TABLE 5.

Gaps in knowledge regarding sex differences in clinical presentation

Gaps in Knowledge
More research is needed to further understand sex differences in cognitive decline in AD. Particularly, longitudinal studies with AD biomarker data are needed to track sex differences across the clinical trajectory of AD, since these differences seem to differ by disease/pathology stage.
The generalizability of the female advantage in verbal memory across race/ethnicity groups is unclear, given that this work extends from predominantly White cohorts. 34 , 195
More studies are needed to investigate how sex differences in the frequency and predictive utility of SCD influence MCI diagnostic rates and accuracy. Longitudinal studies are needed to address sex differences in the temporal pattern of changes in SCD in relation to cognitive decline.
It remains unknown whether sex differences in neuropsychiatric symptoms are driven by different underlying neurobiological mechanisms. This could inform sex‐specific treatment approaches, as it is currently unknown whether the response to pharmacological and non‐pharmacological interventions that target neuropsychiatric symptoms differs by sex/gender. 244 , 245
Uniform reporting of associations by sex is necessary to fully understand whether sex‐specific cut‐points of pathology markers for diagnosis or prognosis are needed.
Further research is needed to better characterize sex differences in (1) the progression of AD pathology, (2) how the progression of different AD pathologies inter‐relate, and (3) how progression of AD pathology relates to cognitive decline across disease stages.
Few studies have examined sex differences in other factors that could contribute to differences in biomarker levels between females and males. For example, blood‐brain barrier permeability is greater in males than females, starting around the age of 6 years, 277 and can impact the concentrations of both blood and CSF‐related biomarkers.

Abbreviations: AD, Alzheimer's disease; MCI, mild cognitive impairment; SCD, subjective cognitive decline.