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Sex differences in Alzheimer's disease and other dementias
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“As sex is a strong factor underlying phenotypic variability in AD”
From Distinct sex-specific DNA methylation differences in Alzheimer’s disease (2022) · cites this paper as [5]
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“Since AD is more prevalent in women than in men [40], more postmortem brain samples of female subjects affected by AD”
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“Although women are more susceptible for developing AD than men (44), we found that ACE treatment in human subjects impaired IQ in men, which may be due to a greater decrease in ACE activity for men than for women after taking ACE inhibitors (35).”
BackgroundImpact of impaired cerebral blood flow autoregulation on cognitive impairment
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“Dementia is one of many disorders with gender differences (Mazure and Swendsen, 2016) and women show a greater prevalence of dementia than men (Winblad et al.”
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“…differential prevalence and course in neurodevelopmental disorders such as autism spectrum disorder (Baron-Cohen et al., 2011), a variety of psychiatric conditions such as schizophrenia (Aleman et al., 2003), and neurodegenerative disorders such as Alzheimer’s disease (Mazure and Swendsen, 2016).”
BackgroundSex differences in the genetic architecture of Alzheimer’s disease
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“27,32 The female sex is another well-recognized risk factor, 64 although the influence of sex on longitudinal PET biomarkers has been rela-tivelylittlestudied.”
BackgroundRECONSIDERING REPURPOSING: LONG-TERM METFORMIN TREATMENT IMPAIRS COGNITION IN ALZHEIMER’S MODEL MICE
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“However, as sex difference is well known in AD [56, 57], sex-speci fi c effects of metformin should be further explored.”
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“Female sex is a known risk factor for both developing AD and more severe pathology [68,69].”
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“the causal relation of those associated genes and variants remain unclear. For example, recent study and data showed that a female with the APOE gene under greater risk than a male with the APOE gene[11, 12]. This strongly indicates that we have little knowledge about how this risk factor effect people. With GWAS summ…”
Müller, E. G., Edwin, T. H., Stokke, C., Navelsaker, S. S., Babovic, A., Bogdanović, N., Knapskog, A., & Revheim, M. E. (2019) · PLoS ONE · doi:10.1371/journal.pone.0221365 · Cited by 48
Spinal muscular atrophy: Broad disease spectrum and sex-specific phenotypes
Singh, N. N., Hoffman, S., Reddi, P. P., & Singh, R. N. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.166063 · Cited by 52
“Major human diseases including cardiovascular diseases, Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) show sex-specific bias in their prevalence [145,150-152].”
BackgroundLiu, J., Yuan, S., Niu, X., Kelleher, R., & Sheridan, H. (2022) · Aging · doi:10.18632/aging.204359 · Cited by 50
“However, since the regulatory mechanisms underlying sex disparity in AD are still poorly understood, efforts to differentiate AD by sex, rather than pooling data for both sexes, could be an important stepping stone to devising new therapeutic directions for personalised treatment and disease management [25].”
Wildfire Smoke Exposure and Incident Dementia
Elser, H. C., Frankland, T. B., Chen, C., Tartof, S. Y., Mayeda, E. R., Lee, G. S., Northrop, A. J., Torres, J. M., Benmarhnia, T., & Casey, J. A. (2024) · JAMA Neurology · doi:10.1001/jamaneurol.2024.4058 · Cited by 51
Hasselgren, C., Ekbrand, H., Halleröd, B., Fässberg, M. M., Zettergren, A., Johansson, L. H., Skoog, I. G., & Dellve, L. (2020) · BMC Psychiatry · doi:10.1186/s12888-020-02820-9 · Cited by 46
“Still, in more general terms, the results underline the importance of attending to education as a ‘gendered’ dementia risk factor [16, 20, 66].”
BackgroundCholinergic Signaling Dynamics and Cognitive Control of Attention
Parikh, V., & Bangasser, D. A. (2020) · Current topics in behavioral neurosciences · doi:10.1007/7854_2020_133 · Cited by 43
Basic Mechanisms of Brain Injury and Cognitive Decline in Hypertension
Baggeroer, C. E., Cambronero, F. E., Savan, N. A., Jefferson, A. L., & Santisteban, M. M. (2023) · Hypertension · doi:10.1161/hypertensionaha.123.19939 · Cited by 47
“103 This has historically been attributed to women living longer, though cardiovascular risk factors like hypertension may play a role in these differences.”
BackgroundSex Differences in Alzheimer’s Disease: Where Do We Stand?
Medeiros, A. D. M., & Silva, R. H. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180213 · Cited by 42
“Our point of view is in line with the conception posed by Mazure and Swendsen [316] that the AD research needs to consider sex-specific disabilities and vulnerabilities over the years and not only what brings more susceptibility to one sex compared to the other.”
Age‐dependent DNA methylation patterns on the Y chromosome in elderly males
Lund, J., Li, S., Christensen, K., Mengel‐From, J., Soerensen, M., Marioni, R. E., Starr, J. M., Pattie, A., Deary, I. J., Baumbach, J., et al. (2019) · Aging Cell · doi:10.1111/acel.12907 · Cited by 43
The sex-specific interaction of the microbiome in neurodegenerative diseases
Cox, L. M., Abou‐El‐Hassan, H., Maghzi, A. H., Vincentini, J., & Weiner, H. L. (2019) · Brain Research · doi:10.1016/j.brainres.2019.146385 · Cited by 44
“Furthermore, women show a faster cognitive decline and may have sex-dependent response to treatment (Li and Singh, 2014; Mazure and Swendsen, 2016).”
BackgroundStall, N. M., Fischer, H. D., Fung, K., Giannakeas, V., Bronskill, S. E., Austin, P. C., Matlow, J. N., Quinn, K. L., Mitchell, S. L., Bell, C. M., et al. (2019) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.9557 · Cited by 42
Marongiu, R. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00242 · Cited by 47
“In rodents, aging or OVX induce changes in ERα and ERβ levels on astrocytes which leads to impaired neurotrophic responses to estrogen (Rozovsky et al., 2002; McAsey et al., 2006; Morgan and Finch, 2015).”
BackgroundUrdánoz‐Casado, A., de Gordoa, J. S., Robles, M., Acha, B., Roldán, M., Zelaya, M. V., Blanco‐Luquin, I., & Mendióroz, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179205 · Cited by 42
“Indeed, to focus on gender differences in AD has been strongly recommended by experts in the field [38].”
BackgroundAyton, S., Janelidze, S., Roberts, B. R., Palmqvist, S., Kalinowski, P., Diouf, I., Belaidi, A. A., Stomrud, E., Bush, A. I., & Hansson, O. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101904 · Cited by 43
Hobel, Z., ageing, F. T. A. D. N. I. A. T. A. I. B. A. L. F. S. O., Isenberg, A. L., Raghupathy, D., Mack, W., & Pa, J. (2019) · Journal of Alzheimer's Disease · doi:10.3233/jad-180859 · Cited by 40
“ified by sex and age is important for determining AD risk [28, 29].”
BackgroundMitochondria-Targeted Therapeutics for Alzheimer's Disease: The Good, the Bad, the Potential
Mi, Y., Qi, G., Brinton, R. D., & Yin, F. (2021) · Antioxidants & Redox Signaling · doi:10.1089/ars.2020.8070 · Cited by 43
“Sex differences in the structure and function of adult brains differentiate the risk for neurodegenerative diseases and therefore require consideration in target identification and therapeutic development (116) (Fig.”
BackgroundHenderson, A., Walsemann, K., & Ailshire, J. A. (2021) · The journals of gerontology. Series B, Psychological sciences and social sciences · doi:10.1093/geronb/gbab034 · Cited by 34
Eede, P., Obst, J., Benke, E., Yvon‐Durocher, G., Richard, B. C., Gimber, N., Schmoranzer, J., Böddrich, A., Wanker, E. E., Prokop, S., et al. (2020) · EMBO Reports · doi:10.15252/embr.201948530 · Cited by 39
Sex Hormones, Sleep, and Memory: Interrelationships Across the Adult Female Lifespan
Harrington, Y. A., Parisi, J. M., Duan, D., Rojo‐Wissar, D. M., Holingue, C., & Spira, A. P. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.800278 · Cited by 42
“Sex differences are also present in the cellular mechanisms underlying both sleep-dependent memory consolidation and non-sleep-specific consolidation (McDevitt et al., 2014).”
BackgroundPaul, K. C., Jerrett, M., & Ritz, B. R. (2018) · Current Environmental Health Reports · doi:10.1007/s40572-018-0176-1 · Cited by 38
Thirunavu, V. M., McCullough, A. A., Su, Y., Flores, S. E., Dincer, A., Morris, J. C., Cruchaga, C., Benzinger, T. L. S., & Gordon, B. A. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190154 · Cited by 37
“Previous studies have shown differences in brain atrophy rates [62], cognitive decline [62, 63, 65], mortality [66], and CSF Aβ1-42 [64] but not Aβ measured with PET [62], so our finding is unsurprising.”
Blanken, A. E., & Nation, D. A. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200245 · Cited by 37
Interactive rather than independent effect of APOE and sex potentiates tau deposition in women
Wang, Y., Pascoal, T. A., Therriault, J., Kang, M. S., Benedet, A. L., Savard, M., Tissot, C., Lussier, F. Z., Arias, J. F., Mathotaarachchi, S. S., et al. (2021) · Brain Communications · doi:10.1093/braincomms/fcab126 · Cited by 37
“Indeed, there is a growing emphasis that highlights sex as an essential consideration in Alzheimer’s disease models to move the field towards more effective prevention and treatment strategies.(18,19) The role that sex plays in Alzheimer’s disease has long been the subject of intense investigation.”
BackgroundAPOE and immunity: Research highlights
Kloske, C. M., Barnum, C. J., Batista, A. F., Bradshaw, E. M., Brickman, A. M., Bu, G., Dennison, J. L., Gearon, M. D., Goate, A., Haass, C., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13020 · Cited by 38
“A hypothesis-driven approach to pro-and anti-inflammatory proteins in Alzheimer’s disease NeuroinflammationhasbeenstronglyassociatedwithAD,andassuch, efforts have been made to obtain discrete CSF measures of inflammatory proteins for both diagnostic and prognostic purposes; however, such discrete…”
InfluentialZhou, C., Chao, F., Zhang, Y., Jiang, L. H., Zhang, L., Luo, Y., Xiao, Q., Chen, L., & Tang, Y. C. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00243 · Cited by 36
“Women diagnosed with AD experiences a faster progression of hippocampal atrophy than did men, whereas men might be more likely to progress to AD in the presence of severe periventricular white matter hyperintensities (WMH) and reduced global cognitive performance (Mazure and Swendsen, 2016).”
BackgroundMa, D., Holmes, H. E., Cardoso, M. J., Modat, M., Harrison, I. F., Powell, N. M., O’Callaghan, J. M., Ismail, O., Johnson, R. A., O’Neill, M. J., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00011 · Cited by 36
“However, sexspecific differences have been reported in AD (Mielke et al., 2014; Mazure and Swendsen, 2016; Laws et al., 2018), such as faster cognitive decline and pathological progression in female than male (Ferretti et al.”
BackgroundArtificial intelligence for neurodegenerative experimental models
Marzi, S. J., Schilder, B. M., Nott, A., Frigerio, C. S., Willaime‐Morawek, S., Bucholc, M., Hanger, D. P., James, C. R., Lewis, P. A., Lourida, I., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13479 · Cited by 35
“82,83 However, many rodent experiments are conducted in animals of one sex only (often males) for practical reasons, leading to conceivably biased findings and often overlooking the sex-specific efficacy of drugs.”
BackgroundThibeau, S., McDermott, K. L., McFall, G. P., Rockwood, K. J., & Dixon, R. A. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-019-0509-9 · Cited by 36
“Notably, females are disproportionately affected by AD in severity, progression, and prevalence [23], and female carriers of the APOE ɛ4 risk allele are at a higher risk for AD than male carriers [24].”
BackgroundFrailty—A promising concept to evaluate disease vulnerability
Ribeiro, A. R., Howlett, S. E., & Fernandes, A. M. A. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111217 · Cited by 37
Qin, W., Li, W., Wang, Q., Gong, M., Li, T., Shi, Y., Song, Y., Li, Y., Li, F., & Jia, J. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210549 · Cited by 37
“Alzheimer’s disease (AD) is the most common form of age-related dementia, accounting for nearly 80% of all cases [1, 2].”
Yanguas‐Casás, N., Torres‐Fuentes, C., Crespo‐Castrillo, A., Díaz-Pacheco, S., Healy, K., Stanton, C., Chowen, J. A., García‐Segura, L. M., Arévalo, M., Cryan, J. F., et al. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105495 · Cited by 36
“Moreover, the fact that prolonged treatment with anti-inflammatory drugs appears to decrease the risk of suffering AD (Int Veld et al., 2001; McGeer et al., 1996) suggests that prevention of the neurologic illness with anti-inflammatory therapies may be feasible.”
Sapkota, S., Huan, T., Tran, T., Zheng, J., Camicioli, R. M., Li, L., & Dixon, R. A. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00296 · Cited by 36
“Sex differences have been observed in AD with significantly higher prevalence in women than men (Mazure and Swendsen, 2016).”
Background
Metadata
- Authors
- Mazure, C. M., & Swendsen, J.
- Affiliations
- Yale University (US)
- Université de Bordeaux (FR)
- Corresponding author
- Mazure, Carolyn M
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 15
- Issue
- 5
- Pages
- 451-452
- ISSN
- 1474-4422 (ISSN-L)
- PMC
- PMC4864429
- OpenAlex
- W2297715268
- Cited by
- 350
- References
- 10
- Citations by year
- 2026: 17 · 2025: 26 · 2024: 35 · 2023: 38 · 2022: 33 · 2021: 55 · 2020: 48 · 2019: 53 · 2018: 29 · 2017: 12 · 2016: 3
- FWCI
- 28.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (P50DA033945)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Keywords
- Alzheimer's disease, dementia, sex differences, sex differences in dementia, dementia costs, population aging, dementia prevention, dementia treatment
- MeSH terms
- Alzheimer Disease, Dementia, Humans, Biomedical Research
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