Slower decline for patients with PARKIN-associated PD

By Eleanor McDermid, Senior medwireNews Reporter

Cognitive and motor decline may be slower in patients with early-onset Parkinson’s disease (PD) if they have PARKIN mutations, suggests an analysis of the Consortium on Risk for Early-Onset PD study.

This may be partly because PARKIN-associated PD pathology remains confined to the substantia nigra, say the researchers.

“Our findings may have important implications for genetic testing and for the counseling of homozygotes and compound heterozygotes who carry PARKIN mutations,” write Roy Alcalay (Columbia University, New York, USA) and team in JAMA Neurology.

Some previous studies, including one involving the same cohort as the current study, found no neurocognitive differences between patients with and without PARKIN mutations. Believing this to be due to relatively short follow-up durations, Alcalay et al confined their analysis to patients with PD lasting longer than 14 years (the median for the cohort).

However, they stress that their study was cross-sectional, and that longitudinal studies are still needed to confirm the findings.

The patients included four homozygous and 17 compound heterozygous PARKIN mutation carriers. They were younger than the 23 patients without PARKIN mutations, and had an earlier age at PD onset, but after adjusting for these characteristics, they performed significantly better than noncarriers on a range of tests.

Patients with PARKIN mutations had significantly better scores than noncarriers on the Mini-Mental State Examination, at 29.2 versus 27.9, and just 9.5% were diagnosed with dementia, compared with 47.8% of noncarriers.

After accounting for confounders including disease duration, education, and levodopa equivalent daily dose, carriers achieved significantly better results in neurocognitive tests of attention, memory, and visuospatial performance.

Carriers also had better motor function, with an average score of 21.0 on the Unified PD Rating Scale (UPDRS) part III, compared with 27.8 for noncarriers. Patients’ UPDRS-III scores correlated tightly with their attention, memory, and visuospatial performance, and also with their performance in tests of executive function.

Indeed, adjusting for UPDRS-III scores negated the relationship of PARKIN carrier status with neurocognitive performance, while accounting for neurocognitive performance abolished the association with UPDRS-III scores.

“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,” say the researchers.

They suggest that these patients “may benefit from the assurance that they have a lower risk for dementia than patients with idiopathic PD.”

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