The “Gender Factor” in Wearing‐Off among Patients with Parkinson’s Disease: A Post Hoc Analysis of DEEP Study

Colombo, Delia; Abbruzzese, Giovanni; Antonini, Angelo; Barone, Paolo; Bellia, Gilberto; Franconi, Flavia; Simoni, Lúcia; Attar, Mahmood; Zagni, Emanuela; Haggiag, Shalom; Stocchi, Fabrizio

doi:10.1155/2015/787451

Cited by 65 publications

(59 citation statements)

References 30 publications

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“…Contrary to some studies but consistent with others, gender was not an independent predictor of either dyskinesia or MF. Caffeine intake, which other studies have shown to be protective, had no effect in our study.…”

Section: Discussionsupporting

confidence: 74%

Predictors of motor complications in early Parkinson's disease: A prospective cohort study

et al. 2019

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Objective The objective of this study was to identify clinical predictors of motor complications (dyskinesia and motor fluctuations) of levodopa in a prospectively recruited PD cohort using longitudinal analysis. Methods An inception cohort (Oxford Discovery) of 734 patients was followed to a maximum of 10 years from diagnosis using a discrete‐time survival analysis. A subset analysis was used to validate an online dyskinesia‐risk calculator developed from the results of the Stalevo Reduction in Dyskinesia Evaluation PD trial. Results A total of 186 cases of dyskinesia and 254 cases of motor fluctuations were observed. Dyskinesia incidence increased with time (risk per 100 participants [95% confidence interval] 13 [11–16] <3.5 years, 16 [13–21] 3.5–5.0 years, 19 [14–26] 5–6.5 years, and 23 [16–33] >6.5 years from diagnosis). Motor complication predictors were grouped as medication predictors, disease predictors and patient predictors. Baseline nonmotor feature severity, low mood, anxiety, and age at symptom onset were associated with motor complications among a number of previously identified predictors. Replication of the Stalevo Reduction in Dyskinesia Evaluation PD calculator was reasonable with the area under the curve for dyskinesia risk score as a predictor of dyskinesia being 0.68 (95% confidence interval, 0.55–0.81). Conclusions This study quantifies risk of motor complications, finds consistent predictors, and demonstrates the novel finding that nonmotor features of PD, particularly low mood and anxiety, are significant risk factors for motor complications. Further validation of dyskinesia risk scores are required as well as evidence to determine if the routine use of such scores can be clinically valuable in enhancing patient care and quality of life. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Section: Discussionsupporting

confidence: 74%

Predictors of motor complications in early Parkinson's disease: A prospective cohort study

et al. 2019

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“…At symptom onset, male PD patients are more likely to present with axial impairment when compared to female patients . Conversely, as the disease progresses, female PD patients seem to be at higher risk to develop treatment‐related motor complications . Indeed, it has been shown that prevalence of wearing‐off is higher in female than in male PD patients .…”

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confidence: 99%

“…2,3 Conversely, as the disease progresses, female PD patients seem to be at higher risk to develop treatment-related motor complications. 4,5 Indeed, it has been shown that prevalence of wearing-off is higher in female than in male PD patients. 5 Similarly, the sex difference has been shown to be the most relevant independent predictor of levodopa-induced dyskinesia, irrespective of body weight 5 and treatment.…”

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confidence: 99%

“…4,5 Indeed, it has been shown that prevalence of wearing-off is higher in female than in male PD patients. 5 Similarly, the sex difference has been shown to be the most relevant independent predictor of levodopa-induced dyskinesia, irrespective of body weight 5 and treatment. 4,6 Compelling evidence suggests that a sex-specific pattern and functioning within the nigrostriatal dopaminergic pathway may underlie these differences.…”

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confidence: 99%

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Sex‐related pattern of intrinsic brain connectivity in drug‐naïve Parkinson's disease patients

et al. 2019

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Background Sex difference is related to specific clinical features in PD patients over the disease course. Objectives To investigate the potential sex‐difference effect on the spontaneous neuronal activity within the most reported resting‐state networks in early untreated PD patients and its correlation with baseline and longitudinal clinical features. Methods Fifty‐six drug‐naïve PD patients (30/26 male/female) and 30 (15/15 male/female) matched controls were enrolled in the study. Topological and spectral resting‐state functional MRI features of the sensorimotor, dorsal and ventral attention, frontoparietal, and default‐mode networks were analyzed for possible sex‐difference effects in both PD patients and controls groups. Additionally, a region‐of‐interest analysis was performed to test for a sex effect on basal ganglia connectivity. Multivariate ordinal regression was used to investigate whether connectivity findings at baseline were predictors of motor impairment over a 2‐year follow‐up period. Results Compared to female PD patients and controls, male PD patients showed an abnormal spectral composition of the sensorimotor and dorsal attention networks in the slow‐5 band. The region‐of‐interest analysis showed an increased connectivity within the basal ganglia in female PD patients compared to males. Functional sensorimotor connectivity changes at baseline showed to be an independent predictor of disease severity at 2‐year follow‐up. Conclusions Our findings revealed the presence of a disease‐related, sex‐specific cortical and subcortical connectivity pattern within the sensorimotor network, in the early stage of PD. We hypothesize that these findings may be related to the presence of different sex‐specific nigrostriatal dopaminergic pathways and might predict PD progression. © 2019 International Parkinson and Movement Disorder Society

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“…The disease is more common in men than in woman by an approximate ratio of 1.5-2:1 [18,19]. In addition to prevalence, several other PD-coupled parameters differ between men and women, including onset of symptoms, types of motor and non-motor symptoms, medication use, the effect size of PD risk factors, levodopa bioavailability, neuropsychiatric, and cognitive changes, development of hallucinations, caregiver utilization and reliance, and the quality of life [20,21]. In women, the age of PD onset has shown a positive correlation with fertility.…”

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confidence: 99%

Delayed Dopamine Dysfunction and Motor Deficits in Female Parkinson Model Mice

Chen

Wang

Huang

et al. 2019

IJMS

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This study analyzed gender differences in the progressive dopamine (DA) deficiency phenotype in the MitoPark (MP) mouse model of Parkinson's disease (PD) with progressive loss of DA release and reuptake in midbrain DA pathways. We found that the progressive loss of these DA presynaptic parameters begins significantly earlier in male than female MP mice. This was correlated with behavioral gender differences of both forced and spontaneous motor behavior. The degeneration of the nigrostriatal DA system in MP mice is earlier and more marked than that of the mesolimbic DA system, with male MP mice again being more strongly affected than female MP mice. After ovariectomy, DA presynaptic and behavioral changes in female mice become very similar to those of male animals. Our results suggest that estrogen, either directly or indirectly, is neuroprotective in the midbrain DA system. Our results are compatible with epidemiological data on incidence and symptom progression in PD, showing that men are more strongly affected than women at early ages.Int. J. Mol. Sci. 2019, 20, 6251 2 of 17 in nigral neurons in aged humans with sharp elevations starting shortly before age 70. This correlates with age being a known major risk factor for PD. A better understanding of the progressive cellular events that precede the appearance of behavioral symptoms will be critical for the early diagnosis of PD and development of more effective treatment strategies.It has been suggested that gender is an important factor in the development of PD. The disease is more common in men than in woman by an approximate ratio of 1.5-2:1 [18,19]. In addition to prevalence, several other PD-coupled parameters differ between men and women, including onset of symptoms, types of motor and non-motor symptoms, medication use, the effect size of PD risk factors, levodopa bioavailability, neuropsychiatric, and cognitive changes, development of hallucinations, caregiver utilization and reliance, and the quality of life [20,21]. In women, the age of PD onset has shown a positive correlation with fertility. Sex hormones, especially estrogen, may thus influence PD pathogenesis and be an important gender differentiation factor [22,23]. Here we use the MitoPark (MP) mouse model of PD where the mitochondrial transcription factor, TFAM, is specifically deleted in midbrain dopamine (DA) neurons. There is subsequent progressive degeneration of midbrain DA neurons which project to both striatum and extrastriatal telencephalic sites. Since the TFAM deletion is driven by the DAT promoter, neurons that do not express DAT are spared. Ovariectomy was used to address gender differences and the possible protective effects of estrogen on the time course of degeneration of DA neurons. ResultsDA release rate was measured by fast scan cyclic voltammetry (FSCV) in ex vivo (in vitro) brain slices. The capacity of axon terminals to release DA was assessed by using one single pulse (for tonic) or 10 pulses (for phasic) stimulation delivered at 25 Hz under 10 volts stimulation intensities....

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The “Gender Factor” in Wearing‐Off among Patients with Parkinson’s Disease: A Post Hoc Analysis of DEEP Study

Cited by 65 publications

References 30 publications

Predictors of motor complications in early Parkinson's disease: A prospective cohort study

Predictors of motor complications in early Parkinson's disease: A prospective cohort study

Sex‐related pattern of intrinsic brain connectivity in drug‐naïve Parkinson's disease patients

Delayed Dopamine Dysfunction and Motor Deficits in Female Parkinson Model Mice

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