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Levine DA, Gross AL, Briceño EM, Tilton N, Giordani BJ, Sussman JB, Hayward RA, Burke JF, Hingtgen S, Elkind MS, Manly JJ, Gottesman RF, Gaskin DJ, Sidney S, Sacco RL, Tom SE, Wright CB, Yaffe K, Galecki AT. Sex Differences in Cognitive Decline Among US Adults. JAMA Netw Open. 2021 Feb 1;4(2):e210169. PubMed.
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University College London (UCL)
Levine et al. find that women have higher baseline cognition than men, but that women experience faster decline in global cognition and executive function over time. In agreement with other studies (for example, Davis et al., 2017) no sex differences were found in memory decline over time.
A great strength of this study is its large sample of over 26,000 participants, achieved by pooling data from five different cohorts. In pooling data, the authors have combined a range of cognitive measures used across the cohorts to generate t-scores for global cognition, executive function, and memory.
Across reported sex differences in cognition literature, inconsistencies are sometimes difficult to interpret due to variations in the cognitive measures used. By combining cognitive measures, Levine et al. enable us to look at the “bigger picture.” We can consider sex differences in global cognition and cognitive domains in a large group of people, rather than looking at performance on individual cognitive tests in smaller groups.
Levine et al. do not find evidence of sex differences in memory decline over time, which is in agreement with previous research. However, as the authors mention, it is somewhat surprising given that memory impairments are a hallmark of Alzheimer’s Disease (AD) and that women have a greater prevalence of AD than men. The possibility that women might experience memory decline at more advanced stages of neurodegenerative disease than men is raised. We should remember, though, that this is a study of cognition in normal aging (not of dementia or AD), and that the sample is relatively young at baseline (age range 51–67 years). We do not know based on this study whether sex differences in memory decline emerge in later life.
The relatively young age of participants also raises the possibility that some women included had yet to experience menopause or were undergoing the menopause transition during the study (menopause usually occurs between 45 and 55 years). Women often report cognitive changes, particularly in memory and attention, during menopause. Research also indicates long-term associations between menopause and cognition in later life (Kuh et al., 2018). While Levine et al. mention that sex hormones may explain sex differences in cognition and cognitive decline, they do not go into detail. An interesting follow-up analysis might be to test whether menopause factors (whether women have undergone menopause or not/their age at menopause/type of menopause/use of hormone replacement treatment) explain the patterns in baseline cognition and cognitive decline seen in women in this study, although authors note they did not have information on participants’ HRT use.
Another consideration is that rates of cognitive decline over time may vary by age at baseline. Separating the analyses by age group could highlight potential effects of menopause and would help in exploring the possibility that sex differences in memory decline might emerge at later ages.
While there is scope to further explore the pattern of sex differences found in this study, Levine et al. present a useful overview of sex differences in baseline cognition and cognitive decline over time using three broad cognitive outcomes in a large sample of U.S. adults.
References:
Davis D, Bendayan R, Muniz Terrera G, Hardy R, Richards M, Kuh D. Decline in Search Speed and Verbal Memory Over 26 Years of Midlife in a British Birth Cohort. Neuroepidemiology. 2017;49(3-4):121-128. Epub 2017 Nov 16 PubMed.
Kuh D, Cooper R, Moore A, Richards M, Hardy R. Age at menopause and lifetime cognition: Findings from a British birth cohort study. Neurology. 2018 May 8;90(19):e1673-e1681. Epub 2018 Apr 11 PubMed.
View all comments by Louisa NeedhamMayo Clinic
The study by Levine and colleagues is important and impactful. The vast majority of studies examining cognitive decline still adjust for sex but do not examine sex differences. This study highlights the critical need to examine cognition by sex across all analyses, particularly since women performed better at baseline, but had greater cognitive decline when followed longitudinally. Understanding these sex differences provides better precision medicine and will improve health for both women and men.
The authors provide an excellent discussion on several of the factors that might contribute to the observed sex differences, and provide ideas for areas of future research. One aspect of the study that was notable to me was that cognition in women in the Framingham Offspring cohort did not slowly decline as compared to in men, as it did in the other three cohorts. This finding is important on a number of fronts. First, it highlights that (as the authors report) there could be socioeconomic, life stress, and environmental factors not currently considered in the analysis that could cause the observed sex differences. Many of these factors are modifiable; future study of these factors could lead to preventive interventions and reduce sex differences. Second, the study highlights geographic differences which can be due to education, lifestyle, diet, and many other factors. Therefore, it is critical to continue to have large epidemiological studies across multiple sites in the U.S. and abroad because one individual location is not representative of all others.
View all comments by Michelle MielkeRush University Medical Center
My impression after reading the paper is caution rather than strong agreement or disagreement. The authors examined change in global cognition in data from more than 34,000 older people from five large and very different longitudinal studies in a pooled analysis. The challenge is that a pooled analysis of data from five observational studies is a fairly limited tool for such fine and demanding analyses. Despite the high quality and size of each of the studies, the very large aggregate size, and the care taken in the analytic methods, this central design feature leaves me uncertain. The results and conclusion may well be correct, but they also may not be.
View all comments by Denis EvansMake a Comment
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