Cognitive and behavioural effects of chronic stimulation of the subthalamic nucleus in patients with Parkinson's disease

Abstract

Objective: To investigate cognitive and behavioural effects of bilateral lead implants for high frequency stimulation (HFS) of the subthalamic nucleus in patients with Parkinson's disease; and to discriminate between HFS and the effects of surgical intervention on cognitive function by carrying out postoperative cognitive assessments with the stimulators turned on or off. Methods: Motor, cognitive, behavioural, and functional assessments were undertaken in 20 patients with Parkinson's disease before implantation and then at three, six, and 12 months afterwards. Nine patients were also examined 18 months after surgery. Postoperative cognitive assessments were carried out with stimulators turned off at three and 18 months, and turned on at six and 12 months. Results: Cognitive assessment showed a significant postoperative decline in performance on tasks of letter verbal fluency (across all postoperative assessments, but more pronounced at three months) and episodic verbal memory (only at three months, with stimulators off). At three, six, and 12 months after surgery, there was a significant improvement in the mini-mental state examination and in a task of executive function (modified Wisconsin card sorting test). On all postoperative assessments, there was an improvement in parkinsonian motor symptoms, quality of life, and activities of daily living while off antiparkinsonian drugs. A significant postoperative decrease in depressive and anxiety symptoms was observed across all assessments. Similar results were seen in the subgroup of nine patients with an 18 month follow up. Following implantation, three patients developed transient manic symptoms and one showed persistent psychic akinesia. Conclusions: Bilateral HFS of the subthalamic nucleus is a relatively safe procedure with respect to long term cognitive and behavioural morbidity, although individual variability in postoperative cognitive and behavioural outcome invites caution. Stimulation of the subthalamic nucleus does not per se appear to impair cognitive performance in patients with Parkinson's disease and may alleviate the postpoperative decline in verbal fluency.

CBT for the treatment of depression in Parkinson’s disease: a promising nonpharmacological approach

“…Deep brain stimulation (DBS) is often used as a late therapeutic option in the treatment of PD when motor symptoms can not be adequately controlled with medication alone [39]. In addition to improving motor function, some studies have also found DBS to be associated with improvements in mood and depression [40,41,42]. The results of these studies are equivocal, however, as some reports have demonstrated adverse reactions, including significant worsening of depressive symptoms and suicidal ideation [41,43,44] and inducement of mania [45,46,47].…”

Cognitive and Behavioural Changes After Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease

“…Such postoperative decline on episodic verbal memory tasks was detectable already 3 months after surgery in some studies (Alegret et al, 2001;Daniele et al, 2003), while in one cohort became not statistically significant at 1-year follow-up (Daniele et al, 2003).…”

“…Such decline on performance on verbal fluency tasks has been usually detected few months after the surgical intervention and has been observed in patients with 1-year (Pillon et al, 2000;Daniele et al, 2003), 3-year (Funkiewiz et al, 2004, 5-year (Contarino et al, 2007;Fasano et al, 2010), and 8-year follow-up (Fasano et al, 2010). A recent study aimed at assessing longterm motor and cognitive outcome 8 years after implants for deep brain stimulation of the subthalamic nucleus in 20 patients with Parkinson's disease (Fasano et al, 2010) detected a decline on phonological verbal fluency task, which was slightly more pronounced 8 years than 5 years after surgery.…”

“…As suggested by a meta-analysis on neuropsychological studies in patients with Parkinson's disease treated by deep brain stimulation of the subthalamic nucleus (Parsons et al, 2006), a statistically significant but small decline of postoperative performance on tasks of episodic verbal memory has been reported in some investigations (Alegret et al, 2001;Daniele et al, 2003;Dujardin et al, 2001;Jahanshahi et al, 2000;Pillon et al, 2000;Saint-Cyr et al, 2000;Trepanier et al, 2000), but not in others. Such postoperative decline on episodic verbal memory tasks was detectable already 3 months after surgery in some studies (Alegret et al, 2001;Daniele et al, 2003), while in one cohort became not statistically significant at 1-year follow-up (Daniele et al, 2003).…”

“…Across all neuropsychological studies assessing cognitive functioning in patients with Parkinson's disease treated by deep brain stimulation of the subthalamic nucleus, a consistently reported finding is a postoperative decline on tasks of phonological and semantic verbal fluency (Ardouin et al 1999;Pillon et al 2000, Daniele et al 2003Funkiewiez et al 2004;Parsons et al, 2006), which was detected already few months after surgery in some studies and gradually increased over time in studies with long-term followup (Contarino et al, 2007;Fasano et al, 2010).…”