Ensayos de Integridad en Pilotes Métodos no destructivos

The trial was designed to test an intervention that could be delivered in routine practice. The groups were feasible and the number of AEs was small. From a physiological perspective, the protocol improved physical fitness parameters and walking speed within a range that would be considered worthwhile.53,61,62_{The sample}

was diverse in baseline fitness, as selection was based predominantly on cognition. The exercise protocol was able to account for higher levels of fitness but this was challenging. Our prespecified subgroup analyses suggest that there is no hidden effect within the sample, for example related to baseline mobility, cognition or broad classification of underlying disease. The choice of exercises was also driven by the underlying hypothesis of targeting cognitive impairment. At the time of designing the intervention, most evidence/theory supported aerobic and strength conditioning as the prime pathways to target. We did not include cognitive training or psychomotor training (for example training reaction time) to ensure that the effects of the intervention could be attributed to aerobic and strength training disease pathways. There was no evidence to suggest that balance exercise could modify cognition at the time of developing the intervention and, therefore, it was not included. Although we did not randomise the behavioural elements underpinning the programme and cannot make robust conclusions about the effects of these elements, the good session compliance suggests that the behavioural support was adequate, at least during the first 4 months of the programme.

We monitored the dose delivered through session records. In contrast to similar high-intensity interventions that improve muscle function in older people without dementia,63_{we started with a higher initial strength}

challenge and then progressed participants at a similar rate. The strength dose was higher than that achieved in residential care settings, in which a similar intervention was found to be ineffective in changing cognitive and BADLS status but improved balance.183,184_{Hence, it seems likely that we have delivered sufficient}

dose. Greater compliance with session attendance was associated with further reduction in cognition and even higher doses may incur greater harm.

The results of this trial disagree with those of many small single-centre studies. Study quality is likely to play a role, with many previous studies having uncertain allocation concealment and very poor levels of masking. There are some limitations to our work. We collected physical parameters only in the exercise arm and, hence, cannot conclude definitively that the intervention improves physical fitness. Subgroup analyses may be underpowered, as the proportion of people in the various strata was not distributed optimally,57,183,184_{but the}

direction of effect estimates support our conclusions. In the absence of definitive guidance and rationale, we used a mixed exercise programme, and it may be that longer periods of a single training modality may be effective. However, the feasibility of getting participants to sustain a single type of activity through an entire session is improbable. We did not include an attention control as our intention was for a pragmatic trial. Participants and carers were not masked to allocation and this is an unavoidable limitation.

On a positive note, the qualitative study suggested that in the small sample interviewed, people were able to exercise safely and they appeared to enjoy the experience and it improved confidence in movement and self-efficacy. We found no evidence of improved mood or quality of life, suggesting that any perceived benefits might be either positive reporting or transitory.

The changes in physical fitness did not translate into improvements in transfers, mobility or functional activities. To achieve these outcomes may require greater motor relearning than we included in our programme. Falls were not reduced and this may be because we did not specifically target balance within the intervention. Carers may also be reluctant to encourage people to re-establish functional activities through fear of their relative falling or because of well-established caring roles. Although the quality of life of carers was not different from the general population, the carer burden was high. Two sessions per week may have provided some respite, but these are likely to be insignificant in comparison with other behavioural challenges.

We updated and expanded a systematic review in this topic area as part of the project. The quality of the reviewed studies was very low and the literature was dominated by small single-centre studies. A review published during the trial suggested that the effect of exercise on cognition may be specific to Alzheimer’s disease.20_{We were unable to support this finding within the cohort of DAPA trial patients}

with Alzheimer’s disease only, which is surprising given the size of the overall effect reported across pooled studies. Addition of the DAPA trial estimates to the systematic review reduced the estimated effect in people with Alzheimer’s disease but did not eradicate it. There remain a number of concerns with the synthesis of the literature for this indication and intervention. There are multiple small studies of low quality. The chance of overestimating effects or conducting a biased experiment are high in these situations. The level of heterogeneity reported in global measures of cognition was also well above accepted levels. When we examined effects in specific areas of cognitive impairment, heterogeneity was much lower and effects were null. There is some preliminary evidence that supports different dementia types (Alzheimer’s disease or vascular dementia) influencing different specific cognitive functions (language or executive function) to varying degrees.185

Another important finding was that this high-intensity exercise intervention was well tolerated by participants. Participants’carers and the physiotherapists delivering the intervention felt it was a suitable structured activity for people with dementia. Despite the intervention group sample displaying a high level of comorbid conditions, including nearly 50% living with a heart/circulatory condition and over 50% living with joint or muscle pain, there were remarkably few AEs.

It was a disappointing finding that there were no changes to carers’quality of life, considering the enjoyment and benefits reported in the qualitative study. However, on reflection of the bigger picture, we can see that the burden on carers is unrelenting. Carers may have found these two sessions per week to be a respite but they then have to cope with a range of challenges throughout the day and night. It is also worth considering that the quality-of-life measurements were taken at 6 and 12 months post intervention. So although they may have enjoyed the intervention when it was running, the continued deterioration of their loved one (an average of 4 ADAS-Cog points per year79_{) will undoubtedly compound their burden and}

the deterioration of their quality of life. It could be argued that a longer period of exercise classes may have had a better effect, but there was no signal of this within a time period that is consistent with physiological change in muscles and the cardiovascular system. Longer-term provision will be more costly and, hence, there is a need to demonstrate even greater benefit to achieve effects at the current levels of willingness to pay. There is also the possibility that longer periods of moderate- to high-intensity exercise may incur greater detriment to cognitive function.