Sex differences for symptoms prior to dementia onset in people with Lewy body pathology compared to pure Alzheimer's disease pathology

BackgroundEarly diagnosis of Lewy body dementia (LBD) is challenging, largely due to clinical heterogeneity and features overlapping with Alzheimer's disease (AD). Clinical differentiation is particularly challenging in females, who are more likely to have a mis- and delayed diagnosis than males with LBD.ObjectiveTo investigate whether there are sex differences in the prodromal symptoms and rate of change preceding dementia in people with Lewy body (LB) and pure AD pathologies.MethodsWe used data from National Alzheimer's Coordinating Center for people with dementia and LB (n = 196; 89 females, 107 males; including mostly people with AD co-pathology) or pure AD pathology (n = 308, 167 females, 141 males, without LB co-pathology). Prevalence of cognitive, behavioral, and parkinsonism symptoms were assessed annually starting with two-years prior to dementia. Changes over time for prevalences were compared between pathology groups and sexes.ResultsCognitive fluctuation prevalence was higher for males with LB than other groups. Compared to males with LB, females with LB had faster increase in judgment, language, visuospatial deficit prevalence and dementia severity. Relative to females with AD, affective symptom prevalence increased slower for females with LB. Relative to males with AD, males with LB had higher prevalence of parkinsonism and attention deficit, with slower increase in attention deficit prevalence.ConclusionsCognition can decline faster for females than males during prodromal LBD. Presence of parkinsonism and cognitive fluctuation can help differentiate LB from AD pathology for males. Such prominent differences may not occur for females, suggesting the need for sex-specific diagnostic approaches.