MAKS therapy had a significant effect on cognitive function in dementia patients and on their ability to carry out ADL in five participating nursing homes after 12 months compared to a control group that received usual care. The MAKS therapy was found to be an easily manageable form of therapy which was well-accepted by the patients. This is reflected in the very low number of missing days. Treatment with cholinesterase inhibitors or memantine, which was neither an inclusion nor an exclusion criterion in our study, had been prescribed to only 13 patients (13.5%; see Table 1) and perhaps had, therefore, no predictive power. The effect sizes of MAKS therapy were in the same range as those that have been reported for cholinesterase inhibitors with respect to cognition and about twice as high as those reported for cholinesterase inhibitors with respect to ADL . One fourth of the patients in the intervention group dropped out during the study period or were lost to follow up, leading to lower effect sizes in our ITT analysis. In the intervention group, the effect sizes in patients with mild to moderate dementia were substantially higher than in patients with severe dementia. As a consequence, MAKS therapy, until further investigation with a larger sample size, should not be used in the latter patient group.
In a systematic search of the literature for comparable multicomponent, non-pharmacological RCTs in which the primary target group consisted of dementia patients and not of their caregiving family members, we were unable to identify any methodologically rigorous studies that had been conducted in a nursing home setting. Our search did reveal, however, that various combinations of non-pharmacological interventions have been conducted in community-dwelling dementia patients to date. Onor et al. , for example, investigated the efficacy of combined cognitive and occupational therapy but were unable, perhaps due to the small size of their sample (n = 32), to find any significant effects for the outcome measures cognition, ADL, or instrumental ADL. In another study, a significant effect on the ADAS-Cog subscale was demonstrated for an intensive intervention with 103 sessions that took place over a 12-month period and combined cognitive and motor elements in a sample similar in size (n = 84) to ours . The evaluators were blinded to treatment allocation. Moreover, all patients had been receiving treatment with an acetylcholinesterase inhibitor and continued to do so during the study period. The authors, however, did not report effect sizes and only cursorily described the effects of the intervention at 12 months. A significant effect on patients' ability to carry out ADL could not be demonstrated. Gitlin et al.  investigated the efficacy of a multicomponent non-pharmacological intervention regarding functional abilities of community-dwelling dementia patients and several other outcomes. The intervention group (n = 102 dyads of dementia patient and caregiver) received up to 10 sessions with occupational therapists aimed at reducing environmental stressors and enhancing caregiver skills. Therapists identified strengths and deficits of the patients and trained caregivers in modifying home environment and communication. Additionally, health related information was assessed and recommendations were provided to the caregiver to share with the patients' physicians. The control dyads (n = 107) received up to three telephone calls from research staff and informational material was provided. After four months, significant improvements in functional dependence could be found for the intervention group compared to the control group. Cohen's d was 0.21, mainly due to an improvement in IADL-abilities. The effect could no longer be found after nine months. Outcome measures were caregiver ratings, obtained by interviewers blinded to participant group. In summary, our literature search revealed that the multicomponent interventions conducted among community-dwelling patients to date have shown only moderate effects. While this may be attributable to the type or intensity of therapy, it may also be related to the lack of consistently applied blinded performance tests. Because there was no evidence that the interventions in any of the identified studies had sustained effects, we defined the PP analysis as our primary evaluation strategy.
The present study has several important limitations. The first of these is the size of its sample, which consisted of 61 dementia patients in the PP analysis. This is in the middle range compared to the study samples in other non-pharmacological, multicomponent RCTs in dementia patients, which have had between 32  and 209  participants, albeit in a community-dwelling rather than a nursing-home setting. Future studies of MAKS therapy should include a larger sample of patients. The second limitation of our study is its lack of a control group receiving placebo treatment. In light of the many drawbacks of non-pharmacological placebo treatments, however, we feel that the use in our study of a control group receiving usual care was appropriate, especially considering that we placed no restrictions on patients in either group with regard to their continuation or initiation of any pharmacological or non-pharmacological treatment during the study period. All control group participants were allowed, for example, to continue to take part in the regular, non-MAKS activities offered by their nursing home, which they did on the average twice a week. As participation in these activities was voluntary, the significant effect on cognition after 12 months might either be due to helpfulness of these activities but also due to a convenience sample.
The treatment effects of MAKS therapy are undoubtedly attributable not only to specific but also to non-specific factors, such as the attention paid to patients by the therapists. To date, however, no studies have been able to demonstrate that paying more attention to patients, as for example is practiced in validation therapy, can produce a significant cognitive improvement in and of itself . It therefore seems unlikely that the effects of MAKS therapy are attributable only to the greater intensity and duration of the attention paid to patients in the intervention group.
Our study also has a number of strengths compared to previous investigations. With only a few exceptions (for example, our decision not to include bed-ridden patients), our choice of inclusion and exclusion criteria closely reflects the clinical reality of dementia patients in nursing homes: Unlike many other studies of non-pharmacological interventions in this patient group, we did not exclude patients who showed poor cognitive function as measured by the MMSE or possible neuropsychiatric symptoms, such as challenging behavior. Another strength of our study was the rigorous standardization of MAKS therapy through the use of a handbook, enabling a high degree of agreement across the participating nursing homes. In addition to repeated trainings of the therapists, additional quality assurance measures were performed with all of the study and nursing home staff who participated in the investigation. Finally, in terms of methodology, another strength of our study was its use of external evaluators who were blinded to treatment allocation to assess both outcome variables. Moreover, additional factors that might influence treatment, such as medication or participation in additional, non-MAKS activities, were included in the multivariate analysis, and any serious adverse events were recorded.
Patients with dementia always experience limitations with respect to an age-appropriate 'participation in life' due to the symptoms of their disease and especially as nursing home residents. These limitations particularly affect social interaction, communication, cognition and everyday practical stimulation. The MAKS therapy aims at restoring this participation appropriate to the resources still available to the patient, and thus is characterized by multimodality, regularity and various degrees of difficulty.
Due to the standardization of the MAKS therapy and publication of a handbook , the therapy is easy to implement and requires little preparation time from the therapists. In the present study, the MAKS therapy was carried out in an intensive form. Performance as group therapy reduces the per-person costs of intervention. With two therapists for ten patients, the therapy costs are below €10/day and person and are thus still in the range of costs of therapy with acetylcholinesterase inhibitors. Moderately higher costs appear justified when the non-drug therapy shows no adverse effects and is at least as effective as therapy with acetylcholinesterase inhibitors. In the future, health economic studies to compare these costs to the possible savings which could result from stabilization of the patient's capabilities, and thus on the costs of care would be desirable.
The German health system includes, for example, so-called supplementary care services for the care of patients with dementia. The aim should be to use these resources in such a way that the dementia patient receives the maximum benefit. Depending on the health system, there are various types of resources which support dementia patients or aid in integrating them in everyday living. It appears promising to make appropriate use of the possibilities of non-drug therapy in the care of dementia patients.