Understanding the impact of sex and gender in Alzheimer's disease: A call to action

Nebel, Rebecca A.; Aggarwal, Neelum T.; Barnes, Lisa L.; Gallagher, Aimee M.; Goldstein, Jill M.; Kantarci, Kejal; Mallampalli, Monica P.; Mormino, Elizabeth C.; Scott, Laura Louise; Yu, Wen H.; Maki, Pauline M.; Mielke, Michelle M.

doi:10.1016/j.jalz.2018.04.008

Cited by 546 publications

(477 citation statements)

References 148 publications

Supporting

Mentioning

415

Contrasting

Unclassified

Order By: Relevance

“…Women have a greater lifetime risk of developing AD, which is not fully explained by greater longevity. 26 Despite the well-described differences in risk of hearing loss between men and women, published studies have not reported whether the association between hearing loss and cognitive decline varies by sex. A recent American Geriatrics Society and National Institute on Aging Conference recommended that in future studies "data need to be stratified according to sex."…”

Section: Introductionmentioning

confidence: 99%

Longitudinal study of self‐reported hearing loss and subjective cognitive function decline in women

Curhan

Willett

Grodstein

et al. 2020

Alzheimer's & Dementia

View full text Add to dashboard Cite

Introduction We investigated the relation between self‐reported hearing loss and risk of subjective cognitive function (SCF) decline among women. Methods We conducted a longitudinal study of 20,193 women in the Nurses’ Health Study aged ≥66 years who reported their hearing status and had no subjective cognitive concerns in 2012. SCF scores were assessed by a 7‐item questionnaire in 2012 and 2014. SCF decline was defined as a new report of at least one cognitive concern during follow‐up. Results Self‐reported hearing loss was associated with higher risk of SCF decline. Compared with women with no hearing loss, the multivariable‐adjusted odds ratios (95% confidence interval) for incident SCF score ≥1 were 1.35 (1.25, 1.47), 1.39 (1.24, 1.56), and 1.40 (1.21, 1.75) among women with mild, moderate, and severe hearing loss, respectively. Recent progression of hearing loss was associated with even higher risk. Discussion Self‐reported hearing loss was associated with higher risk of incident subjective cognitive function decline in women.

show abstract

Section: Introductionmentioning

confidence: 99%

Longitudinal study of self‐reported hearing loss and subjective cognitive function decline in women

Curhan

Willett

Grodstein

et al. 2020

Alzheimer's & Dementia

View full text Add to dashboard Cite

show abstract

“…These seemingly contradictory research findings point to significant gaps in our understanding of the effects of estrogen on brain function [8,9]. Many of these knowledge gaps were recently highlighted by the think tank convened by the Women's Alzheimer's Research Initiative [9] and the Society for Women's Health Research Interdisciplinary Network on AD expert panel [8]. These include the need to better understand how estrogen influences risk at the molecular level [8], the need to resolve discrepancies between animal models and human clinical trials [8,9], the need to understand the role of progesterone [9], and the need to better understand how APOE confers female‐biased risk [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…However, the overall outcomes are controversial due to the findings of the Women's Health Initiative Memory Study (WHIMS) which showed that HRT increased the risk for dementia [29,30]. These seemingly contradictory research findings point to significant gaps in our understanding of the effects of estrogen on brain function [8,9]. Many of these knowledge gaps were recently highlighted by the think tank convened by the Women's Alzheimer's Research Initiative [9] and the Society for Women's Health Research Interdisciplinary Network on AD expert panel [8].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Estrogen activates Alzheimer's disease genes

Ratnakumar¹,

Zimmerman²,

Jordan

et al. 2019

A&D Transl Res & Clin Interv

View full text Add to dashboard Cite

IntroductionWomen are at increased risk for Alzheimer's disease (AD), but the reason why remains unknown. One hypothesis is that low estrogen levels at menopause increases vulnerability to AD, but this remains unproven.MethodsWe compared neuronal genes upregulated by estrogen in ovariectomized female rhesus macaques with a database of >17,000 diverse gene sets and applied a rare variant burden test to exome sequencing data from 1208 female AD patients with the age of onset < 75 years and 2162 female AD controls.ResultsWe found a striking overlap between genes upregulated by estrogen in macaques and genes downregulated in the human postmortem AD brain, and we found that estrogen upregulates the APOE gene and that progesterone acts antagonistically to estrogen genome-wide. We also found that female patients with AD have excess rare mutations in the early menopause gene MCM8.DiscussionWe show with genomic data that the menopausal loss of estrogen could underlie the increased risk for AD in women.

show abstract

“…Sex may modulate not only the prevalence of risk factors for cognitive impairment and AD but also the susceptibility to the effects of risk factors (for a review, see previous works). We found that poorer TICS‐m score was associated with male sex while there was no sex difference in education, age, or APOE ε4 status.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and correlates of dementia and mild cognitive impairment classified with different versions of the modified Telephone Interview for Cognitive Status (TICS‐m)

Lindgrén

Rinne

Palviainen

et al. 2019

Int J Geriat Psychiatry

View full text Add to dashboard Cite

Objectives The modified Telephone Interview for Cognitive Status (TICS‐m) is an efficient and cost‐effective screening instrument of dementia, but there is less support for its utility in the detection of mild cognitive impairment (MCI). We undertook a comprehensive evaluation of the utility of different TICS‐m versions with or without an education‐adjusted scoring method to classify dementia and MCI in a large population‐based sample. Methods Cross‐sectional assessment of cognition (TICS‐m), depressive symptoms (CES‐D), and apolipoprotein E (APOE) ε4 status was performed on 1772 older adults (aged 71‐78 y, education 5‐16 y, 50% female) from the population‐based older Finnish Twin Cohort. TICS‐m classification methods with and without education adjustment were used to classify individuals with normal cognition, MCI, or dementia. Results The prevalence of dementia and MCI varied between education‐adjusted (dementia = 3.7%, MCI = 9.3%) and unadjusted classifications (dementia = 8.5%‐11%, MCI = 22.3%‐41.3%). APOE ε4 status was associated with dementia irrespective of education adjustment, but with MCI only when education adjustment was used. Regardless of the version, poorer continuous TICS‐m scores were associated with higher age, lower education, more depressive symptoms, male sex, and being an APOE ε4 carrier. Conclusions We showed that demographic factors, APOE ε4 status, and depressive symptoms were similarly related to continuous TICS‐m scores and dementia classifications with different versions. However, education‐adjusted classification resulted in a lower prevalence of dementia and MCI and in a higher proportion of APOE ε4 allele carriers among those identified as having MCI. Our results support the use of education‐adjusted classification especially in the context of MCI.

show abstract

Understanding the impact of sex and gender in Alzheimer's disease: A call to action

Abstract: The exclusion of sex and gender has impeded faster advancement in the detection, treatment, and care of AD across the clinical spectrum. Greater attention to these differences will improve outcomes for both sexes.

Cited by 546 publications

References 148 publications

Longitudinal study of self‐reported hearing loss and subjective cognitive function decline in women

Longitudinal study of self‐reported hearing loss and subjective cognitive function decline in women

Estrogen activates Alzheimer's disease genes

Prevalence and correlates of dementia and mild cognitive impairment classified with different versions of the modified Telephone Interview for Cognitive Status (TICS‐m)

Contact Info

Product

Resources

About