For the 13 uncorrected hemispheric brain volumes (cerebral cortex, cerebral WM, hippocampus, amygdala, putamen, caudate, pallidum, accumbens, thalamus, lateral ventricles, inferior lateral ventricles, cerebellum cortex, cerebellum WM), ANCOVA with hemisphere × sex × structure (13 volumes) with age and sample as covariates established that sex and hemisphere did not interact (F [1,1139] = .001, p = .973). Thus, the sum of left and right hemisphere was used in the rest of the analyses. The effect of sex on the volume of the different brain structures are shown in . A GLM with 17 uncorrected volumes, sex, and age was run. Significant effects of sex (F [1,998] = 290.99, p < 10-56) and age (F [75,998] = 4.65, p < 10-29) were found, in addition to structure × sex (F [8.28, 8263.38] = 8.60, p < 10-11), structure × age (F [621.00, 8263.38] = 8.58, p = .000), and structure × sex × age (F [563.04, 8263.38] = 1.30, p < 10-5) interactions. However, sex and age did not interact significantly (F [68,998] = 1.214, p = .119). Post hoc t-tests for each structure are presented in . Men had significantly larger volume than women for all structures. The largest differences were found for cerebral WM and cortex, cerebellum cortex, amygdala, and thalamus, in addition to TBV.
Volumetric differences between women and men
Volume differences between women and men
Correlations between age and structure, split by sex, are presented in . The difference in coefficient strength was assessed by t-tests of Fisher’s z-transformed coefficients. Only for CSF did the age correlations differ significantly between the sexes (.31 vs. .49 for women and men, respectively). Scatterplots are presented in (cerebrum cortex and WM), (subcortical structures) and (CSF compartments). To test whether the lack of sex × age interactions was caused by reduced sensitivity due to merging of different sub-samples, the GLM was re-run in each of the 7 samples separately. For Sample 2 (F [28, 128] = 2.33, p < .001) and Sample 7 (F [36, 159] = 1.96, p < .05), significant age × sex interactions were found, while this was not seen in the other five samples (p ranging from .21 to 1.00). In sample 2, CSF correlated significantly different with age between the sexes (r = .25 vs .51 in women and men, respectively, z = 1.98, p < .05). In sample 7, cerebellum cortex correlated significantly different (r = -.45 vs. -.63 in women and men, respectively, z = 2.03, p < .05).
Age correlations for women and men
Scatterplots of age effects on cerebrum
Scatterplots of age effects on subcortical structures
Scatterplots of aging patterns on CSF compartments
The analyses were repeated with ICV-corrected volumes. Main effects of sex (F [1, 998] = 14.22, p < .001) and age (F [75, 998] = 6.59, p < 10-47) were confirmed. In addition, significant structure × sex (F [8.20, 8187.37] = 3.82, p < .001), structure × age (F [615.28, 8187.37] = 7.97, p < .000), and structure × sex × age (F [557.86, 8187.37] = 1.33, p < 10-6) interactions were found. Age and sex did not interact (F [68, 998] = 0.90, p = .71). T-tests showed significantly larger volumes for the 3rd ventricle, amygdala, brainstem, cerebellum cortex, cerebral cortex, hippocampus, pallidum, putamen, and thalamus, in addition to TBV, for men (). Significant differences in age correlations were observed only for CSF (.36 vs .59 for women and men, respectively) and pallidum (-.49 vs. -.58) (). The GLM was re-run in each of the 7 samples separately, with no significant age × sex interactions (p’s from .22 to .85). The ANOVA for the total sample was repeated for the participants over 60 years of age, to test whether age × sex interactions could be found in this age span. There were still no significant age × sex interaction (F [25, 247] = 0.65, p = .90). The residual variance for each variable was calculated for each sex separately. An ANOVA showed that the residual variance was highly and positively related to age (F [75,998] = 135.91, p < .0001), but no age × sex interaction was seen (F [68, 998] = 1.22, p = .12).
GLM with TBV-corrected volumes confirmed main effects of sex (F [1, 998] = 53.344, p < 10-12). T-tests showed significantly larger TBV-corrected volumes for women for cerebral cortex and accumbens area, while larger volumes for men were found for the ventricular system (3rd ventricle, 4th ventricle, lateral and inferior lateral ventricles, CSF), brainstem, cerebellum cortex, and pallidum ().
Effects of introducing a quadratic term were investigated for the ICV-corrected volumes (). A non-linear fit yielded significantly more explained variance for both women and men for most structures. For pallidum, age2 did not increase amount of explained variance for either of the groups. For cerebral cortex, adding age2 as a predictor increased the amount of explained variance from 45 to 48% (p < 10-6) in women, while the amount of explained variance did not increase significantly for men. The effect of age on cortical volume in women was decreasing with advancing age. For amygdala and cerebellum cortex, increasing effect of age in higher age was seen for men only. Generally, however, the amount of variance explained by age was very similar for men and women, as is illustrated in . CSF and pallidum seemed to be more related to age in men than in women, and when the non-linear component was added cerebral white matter also seemed to be more related to age in the sample of men than in the sample of women.
R2 from multiple regressions with age and age2 as predictors
Correlations with age in women and men
GLMs were run to test for sex differences in cortical thickness and effects of aging (see ). When age was regressed out, only minute and scattered effects of sex were seen, going in both directions (yellow-red: women thicker, blue-green: men thicker). When a commonly used criterion for correction for multiple comparisons were used (False Discovery Rate [FDR] < .05), no effects survived. The same was found when comparing the effects of age between women and men. Some scattered areas of steeper age-slope in women than men (yellow-red) were seen, but did not survive correction for FDR. To test whether lack of effects could be due to merging of data from different samples, sex × age interactions were tested for each of the 7 samples independently. No effects survived the FDR < .05 criterion for any of the samples.
Testing of effects of sex on cortical thickness
ANCOVA with sex, age and 17 uncorrected neuroanatomical volumes, and MMSE and CDR as covariates, yielded an effect of sex (F[1,47]=35.54, p = 10-6, men larger), but no age × sex interaction (F[17,47]=1.58, p = .11). For ICV-corrected volumes, trends were observed for sex (F[1,47]=3.90, p = .054), age (F[28,47]=1.53, p = .10), and sex × age (F[17,47]=1.73, p = .07). Finally, analysis of TBV-corrected volumes yielded no significant results (all p’s > .59). Post hoc multiple regression analyses were run, with each of the 17 structures as dependent variables in turn, and CDR, MMSE, age, sex, and age × sex interaction as predictors. No sex × age interactions were significant.