Cognitive changes across the menopause transition: A longitudinal evaluation of the impact of age and ovarian status on spatial memory

Abstract

Cognitive changes that occur during mid-life and beyond are linked to both aging and the menopause transition. Studies in women suggest that the age at menopause onset can impact cognitive status later in life; yet, little is known about memory changes that occur during the transitional period to the post-menopausal state. The 4-vinylcyclohexene diepoxide (VCD) model simulates transitional menopause in rodents by depleting the immature ovarian follicle reserve and allowing animals to retain their follicle-deplete ovarian tissue, resulting in a profile similar to the majority of perimenopausal women. Here, Vehicle or VCD treatment was administered to ovary-intact adult and middle-aged Fischer-344 rats to assess the trajectory of cognitive change across time with normal aging and aging with transitional menopause via VCD-induced follicular depletion, as well as to evaluate whether age at the onset of follicular depletion plays a role in cognitive outcomes. Animals experiencing the onset of menopause at a younger age exhibited impaired spatial memory early in the transition to a follicle-deplete state. Additionally, at the mid- and post- follicular depletion time points, VCD-induced follicular depletion amplified an age effect on memory. Overall, these findings suggest that the age at the onset of menopause is a critical parameter to consider when evaluating learning and memory across the transition to reproductive senescence. From a translational perspective, this study illustrates how age at menopause onset might impact cognition in menopausal women, and provides insight into time points to explore for the window of opportunity for hormone therapy during the menopause transition period. Hormone therapy during this critical juncture might be especially efficacious at attenuating age- and menopause- related cognitive decline, producing healthy brain aging profiles in women who retain their ovaries throughout their lifespan.

‘When my autism broke’: A qualitative study spotlighting autistic voices on menopause

“…This was beyond our aims in this pilot study, but the problematic implications of relying purely on symptom reporting are several. First, in non-autistic women, menopausal symptoms change across the transition period ( Koebele et al, 2017 ; Woods & Mitchell, 2016 ). If the same is true for autistic people, then comparison of menopausal groups (whether with younger autistic people or non-autistic people) may be obfuscated by individual differences in transition stage.…”

The endocrine-brain-aging triad where many paths meet: female reproductive hormone changes at midlife and their influence on circuits important for learning and memory

“…We found that animals that underwent the transition to menopause in young adulthood exhibited working memory impairments compared to normally aging adult rats, whereas transitionally menopausal middle-aged rats performed similarly to middle-aged control rats. These memory impairments were evident early in the menopause transition, particularly when working memory load was taxed (Koebele et al, 2017). These cumulative findings suggest that it is not only essential to consider hormone type, timing, and dosing regimen, but also an individual’s reproductive history and status, as well as age, as important factors for understanding the potential of hormone therapy to have neuroprotective effects.…”

Presbycusis-Related Tinnitus and Cognitive Impairment: Gender Differences and Common Mechanisms

“…The majority of epidemiological research indicated that women with aging are sensitive to dementia even after controlling for increased life span and education level, which show a rapid decline in a cognitive deterioration compared with agematched men [25]. The animal experiment indicated that follicular depletion might initiate age-related impairments for cognitive flexibility [26]. The postmenopausal women have a two-fold higher lifetime risk of developing AD than men and demonstrate a faster cognition decline [27,28].…”

Accelerated Ovarian Failure as a Unique Model to Study Peri-Menopause Influence on Alzheimer’s Disease

“…Using this model, many laboratories have studied the effect of estrogen loss, and 17β-estradiol and other hormonal formulations, on cognitive function in normal wild type and AD rodents (Diaz Brinton, 2012; Li et al, 2014; Koebele and Bimonte-Nelson, 2016). For instance, administration of 17β-estradiol to OVX females have shown to increase performance in spatial memory behavioral tasks (Koebele and Bimonte-Nelson, 2016; Koebele et al, 2017). As mentioned above, in the 3xTgAD mouse model of AD, there is a significant correlation between decreased mitochondrial and glucose metabolism and Aβ load in the hippocampus of OVX females with respect to intact females (Yao et al, 2009, 2012; Ding et al, 2013a,b).…”

Efecto del extracto acuoso de Tropaeolum tuberosum "mashua" sobre el deterioro de la memoria y lipoperoxidacion inducida con fluoxetina en hi­gado en Rattus rattus var. albinus ooforectomizadas

“…Un ensayo clínico recientemente realizado, concluye que, además, existe evidencia que sugiere qué tratamiento de reemplazo hormonal previene la reducción de la actividad de la corteza prefrontal medida por RMN (12) . Además, estudios en animales de experimentación (13,14) sugieren que estos cambios se inician desde la etapa premenopáusica.…”