Study Rationale:
Mild cognitive impairment in Parkinson's disease (PD-MCI) is the highest risk factor for Parkinson's disease dementia (PDD). The core feature for differentiating PDD from PD-MCI is the loss of the ability to perform activities of daily living (ADL). First signs of ADL impairment can be observed in a subgroup of patients with PD-MCI, suggesting that mild ADL impairment in PD-MCI might characterize those patients at high risk for PDD. As Parkinson's is primarily a movement disorder, the distinction between motor and cognitive contributions to ADL in PD is an obvious challenge, which we aimed to explore in this study.
Hypothesis:
We hypothesize that PD-MCI patients with more pronounced, cognitive-driven ADL impairment are at higher risk for developing PDD.
Study Design:
We will conduct a longitudinal follow-up assessment of 262 non-demented PD patients over the next two years. We will conduct a comprehensive clinical assessment and biomarker sampling to determine genetic risk variants for dementia and examine cerebrospinal fluid markers, as well as analyses of metabolic brain patterns in a subgroup of patients. To assess daily function, we will apply novel scores of the Pfeffer Functional Activities Questionnaire differentiating between cognitive and motor influences on ADL. Our primary outcome will be the conversion to PD-MCI and PDD, as well as the decline in ADL function.
Impact on Diagnosis/Treatment of Parkinson's Disease:
The identification of a high-risk group for PDD among those with PD-MCI is essential, as the rate of cognitive decline can be reduced by therapeutic intervention. Those identified as at high-risk for PDD may be a valuable target group for clinical trials evaluating pharmacological and non-pharmacological cognitive intervention strategies.
Next Steps for Development:
This study may facilitate the use of activities of daily living impairment as a risk factor for future conversion to PDD. Specific differentiation of motor and cognitive contributions to ADL impairment can aid researchers and health care professionals in reaching a definite PDD diagnosis.