (IADL) Scale [4]. A trained neurologist-psychiatrist will examine the participants to provide the final diagnosis of MCI and give them the clearance to participate in the exercise. Only ambulatory older adults, with or without an assistive device, will be included since the interventions are community-based.

Older adults will be excluded if they have a diagnosis of dementia or Alzheimer’s disease; had history of major medical conditions such as cerebrovascular disease, cardiopulmonary condition, serious musculoskeletal disease, cancer, major psychiatric condition; have severe visual and/or hearing impairment; or are illiterate that will hinder them in participating fully and safely in the exercise and/or cognitive training programs. Furthermore, those who have been taking medications such as sedatives, antidepressants, diuretics, anti-epilepsy that might affect their cognitive function will not be included. Deliberately providing false information is a reason for termination of participation. Elevation of blood pressure beyond the expected increase due to exercise or the presence of fever and body pains for several days due to other causes may be reasons for withdrawal to participate. To enhance adherence to the intervention, participants will be receiving a travel allowance and light refreshments every time they attend sessions.

This proposed study is a randomized controlled trial using a 4-group design including three intervention groups (physical training alone or cognitive training alone, or combined physical and cognitive training) and one waitlist control group. The study will comply with the principles of the Declaration of Helsinki 2013 and Good Clinical Practice Guidelines. Ethics approval was secured from the Human Subjects Ethics Sub-committee of the Hong Kong Polytechnic University-Department of Rehabilitation Sciences (HSEARS20170402001) and the Ethics Review Committee of the University of Santo Tomas-College of Rehabilitation Sciences (FI-2017-002). The SPIRIT guidelines were followed in the design of this study protocol.

Trained study personnel will interview the participants using questionnaires to obtain their demographic information and medical history, physical activity level and history of falls, and will conduct cognitive and physical performance tests to determine their eligibility to participate in this study. Only those who signed the informed consent will be included in this study.

Random allocation will be carried out by a third party not involved in the study by random draw to blindly allocate each participant to one of the four groups. To minimize experimental contamination through social interaction and communication among the participants, the interventions will be delivered at different sites.

Measurement points include baseline/pre-intervention, post-intervention, and six months follow-up assessments and will be conducted by trained study personnel blinded to the randomization assignment. Physiotherapists and occupational therapists who will be administering the interventions will not be involved in the outcome assessment. They will also have workshops and discussions to standardize the administration of the different training programs. After the intervention period, aside from a calendar-diary, monthly phone calls will also be done to follow up the participants about their fall status, physical activity, and exercise behavior. Figure 1 illustrates the study flow. Appendix shows the timeline of the study.

The sample size and power calculations will be based on fall rate which is the primary outcome of the study. Using statistical software Gpower 3.1.9.2, a priori power analysis was conducted using the computed effect size (Cohen’s d = .39) from Trombetti et al. (2011) [46]. Assuming 80% power with 5% Type 1 error and four groups, the calculated total sample size is 80. Considering a 16% dropout rate (Trombetti et al., 2011) [46], the total number of participants is inflated to 93. There should be at least 23 participants per group.

The following primary and secondary outcome measures will be performed by trained assessors blinded to the group allocation. Measurements will be taken at baseline, at the conclusion of the intervention period, and 6 months post-intervention. Additional information regarding the exercise behavior and the physical and social activities participated in by the eligible participants in the last 6 months will be obtained during the 6 months post-intervention follow-up assessments [52].

The secondary measures will be assessments that evaluate overall fall risk, cognitive, physical and psychological factors related to falls.

Collected data using a paper-based assessment kit will be encoded in MS Excel by one study personnel blinded to the group allocations. This will be double-checked by another research assistant. The privacy and confidentiality of the participants will be kept by making no personal information available to the public. Signed consent forms and filled data collection sheets will be stored in a locked cabinet. The encoded data will be kept in a password-protected computer folder. Data will be stored for five years and will then be deleted. In the event of any publication involving this study, the participants’ identities will remain confidential. Aside from the researchers, the study monitors from the ethics committee will be granted monthly direct access to the records for purposes of procedure and data verification and interim analyses. Any modifications in the study procedure will be reported to the Human Subjects Ethics Sub-committee of The Hong Kong Polytechnic University-Department of Rehabilitation Sciences and the Ethics Review Committee of the University of Santo Tomas-College of Rehabilitation Sciences, and to ClinicalTrials.​gov. To disseminate the findings of this research, the results and implications will be reported to the participants and presented formally in professional conferences, and published in a reputable journal.

Participants might experience fatigue while doing exercise, and therefore adequate rest periods and breaks will be provided as needed. Vital signs will be constantly monitored before, during and after the interventions every session. Light refreshments will be provided to prevent dehydration. In some activities that will challenge their balance, trained therapists will be close by to provide support to prevent them from falling. The calendar-diary will also be used to monitor changes in health status and record adverse events every session during the intervention period and then every month after the intervention phase. In the case of any untoward incident like dizziness, injuries, or falls during the conduct of the study, appropriate first aid, medical attention or referral to a clinic or hospital, will be immediately done to the participant as soon as reported.