Sex and gender differences in Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis: A narrative review

Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), exhibit high phenotypic variability and they are very common in the general population. These diseases are associated with poor prognosis and a significant burden on patients and their caregivers. Although increasing evidence suggests that biological sex is an important factor for the development and phenotypical expression of some NDs, the role of sex and gender in the diagnosis and prognosis of NDs has been poorly explored. Current knowledge relating to sex- and gender-related differences in the epidemiology, clinical features, biomarkers, and treatment of AD, PD, and ALS will be summarized in this narrative review. The cumulative evidence hitherto collected suggests that sex and gender are factors to be considered in explaining the heterogeneity of these NDs. Clarifying the role of sex and gender in AD, PD, and ALS is a key topic in precision medicine, which will facilitate sex-specific prevention and treatment strategies to be implemented in the near future. •NDs have high prevalence and poor prognosis and are associated with a significant burden on both patients and caregivers.•The possible influence of female sex as an independent risk factor for MCI and AD have yet to be confirmed.•Male sex is associated with a higher prevalence and incidence of PD with a more benign phenotype at onset in women with PD.•ALS appears to have a higher prevalence and incidence in males, but this finding needs to be confirmed in large cohorts.•Analyses stratified by sex, conducted on prospective cohorts, are useful to definitively clarify the role of sex in NDs.