Secondary Logo

Journal Logo

Original Research Articles

Physiotherapy Versus Physiotherapy Plus Cognitive Training on Cognition and Quality of Life in Parkinson Disease

Randomized Clinical Trial

Barboza, Natália Mariano MSc; Terra, Marcelle Brandão MSc; Bueno, Maria Eduarda Brandão MSc; Christofoletti, Gustavo PhD; Smaili, Suhaila Mahmoud PhD

Author Information
American Journal of Physical Medicine & Rehabilitation: June 2019 - Volume 98 - Issue 6 - p 460-468
doi: 10.1097/PHM.0000000000001128


Parkinson disease (PD) is a neurodegenerative disorder characterized by motor symptoms such as bradykinesia, resting tremor, rigidity, and postural instability, and by nonmotor symptoms such as rapid eye movement sleep behavioral disorders, hyposmia or anosmia, constipation, depression, excessive daytime sleepiness, urinary dysfunction, anxiety, apathy, and cognitive impairment. Nowadays, nonmotor symptoms are recognized as part of a complex syndrome, which can be identified early and may precede the onset of motor symptoms.1 They are also recognized as main components that limit the daily life activities and functionality of patients. Furthermore, they impact negatively the quality of life of both patients and their families.2

Among nonmotor symptoms, cognitive decline has an estimated prevalence of 30% to 40%, with variations of up to 80%.3 Even in the early stages of PD, there is impairment in cognition in a variety of subdomains including the following: visuospatial functions (which include visual perception, space-motion, and object-form perception); executive functions (such as poor planning, sequencing, cognitive flexibility, and problem-solving capacities); attention (impaired concentration); and memory (including encoding, recall, and procedural memory).3,4 Unlike motor symptoms, the results of pharmacological therapies that minimize or interrupt cognitive decline in patients with PD are modest.1,5,6

Efforts have been made to conduct pharmacological and nonpharmacological trials. Nonpharmacological options represent a field of growing interest and include neurostimulation, physical exercises, physiotherapy, mental exercises, music, art, and cognitive training.5 To date, although some studies have dealt with the subject, they present methodological weaknesses, such as the absence of control groups, a small sample, and heterogeneity in the application of cognitive tasks and evaluation tools.

Cognitive training may be a treatment option, involving structured and theoretically oriented teaching of strategies or guided practice of tasks that target particular cognitive domains.7 In a recent meta-analysis and systematic review, it was pointed out, respectively, that cognitive training is effective in improving cognition in healthy older adults8 and in individuals with mild cognitive impairment.9 In PD, a recent meta-analysis suggested that cognitive training leads to measurable improvements in cognitive performance but suggests the need for new randomized trials so that the efficacy for this outcome in PD can be better investigated. Nevertheless, the current body of evidence, although still small, indicates that cognitive training is safe and modestly effective for this population.6

The approaches available in the treatment of cognitive disorders in PD suggest that a multidisciplinary approach may be beneficial and represent the best therapeutic option.10 As far as motor symptoms are concerned, the effectiveness of physiotherapy is well established in the literature.11 However, it remains to be studied whether physiotherapy plays a similar role in the treatment of cognitive disorders and, even more so, whether the combination of physiotherapy and cognitive training generates an additional and positive impact on cognitive symptoms in individuals with PD.

Given the frequency of cognitive impairment in PD, its impact on patients and family members, and the lack of available and effective treatments, we hypothesized that the combination of cognitive training and physiotherapy may provide additional benefits in the cognition and quality of life of individuals with PD. Thus, the objective of the study was to verify the effectiveness of physiotherapy combined with cognitive training in improving cognition and quality of life of individuals with PD.


Trial Design

This randomized clinical trial was conducted from March 2015 to March 2017, at the State University of Londrina, in association with the Agape Social Care Center in Londrina, Paraná, Brazil. The study was approved by the Ethics Committee for Research Involving Human Beings at the State University of Londrina under opinion 1.356.676, and registered in the Brazilian Registry of Clinical Trials (REBEC) under number RBR-43SJZ7. This study conforms to all CONSORT guidelines and reports the required information accordingly (see Supplementary Checklist, Supplemental Digital Content 1, After receiving information about the objectives of the study and evaluation procedures, all parties agreed to participate in the study and signed the informed consent form. The subjects were evaluated at the beginning of the study, after being submitted to the intervention, which took 4 mos, and after a 3-mo follow-up.


An independent researcher was responsible for performing a simple randomization. Individuals with PD were randomized by means of a random number generator ( through blind randomization, using identical, opaque, sealed envelopes, with the identification “Motor Group (MG)” or “Cognitive-Motor Group (CMG)”. The envelopes (containing only the acronyms MG or CMG) were opened in the presence of the patients to allocate them to the respective groups.

Participants and Patient Recruitment

The sample size calculation was based on the verbal fluency, which was used as the primary outcome. Based on a previous study,12 we considered a standard deviation of 5.21 and a mean improvement of 4.88 hits, with a significance level (α) of 5% and power (1-β) of 80%. The sample size calculation resulted in 40 patients (20 patients per group). Based on the sample losses, we completed the recruitment with 29 individuals in each group. These individuals were recruited from the Neurology Clinic of the Hospital de Clínicas at the State University of Londrina and through media releases. The consort chart of the study is displayed in Figure 1.

Consort chart of study participants.

The researchers first carried out a telephone triage with standardized questions about the diagnostic confirmation of PD, diagnosis time, current medication, current participation in rehabilitation programs, independence for walking and activities of daily living, personal background, and interest in physiotherapy. The patients screened for the interview were evaluated to establish whether they met the inclusion criteria. Patients with a diagnosis of idiopathic PD according to the London Brain Bank criteria, classified as stages 1.5 to 3 on the modified Hoehn and Yahr scale,13 older than 50 yrs, and independent for walking were included. Subjects with other neurological, musculoskeletal, and associated disorders and cognitive alterations that could interfere in the evaluation process were excluded from the study, according to the cutoff points of Bertolucci et al.14


No physiotherapists engaged in the study (treatment) and responsible for each intervention were involved in the assessment procedures. The evaluations were performed by an independent blinded examiner specialized in Parkinson disease. Furthermore, the intervention was carried out by previously trained physiotherapists. Because of the nature of the interventions, it was not possible to blind the individuals with PD with respect to the two types of training in the study; however, participants were not informed of the specific research hypothesis (cognitive training plus physiotherapy more effective than physiotherapy) and may be considered blind in relation to their allocation.


All evaluations were performed with the patients in the on-stage of medication, always at the same time of day and by the same evaluator, at the following three moments: preintervention, postintervention (duration of 4 mos), and follow-up (3 mos after the end of the intervention). After every two tests, a 10-min break was included, and the tests were applied randomly.

On the first day, the following evaluations were performed: (1) demographic data: age, body mass, height, body mass index, schooling, diagnosis time, Levodopa equivalent daily dose; (2) cognitive assessment using the Mini-Mental State Examination as an inclusion criterion to evaluate general cognitive function15; (3) disease severity using the Unified Parkinson Disease Rating Scale,16 and the modified Hoehn and Yahr Scale13 and Geriatric Depressive Scale.17 On the second day, the following were performed: (1) specific assessments of cognition: Montreal Cognitive Assessment – for general cognitive function,18 Semantic Verbal Fluency Test – for memory, restore information, and executive function,19 Rey Auditory Verbal Learning Test (RAVLT) – for immediate and late memory,20 Cognitive and Perceptual Assessment by pictures21 – for perceptual and visuospatial function; Trail Making Test22 – for executive function, visual attention, task switching speed of processing, and mental flexibility; (2) Clock Drawing Executive Test23 – for executive function, motor planning sequencing, selective attention; and (3) quality-of-life assessment: Parkinson disease Quality of Life Questionnaire.24


After formation of the groups and the evaluation procedures, the physiotherapeutic intervention program started, consisting of 32 therapy sessions (4 mos) that took place twice a week. The MG received 60 min of therapy, whereas the CMG received therapy lasting 90 mins (60-min id of MG plus 30 mins of cognitive training).

The protocols were developed by a physiotherapist with experience in physiotherapeutic treatment for Parkinson disease. Whereas this physiotherapist was in charge of the session, other professionals were present in the ratio of one therapist for each patient. Although this was a group treatment, each patient was individually monitored by a trained physiotherapist.

Motor Group

The MG intervention protocol focused on balance training, sensory integration, agility and motor coordination, exploration of limits of stability, anticipatory and reactive postural adjustments, functional independence, and gait improvement, based on the study published by Santos et al. (2017).25 We used the same protocol (original with 24 sessions) and added additional sessions, with a total of 32. The therapy sessions were divided into four blocks (1st to 8th therapy, 9th to 16th therapy, 17th to 24th therapy, 25th to 32nd therapy) with a gradual increase in exercise complexity, such as the base of support (from broader to narrower), use of unstable therapeutic resources (such as ball and trampoline), association between agility exercises and upper limb, lower limb, and trunk motor coordination, exercises exploring anteroposterior and mediolateral displacements in the frontal, sagittal, and transverse planes, and finally development of gait circuits. The summary description of the MG intervention is shown in Appendix 1 (Supplemental Digital Content 2, and Figure 2.

Intervention description of physiotherapy training according to Appendix 1 (Supplemental Digital Content 2, A, 1st to 8th therapy. B, 9th to 16th therapy. C, 17th to 24th therapy. D, 25th to 32nd therapy.

Cognitive-Motor Group

The CMG intervention protocol was performed in two parts: first, the same protocol was used as in the MG and, at the end of each therapy session, 30 mins of cognitive stimulation activities were added, which took place as follows: the participants performed three cognitive activities, which were performed face-to-face and supervised, and the participants received three more activities to perform at home, which were reviewed in the next session for joint correction with the patient. Activities included the following: memory activities, calculation, concentration, and spatial orientation.21 Individuals were monitored in the activities, so that those with a lower degree of literacy and greater difficulties in carrying out the activities received greater supervision from the therapist, besides more time to perform the proposed activities.

The sessions involved paper-pencil tasks in which individuals observed illustrations and performed activities such as interpreting figures, making associations, completing, solving problems and performing simple calculations, recognizing and circling equal figures among similar images, searching for images amidst different backgrounds, cutting out figures and assembling puzzles by gluing them to the right places, determining mistakes in similar images, finding overlapping figures, and matching shadows to their real images. The level of exercise difficulty was gradually increased. In each session, we sought to stimulate different cognitive domains. The tasks were delivered to patients at the end of the session, and in the next session, they were reviewed for correction. A sheet was used to control the delivery of activities.

Statistical Analysis

Descriptive data were presented as means and standard deviations or as medians and interquartile ranges, according to the normality distribution, analyzed using the Shapiro-Wilk test. The comparison of the individuals' demographic data was analyzed by means of the t test for independent samples or the Mann-Whitney U test, according to the normality of the data, for continuous variables and χ2 test for the sex variable. To compare Montreal Cognitive Assessment and Geriatric Depression Scale data preintervention and postintervention, the Wilcoxon test was used. For data with normal distribution, two-way variance analysis of repeated measures was performed for the variables group, time, and interaction group × time, using Sidak's post hoc test. For data with nonnormal distribution, the Friedman test was used to compare the moments (pre, post, and follow-up). For the intergroup analysis, the difference in means (post-pre, follow-up–pre, follow-up–post) was calculated for successive analysis using the Mann-Whitney test. To verify the magnitude of the changes after the intervention, the effect size (ES) was calculated, based on Cohen's d. Effect size is classified as: small (d = 0.0–0.20), medium (d = 0.30–0.50), and large (d = 0.50–0.80).

The statistical significance was P < 0.05. The analyses were performed in SPSS statistical software, Version 21.0. Statistics were conducted with intention-to-treat analysis. Individuals identified as outliers (values superior or inferior to three times the standard deviation) were excluded from the statistical analysis.


The initial characteristics of the groups are presented in Table 1. Values were expressed as mean and standard deviation or median and interquartile range according to the normality of the data. Both groups were homogeneous at the beginning of the study (P > 0.05) with regard to age, body mass, height, body mass index, H and Y scale, Unified Parkinson Disease Rating Scale, Geriatric Depression Scale, Mini-Mental State Examination and Montreal Cognitive Assessment scores, years of diagnosis, years of schooling, and levodopa equivalent daily dose variables.

Characteristics of the sample - initial evaluation

In Table 2, the comparative values of the Unified Parkinson Disease Rating Scale (activities of daily life, motor function, and total score) and cognitive function from the verbal fluency and RAVLT tests are displayed. Our findings suggest that the motor domain and total score of the Unified Parkinson Disease Rating Scale improved from pretreatment to posttreatment considering a time effect. The total score was statistically significant considering pre and post and pre and follow-up evaluations. It was observed that the MG and CMG groups demonstrated improvement only in the RAVLT test, in phases A1, A2, and A3 and in the recognition memory (number of hits) when considering the time effect (postintervention vs. preintervention and follow-up vs. pre). For these subgroups, the model was statistically significant in relation to time, with medium to large ESs (ESs ranging from 0.32 to 0.62); however, there were no intergroup and time × group interaction differences.

Comparison of cognitive function by UPDRS, verbal fluency test, and RAVLT

Table 3 presents the intragroup and intergroup comparison coefficients for the Cognitive and Perceptual Assessment by pictures test, Clock Drawing Executive Test, and Trail Making Test. Improvement was observed only in the Cognitive and Perceptual Assessment by pictures test in the intragroup comparisons, and only when considering the time effect, both in the MG (Fig. 1: follow-up vs. pre [ES = 0.39]; follow-up vs. post [ES = 0.45]) and CMG (Fig. 1: follow-up vs. pre [ES = 0.15]; Fig. 2: post vs. pre [ES = 0.06]). There were no intergroup and time × group interaction differences.

Intragroup and intergroup comparison of cognitive function by the cognitive and perceptual evaluation tests by means of Cognitive and Perceptual Assessment by pictures (Pictures), Clock Drawing Executive Test (Clox), and Trail Making Test

In relation to general cognition assessed by the Montreal Cognitive Assessment, there was no difference between groups (MG pre: 24 [20–26]; MG post: 24 [20–26]; P = 0.05/CMG pre: 25 [20.50–25.50]; CMG post: 25 [23–27]; P = 0.06).

Regarding quality of life, the CMG demonstrated improvement in all domains investigated by the Parkinson disease Quality of Life Questionnaire when considering the time effect: Parkinsonian symptoms (follow-up vs. pre [ES = 0.44]), systemic symptoms (follow-up vs. pre [ES = 0.28]), emotional functioning (post vs. pre [ES = 0.26]; follow-up vs. pre [ES = 0.43]), social functioning (follow-up vs. pre [ES = 0.33]), and total score (follow up vs. pre [ES = 0.44]). For the MG, improvements were observed only in the domains of Parkinsonian symptoms (post vs. pre [ES = 0.32]), social functioning (post vs. pre [ES = 0.28]), and total score (post vs. pre [ES = 0.29]). There were no intergroup and time × group interaction differences (Table 4).

Comparison of quality of life according to Parkinson Disease Quality of Life Questionnaire

According to the evaluation of depression on the Geriatric Depression Scale scale, there was no difference between groups (MG pre: 3.5 [2.0–5.75]; MG post: 3.0 [1.25–6.00]; P = 0.93/CMG pre: 3.0 [1.25–6.75]; CMG post: 3.0 [2.0–5.0]; P = 0.20). At the beginning of the study, the patients did not present depression (values less than cutoff of 5).

No adverse effects were reported throughout the treatment in either group.


Our study aimed to combine two types of intervention (physiotherapy vs. physiotherapy plus cognitive training) to verify whether the combination of approaches would generate an additional and positive impact on cognition and quality of life of individuals with PD.

Physical exercise has long been used as a treatment for motor symptoms in PD and rehabilitation has been considered an ally of drug and surgical treatments.26 What is new in this scenario are studies that recommend the efficacy of therapeutic approaches focused on cognitive training,12,27 considering the limitations of the pharmacological options for the management of cognitive symptoms and the devastating effects of these symptoms on the daily lives of the patients and their families.28

It is known that both the application of physiotherapy,29 and cognitive training,27 in isolation, can significantly improve cognition in PD. A meta-analysis involving elderly individuals diagnosed with mild cognitive impairment and dementia showed a positive (mild to moderate) effect on cognition produced by physical activity when added to cognitive challenges.30 In this context, studies have demonstrated a trend toward the adoption of multimodal approaches.31,32 To our knowledge, no studies have been carried out, until this moment, to verify the effects of motor-cognitive training by comparing it with motor training in PD. Therefore, our study brings innovative data, which can contribute positively to the management of this population.

Although the pathophysiology underlying all symptoms observed in PD is not well understood, the severe depletion of dopamine resulting from nigrostriatal degeneration is acknowledged as the predominant histological feature. Furthermore, it is becoming increasingly clear that similar pathways are fundamentally important in both cognitive and limbic function.33 Neuronal loss across differing populations including cholinergic, serotonergic, and noradrenergic structures is also well recognized and doubtless contributes to several disease features including cognitive, autonomic, and affective disturbances.33

Our results showed improvement after the intervention program regarding short-term memory and visuospatial function for both groups, evaluated by the RAVLT and Cognitive and Perceptual Assessment by pictures, respectively. Studies with magnetic resonance imagining, which compare individuals with PD with and without cognitive impairments, have evidenced structural differences such as: atrophy of the parietal-temporal lobe, entorhinal cortex, hippocampus, prefrontal cortex, posterior cingulate, and ventricular enlargement.34 In addition, studies in animal models and humans related with exercise and rehabilitation have demonstrated induction of a dynamic interplay between degenerative and regenerative mechanisms and it has been postulated that activity-dependent processes can influence dopaminergic and glutamatergic neurotransmission, thus modulating cortically driven hyperexcitability. Beyond this, these studies documented neuroplasticity of dopaminergic signaling specific grey matter changes that correlated with performance improvements, raised levels of circulating neurotrophic factors, reduced cerebrovascular risk factors, improved tissue oxygenation, and changes in brain connectivity that were comparable with medication. Therefore, exercise-induced brain plasticity is likely to represent the neural basis of rehabilitation for PD.26 Modestly, we can suppose that our intervention may have activated these repair mechanisms.

In terms of clinical research, corroborating with our findings, Zimmermann et al.,35 compared two groups of treatment: a cognition-specific training group (CogniPlus) with a motion-controlled computer game group that combined motor and cognitive tasks (Nintendo Wii) to enhance cognitive performance in patients with PD. In this study, a cognition-specific training program was not superior to nonspecific training for improving cognitive function in patients with PD.35 In opposition, Hagovská et al.,36 analyzed the effects of a combined cognitive and balance training vs. balance training on the cognitive status of seniors with mild cognitive deficit, without PD. In the results, the authors showed that combined cognitive and motor training facilitated higher improvements in cognitive domains.36 However, the motor training protocol was simpler than ours, not supervised, and performed in a domestic environment. These facts could be the reason for the opposed findings. Therefore, the association or addition of cognitive training with motor activities is still not completely clarified.

Although improvement in the CMG was expected because of the specific training, the improvement in the MG can be explained by the practice of motor physiotherapy, because the literature confirms that exercise itself can help preserve or even improve cognitive function,37 especially because of the characteristics of the proposed motor treatment, which required cognitive abilities such as memorization, coordination, agility, accomplishment of dual tasks, and motor planning activities enriched with nonautomatic exercises, which involved sequences and challenges in the motor session. Although these participants did not undergo specific and additional cognitive training, the physiotherapy sessions involved the previously mentioned activities that indirectly stimulated cognition. This fact may explain the nonsuperiority of combined physiotherapy with cognitive training in the CMG, signaling that the application of motor physiotherapy following a model similar to this intervention protocol already offers clear benefits for improved cognition in PD.

On the other hand, the nonsuperiority of the CMG results in relation to the MG may have occurred because of the number of sessions used in the protocol or to the training time of each session, which makes us consider whether it would be necessary to extend the time or protocol for the sake of additional benefits to individuals submitted to specific cognitive training, with a greater chance of retention. Because there are no studies with a design similar to ours, the option for 32 therapy sessions, plus 30 mins of cognitive training, was an arbitrary decision based on studies with motor outcomes.25

Another point to consider is the choice of the cognitive activities used. Our sample was heterogeneous in relation to years of education, characterized mostly by individuals with low educational level, so that simpler activities were selected for this group (CMG), which may have underestimated the ability of some participants with better cognitive function. It is worth mentioning that cognitive retention is stimulated and added up over the course of life. Although we did not evaluate their previous life, the literature shows a correlation between previous aspects of life and acquisition of cognitive reserve. Epidemiological evidence links the importance of early-life factors in influencing late cognition, such as socioeconomic status, educational level, childhood intelligence, and cognitive performance as a young adult, which end up creating a cognitive reserve very early in life.38 This fact reveals the challenge in treating cognitive disorders in PD, because improving cognitive skills in this stage of life (after the onset of the disease process), in individuals who did not receive appropriate stimulus conditions since early childhood, ends up hampering the process of training, retention, and acquisition of the countless cognitive skills that are fundamental to everyday tasks.

Regarding the quality-of-life outcome, our results were similar in both groups, with a slight advantage for the CMG, evidencing that physiotherapy is beneficial in improving physical, cognitive, and quality-of-life symptoms. Possibly, the addition of cognitive training generated a feeling of greater self-confidence in patients, reflected in the positive analysis of their quality of life in relation to the MG. This is a considerable fact, considering the close relation between cognitive function and quality of life,2 which highlights the importance of interventions that focus on cognition to indirectly benefit patient quality of life.

Therapeutic approaches with direct supervision of professionals trained in the management of PD, tightening the physiotherapist-patient relationship, focused attention, group life, and socialization seem to be essential to improve this population's quality of life. Besides this, the limbic loop of the basal ganglia circuitry is responsible for the regulation and control of behaviors underlying motivation, decision-making, and goal-directed reward. Afferent projections from a wide range of cortical areas (including the orbitofrontal, cingulate, and hippocampal formations) and subcortical structures (amygdala and ventral tegmental area) target the ventral striatum, which is composed of the ventromedial part of the caudate nucleus and putamen along with the nucleus accumbens (NAcc) and olfactory tubercle.33

As limitations of this study, we point out the instruments that were chosen in the assessment process and the fact that participants' education level did not guide the cognitive activities used in the CMG, which may have minimized the effect of the treatment. In addition, we did not train the cognitive tasks directly related to patient daily life activities. The training was based on the components of cognition, and therefore, it was not possible to measure the transfer of learning to activities of daily life. Because the transference of the training to daily life tasks is the final phase of learning, this can be considered a limitation of our study. For future studies, more complex and individualized activities for subjects should be used for individuals with more years of education, besides verifying protocols that vary in intensity and duration for the cognition outcome. Finally, investigations on which training delivers better effects on cognition should be performed considering other groups (control, cognitive, motor, and cognitive-motor groups).

Our findings suggest that the two treatment approaches used were effective for the outcomes: short-term memory, visuospatial function, and quality of life in both groups when the preintervention and postintervention moments were compared. These results entail implications for the prescription of exercises in rehabilitation programs when the treatment goal is cognition in individuals with PD.


1. Wang YX, Zhao J, Li DK, et al.: Associations between cognitive impairment and motor dysfunction in Parkinson's disease. Brain Behav 2017;7:e00719
2. Lawson RA, Yarnall AJ, Duncan GW, et al.: Severity of mild cognitive impairment in early Parkinson's disease contributes to poorer quality of life. Parkinsonism Relat Disord 2014;20:1071–5
3. Meireles J, Massano J: Cognitive impairment and dementia in Parkinson's disease: clinical features, diagnosis, and management. Front Neurol 2012;3:88
4. Ventura MI, Edwards JD, Barnes DE: More than just a movement disorder: why cognitive training is needed in Parkinson disease. Neurology 2015;85:1828–9
5. Goldman JG, Weintraub D: Advances in the treatment of cognitive impairment in Parkinson's disease. Mov Disord 2015;30:1471–89
6. Leung IH, Walton CC, Hallock H, et al.: Cognitive training in Parkinson disease: a systematic review and meta-analysis. Neurology 2015;85:1843–51
7. Mowszowski L, Batchelor J, Naismith SL: Early intervention for cognitive decline: can cognitive training be used as a selective prevention technique? Int Psychogeriatr 2010;22:537–48
8. Lampit A, Hallock H, Valenzuela M: Computerized cognitive training in cognitively healthy older adults: a systematic review and meta-analysis of effect modifiers. PLoS Med 2014;11:e1001756
9. Coyle H, Traynor V, Solowij N: Computerized and virtual reality cognitive training for individuals at high risk of cognitive decline: systematic review of the literature. Am J Geriatr Psychiatry 2015;23:335–59
10. Okun MS: Management of Parkinson disease in 2017: personalized approaches for patient-specific needs. JAMA 2017;318:791–2
11. Tomlinson CL, Patel S, Meek C, et al.: Physiotherapy versus placebo or no intervention in Parkinson's disease. Cochrane Database Syst Rev 2012;11:CD002817
12. París AP, Saleta HG, Silvestre E, et al.: Blind randomized controlled study of the efficacy of cognitive training in Parkinson's disease. Mov Disord 2011;26:1251–8
13. Hoehn MM, Yahr MD: Parkinsonism onset, progression, and mortality. Neurology 1967;17:427–7
14. Bertolucci PH, Brucki S, Campacci SR, et al.: O mini-exame do estado mental em uma populaçäo geral: impacto da escolaridade. Arq Neuropsiquiatr 1994;52:1–7
15. Folstein MF, Folstein SE, McHugh PR: “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–98
16. Fahn S, Jenner P, Marsden C, et al.: The Unified Parkinson's Disease Rating Scale. Recent developments in Parkinson's disease. Florham Park, NJ, Macmillan Healthcare Information, 1978
17. Yesavage JA, Brink TL, Rose TL, et al.: Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res 1983;17:37–49
18. Nasreddine ZS, Phillips NA, Bédirian V, et al.: The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005;53:695–9
19. Miller E: Verbal fluency as a function of a measure of verbal intelligence and in relation to different types of cerebral pathology. Br J Clin Psychol 1984;23:53–7
20. Rey AL: Examen Clinique en Psychologie [The Clinical Psychological Examination]. Paris, Presses Universitaires de France, 1964
21. Lemes LB, Batistetti CL, Andrelino de Almeida I, et al.: Desempenho cognitivo-perceptual de indivíduos com doença de Parkinson submetidos à fisioterapia. ConScientiae Saúde 2016;15:44–52
22. Reitan RM: Trail Making Test: Manual for Administration and Scoring. Tucson, AZ: Reitan Neuropsychology Laboratory, 1992
23. Royall DR, Cordes JA, Polk M: CLOX: an executive clock drawing task. J Neurol Neurosurg Psychiatry 1998;64:588–94
24. De Boer A, Wijker W, Speelman J, et al.: Quality of life in patients with Parkinson's disease: development of a questionnaire. J Neurol Neurosurg Psychiatry 1996;61:70–4
25. Santos SM, da Silva RA, Terra MB, et al.: Balance versus resistance training on postural control in patients with Parkinson's disease: a randomized controlled trial. Eur J Phys Rehabil Med 2017;53:173–83
26. Abbruzzese G, Marchese R, Avanzino L, et al.: Rehabilitation for Parkinson's disease: current outlook and future challenges. Parkinsonism Relat Disord 2016;22:S60–4
27. Peña J, Ibarretxe-Bilbao N, García-Gorostiaga I, et al.: Improving functional disability and cognition in Parkinson disease Randomized controlled trial. Neurology 2014;83:2167–74
28. Orgeta V, McDonald KR, Poliakoff E, et al.: Cognitive training interventions for dementia and mild cognitive impairment in Parkinson's Disease. Cochrane Database Syst Rev 2015;11:1–6
29. Cusso ME, Donald KJ, Khoo TK: The impact of physical activity on non-motor symptoms in Parkinson's disease: a systematic review. Front Med 2016;17:35
30. Karssemeijer EGA, Aaronson JA, Bossers WJ, et al.: Positive effects of combined cognitive and physical exercise training on cognitive function in older adults with mild cognitive impairment or dementia: a meta-analysis. Ageing Res Rev 2017;40:75–83
31. Reuter I, Mehnert S, Sammer G, et al.: Efficacy of a multimodal cognitive rehabilitation including psychomotor and endurance training in Parkinson's disease. J Aging Res 2012;2012:235765
32. Han JW, Lee H, Hong JW, et al.: Multimodal cognitive enhancement therapy for patients with mild cognitive impairment and mild dementia: a multi-center, randomized, controlled, double-blind, crossover trial. J Alzheimers Dis 2017;55:787–96
33. Lewis SJ, Barker RA: Understanding the dopaminergic deficits in Parkinson's disease: insights into disease heterogeneity. J Clin Neurosci 2009;16:620–5
34. Svenningsson P, Westman E, Ballard C, et al.: Cognitive impairment in patients with Parkinson's disease: diagnosis, biomarkers, and treatment. Lancet Neurol 2012;11:697–707
35. Zimmermann R, Gschwandtner U, Benz N, et al.: Cognitive training in Parkinson disease: cognition-specific vs nonspecific computer training. Neurology 2014;82:1219–26
36. Hagovská M, Takác P, Dzvoník O: Effect of a combining cognitive and balanced training on the cognitive, postural and functional status of seniors with a mild cognitive deficit in a randomized, controlled trial. Eur J Phys Rehabil Med 2016;52:101–9
37. Garber CE, Blissmer B, Deschenes MR, et al.: American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc 2011;43:1334–59
38. Hindle JV, Martyr A, Clare L: Cognitive reserve in Parkinson's disease: a systematic review and meta-analysis. Parkinsonism Relat Disord 2014;20:1–7

Parkinson Disease; Cognition; Quality of Life

Supplemental Digital Content

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.