Gender Differences in Alzheimer Disease: Brain Atrophy, Histopathology Burden, and Cognition
Open accessAbstract
Multiple studies suggest that females are affected by Alzheimer disease (AD) more severely and more frequently than males. Other studies have failed to confirm this and the issue remains controversial. Difficulties include differences in study methods and male versus female life expectancy. Another element of uncertainty is that the majority of studies have lacked neuropathological confirmation of the AD diagnosis. We compared clinical and pathological AD severity in 1028 deceased subjects with full neuropathological examinations. The age of dementia onset did not differ by gender but females were more likely to proceed to very severe clinical and pathological disease, with significantly higher proportions having a Mini-Mental State Examination score of 5 or less and Braak stage VI neurofibrillary degeneration. Median neuritic plaque densities were similar in females and males with AD but females had significantly greater tangle density scores. In addition, we found that AD-control brain weight differences were significantly greater for females, even after adjustment for age, disease duration, and comorbid conditions. These findings suggest that when they are affected by AD, females progress more often to severe cognitive dysfunction, due to more severe neurofibrillary degeneration, and greater loss of brain parenchyma.
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Women develop greater neurofibrillary degeneration, brain parenchymal loss, and cognitive decline.
“Recent studies suggest that women develop greater neurofibrillary degeneration, brain parenchymal loss, and cognitive decline.52,53,54”
From Sex differences in cognitive decline among US adults (2021) · cites this paper as [53]
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“The reason is that previous studies state that incidence is different in women and men [39,40], and that differences in the brain volume-associated measures are observed for male subjects [41] with an impact on the prevalence of the disease.”
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“One of these studies demonstrated that hippocampal neurofibrillary tangles quantitatively differed by age at death and sex, with women showing more pronounced increases in neurofibrillary tangles in the hippocampus with age compared to men, suggesting a sex-specific neuroanatomic susceptibility (46, 47).”
ResultSex differences in mixed neuropathologies in community-dwelling older adults
Barnes, L. L., Lamar, M., & Schneider, J. A. (2019) · Brain Research · doi:10.1016/j.brainres.2019.05.028 · Cited by 62 · see citing works
“Relative to the large neuropathological literature on AD, few neuropathologic studies, particularly from community-dwelling participants, have systematically addressed this question (Barnes et al., 2005; Corder et al., 2004; Miller, Hicks, D'Amato, & Landis, 1984; Sandberg, Stewart, Smialek, & Troncoso, 2001; Nelson e…”
BackgroundResultSex is a defining feature of neuroimaging phenotypes in major brain disorders
Salminen, L. E., Tubi, M., Bright, J. K., Thomopoulos, S., Wieand, A., & Thompson, P. (2020) · Human Brain Mapping · doi:10.1002/hbm.25438 · Cited by 58 · see citing works
Wang, Y., Therriault, J., Servaes, S., Tissot, C., Rahmouni, N., Macedo, A. C., Arias, J. F., Mathotaarachchi, S. S., Benedet, A. L., Stevenson, J., et al. (2023) · Brain · doi:10.1093/brain/awad397 · Cited by 51 · see citing works
“33,34 This observation motivated investigations focusing on sex differences in tau pathology.”
Oliver, M., Morrison, C., Kamal, F., Graham, J., & Dadar, M. (2022) · Alzheimer's Research & Therapy · doi:10.1186/s13195-022-01138-w · Cited by 42 · see citing works
“Despite evidence indicating biological sex is independently associated with AD prevalence [12, 45], cortical atrophy [15, 29], and clinical progression [14, 62], the relationship between sex, cognition, and SCD classification remains relatively unexplored.”
BackgroundGlycoproteomics Landscape of Asymptomatic and Symptomatic Human Alzheimer’s Disease Brain
Suttapitugsakul, S., Stavenhagen, K., Donskaya, S., Bennett, D. A., Mealer, R., Seyfried, N., & Cummings, R. (2022) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2022.100433 · Cited by 40 · see citing works
“The second most frequent glycan is HexNAc(5)Hex(3)”
BackgroundResultInfluentialChang, K.-P., Ling, J. P., Redding-Ochoa, J., An, Y., Li, L., Dean, S. A., Blanchard, T. G., Pylyukh, T., Barrett, A., Irwin, K. E., et al. (2023) · Acta Neuropathologica · doi:10.1007/s00401-023-02653-2 · Cited by 38 · see citing works
“Some previous studies have also shown higher ADNC pathology scores in females [24, 32], but the presence of a greater frequency of LATE-NC in females has not been previously addressed.”
Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases
Pérez‐Jiménez, M. M., Monje, J. M., Brokate-Llanos, A. M., Venegas‐Calerón, M., Sánchez‐García, A., Sansigre, P., Valladares, A., Esteban-García, S., Suárez‐Pereira, I., Vitórica, J., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20269-y · Cited by 39 · see citing works
Alzheimer disease seen through the lens of sex and gender
Castro‐Aldrete, L., Einsiedler, M., Martínková, J., Depypere, H. T., Ang, T. F. A., Mielke, M. M., Sindi, S., Eyre, H. A., Au, R., Dimech, A. S., et al. (2025) · Nature Reviews Neurology · doi:10.1038/s41582-025-01071-0 · Cited by 39 · see citing works
“…AD indicate that the subgroup of female individuals had higher Braak stages ( P < 0.05) and lower brain weights ( P < 0.001) than those of the male subgroup; the female subgroup also included significantly more individuals with severe (Braak stage VI) neurofibrillary degeneration ( P < 0.001) 57 .”
InfluentialSex differences in the progression of glucose metabolism dysfunction in Alzheimer’s disease
Park, J.-C., Lim, H., Byun, M., Yi, D., Byeon, G., Jung, G., Kim, Y., Lee, D.-Y., Han, S.-H., & Mook-Jung, I. (2023) · Experimental and Molecular Medicine · doi:10.1038/s12276-023-00993-3 · Cited by 36 · see citing works
“Although the average age at onset does not differ between sexes, women are susceptible to more severe clinical and pathological processes, including denser neuro fi brillary tangles, greater changes in brain weight, and more severe cognitive dysfunction, than men 2 – 4 .”
Marongiu, R. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00242 · Cited by 44 · see citing works
Goodwill, A., Campbell, S., Simpson, S., Bisignano, M., Chiang, C., Dennerstein, L., & Szoeke, C. (2018) · Maturitas · doi:10.1016/j.maturitas.2017.10.005 · Cited by 33 · see citing works
Neurochemical and cognitive changes precede structural abnormalities in the TgF344-AD rat model
Fowler, C. F., Goerzen, D., Devenyi, G., Madularu, D., Chakravarty, M. M., & Near, J. (2022) · Brain Communications · doi:10.1093/braincomms/fcac072 · Cited by 32 · see citing works
Sun, L., Yang, S., Sun, H., Li, W., & Duan, S. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13852 · Cited by 32 · see citing works
“Sexual dimorphism in brain structure and function also contributes to sex differences in AD.(5,7) Genetic studies on the association between single‐nucleotide polymorphisms and AD have suggested that the risk of AD is greater in female than in male carriers of the apolipoprotein (Apo)E4 allele.”
Neuropathology of supercentenarians - four autopsy case studies
Takao, M., Hirose, N., Arai, Y., Mihara, B., & Mimura, M. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0368-6 · Cited by 28 · see citing works
“As stated earlier, age and female sex are generally considered to be risk factors for developing AD [16, 17, 40, 43].”
Hu, Y., Boonstra, J. T., McGurran, H., Stormmesand, J., Sluiter, A. A., Balesar, R. A., Verwer, R. W. H., Swaab, D. F., & Bao, A. (2021) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12729 · Cited by 28 · see citing works
Puris, E., Auriola, S. O. K., Petralla, S., Hartman, R., Gynther, M., de Lange, E. C. M., & Fricker, G. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105741 · Cited by 29 · see citing works
Libard, S., & Alafuzoff, I. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0748-9 · Cited by 24 · see citing works
Vascular Lesions, <i>APOE</i> ε4, and Tau Pathology in Alzheimer Disease
Nichols, J. B., Malek-Ahmadi, M., Tariot, P. N., Serrano, G. E., Sue, L. I., & Beach, T. G. (2021) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlaa160 · Cited by 22 · see citing works
Self-citationSex and Sleep Disruption as Contributing Factors in Alzheimer’s Disease
Johnson, C. E., Duncan, M. J., & Murphy, M. P. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230527 · Cited by 34 · see citing works
Berezuk, C., Khan, M., Callahan, B. L., Ramirez, J., Black, S., & Zakzanis, K. (2022) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617722000297 · Cited by 22 · see citing works
“For example, several studies have found that women appear to be more vulnerable to the effects of APOE4 (Altmann et al., 2014; Farrer et al., 1997; Kim et al., 2015) and AD pathology (Filon et al., 2016; Koran et al., 2017).”
Sexual Dimorphism in Neurodegenerative Diseases and in Brain Ischemia
Zalewska, T., Pawelec, P., Ziąbska, K., & Ziemka‐Nałęcz, M. (2022) · Biomolecules · doi:10.3390/biom13010026 · Cited by 22 · see citing works
“The datasets present a higher incidence of Alzheimer’s disease, at a ratio of approximately two to one [46,47], and women experience more progressive cognitive and physical decline [48–51].”
BackgroundSanfilippo, C., Giuliano, L., Castrogiovanni, P., Imbesi, R., Ulivieri, M., Fazio, F., Blennow, K., Zetterberg, H., & Rosa, M. D. (2022) · Current Neuropharmacology · doi:10.2174/1570159x21666221207091209 · Cited by 20 · see citing works
“When affected by AD, females progress more often to severe cognitive dysfunction due to more severe neurofibrillary degeneration and greater loss of brain parenchyma [110].”
BackgroundCastor, K., Shenoi, S., Edminster, S. P., Tran, T. T., King, K. S., Chui, H. C., Pogoda, J. M., Fonteh, A. N., & Harrington, M. G. (2020) · PLoS ONE · doi:10.1371/journal.pone.0231765 · Cited by 21 · see citing works
“Thus, dysfunctional brain mitochondria reported in AD [31, 32] may account for the reduction of some DCAs, while oxidative damage of brain lipids resulting in the loss of brain tissue in AD [33] would increase urinary excretion of oxidized DCAs [34].”
BackgroundBeach, T. G., Sue, L., Scott, S., Intorcia, A. J., Walker, J. E., Arce, R. A., Glass, M. J., Borja, C. I., Cline, M. P., Hemmingsen, S. J., et al. (2023) · Journal of Neuropathology and Experimental Neurology · doi:10.1093/jnen/nlad026 · Cited by 19 · see citing works
Self-citationChromosomal and gonadal factors regulate microglial sex effects in the aging brain
Ocañas, S. R., Ansere, V. A., Kellogg, C. M., Isola, J. V. V., Chucair‐Elliott, A. J., & Freeman, W. M. (2023) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2023.02.008 · Cited by 24 · see citing works
Hosseininasab, S. S. M., Ebrahimi, R., Yaghoobpoor, S., Kazemi, K., Khakpour, Y., Hajibeygi, R., Mohamadkhani, A., Fathi, M., Vakili, K. G., Tavasol, A., et al. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1513095 · Cited by 17 · see citing works
Neubauer, A., Weissenbrunner, D., Pekrun, S., Roeber, S., Ruf, V. C., Feyen, P. L. C., Strübing, F., & Herms, J. (2025) · Acta Neuropathologica · doi:10.1007/s00401-025-02952-w · Cited by 17 · see citing works
“Several studies in humans found increased Aβ and tau load in women [8, 26, 57].”
Steroid hormones: risk and resilience in women’s Alzheimer disease
Calvo, N., & Einstein, G. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1159435 · Cited by 26 · see citing works
“In this respect, postmortem studies have shown that women have more severe neurodegeneration than men (Filon et al., 2016); and transgenic animal models of AD-like brain amyloidosis have found that female mice have increased plaque load burden and higher levels of soluble and insoluble Aβ40/Aβ42 than age-matched males…”
BackgroundSex differences in early‐onset Alzheimer's disease
Contador, J., Pérez‐Millan, A., Guillén, N., Sarto, J., Tort‐Merino, A., Balasa, M., Falgàs, N., Castellví, M., Borrego‐Écija, S., Juncà‐Parella, J., et al. (2022) · European Journal of Neurology · doi:10.1111/ene.15531 · Cited by 21 · see citing works
“On the other hand, women with AD have shown more accelerated longitudinal cortical thinning [32– 35] and more severe neurofibrillary degeneration and brain loss associated with faster cognitive progression [7].”
BackgroundInfluentialImpact of APOE , Klotho, and sex on cognitive decline with aging
Shibata, K., Chen, C., Tai, X. Y., Manohar, S., & Masud Husain, B. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2416042122 · Cited by 17 · see citing works
Epigenetic Mechanisms Underlying Sex Differences in Neurodegenerative Diseases
Stoccoro, A. (2025) · Biology · doi:10.3390/biology14010098 · Cited by 17 · see citing works
Ventricular features as reliable differentiators between bvFTD and other dementias
Manera, A. L., Dadar, M., Collins, D. L., & Ducharme, S. (2022) · NeuroImage Clinical · doi:10.1016/j.nicl.2022.102947 · Cited by 18 · see citing works
“MoCA 28[25-29] 19[12-23] 21[17-22] 21[10-25] 26[25-28] 23[2126] 19[14-21] <0.”
Gender Differences of NLRP1 Inflammasome in Mouse Model of Alzheimer's Disease
Zhang, J.-H., Pei, L.-H., Zang, D., Xue, Y., Wang, X.-H., Chen, Y.-Y., Li, J., Yu, J., Gao, Q.-Z., Di, W., et al. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.512097 · Cited by 15 · see citing works
“Clinical studies have shown that women have a higher risk of suffering AD than men, and the clinical symptoms of female AD patients are more serious than males (Hebert et al., 2010; Filon et al., 2016; Canevelli et al., 2017).”
BackgroundPancani, S., Sofi, F., Cecchi, F., & Macchi, C. (2019) · The Journal of Nutrition, Health & Aging · doi:10.1007/s12603-019-1203-0 · Cited by 15 · see citing works
“Gender differences in brain pathophysiology and dementia development have been reported in the literature (20), and in all population studies that include cohorts of very elderly people, females represent the large part of the population.”
Sex‐ and region‐dependent neuroinflammation in Alzheimer's disease
Acosta‐Martínez, M., Carter, V., Nessim, A., Panchal, R., John, D., Dhawan, J., Beach, T. G., Serrano, G. E., Sundermann, E. E., & Biegon, A. R. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.14603 · Cited by 14 · see citing works
“8,12,13 High sensitivity of aged females to neuroinflammation is also strongly supported by the preclinical and clinical literature, 56–58 reporting higher levels of inflammatory markers and higher pro-inflammatoryresponsetolipopolysaccharide(LPS)inagedfemalemice relative to male mice of the same…”
Self-citationTian, J., Jia, K., Wang, T.-J., Guo, L., Xuan, Z.-Y., Michaelis, E. K., Swerdlow, R., & Du, H. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02958-0 · Cited by 13 · see citing works
“In addition to the tested genes, aging, sex, and ApoE4 status, which are strong risk factors associated with brain atrophy [60 – 62], were also included as critical co-variables in the analysis.”
BackgroundMethodCorrelation of Presynaptic and Postsynaptic Proteins with Pathology in Alzheimer’s Disease
Serrano, G., Walker, J. E., Nelson, C. M., Glass, M. J., Arce, R. A., Intorcia, A. J., Cline, M. P., Nabaty, N., Acuña, A. M., Steed, A. H., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063130 · Cited by 13 · see citing works
“Therefore, the greater brain weight loss that we and others have observed in ADD [10] is most likely due to axonal loss and/or synaptic loss.”
Self-citationNeuropathology and cholinesterase expression in the brains of octogenarians and older
Maxwell, S. P., Cash, M. K., & Darvesh, S. (2022) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2022.110065 · Cited by 15 · see citing works
Cognition and Diabetes: Examining Sex Differences Using a Longitudinal Sample of Older Adults
Palarino, J. V., Boardman, J. D., & Rogers, R. G. (2022) · Research on Aging · doi:10.1177/01640275221084282 · Cited by 12 · see citing works
“Outside the sphere of age-based cognition declines, several studies demonstrate that females experience a greater prevalence of dementia and Alzheimer’s disease than do males (Andersen et al., 1999; Filon et al., 2016; Levine et al., 2021; Li & Singh, 2014).”
BackgroundSakurai, K., Iwase, T., Kaneda, D., Uchida, Y., Inui, S., Morimoto, S., Kimura, Y., Kato, T., Nihashi, T., Ito, K., et al. (2021) · Journal of Alzheimer's Disease · doi:10.3233/jad-210638 · Cited by 12 · see citing works
“…of demographical variables, especially female sex which could cause more severe neurofibrillary degeneration and brain atrophy in AD patients, additional investigation with adjustment for demographical variables will be nec-essarytoclarifytheeffectofsexforthedifferentiation between AD and AGD [32].”
Boon, B. D., Labuzan, S., Peng, Z., Matchett, B. J., Kouri, N., Hinkle, K., Lachner, C., Ross, O., Ertekin-Taner, N., Carter, R., et al. (2023) · Neurology · doi:10.1212/wnl.0000000000207685 · Cited by 11 · see citing works
Cicero, C., Angelini, L., Abbadessa, G., Bruno, M., Fiume, G., Nucera, B., Ornello, R., Arabia, G., Giuliano, L., Guarnieri, B., et al. (2026) · Neurological Sciences · doi:10.1007/s10072-025-08623-8 · Cited by 10 · see citing works
“In a recent study, there was no significant sex difference in baseline Aβ load in AD patients, but females displayed a more widespread tau pathology at follow-up, in line with previous data [21, 22 ].”
Investigation of sex differences in mutation carriers of the Dominantly Inherited Alzheimer Network
Wagemann, O., Li, Y., Hassenstab, J. J., Aschenbrenner, A., Mckay, N. S., Gordon, B., Benzinger, T., Xiong, C., Cruchaga, C., Renton, A., et al. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.13460 · Cited by 10 · see citing works
“…of pathology have been associated with a greater cognitive impairment in females with MCI 6,9,11,18 and studies along the spectrum of sADhavefoundfemalestograduallyperformworseonverbalmemory, verbal fluency, and domains relating to…”
Lansdell, T. A., Xu, H., Galligan, J., & Dorrance, A. (2023) · Journal of Alzheimer's Disease · doi:10.3233/jad-220905 · Cited by 10 · see citing works
Stites, S., Cao, H., James, R., Harkins, K., Coykendall, C., & Flatt, J. (2023) · Alzheimer's & Dementia · doi:10.1002/dad2.12359 · Cited by 10 · see citing works
Giorgio, J., Jonson, C., Wang, Y.-L., Yokoyama, J. S., Wang, J.-S., & Jagust, W. (2024) · Research Square · doi:10.21203/rs.3.rs-4804430/v1 · Cited by 9 · see citing works
“Furthermore, females have consistently been shown to have higher tau tangle load at autopsy then men 27–29 .”
BackgroundRetinal and Choroidal Changes in Men Compared with Women with Alzheimer’s Disease
Mirzania, D., Thompson, A., Robbins, C. B., Soundararajan, S., Lee, J., Agrawal, R. V., Liu, A. J., Johnson, K. G., Grewal, D., & Fekrat, S. (2021) · Ophthalmology Science · doi:10.1016/j.xops.2021.100098 · Cited by 9 · see citing works
Kindler, D., Maschio, C. A., Ni, R., Zerbi, V., Razansky, D., & Klohs, J. (2021) · Journal of Cerebral Blood Flow and Metabolism · doi:10.1177/0271678x211062274 · Cited by 9 · see citing works
“…as compared to men,47,48 but it is also associated with a higher tau cerebrospinal fluid level, cortical tau load and degree of neurodegeneration (Filon et al., 2016; Hohman et al., 2018).49–51 Sexual dimorphism of the behavioral and neuropathological phenotype in animal models of tauopathy have…”
BackgroundReyes-Pablo, A. E., Campa-Córdoba, B. B., Luna-Viramontes, N. I., Ontiveros-Torres, M. A., Villanueva-Fierro, I., Bravo-Muñoz, M., Saenz-Ibarra, B., Barbosa, O., Guadarrama-Ortíz, P., Garcés-Ramírez, L., et al. (2020) · Journal of Alzheimer's Disease · doi:10.3233/jad-191015 · Cited by 9 · see citing works
“Macro-scopically,abrainaffectedbyADpresentssymmetric atrophywithalllobesaffected,increaseddepthofthe grooves(Fig.1,arrow),dilatedventricles(Fig.1A, V),decreasedweightandcerebralvolume(Fig.1A) [18].”
Zhou, F., & Chen, S.-R. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-170983 · Cited by 9 · see citing works
“Epidemiological studies suggested that, due to more severe neurodegeneration and greater loss of brain parenchyma [4], females were more severely and more frequently affected by AD, with greater risk of developing Alzheimer’s dementia, than males with greater risk of developing vascular dementia…”
Raya, M. A., Suemoto, C. K., Paes, V. R., Leite, R. E. P., Pasqualucci, C. A., Naslavsky, M. S., Rodriguez, R. D., Nitríni, R., Ferriolli, E., Allen, I. E., et al. (2026) · JAMA Neurology · doi:10.1001/jamaneurol.2026.0054 · Cited by 10 · see citing works
Seto, M., Clifton, M. J., Gomez, M. L., Coughlan, G., Gifford, K. A., Jefferson, A. L., Jager, P. L. D., Bennett, D. A., Wang, Y., Barnes, L. L., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-64525-5 · Cited by 14 · see citing works
““ Anatomical structure formation involved in morphogenesis ” for males and “ orga-nonitrogen compound biosynthetic process ” in females were most signi fi cant in relation to longitudinal cognition (Supplementary Data 6).”
InfluentialGiorgio, J., Jonson, C., Wang, Y., Yokoyama, J. S., Wang, J., Jagust, W. J., & Initiative, O. B. O. T. A. D. N. (2025) · Nature Communications · doi:10.1038/s41467-025-60370-8 · Cited by 12 · see citing works
Whole-brain functional connectivity predicts regional tau PET in preclinical Alzheimer’s disease
Abuwarda, H., Trainer, A. E., Horien, C., Shen, X.-L., Moret, S., Ju, S., Constable, R., & Fredericks, C. A. (2024) · bioRxiv · doi:10.1093/braincomms/fcaf274 · Cited by 8 · see citing works
“On the other hand, tau appears to travel along paths of FC 18-20 .”
Pan, F., Wang, Y., Wang, Y., Wang, X., Guan, Y., Xie, F., & Guo, Q. (2023) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2023.06.013 · Cited by 9 · see citing works
The role of sex differences in depression in pathologically defined Alzheimer’s disease
Tremblay, C., Choudhury, P., Belden, C. M., Goldfarb, D., Lorenzini, I., Beach, T. G., & Serrano, G. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1156764 · Cited by 8 · see citing works
“Women were also shown to demonstrate a faster cognitive decline and greater clinical and pathological severity (Filon et al., 2016; Koran et al., 2017; Barnes et al., 2019; Zhu et al., 2021).”
BackgroundSelf-citationHamza, E., Moustafa, A. A., Tindle, R., Karki, R., Nalla, S., Hamid, M. S., & el Haj, M. (2023) · Current Alzheimer Research · doi:10.2174/1567205020666230309113749 · Cited by 8 · see citing works
“For example, one study found that females progress faster to AD than males [100].”
Lee, H. I., Kang, M. K., Hwang, K., Kim, C.-Y., Kim, Y. J., Suh, K. J., Choi, B. S., Choe, G., Kim, I. A., & Jang, B. (2022) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2022.09.022 · Cited by 8 · see citing works
Bedada, F., Ntekim, O. E., Nwulia, E., Fungwe, T., Nadarajah, S., & Obisesan, T. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.641758 · Cited by 8 · see citing works
“For example, by eliminating Aβ deposits and preventing plaque formation, the anti-inflammatory subset of peripheral monocytes can enhance neurogenesis and produce reparative growth factors like insulin-like growth factor I (IGF-1; Gate et al., 2010; Malm et al., 2010; Schwartz and Shechter, 2010).”
BackgroundBarnes, C. A., Permenter, M. R., Vogt, J. A., Chen, K.-W., & Beach, T. (2024) · The Journal of comparative neurology · doi:10.1002/cne.25670 · Cited by 7 · see citing works
Self-citationStoisavljevic, S., Ždraljević, M., Radojičić, A., Pavlovic, A., & Mijajlović, M. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e36052 · Cited by 7 · see citing works
“In addition, physiologically, women exhibit greater loss of brain volume over midlife which could be a confounding factor in our cohort [40 – 43].”
BackgroundHosseinzadeh, S., Afshari, S., Molaei, S., Rezaei, N., & Dadkhah, M. (2023) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2023.578206 · Cited by 9 · see citing works
Gender Difference and Dietary Supplemental Vitamin B6: Impact on Colon Luminal Environment.
Nirmagustina, D. E., Yang, Y.-S., Kumrungsee, T., Yanaka, N., & Kato, N. (2018) · Journal of Nutritional Science and Vitaminology · doi:10.3177/jnsv.64.116 · Cited by 7 · see citing works
Wang, Z., Ding, D., Wang, J., Ling, C., Dong, Q., Khamrai, M., Zhou, Y., Ishii, A., Sakata, K., Li, W., et al. (2025) · Cells · doi:10.3390/cells14110843 · Cited by 6 · see citing works
“Furthermore, female patients also tend to develop more severe clinical symptoms even with the same degree of AD pathology as male patients [68,69].”
Sex differences in vulnerability to tau pathology: Impact on cognitive decline
Zeighami, Y., Tremblay, C., & Dadar, M. (2025) · medRxiv · doi:10.1002/alz.70634 · Cited by 6 · see citing works
“TheindirecteffectofAonrate of CDR-SB increase was significant in both sexes, but larger in females (0.437, 95% CI: 0.336–0.544, p 0.001) than in males (0.322, 95% CI: 0.222–0.422, p 0.001), with the proportion of the total effect mediated by T being 47.0% in females (95% CI: 37.2–56.5”
InfluentialAli, M., Garcia, P., Lunkes, L. P., Sciortino, A., Thomas, M. H., Heurtaux, T., Grzyb, K., Halder, R., Skupin, A., Buée, L., et al. (2025) · Acta Neuropathologica Communications · doi:10.1186/s40478-025-02013-z · Cited by 6 · see citing works
“Sex differences extend beyond prevalence; women with AD often experience faster cognitive decline and more severe neuropathological changes, while males tend to die faster with AD [3, 4] and have lower brain resilience to tau pathology [5].”
Alb’ool, B., & Khait, A. F. A. (2023) · Cognitive Neuropsychiatry · doi:10.1080/13546805.2023.2255342 · Cited by 4 · see citing works
“Females were more likely to be emotionally a ff ected by the burden of NPS. Previous research (Colombo et al., 2018; Eikelboom et al., 2021; Filon et al., 2016) has found that the amyloid burden, tau pathology, and brain volume loss seen in females with Alzheimer ’ s disease are due to sex di ff…”
BackgroundShaaban, C. E., Tudorascu, D., Glymour, M. M., Cohen, A. D., Thurston, R. C., Snyder, H. M., Hohman, T. J., Mukherjee, S., Yu, L., & Snitz, B. E. (2022) · Frontiers in Neuroimaging · doi:10.3389/fnimg.2022.978350 · Cited by 8 · see citing works
“Women are consistently found to have more tau accumulation in the brain than men after accounting for age (Filon et al., 2016; Hohman et al., 2018; Oveisgharan et al., 2018; Buckley et al., 2019a,b, 2020; Luchsinger et al., 2020; Edwards et al., 2021; Palta et al., 2021), with few studies reporting no differences or r…”
BackgroundAlterations in Retinal Signaling Across Age and Sex in 3xTg Alzheimer’s Disease Mice
Frame, G., Schuller, A. J., Smith, M. A., Crish, S., & Dengler-Crish, C. (2022) · Journal of Alzheimer's Disease · doi:10.3233/jad-220016 · Cited by 6 · see citing works
Direct Consequences of Cranioplasty to the Brain: Intracranial Pressure Study
Tsianaka, E., Singh, A., Drosos, E., & Fountas, K. (2021) · The Journal of craniofacial surgery (Print) · doi:10.1097/scs.0000000000007945 · Cited by 6
Decoding alzheimer's: The role of EEG rhythms and aperiodic components in cognitive decline.
Zhang, M., Liu, X., Ren, Y.-N., Li, L., Wang, R.-Y., Sun, L., & Ma, Q.-Y. (2025) · Clinical Neurophysiology · doi:10.1016/j.clinph.2025.2111437 · Cited by 5 · see citing works
Karim, F., Delaney, B. A., Mondal, R., Liang, C., Serrano, G., Beach, T., & Mukherjee, J. (2025) · Synapse · doi:10.1002/syn.70024 · Cited by 5 · see citing works
Self-citationNeuropathological comorbidity, genetics and cognition in a Chinese community-based autopsy cohort
Wu, W., Wang, X., Xu, Y.-Y., Ma, C., Qian, X.-J., & Qiu, W.-Y. (2025) · Brain : a journal of neurology · doi:10.1093/brain/awaf039 · Cited by 5 · see citing works
X‐chromosome-wide association study for Alzheimer’s disease
Borgne, J. L., Gomez, L., Heikkinen, S., Amin, N., Ahmad, S., Choi, S. H., Bis, J. C., Grenier‐Boley, B., Rodriguez, O. G., Kleineidam, L., et al. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02838-5 · Cited by 11 · see citing works
“For example, women have a greater tau burden than men [29 – 36] and the impact of APOE variants on the disease risk or on Tau concentration differs between males and females [37, 38].”
Self-citationPuris, E., Saveleva, L., Auriola, S., Gynther, M., Kanninen, K., & Fricker, G. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1365051 · Cited by 5 · see citing works
Knowledge About Alzheimer’s Disease in Saudi Arabia
El-Gamal, F., Alali, A., Mashaabi, M. H., Alsaghah, A. A., Shukr, F. A., & Kadri, S. Y. (2023) · Cureus · doi:10.7759/cureus.50188 · Cited by 5 · see citing works
“This increased risk is related to the depletion of endogenous estrogen in the menopausal period [14].”
BackgroundStructural signature of plasma proteins classifies the status of Alzheimer’s disease
Son, A., Kim, H., Diedrich, J. K., Bamberger, C., Wilkins, H. M., Burns, J. M., Morris, J. K., Rissman, R., Swerdlow, R., & Yates, J. (2026) · Nature Aging · doi:10.1038/s43587-026-01078-2 · Cited by 4 · see citing works
“Almost all individuals with AD develop neuropsychiatric symptoms (NPSs), but women reportedly develop severe cognitive impairment more rapidly than men 15–18 .”
Plasma neurofilament light reflects more severe manifestation of Alzheimer’s disease in men
Cheng, X.-Q., Wang, Z.-H., He, K., Xia, Y., Wang, Y., Guo, Q.-H., Xie, F., & Yuan, P. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03149-z · Cited by 4 · see citing works
Neurofibrillary Tangles Predict Dementia in Patients with Carotid Stenosis
Zahra, S., Khakwani, K. Z. R., Acosta, D., Arias, J. C., French, S. R., Bedrick, E. J., Vitali, F., Beach, T., Serrano, G., & Weinkauf, C. (2025) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2025.02.007 · Cited by 4 · see citing works
Self-citationAlzheimer’s Disease and Sex-Dependent Alterations in the Striatum: A Lesson from a Mouse Model
Barbera, L. L., & D'Amelio, M. (2023) · Journal of Alzheimer's Disease · doi:10.3233/jad-230681 · Cited by 4 · see citing works
“In addition, neuroimaging studies showed a tendency to increased A (cid:2) plaque density, as well as greater neurodegeneration and faster brain atrophy rate in females compared to males [3, 4].”
Sartoretti, T., Ganley, R., Ni, R., Freund, P., Zeilhofer, H., & Klohs, J. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.825996 · Cited by 4 · see citing works
Blazer, D. (n.d.) · doi:10.4135/9781412956208.n161 · Cited by 4
Uncertainty-Aware Multimodal Learning via Conformal Shapley Intervals
Chandy, M., Johnson, M., Shen, J., Mehrotra, D., Zhou, H., Zhou, J., & Dai, X.-W. (2026) · arXiv.org · doi:10.48550/arxiv.2602.00171 · Cited by 3
“These patterns align with evidence that Alzheimer’s disease progression differ by sex (Mei et al., 2025; Arenaza-Urquijo et al., 2024; Filon et al., 2016; Moutinho, 2025).”
Kalumbilo, L., Mpolya, E., & Vianney, J.-M. (2023) · The Pan African Medical Journal · doi:10.11604/pamj.2023.45.1.36831 · Cited by 3 · see citing works
“Additionally, our results are consistent with other CT-scan-based published studies that report that there is more brain atrophy with aging in men than in women [20-24].”
ResultPotential Explanatory Models of the Female Preponderance in Very Late Onset Schizophrenia
Johnstone, S., Cruz, G. A. D., Girard, T., Rajji, T., & Castle, D. J. (2022) · Women · doi:10.3390/women2040033 · Cited by 3 · see citing works
- Authors
- Filon, J. R., Intorcia, A. J., Sue, L. I., Vazquez Arreola, E., Wilson, J., Davis, K. J., Sabbagh, M. N., Belden, C. M., Caselli, R. J., Adler, C. H., Woodruff, B. K., Rapscak, S. Z., Ahern, G. L., Burke, A. D., Jacobson, S., Shill, H. A., Driver-Dunckley, E., Chen, K., Reiman, E. M., Beach, T. G., & Serrano, G. E.
- Affiliations
- University of Arizona (US)
- Corresponding author
- Serrano, Geidy E.
- ORCID
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-06-11
- Volume
- 75
- Issue
- 8
- Pages
- 748-754
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC7299435
- OpenAlex
- W2418237732
- Cited by
- 143
- References
- 58
- Citations by year
- 2026: 20 · 2025: 26 · 2024: 13 · 2023: 20 · 2022: 21 · 2021: 19 · 2020: 6 · 2019: 9 · 2018: 6 · 2017: 2 · 2016: 1
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- NIH
- National Institute of Neurological Disorders and Stroke (U24 NS072026)
- National Institute on Aging (P30 AG19610)
- Arizona Department of Health Services (211002)
- Arizona Biomedical Research Commission (4001, 0011, 05-901, 1001)
- Michael J. Fox Foundation for Parkinson's Research
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, sex differences, brain atrophy, neurofibrillary tangles, Braak stages, neuritic plaques, cognitive impairment, dementia severity, neuropathology, brain weight, Mini-Mental State Examination
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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