The Impact of Parkinson's Disease on Cognitive Function
Dr Oliver Finlay
· Parkinson's Disease is a neurodegenerative disorder that is primarily known for its motor symptoms, such as tremors and rigidity, but also exerts significant effects on the brain's structure and function, which in turn can have a profound impact on cognitive performance.
· Parkinson's Disease is characterised by the loss of dopaminergic neurons in the substantia nigra, leading to striatal dopamine depletion, the formation of Lewy bodies, and disruption of brain network connectivity, resulting in motor and cognitive impairments.
· Cognitive impairments in Parkinson's Disease vary but commonly involve deficits in executive functions, memory, attention, and processing speed due to striatal dopamine depletion and the presence of Lewy bodies.
· Medication management, including optimising dopamine-enhancing medications like Levodopa, is essential for managing cognitive decline in Parkinson's Disease.
· Regular physical exercise, cognitive training, speech therapy, nutritional support, and social engagement are beneficial interventions for individuals with Parkinson’s Disease to mitigate cognitive decline and improve overall well-being.
Parkinson's Disease (PD) is a neurodegenerative disorder that affects millions of individuals worldwide. While it is primarily known for its motor symptoms, such as tremors and rigidity, PD also exerts significant effects on the brain's structure and function, which in turn can have a profound impact on cognitive performance. It is important to understand the physical and physiological changes in the brain associated with PD and how these changes affect cognitive function.
Brain Changes in Parkinson's Disease
Parkinson's Disease is characterised by the degeneration of dopaminergic neurons in a region of the brain called the substantia nigra. The loss of these neurons results in a reduction in the production of dopamine, a neurotransmitter that plays a crucial role in various brain functions, including motor control, mood regulation, and cognition (Mahlknecht et al., 2015).
1. Striatal Dopamine Depletion: One of the hallmark features of PD is a significant decrease in dopamine levels in the striatum, a brain region responsible for coordinating voluntary movements. The reduction in dopamine leads to impaired motor control, which is a primary motor symptom of PD. This depletion also affects cognitive functions such as attention, working memory, and executive functions (Cools, 2006).
2. Lewy Bodies: In PD, abnormal protein aggregates called Lewy bodies accumulate in brain cells. These inclusions disrupt cellular function and have been linked to cognitive impairment. The presence of Lewy bodies in regions like the cortex can lead to memory deficits and problems with reasoning (Aarsland et al., 2017).
3. Connectivity Changes: Parkinson's Disease can disrupt the brain's network connectivity. Research has shown that the disease can affect the default mode network (DMN), a brain network associated with self-reflection and episodic memory. Disruption of the DMN can contribute to cognitive deficits, particularly in memory and attention (Tessitore et al., 2012).
Impact on Cognitive Performance
The brain changes associated with Parkinson's Disease can have a profound impact on cognitive performance. Cognitive deficits in PD are not uniform but vary among individuals. Some common cognitive impairments include:
1. Executive Functions: Executive functions, which encompass abilities like planning, decision-making, and problem-solving, are often compromised in PD due to the striatal dopamine depletion. This can lead to difficulties in managing daily tasks and making complex decisions (Owen et al., 1998).
2. Memory: Memory deficits in PD are linked to the presence of Lewy bodies in regions important for memory, such as the hippocampus and cortex. Individuals with PD may experience difficulties in both short-term and long-term memory, affecting their ability to recall information (Aarsland et al., 2017).
3. Attention and Processing Speed: Reduced dopamine levels in the striatum can lead to attention deficits and slower information processing. PD patients may struggle with sustaining attention and quickly responding to stimuli (Cools, 2006).
Interventions To Mitigate or Slow Cognitive Performance Decline
The common cognitive impairments that those suffering from PD can experience include difficulties in memory, attention, executive functions, and processing speed. These changes can affect daily activities and social interactions (Hindle et al., 2013). However, there are various interventions and strategies that people diagnosed with Parkinson's Disease can adopt to mitigate or slow the decline in cognitive performance.
1. Medication Management: One of the primary interventions for managing cognitive decline in PD is optimising medication. Medications that enhance dopamine levels in the brain, such as Levodopa, can have a positive impact on cognitive function. It is essential for individuals with PD to work closely with their healthcare providers to find the right medication regimen and dosage (Weintraub & Burn, 2011).
2. Physical Exercise: Regular physical exercise has been shown to have numerous benefits for individuals with PD. Exercise not only helps with motor symptoms but can also support cognitive function. Aerobic exercise, resistance training, and balance exercises can improve cognitive performance and general brain health (Tanaka et al., 2009).
3. Cognitive Training: Cognitive training programs can help individuals with PD sharpen their cognitive skills. These programs often focus on memory, attention, problem-solving, and other cognitive functions. Studies have shown that cognitive training can lead to improvements in memory and executive functions (Hindle et al., 2013).
4. Speech and Language Therapy: Communication difficulties, such as speech and language problems, can be common in PD. Speech therapy can help individuals improve their communication skills and maintain social connections. Enhancing communication can positively impact cognitive function and overall well-being (Miller et al., 2017).
5. Nutritional Support: A well-balanced diet rich in antioxidants and omega-3 fatty acids may support brain health. Antioxidants, found in fruits and vegetables, can protect brain cells from damage. Omega-3 fatty acids, found in fish, can help reduce inflammation in the brain, potentially slowing cognitive decline (Barberger-Gateau et al., 2007).
6. Social Engagement: Staying socially active is important for cognitive health. Engaging in social activities, maintaining relationships, and participating in group activities can provide mental stimulation and emotional support. Social interactions can help counteract feelings of isolation and depression, which are often associated with PD (Hindle et al., 2013).
Parkinson's Disease is not only a movement disorder but also has significant impacts on the brain and cognitive function. The depletion of dopamine, the formation of Lewy bodies, and changes in brain connectivity collectively contribute to the cognitive deficits observed in PD patients. Understanding the intricate relationship between the physiological changes in the brain and cognitive performance is crucial for developing effective interventions to improve the quality of life for individuals living with Parkinson's Disease.
Cognitive decline is a significant concern for individuals with Parkinson's Disease, but there are various interventions and strategies that can help mitigate or slow the decline in cognitive performance. These include optimizing medication, engaging in regular exercise, participating in cognitive training, seeking speech and language therapy, following a healthy diet, and maintaining social connections. It is crucial for individuals with PD to work closely with healthcare professionals to develop a personalized plan that addresses their specific needs and challenges.
References and Scientific Power Evaluation
Aarsland, D., Bronnick, K., Williams-Gray, C., Weintraub, D., Marder, K., Kulisevsky, J., Burn, D., Barone, P., Pagonabarraga, J., Allcock, L. and Santangelo, G., 2010. Mild cognitive impairment in Parkinson disease: a multicenter pooled analysis. Neurology, 75(12), pp.1062-1069.
OVERVIEW: The study investigates cognitive impairment in individuals with Parkinson's Disease (PD). The authors aimed to understand the prevalence and characteristics of mild cognitive impairment (MCI) in PD patients by pooling data from multiple centres.
STRENGTHS: One of the strengths of this study is its multicentre design, which allows for a larger and more diverse sample, increasing the generalisability of the findings. The researchers used standardised criteria to diagnose MCI, enhancing the reliability of their results. They also conducted comprehensive cognitive assessments, which included various cognitive domains, providing a detailed understanding of the cognitive profile in PD patients.
LIMITATIONS: Despite its strengths, this study has some limitations. The definition of MCI in PD can be challenging, and there may be variability in diagnosing it across different centres. The study focuses on cross-sectional data, so it cannot establish causal relationships or predict the progression of cognitive impairment over time. Additionally, the study does not delve into potential underlying mechanisms of cognitive impairment in PD.
CONCLUSION: The study provides valuable insights into the prevalence and characteristics of MCI in Parkinson's Disease. It highlights the importance of recognising and assessing cognitive impairments in PD patients, as early identification can lead to better management and improved quality of life. However, more research is needed to understand the underlying mechanisms and the long-term progression of cognitive decline in PD.
SCIENTIFIC POWER: MODERATE - The study's multicentre design enhances the reliability and generalisability of the findings. However, the study's cross-sectional nature and the lack of investigation into underlying mechanisms limit its scientific power. To achieve a stronger rating, a longitudinal approach and further exploration of causal factors would be necessary. In summary, the study sheds light on the prevalence of MCI in PD patients, emphasising the importance of early assessment and intervention. However, future research is needed to deepen our understanding of cognitive decline in Parkinson's Disease.
Barberger-Gateau, P., Raffaitin, C., Letenneur, L., Berr, C., Tzourio, C., Dartigues, J.F. and Alpérovitch, A., 2007. Dietary patterns and risk of dementia: the Three-City cohort study. Neurology, 69(20), pp.1921-1930.
OVERVIEW: The article explores the relationship between dietary habits and the risk of developing dementia. It is based on a study conducted in three French cities, aiming to understand if certain dietary patterns can influence the likelihood of developing dementia in older adults.
STRENGTHS: One major strength of this study is its large sample size and long follow-up period. The researchers collected data from a significant number of participants over many years, which enhances the credibility of their findings. They used comprehensive dietary questionnaires to assess participants' eating habits, providing detailed information for their analysis. Additionally, the study accounted for potential confounding factors such as age, education, and other health conditions, which strengthens the validity of their results.
LIMITATIONS: One limitation of the study is that dietary patterns were self-reported, which can be subject to recall bias. Additionally, dietary habits can change over time, and the study did not consider these changes in their analysis. While the study adjusted for several potential confounding factors, there may still be unmeasured variables that could influence the results.
CONCLUSION: The study suggests that a healthy dietary pattern, characterised by a high intake of fruits, vegetables, and fish, may be associated with a reduced risk of developing dementia in older adults. However, more research is needed to confirm these findings and to explore the specific components of the diet that provide the most significant benefits.
SCIENTIFIC POWER: MODERATE – The study has a large sample size, long follow-up period, and comprehensive analysis of dietary patterns and dementia risk. However, the self-reported nature of dietary data and potential unmeasured confounders limit the study's scientific power. To achieve a stronger rating, more controlled experiments and further investigation into the specific dietary components would be necessary. In summary, the study suggests that a healthy diet may play a role in reducing the risk of dementia, but additional research is essential to confirm and expand on these findings.
Cools, R., 2006. Dopaminergic modulation of cognitive function-implications for L-DOPA treatment in Parkinson's disease. Neuroscience & Biobehavioral Reviews, 30(1), pp.1-23.
OVERVIEW: The article explores how the neurotransmitter dopamine affects cognitive functions, with a focus on its role in Parkinson's Disease (PD) and the potential implications for L-DOPA treatment. Dopamine is a critical chemical messenger in the brain, and its disruption is a hallmark of PD, leading to motor and cognitive challenges.
STRENGTHS: This article provides a concise and focused overview of the relationship between dopamine and cognitive functions. It highlights the importance of dopamine in various cognitive processes, including attention, working memory, and executive functions. The article also discusses the impact of L-DOPA, a medication used to increase dopamine levels, on cognitive function in PD. The author uses scientific evidence to support the points made in the article.
LIMITATIONS: While the article offers valuable insights, it is a review rather than an original research study. This means it summarises existing research rather than presenting new data. It does not provide specific experiments or data of its own, which could limit the depth of its conclusions. The review also does not address recent developments in the field, as the article's publication date is 2006, and our understanding of the topic may have evolved since then.
CONCLUSION: The article provides a solid foundation for understanding the relationship between dopamine, cognitive functions, and the implications for L-DOPA treatment in Parkinson's Disease. It underscores the intricate role of dopamine in various cognitive processes and how medications like L-DOPA can impact these functions.
SCIENTIFIC POWER: MODERATE - The article provides a comprehensive and evidence-based overview of the topic. However, it lacks recent data and original research, which could have strengthened its scientific power. To achieve a stronger rating, the article could have incorporated more recent findings and experiments. In summary, the article serves as an informative introduction to the impact of dopamine on cognitive function, particularly in the context of Parkinson's Disease and L-DOPA treatment. However, be aware that it is a review article and not a primary research study.
Hindle, J.V., Petrelli, A., Clare, L. and Kalbe, E., 2013. Nonpharmacological enhancement of cognitive function in Parkinson's disease: a systematic review. Movement Disorders, 28(8), pp.1034-1049.
OVERVIEW: The article is a comprehensive examination of non-drug-based methods to improve cognitive function in individuals with Parkinson's Disease (PD). The authors conducted a systematic review, which means they gathered and analysed findings from various studies to provide a comprehensive understanding of non-drug interventions for cognitive enhancement in PD.
STRENGTHS: One of the strengths of this article is its systematic review methodology. The authors searched for and reviewed a wide range of studies, providing a thorough overview of the topic. This approach enhances the credibility of the findings. Additionally, the study addresses an important aspect of PD care, as cognitive issues often affect the quality of life. The article covers various nonpharmacological interventions, such as cognitive training and physical exercise, and summarises their effectiveness.
LIMITATIONS: While the systematic review is a robust approach, it is dependent on the quality and quantity of available studies. The authors mention the heterogeneity of studies in terms of methodologies and outcome measures, which can make it challenging to draw definitive conclusions. Moreover, the article does not provide specific recommendations for which interventions are most effective, as it aims to summarise the existing research rather than conduct new experiments.
CONCLUSION: The article offers valuable insights into nonpharmacological interventions for enhancing cognitive function in Parkinson's Disease. The findings suggest that various strategies, such as cognitive training and exercise, may have positive effects on cognitive performance in PD. However, more research is needed to determine which interventions work best for different individuals.
SCIENTIFIC POWER: MODERATE - The article employs a systematic review methodology, which is a strong approach for summarising existing research. However, the variability in the quality and methods of the included studies and the lack of specific recommendations limit its scientific power. To achieve a stronger rating, more controlled experiments focusing on the most effective interventions would be necessary. In summary, the article offers a valuable overview of nonpharmacological approaches to enhance cognitive function in Parkinson's Disease. It highlights the importance of further research to determine the most effective strategies for individualised care.
Mahlknecht, P., Seppi, K. and Poewe, W., 2015. The concept of prodromal Parkinson’s disease. Journal of Parkinson's disease, 5(4), pp.681-697.
OVERVIEW: The article delves into the idea of "prodromal" Parkinson's Disease (PD). It explores the early signs and symptoms that may precede the full-blown onset of PD, aiming to improve our understanding of this condition's development.
STRENGTHS: The article provides a comprehensive overview of the concept of prodromal PD, including potential early signs and markers. The authors have reviewed multiple studies, contributing to the breadth and depth of their analysis. The study discusses the importance of identifying prodromal PD as it can facilitate early intervention and potentially slow disease progression.
LIMITATIONS: One limitation is that the concept of prodromal PD is still a developing field, and the criteria for diagnosing it may not be universally agreed upon. The article acknowledges this issue. Additionally, the article doesn't present new experimental data but rather summarises existing research. While this is a valid approach for a review article, it means the findings are based on other researchers' work.
CONCLUSION: The article offers a valuable overview of the emerging field of prodromal PD. It highlights the importance of recognising early signs and symptoms, potentially enabling early intervention and improved care. However, as the field is still evolving, further research is required to standardise criteria and better understand prodromal PD.
SCIENTIFIC POWER: MODERATE - The article provides a comprehensive overview of the concept of prodromal PD and the existing research. However, as it is a review article, it does not present new experimental data. The variability in criteria for diagnosing prodromal PD also affects the scientific power. To achieve a stronger rating, original research or consensus on diagnostic criteria would be necessary. In summary, the article contributes to our understanding of prodromal PD, emphasising the significance of early recognition. It serves as a foundation for further research in this evolving field.
Miller, N., Allcock, L., Hildreth, A. J., and Jones, D., 2017. Speech and language therapy for dysarthria in Parkinson's disease: a pilot study. International Journal of Language & Communication Disorders, 52(6), pp.849-861.
OVERVIEW: The article investigates the potential benefits of speech and language therapy for people with Parkinson's disease (PD) who experience a speech disorder called dysarthria. Dysarthria can make speech difficult to understand, affecting communication and quality of life for PD patients.
STRENGTHS: One of the key strengths of this article is that it is a pilot study, which means it's an initial, small-scale investigation to explore the potential benefits of speech and language therapy for dysarthria in PD. The study provides valuable insights into a previously understudied area. The research involved assessing patients before and after therapy, which allows for comparisons and measuring the therapy's effectiveness. This is an essential first step in understanding how therapy can help individuals with PD manage their communication challenges.
LIMITATIONS: As a pilot study, this research has limitations. It has a relatively small sample size, which can make it challenging to generalise the findings to a broader population. The study also lacks a control group, which would be necessary for making more robust conclusions about the effectiveness of the therapy. Additionally, the article acknowledges that longer-term studies are needed to assess the sustained benefits of speech and language therapy for dysarthria in PD.
CONCLUSION: The pilot study is a promising start in exploring the benefits of speech and language therapy for individuals with PD who have dysarthria. It suggests that therapy may have a positive impact on speech clarity, potentially improving the lives of those affected. However, more extensive studies with larger samples and control groups are needed to confirm and expand on these initial findings.
SCIENTIFIC POWER: LOW to MODERATE - This article is a pilot study with a small sample and lacks a control group. While the study provides valuable preliminary insights, more robust research with larger samples and controlled experiments would be necessary for a higher rating. In summary, the article represents a valuable initial step in exploring speech and language therapy for dysarthria in Parkinson's Disease. It indicates potential benefits, but further research is required to establish the therapy's effectiveness with more confidence.
Owen, A.M., Doyon, J., Dagher, A., Sadikot, A. and Evans, A.C., 1998. Abnormal basal ganglia outflow in Parkinson's disease identified with PET. Implications for higher cortical functions. Brain: A Journal of Neurology, 121(5), pp.949-965.
OVERVIEW: The article explores the brain changes in Parkinson's Disease (PD) and their impact on higher cortical functions. The researchers used positron emission tomography (PET) to investigate how PD affects the basal ganglia, a critical part of the brain involved in movement and cognitive functions.
STRENGTHS: This study has several strengths. The use of PET imaging allowed the researchers to observe the brain in action, providing valuable insights into the neural activity associated with PD. The article highlights the significance of the basal ganglia, not only in controlling movement but also in influencing higher cognitive functions. This multidimensional approach strengthens the understanding of PD's impact on the brain.
LIMITATIONS: The study involves a relatively small sample of PD patients, which may not represent the entire PD population. Additionally, while the study identifies abnormal basal ganglia outflow, it doesn't delve into the specific mechanisms causing these abnormalities. Furthermore, the article is from 1998, and the field of PD research has evolved since then, with new imaging technologies and discoveries.
CONCLUSION: The study provides critical insights into the neural abnormalities associated with PD and their implications for higher cortical functions. It underscores the importance of the basal ganglia not only in motor control but also in cognitive processes. However, further research and more current studies are needed to fully understand the underlying mechanisms and developments in the field.
SCIENTIFIC POWER: MODERATE - While it offers valuable insights into the brain changes in PD, the limitations, including the small sample size and the outdated publication date, affect its scientific power. To achieve a stronger rating, larger and more recent studies would be necessary. In summary, the article sheds light on the neural abnormalities associated with PD, emphasising the crucial role of the basal ganglia. However, it is essential to recognise that the field of PD research has evolved, and more contemporary research is needed to build upon these findings.
Tanaka, K., de Quadros Jr, A.C., Santos, R.F., Stella, F., Gobbi, L.T.B. and Gobbi, S., 2009. Benefits of physical exercise on executive functions in older people with Parkinson’s disease. Brain and Cognition, 69(2), pp.435-441.
OVERVIEW: The article investigates how physical exercise can impact the cognitive abilities known as "executive functions" in older individuals with Parkinson's Disease (PD). Executive functions include skills like problem-solving, planning, and decision-making.
STRENGTHS: One of the significant strengths of this study is its focus on physical exercise, which is a non-pharmacological intervention. The authors conducted a controlled experiment with a group of older PD patients who participated in an exercise program. By comparing the exercise group with a control group that did not exercise, they were able to assess the direct impact of physical activity on executive functions. This approach provides strong evidence for the benefits of exercise on cognitive abilities in PD.
LIMITATIONS: While the study design is robust, it is essential to recognise its limitations. The sample size in this study was relatively small, which can affect the generalisability of the findings to a larger PD population. Additionally, the study's duration was relatively short, and it is uncertain if the benefits of exercise on executive functions are sustained over a more extended period.
CONCLUSION: The study highlights the positive impact of physical exercise on executive functions in older individuals with Parkinson's Disease. It suggests that regular exercise can improve cognitive abilities such as problem-solving and decision-making, which are often affected by PD. However, longer-term studies with larger sample sizes are needed to better understand the duration and extent of these benefits.
SCIENTIFIC POWER: MODERATE - The controlled experimental design and the focus on non-pharmacological intervention are strengths. However, the small sample size and the relatively short duration of the study limit the generalisability and long-term applicability of the findings. To achieve a stronger rating, larger, longer-term studies would be necessary. In summary, the article highlights the positive effects of physical exercise on the cognitive functions of individuals with Parkinson's Disease. While it provides valuable insights, further research is needed to confirm and extend these findings.
Tessitore, A., Giordano, A., De Micco, R., Caiazzo, G., Russo, A., Cirillo, M., Esposito, F. and Tedeschi, G., 2016. Functional connectivity underpinnings of fatigue in “Drug‐Naïve” patients with Parkinson's disease. Movement Disorders, 31(10), pp.1497-1505.
OVERVIEW: The article investigates the relationship between brain connectivity and fatigue in individuals with Parkinson's Disease (PD) who have not yet received medication. Fatigue is a common symptom in PD and can significantly impact a person's daily life.
STRENGTHS: One of the strengths of this study is its focus on "drug-naïve" PD patients, meaning those who have not started taking medication for their PD. This allows the researchers to examine the natural state of the disease. The study uses advanced brain imaging techniques to assess functional connectivity in the brain, providing insights into how different brain regions communicate with each other. This approach allows for a deep understanding of the relationship between brain connectivity and fatigue in PD.
LIMITATIONS: The sample size is relatively small, which may limit the generalisability of the findings to a broader PD population. Additionally, the study is cross-sectional, meaning it examines a single point in time, which makes it challenging to draw conclusions about cause and effect. Longitudinal studies that follow patients over time could provide more insights into the progression of fatigue in PD.
CONCLUSION: The study highlights the role of functional brain connectivity in the experience of fatigue in "drug-naïve" PD patients. It suggests that alterations in brain connectivity may contribute to the development of fatigue in PD. However, more extensive research, including longitudinal studies, is needed to fully understand the dynamics of fatigue in PD.
SCIENTIFIC POWER: MODERATE - The use of advanced brain imaging and the focus on drug-naïve patients are strengths. However, the small sample size and the cross-sectional design limit the generalisability and the ability to draw definitive conclusions about causality. To achieve a stronger rating, larger samples and longitudinal research would be necessary. In summary, the article provides valuable insights into the relationship between brain connectivity and fatigue in "drug-naïve" PD patients. It suggests that brain connectivity alterations may contribute to fatigue, but further research is essential to confirm these findings and understand their progression over time.
Weintraub, D. and Burn, D.J., 2011. Parkinson's disease: the quintessential neuropsychiatric disorder. Movement Disorders, 26(6), pp.1022-1031.
OVERVIEW: The article delves into the complex relationship between Parkinson's Disease (PD) and neuropsychiatric symptoms. It examines how PD, primarily known for its motor symptoms, is also associated with a range of psychiatric and cognitive issues.
STRENGTHS: This article emphasises an essential aspect of PD that often goes underrecognised: the neuropsychiatric symptoms. It provides a comprehensive overview of these symptoms, including depression, anxiety, and cognitive impairment, and how they can significantly impact a person's quality of life. The authors discuss the importance of recognising and managing these non-motor aspects of PD, enhancing our understanding of the disease.
LIMITATIONS: One limitation of this article is that it is primarily a review article, summarising existing research, rather than presenting new data or experiments. While it provides a valuable overview of the topic, it does not delve into the latest developments and research in the field. Additionally, the term "quintessential" in the title might be seen as a subjective opinion, and the article doesn't offer concrete solutions for managing neuropsychiatric symptoms in PD.
CONCLUSION: The article underscores the significance of neuropsychiatric symptoms in Parkinson's Disease. It highlights the need for a holistic approach to PD care that considers both motor and non-motor aspects. However, it is important to remember that it is a review article and does not provide new experimental data or specific treatment recommendations.
SCIENTIFIC POWER: LOW to MODERATE - The article is primarily a review article that summarises existing research. While it offers a comprehensive overview of the topic, it does not present new experimental data or solutions for managing neuropsychiatric symptoms in PD. To achieve a stronger rating, more controlled experiments or clinical recommendations would be necessary. In summary, the article emphasises the importance of recognizing and addressing the neuropsychiatric symptoms in Parkinson's Disease. It provides a valuable overview of the topic but does not offer specific treatment strategies. Further research and clinical guidelines are needed to address these non-motor aspects of PD effectively.