The main outcome of this study is that in PD a PIGD motor subtype is generally associated with a more rapid rate of cognitive decline than a TD or IND subtype. Furthermore, incident dementia occurs more commonly in the PIGD subtype of PD, compared with indeterminate and TD subtypes.
The mean annual rates of cognitive decline, using the MMSE, in our study for PD and PDD are similar to those reported by Aarsland and colleagues.4
Those authors determined an annual decline in MMSE of 2.3 for PDD, in comparison with our figure of 2.25. Mean cognitive decline in non‐demented PD groups was negligible in both studies, at less than 0.1 points per annum. In contrast with the Aarsland study, we also studied DLB subjects, who displayed a similar annual MMSE decline to PDD of nearly two points. This is somewhat less than the annualised decline in MMSE noted by other studies for DLB, where mean values of 4.314
have been reported. These inter‐study differences cannot easily be explained by age of the DLB subjects or in their disease duration, although there were large standard deviations for the mean values presented in all studies. Furthermore, the MMSE may be a rather insensitive instrument for reflecting cognitive decline in DLB (and also in PDD), where executive deficits may be prominent. The mean decline in CAMCOG scores in our study was also similar for both PDD (11 points over two years) and DLB (10 points) groups, suggesting a degree of internal consistency in the data.
Annual rate of motor decline in PD, as evidenced by a worsening of nearly 2.5 points on the UPDRS III scale, was in keeping with other studies,16
although direct comparison is difficult because rate of progression in PD may not be linear.17
Our UPDRS data contrast with the findings of Jankovic and Kapadia, who reported a more rapid decline in UPDRS III in PIGD compared with TD patients, after adjustment for age at initial visit.17
We found no statistically significant difference between rate of UPDRS III progression and motor subtype in the PD subjects in our study, although the absolute deterioration at two years was greater in the PIGD subgroup than in the TD patients (8.9 and 3.6 points, respectively). This disparity may be accounted for by the longer period of follow up in the Jankovic study and the comparatively low numbers of PD subjects in each motor subtype in our study at baseline. Further follow up in our cohort may show a divergence in the rate of motor decline between subtypes. Interestingly, the rate of deterioration in motor function was almost twice as rapid in both of our demented groups (PDD and DLB), compared with PD subjects. We found no significant difference in the rate of either cognitive or motor decline between PD and PDD patients of short compared with long disease duration. The comparatively small numbers in each group and the comparatively short period of follow up necessitate caution in interpreting this finding, however.
Evolution of motor subtype and incident dementia in PD are likely to represent variable involvement of, and rate of neurodegeneration in, diverse neurochemical systems. Increasing cell loss in cholinergic nuclei is likely to underpin cognitive decline in PD,5,18
as well as the emergence of L‐dopa refractory motor features, while recent PET evidence suggests that cell loss in the serotonergic median raphe nucleus may correlate with tremor severity in PD.19
Furthermore, bradykinesia, rigidity, gait, and balance have previously been reported to progress at the same rate in people with PD, while change in tremor was independent of these signs.16
More severe motor symptoms, relating to putative non‐dopaminergic lesions, may be predictive of more rapid cognitive decline,4
and have been associated with incident dementia.6
Our finding, of 25% of the PIGD PD patients developing dementia during the course of this study, compared with no non‐PIGD subtype patients, would support these observations. Differential rates of neurodegeneration within neurochemically diverse brain stem nuclei could also provide a pathophysiological explanation as to why several patients in the PD group evolved from a TD subtype at baseline to indeterminate and PIGD subtypes during follow up.
Strengths of this prospective study include the inclusion of patients diagnosed according to formal diagnostic criteria and verified by consensus agreement, and the use of both CAMCOG and MMSE to record cognitive changes. Furthermore, this is the first study that we are aware of to compare rates of cognitive and motor decline in DLB subjects, as well as PD and PDD groups.
Potential weaknesses include the comparatively high drop out rate during the study and, subsequently, the small patient numbers in some motor subtype groups at follow up. More demented patients were lost to follow up, mainly because of increased mortality. We believe that this is unlikely to have significantly changed the conclusions of the study, however, because such patients would be predicted to have more rapid rates of cognitive and motor decline. Thus, our data for PDD and DLB groups would be, if anything, a conservative estimate. Only five of 40 PD subjects (12.5%) were lost to follow up, so it is improbable that our conclusions relating to motor phenotype and cognitive decline in PD would have been affected. A follow up period of two years is still comparatively short, however, and it must be acknowledged that rate of decline in both cognitive and motor performance is unlikely to be linear over the natural history of Lewy body disease.17,20,21
Furthermore, recruitment of all study groups was from outpatient clinics, while all PD subjects were aged 65 or over, thereby potentially limiting the generalisability of our results.
In conclusion, a PIGD motor subtype of PD is associated with a more rapid rate of cognitive decline, while incident dementia occurs more commonly in this subtype of PD. This information may be useful in informing future trials of putative cognitive neuroprotective agents in PD populations.