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Sex and Gender Differences in Parkinson's Disease
Abstract
The lower prevalence of Parkinson disease (PD) in females is not well understood but may be partially explained by sex differences in nigrostriatal circuitry and possible neuroprotective effects of estrogen. PD motor and nonmotor symptoms differ between sexes, and women experience disparities in care including undertreatment with DBS and less access to caregiving. Our knowledge about PD in gender diverse individuals is limited. Future studies should improve our understanding of the role of hormone replacement therapy in PD, address gender-based inequities in PD care and expand our understanding of PD in SGM and marginalized communities.
... Idiopathic PD is an aging-related movement disorder characterized by degeneration of dopaminergic neurons in the substantia nigra that occurs about twice as frequently in men than women. Interestingly, female predominance has not been observed in leucine-rich repeat kinase 2 (LRRK2)-associated PD, the most common monogenic form of the illness (32). A large-scale study comparing drug-naïve men and women with early-stage idiopathic PD, matched for motor impairment, found notable gender differences in nonmotor symptoms: men showed more pronounced deficits in olfaction and in specific cognitive areas (global cognition, memory, and visuospatial skills), while women exhibited higher levels of trait anxiety (32,33). ...
... Interestingly, female predominance has not been observed in leucine-rich repeat kinase 2 (LRRK2)-associated PD, the most common monogenic form of the illness (32). A large-scale study comparing drug-naïve men and women with early-stage idiopathic PD, matched for motor impairment, found notable gender differences in nonmotor symptoms: men showed more pronounced deficits in olfaction and in specific cognitive areas (global cognition, memory, and visuospatial skills), while women exhibited higher levels of trait anxiety (32,33). Initial anecdotal reports indicated that exposure to exogenous estrogen may worsen both idiopathic and neuroleptic-induced parkinsonism, ostensibly by dampening dopaminergic neurotransmission in the nigrostriatum. ...
... Sex differences in responses to treatment of PD have been recognized and may be driven, at least in part, by hormonal factors. Men tend to respond better to motor symptom control with dopaminergic agents and deep brain stimulation (DBS) than women; the latter may be more prone to levodopa-induced dyskinesias (involuntary movements) and are more likely to experience mood-related adverse effects of DBS (32,43). ...
The influence of gonadal hormones on neurological health and disease is a rapidly developing domain in fundamental and clinical neuroscience. Sex hormones, directly or via their neurosteroid metabolites, impact monoaminergic, cholinergic, and peptidergic neurotransmission and play essential roles in shaping brain organization and function under normal and pathological conditions. The clinical expression of various neurological disorders may be modified by hormonal fluctuations related to the menstrual cycle, pregnancy, menopause, and oral contraceptive use. Understanding these interactions could lead to targeted hormonal and antihormonal therapies for diverse neurological conditions, including but not limited to catamenial epilepsy, Parkinson disease, and acute intermittent porphyria.
... DLB and PDD are characterized by the accumulation of α-synuclein in brain Lewy bodies and neurites, as well as a depletion of tegmental dopamine and loss of basal forebrain cholinergic cells (Barker and Williams-Gray, 2016;Gomperts et al., 2016;Hall et al., 2014;Hepp et al., 2016). Notably, previous studies showed that the incidence and prevalence of PDD are higher in males than in females (Savica et al., 2013a(Savica et al., , 2013bIrwin et al., 2017;Lemstra et al., 2017;Patel and Kompoliti, 2023;Ben-Shlomo et al., 2024;Grotewold and Albin, 2024). ...
... In this exploratory study, we tested whether cortical sources of rsEEG delta and alpha rhythms underpinning the quiet vigilance dysregulation in DLB and PDD patients may vary depending on the sex factor. The hypothesis stems from the higher prevalence of males than females in those patients (Savica et al., 2013a(Savica et al., , 2013bIrwin et al., 2017;Lemstra et al., 2017;Patel and Kompoliti, 2023;Ben-Shlomo et al., 2024;Grotewold and Albin, 2024) and the sensitivity of rsEEG rhythms to the sex factor (Veldhuizen et al., 1993;Duffy et al., 1993;Wada et al., 1994;Babiloni et al., 2022). The different disease prevalences in males and females may unveil sex-dependent neuroprotective/compensatory neurophysiological mechanisms in PDD and DLB patients, reflected by rsEEG rhythms. ...
... While Peirera and colleagues found that female sex was associated with more willingness to deprescribe [23], others observed no association between gender and willingness to deprescribe in their study samples [15,19] even when there was an association between female sex and satisfaction with current medications [15]. Over the past decade, the amount of evidence supporting the notion that there are sex differences in PD symptoms and outcomes [24,25] involving biological (comorbid disease, symptoms burden), sociocultural (e.g., caregiving norms, tolerance for disability), and healthcare factors (e.g., clinician bias, specialty care access) has grown considerably. Women with PD underutilize treatment resources and research opportunities, likely due in part to having less social support, difficulty accessing specialty care, as well as competing demands and expectations to be a caregiver to others [24,25], etc. ...
... Over the past decade, the amount of evidence supporting the notion that there are sex differences in PD symptoms and outcomes [24,25] involving biological (comorbid disease, symptoms burden), sociocultural (e.g., caregiving norms, tolerance for disability), and healthcare factors (e.g., clinician bias, specialty care access) has grown considerably. Women with PD underutilize treatment resources and research opportunities, likely due in part to having less social support, difficulty accessing specialty care, as well as competing demands and expectations to be a caregiver to others [24,25], etc. Our data support the growing understanding that it is necessary to tailor interventions and care models to reduce known sex disparities in PD. ...
Background
Deprescribing of potentially inappropriate medications is recommended for older adults and may improve health outcomes and quality of life in persons living with Parkinson disease (PD). Patient attitudes, beliefs, and preferences play a crucial role in the success of deprescribing interventions. We aimed to examine the attitudes and beliefs about medication burden and deprescribing among persons living with PD.
Methods
We administered a survey to participants of Fox Insight, a prospective longitudinal study of persons living with PD. The survey included the revised Patients’ Attitudes Towards Deprescribing (rPATD) questionnaire and additional questions about adverse drug effects. We used logistic regression models to explore potential predictors of treatment dissatisfaction and willingness to deprescribe.
Results
Of the 4945 rPATD respondents, 31.6% were dissatisfied with their current medications, and 87.1% would be willing to deprescribe medications. Male sex was associated with a greater willingness to deprescribe (adjusted odds ratio [aOR] 1.62, 95% confidence interval [CI] 1.37–1.93). A greater belief that the medication burden was high or that some medications were inappropriate was associated with treatment dissatisfaction (aORs 3.74, 95% CI 3.26–4.29 and 5.61, 95% CI 4.85–6.50), and more willingness to deprescribe (aORs 1.74, 95% CI 1.47–2.06 and 2.87, 95% CI 2.41–3.42). Cognitive impairment was the adverse drug effect participants were most concerned about when prescribed new medications to treat nonmotor symptoms.
Conclusions
Persons with PD are often dissatisfied with their overall medication load and are open to deprescribing. Medications that are associated with cognitive impairment might be prioritized targets for deprescribing interventions in this population.
... Biological and environmental factors may contribute to the epidemiological differences observed in PD between genders [13]. While estrogens are recognized for their potential neuroprotective effects [13], other hormones like prolactin may play a sex-specific role in motor fluctuations. ...
... Biological and environmental factors may contribute to the epidemiological differences observed in PD between genders [13]. While estrogens are recognized for their potential neuroprotective effects [13], other hormones like prolactin may play a sex-specific role in motor fluctuations. Research suggests that prolactin levels are higher in women experiencing wearing-off and dyskinesias compared to those without fluctuations [14]. ...
Introduction: The wearing-off phenomenon is characterized by the recurrence of motor and non-motor symptoms of Parkinsonism during a period free from levodopa. It is a pivotal aspect marking the end of the pharmacological "honeymoon" period in Parkinson's disease (PD). A growing body of literature is connecting sex with the likelihood of developing fluctuations. We investigated such an association in a post-hoc analysis of the large WORK-PD study. Methods: WORK-PD analyzed the usability of the wearing-off questionnaire 19 (WOQ19) in clinical practice and included cross-sectional data on age, disease duration, time on levodopa, Hoehn and Yahr stage, and WOQ19 scores of 532 PD patients. In the present study, we selected patients with an exposure time to levodopa of at least 1 year. Results: A total of 380 patients were included. Women reported a higher number of wearing-off symptoms than men (6.09 ± 3.39 vs 4.96 ± 3.11, p = 0.0006). Sex groups also differed in non-motor symptoms (2 ± 1.9 vs 1.5 ± 1.5, p = 0.021), particularly behavioral wearing-off scores being higher in women (p < 0.001). The latter were primarily featured by anxiety-related phenomena. Finally, there was a significant interaction between behavioral symptoms, sex, and age at onset (df = 2, F = 9.79, p < 0.0001), whereas no such interaction was observed with levodopa exposure and motor impairment, unlike motor symptoms. Discussion: Women showed a greater propensity than men to experience wearing-off, particularly non-motor fluctuations on the anxiety spectrum. The latter may demonstrate a lesser reliance on dopamine compared to motor symptoms. This observation could be underpinned by biological variances between genders at the neu-rotransmitter level.
... However, disparities, experiences, behaviors, health outcomes, and disease risk differ across individual SGM groups (Stacey et al., 2022). The lack of available data and research efforts in the PD field makes it challenging to identify the individual experiences and needs of SGM groups (Patel et al., 2022;Patel & Kompoliti, 2023;Roy Lin et al., 2021). With growing literature on neurodegenerative diseases showing that risk, progression, outcomes, and impact for older adults identifying as SGM differ from older adults not identifying as SGM (Flatt et al., 2021;, 2022Hsieh et al., 2021), we hope more attention, investment, time, and effort will be directed to PwP identifying as SGM. ...
... This may explain the previous studies reporting no sex difference or higher PDD risk for women (Gao et al., 2015;umeh et al., 2022). Women with PD face more disparities in healthcare utilization, treatment, and caregiving (Patel & Kompoliti, 2023). Our findings suggest that sex differences in PDD risk, potentially due to the interplay between genetic, hormonal, molecular, and environmental factors (Vaidya et al., 2021) can be modified by social determinants. ...
... Una de las hipótesis más estudiadas para explicar estas diferencias apunta al papel de los estrógenos, los cuales parecen influir en la respuesta a los tratamientos farmacológicos [5]. Se ha planteado además que los estrógenos otorgan neuroprotección, haciendo que la incidencia de EP en mujeres jóvenes sea menor, igualándose a la de los hombres en edades más avanzadas [6]. El proceso de envejecimiento en mujeres también influye en la evolución de la enfermedad. ...
... There is increasing evidence of the interconnectedness between the neurobiological underpinnings of Parkinson's disease, cognitive function, and mood disorders [25,26]. The pathophysiological changes associated with PD, in-cluding dopaminergic system dysfunction, neuroinflammation, and neurodegeneration, can impact mood regulation and cognitive processes, contributing to the development of depression [27]. ...
Background
Depression is a widely recognized neuropsychiatric condition that often occurs as a comorbidity with various medical illnesses, including neurodegenerative disorders like Parkinson’s disease (PD). This study aimed to identify the age of onset and underlying disease characteristics associated with patients exhibiting mild to moderate depression comorbid with PD.
Methods
This retrospective case-control study included 114 elderly patients (age ≥65 years) diagnosed with Parkinson’s disease. The patients were divided into two groups: the non-depressed group (n = 65) and the mild to moderate depression group (n = 49). Patients’ emotional and affective symptoms, cognitive function, and clinical characteristics were assessed using standardized scales. Statistical analyses, including chi-square tests, Wilcoxon rank-sum tests, and logistic regression analysis, were performed to evaluate associations and correlations between the variables of interest.
Results
Our findings revealed that patients in the mild to moderate depression group exhibited a significantly lower onset age of PD (52.33 ± 3.87 years) compared to the non-depressed group (59.27 ± 3.62 years, p < 0.001). Furthermore, patients with mild to moderate depression showed significantly higher scores in mood and affective symptoms measures, including the Hamilton Anxiety Scale (HAM-A) (p < 0.001) and Apathy Scale (p < 0.001). Additionally, the duration of Parkinson’s disease was significantly longer in the mild to moderate depression group (6.78 ± 2.01 years) compared to the non-depressed group (3.45 ± 1.52 years, p < 0.001). Similarly, patients in the mild to moderate depression group exhibited significantly poorer performance on the Mini-Mental State Examination (MMSE) (p < 0.001), Montreal Cognitive Assessment (MoCA) (p = 0.025), verbal fluency (p < 0.001), and Trail Making Test (p = 0.005). Additionally, correlation and logistic regression analysis revealed associations and predictive value of these variables with the presence of mild to moderate depression in Parkinson’s disease.
Conclusion
The study highlights the complex interaction of age and underlying disease characteristics in patients with mild to moderate depression comorbid with Parkinson’s disease. Early recognition and tailored management of depressive symptoms, mood and affective disturbances, cognitive impairment, and disease-specific characteristics are crucial for optimizing patient care and improving outcomes in individuals with Parkinson’s disease. These findings underscore the need for a comprehensive, patient-centered approach that considers the diverse interaction of demographic, clinical, and cognitive variables.
... Notably, sex-specific differences emerged at week six, with a higher proportion of male flies expressing one or two copies of α-Syn remaining in zone 1 compared to their female counterparts, indicating more severe locomotor deficits. These sex-specific differences mirror observations in human populations, where PD is more common in men, with around 65% of patients being male 70,71 . ...
Parkinson's Disease (PD) is a prevalent neurodegenerative disorder with the accumulation and aggregation of alpha-synuclein (α-Syn) as a central pathological hallmark. Misfolding and aggregation of α-Syn disrupts cellular homeostasis, hinders mitochondrial function, and activates neuroinflammatory responses, ultimately resulting in neuronal death. Recent biomarker research indicated a notable increase in the serum concentrations of three L-ornithine-derived polyamines (PAs): putrescine, spermidine, and spermine, each correlating with the progression of PD and its clinical subtypes. However, the role of PA pathways in PD pathology is poorly understood; it is unclear whether elevated PA concentrations are linked to PD pathology or whether they represent a secondary effect. In this study, we targeted PAs through RNAi knockdown of different PA-interconversion enzymes (PAIE) in a Drosophila melanogaster model of PD that overexpresses human, wild-type α-Syn. Our findings reveal a significant impact on both the lifespan and motility of PD-model flies when crucial PAIE, such as ornithine decarboxylase 1 (ODC1), spermidine synthase (SRM), spermidine/spermine N1-acetyltransferase 1 (SAT1), and spermine oxidase (SMOX), are targeted. The overexpression of SAT1 and SMOX in this PD model had positive, enduring effects on fly lifespan. Additionally, we noted significant alterations in α-Syn protein levels when PAIE are either knocked down or overexpressed. These findings underscore the role of PA pathways in PD and their potential targeting to modulate α-Syn levels and mitigate neurodegeneration in PD.
... PD affects over 450,000 people in Pakistan; more men than women get the condition. (6,7) PD is recognized as a disease of the motor system, the primary characteristics of this condition include tremors, stiffness, slowed movement and difficulty in maintaining balance. (8) Additional signs of motor dysfunction encompass a decline in muscle power and function as well as abnormalities in walking pattern. ...
Background: Parkinson’s disease (PD) is a degenerative movement disorder characterized by the presence of Lewy bodies in the midbrain and the loss of dopamine producing neurons in the substantia nigra. PD presents with a wide range of symptoms, encompassing both motor or non-motor aspects. Objective: To assess the relationship between gait freezing and fear of falling in individuals diagnosed with Parkinson’s disease. Methods: A cross-sectional study having ethical approval number LCPT/DPT/18/804 was conducted on 72 PD patients at Stage III (Hoehn & Yahr), aged between 55 to 75 years, using convenient non-probability sampling. Participants were recruited from multiple hospitals in Lahore, while patients with comorbidities, cognitive dysfunction and secondary Parkinsonism were excluded. Gait freezing was assessed using Freezing of Gait Questionnaire (FOG-Q), with a validity of 0.96 and reliability 0.95; whereas, fear of falling was evaluated using Fall Efficacy Scale- International (FES-I), which has a validity of 0.84 and reliability 0.95 among PD patients. The duration of study was 6 months from June 2022 to Jan 2023. Results: Among the 72 patients, 42 individuals (58.3%) were male, while 30 individuals (41.7%) were female. Mean age of study subjects was 62.09±5.93 years. The results of the study showed that freezing of gait and fear of fall were moderately positively correlated, with the correlation coefficient of r= 0.611 and a p-value of < 0.001. Conclusion: Moderate Correlation was reported between gait freezing and fear of falling in individuals diagnosed with third stage of Parkinson’s disease.
... As in other neuropsychiatric conditions, significant sex differences have been shown to characterize key clinical features of PD (22)(23)(24)(25). Most relevant to this study are consensus findings that link male sex to increased risk for mild cognitive deficits in PD and show that mild cognitive deficits appear earlier, with greater frequency and/or with greater severity in male compared to female patients with PD (26)(27)(28)(29)(30)(31) In addition, sex differences have also been shown in the efficacies of an already limited pool of therapeutic options available to effectively treat these non-motor symptoms (32)(33)(34). ...
Many patients with Parkinsons disease (PD) experience early, sometimes prodromal non-motor deficits involving cognition and memory. These so-called mild cognitive impairments hold dire predictions for future risk of freezing, falls and developing PD-related dementia. Moreover, due to a dearth of effective treatments, these symptoms persist and progressively worsen. Thus, there is an urgent need to better understand and better treat these debilitating signs. Sex differences in incidence, severity and treatment sensitivities predict that the answers to these questions are sex-specific. The work presented here highlights new ways in which rats with knockout of PTEN-induced putative kinase 1 gene (Pink1-/-) emulate PDs mild cognitive deficits and their clinical sex differences. Specifically, longitudinal behavioral testing confirmed that male Pink1-/- rats developed significant deficits in Novel Object Recognition and Novel Object Location tasks by 5 months old but that female Pink1-/- were unimpaired in these and the Object-in-Place task through 12 months of age. Further, What, Where, When Episodic-like Memory testing identified enduring deficits in all three memory domains in Pink1-/- males by 3 months of age whereas in Pink1-/- females, non-significant impairments emerged at 7 months of age and progressed to significant memory deficits by 12 months of age. Together, these data show that Pink1-/- rats model the generally greater vulnerability of male PD patients to cognitive and memory deficits in PD, the growing risk for higher order deficits in female patients as they age, and features including early onset that distinguish episodic memory impairments from other at-risk processes in this disorder.
... PD is more prevalent in males than in females. The increased risk of PD in postmenopausal women indicates that estrogen (E2) has neuroprotective effects [187,188]. Oxidative stress is an important pathogenic mechanism of PD. E2 up-regulates the expression of Nrf2 through estrogen receptor α (ERα), and Nrf2 is an important antioxidative stress factor in cells [189]. ...
Parkinson's disease (PD) is the second most common neurodegenerative disorder. PD patients exhibit varying degrees of abnormal glucose metabolism throughout disease stages. Abnormal glucose metabolism is closely linked to the PD pathogenesis and progression. Key glucose metabolism processes involved in PD include glucose transport, glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, the pentose phosphate pathway, and gluconeogenesis. Recent studies suggest that glucose metabolism is a potential therapeutic target for PD. In this review, we explore the connection between PD and abnormal glucose metabolism, focusing on the underlying pathophysiological mechanisms. We also summarize potential therapeutic drugs related to glucose metabolism based on results from current cellular and animal model studies.
... Additionally, men are 1.5 times more likely to develop PD compared to women (Hirsch et al., 2016). These disparities underscore the importance of studying sex-specific differences, which may be influenced by genetic, hormonal, or transcriptional factors (Patel and Kompoliti, 2023). Although the precise mechanisms remain unclear, our findings highlight the need for further investigation into the cellular and molecular bases of sexual dimorphism in neurodegenerative diseases. ...
Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting millions of individuals worldwide. A hallmark of PD pathology is the accumulation of α-synuclein (α-Syn), a small protein known to support neuronal development and function. However, in PD, α-Syn cumulatively misfolds into toxic aggregates that disrupt cellular processes and contribute to neuronal damage and neurodegeneration. Previous studies implicated the AKT signaling pathway in α-Syn toxicity in cellular models of PD, suggesting AKT as a potential therapeutic target. Here, we investigated the effect of AKT inhibition in a Drosophila model of synucleinopathy. We observed that administration of the AKT inhibitor, A-443654 led to mild improvements in both survival and motor function in flies expressing human α-Syn. Genetic studies revealed that reduction of AKT levels decreased α-Syn protein levels, concomitant with improved physiological outcomes. The protective effects of AKT reduction appear to operate through the fly ortholog of NF-κB, Relish, suggesting a link between AKT and NF-κB in regulating α-Syn levels. These findings highlight the AKT cascade as a potential therapeutic target for synucleinopathies and provide insights into mechanisms that could be utilized to reduce α-Syn toxicity in PD and related disorders, such as multiple system atrophy.
... PD occurs about twice as frequently in biological males than in females; however, the disease tends to progress more rapidly and produces higher mortality in women. The reasons underlying the epidemiologic difference between sexes are unknown, although they may be related to biological, environmental, aging, genetics, and immune status, among others [2,3]. The lower prevalence of PD in females is not well understood but may be partially explained by sex differences in nigrostriatal circuitry and possible neuroprotective effects of estrogen (although the therapeutic value of hormone therapy in PD is unclear). ...
... Parkinson's disease (PD) is a progressive neurological disorder that affects both sexes [1]. While research and clinical trials have made significant strides in both understanding and treating PD, there is a growing concern about the underrepresentation of female patients in these studies [2,3]. ...
Background
Parkinson's disease (PD) is a neurodegenerative disorder affecting both sexes, but differences exist between male and female in clinical manifestations, functional impact of symptoms and hormonal influences. Therefore, representativeness of females in PD trials indirectly determines the external validity of the clinical research in this field.
Objective
To estimate the representativeness of female in infusion therapy trials for advanced PD.
Methods
PubMed and EMBASE databases were searched (1980 to September 2023), along with congress abstracts, to identify controlled clinical trials and large non‐controlled studies on infusion therapies in PD enrolling >100 patients. Random‐effect meta‐analysis was conducted to estimate mean pooled prevalence of females included in the studies. Subgroup analyses were conducted accordingly to study design and intervention.
Results
We included 15 studies (six studies on levodopa‐carbidopa intestinal gel, six on subcutaneous levodopa, two on subcutaneous apomorphine, and one on levodopa‐carbidopa‐entacapone intestinal gel). Sex was not a randomisation stratification factor in any of these studies. Only one study explored differences in the outcome estimated according to sex. Overall, the proportion of female included was 38% (95% CI:33%–43%; I² = 74%), without differences between studies assessing different type of interventions (p = 0.72) or between study design (p = 0.35). In two studies, females represented the majority of included patients.
Conclusion
Female with advanced PD are underrepresented in infusion therapy trials. Most trials have overlooked sex‐based biological differences that can impact clinical and functional outcomes, raising concerns about the generalizability of these findings to real‐world contexts.
... Gender dimorphism is a common feature of immune responses and numerous diseases, including inflammation, autoimmune diseases, infectious diseases, Parkinson's disease, T2DM, cardiovascular diseases, Alzheimer's disease, and cancer (Reckelhoff and Samson, 2015;Ortona et al., 2016;Dart, 2020;Di Florio et al., 2020;Gay et al., 2021;Kautzky-Willer et al., 2023;Dai et al., 2023;Patel and Kompoliti, 2023;Lopez-Lee et al., 2024;Puttur and Lloyd, 2024). An abundance of data demonstrates that the gut microbiota is involved in many of the diseases mentioned above. ...
Background
The gut microbiome has a significant impact on human wellness, contributing to the emergence and progression of a range of health issues including inflammatory and autoimmune conditions, metabolic disorders, cardiovascular problems, and psychiatric disorders. Notably, clinical observations have revealed that these illnesses can display differences in incidence and presentation between genders. The present study aimed to evaluate whether the composition of gut microbiota is associated with sex-specific differences and to elucidate the mechanism.
Methods
16S-rRNA-sequencing technology, hormone analysis, gut microbiota transplantation, gonadectomy, and hormone treatment were employed to investigate the correlation between the gut microbiome and sex or sex hormones. Meanwhile, genes and proteins involved bile acid signaling pathway were analyzed both in the liver and ileum tissues.
Results
The composition and diversity of the microbiota from the jejunum and feces and the level of sex hormones in the serum differed between the sexes in young and middle-aged Sprague Dawley (SD) rats. However, no similar phenomenon was found in geriatric rats. Interestingly, whether in young, middle-aged, or old rats, the composition of the microbiota and bacterial diversity differed between the jejunum and feces in rats. Gut microbiota transplantation, gonadectomy, and hormone replacement also suggested that hormones, particularly testosterone (T), influenced the composition of the gut microbiota in rats. Meanwhile, the mRNA and protein level of genes involved bile acid signaling pathway (specifically SHP, FXR, CYP7A1, and ASBT) exhibited gender-specific differences, and T may play a significant role in mediating the expression of this pathway.
Conclusion
Sex-specific differences in the structure of the gut microbiota are mediated by T through the bile acid signaling pathway, pointing to potential targets for disease prevention and management techniques by indicating that sex differences and T levels may alter the composition of the gut microbiota via the bile acid signaling pathway.
... In a recent prospective study involving 412,413 U.S. adults [67], researchers discovered that women reaped greater benefits in cardiovascular mortality risk reduction from the same level of PA compared to men. The study [68,69], also noted that this benefit might be associated with the neuroprotective effects of estrogen (estradiol) in women and highlighted sex differences in the nigrostriatal circuitry of the population, potentially diminishing the relative significance of PA in females. ...
Background and objectives
Although recent meta-analyses have shown that the association between physical activity (PA) and the risk of developing Parkinson’s disease (PD) is influenced by gender differences, a growing number of studies are revealing the general applicability of this association across genders. This study aimed to reassess the association and dose–response relationship between PA and PD risk in populations.
Methods
A systematic search of PubMed, Embase, Cochrane Library, and Web of Science databases was conducted in this study from inception to February 1, 2024, without language restrictions. Stratified analyses were conducted to explore the association between PA and PD risk, combining multivariate-adjusted effect estimates via random-effects models, and to validate the dose–response relationship between the two.
Results
This study included 21 observational studies, comprising 13 cohort studies and 8 case–control studies. The pooled analysis revealed that PA significantly reduced the risk of developing PD [relative risk (RR) = 0.77, 95% CI 0.70–0.85]. In addition, the dose–response analysis revealed both linear and nonlinear associations, with linear results indicating a 9% reduction in PD risk for every 10 MET-h/wk increase in PA. The study also demonstrated that the protective effect of PA against PD was significant for both sexes. Moreover, no statistically significant effects of PA on preventing PD were observed in individuals with a BMI > 26 (RR = 0.35, 95% CI 0.12–1.02) or in Asian populations (RR = 0.78, 95% CI 0.60–1.01); however, the trends suggest potential protective effects, warranting further investigation. Sensitivity analyses confirmed the robustness of these findings.
Conclusion
This meta-analysis produced substantial evidence to reaffirm the protective effect of high PA on PD across various population groups and the inverse dose–response relationship with PD risk, and to validate the protective effect of PA among different demographic groups.
... It is known that PD is more frequent in men than in women and that the age of disease onset is 2.1 years later in women as compared to men (8,9). On the other hand, women usually take longer to seek treatment, encounter more problems during management and report a lower quality of life (8,10). Moreover, women suffer from troublesome dyskinesias more frequently than men, due to different levodopa pharmacokinetics (8,11). ...
Background
Gender differences in the access to advanced therapies for Parkinson’s disease (PD) are poorly investigated.
Objective
The objective of this study was to investigate the presence of any gender disparity in the access to advanced therapies for PD.
Design
Retrospective study.
Methods
Data from patients with consistent access to the Parkinson’s and Movement Disorder Center of L’Aquila over the last 10-year period were screened. Patients selected for advanced therapies were included.
Results
Out of 1,252 patients, 200 (mean age ± SD 71.02 ± 9.70; 72% males; median Hoen Yahr level: 3, minimum 1 maximum 5) were selected for advanced therapies: 133 for Magnetic Resonance guided Focused Ultrasound (MRgFUS) thalamotomy (mean age ± SD 70.0 ± 8.9; 77% males), 49 for Levodopa/Carbidopa Intestinal Gel (LCIG) infusion (mean age ± SD 74.3 ± 11.4; 59% males), 12 for Deep Brain Stimulation (DBS) (mean age ± SD 71.2 ± 6.3; 75% males), and 7 for Continuous Subcutaneous Apomorphine Infusion (CSAI) (mean age ± SD 69.7 ± 5.5; 43% males). No sex differences were found in relation to age (MRgFUS group: males vs. females 70.2 ± 8.9 vs. 70.8 ± 8.9, p-value = 0.809; LCIG group: males vs. females 73.5 ± 13.0 vs. 75.5 ± 8.5, p-value = 0.557; DBS group: males vs. females 77.2 ± 8.1 vs. 67.3 ± 8.6, p-value = 0.843; CSAI group: males vs. females 73.3 ± 4.0 vs. 67.0 ± 5.2, p-value = 0.144) and disease duration (MRgFUS group: males vs. females 8.3 ± 4.4 vs. 9.6 ± 6.7, p-value = 0.419; LCIG group: males vs. females 14.5 ± 5.81 vs. 17.3 ± 5.5; p-value = 0.205; DBS group: males vs. females 15.0 ± 9.6 vs. 15.5 ± 7.7, p-value = 0.796; CSAI group: males vs. females 11.7 ± 3.7 vs. 10.3 ± 3.7, p-value = 0.505).
Conclusion
The predominance of males is higher than that expected based on the higher prevalence of PD in men. Women are less confident in selecting advanced therapies during the natural progression of their disease. Factors accounting for this discrepancy deserve further investigation.
... This predominance of PD in men is in accordance with the literature. The lower prevalence of PD in females is not well understood but may be partially explained by sex differences in nigrostriatal circuitry and possible neuroprotective effects of estrogen [53]. ...
Background: Parkinson’s Disease (PD) is a progressive neurodegenerative condition associated with deficit in reaction time which can lead to falls, resulting in limited independence, diminished quality of life, heightened rates of institutionalization and increased healthcare costs. We aimed to examine the effects of an acupuncture protocol in motor time response after an auditory stimulus. Methods: This study employed a case series design. Reaction time to exposed rhythmic and random auditory stimuli outcomes were evaluated at six different moments over a month-long acupuncture treatment protocol using the MP 36 system from Biopac Systems. Results: We observed a tendency to have more pronounced improvements in the time response in the more affected side of the body compared with the contralateral one. Patients tended to show better values of response to random auditory stimuli compared to rhythmic auditory ones. We also observed a tendency to obtain better results when considering the accumulative effects of the acupuncture protocol. Conclusions: Our findings indicated a possible role of reaction time as a sensitive and useful tool for motor function assessment in PD patients. Also, from our results, we concluded that the acupuncture protocol used may lead to an improvement in efficacy of motor response after aleatory and rhythmic stimulus; we also found a tendency for a higher efficacy of acupuncture in random stimuli responses in the first stages of the disease. However, further in-depth research, including a statistical evaluation with a larger participant pool, is necessary to validate and confirm these promising results.
... The National Institutes of Health in the United States emphasizes the importance of biological sex and considers it a critical variable in rigorous research. Epidemiological and clinical sex differences in PD are also quite common (37,38). Analyzing the reasons for these results may be due to physiological differences between men and women, not just in body structure, but also including the distribution of fat and muscle, hormone levels, and changes in the body with age, such as muscle loss and fat gain; the mechanisms of PD are complex and also differ between sexes; the relationship between BMI and cognitive impairment is also very complex; the lifestyles and social relationships of men and women are different. ...
Objective
This study utilized a binary logistic regression model to explore the relationship between Body Mass Index (BMI) and cognitive function in Parkinson’s disease (PD) patients.
Methods
In this cross-sectional study, data were obtained from 1,005 Parkinson’s patients enrolled in the Parkinson’s Progression Markers Initiative (PPMI) from 2010 to 2023, including 378 females and 627 males. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and the correlation between BMI and cognitive function was determined using binary logistic regression.
Results
The median age of enrollment was 63.6 (56.2, 69.6) years old, including 378 (37.6%) females and 627 (62.4%) males. In the final adjusted model, a significant positive correlation was found between BMI and the prevalence of cognitive impairment in females (OR = 1.06, 95% CI = 1.01 ~ 1.12, p = 0.022), while no correlation was found in males (OR = 1.03, 95% CI = 0.99 ~ 1.08, p = 0.165). The results after categorizing BMI indicate that, among females, the risk of cognitive impairment increases for both groups with BMI ≥ 30 kg/m² and those with 25 ≤ BMI < 30 kg/m² compared to the reference group with BMI < 25 kg/m², with a p for trend <0.001 indicating a stable and strong association between BMI and cognitive impairment in females. In males, the results were not significant. The trend of linear fitting was consistent with the above results.
Conclusion
In female Parkinson’s patients, there is a positive correlation between BMI and cognitive impairment, while no correlation was found in male patients. This study provides new evidence of sex differences in the correlation between BMI and cognitive impairment among Parkinson’s patients. The role of sex differences in the relationship between BMI and cognitive impairment should be considered in future research.
... Supported by animal models, several researchers have hypothesized that estrogen may play a neuroprotective role by overall increasing the availability of dopamine [39]. This hypothesis is supported by the observations that greater age at menopause, greater fertile life duration and greater number of pregnancies may be associated with delayed age of PD onset [40,41]. Interestingly, this sex difference is not observed in certain genetic cohorts, including LRRK2 patients [42]. ...
Purpose of Review
In recent decades, epidemiological understanding of Parkinson disease (PD) has evolved significantly. Major discoveries in genetics and large epidemiological investigations have provided a better understanding of the genetic, behavioral, and environmental factors that play a role in the pathogenesis and progression of PD. In this review, we provide an epidemiological update of PD with a particular focus on advances in the last five years of published literature.
Recent Findings
We include an overview of PD pathophysiology, followed by a detailed discussion of the known distribution of disease and varied determinants of disease. We describe investigations of risk factors for PD, and provide a critical summary of current knowledge, knowledge gaps, and both clinical and research implications. We emphasize the need to characterize the epidemiology of the disease in diverse populations.
Summary
Despite increasing understanding of PD epidemiology, recent paradigm shifts in the conceptualization of PD as a biological entity will also impact epidemiological research moving forward and guide further work in this field.
... This could suggest that the presence of hormones influences the course of this neurodegenerative disease. This observation is particularly interesting, especially when considering data obtained by Patel and Kompoliti, which showed a lower prevalence of PD among females [51]. Ultimately, we can only speculate on the influence of the hormonal or menopausal status of our female participants. ...
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders globally and leads to an excessive loss of dopaminergic neurons in the substantia nigra of the brain. Circulating cell-free DNA (ccf-DNA) are double-stranded DNA fragments of different sizes and origins that are released into the serum and cerebrospinal fluid (CSF) due to cell death (i.e., necrosis and apoptosis) or are actively released by viable cells via exocytosis and NETosis. Using droplet digital polymerase chain reaction (ddPCR), we comprehensively analyzed and distinguished circulating cell-free mitochondrial DNA (ccf mtDNA) and circulating cell-free nuclear DNA (ccfDNA) in the serum and CSF of PD and control patients. The quantitative analysis of serum ccf-DNA in PD patients demonstrated a significant increase in ccf mtDNA and ccfDNA compared to that in healthy control patients and a significantly higher copy of ccf mtDNA when compared to ccfDNA. Next, the serum ccf mtDNA levels significantly increased in male PD patients compared to those in healthy male controls. Furthermore, CSF ccf mtDNA in PD patients increased significantly compared to ccfDNA, and ccf mtDNA decreased in PD patients more than it did in healthy controls. These decreases were not statistically significant but were in agreement with previous data. Interestingly, ccf mtDNA increased in healthy control patients in both serum and CSF as compared to ccfDNA. The small sample size of serum and CSF were the main limitations of this study. To the best of our knowledge, this is the first comprehensive study on serum and CSF of PD patients using ddPCR to indicate the distribution of the copy number of ccf mtDNA as well as ccfDNA. If validated, we suggest that ccf mtDNA has greater potential than ccfDNA to lead the development of novel treatments for PD patients.
... However, different rates are shown when they are restricted to specific geographic regions [10,96,110,111]. In addition, women with PD experience difficulties in receiving treatment and caregiving [112]. ...
Despite recent efforts to search for biomarkers for the pre-symptomatic diagnosis of Parkinson's disease (PD), the presence of risk factors, prodromal signs, and family history still support the classification of individuals at risk for this disease. Human epidemiological studies are useful in this search but fail to provide causality. The study of well-known risk factors for PD in animal models can help elucidate mechanisms related to the disease's etiology and contribute to future prevention or treatment approaches. This narrative review aims to discuss animal studies that investigated four of the main risk factors and/or prodromal signs related to PD: advanced age, male sex, sleep alterations, and depression. Different databases were used to search the studies, which were included based on their relevance to the topic. Although still in a reduced number, such studies are of great relevance in the search for evidence that leads to a possible early diagnosis and improvements in methods of prevention and treatment.
... This could suggest that the presence of hormones influences the course of this neurodegenerative disease. This observation is particularly interesting, especially when considering data obtained by Patel and Kompoliti, which showed lower prevalence of PD among females [49]. Ultimately, we can only speculate on the influence of hormonal or menopausal status of our female participants. ...
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders globally, and leads to an excessive loss of dopaminergic neurons in the substantia nigra of the brain. Circulating cell-free DNA (ccf-DNA) are double-stranded DNA fragments of different sizes and origins that are released into the serum and cerebrospinal fluid (CSF) due to cell death (i.e., necrosis and apoptosis) or are actively released by viable cells via exocytosis and NETosis. Methods: Using droplet digital polymerase chain reaction (ddPCR) we comprehensively analyzed and distinguished ccfDNA and ccf mtDNA in the serum and CSF of PD and control patients. Results: The quantitative analysis of serum ccf-DNA in PD patients demonstrated significant increase of ccf mtDNA and ccfDNA compared to healthy control patients and significantly higher copy of ccf mtDNA when compared to ccfDNA. Next, the serum ccf mtDNA levels significantly increased in male PD patients compared to healthy male controls. Furthermore, CSF ccf mtDNA in PD patients increased significantly compared to ccfDNA, and ccf mtDNA decreased in PD patients compared to healthy controls. These decreases were not statistically significant, but were in agreement with previous data. In-terestingly, ccf mtDNA increased in healthy control patients in both serum and CSF as compared to ccfDNA. Limitations: the small sample size of serum and CSF were the main limitations of this study. Conclusion: To the best of our knowledge, this is the first comprehensive study on serum and CSF of PD patients using ddPCR and indicating the distribution of the copy number of ccf mtDNA, as well as ccfDNA. If validated, we suggest that ccf mtDNA has greater than ccfDNA potential to lead the development of novel treatments for PD patients.
... Men may exhibit more improvement in bradykinesia subscores (16,30). Interestingly, within the general PD population gender differences are seen in some motor symptoms, such as more dyskinesias and tremor-dominant PD in women (13,64,65), but not in bradykinesia. Therefore, a possible gender-specific difference in the bradykinesia response to STN-DBS is not clear and requires further research. ...
Available data suggest that there may be gender differences in the effect of STN-DBS in the treatment of Parkinson’s disease (PD). The aim of this study was to review data on gender discrepancies and gender differences in clinical outcomes in PD patients treated with deep brain stimulation of the subthalamic nucleus (STN-DBS). Included were original studies that specifically examined gender discrepancies or gender differences in PD patients with STN-DBS. Men receive more DBS than women, for various indications. The decision-making process for DBS in women compared to men is more influenced by personal preferences and external factors. Motor symptoms improve in both genders, but bradykinesia improves more in men. The postoperative reduction of the levodopa equivalent daily dose seems to be more pronounced in men. Men show more cognitive deterioration and less improvement than women after STN-DBS. Women show more depressive symptoms before surgery, but they improve similarly to men. Men show more improvement in impulsivity and less decrease in impulsive behaviour symptoms than women. Anxiety and personality traits remain unchanged in both genders. Voice quality improves more in men and deteriorates less often than in women. Men gain fat-free mass and fat mass, but women only gain fat mass. Regarding sexual function the evidence is inconsistent. More urinary symptoms improve in women than in men. Pain and restless leg syndrome seems to improve more in men. Regarding quality of life, the evidence seems to be inconsistent, and activities of daily living seems to improve in both genders. Better prospective controlled studies, focusing directly on gender differences in PD patients treated with STN-DBS, are needed to better explain gender differences in STN-DBS for PD.
... Given the same PRS, the odds of PD for men are signi cantly higher than those of women. In fact, males are twice as likely to develop PD as females, which may be due to the nigrostriatal dopaminergic pathway and the potential neuroprotective effects of estrogen 31 . In addition, we also found an interaction between PRS and UPDRS. ...
Parkinson’s disease (PD) is a complex neurodegenerative disorder with unclear etiology and ineffective treatments. Integrating multimodal data for PD prediction remains challenging. We analyzed data obtained from the Parkinson’s Progression Markers Initiative, using polygenic risk scores (PRS) to reflect genetic susceptibility to PD. We compared the prediction accuracy of models with PRS, demographics, clinical assessment, and biomarkers progressively integrated and investigated relationships. The SDPR-based PRS exhibited the highest prediction performance with an AUC of 0.75. Models combining PRS, demographic, and clinical variables achieved an AUC of 0.91, surpassing models without PRS and matching those with biomarkers. PRS correlated with olfactory function and Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), with its influence on PD risk dependent on gender and MDS-UPDRS. Our study illuminates PD etiology and provides a practical risk assessment framework, highlighting its omnigenic architecture, and the potential for accurate prediction using PRS and non-invasive clinical data.
Brain functional networks are associated with parkinsonism in observational studies. However, the causal effects between brain functional networks and parkinsonism remain unclear. We aimed to assess the potential bidirectional causal associations between 191 brain resting-state functional magnetic resonance imaging (rsfMRI) phenotypes and parkinsonism including Parkinson’s disease (PD) and drug-induced parkinsonism (DIP). We used Mendelian randomization (MR) to assess the bidirectional associations between brain rsfMRI phenotypes and parkinsonism, followed by several sensitivity analyses for robustness validation. In the forward MR analyses, we found that three rsfMRI phenotypes genetically determined the risk of parkinsonism. The connectivity in the visual network decreased the risk of PD (OR = 0.391, 95% CI = 0.235 ~ 0.649, P = 2.83 × 10−4, P_FDR = 0.039). The connectivity of salience and motor networks increased the risk of DIP (OR = 4.102, 95% CI = 1.903 ~ 8.845, P = 3.17 × 10−4, P_FDR = 0.044). The connectivity of limbic and default mode networks increased the risk of DIP (OR = 14.526, 95% CI = 3.130 ~ 67.408, P = 6.32 × 10−4, P_FDR = 0.0437). The reverse MR analysis indicated that PD and DIP had no effect on brain rsfMRI phenotypes. Our findings reveal causal relationships between brain functional networks and parkinsonism, providing important interventional and therapeutic targets for different parkinsonism.
Background . Despite the comprehensive study of Parkinson’s disease (PD), studying the quality of life (QoL) of patients, especially the prediction of low QoL, remains an unresolved issue. The aim . To create a prognostic model for low quality of life in patients with Parkinson’s disease by studying the severity of clinical features. Materials and methods . The cross-sectional study included 104 patients diagnosed with PD (56 % of men, 48 % of women); the median age was 67.0 [60.0; 71.0] years; the median duration of the disease was 5.0 [2.0; 8.0] years. We assessed motor and non-motor symptoms of PD in all patients. The PDQ-39 (Parkinson’s Disease Questionnaire) scale was used to assess the patients’ QoL. We conventionally accepted a PDQ-39 score of 50 or more as a low QoL level in a patient. Binary logistic regression using the stepwise exclusion method was used to create a prognostic model for a low QoL level in a patient with PD. Results . To predict the probability of low QoL in patients with PD depending on the studied clinical manifestations, we proposed a function according to which female gender has the greatest impact on low QoL (odds ratio – 20.0; 95% confidence interval (95% CI): 1.82–222.26). An increase in the PD stage according to the Hoehn – Yahr scale by 1 unit causes 8.77 times increase (95% CI: 2.11–36.49) in the probability of low QoL, an increase on the Epworth sleepiness scale by 1 point – 2.33 times increase (95% CI: 1.24–4.38), an increase in the level of depression according to the HADS (Hospital Anxiety and Depression Scale) by 1 point – 1.93 times increase (95% CI: 1.13–3.32). The sensitivity and specificity of the obtained function were 95.9 and 80%, respectively. Conclusion . The proposed prognostic formula can be used in neurologists’ appointments to determine the probability of low quality of life in patients with Parkinson’s disease.
Sex and gender differences play a significant role in the pathogenesis, clinical presentation, and treatment outcomes of various diseases. These differences arise from a complex interplay between biological, hormonal, genetic, and sociocultural factors. Understanding and recognizing these differences is crucial for providing personalized and effective healthcare. In terms of pathogenesis, sex and gender differences can influence disease susceptibility and progression. Hormonal factors, such as estrogen and testosterone, have been found to modulate immune responses, leading to variations in disease development and severity. For example, autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are more prevalent in females, suggesting hormonal influences on immune dysregulation. Additionally, genetic and epigenetic factors may differ between sexes, contributing to variations in disease susceptibility and response to treatment. Clinical presentation of diseases also shows sex and gender differences. Symptoms and manifestations of diseases can vary between males and females due to anatomical, physiological, and hormonal factors. For example, heart attack symptoms can differ between sexes, with females often experiencing atypical symptoms that may be overlooked or misdiagnosed. Similarly, mental health disorders may present differently in males and females, with females more commonly experiencing mood disorders and males more prone to externalizing behaviors. Treatment outcomes can also be influenced by sex and gender differences. Pharmacokinetics and pharmacodynamics may …
Introduction:
The increasing global population and aging have made Parkinson's disease (PD) a significant public health concern. Comprehensive evaluations of PD burden trends in Asian subregions and countries are lacking. This study investigated PD burden in Asia from 1990 to 2021, categorized by age, sex, and region.
Methods:
Data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 were analyzed to assess the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) across five Asian subregions and 34 countries/territories, using join-point regression, decomposition analysis, frontier analysis, and Bayesian models to examine changes, influencing factors, and predict future trends.
Results:
In 2021, the age-standardized PD incidence and prevalence in Asia were higher than the global average, particularly in East Asia (24.16 and 243.46/100,000, respectively). From 1990 to 2021, the incidence of PD in Asia rose by 198.01%, its prevalence rose by 284.35%, mortality rose by 111.27%, and DALY rose by 144.45%. Males consistently presented a greater PD burden than females did, with a growing sex gap over time. PD burden increased with age, especially among those aged 65 years and older. Population aging was the primary driver of new PD cases, and increasing etiological factors led to more patients. Inequalities in the PD burden have increased between high- and low-income areas, with low-income regions being more affected. By 2036, PD incidence is projected to increase in all subregions except the High-income Asia-Pacific region, with males experiencing a higher rate of increase.
Conclusion:
The PD burden in Asia has significantly increased over the past three decades, particularly in middle-aged and elderly males, middle- and low-SDI countries, and individuals already suffering from PD. The increasing incidence and aging population necessitate the reallocation of medical resources, improved chronic disease management systems, stronger public health interventions, and sustainable development efforts. Research into etiological factors, pathogenesis, early diagnosis, preventive interventions, and regional management is critical.
Sex and gender differences play a significant role in the pathogenesis, clinical presentation, and treatment outcomes of various diseases. These differences arise from a complex interplay between biological, hormonal, genetic, and sociocultural factors. Understanding and recognizing these differences is crucial for providing personalized and effective healthcare. In terms of pathogenesis, sex and gender differences can influence disease susceptibility and progression. Hormonal factors, such as estrogen and testosterone, have been found to modulate immune responses, leading to variations in disease development and severity. For example, autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are more prevalent in females, suggesting hormonal influences on immune dysregulation. Additionally, genetic and epigenetic factors may differ between sexes, contributing to variations in disease susceptibility and response to treatment. Clinical presentation of diseases also shows sex and gender differences. Symptoms and manifestations of diseases can vary between males and females due to anatomical, physiological, and hormonal factors. For example, heart attack symptoms can differ between sexes, with females often experiencing atypical symptoms that may be overlooked or misdiagnosed. Similarly, mental health disorders may present differently in males and females, with females more commonly experiencing mood disorders and males more prone to externalizing behaviors. Treatment outcomes can also be influenced by sex and gender differences. Pharmacokinetics and pharmacodynamics may …
Background: There is a lack of enough evidence regarding the epidemiology of Young-onset Parkinson’s disease
(YOPD) which is needed by clinicians and healthcare policymakers.
Aim: Herein, in this systematic review and meta-analysis, we aimed to estimate the global prevalence and
incidence rates of YOPD.
Methods: We searched the literature in PubMed, Scopus, and Web of Science in May 2022. We included retrospective,
prospective, cross-sectional observational population-based studies that reported the prevalence or
incidence of PD in individuals younger than 40 years with known diagnostic criteria.
Results: After two-step screening, 50 studies were eligible to be included in our study. The age-standardized
prevalence of YOPD was 10.2 per 100,000 persons globally while it was 14.7 per 100,000 population in European
countries. Age-standardized prevalence estimates for 5-year age bands showed that the YOPD prevalence
estimates varied from 6.1 per 100,000 population in the group aged 20–24 to 16.1 per 100,000 population in the
group aged 35–39. Also, the age-standardized incidence of YOPD was 1.3 per 100,000 person-years population
worldwide and 1.2 per 100,000 person-years in the European population.
Conclusion: Based on this systematic review and meta-analysis, the overall prevalence of YOPD is 10.2 per
100,000 population, although estimates of the prevalence and incidence in low-income countries remain scarce.
To improve monitoring and certain diagnoses of YOPD, healthcare providers and policymakers should be aware
that much more effective tools are required.
Sexual and gender minority (LGBT+) people face unique health disparities that must be considered by health-care providers to ensure equitable and inclusive care. Although traditionally LGBT+ health has not been integrated into neurology training, sexual orientation and gender identity have direct relevance to neurological health, driven by both systemic and interpersonal factors. In this Review, we summarize the evidence for associations between sexual orientation and gender identity with the prevalence and outcomes of various neurological conditions, including neurodegenerative diseases, epilepsy, stroke and neurodevelopmental disorders, among others. We describe important clinical considerations pertaining to LGBT+ people and recommend language and practices to promote inclusive care, as well as highlight gaps in need of further research and possible strategies to minimize these, including systematic collection of sexual orientation and gender identity and use of inclusive language.
Sex and gender differences play a significant role in the pathogenesis, clinical presentation, and treatment outcomes of various diseases. These differences arise from a complex interplay between biological, hormonal, genetic, and sociocultural factors. Understanding and recognizing these differences is crucial for providing personalized and effective healthcare. In terms of pathogenesis, sex and gender differences can influence disease susceptibility and progression. Hormonal factors, such as estrogen and testosterone, have been found to modulate immune responses, leading to variations in disease development and severity. For example, autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are more prevalent in females, suggesting hormonal influences on immune dysregulation. Additionally, genetic and epigenetic factors may differ between sexes, contributing to variations in disease susceptibility and response to treatment. Clinical presentation of diseases also shows sex and gender differences. Symptoms and manifestations of diseases can vary between males and females due to anatomical, physiological, and hormonal factors. For example, heart attack symptoms can differ between sexes, with females often experiencing atypical symptoms that may be overlooked or misdiagnosed. Similarly, mental health disorders may present differently in males and females, with females more commonly experiencing mood disorders and males more prone to externalizing behaviors. Treatment outcomes can also be influenced by sex and gender differences. Pharmacokinetics and pharmacodynamics may vary between sexes, affecting drug efficacy and safety profiles. For instance, medications metabolized differently in males and females may require adjusted dosing regimens. Moreover, social and cultural factors associated with gender roles and expectations can impact treatment adherence and access to healthcare. In conclusion, sex and gender differences significantly impact the pathogenesis, clinical presentation, and treatment outcomes of diseases. Recognizing and understanding these differences is essential for providing personalized and effective healthcare. Further research is needed to elucidate the underlying mechanisms and develop evidence-based guidelines that consider sex and gender disparities in disease management. By embracing a sex- and gender-specific approach, healthcare professionals can optimize patient care and improve health outcomes.
Objective
Parkinson's disease (PD) is a neurodegenerative disease involving multiple systems that can affect mortality. This study aimed to compare all-cause and cause-specific mortality between people with PD and without PD.
Methods
This population-based prospective cohort study is based on Korean National Health Insurance Service data. The primary outcome was the hazard ratio (HR) of all-cause and cause-specific mortality for PD from 2010 to 2019. Cox proportional hazards regression was applied to calculate HRs under crude and three adjusted models with epidemiologic variables.
Results
A total of 8,220 PD patients and 41,100 age- and sex-matched controls without PD were registered. Ten-year mortality was 47.9% in PD patients and 20.3% in non-PD controls. The mortality rate was higher among older and male participants. The leading cause of death in PD was nervous system diseases (38.73%), and 97.1% of those were extrapyramidal and movement disorders, followed by circulatory diseases (15.33%), respiratory diseases (12.56%), and neoplasms (9.7%). PD contributed to an increased risk of all-cause death with an HR of 2.96 (95% CI = 2.84–3.08). HRs of death for PD were 3.07 (95% CI = 2.74–3.45) from respiratory diseases, 1.93 (95% CI = 1.75–2.13) from circulatory diseases, 2.35 (95% CI = 2.00–2.77) from external causes, and 2.69 (95% CI = 2.10–3.43) from infectious diseases.
Conclusion
These results showed that PD was related to a higher risk of mortality in all ages and sexes. The leading causes of death in PD were nervous, circulatory, respiratory, infectious diseases, and external causes.
Background
Levodopa (LD) is the most effective drug in the treatment of Parkinson’s disease (PD). Unfortunately, prolonged use of LD leads to complications, mainly motor/non-motor fluctuations (MNMF) and dyskinesias (DYS). Women seem more prone to develop such LD-related complications. Nonetheless, there is a paucity of prospective studies examining gender-related predictors of MNMF and DYS. Among several factors, which concur with a very complex scenario, changes in LD pharmacokinetics influence the drug’s effectiveness. The present study aimed to assess gender-related differences in LD pharmacokinetics in patients with PD at their first-ever intake of LD.
Materials and Methods
This is a multicentric study enrolling patients with PD, who were LD-naïve and received a single dose of LD/benserazide (100/25 mg) formulation. All participants gave their written informed consent, and the study was approved by the local Ethics Committees. To measure plasma LD concentrations and pharmacokinetic parameters (AUC, Cmax, Tmax, t 1/2 ), fasting blood samples were collected before drug intake and then at 8-time points until 260 min. LD concentrations were measured by ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). Multiple linear regression analyses were performed to identify the predictors of the parameters.
Results
Thirty-five patients (16 women and 19 men) were consecutively enrolled. Area under curve (AUC) and maximum plasma concentration (Cmax) were significantly higher in women than men ( p = 0.0006 and p = 0.0014, respectively). No statistically significant difference was found regarding Tmax and t 1/2 . Multiple linear regression analyses revealed that female sex (β = 1.559116, 95% CI 0.8314479 2.286785; p < 0.0001) and body mass index (BMI) (β = −0.0970631, 95% CI −0.1733004 −0.0208258; p = 0.014) significantly predicted AUC. Only female sex significantly predicted Cmax (β = 1,582.499, 95% CI 731.581 2,433.417; p = 0.001). Moreover, only BMI significantly predicted t 1/2 (β = 0.0756267, 95% CI 0.0143407 0.1369126; p = 0.017). Stratifying by gender, BMI was confirmed to significantly predict t 1/2 in women (β = 0.1300486, 95% CI 0.0172322 0.242865; p = 0.027), but not in men.
Conclusion
This study provides novel insights on gender differences in LD pharmacokinetics, possibly contributing to the later development of motor complications and dyskinesia in PD.
Previous studies have shown less access to deep brain stimulation (DBS) for Parkinson's disease (PD) in women compared to men raising concerns about a potential gender gap resulting from nonclinical factors or gender differences in clinical efficacy for postoperative quality of life (QoL), motor, and nonmotor symptoms (NMS) outcomes. This was a cross-sectional and a longitudinal, prospective, observational, controlled, quasi-experimental, international multicenter study. A total sample size of 505 consisted of 316 consecutively referred patients for DBS indication evaluation at the University Hospital Cologne (01/2015-09/2020) and 189 consecutively treated patients at DBS centers in the University Hospitals Cologne and Marburg, Salford's Royal Hospital Manchester, and King's College Hospital London. In the cross-sectional cohort, we examined gender proportions at referral, indication evaluations, and DBS surgery. In the longitudinal cohort, clinical assessments at preoperative baseline and 6-month follow-up after surgery included the PD Questionnaire-8, NMSScale, Scales for Outcomes in PD-motor scale, and levodopa-equivalent daily dose. Propensity score matching resulted in a pseudo-randomized sub-cohort balancing baseline demographic and clinical characteristics between women with PD and male controls. 316 patients were referred for DBS. 219 indication evaluations were positive (women n = 102, respectively n = 82). Women with PD were disproportionally underrepresented in referrals compared to the general PD population (relative risk [RR], 0.72; 95%CI, 0.56-0.91; P = 0.002), but more likely to be approved for DBS than men (RR, 1.17; 95%CI, 1.03-1.34; P = 0.029). Nonetheless, their total relative risk of undergoing DBS treatment was 0.74 (95%CI, 0.48-1.12) compared to men with PD. At baseline, women had longer disease duration and worse dyskinesia. Exploring QoL domains, women reported worse mobility and bodily discomfort. At follow-up, all main outcomes improved equally in both genders. Our study provides evidence of a gender gap in DBS for PD. Women and men with PD have distinct preoperative nonmotor and motor profiles. We advocate that more focus should be directed toward the implementation of gender equity as both genders benefit from DBS with equal clinical efficacy. This study provides Class II evidence of beneficial effects of DBS in women with PD compared to male controls. npj Parkinson's Disease (2022) 8:47 ; https://doi.org/10.1038/s41531-022-00305-y INTRODUCTION Deep brain stimulation (DBS) is an effective treatment in advanced Parkinson's disease (PD) improving quality of life (QoL) 1,2 , motor 3 , and nonmotor symptoms (NMS) 4-6. PD affects men more frequently than women with an overall prevalence gender-ratio of 1.48:1 (M:F) 7-9. In advanced stages of PD, women are at higher risk than men to develop motor complications, such as dyskinesia or motor fluctuations and manifest different nonmotor profiles than men 10,11. Previous studies have shown disparities in access to DBS between men and women as women are less likely to undergo DBS 10,12,13 , which is out of proportion to prevalence data 8. However, it is unclear, at which key steps from referral through indication evaluation until surgical procedures the
Epidemiological studies of Parkinson’s disease (PD) show variable and partially conflicting findings with regard to incidence, prevalence, and mortality. These differences are commonly attributed to technical and methodological factors, including small sample sizes, differences in diagnostic practices, and population heterogeneity. We leveraged the Norwegian Prescription Database, a population-based registry of drug prescriptions dispensed from Norwegian pharmacies to assess the incidence, prevalence, and mortality of PD in Norway. The diagnosis of PD was defined based on the prescription of dopaminergic drugs for the indication of PD over a continuous time. During 2004–2017, 12,229 males and 9831 females met our definition for PD diagnosis. PD prevalence increased over the observation period, with larger changes observed in the older age groups. Incidence and prevalence of PD increased with age, peaking at 85 years. The male/female prevalence ratio was 1.5 across all ages, whereas the incidence ratio increased with age, from 1.4 in those 60 years, to 2.03 among those >90 years. While PD mortality was generally higher than that of the general population, mortality odds ratios decreased with age, approaching 1.0 among individuals >90 years old. When adjusted for the sex-specific mortality of the general population, the mortality among females with PD was equal to or higher than the mortality among males with PD. Our findings demonstrate that the epidemiological features of PD, including sex-differences, are age and time-period dependent and indicate that sex differences in PD mortality are unlikely to stem from disease-specific negative impact of survival in males.
Background
Traditional in-person Parkinson’s disease (PD) research studies are often slow to recruit and place unnecessary burden on participants. The ongoing COVID-19 pandemic has added new impetus to the development of new research models.
Objective
To compare recruitment processes and outcomes of three remote decentralized observational PD studies with video visits.
Methods
We examined the number of participants recruited, speed of recruitment, geographic distribution of participants, and strategies used to enhance recruitment in FIVE, a cross-sectional study of Fox Insight participants with and without PD (n = 203); VALOR-PD, a longitudinal study of 23andMe, Inc. research participants carrying the LRRK2 G2019S variant with and without PD (n = 277); and AT-HOME PD, a longitudinal study of former phase III clinical trial participants with PD (n = 226).
Results
Across the three studies, 706 participants from 45 U.S. states and Canada enrolled at a mean per study rate of 4.9 participants per week over an average of 51 weeks. The cohorts were demographically homogenous with regard to race (over 95%white) and level of education (over 90%with more than a high school education). The number of participants living in primary care Health Professional Shortage Areas in each study ranged from 30.3–42.9%. Participants reported interest in future observational (98.5–99.6%) and interventional (76.1–87.6%) research studies with remote video visits.
Conclusion
Recruitment of large, geographically dispersed remote cohorts from a single location is feasible. Interest in participation in future remote decentralized PD studies is high. More work is needed to identify best practices for recruitment, particularly of diverse participants.
Background
The presence of rapid eye movement sleep behavior disorder (RBD) contributes to increase cognitive impairment and brain atrophy in Parkinson’s disease (PD), but the impact of sex is unclear. We aimed to investigate sex differences in cognition and brain atrophy in PD patients with and without probable RBD (pRBD).
Methods
Magnetic resonance imaging and cognition data were obtained for 274 participants from the Parkinson's Progression Marker Initiative database: 79 PD with pRBD (PD-pRBD; male/female, 54/25), 126 PD without pRBD (PD-non pRBD; male/female, 73/53), and 69 healthy controls (male/female, 40/29). FreeSurfer was used to obtain volumetric and cortical thickness data.
Results
Males showed greater global cortical and subcortical gray matter atrophy than females in the PD-pRBD group. Significant group-by-sex interactions were found in the pallidum. Structures showing a within-group sex effect in the deep gray matter differed, with significant volume reductions for males in one structure in in PD-non pRBD (brainstem), and three in PD-pRBD (caudate, pallidum and brainstem). Significant group-by-sex interactions were found in Montreal Cognitive Assessment (MoCA) and Symbol Digits Modalities Test (SDMT). Males performed worse than females in MoCA, phonemic fluency and SDMT in the PD-pRBD group.
Conclusion
Male sex is related to increased cognitive impairment and subcortical atrophy in de novo PD-pRBD. Accordingly, we suggest that sex differences are relevant and should be considered in future clinical and translational research.
Cognitive impairment is a common non-motor symptom in Parkinson’s Disease (PD) and an important source of patient disability and caregiver burden. The timing, profile and rate of cognitive decline varies widely among individuals with PD and can range from normal cognition to mild cognitive impairment (PD-MCI) and dementia (PDD). Beta-amyloid and tau brain accumulation, oxidative stress and neuroinflammation are reported risk factors for cognitive impairment. Traumatic brain injury and pesticide and tobacco exposure have also been described. Genetic risk factors including genes such as COMT, APOE, MAPT and BDNF may also play a role. Less is known about protective factors, although the Mediterranean diet and exercise may fall in this category. Nonetheless, there is conflicting evidence for most of the factors that have been studied. The use of inconsistent criteria and lack of comprehensive assessment in many studies are important methodological issues. Timing of exposure also plays a crucial role, although identification of the correct time window has been historically difficult in PD. Our understanding of the mechanism behind these factors, as well as the interactions between gene and environment as determinants of disease phenotype and the identification of modifiable risk factors will be paramount, as this will allow for potential interventions even in established PD.
Objective: We investigated the prevalence, evolution, associated factors, and risk factors of apathy in a cohort of patients with early-stage Parkinson's disease (PD), who underwent a 4-years prospective follow-up.
Methods: This study included 188 patients with PD (baseline disease duration <3 years) who underwent an annual evaluation using the Lille Apathy Rating Scale (LARS). Based on the cut-off value of −21 observed on the LARS, patients were categorized as PD with and without apathy. The generalized estimating equations (GEE) model was utilized to determine the factors associated with apathy, and the Cox proportional-hazards regression model was used to determine the predictors of apathy.
Results: Apathy increased from a baseline rate of 18.6–28.8% after 4 years; notably, this rate was not persistent across patients' visits. The LARS score was independently associated with the male sex (B 8.131, p = 0.009), low Frontal Assessment Battery (FAB) scores (B 0.567, p = 0.011), low attention scores on the Montreal Cognitive Assessment (MOCA) test (B 0.217, p = 0.026), high Hamilton Depression Rating Scale (HDRS) scores (B 1.362, p < 0.001), high Unified Parkinson's Disease Rating Scale (UPDRS) part III scores (B 1.147, p < 0.001), and prolonged follow-up time (B 1.785, p = 0.048). A high HDRS score was the only predictor of apathy in PD [hazard ratio (HR) 1.043, p = 0.026].
Conclusions: The risk of apathy is higher in men with progressive PD accompanied by disease-specific motor and non-motor symptoms. Depression during early-stage PD is a primary risk factor for apathy in PD.
There are conflicting finds in the literature regarding the association of female estrogen status and the incidence of Parkinson’s disease (PD). We aimed to investigate whether female reproductive factors are associated with PD. Using the Korean National Health Insurance System database, 4,729,546 postmenopausal women without PD were identified. The new incidence of PD was defined as subjects with an ICD-10 code for PD (G20) and with a rare intractable disease registration code for PD (V124). The Cox proportional hazard models were used to evaluate the associations of various reproductive factors with incidence of PD. During the median follow-up of 5.84 years, 20,816 individuals were diagnosed with PD. An increased risk of PD was observed in subjects with a later age at menarche (≥ 17 years) compared with reference subjects (13 years ≤ age at menarche ≤ 14 years) (adjusted hazard ratio, aHR 1.10, 95% confidence interval, CI 1.05–1.16). As age at menopause increased, risk of PD decreased (P for trend 0.019). Consistently, decreased risk of PD was observed (aHR 0.91, 95% CI 0.85–0.96) in subjects with longer duration of fertility (≥ 40 years of age) compared with shorter duration of fertility (< 30 years of age). Hormone replacement therapy and oral contraceptives independently increased the risk of PD by 17% and 7%, respectively. Female reproductive factors are independent risk factors for PD, with higher risk associated with shorter lifetime exposure to endogenous estrogen.
Objective
It is unknown how sex affects the prevalence of freezing of gait (FOG). We conducted a systematic review and meta-analysis to establish the sex-specific prevalence of FOG in persons with Parkinson’s disease (PD). In addition, we investigated whether men and women were represented accurately in intervention trials targeting FOG.Methods
We queried the EMBASE and PubMed databases and identified 2637 articles. Of these, 16 epidemiological studies were included in the meta-analysis, and 51 intervention studies were included in the comparative analysis.ResultsIn total, 5702 persons were included in the final meta-analysis of epidemiological studies. The pooled estimate of overall FOG prevalence was 43% [95% CI 33–53%]. We found no difference in FOG prevalence between men [44% (34–54%)] and women [42% (31–52%)] with PD. However, women were markedly underrepresented in intervention trials targeting FOG, with an average proportion of only 29.6% of women in trial populations. The percentage of women included in trials was similar across intervention types but differed greatly across geographical regions.Conclusion
Sex is not a predictor of FOG. This could aid clinicians in counseling persons with PD about FOG. Importantly, a global effort is needed to include more women into clinical trials. Given the skewed distribution of men and women included in intervention trials targeting FOG, caution might be warranted when extrapolating results from FOG trials to women.
Background
Advances in treatment of Parkinson’s disease (PD) and changes in general life expectancy may have improved survival in PD patients.
Objective
To investigate recent trends in PD mortality.
Methods
In total, 1521 PD patients in local and national registries were followed for 11 years (2006‐2016) from diagnosis until exit date or death, and causes of death were recorded.
Results
The survival of men with PD improved during the follow‐up period, but no change was observed in women (2‐year post‐diagnosis survival: men: 79.0 to 86.3%, p=0.03; women: 82.8 to 87.5%, p=0.42). Pneumonia was the most common immediate cause of death.
Discussion
The survival of men with PD has improved in Finland without a similar change in women. Since changes in treatment likely affect both sexes similarly, the results may reflect the decreasing sex gap in life expectancy. This phenomenon will likely increase the already high male‐to‐female prevalence ratio of PD.
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Background
Clinical research in Parkinson’s disease (PD) faces practical and ethical challenges due to two interrelated problems: participant under-recruitment and lack of diversity. Fox Insight (FI) is a web-based longitudinal study collecting patient-reported outcomes and genetic data worldwide to inform therapeutic studies. FI’s online platform provides an opportunity to evaluate online strategies for recruiting large, diverse research cohorts.
Objective
This project aimed to determine 1) whether FI’s digital marketing was associated with increased enrollment overall and from under-represented patient groups, compared to traditional recruitment methods; 2) the clinical and demographic characteristics of samples recruited online, and 3) the cost of this online recruitment.
Method
FI recruitment during a 6-week baseline period without digital promotion was compared to recruitment during several periods of digital outreach. Separate online recruiting intervals included general online study promotion and unique Facebook and Google ad campaigns targeting under-represented subgroups: early PD, late/advanced PD, and residents of underrepresented/rural geographic areas.
Results
Early PD, late PD, and geotargeting campaigns enrolled more individuals in their respective cohorts compared to baseline. All online campaigns also yielded greater total FI enrollment, attracting more participants who were non-White, Hispanic, older, female, and had lower educational attainment and income, and more medical comorbidities. Cost per new participant ranged from 108 (Google).
Conclusion
Digital marketing may allow researchers to increase, accelerate, and diversify recruitment for PD clinical studies, by tailoring digital ads to target PD cohort characteristics.
Background: Estrogen replacement therapy (ERT) is a common treatment method for menopausal syndrome; however, its therapeutic value for the treatment of neurological diseases is still unclear. Epidemiological studies were performed, and the effect of postmenopausal ERT on treating neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), was summarized through a meta-analysis.
Methods: Twenty-one articles were selected using a systematic searching of the contents listed on PubMed and Web of Science before June 1, 2019. Epidemiological studies were extracted, and relevant research data were obtained from the original articles based on the predefined inclusion criteria and data screening principles. The Comprehensive Meta-Analysis Version 2 software was used to pool effective size, test heterogeneity, conduct meta-regression and subgroup analysis, and to calculate publication bias.
Results: Our results showed that ERT significantly decreased the risk of onset and/or development of AD [odds ratio (OR): 0.672; 95% CI: 0.581–0.779; P < 0.001] and PD (OR: 0.470; 95% CI: 0.368–0.600; P < 0.001) compared with the control group. A subgroup and meta-regression analysis showed that study design and measure of effect were the source of heterogeneity. Age, sample size, hormone therapy ascertainment, duration of the treatment, or route of administration did not play a significant role in affecting the outcome of the meta-analysis.
Conclusion: We presented evidence here to support the use of estrogen therapy for the treatment of AD and PD.
The role of specific sex-related patterns in olfactory dysfunctions of Parkinson’s disease (PD) patients is unclear. The aim of this study was to assess the presence of specific sex-related patterns in olfactory dysfunctions excluding the possibility of confounding effects in patients with Parkinson’s disease. One hundred and sixty-eight participants (99 PD patients and 69 controls) were enrolled and evaluated using Sniffin’ Sticks Extended test (SSET). There was no significant sex difference in the control group for the SSET parameters. By contrast, in the PD group male patients scored significantly lower on odor discrimination (OD), identification (OI), and Threshold-Discrimination-Identification (TDI) score than females. On multivariable linear regression analysis, the only significant predictors of TDI score were sex and apathy. Among PD patients, men showed a significantly greater impairment compared to women in OI, OD and TDI score, but not in odor threshold (OT). These findings highlighted the possible role of sex differences in the development of associated PD non-motor symptoms.
Objective: To analyze the multivariate associations between self-rated level of physical activity and demographic characteristics, self-efficacy for physical activity, fall-related self-efficacy, fear of falling, enjoyment from participation in physical activity, social support, fatigue, and health-related quality of life in persons with PD with a focus on gender.
Method: Participants were persons with PD (n = 285, mean age 69.1 ± 7 years). Self-reported scales measuring level of physical activity (Physical Activity Disability Survey–Revised), enjoyment of physical activity (study- specific questions), self-efficacy for physical activity (Exercise Self-Efficacy Scale), fall-related self-efficacy (Falls Efficacy Scale), social support (Social Influences on Physical Activity), fatigue (Fatigue Severity Scale) and health-related quality of life (Parkinson’s Disease Questionnaire-39) were used. The response rate was 58.2%.
Results: Multiple regression analyses showed that 54.5% of the level of physical activity was explained by low-degree limitations in mobility and activities of daily life (ADL), being younger, higher self-efficacy for physical activity, communication limitations, bodily discomfort, social support and shorter time since diagnosis. Enjoyment of physical activity explained the level of physical activity for women, whereas self-efficacy for physical activity explained the level of physical activity for men.
Conclusion: Implementing strategies to increase functional mobility, self-efficacy for physical activity, social support, and enjoyment of physical activity might facilitate persons with PD beginning and/or maintain different physical activities.
Background
Women with Parkinson’s disease (PD) are more likely to be older, have greater disease severity and comorbidities, and yet are less likely to receive care from a neurologist, as compared with men with PD. Within the PD population, homebound individuals are a particularly vulnerable group facing significant barriers to care, yet within this understudied population, sex-related differences have not been reported.
Purpose
To identify and describe differences in homebound men and women with advanced PD and related disorders, participating in an interdisciplinary home visit program.
Patients and methods
This was an exploratory analysis of homebound patients seen between February 2014 and July 2016 using data collected via in-person interviews and chart review.
Results
We enrolled 85 patients, of whom 52% were women. PD was the most common diagnosis (79%), followed by dementia with Lewy bodies (5%), and other atypical parkinsonism (16%). Men were more likely to have a PD dementia diagnosis than women (17.1% vs 2.3%, p=0.03). Women were more likely to live alone (18.1% of women had no caregiver vs 2.4% of men, p=0.05).
Conclusion
The role of the caregiver in facilitating safe aging-in-place is crucial. Among homebound individuals with advanced PD, women were far more likely to live alone. The absence of a spouse or care partner may be due in part to variable sex-based life expectancies. Our findings suggest that homebound women with advanced PD may face greater barriers to accessing support.
This study aimed to investigate the potential beneficial effects of estrogen on nigrostriatal dopaminergic neuron degeneration in postmenopausal drug-naïve Parkinson’s disease (PD). Based on the ratio of lifetime estrogen exposure length to the total length of the estrogen exposure and deprivation period, postmenopausal women with drug-naïve PD were divided into low (n = 31) and high (n = 31) estrogen exposure ratio groups. We performed a comparative analysis of the striatal dopamine transporter (DAT) availability between the two groups. Additionally, we evaluated the longitudinal change in the levodopa equivalent dose per month using a linear mixed model. The motor symptoms were more severe in the low estrogen exposure ratio group than in the high estrogen exposure ratio group (P = 0.016). PD patients in the two groups had significantly lower DAT availability on all striatal sub-regions except for ventral striatum than did age- and sex-matched normal controls. When comparing the two groups, PD patients in the low estrogen exposure ratio group exhibited significantly lower DAT availability in the posterior putamen (P = 0.024) and in the ventral putamen (P = 0.036) than those in the high estrogen exposure ratio group. The estimated monthly levodopa equivalent dose changes were 10.9 in the low estrogen exposure ratio group and 7.1 in the high estrogen exposure ratio group with a significant interaction between the two groups (P = 0.001). These in vivo data provide indirect evidence showing that estrogen may elicit a beneficial effect on nigrostriatal dopamine neurons in PD.
Increasing evidence points to biological sex as an important factor in the development and phenotypical expression of Parkinson’s disease (PD). Risk of developing PD is twice as high in men than women, but women have a higher mortality rate and faster progression of the disease. Moreover, motor and nonmotor symptoms, response to treatments and disease risk factors differ between women and men. Altogether, sex-related differences in PD support the idea that disease development might involve distinct pathogenic mechanisms (or the same mechanism but in a different way) in male and female patients. This review summarizes the most recent knowledge concerning differences between women and men in PD clinical features, risk factors, response to treatments and mechanisms underlying the disease pathophysiology. Unraveling how the pathology differently affect the two sexes might allow the development of tailored interventions and the design of innovative programs that meet the distinct needs of men and women, improving patient care.
The leucine-rich repeat kinase 2 (LRRK2) gene and α-synuclein gene (SNCA) are the key influence factors of Parkinson's disease (PD). It is reported that dysfunction of LRRK2 may influence the accumulation of α-synuclein and its pathology to alter cellular functions and signaling pathways by the kinase activation of LRRK2. The accumulation of α-synuclein is one of the main stimulants of microglias acitiviton. Microglias are macrophages resided in the brain, and activation of microglials is believed to contribute to neuroinflammation and neuronal death in PD. Therefore, clarifying the complex relation among LRRK2, α-synuclein and microglials could offer targeted clinical therapies for PD. Here, we provide an update review focused discussion of the evidence supporting some of the key mechanisms that are important for LRRK2-dependent neurodegeneration in PD.
Available data indicate that there are gender differences in many features of Parkinson's disease (PD). Precise identification of the gender differences is important to tailor treatment, predict outcomes, and meet other individual and social needs in women and men with PD. The aim of this study was to review the available clinical data on gender differences in PD. Original articles and meta-analyses published between 1990 and 2016 systematically exploring gender differences in PD were reviewed. There is slight male preponderance in incidence and prevalence of PD. PD starts earlier in men. Women tend to be more prone to develop tremor-dominant PD but are less rigid than men. Motor improvement after deep brain stimulation is equal in both sexes, but women tend to show better improvement in activities of daily living. Furthermore, women with PD show better results on tests for general cognitive abilities, outperform men in verbal cognitive tasks, show more pain symptoms, and score higher on depression scales. It seems, however, that the differences in cognition, mood, and pain perception are not disease specific as similar gender differences can be found in healthy subjects and in other neurological conditions. Despite PD being the most frequently studied movement disorder, studies investigating gender differences in PD are still scarce with most of the studies being cross-sectional. Good-quality, prospective, longitudinal studies analyzing gender differences in PD and comparing them to matched healthy controls are needed in order to properly address the issues of gender differences in PD.
Background:
Parkinson's disease (PD) is 1.5 times more frequent in men than women. Whether age modifies this ratio is unclear. We examined whether male-to-female (M-F) ratios change with age through a French nationwide prevalence/incidence study (2010) and a meta-analysis of incidence studies.
Methods:
We used French national drug claims databases to identify PD cases using a validated algorithm. We computed M-F prevalence/incidence ratios overall and by age using Poisson regression. Ratios were regressed on age to estimate their annual change. We identified all PD incidence studies with age/sex-specific data, and performed a meta-analysis of M-F ratios.
Results:
On the basis of 149 672 prevalent (50% women) and 25 438 incident (49% women) cases, age-standardised rates were higher in men (prevalence=2.865/1000; incidence=0.490/1000 person-years) than women (prevalence=1.934/1000; incidence=0.328/1000 person-years). The overall M-F ratio was 1.48 for prevalence and 1.49 for incidence. Prevalence and incidence M-F ratios increased by 0.05 and 0.14, respectively, per 10 years of age. Incidence was similar in men and women under 50 years (M-F ratio <1.2, p>0.20), and over 1.6 (p<0.001) times higher in men than women above 80 years (p trend <0.001). A meta-analysis of 22 incidence studies (14 126 cases, 46% women) confirmed that M- F ratios increased with age (0.26 per 10 years, p trend=0.005).
Conclusions:
Age-increasing M-F ratios suggest that PD aetiology changes with age. Sex-related risk/protective factors may play a different role across the continuum of age at onset. This finding may inform aetiological PD research.
To improve our understanding of sex differences in the clinical characteristics of Parkinson's Disease, we sought to examine differences in the clinical features and disease severity of men and women with early treated Parkinson's Disease (PD) enrolled in a large-scale clinical trial.
Analysis was performed of baseline data from the National Institutes of Health Exploratory Trials in Parkinson's Disease (NET-PD) Long-term Study-1, a randomized, multi-center, double-blind, placebo-controlled study of 10 grams of oral creatine/day in individuals with early, treated PD. We compared mean age at symptom onset, age at PD diagnosis, and age at randomization between men and women using t-test statistics. Sex differences in clinical features were evaluated, including: symptoms at diagnosis (motor) and symptoms at randomization (motor, non-motor, and daily functioning).
1,741 participants were enrolled (62.5% male). No differences were detected in mean age at PD onset, age at PD diagnosis, age at randomization, motor symptoms, or daily functioning between men and women. Differences in non-motor symptoms were observed, with women demonstrating better performance compared to men on SCOPA-COG (Z = 5.064, p<0.0001) and Symbol Digit Modality measures (Z = 5.221, p<0.0001).
Overall, men and women did not demonstrate differences in clinical motor features early in the course of PD. However, the differences observed in non-motor cognitive symptoms suggests further assessment of the influence of sex on non-motor symptoms in later stages of PD is warranted.
Background:
The early detection of wearing-off in Parkinson disease (DEEP) observational study demonstrated that women with Parkinson's disease (PD) carry an increased risk (80.1%) for wearing-off (WO). This post hoc analysis of DEEP study evaluates gender differences on WO and associated phenomena.
Methods:
Patients on dopaminergic treatment for ≥ 1 year were included in this multicenter observational cross-sectional study. In a single visit, WO was diagnosed based on neurologist assessment as well as the use of the 19-item wearing-off questionnaire (WOQ-19); WO was defined for scores ≥ 2. Post hoc analyses were conducted to investigate gender difference for demographic and clinical features with respect to WO.
Results:
Of 617 patients enrolled, 236 were women and 381 were men. Prevalence of WO was higher among women, according to both neurologists' judgment (61.9% versus 53.8%, P = 0.045) and the WOQ-19 analysis (72.5% versus 64.0%, P = 0.034). In patients with WO (WOQ-19), women experienced ≥ 1 motor symptom in 72.5% versus 64.0% in men and ≥ 1 nonmotor symptom in 44.5% versus 36.7%, in men.
Conclusions:
Our results suggest WO as more common among women, for both motor and nonmotor symptoms. Prospective studies are warranted to investigate this potential gender-effect.
Deep brain stimulation (DBS) is an established treatment for patients with advanced parkinson's disease (PD). Research shows that women are under-represented among patients undergoing DBS surgery. This may be due to gender-biased selection of patients, but patients' wishes and attitudes may also contribute. This study investigated the decision making process to undergo DBS from the patient's perspective, and explored any gender patterns in the participants' decision-making.
All patients operated on with DBS for PD at the University Hospital of Northern Sweden between January 2002 and April 2010 were invited to an interview study. In this way 39 patients were recruited, 31 men and eight women. Three additional women, operated elsewhere, were recruited to acheive a more gender-balanced sample. In a mixed-method analysis, the interviews were analysed according to the constant comparison technique in grounded theory and descriptive statistics was used to present demographics and compare categories.
Three different approaches to DBS were identified among the patients. 'Taking own initiative', included 48% of the patients and implied that the patients' own initiatives and arguments had been crucial for having surgery. 'Agreeing when offered', and accepting DBS when suggested by doctors embraced 43%. The third approach, 'Hesitating and waiting' included < 10% of the patients. Most of the men were either 'taking own initiative' or 'agreeing when offered'. The 11 women were evenly distributed in all three approaches. Among the interviewed, more women than men expressed strong fear of complications and more women consulted friends and relatives prior to deciding about DBS. Half of the patients had held a leadership position at work or in another organisation, and among patients 'taking own initiative' the proportion with leadership experiences was 80%. At time for surgery ten men but no woman were professionally active.
This study suggests that many patients with advanced PD have to argue and struggle with their clinicians in order to be referred to a DBS-team. The study further suggests that patients' wishes, behaviour and position in society may all contribute to the skewed gender distribution among patients treated with DBS.
Personalized medicine considering sex, gender, and cultural context has become the vanguard of delivery of care. However, women's issues in Parkinson disease (PD), especially from a psychosocial standpoint, have been an overlooked field. The key research areas include women‐inclusive drug and device studies and genetic and hormonal considerations. Moreover, women with PD need to be educated and empowered on how to communicate their symptoms and needs, get engaged in research, get organized as a community, and support one another. Women with PD need tools to help track and convey their unique motor and nonmotor symptoms and psychological and social support needs. The management of PD needs to be customized to include the unique stages of women's lives, including menstrual cycles, pregnancy, perimenopause, menopause, and postmenopause. Specific guidelines for the use of hormonal treatments and customized dopamine replacement dosing need to be developed. Women need guidance on culturally sensitive wellness and self‐care strategies that are customized for them. Basic core competencies in knowledge for all clinicians treating women with PD need to be established, including how to accurately diagnose, proactively identify, and treat the symptoms of PD in women and to ensure timely referral for specialty care, advanced therapies, and research studies. Caregivers and families need guidance on holistically supporting women with PD. The voices of women living with PD must be amplified to catalyze real change in this neglected field. This paper provides an overview of the current knowledge, gaps, and possible strategies to deal with the unmet needs of women living with PD with a focus on the clinical and psychosocial aspects. © 2022 International Parkinson and Movement Disorder Society
Background:
Studies of Parkinson's disease (PD) and the association with age at menarche or menopause have reported inconsistent findings. Mendelian randomization (MR) may address measurement errors because of difficulties accurately reporting the age these life events occur.
Objective:
We used MR to assess the association between age at menopause and age at menarche with PD risk.
Methods:
We performed inverse variant-weighted (IVW) MR analysis using external genome-wide association study (GWAS) summary data from the United Kingdom biobank, and the effect estimates between genetic variants and PD among two population-based studies (Parkinson's disease in Denmark (PASIDA) study, Denmark, and Parkinson's Environment and Gene study [PEG], United States) that enrolled 1737 female and 2430 male subjects of European ancestry. We, then, replicated our findings for age at menopause using summary statistics from the PD consortium (19 773 women), followed by a meta-analysis combining all summary statistics.
Results:
For each year increase in age at menopause, the risk for PD decreased (odds ration [OR], 0.84; 95% confidence interval [CI], 0.73-0.98; P = 0.03) among women in our study, whereas there was no association among men (OR, 0.98; 95% CI, 0.85-1.11; P = 0.71). A replication using summary statistics from the PD consortium estimated an OR of 0.94 (95% CI, 0.90-0.99; P = 0.01), and we calculated a meta-analytic OR of 0.93 (95% CI, 0.89-0.98; P = 0.003). There was no indication for an association between age at menarche and PD (OR, 0.75; 95% CI, 0.44-1.29; P = 0.29).
Conclusions:
A later age at menopause was associated with a decreased risk of PD in women, supporting the hypothesis that sex hormones or other factors related to late menopause may be neuroprotective in PD. © 2021 International Parkinson and Movement Disorder Society.
The term sexual and gender minority (SGM) includes lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI) communities and populations whose sex, gender identity, and sexual orientation do not correspond to binary constructs.¹ SGM individuals are diverse and are not a monolithic group. Throughout this article, we use the terms “SGM communities” or “SGM populations” as a shorthand, without any intent to minimize the richness and diversity of these groups. The American Medical Association practice guidelines recommend training LGBTQI-responsive professionals to provide culturally-sensitive and quality-assured care.² Similarly, the American Academy of Neurology identified that it is necessary to enhance the practicing neurologists’ SGM education to improve the community’s healthcare quality.³ Since recognizing the importance of SGM acceptance and awareness in neurology in 2015,⁴ the number of neurological studies inclusive of SGM individuals has increased; however, the field of movement disorders remains understudied.⁵ The investigation of the intersection between movement disorders and SGM health is disproportionately skewed to the clinical manifestations of the human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS),⁶ which only represent a portion of the health care needs of this population. In 2019, the Michael J. Fox Foundation embedded its classic logo in the rainbow flag to honor the community on the 50th anniversary of the Stonewall Inn riots and express the concept that “Parkinson’s disease (PD) does not discriminate.”⁷ This example highlights the importance of researching the intersection of movement disorders and SGM identity to identify and address potential disparities in healthcare access and outcomes for SGM individuals with movement disorders.
For every gap in health and well-being whose contours we have mapped, the widespread lack of comprehensive data collection means that many more disparities — and the policy and programmatic interventions that might address them — remain unknown.
Background:
Results regarding the association between hormonal exposure and risk of Parkinson's disease (PD) are heterogeneous.
Objectives:
To investigate the association of reproductive life characteristics with PD among postmenopausal women.
Methods:
The PARTAGE case-control included 130 female cases and 255 age-matched female controls. Information on gynecological history was obtained from a standardized questionnaire and PD was validated by neurological examination. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression.
Results:
After adjustment for education level, smoking status, professional exposure to pesticides, and coffee and alcohol drinking, bilateral oophorectomy (OR = 3.55, 95%CI = 1.75-7.20), but neither menopause before age 50 years (OR = 1.24, 95%CI = 0.74-2.09) nor hormone therapy (HT; OR = 1.07, 95%CI = 0.62-1.86), was associated with PD.
Conclusion:
Our findings suggest that bilateral oophorectomy is associated with increased risk of PD. © 2021 International Parkinson and Movement Disorder Society.
Importance
Little is known about the neurologic health needs of sexual and gender minority (SGM) individuals, and existing research indicates health care disparities for this group.
Objective
To describe the current state of science in SGM neurology and highlight areas of knowledge and gaps to guide future research.
Evidence Review
All articles published before April 12, 2020, in PubMed, Embase, Web of Science, PsycInfo, CINAHL, and BIOSIS Previews were searched using a search string encompassing SGM descriptors and neurologic disorders. A total of 8359 items were found and entered into EndNote, and 2921 duplicates were removed. A blind title and abstract review was performed followed by full-text review in duplicate, with conflicts settled through consensus, to identify 348 articles eligible for data abstraction. Articles presenting primary data about an identified adult SGM population addressing a clinical neurology topic were included. Descriptive statistics were used for abstracted variables.
Findings
Of 348 studies, 205 (58.9%) were case reports or series, 252 (72.4%) included sexual minority cisgender men, and 247 (70.9%) focused on HIV. An association was found between autism spectrum disorder and gender dysphoria in 9 of 16 studies (56.3%), and a higher risk of ischemic stroke in transgender women was shown in other studies. Literature in neuroinfectious disease, the most common topic, largely focused on HIV (173 of 200 studies [86.5%]). Findings in other neurologic topics were limited by lack of data.
Conclusions and Relevance
In this rigorous compendium of SGM neurology literature, several deficiencies were found: most studies focused on a limited breadth of neurologic pathology, included only a portion of the overall SGM community, and did not assess other aspects of sociodemographic diversity that may contribute to disparities in health care access and outcomes among SGM individuals. Expanding neurologic research to include broader representation of SGM individuals and incorporating sociodemographic factors, like race/ethnicity and socioeconomic status, are essential steps toward providing equitable neurologic care for this community.
Background
Tamoxifen, a selective estrogen receptor modulator, has been shown to variably affect Parkinson's disease (PD) risk.
Objective
The aim of this study was to review epidemiological literature and evaluate the rate of PD in women with breast cancer with tamoxifen exposure in a US population.
Methods
A literature search was conducted to identify relevant studies. We performed a retrospective cohort analysis using the Nurses' Health Study Version One to report descriptive statistics.
Results
Most studies suggest there may be a time‐dependent effect of tamoxifen on PD risk, with the risk increasing with time from exposure. However, rates of PD in persons exposed to tamoxifen overall appear to be low. In our cohort, PD was evident in 6.2 per 1,000 of those with tamoxifen use and 3.6 per 1,000 of those without tamoxifen use. Time from breast cancer to PD diagnosis was 9.7 years among women with tamoxifen exposure and 11.7 among women without.
Conclusions
Tamoxifen may be associated with an increased risk for PD. Further research is needed to elucidate the role of estrogen and selective estrogen antagonism in PD. © 2021 International Parkinson and Movement Disorder Society
Parkinson's disease varies in severity and age of onset. One source of this variability is sex. Males are twice as likely as females to develop Parkinson's disease, and tend to have more severe symptoms and greater speed of progression. However, to date, there is little information in large cohorts on sex differences in the patterns of neurodegeneration. Here we used MRI and clinical information from the Parkinson Progression Markers Initiative to measure structural brain differences between sexes in Parkinson's disease after regressing out the expected effect of age and sex. We derived atrophy maps from deformation-based morphometry of T1-weighted MRI and connectivity from diffusion-weighted MRI in de novo Parkinson's disease patients (149 males: 83 females) with comparable clinical severity, and healthy control participants (78 males: 39 females). Overall, even though the two patient groups were matched for disease duration and severity, males demonstrated generally greater brain atrophy and disrupted connectivity. Males with Parkinson's disease had significantly greater tissue loss than females in 11 cortical regions including bilateral frontal and left insular lobe, right postcentral gyrus, left inferior temporal and cingulate gyrus and left thalamus, while females had greater atrophy in six cortical regions, including regions in the left frontal lobe, right parietal lobe, left insular gyrus and right occipital cortex. Local efficiency of white matter connectivity showed greater disruption in males in multiple regions such as basal ganglia, hippocampus, amygdala and thalamus. These findings support the idea that development of Parkinson's disease may involve different pathological mechanisms and yield distinct prognosis in males and females, which may have implications for research into neuroprotection, and stratification for clinical trials.
Introduction:
Females have a reduced risk of Parkinson's disease (PD). However, it is unclear if sex is a prognostic factor. We aimed to examine differences in presentation, physician- and patient-reported PD outcomes, and progression by sex in a large clinical cohort.
Methods:
This study was a secondary analysis of a cohort of PD patients seen at a tertiary care center. Sociodemographic and clinical characteristics, treatment, care timing, and outcomes were examined by sex. Sex differences in progression of impairment, disability, and health-related quality of life (HRQoL) were tested with five-year piecewise linear mixed-effects models. A mediation analysis assessed drivers of sex differences.
Results:
The study included 914 males and 549 females. Females had significantly less social support, more psychological distress, and worse self-reported (but not physician-reported) disability and HRQoL at initial PD care visits, compared to males. Addressing anxiety symptoms may attenuate this difference. PD progression sex differences were minimal.
Conclusion:
PD progression does not differ by sex, yet patient-reported measures of disease severity are worse in females than males. To attenuate this sex difference in disease experience, psychological distress screening and management, particularly targeting females, should be implemented as part of PD clinical care.
Introduction:
Better awareness of the cognitive domains affected in non-demented Parkinson's Disease (PD) should improve understanding of cognitive disease mechanisms. A complete understanding of the cognitive areas impaired in non-demented PD is hindered because most studies use small clinical samples without comparison to healthy controls. This meta-analysis examined cumulative evidence across studies to determine if there were impairments in non-demented PD in the three cognitive domains thought to be most widely affected in PD: frontal executive, visuospatial, and verbal memory. Because there are well-documented sex differences in PD, a second objective was to explore sex differences in these findings.
Methods:
MEDLINE, EMBASE and PsycINFO databases were searched (1988-March 2017). Random effects models were used to compute and compare effect sizes of differences between PD patients and controls within cognitive domains. Sex differences in effect sizes were also examined in these comparisons. Moderating factors including age, disease duration, motor symptom severity, levodopa dosage, and depression were examined through meta-regression.
Results:
PD patients showed deficits of moderate effect sizes in all three cognitive domains relative to controls. Significant sex differences were observed only for frontal executive abilities, with male PD patients showing greater deficits than female PD patients relative to controls. No moderators of effect sizes were identified in the domain specific overall or sex-segregated meta-analyses.
Conclusions:
Results indicate that non-demented PD patients have deficits of moderate magnitude in frontal executive, verbal memory, and visuospatial abilities. Our findings of greater frontal executive deficits in males warrant further confirmation.
Introduction:
The current study was designed to determine whether the degree of presynaptic striatal dopamine depletion can predict the later development of freezing of gait (FOG) in Parkinson's disease (PD).
Methods:
This retrospective cohort study included 390 de novo patients with PD without FOG at baseline. The participants were divided into tertiles according to the baseline dopamine transporter (DAT) uptake of each striatal subregion, and the cumulative risk of FOG was compared using the Kaplan-Meier method. Cox proportional hazard models were used to assess the predictive power of DAT uptake of striatal subregions for the development of FOG.
Results:
During a median follow-up period of 4.0 years, 143 patients with PD (36.7%) developed FOG. The severe reduction group of DAT uptake in the caudate nucleus and putamen had a significantly higher incidence of FOG than that of the mild and moderate reduction groups. Multivariate Cox regression analyses showed that DAT uptakes in the caudate nucleus (hazard ratio [HR] 0.551; 95% confidence interval [CI] 0.392-0.773; p = 0.001) and putamen (HR 0.441; 95% CI 0.214-0.911; p = 0.027) predicted the development of FOG. In addition, male sex, higher postural instability and gait difficulty score, and a lower Montreal Cognitive Assessment score were also significant predictors of FOG.
Conclusion:
Our finding suggests that presynaptic striatal dopaminergic denervation predicts the later development of FOG in de novo patients with PD, which may provide reliable insight into the mechanism of FOG in terms of nigrostriatal involvement.
Background:
Studies suggesting a protective effect of estrogen in neurodegenerative diseases prompted us to investigate this relationship in progressive supranuclear palsy (PSP).
Methods:
This case-control study evaluated the self-reported reproductive characteristics and estrogen of 150 women with PSP and 150 age-matched female controls who participated in the Environmental Genetic-PSP study. Conditional logistic regression models were generated to examine associations of PSP with estrogen.
Results:
There was no association between years of estrogen exposure duration and PSP. There was a suggestion of an inverse association between composite estrogen score and PSP that did not reach statistical significance (P = .06). Any exposure to estrogen replacement therapy halved the risk of PSP (odds ratio = 0.52; 95% confidence interval = 0.30-0.92; P = .03). Among PSP cases, earlier age at menarche was associated with better performance on Hoehn and Yahr stage (β = -0.60; SE = 0.26; P = .02) and Unified Parkinson's Disease Rating Scale II score (β = -5.19; SE = 2.48; P = .04) at clinical examination.
Conclusions:
This case-control study suggests a protective role of lifetime estrogen exposure in PSP. Future studies will be needed to confirm this association. © 2018 International Parkinson and Movement Disorder Society.
Objective:
To examine sex differences and trends in comorbid disease and health care utilization in individuals with newly diagnosed Parkinson disease (PD).
Design:
Retrospective cohort study.
Participants:
Over 133,000 Medicare beneficiaries with a new PD diagnosis in 2002 followed through 2008.
Methods:
We compared the prevalence and cumulative incidence of common medical conditions, trends in survival and health care utilization between men and women with PD.
Results:
Female PD patients had higher adjusted incidence rate ratio (IRR) of depression (IRR: 1.28, 1.25-1.31), hip fracture (IRR: 1.51, 1.45-1.56), osteoporosis (3.01, 2.92-3.1), and rheumatoid/osteoarthritis (IRR: 1.47, 1.43-1.51) than men. In spite of greater survival, women with PD used home health and skilled nursing facility care more often, and had less outpatient physician contact than men throughout the study period.
Conclusions:
Women experience a unique health trajectory after PD diagnosis as suggested by differing comorbid disease burden and health care utilization compared to men. Future studies of sex differences in care needs, care quality, comorbidity related disability, PD progression, and non-clinical factors associated with disability are needed to inform research agendas and clinical guidelines that may improve quality survival for women with PD.
Objective:
To compare access to caregiving between men and women with Parkinson disease (PD).
Methods:
This was a cross-sectional and longitudinal study among participants with PD enrolled in the National Parkinson Foundation Parkinson's Outcomes Project from 2009 to 2014 at 21 international sites. The primary outcome measures were presence of a caregiver at the baseline visit, caregiver burden as measured by the Multidimensional Caregiver Strain Index (MCSI) at baseline, and time to first paid caregiver.
Results:
A total of 7,209 participants (63% men, 37% women) with PD were evaluated. Men had a mean age of 66.0 (SD 9.8) years, and women had a mean age of 66.9 (SD 9.7) years. More men than women had a caregiver (88.4% vs 79.4%, p < 0.0001). Caregivers of men reported greater strain than those of women (MCSI score 19.9 vs 16.4, p < 0.0001). These differences persisted after controlling for age, disease stage, number of comorbidities, cognitive and mobility measures, and health-related quality of life. In addition, the odds of caregiver accompaniment at baseline visit were lower for women compared to men (odds ratio 0.76, 95% confidence interval [CI] 0.67-0.86), and women had a faster rate to using a paid caregiver than men (hazard ratio 1.76, 95% CI 1.35-2.28) after controlling for potential confounders.
Conclusions:
Informal caregiving resources are lower for women than men with PD, despite the finding that their caregivers report less strain than those of men. In addition, women are more likely to use formal, paid caregivers. Strategies to improve access to caregiving, particularly for women, are needed.
Evidence on the relationship between reproductive factors, use of oral contraceptives (OCs) and the incidence of Parkinson’s disease (PD) remain inconclusive. The aim of this meta-analysis is to evaluate whether relevant reproductive factors including age at menarche, age at menopause, fertile lifespan, parity, type of menopause (surgical versus natural), and use of OCs are associated with risk of PD in women via random-effects model. PubMed and EMBASE database were used to search for case-control or cohort studies published before February17, 2017. 6 case-control and 5 cohort studies were included in the meta-analysis. The pooled relative risks (RRs) of PD risk were 1.00 (95% CI: 0.79–1.28) for use of OCs (ever versus never), 1.03 (95% CI: 0.84–1.26) for age at menarche, 0.98 (95% CI: 0.75–1.29) for age at menopause, 0.98(95% CI: 0.77–1.25) for fertile lifespan, 0.99(95% CI:0.0.79–1.25) for parity, 0.93 (95% CI:0.68–1.29) for type of menopause (surgical versus natural). In the subgroup analysis stratified by study design, age, caffeine intake and smoking, an inverse association was found between surgical menopause and risk of PD for those adjusting for caffeine intake (RR: 0.67, 95% CI: 0.45–0.99) and smoking (RR: 0.77, 95% CI: 0.63–0.94); while a positive association was found between surgical menopause and PD risk for those not adjusting for smoking (RR: 1.91, 95% CI: 1.29–2.83). In conclusion, our meta-analysis provided little epidemiological support for the role of reproductive factors in the incidence of PD. Whether surgical menopause is inversely associated with the risk of PD requires further explorations.
Impulse control disorders (ICDs), such as compulsive gambling, buying, sexual, and eating behaviors, are a serious and increasingly recognized complication in Parkinson's disease (PD), occurring in up to 20% of PD patients over the course of their illness. Related behaviors include punding (stereotyped, repetitive, purposeless behaviors), dopamine dysregulation syndrome (DDS) (compulsive medication overuse), and hobbyism (e.g., compulsive internet use, artistic endeavors, and writing). These disorders have a significant impact on quality of life and function, strain interpersonal relationships, and worsen caregiver burden, and are associated with significant psychiatric comorbidity. ICDs have been most closely related to the use of dopamine agonists (DAs), while DDS is primarily associated with shorter acting, higher potency dopamine replacement therapy (DRT), such as levodopa. However, in preliminary research ICDs have also been reported to occur with monoamine oxidase inhibitor-B and amantadine treatment, and after deep brain stimulation (DBS) surgery. Other risk factors for ICDs may include sex (e.g., male sex for compulsive sexual behavior, and female sex for compulsive buying behavior); younger age overall at PD onset; a pre-PD history of an ICD; personal or family history of substance abuse, bipolar disorder, or gambling problems; and impulsive personality traits. Dysregulation of the mesocorticolimbic dopamine system is thought to be the major neurobiological substrate for ICDs in PD, but there is preliminary evidence for alterations in opiate and serotonin systems too. The primary treatment of ICDs in PD is discontinuation of the offending treatment, but not all patients can tolerate this due to worsening motor symptoms or DA withdrawal syndrome. While psychiatric medications and psychosocial treatments are frequently used to treat ICDs in the general population, there is limited empirical evidence for their use in PD, so it is critical for patients to be monitored closely for ICDs from disease onset and routine throughout its course. In the future, it may be possible to use a precision medicine approach to decrease the incidence of ICDs in PD by avoiding DA use in patients determined to be at highest risk based on their clinical and neurobiological (e.g., motor presentation, behavioral measures of medication response, genetics, dopamine transporter neuroimaging) profile. Additionally, as empirically validated treatments for ICDs and similar disorders (e.g., substance use disorders) emerge, it will also be important to examine their efficacy and tolerability in individuals with comorbid PD.
It is currently under debate whether there is a sex effect in LRRK2-associated Parkinson disease (PD), as several studies suggested such effect while others did not.
All case-control studies describing LRRK2 mutations and PD were examined, and papers with data on sex and LRRK2 mutations in both patients and controls were included (n = 17) in a sex-stratified meta-analysis. Additional studies (n = 33) that included data on male:female ratio only in patients with LRRK2 mutations, were included in further analysis of male:female ratio in LRRK2-assocoiated PD patients.
Similar risk estimates were calculated for men and women. Among men, LRRK2 mutation carriers had a pooled OR for PD of 4.20 (95% CI 2.95-5.99, p < 0.0001) and among women, LRRK2 mutation carriers had a pooled OR for PD of 4.73 (95% CI 3.26-6.86, p < 0.0001). Similar risk estimates for men and women were also observed when analysing specific LRRK2 mutations. A total of 1080 LRRK2-associated PD patients with sex information were identified. The male:female ratio was 1.02:1.00 (50.6% men and 49.4% women).
While sporadic PD is characterized by a sex effect, with more affected men than women, LRRK2-associated PD lacks a sex effect, as typically seen in autosomal dominant traits.
Copyright © 2015 Elsevier Ltd. All rights reserved.
To examine potential sex differences in nonmotor symptoms (NMS) among drug-naive patients with Parkinson disease (PD), and to identify NMS that can best differentiate patients with early PD from controls.
Our cross-sectional analysis included 414 newly diagnosed, untreated patients with PD (269 men and 145 women) and 188 healthy controls (121 men and 67 women) in the Parkinson's Progression Markers Initiative Study. NMS were measured using well-validated instruments covering sleep, olfactory, neurobehavioral, autonomic, and neuropsychological domains.
Male and female patients with PD were fairly comparable on motor presentations but differed on several nonmotor features. Male patients with PD had significantly more pronounced deficits in olfaction (p = 0.02) and in certain cognitive measurements (all p < 0.01) than female patients, whereas female cases experienced higher trait anxiety (p = 0.02). Multiple stepwise logistic regression analysis showed that the combination of NMS measures-University of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT), and state anxiety from the State-Trait Anxiety Inventory-effectively differentiated patients with PD from controls with an area under the receiver operating characteristic curve (AUC) of 0.913 (95% confidence interval [CI]: 0.89-0.94). UPSIT, MoCA, and SCOPA-AUT were the most predictive NMS measurements in men (AUC = 0.919; 95% CI: 0.89-0.95) as compared to UPSIT, MoCA, and REM Sleep Behavior Disorder Screening Questionnaire in women (AUC = 0.903; 95% CI: 0.86-0.95).
Our analysis revealed notable sex differences in several nonmotor features of patients with de novo PD. Furthermore, we found a parsimonious NMS combination that could effectively differentiate de novo cases from healthy controls.
© 2015 American Academy of Neurology.
To investigate sex differences in cognitive function in Parkinson’s disease patients, a cohort of 172 male patients and 139 female patients were recruited for this study. Their demographic and clinical features, including age, disease duration, education level, Unified Parkinson’s Disease Rating Scale-III, Hoehn–Yahr Scale, activities of daily living, Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale score were recorded. The Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC) and Wechsler Memory Scale-Chinese Revision (WMS-RC) scores were compared to distinguish the cognitive properties between the two groups. The MMSE values did not show a significant difference between the groups. However, the MoCA scores of male patients were significantly higher than those of female patients (adjusted p < 0.05). The male group demonstrated better performances with respect to visuospatial function, naming and abstraction (adjusted p < 0.05). The WAIS-RC data showed that female patients had lower scores in information, vocabulary, picture completion, block design and picture arrangement (adjusted p < 0.05), and the WMS-RC data showed that 100-1 and cumulative addition abilities were significantly weaker in females than males (adjusted p < 0.05). Cognitive disturbances were more prevalent and severe in women among Chinese Parkinson’s disease patients.
Hormone therapy (HT) is a class of medications widely prescribed to women in the Western world. Evidence from animal models and in vitro studies suggests that estrogen may protect against nigrostriatal system injury and increase dopamine synthesis, metabolism, and transport. Existing epidemiologic research indicates a possible reduced risk of Parkinson's disease (PD) associated with HT use. The objective of this study was to evaluate PD risk associated with specific HT formulations. Neurologist-confirmed cases and age-matched controls were identified from Group Health Cooperative (GHC) of Washington State. Final analysis included 137 female cases and 227 controls. Hormone therapy use was ascertained from the GHC pharmacy database, further classified as conjugated estrogens, esterified estrogens, and progestin. Ever use of HT formulation demonstrated a suggested elevated risk with esterified estrogen use (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.0-9.8), and no risk associated with conjugated estrogen use (OR, 0.6; 95% CI, 0.6-1.3). Restricting this analysis to prescriptions that included progestin further elevated the risk associated with esterified estrogen use (OR, 6.9; 95% CI, 2.1-22.9); again, no risk was associated with conjugated estrogen use (OR, 1.7; 95% CI, 0.6-5.0). The findings from this study suggest an increase in PD risk associated with esterified estrogen use combined with progestin, and no risk associated with conjugated estrogen with progestin. These findings could have important implications for choice of HT in clinical practice. © 2014 International Parkinson and Movement Disorder Society
Background:
Parkinson's disease (PD) is a common neurodegenerative disorder. Epidemiological studies on the incidence of PD are important to better understand the risk factors for PD and determine the condition's natural history.
Objective:
This systematic review and meta-analysis examine the incidence of PD and its variation by age and gender.
Methods:
We searched MEDLINE and EMBASE for epidemiologic studies of PD from 2001 to 2014, as a previously published systematic review included studies published until 2001. Data were analyzed separately for age group and gender, and meta-regression was used to determine whether a significant difference was present between groups.
Results:
Twenty-seven studies were included in the analysis. Meta-analysis of international studies showed rising incidence with age in both men and women. Significant heterogeneity was observed in the 80+ group, which may be explained by methodological differences between studies. While males had a higher incidence of PD in all age groups, this difference was only statistically significant for those in the age range 60-69 and 70-79 (p < 0.05).
Conclusion:
PD incidence generally increases with age, although it may stabilize in those who are 80+.
