Sex Differences in Clinical Features of Early, Treated Parkinson’s Disease

Augustine, Erika F.; Pérez, Adriana; Dhall, Rohit; Umeh, Chizoba C.; Videnović, Aleksandar; Cambi, Franca; Wills, Anne Marie; Elm, Jordan; Zweig, Richard M.; Shulman, Lisa M.; Nance, Martha; Bainbridge, Jacquelyn; Suchowersky, Oksana

doi:10.1371/journal.pone.0133002

Cited by 56 publications

(59 citation statements)

References 39 publications

(46 reference statements)

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“…The small sex differences in disease severity that we observed could reflect previous treatment differences prior to receipt of care at the study sites (Saunders-Pullman et al, 2011) or the overall older age of women when compared to men in our sample. This finding is supported by the findings by Augustine et al: no differences in disease severity between men and women were observed as part of a large, clinical trial in which individuals were on similar treatment regiments before enrollment and were in the early stages of disease (Augustine et al, 2015). It is also possible that despite similar disease durations, women have a more severe disease course than men.…”

Section: Discussionsupporting

confidence: 78%

“…However, results have been conflicting partly due to differences in sample characteristics and sizes, as well as measurement tools used. In a recent, large cross-sectional study of subjects enrolled in a randomized-clinical treatment trial, no significant differences were seen in health-related quality of life or disease severity between men and women (Augustine et al, 2015). However, investigators did find that women performed better on tests of cognitive function than men.…”

mentioning

confidence: 99%

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Sex Differences in the Clinical Progression of Parkinson's Disease

Dahodwala¹,

Pei²,

Schmidt³

2016

Journal of Obstetric, Gynecologic & Neonatal Nursing

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Objective To describe characteristics of Parkinson’s disease (PD) by sex among a large, population-based cohort of patients and determine if differences in disease progression exist. Design Longitudinal, observational study. Setting Twenty-one international National Parkinson Foundation (NPF) Centers of Excellence. Participants Patients (N=4,679; 63% men and 37% women with idiopathic PD. Methods Demographic and clinical data at enrollment and after one year were collected. We defined progression as a one-year change in functional health outcome measures: a) Health related quality of life (Parkinson’s disease questionnaire-39; PDQ-39); b) Timed up and go (TUG); c) Cognitive function; d) Number of medications. We compared baseline characteristics between men and women. Then, linear regression models were built to assess the independent contribution of sex to progression while controlling for potential confounders. Results At baseline, women were significantly more likely to be older and have greater disease severity and more co-morbidities than men despite similar duration of disease. This finding corresponded to worse function as assessed by PDQ-39 and TUG but not number of medications and cognitive function. After one year, declines across all functional measures except delayed recall occurred. No significant changes in PDQ-39, TUG, number of medications or verbal fluency between men and women occurred. Women did have a more significant improvement in delayed recall than men. Conclusion Numerous, small, baseline differences between men and women with PD occurred, although differences in markers of progression were few. Findings suggest clinical manifestations and prognosis appear similar by sex under the same treatment conditions.

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Section: Discussionsupporting

confidence: 78%

mentioning

confidence: 99%

Sex Differences in the Clinical Progression of Parkinson's Disease

Dahodwala¹,

Pei²,

Schmidt³

2016

Journal of Obstetric, Gynecologic & Neonatal Nursing

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“…In this population‐based study of diabetic patients, we observed a higher risk of PD in female relative to male subjects. In general population studies, PD incidence is a little higher in males, but in diabetic populations, females have higher risk of PD; the mechanisms are not still known. The possible mechanisms may be related to estrogen effects on dopaminergic neurons and pathways in the brain .…”

Section: Discussionmentioning

confidence: 96%

Statin therapy prevents the onset of Parkinson disease in patients with diabetes

Lin

Yang

Lee

et al. 2016

Annals of Neurology

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Objective: We studied the association between the statin dosage and the risk of Parkinson disease (PD) in diabetic patients in Taiwan. Methods: One million patients were randomly sampled from a National Health Insurance (NHI) database and followed from 2001 to 2008. Diabetic patients were screened by diagnosis of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, and statin dosage was determined according to the NHI pharmacy database. PD was diagnosed on the basis of ICD-9-CM codes and anti-Parkinson medication use. Statin users was classified by statin dose-duration-day > 28 and matched with nonusers of statins using a coarsened exact matching method. There were 50,432 patients, and half of them were statin users. We examined the risk of PD between statin users and nonusers of statins and further tested the trends of the relative risk between the statin dosage and PD. Results: The PD incidence rate was lower in statin users than in nonusers of statins. The crude hazard ratio of PD incidence in statin users was 0.65 (95% confidence interval [CI] 5 0.57-0.74) in females and 0.60 (95% CI 5 0.51-0.69) in males compared with nonusers of statins. After Cox regression analysis, all statins except lovastatin exerted protective effects on PD incidence and had a significant dose-dependent trend. Interpretation: In Taiwanese diabetic patients, the risk of PD is lower in statin users than in nonusers of statins. Statin users, except lovastatin users, are dose-dependently associated with a decreased incidence of PD compared with nonusers of statins. This finding provides a new indication for statin beyond lipid control and cardiovascular events in diabetic patients. ANN NEUROL 2016;80:532-540 P arkinson disease (PD) is the second most common neurodegenerative disease. It causes irreversible, progressive disability that is characterized by muscle rigidity, slowing of physical movements, behavioral abnormalities, and autonomic impairments. 1,2 PD causes progressive disability and imposes a burden on patients and their families. The etiology of PD is inconclusive but is associated with multiple factors, such as genetic variety, oxidative stress, and progressive neuroinflammation. 3 According to recent reports, diabetes mellitus (DM) and elevated cardiovascular risk factors might play a role in the development of PD. 4-6 Some studies on animal and human models have indicated that tumor necrosis factora, nitric oxide, inducible nitric oxide synthase (iNOS), and oxygen-derived free radicals play a role in the development of PD. 3,7,8 Statin is a competitive 3-hydroxy-3-methylglutarylcoenzyme A reductase competitive inhibitor and is widely used for treating hypercholesterolemia, particularly for maintaining low-density lipoprotein (LDL) cholesterol View this article online at wileyonlinelibrary.com.

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“…For this research, the exclusive use of male rats was chosen due to the greater incidence of this pathological process in men. Additionally, it has been shown that there are significant differences in the survival rate of dopaminergic neurons between male and female rats exposed to a 6‐OHDA infusion, which is a consequence of increased estrogen in females, a well‐recognized neuroprotective factor against dopaminergic depletion, and the increased vulnerability of the nigrostriatal dopaminergic pathway in male rats (Augustine et al, ; Cantuti‐Castelvetri et al, ; Gillies, Pienaar, Vohra, & Qamhawi, ). These factors could have been confounding to our results if we had included female rats in assessment of locomotor recovery.…”

Section: Discussionmentioning

confidence: 99%

Physical exercise and human adipose‐derived mesenchymal stem cells ameliorate motor disturbances in a male rat model of Parkinson's disease

Cucarián

Berrío

Rodrigues

et al. 2019

J of Neuroscience Research

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Parkinson's disease (PD) is a disabling and highly costly neurodegenerative condition with worldwide prevalence. Despite advances in treatments that slow progression and minimize locomotor impairments, its clinical management is still a challenge. Previous preclinical studies, using mesenchymal stem cell (MSC) transplantation and isolated physical exercise (EX), reported beneficial results for treatment of PD. Therefore, this experimental randomized study aimed to elucidate the therapeutic potential of combined therapy using adipose-derived human MSCs (ADSCs) grafted into the striatum in conjunction with aerobic treadmill training, specifically in terms of locomotor performance in a unilateral PD rat model induced by 6-hydroxydopamine (6-OHDA). Forty-one male Wistar rats were categorized into five groups in accordance with the type of treatment to which they were subjected (Sham, 6-OHDA − injury, 6-OHDA + exercise, 6-OHDA + cells, and 6-OHDA + combined). Subsequently, dopaminergic depletion was assessed by the methylphenidate challenge and the specified therapeutic intervention was conducted in each group. The foot fault task was performed at the end of the experiment to serve as an assessment of motor skills. The results showed that despite disturbances in motor balance and coordination, locomotor dysfunction was ameliorated in all treatment categories in comparison to the injury group (sign test, p < 0.001, effect size: 0.71). The exercise alone and combined groups were the categories that exhibited the best recovery in terms of movement performance (p < 0.001). Overall, this study confirms that exercise is a powerful option to improve motor function and a promising adjuvant intervention for stem cell transplantation in the treatment of PD motor symptoms.

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Sex Differences in Clinical Features of Early, Treated Parkinson’s Disease

Cited by 56 publications

References 39 publications

Sex Differences in the Clinical Progression of Parkinson's Disease

Sex Differences in the Clinical Progression of Parkinson's Disease

Statin therapy prevents the onset of Parkinson disease in patients with diabetes

Physical exercise and human adipose‐derived mesenchymal stem cells ameliorate motor disturbances in a male rat model of Parkinson's disease

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