title: 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 postmenopausal 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 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.
authors: Department of Psychology, Arizona State University, Tempe, AZ 85287, United States; Arizona Alzheimer's Consortium, Phoenix, AZ 85006, United States.
authors: Stephanie V
authors: SV
authors: Koebele
authors: Department of Psychology, Arizona State University, Tempe, AZ 85287, United States; Arizona Alzheimer's Consortium, Phoenix, AZ 85006, United States.
authors: Sarah E
authors: SE
authors: Mennenga
authors: Department of Psychology, Arizona State University, Tempe, AZ 85287, United States; Arizona Alzheimer's Consortium, Phoenix, AZ 85006, United States.
authors: Ryoko
authors: R
authors: Hiroi
authors: Department of Psychology, Arizona State University, Tempe, AZ 85287, United States; Arizona Alzheimer's Consortium, Phoenix, AZ 85006, United States.
authors: Alicia M
authors: AM
authors: Quihuis
authors: Department of Psychology, Arizona State University, Tempe, AZ 85287, United States; Arizona Alzheimer's Consortium, Phoenix, AZ 85006, United States.
authors: Lauren T
authors: LT
authors: Hewitt
authors: Department of Psychology, Arizona State University, Tempe, AZ 85287, United States; Arizona Alzheimer's Consortium, Phoenix, AZ 85006, United States.
authors: Mallori L
authors: ML
authors: Poisson
authors: Senestech, Inc., 3140 N Caden Court, Flagstaff, AZ 86004, United States.
authors: Christina
authors: C
authors: George
authors: Senestech, Inc., 3140 N Caden Court, Flagstaff, AZ 86004, United States.
authors: Loretta P
authors: LP
authors: Mayer
authors: Senestech, Inc., 3140 N Caden Court, Flagstaff, AZ 86004, United States.
authors: Cheryl A
authors: CA
authors: Dyer
authors: Department of Psychology, Arizona State University, Tempe, AZ 85287, United States.
authors: Leona S
authors: LS
authors: Aiken
authors: The Pennsylvania State University College of Medicine, The M. S. Hershey Medical Center, Hershey, PA 17033, United States.
authors: Laurence M
authors: LM
authors: Demers
authors: Department of Psychology, Arizona State University, Tempe, AZ 85287, United States; Arizona Alzheimer's Consortium, Phoenix, AZ 85006, United States.
authors: Catherine
authors: C
authors: Carson
authors: Department of Psychology, Arizona State University, Tempe, AZ 85287, United States; Arizona Alzheimer's Consortium, Phoenix, AZ 85006, United States. Electronic address: bimonte.nelson@asu.edu.
authors: Heather A
authors: HA
authors: Bimonte-Nelson
mesh_terms: D000375:Aging / Q000523:psychology*; D000818:Animals; D003071:Cognition / Q000502:physiology*; D053138:Cyclohexenes / Q000494:pharmacology; D005260:Female; D008593:Menopause / Q000187:drug effects / Q000523:psychology*; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects; D065851:Ovarian Reserve / Q000187:drug effects / Q000502:physiology*; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology*; D014753:Vinyl Compounds / Q000494:pharmacology
chemical_list: D053138:Cyclohexenes; D014753:Vinyl Compounds; C012606:4-vinyl-1-cyclohexene dioxide
keywords: Aging; Cognition; Hormone; Learning; Memory; Menopause; Ovary; VCD