Impact of atomoxetine on subjective attention and memory difficulties in perimenopausal and postmenopausal women.

In clinical practice, midlife onset of decline in cognitive functions, particularly short-term memory, sustaining attention, and activating/organizing for work, is a frequent complaint of perimenopausal and postmenopausal-aged women. Mitchell and Woods1 reported that 60% of their sample of women transitioning through menopause reported increased memory problems; others have reported similar concerns.2,3 Such impairments occurring for the first time during midlife can cause affected women difficulties in their professional and personal lives; they can also cause unwarranted fears of early-onset dementia. However, despite the high frequency of such clinical complaints, research on links between menopause and cognitive impairments has yielded contradictory results. Several studies found no differences cross-sectionally among premenopausal, perimenopausal, and postmenopausal women in their performance on cognitive tests.4-6 In contrast, others have reported significant differences among these groups on one or more tests of cognitive performance.7,8 Luetters et al6 speculated that such contradictory findings may be due to variation in the menopausal stages compared, inadequate assessment of covariates, and/or use of a wide variety of cognitive tests, each of which taps discrete cognitive functions. This study assessed perimenopausal and postmenopausal women who reported midlife onset of impairments of concentration/attention, memory, and work organization. For our primary measure, we used a normed, self-report rating scale used to assess cognitive impairments of attention-deficit/ hyperactivity disorder (ADHD) in adults, which has been demonstrated to be effective in capturing similar cognitive impairments in adults with ADHD. In addition to this primary measure, this study also used a number of neuropsychological tests used in previous studies to assess cognition in postmenopausal women. It has been proposed that a menopause-related decline in estrogen input to the prefrontal cortex9,10 may reduce the effectiveness of neurotransmitters implicated in attention, arousal regulation, organization, and working memory, aspects of cognition often referred to as executive functions.11-14 Although there is a wealth of preclinical evidence demonstrating the neuroprotective and cognitive enhancing role of estradiol,15-18 data from clinical populations have been conflicting and thus difficult to interpret.19-22 Moreover, even if estrogen therapy (ET) were unambiguously helpful in improving menopausal-onset cognitive difficulties, a substantial proportion of perimenopausal and postmenopausal women are wary of ET and/or have medical contraindications that limit their ability to use hormone therapy (HT).22 Thus, an alternative to HT for these midlife-onset cognitive concerns could be useful. Atomoxetine (ATX; Strattera, Eli Lilly & Company, Indianapolis, IN), a selective norepinephrine reuptake inhibitor,23,24 has demonstrated efficacy in the treatment of ADHD symptoms, including cognitive impairments in children and adults.25-27 Acute and chronic administration of ATX increases both extracellular norepinephrine and dopamine levels in the prefrontal cortex, but not the striatum.23,28 We examined the effects of ATX on subjective reports of executive function and cognitive performance on neuropsychological tests in perimenopausal and postmenopausal women who had no history of ADHD but were distressed by what they perceived as deterioration in their short-term memory, organizational skills, and ability to sustain attention to tasks after onset of the menopausal transition.