Vol. 13 nº 4 - Oct/Nov/Dec de 2019
Views & Reviews Pages 367 to 377

How is cognition in subthalamic nucleus deep brain stimulation Parkinson's disease patients? 2007-2017 Systematic Review
Como é a cognição em pacientes com doença de parkinson com estimulação cerebral profunda no núcleo subtalâmico? Uma revisão sistemática

Authors: Eduarda Naidel Barboza e Barbosa1; Helenice Charchat Fichman2


Descriptors: Parkinson's disease; deep brain stimulation; subthalamic nucleus; cognition.
doença de Parkinson; estimulação cerebral profunda; núcleo subtalâmico; cognição.

The impairments in cognitive functions such as memory, executive function, visuospatial skills and language in Parkinson's disease (PD) are drawing increasing attention in the current literature. Studies dedicated to investigating the relationship between subthalamic nucleus deep brain stimulation (STN-DBS) and cognitive functioning are contradictory. This systematic review aims to analyze the impact on the cognitive functioning of patients with PD and STN-DBS. Articles published in the 2007-2017 period were retrieved from the Medline/Pubmed databases using PRISMA criteria. The analysis of 27 articles revealed many conflicting results, precluding a consensus on a cognitive functioning standard and hampering the establishment of a neuropsychological profile for PD patients who underwent STN-DBS surgery. Further studies investigating this relationship are needed.

As deficiências nas funções cognitivas, como memória, função executiva, habilidades visuoespaciais e linguagem na doença de Parkinson (DP), estão cada vez mais chamando a atenção na literatura atual. Estudos dedicados a investigar a relação entre a estimulação cerebral profunda do núcleo subtalâmico (ECP-NST) e o funcionamento cognitivo são contraditórios. Esta revisão sistemática tem como objetivo analisar o impacto no funcionamento cognitivo de pacientes com DP e ECP-NST. Os artigos foram coletados nas bases de dados Medline / Pubmed publicadas no período de 2007-2017, utilizando os critérios do PRISMA. Após a análise de 27 artigos observou-se muitos resultados opostos, não sendo possível convencionar um padrão de funcionamento cognitivo o que dificulta o estabelecimento de um perfil neuropsicológico para pacientes com essa doença que foram submetidos à cirurgia de ECP-NST, sendo necessários mais estudos.

The diagnosis of PD is performed using clinical criteria by trained professionals, such as neurologists. These criteria are based on the identification of clinical manifestations and pure motor symptoms. Patients with PD present, in addition to motor impairments, non-motor impairments manifesting as a variety of neuropsychiatric symptoms,1,2 changes in sleep, behavior and cognition,3,4 and which may lead to dementia.5,6

The impairments in cognitive functions, such as memory, executive function, visuospatial skills and language in PD, are drawing increasing attention in the current literature.6 One in three patients with PD presents cognitive impairment at the time of (or soon after) diagnosis, which progressively worsens and may even cause dementia in the later stages of the disease.7

Since 1940, surgical treatment of PD has been performed. More recently, since 1998, ablation has given rise to deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) or globus pallidus internus (GPi).5,8 The target most chosen by centers performing the surgery is the STN due to the possibility of decreasing drug doses and, consequently, reducing adverse effects.

The literature points to evident motor and QoL improvement after DBS in patients with PD. However, studies dedicated to investigating the relationship between STN-DBS and cognitive functioning are controversial, and further studies investigating this relationship are needed.

In this context, the investigation of the cognitive effects of STN-DBS in PD becomes paramount. The objective of this study is to analyze the effects of subthalamic nucleus (STN) DBS on the cognition of PD patients through a systematic review. The Preferred Reporting Items for Systematic Review and Meta-Analyzes (PRISMA) Checklist was employed.


The systematic review is a type of scientific research that aims to gather, critically evaluate and conduct a synthesis of multiple primary studies.10

Bibliographic survey

We designed a systematic review of the literature according to the Preferred Reporting Items for Systematic Review and Meta-Analyzes (PRISMA) criteria. The following terms were used: "Deep Brain Stimulation", "DBS", "Cognitive Functions" and "Parkinson Disease" with the Boolean operator "AND". We selected scientific papers published in English between January 2007 and January 2017, with comparative clinical trials in humans, on the Medline/Pubmed databases. Articles published before 2007, systematic reviews, case studies, books chapters and studies using animals were excluded.

Studies selection

Initially, this method retrieved 345 papers (Figure 1). To refine the research, the following topics were selected: "Parkinson's Disease", "Subthalamic Nucleus", "Deep Brain Stimulation", "DBS", "Cognition" (263), published on the Medline/Pubmed databases (223) between 2007 and 2017 (195). For the papers selected, a title and abstract analysis was performed manually to consider only studies with human clinical trials (66). Literature reviews and case studies were excluded, as were articles containing problems in the methodology, such as absence of: (a) inclusion and exclusion criteria; (b) complete assessment protocol; and (c) pre or post-surgery assessment (27). The researchers selected the articles independently: they considered suitable studies that: (a) evaluated cognition of PD patients with STN-DBS; (b) presented the instruments and domains evaluated; and (c) reported pre and post-surgical results of articles.

Figure 1. Article search flow diagram.


The final list of included articles that met the study criteria, in ascending order of year, together with objectives and results, is given in Table 1. A list of studies, grouped according to the effects of DBS on specific cognitive domains, with neuropsychological tasks (carried out in each study assessed) is given in Table 2.

There were 27 studies involving a total of 832 patients with STN-DBS and 458 patients with DBS and/or healthy subjects in the control group who did not undergo surgery. Age ranged from 51 to 67 years, disease duration ranged from 9.7 to 15.75 years, education (when reported) ranged from 1.9 to 14.5 years, while pre-surgical evaluation occurred 2 weeks before surgery and postoperative up to 132 months after surgery (11 years).

Global cognitive functioning

Most studies9-21 evaluated global cognitive functioning with 3 different instruments and observed no significant change in subject performance. Only 3 articles22-24 reported impairment in the overall cognitive functioning of their sample.


Memory,10,14 as well as specific aspects such as verbal memory,10,11,13,17,18,20 verbal learning,17,18 recognition27 and spatial memory,17,18 showed no significant difference before and after surgery, although there was a decline in specific aspects in 6 articles.9,13,16,19,23,27

Executive function

Several EF aspects were evaluated: visuospatial working memory, stimulus-action-reward association, behavior regulation, semantic and phonemic verbal fluency, cognitive flexibility, abstract concept development, initiation and inhibition responses and working memory. Thirteen articles 11,12,15,17,18,20,21,25-30 reported patient stability or improvement in their results. However, the results presented by the majority of articles9-14,17-19,22-25,27,28,31-35 were the opposite to those observed above, in verbal semantic and phonemic verbal fluency, working memory, planning and cognitive flexibility.

Perception and attention

For these two cognitive functions, only two articles16,19 found cognitive decline after STN-DBS in attention, whereas 7 other articles10,11,13,18,20,27,28 found no significant change.


Five articles13,20,21,27,33 showed better or stable performance in language, production of words,12 semantic and phonemic verbal fluency tasks,19 and vocabulary subtest of the Wechsler Abbreviated Scale24 postoperatively.

Visuoconstructive and visuospatial skills

Two articles16,19 reported decline in Visuoconstructive and visuospatial skills, while 3 articles10,12,20 showed no difference pre and post-operatively.

Motor and sensory coordination

There was no decline in coordination.9,13,26


This systematic review sought to investigate the cognitive functions most affected by STN-DBS according to studies published in the last 10 years.

Analysis of the results of all 27 articles revealed no consensus among studies on the effect of this surgery on patients. In most articles that evaluated global cognitive functioning, cognition either improved or did not worsen, a good finding since the technique does not target non-motor symptoms. However, STN-DBS can promote an improvement in cognition indirectly in that, once the subject has reduced or eliminated motor symptoms, their quality of life (QoL) improves, allowing them to return to previously discontinued tasks and habits. This behavioral change can yield both cognitive and mood benefits. To confirm this hypothesis would require studies comparing mood (anxiety, depression) before and after stimulation.

In general, this heterogeneity of results can be due to several factors, as discussed below. The aggravation of cognitive disorders can be strongly predicted by neuropsychological tests in the early stage of the disease, with or without timely medical treatment. On average, 25-50% of PD patients develop MCI or dementia or progress from MCI to dementia within 5 years of diagnosis.36 Thus, the selection of instruments is of paramount importance and needs to be accompanied by certain precautions. There is no specific protocol defining the most appropriate instruments for this evaluation, but knowing which functions are influenced by PD makes choosing the tests easier. Establishing a protocol to be used by studies and research centers would render it easier to access, understand and compare results, leading to further investigation of the impaired aspects.37 Any change indicated by the tests is subtle, as cognitive impairment detected in specialized tests is not commonly reported by patients, caregivers or health professionals. As stated above, QoL assessments in these patients show improvement, even when cognitive impairment is detected. With regard to memory impairment, for example, there are several associated factors, such as the subject's age, duration of illness, and even executive functioning. In the case of the articles, the recognition memory9,13 and recall18,19,27,28 were impaired and this is observed in the literature, indicating a possible evolution to dementia in PD.36 EFs are an umbrella concept that cover several aspects and, consequently, feature as the most evaluated functions and with the most discrepant results. Commonly, these functions appear to be impaired earlier in the disease and are directly associated with daily activities, impacting patient QoL.38 Verbal fluency worsened in many studies.9-12,14-16,22-24,27,28,31,35 In fact, worsening on category fluency tasks is the most frequent cognitive sequela reported after STN-DBS. This is in accordance with recent evidence suggesting that the STN is a potent regulator of basal ganglia and thalamocortical limbic and associative circuits. Frontal lobe-related cognitive changes after DBS may be determined by the modulation of these distinct neural networks.39 Impairment of visuospatial skills, in which motor involvement is the main criteria, even in the early stages of the disease, is expected in PD - at odds with the fact that only 5 articles evaluated this function.10,12,16,19,20

One of the inclusion criteria was surgery targeting the STN, and this was one of the limitations found in the studies. STNs are considered to produce more cognitive side effects in patients than when electrodes are implanted in the globus pallidus.39 Patient age ranged from 51 to 67 years at the time of surgery and the literature indicates a higher risk of cognitive decline associated with older age. The medication or stimulation parameters in study participants were not controlled, and there may be an influence of reductions in postoperative medication or differences in DBS parameters. On top of this, there are differences regarding follow-ups, making it difficult to understand and establish "specific milestones", with which improvement or worsening of effects over months/years can be predicted. Thus, while certain articles reported follow-up effects for 36,22,24 8422,26 or up to 13219 months, others had data for 12,24,26 613,15,20,24 and up to 317,22,31 months. This discrepancy makes a fair comparison and reliable analysis of the data unfeasible. Using the same battery of tests at such widely varying time intervals may give the impression of an improvement simply by the learning effect of a short-term reassessment and a marked worsening as the disease progresses naturally over a long-term reassessment.37

There was an absence of reports on the subjective impact of daily cognitive decline associated with motor symptoms28 and of preoperative follow-up on cognitive function.33 There were no other evaluations of impairment to activities of daily living associated with the disease, which interferes with the subjective perspective of patient abilities. These aspects are directly influenced when motor improvement occurs. Thus, from the recovery of skills, new perspectives emerge, which can have a positive repercussion on non-motor symptoms, such as cognition. The angle of the surgical trajectory and proximity of the STN-DBS electrodes greatly influences the outcomes seen after surgery, where these aspects may be related to changes in the cognitive and emotional functioning of patients.12,33 Thus, the results are expected to vary from one another - as has been seen. This disparity is mainly due to variations in the characteristics of patients selected for surgery across different centers (age,21,26 preoperative state10,24 and comorbidity with other conditions such as psychiatric disorders11,12), making conclusions difficult to compare and analyze.

Thus, it was not possible to establish a neuropsychological profile of PD patients with STN-DBS. This is cause for concern since patients with MCI in PD are more likely to progress to dementia as the disease progresses, and it is necessary to understand which cognitive functions become impaired in this disease after DBS implantation to avoid miscalculating normal with worsening evolution. Much of this can also be attributed to the lack of a specific PD assessment protocol.37

The results of this review highlight the need to establish a neuropsychological profile of PD patients to understand and investigate the effects of implantation of STN-DBS on cognitive non-motor symptoms. Future studies intend to develop a neuropsychological battery and evaluate patients with PD and STN-DBS to discriminate the aspects affected in these subjects and understand which factors contribute to outcomes.


Eduarda Naidel Barboza e Barbosa: study concept and design, literature search, drafting and revising the manuscript. Helenice Fichman: contribution during the writing process with suggestions and corrections.


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1. Master, Pontifical Catholic University of Rio de Janeiro (PUC-Rio), Rio de Janeiro, RJ, Brazil
2. Professor, Pontifical Catholic University of Rio de Janeiro (PUC-Rio), Rio de Janeiro, RJ, Brazil

This study was conducted at the Pontifical Catholic University of Rio de Janeiro, RJ, Brazil.

Eduarda Naidel
Pontifical Catholic University
Rua Marquês de São Vicente, 225 / Gávea
22451-900 Rio de Janeiro RJ - Brazil
Email: psienbb@gmail.com

Received May 21, 2019.
Accepted after revision September 25, 2019.


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