Background and purpose
Subtle executive dysfunction is common in people newly diagnosed with Parkinson disease (PD), even when general cognitive abilities are intact. This study examined the Short ...Weekly Calendar Planning Activity (WCPA‐10)'s known‐group construct validity, comparing persons with PD to healthy controls (HCs) and nonmanifesting carriers of LRRK2 and GBA gene mutations to HCs. Additionally, convergent and ecological validity was examined.
Methods
The study included 73 participants: 22 with idiopathic PD (iPD) who do not carry any of the founder GBA mutations or LRRK2‐G2019S, 29 nonmanifesting carriers of the G2019S‐LRRK2 (n = 14) and GBA (n = 15) mutations, and 22 HCs. Known‐group validity was determined using the WCPA‐10, convergent validity by also using the Montreal Cognitive Assessment (MoCA) and Color Trails Test (CTT), and ecological validity by using the WCPA‐10, Schwab and England Activities of Daily Living Scale (SE ADL), and Physical Activity Scale for the Elderly (PASE).
Results
Known‐group validity of the WCPA‐10 was established for the iPD group only; they followed fewer rules (p = 0.020), were slower (p = 0.003) and less efficient (p = 0.001), used more strategies (p = 0.017) on the WCPA‐10, and achieved significantly lower CTT scores (p < 0.001) than the HCs. The nonmanifesting carriers and HCs were similar on all cognitive tests. Convergent and ecological validity of the WCPA‐10 were partially established, with few correlations between WCPA‐10 outcome measures and the MoCA (r = 0.50, r = 0.41), CTT‐2 (r = 0.43), SE ADL (r = 0.41), and PASE (r = 0.54, r = 0.46, r = 0.31).
Conclusions
This study affirms the known‐group validity for most (four) WCPA‐10 scores and partially confirms its convergent and ecological validity for PD.
To test for an association between the LRRK2‐G2019S mutation and gait, we studied 52 first‐degree relatives of patients with Parkinson's disease (PD) who carry this mutation. An accelerometer ...quantified gait during usual‐walking, fast‐walking, and dual‐tasking. Noncarriers (n = 27) and carriers (n = 25) were similar with respect to age, gender, height, and gait speed during all conditions. During dual‐tasking and fast‐walking, gait variability and the amplitude of the dominant peak of the accelerometer signal were significantly altered among the carriers. These findings support the possibility of previously unidentified, presymptomatic motor changes among relatives who have an increased risk of developing PD. Ann Neurol 2010
Non‐manifesting carriers (NMC) of the G2019S mutation in the LRRK2 gene represent an “at risk” group for future development of Parkinson's disease (PD) and have demonstrated task related fMRI ...changes. However, resting‐state networks have received less research focus, thus this study aimed to assess the integrity of the motor, default mode (DMN), salience (SAL), and dorsal attention (DAN) networks among this unique population by using two different connectivity measures: interregional functional connectivity analysis and Dependency network analysis (DEPNA). Machine learning classification methods were used to distinguish connectivity between the two groups of participants. Forty‐four NMC and 41 non‐manifesting non‐carriers (NMNC) participated in this study; while no behavioral differences on standard questionnaires could be detected, NMC demonstrated lower connectivity measures in the DMN, SAL, and DAN compared to NMNC but not in the motor network. Significant correlations between NMC connectivity measures in the SAL and attention were identified. Machine learning classification separated NMC from NMNC with an accuracy rate above 0.8. Reduced integrity of non‐motor networks was detected among NMC of the G2019S mutation in the LRRK2 gene prior to identifiable changes in connectivity of the motor network, indicating significant non‐motor cerebral changes among populations “at risk” for future development of PD.
ABSTRACT
Background: The G2019S mutation in the LRRK2 gene generates a milder PD phenotype compared with GBA‐PD; however, genetic based survival studies are lacking.
Objectives: To compare mortality ...rates between LRRK2‐PD, GBA‐PD, and idiopathic PD patients (iPD).
Methods: Patients were screened for the G2019S mutation in the LRRK2 gene and the seven common GBA mutations among Ashkenazi Jews, classified as mild and severe (mGBA, sGBA). Motor symptoms onset and date of death were ascertained, with mortality rates calculated for each group of patients.
Results: Overall, 380 of 1,086 idiopathic PD patients, 49 of 159 LRRK2‐PD, 56 of 148 mGBA‐PD, and 13 of 49 sGBA‐PD participants died by the time of analysis. LRRK2‐PD tended to have longer survival compared to idiopathic PD whereas GBA status did not affect mortality. Genetic status did not predict mortality in a multivariate analysis.
Conclusion: Survival of patients with PD does not seem to be related to GBA status, whereas LRRK2 might confer higher survival rates.
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