Later brain stimulation linked to faster decline in some with Parkinson’s

People with Parkinson’s disease who carry GBA1 variants may experience faster cognitive decline when deep brain stimulation (DBS) is performed later rather than earlier in the disease course, a new study found.

“These results should inform shared decision making between clinicians and patients and provide a rationale for prospective studies evaluating whether earlier [DBS] can optimize long-term cognitive and functional outcomes in [Parkinson’s patients with GBA1 variants],” the researchers wrote.

The study, “Timing of Deep Brain Stimulation and Cognitive Trajectories in GBA1-Associated Parkinson’s Disease,” was published in Movement Disorders.

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Parkinson’s is a neurological disorder marked by motor symptoms such as slowed movements and tremor. People with Parkinson’s also commonly experience nonmotor symptoms, including problems with thinking and memory.

The causes of Parkinson’s aren’t fully understood, but changes in certain genes can contribute to the disease in some people. One gene linked to Parkinson’s is GBA1. People with variants in this gene tend to experience more severe movement problems and faster cognitive decline than those without them.

DBS is a surgical treatment in which electrodes are implanted in specific areas of the brain to deliver electrical stimulation. This can help ease motor symptoms.

Some studies have reported that Parkinson’s patients with GBA1 variants experience rapid cognitive decline after undergoing DBS. However, the available evidence has not established whether DBS contributes to this decline or whether it results from the disease itself.

In this study, researchers examined whether the timing of DBS was linked to cognitive decline in Parkinson’s patients with GBA1 variants. They tracked changes in cognitive function over time in 91 patients with these variants and 252 patients without them. All 343 patients underwent bilateral subthalamic nucleus DBS (STN-DBS), which targets a brain region involved in controlling movement.

The researchers found that patients with GBA1 variants who underwent DBS later tended to experience faster cognitive decline than those treated earlier. This finding held after accounting for age and, in additional analyses, medication doses. But among Parkinson’s patients without GBA1 variants, the difference in cognitive decline between earlier and later DBS was not significant in the quartile-based analysis.

The researchers wrote that “these findings highlight the potential impact of STN-DBS timing on cognitive trajectories in this genetically defined subgroup.”

In additional analyses, researchers tested different cutoff points for when DBS was performed. Among patients with GBA1 variants, the differences in cognitive decline between earlier and later treatment were most pronounced when researchers used cutoffs of seven and eight years after Parkinson’s onset. These findings “suggest that the timing of surgery should be carefully considered as part of individualized treatment planning” for Parkinson’s patients with GBA1 variants, the researchers said.

The researchers called for further studies to validate their findings and prospectively assess whether earlier DBS initiation can consistently yield better long-term cognitive outcomes. They also noted that the study was observational and that a comparison group of patients with GBA1 variants who had not undergone DBS was not available across all study sites. As a result, the researchers wrote that they could not determine whether cognitive decline was related to GBA1 variants, DBS, or a possible interaction between the two.