Effects of the multimodal exercise program on spatiotemporal gait parameters
This multicenter randomized controlled trial aimed to investigate the effectiveness of a dementia-specific MEP, which combined motor and cognitive tasks, on gait performance. As we did not observe any statistically significant time*group effects, our primary hypothesis that a 16-week MEP may have a differential effect on gait performance in IWD as compared to conventional treatment alone could not be confirmed. This may be explained by the heterogeneity of the study sample or the relatively low amount of walking tasks included in the intervention.
With regard to sample characteristics as well as motor, cognitive, and gait performance at baseline, we observed large standard deviations indicating that the sample of IWD was highly heterogeneous in our study (see Tables 2 and 3, and Additional file 4). Due to this large heterogeneity, it was very difficult to adequately tailor one standardized physical activity intervention to the needs of all participants, and we postulate that there is likely no standard physical activity intervention that fits all IWD.
With respect to the applied intervention, an analysis of components of the MEP showed that it did not include a large amount of specific walking tasks. Even though we had planned to increase the number of exercises focusing on walking throughout the intervention, this was often not possible due to our principle of ensuring the safety of participants at all times during the MEP. Additionally, we assumed that tasks aiming to improve balance, mobility, strength and function of lower limbs may be sufficient to positively affect gait performance [75,76,77,78]. However, based on our findings, this assumption could not be confirmed. Thus, including a sufficient amount of specific walking exercises should be ensured in future physical activity interventions that aim at improving gait performance.
Differences in characteristics between positive, negative, and non-responders and impact of changes in underlying motor and cognitive performance on changes in gait performance
Despite not having observed positive overall effects, additional analyses showed that between 61 and 81% of participants in the IG improved or maintained their gait performance after participating in the MEP. In studies among IWD, who usually experience rapid decline of motor, cognitive, and gait performance , even maintaining the current levels of performance is indicative of a beneficial effect. In order to better understand the prerequisites and impacts to induce such benefits from physical activity interventions, we conducted secondary analyses that focused on examining differences of baseline performance and sample characteristics between positive, non-, and negative responders, and also considered impacts of underlying changes in motor and cognitive performance on changes in gait performance.
As compared to negative and non-responders, positive responders primarily showed lower gait performance at baseline and additionally demonstrated lower performance in single motor assessments. Moreover, non-responders were less cognitively impaired than negative responders. Accordingly, low motor and gait performance as well as increased cognitive performance appear to be prerequisites for IWD in order to benefit from the MEP. Additionally, stepwise regression analyses supported the hypothesis that changes in underlying motor and cognitive performance have an impact on changes in gait performance. Indeed, the respective statistical models explained between 12.6 and 39.4% of the overall variance.
Focusing on prerequisites related to the effectiveness of the MEP, the observed lower motor performance of positive responders compared to non- and negative responders at baseline may indicate a greater potential for performance improvements for participants who enter the intervention with lower baseline levels of motor performance. As described above, it was not always possible to include more complex walking tasks throughout our intervention. Accordingly, the requirements necessary to induce improvements may not have reached critical thresholds in all participants. Moreover, our findings support the assumption that IWD must have sufficient cognitive capacities in order for them to successfully participate in physical activity interventions. In contrast, severe cognitive impairments may affect IWD in following instructions or adequately performing exercise tasks. Individuals with more severe cognitive impairments may depend even more on specific didactic concepts.
Surprisingly, we observed a statistically significant higher cognitive performance only among non-responders and in single task conditions. Positive responders also showed higher cognitive performance than negative responders, albeit not reaching statistical significance possibly due to a relatively lower number of positive responders. When we compared cognitive performance of participants in single and dual task conditions, we observed that participants with more severe cognitive impairments were less likely to successfully perform the walking with additional dual tasks (single task: MMSE = 16.9 (4.5), 45% with MMSE < 17; dual task: MMSE = 18.4 (4.0)/17.8 (4.3) 29%/26% with MMSE < 17). Accordingly, cognitive performance of participants who completed dual task conditions was more consistent and this may explain why cognitive performance did not differ between positive, non-, and negative responders.
Stepwise regression analyses showed differential impacts of changes in underlying motor and cognitive performance, depending on spatiotemporal gait parameter and walking condition. As expected, improvements in gait performance were associated with improvements in underlying motor and cognitive performance. The observed opposite relation between stride length in dual task naming animals condition and the Clock Drawing Test requires further examination. The amount of explained variance was higher for dual task than single task conditions. In dual task conditions, changes in motor and cognitive performance were statistically significant predictors, while gait parameters in the single task condition were only affected by motor predictors. Accordingly, changes in cognitive performance may be particularly required for changes in dual task conditions, which are primarily determined by motor and cognitive demands. Dual task performance while walking is highly relevant with regard to fall prevention, and worse performance is associated with increased risk of falls . Thus, fall prevention interventions should consider dual tasks and include both, motor and cognitive exercises.
At the motor level, changes in strength and function of lower limbs as well as mobility were statistically significant predictors. The related performance was assessed with modified 30s CST, modified SPPB, which considers balance, mobility, and strength, and TUG. These findings indicate that there are several motor impacts related to changes in gait performance, and further emphasize the importance of multimodal interventions. Unexpectedly, changes in balance performance were not a statistically significant predictor. However, we assessed balance only in static positions, which may have different demands as compared to dynamic balance conditions while walking [79, 80]. Moreover, the frequent use of walking aids may have eliminated the potential impact of changes in balance performance . Assumptions at the cognitive level could not be made, as cognitive predictors differed across established regression models.
Comparison with previous studies
The findings of this randomized controlled trial are not fully in line with those observed in previous studies. In contrast to previous studies, which predominantly reported positive effects for stride length and stride time in single and dual task conditions [39,40,41,42,43,44,45,46], our investigation did not confirm the effectiveness of an MEP for these spatiotemporal gait parameters. In accordance with 20 previous studies, we did not observe statistically significant effects on walking speed [24,25,26,27,28,29,30,31,32,33,34,35,36,37,38, 42, 44, 47, 48] and percent of double support [44, 45], while twelve others did for single [17,18,19,20,21,22,23, 40, 41, 43, 46] and dual task conditions .
These inconsistent findings may be related to different study designs, gait assessments, interventions, and sample characteristics between previous research and our study. For example, studies considering walking speed in single task condition and reporting positive effects are characterized by more walking tasks included in the intervention [17, 19,20,21, 23, 40, 41, 43], higher exercise intensities [19, 20, 43], participants with less cognitive impairments [19, 21, 43], worse baseline walking performance [17, 18, 22, 23, 46], better baseline walking performance [19, 20, 43], as well as assessing gait performance during fast walking [27, 29, 31, 48] compared to our study. While the first four observations reflect the results and indications of this study, better baseline walking performance may enable instructors to implement higher exercise intensities and larger amounts of specific walking tasks. Moreover, fast walking speed may be a more specific indicator for changes. However, these indications need to be considered with caution, as several impacts and the heterogeneity of previous studies hamper comparisons.
Heterogeneity is a challenge also occurring in other studies. Some differences between our study and studies showing positive effects (considering walking speed in single task condition) may be due to less cognitive impairments of participants [19, 21, 43], only including participants able to walk without walking aids [19, 40, 43, 46], hints of enhanced individual supervision [20, 21, 23, 40, 41, 46], or classification in homogeneous subgroups . One may argue that the negative impact of heterogeneity is less critical in groups of participants in mild stages of dementia, as these participants are rather able to implement different instructions. Moreover, it can be assumed that participants not dependent on walking aids are less likely to fall. Accordingly, it is possible to apply the same exercise for those participants, even if they differ in their walking performance. In contrast, participants with enhanced fall risks rely on several modifications due to safety reasons. Besides these differences related to sample characteristics, an enhanced individual supervision allows the individualization of exercise tasks and adapted support. However, such concepts cannot always be transferred into practice because of limited personal resources. Accordingly, new approaches feasible in group settings are necessary, such as the classification of homogeneous subgroups.
In addition, the etiology or underlying causes of dementia, as well as frequency and duration of physical activity interventions differ considerably among previous studies and make a comparison somewhat difficult. For example, previous studies have included participants with AD, whereas other have included individuals with mixed etiologies or have not reported etiologies. Due to differences in underlying pathologic changes, various etiologies may have a differential impact on the effects of physical activity on motor or cognitive performance. In addition, duration and frequency of physical activity interventions in previous studies vary between 3 weeks and 36 months, with sessions carried out once per week to twice daily. However, most studies applied a protocol consisting of two to three sessions per week for at least 12 weeks. This is in line with recommendations of recent systematic reviews and seems to be most effective in eliciting any effects on motor and cognitive performance in IWD [82,83,84,85,86]. Accordingly, our intervention had a duration of 16 weeks with a frequency of two sessions per week.
To the best of our knowledge, there are no published studies that compared the characteristics of positive, non-, and negative responders or investigated impacts of changes in underlying motor and cognitive performance on changes in gait performance.
Strengths and limitations
With this multicenter randomized controlled trial, we aimed at conducting high-quality research to investigate the effectiveness of a physical activity intervention on gait performance in IWD. The strengths of the study include the emphasis on high-quality methods and a detailed reporting of our methods and findings . Of note, we had a large sample size of over 300 individuals with mild to moderate dementia, our assessments were deemed adequate for IWD by an expert panel , and our MEP was specifically tailored to fit the needs and characteristics of IWD (please refer to ).
Nevertheless, several limitations pertain. First, multimodal interventions do not allow to unambiguously draw conclusions about causality, i.e. observed effects may be related to the MEP itself, but could also be due to the group setting and thus enhanced social interaction, or additional attention that participants received from the exercise instructors. Therfore, additional control conditions such as non-exercise groups that engage in mentally stimulating or social activities such as singing or playing cards together could have helped to limit this potential bias. Second, insufficient intensity and specificity may be potential limitations of the MEP related to the primary aim to improve spatiotemporal gait parameters. Several factors, such as characteristics of participants, group setting, or field conditions did not allow us to reach higher intensity levels, a larger amount of specific walking tasks, and progression of the MEP as initially planned. Importantly, the MEP was mainly performed in a seated position which may have limited impact on gait performance albeit we chose exercises with medium to submaximal intensity. One potential strategy to overcome this limitation is to conduct exercise interventions with smaller groups to ensure safety of participants while reaching higher intensities at the same time. In line with this, the secondary analysis showed that participants who benefitted had a lower motor baseline performance. Future interventions need to better consider individual prerequisites of participants and accordingly adapt intensity, specificity, as well as progression of exercises. Third, the assessments to determine motor performance used in this study are widely used in research but have not been specifically developed for IWD. Even though we intensively discussed the adequateness of these assessments during an expert panel  and carefully selected the most appropriate ones, we cannot rule out the possibility that the use of existing assessments not specifically designed for IWD may have led to biased results. For example, these assessments often do not sufficiently take into account fluctuating daily forms and motivational aspects that may play a role when examining IWD. Accordingly, results could reflect unfavorable conditions, reduced motivation, or lack of interest instead of actual motor performance. Therefore, it is critically important for future research to explore tailored motor assessments for use in IWD. Finally, our study sample included participants that did not have a confirmed diagnosis of dementia, in most cases due to limited financial resources or access to diagnostic tools and assessments. This may have an impact on the interpretability of findings.