Sex differences in dementia with Lewy bodies: a systematic review
TL;DR
Compared to males, female patients with DLB were less likely to present with Rapid Eye Movement (REM) Sleep Behaviour Disorder, CSF biomarkers showed more Alzheimer’s Disease (AD) co-pathology, potentially contributing to misdiagnosis of DLB.
Abstract
Sex differences are increasingly recognized across neurodegenerative disorders, including Dementia with Lewy Bodies (DLB). Despite ongoing refinement of diagnostic criteria, DLB remains frequently misdiagnosed—particularly among females—reflecting gaps in our understanding of sex-specific disease presentation. Thus, there is a need to understand how clinical features, symptom patterns, and biomarkers manifest differently in female versus male patients with DLB. This review aims to synthesize current evidence on sex differences in DLB. Following PRISMA guidelines, we included 54 studies examining sex-related variations in DLB in core clinical features, cerebrospinal fluid (CSF) biomarkers, genetics, and neuroimaging findings. Compared to males, female patients with DLB were less likely to present with Rapid Eye Movement (REM) Sleep Behaviour Disorder (RBD), CSF biomarkers showed more Alzheimer’s Disease (AD) co-pathology, potentially contributing to misdiagnosis of DLB. Furthermore, the most prominent genetic correlation to DLB studied, APOE, did not show any sex differences. Included studies enrolled fewer females than males, and female participants were typically older, highlighting persistent sampling bias that may obscure sex-specific disease characteristics. Together, these findings underscore the need for more robust, sex-stratified research to better understand the clinical features, improve diagnosis and understanding of underlying pathology of DLB in females to ultimately reduce sex-related disparities in clinical care.