Dr Doreen GruberDoreen Gruber, MD
Deep brain stimulation (DBS) may increase the risk of dementia and cognitive decline in patients with Parkinson disease who also have mild cognitive impairment (MCI), new research has suggested.1

The results found that disease duration, but not age, at the time of DBS surgery was significantly related to the risk of developing dementia.

Ultimately, those treated with subthalamic DBS deteriorated by 1.6 points per year on the modified Mattis Dementia Rating Scale (mMDRS), and preoperative MCI correlated with conversion to dementia. After undergoing the DBS implantation, 18.9% (n = 7) patients had no cognitive impairment while the remaining 81% of patients were diagnosed with either MCI (40.5%; n = 15) or dementia (40.5%; n = 15).

The investigators, led by Doreen Gruber, MD, a senior physician at Kliniken Beelitz, in Germany, noted that a “lack of a matched control group precludes final conclusions regarding the possible influence of [subthalamus]-DBS on disease course with respect to conversion to dementia.” Although, in light of that, they did acknowledge that “the present data complies with previous studies on a cognitive decline in medically treated patients [with Parkinson]. The gradual deterioration of global cognitive impairment measured by MDRS and the conversion to dementia was associated with disease duration, but not with age of patients.”

The observational, “real-life” study explored 104 patients with a mean age of 67.6 years (±6.9) with a disease duration of 17.1 years (±5.1), of which 79 patients had neuropsychological results available preoperatively. In total, 37 patients with a mean age of 67.6 years (±6.9) and a mean disease duration of 11.3 years (±4.1) were available for long-term follow-up. Of those 37 patients, preoperatively, 24.3% (n = 9) showed no MCI and 75.7% (n = 28) showed MCI.

At 6.3 years (±2.2) of follow-up, Unified Parkinson’s Disease Rating Scale motor subscores worsened post- versus pre-surgery (P <.01) by a difference of 7.1 points (±14.1). Levodopa equivalent dose (LED) showed a sustained reduction trend of 39.1% compared to presurgical levels (P <.01). “Importantly, all patients had at least one replacement of their implantable pulse generator during an observation period (October 2018), suggesting a continued benefit of motor symptoms via [subthalamus]-DBS,” Gruber and colleagues wrote.

Of the 28 patients pre-surgically identified with Parkinson MCI, 46.4% (n = 13) converted to Parkinson dementia following 6.3 years with the DBS. In contrast, the conversion rate to dementia from the 9 patients with Parkinson and normal cognitive function was 22.2% (n = 2).

There was a trend toward an association between preoperative MCI and conversion to dementia during the postoperative observation period with respect to baseline age, sex, and education (adjusted odds ratio [aOR], 10.8; 95% CI, 1.0 to 119.0; P = .052).

In comparison to the non-demented patients with Parkinson, (those who were cognitively normal or with MCI) those patients with dementia showed a longer disease duration of 5.2 years (P <.01).

Additionally, those with dementia showed more severe motor impairment, with mean UPDRSm scores of 36.1 (±12.9) compared to 23.7 (±7.8) for those without dementia (P <.01). Patients with Parkinson with dementia showed a more pronounced deterioration of UPDRSm scores for bradykinesia (P = .012), rigidity (P = .018), and axial symptoms (summary score of speech, posture, gait, and postural stability; P = .032).

Gruber and colleagues noted that study limitations consisted of the lack of a control group, and a high dropout rate of 53%, which they noted “might have biased the present results since [Parkinson] dementia may be associated with reduced study participation and death” in 12 and 21 participants, respectively, of the 79 with data. “However, this bias is difficult to avoid in real-life studies despite home visits as performed in the present study, but may certainly alter the real dementia prevalence and the correlation between dementia and age,” they wrote.

“This observational, ‘real-life’ study provides long-term results of cognitive decline in [subthalamus]-DBS-treated patients with presurgical MCI possibly predicting the conversion to dementia,” Gruber and colleagues concluded. "Comparison with other studies on cognition and [Parkinson] do not support a disease-modifying effect of [subthalamus]-DBS on cognitive domains.”
REFERENCES
1. Gruber D, Calmbach L, Kühn AA, et al. Longterm outcome of cognition, affective state, and quality of life following subthalamic deep brain stimulation in Parkinson’s disease. J Neural Transm. Published online January 25, 2019. doi:10.1007/s00702-019-01972-7.