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

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS) exhibit high phenotypic variability, poor prognosis, and a significant burden on patients and caregivers. To date, definitive disease-modifying treatments for these diseases are still unavailable.  

The role of sex and gender in the diagnosis and prognosis of these conditions is potentially significant but has been underexplored.  

In the following narrative review by the Gender Neurology Study Group of the Italian Society of Neurology, titled “Sex and gender differences in Alzheimer’s disease, Parkinson’s disease, and Amyotrophic Lateral Sclerosis: A narrative review”, we collaborated in summarizing current knowledge of sex- and gender-related differences in several important parameters of AD, PD, and ASL.  

The main takeaways were:  

Alzheimer’s disease: 

1. The most important sex-related difference in AD is a higher prevalence in women than in men 

2. APOEε4 genotype seems to be increasing the risk of AD in women compared to men 

3. Aβ- and tau-mediated neuropathology appears to be modulated by the APOE genotype differently in the two sexes, even though the current data shows no differences between the two sexes regarding amyloid- and tau-related biomarkers 

Parkinson’s disease: 

1. PD is more prevalent and has a higher incidence in men than in women 

2. Women have a higher risk of early dyskinesias and wearing-off phenomena but a higher prevalence of depression, anxiety, pain, and fatigue compared to men

3. Men with PD have urinary dysfunction, sexual, and cognitive decline more frequently than women 

Amyotrophic lateral sclerosis: 

1. ALS data suggest a higher prevalence and incidence in men than women 

2. Androgens might increase the risk of ALS, while endogenous estrogens would be protective for disease development 

In conclusion, the sex differences data in clinical phenotypes, biomarkers, and the progression of AD, PD are still inconclusive. However, the gathered data suggests that sex and gender are particularly relevant factors to be considered when planning randomized clinical trials for these diseases.  

Click to read our publication

We thank again the authors of this review, for their wonderful work! 

Alessandra Nicoletti , Roberta Baschi, Calogero Edoardo Cicero, Salvatore Iacono, Vincenzina Lo Re, Antonina Luca, Giuseppe Schirò, Roberto Monastero 

Support the advancement of brain and mental health!

Donate Now with GoFundMe or using TWINT

Our Women's Quota campaign has been co-created with Ogilvy Switzerland

Article Editor | Benedetta Romeo

#alzheimersdisease #parkinsonsdisease #amyotrophiclateralsclerosis #sexdifferences #genderdifferences #riskfactors #treatments #biomarkers #epidemiology #WBF