Parkinson’s disease (PD) has an enormous impact on quality of life (1–3). Many patients lose the ability to live independently at home (3–6). Important reasons for nursing home admission include cognitive deterioration, hallucinations, older age and the loss of activities of daily life (7–12). PD patients in nursing homes are the most expensive group to treat, increasing the overall costs by approximately 4 times the costs of living at home (13). No intervention in aPD patients thus far has shown any delay or prevention of nursing home admission.

This study investigated whether a combined multidisciplinary in/outpatient rehabilitation program, focusing on ADL functioning, was able to delay definite nursing home admission. For this purpose, we performed a non-randomized controlled trial during 2 years, to analyze the short-and long-term effectiveness of a 6-week inpatient rehabilitation program, followed by a multidisciplinary support program during 2 years in aPD patients, who were on the brink of losing their independence.

This study describes the positive outcomes of a long-term, controlled trial on the efficacy of an in/outpatient, multidisciplinary Parkinson rehabilitation program, including medication optimization. Importantly, only aPD patients were included, who were not longer able to live independently at home at the time of inclusion. Our data indicate that a multidisciplinary intervention, is able to keep these aPD patients stable for at least 2 years, as shown by the functional ALDS scores, which was not the case in the controls with care as usual. Moreover, the controls experienced a significant decrease in their functional capability, which is in line with previous data showing that PD patients in a nursing home with moderate cognitive impairment showed deterioration of MDS-ADL scores of 1.78 points in 6 months (38). Post-hoc analysis of the baseline ALDS scores of treated patients indicated that returning home was correlated to higher baseline ALDS scores (Supplementary Figure S1).

Our study reports for the first time that multidisciplinary rehabilitation of aPD patients is able to postpone definite nursing home admission by at least 2 years in 65% of cases. None of the control patients left the nursing home during the same period.

An important difference between both groups was the level of dopaminergic stimulation. The intervention group showed a significant increase in LEDD, including initiation or optimization of continuous infusion therapies in some patients. This suggests that optimal pharmacotherapy offers important advantages on the short-and long-term. The pharmacotherapy for PD patients in nursing homes is suboptimal, with 44% of PD patients being most of the time ‘off’, and low LEDDs, varying from 400 to 500 mg/day, while patients had already PD for at least 7 years (10, 39). In our study the mean LEDD at baseline of the intervention group was 1097.5 mg, but still 75% of included patients were considered to be underdosed.

The other secondary endpoints showed that the effect of the inpatient rehabilitation (phase I) was most optimal directly thereafter, which decreased over time during phase II, resulting in comparable outcomes at 2 years follow-up, except for the NPI, which improved significantly in the intervention group, despite a higher LEDD in the intervention group, which could have increased hallucinations, but that did not happen (40–42). The increased dosages of apomorphine, CHEI’s and clozapine in our study are the most likely explanation for this finding (43–47). This is an important result, because visual hallucinations are the strongest predictor of definite placement in nursing homes (9, 11, 12). The intervention program also included a small group without the need to change their LEDD. These patients also improved on their motor-and ADL scores, stressing the importance of allied therapies and other disciplines involved in our rehabilitation program. These findings strengthen the evidence of the effect of allied therapies within a multidisciplinary rehabilitation treatment (without medication adjustments) on patients with early stage PD on ADL functioning and QoL (48, 49).

Improvement of the cognition is very likely due to optimization of medication. Suppletion of the cholinergic deficit with rivastigmine, eventually in combination with optimization of the levodopa dose. In 54% of the PD patients rivastigmine was added to their medication regimen during the treatment. Overall 87% of the PD patients showed improved scores (SCOPA-COG) with an average of 6 points. This is in line with other studies, which found improvement of cognition after optimized treatment as well (45–47).

This study also has some limitations. Both arms included relatively small numbers of patients, although this was based on our power calculations before study onset. The fact that this small sample already resulted in significantly positive outcomes supports the strength of our rehabilitation concept. We performed bootstrapping to provide a more representative outcome, to control for the relatively small sample size. However, the outcomes after bootstrapping were not significantly different from the original data.

At 2 years follow-up, seven patients in the intervention group (29.2%) and eight patients in the control group (42.1%) had died. This means that the loss-to-follow-up is a potential threat to validity and might cause significant bias (50). A chi-square test was performed to control for these differences and no dissimilarities were found (0.7816; p = 0.3766) between the intervention and control group. The differences in ALDS-and SCOPA-COG scores at baseline might also have impacted the effect size. However, regression analysis with adjustment for these baseline values and analysis of covariance with adjustment for the baseline values gave exactly the same output, suggesting there was no serious influence on the effect size.

Another limitation is the lack of QoL data in our control group. This would have offered an extra possibility to discuss the observed functional improvements in this study. Living longer at home and greater independence in activities of daily living provide better QoL in late-stage Parkinson, as was shown previously (3).

Finally, neither patients nor the assessors were blinded with respect to the intervention. This might have influenced the final outcomes. However, the most important finding, being the percentage of patients returning home after the intervention, and still staying at home after 2 years in 65% of cases, cannot be explained by this open assessments, which is also the case for the LEDD changes, which are the result of a particular vision on optimal treatment of aPD, instead of assessment bias. Therefore, the stabilization in the rehabilitation group and the clear worsening in the control group can be considered as real and important effects of our rehabilitation program.

Our findings potentially have large implications. If in/outpatient aPD rehabilitation, with a focus on optimization of pharmacotherapy, is able to stabilize advanced PD patients and delay nursing home admission, many more advanced PD patients should be offered similar programs. This would not only improve their independence but would also significantly save costs of nursing home admission (around 90.000 Euro per patient per year in the Netherlands). A Norwegian study showed that costs arising from nursing home placement were 5 times higher for PD patients compared to controls (51) For exact cost-effectiveness of this particular concept further research is necessary. The costs of the control group are related especially to the costs of institutional care. The costs of the intervention group exist of the inpatient intervention/rehabilitation period and the outpatient support program. The inpatient program costs are estimated on 300 Euro per day, which makes around 12.500 Euro for 6 weeks. The costs of the outpatient program are based on a questionnaire covering the health-care costs during the previous 3 months, including medical care, allied health care, home care nursing as well domestic informal care, and even hospital admissions, if needed. These costs summed up to 4.000 Euro/3 months, which means a yearly cost of 16.000 Euro/patient in the intervention group. If it is hypothesized that those costs were kept at the same level during the 2 year follow-up, this would mean an overall cost of the intervention group of 44.500 Euro vs. 180.000 Euro of the nursing home group. This means that not only the QoL is improved by our intervention, but that the prevention of definite nursing home admission also implicates a huge financial benefit of almost 70.000 Euro per patient per year.

The most important message of our study is the huge benefit of intensive rehabilitation for advanced PD patients. We have shown the impact on living independently at their own houses, which is a significant contribution to their quality of life. Therefore, in every country neurologists should take responsibility to create places where advanced PD patients are rehabilitated, in order to prevent definite nursing home admission. The place where this rehabilitation should take place will differ between countries, and may vary between hospital settings (which is mostly too expensive), rehabilitation centers or, as in our case, specialized nursing homes, creating a setting without time–pressure, but offering a stimulating atmosphere, created by an educated multidisciplinary PD team. Without these rehabilitation options, advanced PD patients will have a reduced quality of life at high costs, because our study also shows the huge financial benefit of delaying definite nursing home admission.

However, before this approach can be recommended to all advanced PD patients or even be more widely used in chronic patients on the brink of nursing home admission, our data have to be confirmed in larger samples, preferably in other clinics, and in other countries, in order to validate our PD rehabilitation concept.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Trial registration: filenumber M10.091051; ABR code NL32699.042.10. The patients/participants provided their written informed consent to participate in this study.

ES-O and TL contributed to the research design. ES-O wrote the first draft of the manuscript. TL and BB were responsible for revisions. ES-O and NW were responsible for data collection. JV was responsible for statistics. All authors made a substantial, intellectual contribution to the work read and approved the final manuscript.

This study was supported by the UMCG innovation fund and prof. Van der Valk Stichting.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fneur.2023.1128891/full#supplementary-material