STRUCTURAL INTEGRITY OF THE MEDIAL TEMPORAL LOBE AND RECOGNITION MEMORY FOLLOWING NATURAL AND SURGICAL MENOPAUSE

Abstract

Women bear the greatest burden of Alzheimer's disease (AD). Menopause-associated estrogen (E) loss may contribute to the higher rate among women, and surgical menopause prior to the age of 45 may further increase the risk. Neurodegeneration and atrophy in medial temporal lobe (MTL) structures including the perirhinal (PRC) and entorhinal (ERC) cortices occur in the very early stages of AD (e.g. Khan et al., 2013; Wolk et al., 2017). Emerging evidence suggests that visual recognition memory (VRM), which depends on the PRC, is impaired in individuals at risk for AD. While studies in rodents demonstrate that estrogens mediate PRC and VRM performance, limited data exists in humans. The present study asked whether oophorectomy prior to 45 years is associated with smaller relative volumes of the ERC and PRC, and impaired VRM relative to age-matched controls and naturally postmenopausal women. Demographic and cognitive measures were administered to women with either 1) an oophorectomy at 45 years or younger, 2) intact ovaries and not yet in menopause, and 3) naturally postmenopausal women. Total gray/white matter, cerebral spinal fluid and white matter hyperintensity load were quantified from whole-brain T1-weighted imaging scans. Volumes of hippocampal subfields and medial temporal cortical regions were quantified using high-resolution T2-weighted scans using a 3T Siemens scanner. In addition, urine samples were collected for ovarian hormone measures (estrogen and progesterone metabolites). VRM was assessed using the interference-match-to-sample (IMTS) task. Preliminary group analyses were conducted on relative volumes of each quantified structure and show smaller volumes for PRC and ERC among women that had an oophorectomy (p < .01). Performance on the IMTS was also examined, and correlations between performance (accuracy and response times) and relative volumes were conducted. The results of the present study provide preliminary evidence implicating the usefulness of medial temporal lobe measurements and the evaluation of associated cognitive abilities in early detection among middle-aged women at increased risk of AD.