Mutation signals slower Parkinson progression

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PARKIN mutation carriers showed better cognitive and motor performance than noncarriers with long Parkinson disease (PD) duration, implicating slower disease progression, according to a study published in the January issue of JAMA Neurology.

The most common genetic mutations associated with early-onset Parkinson disease (EOPD) are PARKIN mutations. Previously, two cross-sectional studies investigated the cognitive performance of patients with EOPD and discovered similar neuropsychological results between homozygous and compound heterozygous (H/CH) carriers and noncarriers.

“However, it has been hypothesized that H/CH carriers are less likely than noncarriers to develop dementia and that longer follow-up is required to differentiate between the cognitive performances of H/CH carriers and those of noncarriers,” wrote the study’s lead author, Roy N. Alcalay, MD, MSc, of Columbia University in New York City, and colleagues.

Alcalay et al repeated analyses of the Consortium on Risk for Early-Onset PD (CORE-PD) after adding more participants and restricting analyses to those with more than 14 years of disease duration. The new cross-sectional analysis included 44 participants at 17 different movement disorder centers that were in the CORE-PD study. This population was comprised of four homozygotes, 17 compound heterozygotes (carriers), and 23 noncarriers.

The study’s results indicated that carriers had an earlier age at onset of PD and were younger at the time of examination than noncarriers. Carriers performed better than noncarriers on the Mini-Mental State Examination and were more likely to score lower on the Clinical Dementia Rating. Multivariate analysis showed that carriers performed better than noncarriers on the Unified Parkinson Disease Rating Scale Part III and on tests of attenuation, memory, and visuospatial cognitive domains.

“Considering that homozygotes and compound heterozygotes who carry  PARKIN mutations develop PD at a younger age than noncarriers, they may be concerned about their risk for dementia and their long-term ability to work,” wrote Alcalay and colleagues. “These H/CH carriers may benefit from the assurance that they have a lower risk for dementia than patients with idiopathic PD.”

Future studies should investigate the effects of disease duration on cognitive and motor function in order to confirm that PARKIN-associated PD progresses more slowly than idiopathic PD, according to the authors.