{'fraction_non_alphanumeric': 0.027314814814814816, 'fraction_numerical': 0.011574074074074073, 'mean_word_length': 4.7383798140770255, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 1, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
What Matters in Parkinson's Disease: Sex, Number of Children, or Birth Cohort?

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, and its descriptive epidemiology is noteworthy for sex differences in disease risk. PD appears to be more common in men than in women, with a median male:female incidence rate ratio of 1.8 (range, 1.4 to 2.0), although in some Asian countries the incidence appears similar in men and women. The lower PD risk observed in women has been hypothesized to be because of biological or environmental differences. To explore the role of biological differences, studies have evaluated the associations of reproductive factors such as age at menarche, age at menopause, parity, and oral contraceptive use with the risk of Parkinson’s disease in women. However, a meta-analysis by Lv et al that included 6 case-control and 5 cohort studies provided little support for associations of these reproductive factors with PD. The association of parity (number of live-born children) with age at onset of PD has been evaluated in 3 studies. In these studies, age at disease onset was defined as the year when first symptoms were observed. Parity was positively correlated with age at onset, and for each additional child, the age at onset was delayed by approximately 2.6 to 2.7 years. However, all 3 studies solely included women with PD because controls do not have age at onset. In this issue of Movement Disorders, MacAskill and colleagues report results from the first study to evaluate the relationship between number of children and age at diagnosis (not age at onset) in men and women. Using men as “controls,” they hypothesized that if number of children has a biological effect on delaying age at diagnosis, then a positive correlation would be observed in women and not in men. The researchers first evaluated the correlation between age at diagnosis and number of children using incident cases from the Parkinson’s Progressive Markers Initiative (PPMI) study that included 145 women and 276 men and replicated the analysis in a prevalence sample from the New Zealand Brain Research Institute (NZBRI) that included 210 women and 390 men. The correlation between age at diagnosis and number of children was evaluated separately in men and women using simple Bayesian linear models with priors based on results from the 3 previous studies. Bayes factor (BF), which is the ratio of the likelihood of the data in a model that includes the independent predictor (number of children) to the likelihood of the data in the intercept-only model, was estimated. In the PPMI sample that included incident cases, age at diagnosis was delayed by 1.1 and 1.4 years per child in women (BF = 1.5) and men (BF = 4.9), respectively. In the NZBRI replication sample, the average delay in age at diagnosis was 0.5 years per child in women (BF = 0.1) and 0.4 years per child in men (BF = 0.2), providing weak evidence for a correlation between number of children and age at diagnosis. Based on the results of the PPMI sample, the authors concluded that the correlation between number of children and age at diagnosis is unlikely to be a biological one because the correlation is stronger in men than in women. They also tested a nonbiological explanation, generational or cohort effect, which results in variation in the risk of a health outcome according to the year of birth, arising from changes in the population exposure to risk factors (environmental or societal) over time. In this study, the researchers hypothesized that older people would be more likely to have larger families compared with those born more recently and that this generational effect would be likely to affect both men and women. To explore the cohort effect, they analyzed the association of number of children with year of birth, which would estimate on average how many years earlier (or later) we would expect a case to have been born as a function of the number of children they had. In both the PPMI and NZBRI samples, on average, the slope was approximately -1.0 years, suggesting that each additional child was associated with the average case having been born (approximately) 1 year earlier. The authors explain that because age at diagnosis © 2020 International Parkinson and Movement Disorder Society