Hypogyrification in midlife women with surgical menopause, a population at risk for late life Alzheimer’s

Abstract Background Women with early ovarian hormone deprivation due to bilateral salpingo‐oophorectomy (BSO; ovarian and fallopian tube removal) are at risk for later life Alzheimer’s disease (AD), but estradiol therapy (ET) may be protective (Rocca et al., 2007). Working memory (WM), temporarily maintaining and manipulating information in mind, depends on structural integrity of fronto‐parietal brain regions (Burzynska et al., 2012). WM declines have been observed in midlife women with BSO not taking ET (Gervais et al., 2020), however, structural brain–WM relationships in this midlife population remain unexplored. This study aimed to: 1) Investigate fronto‐parietal cortical thickness and gyrification (folding) changes in younger women after early BSO and their relationship to WM, and 2) Explore whether ET ameliorates these changes. Method Women with early BSO taking ET (BSO+ET: M±SD age = 45±5.1; n = 26), or not taking ET (BSO: M±SD age = 46±5.0y; n = 26) were compared to premenopausal, age‐matched controls (AMC: M±SD age = 44±2.9y; n = 42) from Toronto and Montreal, Canada, and Linköping, Sweden. T1‐weighted scans were acquired on Siemens Prisma/Philips 3T scanners. WM was measured using Digit Span Backwards (Wechsler, 1945) maximum span and Digit Ordering Task (Petrides et al., 1993) errors. Average cortical thickness and gyrification of fronto‐parietal regions were calculated from CIVET (Ad‐Dab’bagh et al. 2005), adjusting for scanner and past cancer treatment. Result Linear models showed no group differences in cortical thickness or WM. However, they showed BSO had significant hypogyrification (reduced cortical folding) in the supplementary motor area (SMA), part of the posterior prefrontal cortex, compared to AMC (adjusted for brain volume; FDR‐corrected p = 0.028). BSO+ET had intermediate SMA gyrification, and did not differ from either group. SMA gyrification was unrelated to WM, and gyrification–WM relationships did not differ by group. Conclusion We found SMA hypogyrification in younger women with BSO compared to AMC and BSO+ET. The SMA supports WM manipulation and is an early area affected by age‐related gyrification declines (Madan, 2021). Moreover, hypogyrification may reflect reduced brain connectivity, and gyrification globally declines with AD severity (Liu et al., 2012). Although SMA hypogyrification in women with BSO was unrelated to WM, it may serve as an early sign of later life cognitive decline.