The results of this study confirm that there is a strong association between cognitive impairment and ADL difficulties in patients with PD and show that this association persists among nondemented patients with PD. It is also present to some extent in patients with nominally intact cognition, even after adjustment for covariates including mood and motor performance.
A secondary purpose of this study was to compare the usefulness of the MMSE and the DRS-2 in identifying clinically meaningful cognitive impairment. Not surprisingly, the DRS-2 was substantially more accurate than the MMSE, particularly in the case of more mildly impaired subjects. This finding is consistent with the frequent observation that the MMSE is not sensitive to mild cognitive deficits.20-22
In this study, the MMSE was both less sensitive and less specific than the DRS-2. Although the DRS-2 requires substantially more time to complete than the MMSE, relying on the MMSE alone opens the possibility of missing instances of clinically relevant cognitive impairment.
Our data show that the association between cognition and ADL function depends substantially on IADLS. This finding is consistent with a prior study that showed that cognitive deficits were associated with impairment in IADL but not BADL function in PD patients.2
Our study extends these findings by demonstrating that the same associations are present in patients with PD not diagnosed with dementia. IADL function was associated with cognition across all subgroups in our study. In cognitively intact patients, the association between overall ADL function and cognition was not statistically significant, but the association between cognition and IADL function remained. Other studies that have investigated the relationship between cognitive impairment and ADL function in nondemented patients with PD have not found as strong a relationship.6
One explanation for this discrepancy is the way that ADL function was assessed. The ADCSADL scale emphasizes IADLs that depend highly on cognitive processes such as memory and organization. Instruments used in prior studies have not focused on IADLs. For example, an analysis using the AMC linear disability scale did not find an association between cognition and ADL function in nondemented patients with PD.6
The AMC scale emphasizes tasks dependent on motor rather than cognitive function and may not be as sensitive to the impact of cognitive impairment on ADL function as the ADCS-ADL scale.23,24
Disorder Society (MDS) task force on PDD has recently published a recommended definition of PDD,25
and a detailed procedure for implementing the definition.19
The MDS definition of PDD states that there must be a decline in cognitive function from a premorbid level and that decline must involve at least two cognitive domains. It also includes a criterion that cognitive symptoms must be severe enough to affect daily life independent of the effects of motor or autonomic symptoms of PD. Although we used DSM criteria rather than the MDS criteria to define dementia, this study is relevant to the MDS definition in several ways. First, we demonstrate an independent effect of cognition on ADL function in the setting of coexisting motor impairment. Second, our analyses supports the recommended cut-off of >25 on the MMSE, which was optimal for categorizing both moderate and severe disability. However, the sensitivity and specificity of the MMSE for mild disability is modest, and ADL function is affected in individuals with MMSE scores above 25. Thus, our data leaves open the possibility that some individuals who are not “demented” based on MDS criteria, may nonetheless have significant disability on the basis of cognitive dysfunction. This situation is probably more common when applying the published DRS-2 cut-off of ≤123.13
Even though the overall accuracy of the DRS-2 is superior to the MMSE, this benchmark proved to be less specific for disability than a MMSE score of >25.
Our study has several limitations. All patients had motor ratings obtained while taking regularly scheduled dopaminergic medications. Ratings in the medication “on” state may not accurately capture motor disability. To mitigate this problem, we used Hoehn and Yahr stage rather than UPDRS scores to adjust for motor impairment. HY stage is largely driven by axial symptoms, which are less influenced by dopaminergic medication and highly related to disability.6,26
However, HY stage is also correlated with cognitive dys-function. Thus, adjusting for motor performance with the HY may underestimate the impact of cognitive impairment on daily function. Another limitation is that the study uses a convenience sample recruited from a specialty clinic. As a result, our subjects may not be representative of the population of community-dwelling patients. In particular, our subjects were notably well-educated and nondepressed, and neither of these factors was associated with impaired ADL function in our sample. Additionally, the ADCS-ADL is completed by caregivers, which may mitigate the impact of depressive symptoms experienced by the patients. While the frequency of cognitive impairment may be different in a population-based sample, it is less likely that selection bias would result in a different relationship between cognition and ADL function. Finally, the ADCS-ADL cut-offs we chose to define disability have not been validated. To our knowledge, there is no data on appropriate cut-offs on this scale. We chose scores that had been obtained in well-defined clinical trial populations for the moderate and severe cut-off. The mild cut-off was defined as a level of disability significantly worse than would be seen in patients with PD with mild to moderate motor signs and relatively preserved cognition. This cut-off may greater disability than a cut-off that was obtained from normal individuals. Additional studies would be needed to validate these cut-offs against a criterion measure of disability.
In summary, this study demonstrates that cognitive impairment significantly affects daily function in non-demented patients with PD as well as those with dementia and has some impact on ADL function even in very mildly impaired individuals. It may be reasonable for clinicians to begin to consider medical and non-medical therapies for cognitive impairment before definitive signs of dementia are present. Our data also show that the DRS-2 is a more accurate test than the MMSE for detecting functionally significant cognitive changes. It is unlikely that physicians will choose to administer this test in a clinical setting because of its length. Rather, a brief and accurate screen for functionally significant cognitive impairment is needed. The Montreal Cognitive Assessment (MoCA), a 10-min cognitive screening tool, has demonstrated high sensitivity and specificity for detecting MCI27
and has been shown in PD to be more sensitive than the MMSE for detecting mild cognitive deficits.20,28
Further analysis of the relationship between the MoCA and ADL dys-function in PD may demonstrate the means to feasibly detect mild, but functionally significant cognitive decline in patients with PD.