Cognitive decline in Parkinson's disease: the impact of the motor phenotype on cognition

This is a nice large study looking at the relationship between different motor features of Parkinson's and having more severe cognitive features.

We already know that patients with a mainly shaky (tremulous) form of Parkinson's tend a run a milder course compared to those patients that have a very slow & stiff (akinetic rigid) form of Parkinson's. For example, patients with the tremulous form of Parkinson's also seem to live for longer than those with the akinetic rigid form. Of course these categories overlap substantially but they are generally well recognised.

Here the researchers show that in patients who tended to be more slow and stiff, scores on a variety of cognitive tests were worse than in the patients that had predominant tremor.

The study design was cross-sectional, which means that movement and cognition were measured at the same time. This means that strict conclusions cannot be drawn about the progression of movement or cognitive abnormalities either separately or together. The explanation for the association between akinetic-rigidity and worse cognition is likely due to involvement of common structures brain (more so than the structures that are involved in tremor), the overall burden of disease (likely to be less in those with predominant tremor), and shared risk factors (including genetic determinants).

- Alastair Noyce

J Neurol Neurosurg Psychiatry. 2018 Oct 8. pii: jnnp-2018-319008. doi: 10.1136/jnnp-2018-319008.

Wojtala J, Heber IA, Neuser P, Heller J, Kalbe E, Rehberg SP, Storch A, Linse K, Schneider C, Gräber S, Berg D, Dams J, Balzer-Geldsetzer M, Hilker-Roggendorf R, Oberschmidt C, Baudrexel S, Witt K, Schmidt N, Deuschl G, Mollenhauer B, Trenkwalder C, Liepelt-Scarfone I, Spottke A, Roeske S, Wüllner U, Wittchen HU, Riedel O, Dodel R, Schulz JB, Reetz K.

https://jnnp.bmj.com/content/early/2018/10/07/jnnp-2018-319008.long

OBJECTIVES: Parkinson's disease (PD) is the second most common neurodegenerative disorder and is further associated with progressive cognitive decline. In respect to motor phenotype, there is some evidence that akinetic-rigid PD is associated with a faster rate of cognitive decline in general and a greater risk of developing dementia.The objective of this study was to examine cognitive profiles among patients with PD by motor phenotypes and its relation to cognitive function.

METHODS: Demographic, clinical and neuropsychological cross-sectional baseline data of the DEMPARK/LANDSCAPE study, a multicentre longitudinal cohort study of 538 patients with PD were analysed, stratified by motor phenotype and cognitive syndrome. Analyses were performed for all patients and for each diagnostic group separately, controlling for age, gender, education and disease duration.

RESULTS: Compared with the tremor-dominant phenotype, akinetic-rigid patients performed worse in executive functions such as working memory (Wechsler Memory Scale-Revised backward; p=0.012), formal-lexical word fluency (p=0.043), card sorting (p=0.006), attention (Trail Making Test version A; p=0.024) and visuospatial abilities (Leistungsprüfungssystem test 9; p=0.006). Akinetic-rigid neuropsychological test scores for the executive and attentive domain correlated negatively with non-tremor motor scores. Covariate-adjusted binary logistic regression analyses showed significant odds for PD-mild cognitive impairment for not-determined as compared with tremor-dominant (OR=3.198) and akinetic-rigid PD (OR=2.059). The odds for PD-dementia were significant for akinetic-rigid as compared with tremor-dominant phenotype (OR=8.314).

CONCLUSION: The three motor phenotypes of PD differ in cognitive performance, showing that cognitive deficits seem to be less severe in tremor-dominant PD. While these data are cross-sectional, longitudinal data are needed to shed more light on these differential findings.