Comorbidity and Aging in Rehabilitation Patients: the influence on Activities; substudy Parkinon's disease, follow-up after 8, 10, 12 and 15 years

There is considerable variation in the clinical course of Parkinson*s disease
(PD) between individual patients. In clinical practice, the heterogeneity of PD
impedes the adequate counseling of patients about the prognosis of the disease,
and it may lead to diagnostic difficulties. In the clinical research setting,
the heterogeneity of PD has consequences for samples sizes needed in clinical
trials. The recent surge of interest in neuroprotective therapies has further
increased the demand of data on the clinical course of PD and its possible
prognostic factors. There are numerous studies describing the progress of the
disease, and synthesized data from systematic reviews are available. The
reviews pointed towards older age at onset and a postural instability and gait
difficulty (PIGD) phenotype at baseline as prognostic factors for worse
progression of disability. They found conflicting or limited evidence for other
prognostic factors of motor impairments and disability. Furthermore, they
concluded that research on the progression of PD to date is not fulfilling the
high standards applied nowadays. Main critiques on available studies were the
use of prevalent cases or patients who were originally enrolled in a
therapeutic trial, which both can lead to selection bias with an
underestimation of disease progression. In addition, the majority of available
studies had a relatively short duration of follow up. To gather more data on
the clinical course and to identify prognostic factors for disease progression
in an unbiased cohort of PD patients the CARPA-project was initiated eight
years ago.

The aim is to further track the course of motor symptoms and functional status,
and to establish conversion to Parkinson*s disease dementia (PDD).

At baseline and after 1, 2, 3, and 5 years a set of rating scales and
questionnaires was used for assessment of disease progression. We intend to use
the same set at the follow-up visits at 8, 10, 12 and 15 year.
This set will be extended with the Parkinson Disease * Cognitive Rating Scale
(PD-CRS) to increase sensitivity for Parkinson*s Disease Dementia (PDD).
- Unified Parkinson Disease Rating Scale;
- Hoehn and Yahr scale;
- Cumulative Illness Rating Scale (comorbidity);
- Schwab and England Activities of Daily Living Scale;
- Functional Independence Measure and the AMC Linear Disability Score;
- PD Quality of Life questionnaire (PDQL) and Short Form Health Survey (SF-36);
- Mini Mental State Examination (MMSE);
- Parkinson Disease * Cognitive Rating Scale (PD-CRS)
- Hospital Anxiety and Depression Scale (HADS).
For the diagnosis of PDD, we will use the diagnostic procedure as proposed by
the Movement Disorders Society. In case of diagnostic doubt, a neurologist
specialized in movement disorders will contact the treating neurologist, or if
necessary, will visit the patient for neurological evaluation.
Annual disease progression and the impact of prognostic factors will be
described using linear mixed models for continuous data. The proportion of
demented patients at each follow-up visit will be reported, and the influence
of prognostic factors will be analyzed using logistic (or Cox) regression
analysis. The proportions of deceased patients will be reported using
descriptive statistics, and the influence of prognostic factors will be
analyzed using Cox proportional hazards model.

Each assessment will take about one to two hours. All patients will be visited
at their home. If individual patients experience a home visit as inconvenient
we will offer to perform the assessment at the out-patient clinic. The study
visit comprises of a brief physical and cognitive examination, and the filling
in of health related questionnaires. Study participants are therefore not
exposed to health-related risks. If a participant experiences the visit as
inconvenient (eg. due to cognitive dysfunction), the visit will be shortened.
The proposed study will lead to a total follow-up period of 15 years from the
moment of diagnosis. It will render data on the conversion to dementia,
progression of motor and cognitive symptoms, and its impact on disability and
quality of life in mid-term to late stage PD. Prognostic models can be made
using the data that are already available from the earlier follow-ups. In this
way, the value of the baseline assessment and neuropsychological follow-ups
performed earlier in the study will increase. The data from this project will
be directly ready to use for patient counselling regarding disease prognosis.
Since the large variability in the clinical course of PD has been an important
limiting factor in patient counselling, the identification of prognostic
variables in the present study will improve the predictions of prognosis for
individual patients. In addition to the direct benefit for patient counselling,
the knowledge about the clinical course of PD can also lead to an increased
efficiency of future clinical trials.