Managing perimenopausal CNS symptoms

Abstract

Complaints of cognitive difficulties are more common, and performance on objective cognitive tests declines, in the perimenopause compared to the premenopause. In longitudinal studies, the cognitive ability affected most reliably during the transition is verbal learning and memory, with some studies also showing effects on processing speed. These stage-related changes in cognition are not fully accounted for by age, mood or menopause symptoms, suggesting that changes in ovarian hormones likely play an important role. Studies of surgical menopause support that hypothesis. In addition, vasomotor symptoms (VMS), sleep disturbance and mood difficulties contribute to these changes. Increased frequency of VMS during the day and particularly at night, have been linked to changes in memory, as well as brain function, connectivity and structure. Initial evidence suggests that treating VMS may improve cognition, and large clinical trials are underway to determine if VMS may play a causal role in such changes. Importantly, the link between VMS and brain health is observed only when VMS are measured objectively using ambulatory skin conductance monitors. If these associations are found to be causal in future studies, then the treatment of VMS may be indicated to maintain cognitive performance. Nighttime VMS are associated with awakenings, and disturbed sleep is a key determinant of cognitive performance. Behavioral interventions for sleep disturbance, including sleep hygiene and insomnia cognitive behavioral therapy (iCBT) are evidence based to improve sleep. Depression and anxiety symptoms increase in the perimenopause and are associated with cognitive difficulties. Treating mood and anxiety with CBT and lifestyle interventions (i.e., exercise, yoga is therefore also important to optimizing cognition. Head-to-head clinical trial data suggests that conjugated equine estrogen but not oral estradiol improves mood in euthymic midlife women. Most women with a history of major depression depressive disorder (MDD) will experience a recurrence of MDD during the perimenopause. Although treating MDD is likely to improve cognition, research indicates that those with MDD continue to experience cognitive problems even when not experiencing a major depressive episode. There are no large randomized trials of hormone therapy on cognition in the perimenopause, though treating VMS with hormone therapy theoretically may confer benefits, particularly if those VMS are disrupting sleep.