Einstein, G. | bioRxiv Science

bioRxiv2023

Gray matter volume in women with the BRCA mutation with and without ovarian removal

ObjectiveOvarian removal prior to spontaneous/natural menopause (SM) is associated with increased risk of late life dementias including Alzheimers disease. This increased risk may be related to the sudden and early loss of endogenous estradiol. Women with breast cancer gene mutations (BRCAm) are counselled to undergo oophorectomy prior to SM to significantly reduce their risk of developing breast, ovarian, and cervical cancers. There is limited evidence of the neurological effects of ovarian removal prior to the age of SM and this is in women without the BRCAm showing cortical thinning in medial temporal lobe structures. A second study in women with BRCAm and BSO noted changes in cognition. MethodsThe present study looked at whole-brain changes in gray matter volume using high-resolution, quantitative MRI in women with BRCAm and intact ovaries (BRCA-preBSO) and after surgery with (BSO+ERT) and without (BSO) post-surgical estradiol hormone replacement therapy compared with agematched women (AMC) with their ovaries. ResultsThe BRCA-preBSO and BSO groups showed significant gray matter loss in left medial temporal and frontal lobe structures. BSO+ERT exhibited few areas of gray matter reductions compared to AMC. Novel to this study, we also observed that all three BRCAm groups exhibited gray matter increases compared with AMC, suggesting continued plasticity. ConclusionsThe present study provides evidence, through gray matter volume reductions, to support both the possibility that the BRCAm, alone, and early life BSO may play a role in increasing the risk for late-life dementia. At least for BRCAm with BSO, post-surgical ERT seems to ameliorate gray matter losses.

neuroscience↗

bioRxiv2023

The influence of chronological age and menopause status on the functional neural correlates of spatial context memory in middle-aged females.

Reductions in the ability to encode and retrieve past experiences in rich spatial contextual detail (episodic memory) are apparent by midlife - a time when most females experience spontaneous menopause. Yet, little is known about how menopause status affects episodic memory-related brain activity at encoding and retrieval in middle-aged pre- and post-menopausal females, and whether any observed group differences in brain activity and memory performance correlate with chronological age within group. We conducted an event-related task fMRI study of episodic memory for spatial context to address this knowledge gap. Multivariate behavioral partial least squares (PLS) was used to investigate how chronological age and retrieval accuracy correlated with brain activity in 31 premenopausal (age range: 39.55 - 53.30 yrs, Mage = 44.28 yrs, SDage = 3.12 yrs) and 41 postmenopausal females (age range: 46.70 to 65.14 yrs, Mage = 57.56 yrs, SDage = 3.93 yrs). We found that postmenopausal status, and advanced age within post-menopause, was associated with lower spatial context memory. The fMRI analysis showed that only in postmenopausal females, advanced age was correlated with decreased activity in occipitotemporal, parahippocampal, and inferior parietal during encoding and retrieval, and poorer spatial context memory performance. In contrast, only premenopausal females exhibited an overlap in encoding and retrieval activity in angular gyrus, midline cortical regions, and prefrontal cortex, which correlated with better spatial context retrieval accuracy. These results highlight how menopause status and chronological age, nested within menopause group, affect episodic memory and its neural correlates at midlife. Significance StatementThis is the first fMRI study to examine how pre- and post-menopause status affects the neural correlates of episodic memory encoding and retrieval, and how chronological age contributes to any observed group similarities and differences. We found that both menopause status (endocrine age) and chronological age affect spatial context memory and its neural correlates. Menopause status directly affected the direction of age- and performance-related correlations with brain activity in inferior parietal, parahippocampal and occipitotemporal cortices across encoding and retrieval. Moreover, we found that only premenopausal females exhibited cortical reinstatement of encoding-related activity in midline cortical, prefrontal, and angular gyrus, at retrieval. This suggests that spatial context memory abilities may rely on distinct brain systems at pre-compared to post-menopause.

neuroscience↗