Advancing Personalized Medicine in Common Forms of Parkinson’s Disease through Genetics: Current Therapeutics and the Future of Individualized Management

Parkinson’s disease (PD) is a condition with heterogeneous clinical manifestations that vary in age at onset, rate of progression, disease course, severity, motor and non-motor symptoms, and a variable response to antiparkinsonian drugs. It is considered that there are multiple PD etiological subtypes, some of which could be predicted by genetics. The characterization and prediction of these distinct molecular entities provides a growing opportunity to use individualized management and personalized therapies. Dissecting the genetic architecture of PD is a critical step in identifying therapeutic targets, and genetics represents a step forward to sub-categorize and predict PD risk and progression. A better understanding and separation of genetic subtypes has immediate implications in clinical trial design by unraveling the different flavors of clinical presentation and development. Personalized medicine is a nascent area of research and represents a paramount challenge in the treatment and cure of PD. This manuscript summarizes the current state of precision medicine in the PD field and discusses how genetics has become the engine to gain insights into disease during our constant effort to develop potential etiological based interventions.

Download Full-text

Parkinson’s Disease Subtyping Using Clinical Features and Biomarkers: Literature Review and Preliminary Study of Subtype Clustering

Diagnostics ◽

10.3390/diagnostics12010112 ◽

2022 ◽

Vol 12 (1) ◽

pp. 112

Author(s):

Seung Hyun Lee ◽

Sang-Min Park ◽

Sang Seok Yeo ◽

Ojin Kwon ◽

Mi-Kyung Lee ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Personalized Medicine ◽

Clinical Features ◽

Neurodegenerative Disorder ◽

Clinical Manifestations ◽

Motor Symptoms ◽

Gait Features ◽

Non Motor Symptoms

The second most common progressive neurodegenerative disorder, Parkinson’s disease (PD), is characterized by a broad spectrum of symptoms that are associated with its progression. Several studies have attempted to classify PD according to its clinical manifestations and establish objective biomarkers for early diagnosis and for predicting the prognosis of the disease. Recent comprehensive research on the classification of PD using clinical phenotypes has included factors such as dominance, severity, and prognosis of motor and non-motor symptoms and biomarkers. Additionally, neuroimaging studies have attempted to reveal the pathological substrate for motor symptoms. Genetic and transcriptomic studies have contributed to our understanding of the underlying molecular pathogenic mechanisms and provided a basis for classifying PD. Moreover, an understanding of the heterogeneity of clinical manifestations in PD is required for a personalized medicine approach. Herein, we discuss the possible subtypes of PD based on clinical features, neuroimaging, and biomarkers for developing personalized medicine for PD. In addition, we conduct a preliminary clustering using gait features for subtyping PD. We believe that subtyping may facilitate the development of therapeutic strategies for PD.

Download Full-text

Optimizing Cognitive Training for the Treatment of Cognitive Dysfunction in Parkinson’s Disease: Current Limitations and Future Directions

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.709484 ◽

2021 ◽

Vol 13 ◽

Author(s):

Bianca Guglietti ◽

David Hobbs ◽

Lyndsey E. Collins-Praino

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Dysfunction ◽

Cognitive Training ◽

Assistive Technologies ◽

Motor Impairments ◽

Future Directions ◽

Cognitive Domains ◽

Current State ◽

Non Motor Symptoms

Cognitive dysfunction, primarily involving impairments in executive function, visuospatial function and memory, is one of the most common non-motor symptoms of Parkinson’s disease (PD). Currently, the only pharmacological treatments available for the treatment of cognitive dysfunction in PD provide variable benefit, making the search for potential non-pharmacological therapies to improve cognitive function of significant interest. One such therapeutic strategy may be cognitive training (CT), which involves the repetition of standardized tasks with the aim of improving specific aspects of cognition. Several studies have examined the effects of CT in individuals with PD and have shown benefits in a variety of cognitive domains, but the widespread use of CT in these individuals may be limited by motor impairments and other concerns in study design. Here, we discuss the current state of the literature on the use of CT for PD and propose recommendations for future implementation. We also explore the potential use of more recent integrative, adaptive and assistive technologies, such as virtual reality, which may optimize the delivery of CT in PD.

Download Full-text

A clinical-anatomical signature of Parkinson’s Disease identified with partial least squares and magnetic resonance imaging

10.1101/168989 ◽

2017 ◽

Cited By ~ 3

Author(s):

Yashar Zeighami ◽

Seyed-Mohammad Fereshtehnejad ◽

Mahsa Dadar ◽

D. Louis Collins ◽

Ronald B. Postuma ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Least Squares ◽

Partial Least Squares ◽

Large Scale ◽

De Novo ◽

Neurodegenerative Disorder ◽

Clinical Manifestations ◽

Motor Symptoms ◽

Non Motor Symptoms

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by a wide array of motor and non-motor symptoms. It remains unclear whether neurodegeneration in discrete loci gives rise to discrete symptoms, or whether network-wide atrophy gives rise to the unique behavioural and clinical profile associated with PD. Here we apply a data-driven strategy to isolate large-scale, multivariate associations between distributed atrophy patterns and clinical phenotypes in PD. In a sample of N = 229 de novo PD patients, we estimate disease-related atrophy using deformation based morphometry (DBM) of T1 weighted MR images. Using partial least squares (PLS), we identify a network of subcortical and cortical regions whose collective atrophy is associated with a clinical phenotype encompassing motor and non-motor features. Despite the relatively early stage of the disease in the sample, the atrophy pattern encompassed lower brainstem, substantia nigra, basal ganglia and cortical areas, consistent with the Braak hypothesis. In addition, individual variation in this putative atrophy network predicted longitudinal clinical progression in both motor and non-motor symptoms. Altogether, these results demonstrate a pleiotropic mapping between neurodegeneration and the clinical manifestations of PD, and that this mapping can be detected even in de novo patients.

Download Full-text

3.421 The impact of Parkinson's disease age at onset on quality of life: its effect on non-motor symptoms

Parkinsonism & Related Disorders ◽

10.1016/s1353-8020(08)70923-4 ◽

2007 ◽

Vol 13 ◽

pp. S185

Author(s):

N. Klepac ◽

M. Relja

Keyword(s):

Quality Of Life ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Age At Onset ◽

Motor Symptoms ◽

The Impact ◽

Non Motor Symptoms

Download Full-text

A systematic review of associations between common SNCA variants and clinical heterogeneity in Parkinson’s disease

npj Parkinson s Disease ◽

10.1038/s41531-021-00196-5 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Camilla Christina Pedersen ◽

Johannes Lange ◽

Marthe Gurine Gunnarsdatter Førland ◽

Angus D. Macleod ◽

Guido Alves ◽

...

Keyword(s):

Systematic Review ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Age At Onset ◽

Clinical Trial Design ◽

Clinical Feature ◽

Clinical Heterogeneity ◽

Research Reporting ◽

Established Risk Factor ◽

Great Heterogeneity

AbstractThere is great heterogeneity in both the clinical presentation and rate of disease progression among patients with Parkinson’s disease (PD). This can pose prognostic difficulties in a clinical setting, and a greater understanding of the risk factors that contribute to modify disease course is of clear importance for optimizing patient care and clinical trial design. Genetic variants in SNCA are an established risk factor for PD and are candidates to modify disease presentation and progression. This systematic review aimed to summarize all available primary research reporting the association of SNCA polymorphisms with features of PD. We systematically searched PubMed and Web of Science, from inception to 1 June 2020, for studies evaluating the association of common SNCA variants with age at onset (AAO) or any clinical feature attributed to PD in patients with idiopathic PD. Fifty-eight studies were included in the review that investigated the association between SNCA polymorphisms and a broad range of outcomes, including motor and cognitive impairment, sleep disorders, mental health, hyposmia, or AAO. The most reproducible findings were with the REP1 polymorphism or rs356219 and an earlier AAO, but no clear associations were identified with an SNCA polymorphism and any individual clinical outcome. The results of this comprehensive summary suggest that, while there is evidence that genetic variance in the SNCA region may have a small impact on clinical outcomes in PD, the mechanisms underlying the association of SNCA polymorphisms with PD risk may not be a major factor driving clinical heterogeneity in PD.

Download Full-text

Smoking and age-at-onset of both motor and non-motor symptoms in Parkinson's disease

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2017.09.022 ◽

2017 ◽

Vol 45 ◽

pp. 94-96 ◽

Cited By ~ 7

Author(s):

Angelo Fabio Gigante ◽

Tommaso Martino ◽

Giovanni Iliceto ◽

Giovanni Defazio

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Age At Onset ◽

Motor Symptoms ◽

Non Motor Symptoms

Download Full-text

Gender Differences and Quality of Life in Parkinson’s Disease

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18010198 ◽

2020 ◽

Vol 18 (1) ◽

pp. 198

Author(s):

Pietro Crispino ◽

Miriam Gino ◽

Elena Barbagelata ◽

Tiziana Ciarambino ◽

Cecilia Politi ◽

...

Keyword(s):

Quality Of Life ◽

Parkinson’S Disease ◽

Gender Differences ◽

Parkinson's Disease ◽

Clinical Manifestations ◽

Health Related Quality ◽

Related Quality ◽

Health Related ◽

Non Motor Symptoms

Parkinson’s disease has been found to significantly affect health-related quality of life. The gender differences of the health-related quality of life of subjects with Parkinson’s disease have been observed in a number of studies. These differences have been reported in terms of the age at onset, clinical manifestations, and response to therapy. In general, women with Parkinson’s disease showed more positive disease outcomes with regard to emotion processing, non-motor symptoms, and cognitive functions, although women report more Parkinson’s disease-related clinical manifestations. Female gender predicted poor physical functioning and socioemotional health-related quality of life, while male gender predicted the cognitive domain of health-related quality of life. Some studies reported gender differences in the association between health-related quality of life and non-motor symptoms. Depression and fatigue were the main causes of poorer health-related quality of life in women, even in the early stages of Parkinson’s disease. The aim of this review was to collect the best available evidence on gender differences in the development of Parkinson’s disease symptoms and health-related quality of life.

Download Full-text

Mood Disorders and Anxiety in Parkinson’s Disease: Current Concepts

Journal of Geriatric Psychiatry and Neurology ◽

10.1177/08919887211018267 ◽

2021 ◽

Vol 34 (4) ◽

pp. 280-288

Author(s):

Hendrik Lintel ◽

Timothy Corpuz ◽

Saif-ur-Rahman Paracha ◽

George T. Grossberg

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mood Disorders ◽

Treatment Options ◽

Treatment Modalities ◽

Anxiety And Depression ◽

Current State ◽

Non Motor Symptoms ◽

Impaired Quality

Mood disorders and anxiety significantly impact the prognosis and disease course of Parkinson’s disease. Non-motor symptoms of Parkinson’s disease such as apathy, anhedonia, and fatigue overlap with diagnostic criteria for anxiety and depression, thus making accurate diagnosis of mood disorders in Parkinson’s disease patients difficult. Furthermore, treatment options for mood disorders can produce motor complications leading to poor adherence and impaired quality of life in Parkinson’s disease patients. This review aims to clarify the current state of diagnostic and treatment options pertaining to anxiety and mood disorders in Parkinson’s disease. It explores both the pharmacologic and non-pharmacologic treatment modalities for various mood disorders in comorbid Parkinson’s disease with a brief discussion of the future outlook of the field given the current state of the literature.

Download Full-text