a, Quantitative clinico-pathological measurement comparison between male and female individuals (n = 24 female and n = 24 male individuals; two-sided Wilcoxon rank-sum test). Violin plots are centred around the median with interquartile ranges, and the shape represents individual distribution. The quantitative clinico-pathological variables considered were overall amyloid level, neuritic plaque burden, neurofibrillary tangle burden, tangle density, global cognitive function, and global AD pathology burden. b, Violin plots showing aggregate expression levels (z-scaled) across excitatory neurons in female (red) versus male (blue) individuals (n = 12 each) of the top 10 marker genes of the AD-associated Ex4 subpopulation of excitatory neurons. c, Hierarchical clustering of pathology-affected individuals (columns) based on average expression level (colour) of the top 10 marker genes (rows) of the AD-enriched Ex4 subpopulation of excitatory neurons for female versus male individuals. d, e, Statistical comparison of in vivo brain MRI imaging from ROSMAP cohorts. d, Intracranial volume-normalized WMH (wmh.icv) measures for female (n = 399) and male (n = 106) individuals and high-cognition (n = 252 female and n = 63 male individuals) and low-cognition (n = 147 female and n = 43 male individuals) groups. Groups were defined based on whether subjects had an overall cognition score lower (low.cog, z-score < 0) or higher (high.cog, z-score > 0) than the average. Mean rank-difference values between cognition groups were compared using the two-sided Wilcoxon rank-sum test. e, Statistical estimation of significant difference in WMH between low-cognition and high-cognition groups in females, and between low-cognition and high-cognition groups in males, assessed by bootstrap point and 95% confidence interval estimation of the effect size (mean difference) between groups. Bootstrap resampling was performed by resampling n = 40 observations per group 1,000 times. Horizontal line highlights zero difference. The positive effect-size points and confidence interval estimates do not overlap the zero line in the female group, which provides statistical evidence of an increment in WMH (wmh.icv) in the low-cognition group relative to the high-cognition group in females but not in males.