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Systematic review of neuropsychological instruments used in subthalamic nucleus deep brain stimulation in Parkinson´s disease patients

Revisão Sistemática de Instrumentos Neuropsicológicos usados em Pacientes com Doença de Parkinson e Estimulação Cerebral Profunda no Núcleo Subtalâmico

ABSTRACT.

In addition to drug treatment, surgical intervention represents an alternative to PD patients with motor deficits. The most common intervention is subthalamic nucleus deep brain stimulation (STN-DBS). It is extremely important to perform a neuropsychological assessment in patients with STN-DBS, not only to identify losses related to the disease, but also to compare influence on cognition both pre and postoperatively.

Objective:

the objective of this systematic review was to investigate the instruments frequently used in studies related to STN-DBS in PD patients.

Methods:

articles were retrieved from Medline/Pubmed databases published in the 2007-2017 period using PRISMA criteria.

Results:

after analyzing 27 articles, the absence of a specific evaluation protocol for PD with STN-DBS was evident.

Conclusion:

non-motor symptoms are not given due importance in neuropsychological assessments. It is crucial to acknowledge that these symptoms have a major impact on the quality of life of patients. Greater engagement in assessing these aspects is required, in order to bridge the gaps in research.

Key words:
Parkinson’s disease; deep brain stimulation; neuropsychological instruments; neuropsychological assessment

RESUMO.

Além do tratamento medicamentoso, a intervenção cirúrgica é uma alternativa aos pacientes com DP com déficits motores. A mais comum é a estimulação cerebral profunda do núcleo subtalâmico (ECP-NST). É extremamente importante realizar uma avaliação neuropsicológica em pacientes com ECP-NST, não apenas para identificar perdas relacionadas à doença, mas também para comparar a influência na cognição em cirurgias pré e pós-operatórias.

Objetivo:

esta revisão sistemática teve como objetivo investigar os instrumentos frequentemente utilizados em pesquisas relacionadas a ECP-NST em pacientes com DP.

Métodos:

Os artigos foram coletados nas bases de dados Medline / Pubmed publicadas no período de 2007-2017, utilizando os critérios do PRISMA.

Resultados:

após a análise de 27 artigos, percebeu-se a ausência de um protocolo de avaliação específico para a DP com ECP-NST.

Conclusão:

os sintomas não motores não tem recebido a devida importância na avaliação neuropsicológica. É fundamental reconhecer que eles representam grande influência na qualidade de vida dos pacientes. É necessário maior engajamento na avaliação desses aspectos, a fim de preencher as lacunas das pesquisas.

Palavras-chave:
doença de Parkinson; estimulação cerebral profunda; instrumentos neuropsicológicos; avaliação neuropsicológica

Parkinson’s disease (PD) is considered the second-most-common neurodegenerative disease, preceded only by Alzheimer’s disease (AD).11 Pavão R. Aprendizagem Implícita e Doença de Parkinson. Dissertação de mestrado - Instituto de Biociências da Universidade de São Paulo. Departamento de Fisiologia, 2007.,22 de Paixão AO, de Jesus AVF, Silva FS, Messias GMS, Nunes TLGM, Nunes TLGM, Santos TB, Gomes MZ, Correia MGS. Doença de Parkinson: Uma Desordem Neurodegenerativa. Cadernos de Graduação - Ciências Biológicas e da Saúde. 2016; 1(16):57-65. PD’s motor characteristics are much better known than its non-motor ones, but patients also have functional impairment.11 Pavão R. Aprendizagem Implícita e Doença de Parkinson. Dissertação de mestrado - Instituto de Biociências da Universidade de São Paulo. Departamento de Fisiologia, 2007.,33 Machado FA, Reppold CT. The effect of deep brain stimulation on motor and cognitive symptoms of Parkinson's disease - A literature review. Dement Neuropsychol. 2015;9(1):24-31.

4 Werneck ALS. Doença de Parkinson: Etiopatogenia, Clínica e Terapêutica. Rev Hosp Univ Pedro Ernesto. 2010;9:10-9.
-55 Heluani, AS. Cognição, humor e atividades funcionais em pacientes com doença de Parkinson submetidos à estimulação cerebral profunda bilateral em núcleo subtalâmico. Dissertação de mestrado - Faculdade de Medicina da Universidade de São Paulo, 2014. When PD was first described, cognition was believed to be preserved, but current research66 Nombela C, Rowe JB, Winder-Rhodes SE, Hampshire A, Owen AM, Breen DP, et al. Genetic impact on cognition and brain function in newly diagnosed Parkinson's disease: ICICLE-PD study. Brain. 2016;137: 2625-31.,77 Ding W, Ding LJ, Li FF, Han Y, Mu L. Neurodegeneration and cognition in Parkinson's disease: a review. Eur Rev Med Pharmacol Sci. 2015;19: 2275-81. reports cognitive decline. Besides drug treatment, surgical intervention can be used in some cases. One of these methods is deep brain stimulation (DBS), consisting of electrical stimulation of subcortical structures. The main objective of DBS is motor control of symptoms; however, the stimulated areas are also potentially able to stimulate some cognitive functions secondarily.88 Aguilar OM, Soto CA, Esguerra M. Cambios neuropsicológicos asociados a estimulación cerebral profunda en enfermedad de parkinson: revisión teórica. Suma Psicológica. 2011;18(2):89-98.

Studies usually promote cognitive screening in patients to characterize the sample and identify the impairments to be analyzed. However, comparing cognitive data from different populations and based on different tests can produce conflicts in the literature, mainly because some screening instruments do not provide the sensitivity to assess cognitive functioning sufficiently55 Heluani, AS. Cognição, humor e atividades funcionais em pacientes com doença de Parkinson submetidos à estimulação cerebral profunda bilateral em núcleo subtalâmico. Dissertação de mestrado - Faculdade de Medicina da Universidade de São Paulo, 2014., while others employ different versions of the same test or use non-standard tasks.

The objective of this review was to learn about and understand the use of some instruments used in studies of PD patients with STN-DBS and to relate these findings with the literature in general. The search included articles published between January 2007 and January 2017, based on The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) criteria.

METHODS

The systematic review is a type of scientific study that aims to gather, critically evaluate and produce a synthesis of multiple primary studies.99 Stella F, Gobbi LTB, Gobbi S, Oliani MM, Tanaka K, Pieruccini-Faria F. Early impairment of cognitive functions in Parkinson's disease. Arq Neuropsiquiatr. 2007;65(2b):406-10.

Bibliographic survey

We designedasystematic 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, involving comparative clinical trials in humans, from the Medline/Pubmed databases. Articles published before 2007, systematic reviews, case studies, book chapters and studies using animals were excluded.

Study selection

Initially, this method retrieved 345 studies (Figure 1). To refine the search, the following topics were selected: “Parkinson’s Disease”, “Subthalamic Nucleus”, “Deep Brain Stimulation”, “DBS”, “Cognition” (263), published on the Medline/Pubmed database (223) between 2007 and 2017 (195). From the material retrieved, we examined titles and abstracts for studies involving only human clinical trials (66). Literature reviews and case studies were excluded, as were articles with 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: considering suitable studies that (a) evaluated PD patient cognition with STN-DBS; (b) reported the instruments and domains evaluated; and (c) presented pre and post-surgical results.

Figure 1
Article search flow diagram.

RESULTS

The final list of articles included based on the search criteria in order of year, with Objectives and Results (Table 1), a list of instruments with quantity, separated by domains (Table 2) and a list of instruments used before and after DBS implantation to assess the cognitive aspects of the patients (Table 3) are given below.

Table 1
List of articles included in the systematic review criteria.
Table 2
List and frequency of instruments used by domain.
Table 3
Instruments most used pre and post-DBS.

DISCUSSION

A total of 61 (sixty-one) instruments were used to evaluate different aspects of patients, including batteries, subtests, scales and tasks (Table 2). These can be ordered from the most evaluated to least used, as follows: executive functions (14), global cognitive functioning (10) and mood (10), memory (9), language (5), psychiatric symptoms (3) and sensory-motor coordination (3), patient quality of life (2) and visuoconstructive skills (2) and attention (1), perception (1) and activities of daily living (1). Early in the onset of symptoms, 24% of patients presented cognitive impairment, especially memory problems, and executive function disorders: selective attention, flexibility in reasoning and planning capacity, visuoconstructive skills and naming ability.99 Stella F, Gobbi LTB, Gobbi S, Oliani MM, Tanaka K, Pieruccini-Faria F. Early impairment of cognitive functions in Parkinson's disease. Arq Neuropsiquiatr. 2007;65(2b):406-10.

What justifies the most evaluated domains in the selected articles? PD patients with mild cognitive impairment (MCI), compared with PD patients without MCI, have significantly poorer performance on almost all cognitive domains: executive functions, attention, memory, and language.77 Ding W, Ding LJ, Li FF, Han Y, Mu L. Neurodegeneration and cognition in Parkinson's disease: a review. Eur Rev Med Pharmacol Sci. 2015;19: 2275-81. One in three patients with PD has cognitive impairment at the time of, or shortly after, diagnosis, progressively worsening or even causing dementia in the advanced stages.66 Nombela C, Rowe JB, Winder-Rhodes SE, Hampshire A, Owen AM, Breen DP, et al. Genetic impact on cognition and brain function in newly diagnosed Parkinson's disease: ICICLE-PD study. Brain. 2016;137: 2625-31. However, cognitive alterations are common even in non-PD patients.1010 Schneider JS, Sendek S, Yang C. Relationship between Motor Symptoms, Cognition, and Demographic Characteristics in Treated Mild/Moderate Parkinson's Disease. PLoS One. 2015;10(4):1-11. Cognitive impairment increases the risk of dementia, by 1.7 to 5.9, and early detection and identification of dementia risk is a major challenge due to the heterogeneity of patient profiles.66 Nombela C, Rowe JB, Winder-Rhodes SE, Hampshire A, Owen AM, Breen DP, et al. Genetic impact on cognition and brain function in newly diagnosed Parkinson's disease: ICICLE-PD study. Brain. 2016;137: 2625-31. The prevalence of dementia in PD is 24 to 31%,1111 de Oliveira MD, Machado DMS. Cognitive decline in Parkinson's disease: contributions of Neuropsychology. Rev Med Minas Gerais. 2015;24(3): 349-54. thus, evaluating the PD patient in a global and continuous way is the best path for monitoring the evolution of the effects of the disease. Comorbidity with dementia can be justified when we consider the ascending involvement of the brainstem to the cortical area. Microscopic modifications may be incorporated into its pathophysiology, including losses of neurons, gliosis, while surviving neurons may contain Lewy bodies. The loss of neurons markedly affects the substantia nigra, although it is not restricted to it. The damage also affects the aminergic nuclei of the brainstem, Meynert’s basal nucleus, hypothalamic nuclei and olfactory bulb.1212 Lang AE, Lozano AM. Parkinson's disease. First of two parts. New England J Med. 1998;339(15):1044-53. For this reason, it is essential to investigate the effects of surgery, such as STN-DBS, on the different aspects of a subject with PD.

The MMSE was the most used instrument1313 Cilia R, Siri C, Marotta G, Gaspari D, Landi A, Mariani CB, Benti R, Isaias IU, Vergani F, Pezzoli G, Antonini A. Brain networks underlining verbal fluency decline during STN-DBS in Parkinson's disease: An ECD-SPECT study. Parkinson Relat Disord. 2007;13(5):290-4.

14 Heo JH, Lee KM, Paek SH, Kim MJ, Lee JY, KimJY, et al. The effects of bilateral Subthalamic Nucleus Deep Brain Stimulation (STN DBS) on cognition in Parkinson disease. J Neurol Sci. 2008;273(1):19-24.

15 Lueken U, Schwarz M, Hertel F, Schweiger E, Wittling W. Impaired performance on the Wisconsin Card Sorting Test under left- when compared to right-sided deep brain stimulation of the subthalamic nucleus in patients with Parkinson's disease. J Neurol. 2008;255(12):1940-8.

16 Zangaglia R, Pacchetti C, Pasotti C, Mancini F, Servello D, Sinforiani E, et al. Deep brain stimulation and cognitive functions in Parkinson's disease: A three-year controlled study. Mov Disord. 2009; 24(11):1621-8.

17 York MK, Wilde EA, Simpson R, Jankovic J. Relationship between neuropsychological outcome and DBS surgical trajectory and electrode location. J Neurol Sci. 2009;287(1):159-71.

18 Fasano A, Romito LM, Daniele A, Piano C, Zinno M, Bentivoglio AR, Albanese A. Neuropsychological changes 1-year after subthalamic DBS in PD patients: A prospective controlled study. Brain. 2010; 133(9):2664-76

19 Van Wouwe NC, Ridderinkhof KR, Van Den Wildenberg WP, Band GP, Abisogun A, Elias WJ, et al. Deep Brain Stimulation of the Subthalamic Nucleus Improves Reward-Based Decision-Learning in Parkinson's Disease. Front Hum Neurosci. 2011;5:30.

20 Israeli-Korn S, Hocherman S, Hassin-Baer S, Cohen O, Inzelberg R. Subthalamic Nucleus Deep Brain Stimulation Does Not Improve Visuo-Motor Impairment in Parkinsons Disease. PLoS One. 2013;8(6):e65270.

21 Kim HJ, Jeon B, Yun J, Kim Y, Yang HJ, Paek S. Initial cognitive dip after subthalamic deep brain stimulation in Parkinson disease. J Neurol. 2013;260(8):2130-3.

22 Asahi T, Nakamichi N, Takaiwa A, Kashiwazaki D, Koh M, Dougu N, et al. Impact of bilateral subthalamic stimulation on motor/cognitive functions in Parkinson's disease. Neurol Med Chirurg. 2014;54(7):529-36.

23 Rizzone MG, Fasano A, Daniele A, Zibetti M, Merola A, Rizzi L, et al. Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: From the advanced phase towards the late stage of the disease? Parkinson Relat Disord. 2014;20(4):376-81.

24 Markser A, Maier F, Lewis C, Dembek T, Pedrosa D, Eggers C, Timmermann L, Kalbe E, Fink G, Burghaus L. Deep brain stimulation and cognitive decline in Parkinson's disease: The predictive value of electroencephalography. J Neurol. 2015;262(10):2275-84.
-2525 Krishnan S, Prasad S, Pisharady K, Sarma G, Sarma S, Kishore A. The decade after subthalamic stimulation in advanced Parkinson's disease: A balancing act. Neurol India. 2016;64(1):81. for assessing global cognitive functioning among the selected studies. It was followed by the MDRS1717 York MK, Wilde EA, Simpson R, Jankovic J. Relationship between neuropsychological outcome and DBS surgical trajectory and electrode location. J Neurol Sci. 2009;287(1):159-71.,2424 Markser A, Maier F, Lewis C, Dembek T, Pedrosa D, Eggers C, Timmermann L, Kalbe E, Fink G, Burghaus L. Deep brain stimulation and cognitive decline in Parkinson's disease: The predictive value of electroencephalography. J Neurol. 2015;262(10):2275-84.,2626 Klempírová O, Jech R, Urgosík D, Klempír J, Spacková N, Roth J, Ruzicka E. Deep brain stimulation of the subthalamic nucleus and cognitive functions in Parkinson's disease. Prague Med Rep. 2007;108(4): 315-23.

27 Witt K, Daniels C, Reiff J, Krack P, Volkmann J, Pinsker MO, et al. Neuropsychological and psychiatric changes after deep brainstimulation for Parkinson's disease: a randomised, multicentre study. Lancet Neurol. 2008;7(7):605-14.

28 Hariz M. Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson's disease. Lancet Neurol. 2009;8(3):223-4.

29 Daniels C, Krack P, Volkmann J, Pinsker MO, Krause M, Tronnier V, et al. Risk factors for executive dysfunction after subthalamic nucleus stimulation in Parkinson's disease. Mov Disord. 2010;25(11):1583-9.

30 Houvenaghel JF, Jeune F, Dondaine T, Esquevin A, Robert G, Péron J, et al. Reduced Verbal Fluency following Subthalamic Deep Brain Stimulation: A Frontal-Related Cognitive Deficit? PLoS One. 2015;10(10): e0140083.
-3131 Pham UHG, Andersson S, Toft M, Pripp AH, Konglund AE, Dietrichs E, et al. Self-Reported Executive Functioning in Everyday Life in Parkinson's Disease after Three Months of Subthalamic Deep Brain Stimulation. Parkinsons Dis. 2015;2015:461453. and RPM.1313 Cilia R, Siri C, Marotta G, Gaspari D, Landi A, Mariani CB, Benti R, Isaias IU, Vergani F, Pezzoli G, Antonini A. Brain networks underlining verbal fluency decline during STN-DBS in Parkinson's disease: An ECD-SPECT study. Parkinson Relat Disord. 2007;13(5):290-4.,1616 Zangaglia R, Pacchetti C, Pasotti C, Mancini F, Servello D, Sinforiani E, et al. Deep brain stimulation and cognitive functions in Parkinson's disease: A three-year controlled study. Mov Disord. 2009; 24(11):1621-8.,1818 Fasano A, Romito LM, Daniele A, Piano C, Zinno M, Bentivoglio AR, Albanese A. Neuropsychological changes 1-year after subthalamic DBS in PD patients: A prospective controlled study. Brain. 2010; 133(9):2664-76,3232 Castelli L, Lanotte M, Zibetti M, Caglio M, Rizzi L, Ducati A, et al. Apathy and verbal fluency in STN-stimulated PD patients. J Neurol. 2007; 254(9):1238-43. The MMSE has several favorable qualities such as fast administration, easy interpretation for use during medical consultation; patient acceptability; cultural independence; and both language and education, which makes it easier to reproduce in different studies and provides similar performance among examiners. In contrast, the instrument is influenced by subjective or non-standardized application and interpretation by professionals. Screening tests, such as these, known and widely used, are highly dependent on a minimal educational level and have low sensitivity and specificity.3333 Barbosa ENB, Charchat-Fichman H. (Advisor). Neuropsychological assessment contribuition to Mild Cognitive Impairment (MCI): methodological issues. Rio de Janeiro, 2015. 144p. MSc. Dissertation - Psychological Departament, Pontifícia Universidade Católica do Rio de Janeiro. Thus, an evaluation protocol containing only this instrument to evaluate global cognitive functioning would have little range in terms of the patient´s cognitive loss.

Several instruments were used to assess the EF of PD patients with STN-DBS, but the most recurrent were verbal fluency tasks, both semantic and phonemic,1313 Cilia R, Siri C, Marotta G, Gaspari D, Landi A, Mariani CB, Benti R, Isaias IU, Vergani F, Pezzoli G, Antonini A. Brain networks underlining verbal fluency decline during STN-DBS in Parkinson's disease: An ECD-SPECT study. Parkinson Relat Disord. 2007;13(5):290-4.,1414 Heo JH, Lee KM, Paek SH, Kim MJ, Lee JY, KimJY, et al. The effects of bilateral Subthalamic Nucleus Deep Brain Stimulation (STN DBS) on cognition in Parkinson disease. J Neurol Sci. 2008;273(1):19-24.,1616 Zangaglia R, Pacchetti C, Pasotti C, Mancini F, Servello D, Sinforiani E, et al. Deep brain stimulation and cognitive functions in Parkinson's disease: A three-year controlled study. Mov Disord. 2009; 24(11):1621-8.

17 York MK, Wilde EA, Simpson R, Jankovic J. Relationship between neuropsychological outcome and DBS surgical trajectory and electrode location. J Neurol Sci. 2009;287(1):159-71.
-1818 Fasano A, Romito LM, Daniele A, Piano C, Zinno M, Bentivoglio AR, Albanese A. Neuropsychological changes 1-year after subthalamic DBS in PD patients: A prospective controlled study. Brain. 2010; 133(9):2664-76,2020 Israeli-Korn S, Hocherman S, Hassin-Baer S, Cohen O, Inzelberg R. Subthalamic Nucleus Deep Brain Stimulation Does Not Improve Visuo-Motor Impairment in Parkinsons Disease. PLoS One. 2013;8(6):e65270.,2121 Kim HJ, Jeon B, Yun J, Kim Y, Yang HJ, Paek S. Initial cognitive dip after subthalamic deep brain stimulation in Parkinson disease. J Neurol. 2013;260(8):2130-3.,2323 Rizzone MG, Fasano A, Daniele A, Zibetti M, Merola A, Rizzi L, et al. Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: From the advanced phase towards the late stage of the disease? Parkinson Relat Disord. 2014;20(4):376-81.,2626 Klempírová O, Jech R, Urgosík D, Klempír J, Spacková N, Roth J, Ruzicka E. Deep brain stimulation of the subthalamic nucleus and cognitive functions in Parkinson's disease. Prague Med Rep. 2007;108(4): 315-23.,2727 Witt K, Daniels C, Reiff J, Krack P, Volkmann J, Pinsker MO, et al. Neuropsychological and psychiatric changes after deep brainstimulation for Parkinson's disease: a randomised, multicentre study. Lancet Neurol. 2008;7(7):605-14.,2929 Daniels C, Krack P, Volkmann J, Pinsker MO, Krause M, Tronnier V, et al. Risk factors for executive dysfunction after subthalamic nucleus stimulation in Parkinson's disease. Mov Disord. 2010;25(11):1583-9.,3030 Houvenaghel JF, Jeune F, Dondaine T, Esquevin A, Robert G, Péron J, et al. Reduced Verbal Fluency following Subthalamic Deep Brain Stimulation: A Frontal-Related Cognitive Deficit? PLoS One. 2015;10(10): e0140083.,3232 Castelli L, Lanotte M, Zibetti M, Caglio M, Rizzi L, Ducati A, et al. Apathy and verbal fluency in STN-stimulated PD patients. J Neurol. 2007; 254(9):1238-43.,3434 Castelli L, Rizzi L, Zibetti M, Angrisano S, Lanotte M, Lopiano L. Motor and cognitive outcome in patients with Parkinson's disease 8 years after subthalamic implants. Parkinson Relat Disord. 2010;16(2):115-18.,3535 Yágüez L, Costello A, Moriarty J, Hulse N, Selway R, Clough C, et al. Cognitive predictors of cognitive change following bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease. J Clin Neurosci. 2014;21(3):445-50.,3737 Tremblay C, Macoir J, Langlois M, Cantin L, Prudhomme M, Monetta L. The effects of subthalamic deep brain stimulation on metaphor comprehension and language abilities in Parkinson's disease. Brain Lang. 2015; 141:103-9.,3838 Vonberg I, Ehlen F, Fromm O, Kühn A, Klostermann F. Deep Brain Stimulation of the Subthalamic Nucleus Improves Lexical Switching in Parkinsons Disease Patients. PLoS One. 2016;11(8):e0161404 followed by the WCST.1313 Cilia R, Siri C, Marotta G, Gaspari D, Landi A, Mariani CB, Benti R, Isaias IU, Vergani F, Pezzoli G, Antonini A. Brain networks underlining verbal fluency decline during STN-DBS in Parkinson's disease: An ECD-SPECT study. Parkinson Relat Disord. 2007;13(5):290-4.

14 Heo JH, Lee KM, Paek SH, Kim MJ, Lee JY, KimJY, et al. The effects of bilateral Subthalamic Nucleus Deep Brain Stimulation (STN DBS) on cognition in Parkinson disease. J Neurol Sci. 2008;273(1):19-24.

15 Lueken U, Schwarz M, Hertel F, Schweiger E, Wittling W. Impaired performance on the Wisconsin Card Sorting Test under left- when compared to right-sided deep brain stimulation of the subthalamic nucleus in patients with Parkinson's disease. J Neurol. 2008;255(12):1940-8.
-1616 Zangaglia R, Pacchetti C, Pasotti C, Mancini F, Servello D, Sinforiani E, et al. Deep brain stimulation and cognitive functions in Parkinson's disease: A three-year controlled study. Mov Disord. 2009; 24(11):1621-8.,1818 Fasano A, Romito LM, Daniele A, Piano C, Zinno M, Bentivoglio AR, Albanese A. Neuropsychological changes 1-year after subthalamic DBS in PD patients: A prospective controlled study. Brain. 2010; 133(9):2664-76,2323 Rizzone MG, Fasano A, Daniele A, Zibetti M, Merola A, Rizzi L, et al. Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: From the advanced phase towards the late stage of the disease? Parkinson Relat Disord. 2014;20(4):376-81.,3030 Houvenaghel JF, Jeune F, Dondaine T, Esquevin A, Robert G, Péron J, et al. Reduced Verbal Fluency following Subthalamic Deep Brain Stimulation: A Frontal-Related Cognitive Deficit? PLoS One. 2015;10(10): e0140083.,3232 Castelli L, Lanotte M, Zibetti M, Caglio M, Rizzi L, Ducati A, et al. Apathy and verbal fluency in STN-stimulated PD patients. J Neurol. 2007; 254(9):1238-43.,3434 Castelli L, Rizzi L, Zibetti M, Angrisano S, Lanotte M, Lopiano L. Motor and cognitive outcome in patients with Parkinson's disease 8 years after subthalamic implants. Parkinson Relat Disord. 2010;16(2):115-18. These tasks, in particular, underwent different adaptations in each article. Evaluating EFs is a major challenge, as is defining the concept. In general, it is understood as abilities that involve planning, organization, flexibility, monitoring and inhibitory control,3939 Lourenço RA, Veras RP, Ribeiro PCC. Confiabilidade teste-reteste do mini-exame do estado mental em uma população idosa assistida em uma unidade ambulatorial de saúde. Rev Bras Geriatr Gerontol. 2008; 11:7-16. presenting an adaptive value for the subject, since their performance on activities related to personal, professional and other domains also become impaired.4040 Macuglia GR, Rieder CRM, de Almeida RMM. Funções executivas na doença de Parkinson: Revisão da Literatura. PSICO. 2012;43(4):552-61. Executive dysfunction is not always associated with memory, language or visuospatial skill impairment, among others, but rather a functional decline that can often be assessed based on self-report or a caregiver and/or family member informant. In patients with PD, it is a predictor of impairment, leading to ADL deficits.88 Aguilar OM, Soto CA, Esguerra M. Cambios neuropsicológicos asociados a estimulación cerebral profunda en enfermedad de parkinson: revisión teórica. Suma Psicológica. 2011;18(2):89-98.

A number of studies1414 Heo JH, Lee KM, Paek SH, Kim MJ, Lee JY, KimJY, et al. The effects of bilateral Subthalamic Nucleus Deep Brain Stimulation (STN DBS) on cognition in Parkinson disease. J Neurol Sci. 2008;273(1):19-24.,1616 Zangaglia R, Pacchetti C, Pasotti C, Mancini F, Servello D, Sinforiani E, et al. Deep brain stimulation and cognitive functions in Parkinson's disease: A three-year controlled study. Mov Disord. 2009; 24(11):1621-8.

17 York MK, Wilde EA, Simpson R, Jankovic J. Relationship between neuropsychological outcome and DBS surgical trajectory and electrode location. J Neurol Sci. 2009;287(1):159-71.
-1818 Fasano A, Romito LM, Daniele A, Piano C, Zinno M, Bentivoglio AR, Albanese A. Neuropsychological changes 1-year after subthalamic DBS in PD patients: A prospective controlled study. Brain. 2010; 133(9):2664-76,2121 Kim HJ, Jeon B, Yun J, Kim Y, Yang HJ, Paek S. Initial cognitive dip after subthalamic deep brain stimulation in Parkinson disease. J Neurol. 2013;260(8):2130-3.,2323 Rizzone MG, Fasano A, Daniele A, Zibetti M, Merola A, Rizzi L, et al. Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: From the advanced phase towards the late stage of the disease? Parkinson Relat Disord. 2014;20(4):376-81.,2727 Witt K, Daniels C, Reiff J, Krack P, Volkmann J, Pinsker MO, et al. Neuropsychological and psychiatric changes after deep brainstimulation for Parkinson's disease: a randomised, multicentre study. Lancet Neurol. 2008;7(7):605-14.,2929 Daniels C, Krack P, Volkmann J, Pinsker MO, Krause M, Tronnier V, et al. Risk factors for executive dysfunction after subthalamic nucleus stimulation in Parkinson's disease. Mov Disord. 2010;25(11):1583-9.,3232 Castelli L, Lanotte M, Zibetti M, Caglio M, Rizzi L, Ducati A, et al. Apathy and verbal fluency in STN-stimulated PD patients. J Neurol. 2007; 254(9):1238-43.,3434 Castelli L, Rizzi L, Zibetti M, Angrisano S, Lanotte M, Lopiano L. Motor and cognitive outcome in patients with Parkinson's disease 8 years after subthalamic implants. Parkinson Relat Disord. 2010;16(2):115-18.,3535 Yágüez L, Costello A, Moriarty J, Hulse N, Selway R, Clough C, et al. Cognitive predictors of cognitive change following bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease. J Clin Neurosci. 2014;21(3):445-50.,3636 Tang V, Zhu C, Chan D, Lau C, Chan A, Mok V, et al. Evidence of improved immediate verbal memory and diminished category fluency following STN-DBS in Chinese-Cantonese patients with idiopathic Parkinson's disease. Neurol Sci. 2015;36(8):1371-7.,4141 Ventre-Dominey J, Mollion H, Thobois S, Broussolle E. Distinct effects of dopamine vs STN stimulation therapies in associative learning and retention in Parkinson disease. Behav Brain Res. 2016;302:131-41. used 9 different types of tests to evaluate memory, predominantly the RAVLT (memory and verbal learning) and CBTT (memory and visual learning). The neocortex and striatum are structures involved in implicit memory processing and dopamine is the neurotransmitter involved in the formation of these memories.22 de Paixão AO, de Jesus AVF, Silva FS, Messias GMS, Nunes TLGM, Nunes TLGM, Santos TB, Gomes MZ, Correia MGS. Doença de Parkinson: Uma Desordem Neurodegenerativa. Cadernos de Graduação - Ciências Biológicas e da Saúde. 2016; 1(16):57-65.,4242 Rita HJP, Reis AI. (Advisor) Dissociação da memória explícita e implícita da Doença de Parkinson. MSc. Dissertation - Human Sciences and Social College. Universidade do Algarve. 2012. Therefore, with the dopaminergic deficit and degeneration of the basal nuclei involved in PD pathology, this processing and pre-activation of the priming and learning procedures are impaired. In the early stages of PD, there are deficits in the implicit learning of new tasks. Implicit learning is the process through which we become sensitive to certain regularities in the environment, in the absence of the intention to learn about these same regularities and in such a way that the resulting knowledge is difficult to express. In other words, implicit learning refers to the incidental or casual, and sometimes seemingly small, acquisition of a given event. It can generate significant future consequences.4242 Rita HJP, Reis AI. (Advisor) Dissociação da memória explícita e implícita da Doença de Parkinson. MSc. Dissertation - Human Sciences and Social College. Universidade do Algarve. 2012.

Few articles assessed Language,1414 Heo JH, Lee KM, Paek SH, Kim MJ, Lee JY, KimJY, et al. The effects of bilateral Subthalamic Nucleus Deep Brain Stimulation (STN DBS) on cognition in Parkinson disease. J Neurol Sci. 2008;273(1):19-24.,3535 Yágüez L, Costello A, Moriarty J, Hulse N, Selway R, Clough C, et al. Cognitive predictors of cognitive change following bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease. J Clin Neurosci. 2014;21(3):445-50.,3737 Tremblay C, Macoir J, Langlois M, Cantin L, Prudhomme M, Monetta L. The effects of subthalamic deep brain stimulation on metaphor comprehension and language abilities in Parkinson's disease. Brain Lang. 2015; 141:103-9. Attention,2323 Rizzone MG, Fasano A, Daniele A, Zibetti M, Merola A, Rizzi L, et al. Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: From the advanced phase towards the late stage of the disease? Parkinson Relat Disord. 2014;20(4):376-81. Perception3535 Yágüez L, Costello A, Moriarty J, Hulse N, Selway R, Clough C, et al. Cognitive predictors of cognitive change following bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease. J Clin Neurosci. 2014;21(3):445-50. and Visuospatial Skills.2727 Witt K, Daniels C, Reiff J, Krack P, Volkmann J, Pinsker MO, et al. Neuropsychological and psychiatric changes after deep brainstimulation for Parkinson's disease: a randomised, multicentre study. Lancet Neurol. 2008;7(7):605-14.,3636 Tang V, Zhu C, Chan D, Lau C, Chan A, Mok V, et al. Evidence of improved immediate verbal memory and diminished category fluency following STN-DBS in Chinese-Cantonese patients with idiopathic Parkinson's disease. Neurol Sci. 2015;36(8):1371-7. One study4343 Poliakoff E, Smith-Spark JH. Everyday cognitive failures and memory problems in Parkinson's patients without dementia. Brain Cogn. 2008; 67(3):340-50. reported PD patients without dementia who exhibited impairment in verbal comprehension, grammatically complex sentence identification, repetitive speech, decreased abstraction capacity, slow processing speed and attention deficit.4444 Melo LM, Barbosa ER, Caramelli P. Declínio cognitivo e demência associados à doença de Parkinson: características clínicas e tratamento. Rev Psiquiatr Clín. 2007;34(4):176-83. There is greater impairment in naming ability and verbal fluency.88 Aguilar OM, Soto CA, Esguerra M. Cambios neuropsicológicos asociados a estimulación cerebral profunda en enfermedad de parkinson: revisión teórica. Suma Psicológica. 2011;18(2):89-98. Language difficulties may be related to EF, which plays an important role in language. We also found difficulties in understanding grammatically complex sentences, disorders involving communication and repetitive speech.4444 Melo LM, Barbosa ER, Caramelli P. Declínio cognitivo e demência associados à doença de Parkinson: características clínicas e tratamento. Rev Psiquiatr Clín. 2007;34(4):176-83. Attention is impaired in PD, causing reduction of latency in simple and choice reaction times. After dopamine replacement, there is an improvement in the identification of stimuli.4040 Macuglia GR, Rieder CRM, de Almeida RMM. Funções executivas na doença de Parkinson: Revisão da Literatura. PSICO. 2012;43(4):552-61. Regarding Visuospatial and Perception skills, these require the recruitment of certain subcortical structures, in addition to the occipital, parietal and frontal lobes.4545 Galhardo MMAMC, do Amaral AKFJ, Vieira ACC. Caracterização dos distúrbios cognitivos na Doença de Parkinson. Revista CEFAC. 2009;11(2):251-7. Deficits in this function in PD correlate with postural instability and gait difficulty.4444 Melo LM, Barbosa ER, Caramelli P. Declínio cognitivo e demência associados à doença de Parkinson: características clínicas e tratamento. Rev Psiquiatr Clín. 2007;34(4):176-83. Sensory-motor coordination also had only 2 instruments for its evaluation.1414 Heo JH, Lee KM, Paek SH, Kim MJ, Lee JY, KimJY, et al. The effects of bilateral Subthalamic Nucleus Deep Brain Stimulation (STN DBS) on cognition in Parkinson disease. J Neurol Sci. 2008;273(1):19-24.,2020 Israeli-Korn S, Hocherman S, Hassin-Baer S, Cohen O, Inzelberg R. Subthalamic Nucleus Deep Brain Stimulation Does Not Improve Visuo-Motor Impairment in Parkinsons Disease. PLoS One. 2013;8(6):e65270.

Only 3 articles2020 Israeli-Korn S, Hocherman S, Hassin-Baer S, Cohen O, Inzelberg R. Subthalamic Nucleus Deep Brain Stimulation Does Not Improve Visuo-Motor Impairment in Parkinsons Disease. PLoS One. 2013;8(6):e65270.,3131 Pham UHG, Andersson S, Toft M, Pripp AH, Konglund AE, Dietrichs E, et al. Self-Reported Executive Functioning in Everyday Life in Parkinson's Disease after Three Months of Subthalamic Deep Brain Stimulation. Parkinsons Dis. 2015;2015:461453.,3838 Vonberg I, Ehlen F, Fromm O, Kühn A, Klostermann F. Deep Brain Stimulation of the Subthalamic Nucleus Improves Lexical Switching in Parkinsons Disease Patients. PLoS One. 2016;11(8):e0161404 used instruments to assess psychiatric symptoms in PD (PANDA, BPRS and Visual Analogue Mood Scale). Some authors4646 Grover S, Somaiya M, Kumar S, Avasthi A. Psychiatric aspects of Parkinson´s disease. J Neurosci Rural Pract. 2015;6(1):65-76. investigated the existence of information on various psychiatric conditions in patients with PD and found that more than 50% of non-motor symptoms are not identified in clinical practice. They observed the prevalence of depression (2% - 31%), psychosis (15% - 75%), anxiety (19% - 67%), sleep disorder (15% - 87%) and cognitive deficits (MCI 18% - 55% and dementia 31%), among others. Psychiatric symptoms were associated with the stage of PD and cognitive impairment of the patient, but not with age, duration of illness, levodopa dose or ‘ON’ or ‘OFF’ stage. Although common, psychiatric changes in PD are not criteria for clinical diagnosis.4747 Aarsland D, Larsen JP, Lim NG, Janvin C, Karlsen K, Tandberg E, Cummings JL. Range of neuropsychiatric disturbances in patiens with Parkinson´s disease. J Neurol Neurosurg Pshychiatry. 2009;67: These changes can become more disabling than motor deficits and may be a consequence of complications of the pharmacological treatment for the motor symptoms of the disease or as an integral part of the PD clinical manifestations.4848 Junior AS, Cabral ACJ. Alterações Psiquiátricas na Doença de Parkinson. In Forlenza, OV; Caramelli, P. Neuropsiquiatria geriátrica. São Paulo: Editora Atheneu; 2000.

Only 2 scales were used for assessing PD Quality of Life (QoL): PDQ-394949 Chrischilles EA, Rubenstein LM, Voelker MD, Wallace RB, Rodnitzky RL. Linking clinical variables to health-related quality of life in Parkinson´s disease. Parkinson Relat Disord. 2003;8:199-209. and PDQL.5050 De Boer AGEM, Spruijt RJ, Sprangers MAG, de Haes JCJM. Disease-specific quality of life: is it one construct? Qual Life Res. 1998;7:135-42. Regarding mood, several scales were used, with use of depression inventory being the most often cited.1414 Heo JH, Lee KM, Paek SH, Kim MJ, Lee JY, KimJY, et al. The effects of bilateral Subthalamic Nucleus Deep Brain Stimulation (STN DBS) on cognition in Parkinson disease. J Neurol Sci. 2008;273(1):19-24.,2020 Israeli-Korn S, Hocherman S, Hassin-Baer S, Cohen O, Inzelberg R. Subthalamic Nucleus Deep Brain Stimulation Does Not Improve Visuo-Motor Impairment in Parkinsons Disease. PLoS One. 2013;8(6):e65270.,2121 Kim HJ, Jeon B, Yun J, Kim Y, Yang HJ, Paek S. Initial cognitive dip after subthalamic deep brain stimulation in Parkinson disease. J Neurol. 2013;260(8):2130-3.,2323 Rizzone MG, Fasano A, Daniele A, Zibetti M, Merola A, Rizzi L, et al. Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: From the advanced phase towards the late stage of the disease? Parkinson Relat Disord. 2014;20(4):376-81.,2525 Krishnan S, Prasad S, Pisharady K, Sarma G, Sarma S, Kishore A. The decade after subthalamic stimulation in advanced Parkinson's disease: A balancing act. Neurol India. 2016;64(1):81.,2727 Witt K, Daniels C, Reiff J, Krack P, Volkmann J, Pinsker MO, et al. Neuropsychological and psychiatric changes after deep brainstimulation for Parkinson's disease: a randomised, multicentre study. Lancet Neurol. 2008;7(7):605-14.,3232 Castelli L, Lanotte M, Zibetti M, Caglio M, Rizzi L, Ducati A, et al. Apathy and verbal fluency in STN-stimulated PD patients. J Neurol. 2007; 254(9):1238-43.,3636 Tang V, Zhu C, Chan D, Lau C, Chan A, Mok V, et al. Evidence of improved immediate verbal memory and diminished category fluency following STN-DBS in Chinese-Cantonese patients with idiopathic Parkinson's disease. Neurol Sci. 2015;36(8):1371-7.,3737 Tremblay C, Macoir J, Langlois M, Cantin L, Prudhomme M, Monetta L. The effects of subthalamic deep brain stimulation on metaphor comprehension and language abilities in Parkinson's disease. Brain Lang. 2015; 141:103-9. Together with the QoL scales, these instruments enable a more in-depth examination of the individual and impacts of the disease on their life.

Some of the limitations of the study were the instruments used at different stages of the studies, albeit for the inclusion and/or exclusion criteria and during the pre and post-operative evaluation of patients. Besides the large diversity of instruments, other aspects such as version, validation and cut-off points were also heterogeneous.

The instruments used before and after DBS implantation to assess the cognitive aspects of patients are shown in Table 3. Generically speaking, we could consider them as a possible battery for evaluating the effects of surgery. The literature has shown that most authors consider these instruments sufficient to identify the patient’s diagnostic profile. These aspects are extremely relevant to analyze the results of a study. Differences in each of them may engender results that differ from those expected. These changes range from severely compromised to slightly compromised. Another example is the use of tailored tasks, Verbal Fluency Tasks1313 Cilia R, Siri C, Marotta G, Gaspari D, Landi A, Mariani CB, Benti R, Isaias IU, Vergani F, Pezzoli G, Antonini A. Brain networks underlining verbal fluency decline during STN-DBS in Parkinson's disease: An ECD-SPECT study. Parkinson Relat Disord. 2007;13(5):290-4.,1414 Heo JH, Lee KM, Paek SH, Kim MJ, Lee JY, KimJY, et al. The effects of bilateral Subthalamic Nucleus Deep Brain Stimulation (STN DBS) on cognition in Parkinson disease. J Neurol Sci. 2008;273(1):19-24.,1616 Zangaglia R, Pacchetti C, Pasotti C, Mancini F, Servello D, Sinforiani E, et al. Deep brain stimulation and cognitive functions in Parkinson's disease: A three-year controlled study. Mov Disord. 2009; 24(11):1621-8.

17 York MK, Wilde EA, Simpson R, Jankovic J. Relationship between neuropsychological outcome and DBS surgical trajectory and electrode location. J Neurol Sci. 2009;287(1):159-71.
-1818 Fasano A, Romito LM, Daniele A, Piano C, Zinno M, Bentivoglio AR, Albanese A. Neuropsychological changes 1-year after subthalamic DBS in PD patients: A prospective controlled study. Brain. 2010; 133(9):2664-76,2020 Israeli-Korn S, Hocherman S, Hassin-Baer S, Cohen O, Inzelberg R. Subthalamic Nucleus Deep Brain Stimulation Does Not Improve Visuo-Motor Impairment in Parkinsons Disease. PLoS One. 2013;8(6):e65270.,2121 Kim HJ, Jeon B, Yun J, Kim Y, Yang HJ, Paek S. Initial cognitive dip after subthalamic deep brain stimulation in Parkinson disease. J Neurol. 2013;260(8):2130-3.,2323 Rizzone MG, Fasano A, Daniele A, Zibetti M, Merola A, Rizzi L, et al. Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: From the advanced phase towards the late stage of the disease? Parkinson Relat Disord. 2014;20(4):376-81.,2626 Klempírová O, Jech R, Urgosík D, Klempír J, Spacková N, Roth J, Ruzicka E. Deep brain stimulation of the subthalamic nucleus and cognitive functions in Parkinson's disease. Prague Med Rep. 2007;108(4): 315-23.,2727 Witt K, Daniels C, Reiff J, Krack P, Volkmann J, Pinsker MO, et al. Neuropsychological and psychiatric changes after deep brainstimulation for Parkinson's disease: a randomised, multicentre study. Lancet Neurol. 2008;7(7):605-14.,2929 Daniels C, Krack P, Volkmann J, Pinsker MO, Krause M, Tronnier V, et al. Risk factors for executive dysfunction after subthalamic nucleus stimulation in Parkinson's disease. Mov Disord. 2010;25(11):1583-9.,3030 Houvenaghel JF, Jeune F, Dondaine T, Esquevin A, Robert G, Péron J, et al. Reduced Verbal Fluency following Subthalamic Deep Brain Stimulation: A Frontal-Related Cognitive Deficit? PLoS One. 2015;10(10): e0140083.,3232 Castelli L, Lanotte M, Zibetti M, Caglio M, Rizzi L, Ducati A, et al. Apathy and verbal fluency in STN-stimulated PD patients. J Neurol. 2007; 254(9):1238-43.,3434 Castelli L, Rizzi L, Zibetti M, Angrisano S, Lanotte M, Lopiano L. Motor and cognitive outcome in patients with Parkinson's disease 8 years after subthalamic implants. Parkinson Relat Disord. 2010;16(2):115-18.

35 Yágüez L, Costello A, Moriarty J, Hulse N, Selway R, Clough C, et al. Cognitive predictors of cognitive change following bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease. J Clin Neurosci. 2014;21(3):445-50.
-3636 Tang V, Zhu C, Chan D, Lau C, Chan A, Mok V, et al. Evidence of improved immediate verbal memory and diminished category fluency following STN-DBS in Chinese-Cantonese patients with idiopathic Parkinson's disease. Neurol Sci. 2015;36(8):1371-7.,3838 Vonberg I, Ehlen F, Fromm O, Kühn A, Klostermann F. Deep Brain Stimulation of the Subthalamic Nucleus Improves Lexical Switching in Parkinsons Disease Patients. PLoS One. 2016;11(8):e0161404 the n-back task and dual task5151 Alberts JL, Voelcker-Rehage C, Hallahan K, Vitek M, Bamzai R, Vitek JL. Bilateral subthalamic stimulation impairs cognitive-motor performance in Parkinson's disease patients. Brain. 2008;131(12):3348-60. rather than standardized tests, such as the Wechsler Adult Intelligence Scale2727 Witt K, Daniels C, Reiff J, Krack P, Volkmann J, Pinsker MO, et al. Neuropsychological and psychiatric changes after deep brainstimulation for Parkinson's disease: a randomised, multicentre study. Lancet Neurol. 2008;7(7):605-14.,3535 Yágüez L, Costello A, Moriarty J, Hulse N, Selway R, Clough C, et al. Cognitive predictors of cognitive change following bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease. J Clin Neurosci. 2014;21(3):445-50. and Hooper Visual Organization Test.3636 Tang V, Zhu C, Chan D, Lau C, Chan A, Mok V, et al. Evidence of improved immediate verbal memory and diminished category fluency following STN-DBS in Chinese-Cantonese patients with idiopathic Parkinson's disease. Neurol Sci. 2015;36(8):1371-7.

The results of this review point to the absence of a specific assessment protocol for PD with STN-DBS, revealing extensive variability of instruments used in different studies. However, analysis of each methodology yielded a possible battery for investigating the effects of surgery based on the frequency of use of instruments in the studies. The feasibility of using this battery and its findings should be the focus of future studies to establish a standard for assessment.

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

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Publication Dates

  • Publication in this collection
    18 June 2019
  • Date of issue
    Apr-Jun 2019

History

  • Received
    26 Feb 2018
  • Accepted
    06 Apr 2019
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