Christina A. Metcalf

Purpose of Review To review recent research regarding cognitive problems during perimenopause, including which menopause-related symptoms, demographic variables, stress exposures, and neural biomarkers are associated with cognitive problems and which interventions demonstrate efficacy at improving cognitive performance. Recent Findings Cognitive problems are common during perimenopause and have a significant impact on a substantial proportion of women. Evidence continues to indicate that verbal learning and verbal memory are the cognitive functions that are most negatively affected during perimenopause, and new research suggests that perimenopause may also be associated with deficits in processing speed, attention, and working memory. Recent research suggests that the cognitive profiles of women transitioning through perimenopause are heterogenous – with some showing strengths and others demonstrating weaknesses in particular cognitive domains. Depression, sleep problems, and vasomotor symptoms in perimenopause may be associated with cognitive difficulties. Recent neuroimaging studies are identifying changes in activity patterns within brain regions that correlate with cognitive performance in perimenopause, but future causal studies are needed to understand the neural mechanisms of cognitive problems during this time. Although clinical treatment studies for cognitive concerns have historically focused on postmenopause, some small trials in perimenopausal samples have been conducted recently but are frequently underpowered. Current guidelines from the North American Menopause Society do not support the use of hormone therapy at any age for cognitive problems. Animal research demonstrates that estradiol and levonorgestrel combined may alleviate working memory problems. Summary Much progress has been made in understanding how perimenopause impacts cognition, and more research is needed to better identify who is at highest risk and how to meaningfully prevent and alleviate cognitive problems during this reproductive stage. Larger-scale randomized intervention trials specifically during perimenopause are urgently needed to address cognitive concerns in this population of women. More consistent reproductive staging, inclusion of covariates, and analyses examining perimenopause specifically would improve study quality and the ability to draw clear conclusions from this research.

To determine whether the relationship between inflammatory factors and clinically significant depression symptoms is moderated by high exposure to adverse childhood experiences and current life stressors in a longitudinal community cohort of midlife women. Methods: Participants from the Penn Ovarian Ageing Study community cohort (age at baseline: M = 45.3 [SD = 3.8]) were included in analyses if they had a blood sample measuring basal inflammatory markers during at least one visit where depression symptom severity and current stressful life events were also assessed (N = 142, average number of visits per participant = 1.75 [SD = 0.92]). Approximately annually over the course of 16 years, participants self‐reported depression symptom severity using the Centre for Epidemiologic Studies Depression (CESD) Scale, provided menstrual diaries to determine menopause stage, and contributed blood samples. Residual blood samples were assayed for interleukin (IL)‐6, IL 1‐beta (IL‐1β), tumour necrosis factor alpha (TNF‐α), and high sensitivity C‐reactive protein (hsCRP). Early life stress was quantified using the Adverse Childhood Experiences questionnaire (low [0–1 experience(s)] versus high [≥ 2 experiences]). Current stressful life events were assessed using a structured interview (low [0–1 events] vs. high [≥ 2 events]). Generalised estimating equation models were used to model associations with the outcome of interest—clinically significant depression symptoms (CESD ≥16)—and risk factors: inflammatory marker levels (log transformed), adverse childhood experiences group, and current life stressors group. Covariates included menopause stage, age at study baseline, body mass index, race, and smoking status. We found a significant three‐way interaction between log hsCRP levels, adverse childhood experiences group, and current life stressors group on likelihood of experiencing clinically significant depression symptoms (OR: 4.33; 95% CI: 1.22, 15.46; p = 0.024) after adjusting for covariates. Solely for women with high adverse childhood experiences and with high current life stressors, higher hsCRP was associated with higher odds of having clinically significant depression symptoms (OR: 1.46; 95% CI 1.07, 1.98; p = 0.016). This three‐way interaction was not significant for IL‐6, IL‐1β, or TNF‐α. For women in midlife with exposure to high adverse childhood experiences and multiple current life stressors, elevated levels of CRP were uniquely associated with clinically significant depression symptoms. Early life adversity and current life stressors represent identifiable individual risk factors whose negative impact may be curtailed with inventions to target inflammation in midlife women.

Everyday life contexts and interactions are influential for the well-being of both postpartum women and their infants. We collected naturalistic observational recordings of the daily environments and social interactions of primiparous postpartum women (N = 50) using the electronically activated recorder (EAR). We addressed two aims. First, we examined the feasibility, acceptability, and compliance of collecting naturalistic ambient sounds with postpartum women. We found the EAR to be acceptable, feasible, and associated with good compliance. Second, we evaluated the frequency and interrater reliability of social- emotional characteristics using a novel coding system developed for this population. In general, the frequency of social and emotion behavior variables was adequate and interrater reliability among trained research assistants was moderate to excellent. This study was the first to use the EAR with postpartum women and suggests that the EAR shows promise as a method to enrich our understanding of social- emotional daily life during the postpartum period.

Generalized anxiety disorder (GAD) is a condition characterized by worry and physiological arousal symptoms that causes significant disabilities in patients’ lives. In order to improve psychotherapeutic interventions, a careful characterization of the deficiencies of this population as well as factors that ameliorate disability is crucial. Variables that have not traditionally been the focus of research should be considered, such as trait mindfulness and self-compassion. We investigated whether GAD patients would report lower mindfulness and self-compassion levels than healthy stressed individuals. Eighty-seven GAD patients and 49 healthy controls completed the Five Facet Mindfulness Questionnaire, the Self-Compassion Scale, and measures of anxiety. Patients with GAD also completed the Sheehan Disability Scale. Results showed that GAD patients had lower mindfulness and self-compassion than healthy stressed controls, and both were negatively correlated with levels of anxiety, worry, and anxiety sensitivity. In patients, mindfulness was a better predictor of disability than actual anxiety symptom scores. These findings highlight that in the presence of anxiety symptoms, mindfulness can be a factor that helps protect against feeling disabled by the disorder. The findings thereby add an important variable to the characterization of this disorder and should be taken into consideration for future treatment development.