CoChat
Sign Up
Cited by 440Dementia and Cognitive Impairment ResearchMenopause: Health Impacts and TreatmentsCognitive Abilities and Testing

Sex differences in cognitive decline among US adults

Open access
Levine, Deborah A., Gross, Alden L., Briceño, Emily M., Tilton, Nicholas, Giordani, Bruno J., Sussman, Jeremy B., Hayward, Rodney A., Burke, James F. +11 more·2021·JAMA Network Open
DOI 10.1001/jamanetworkopen.2021.0169PMC PMC7907956
Open this paper in CoChat — free accountOpen PDF

Abstract

Importance: Sex differences in dementia risk are unclear, but some studies have found greater risk for women. Objective: To determine associations between sex and cognitive decline in order to better understand sex differences in dementia risk. Design, Setting, and Participants: This cohort study used pooled analysis of individual participant data from 5 cohort studies for years 1971 to 2017: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Linear mixed-effects models were used to estimate changes in each continuous cognitive outcome over time by sex. Data analysis was completed from March 2019 to October 2020. Exposure: Sex. Main Outcomes and Measures: The primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Results: Among 34 349 participants, 26 088 who self-reported Black or White race, were free of stroke and dementia, and had covariate data at or before the first cognitive assessment were included for analysis. Median (interquartile range) follow-up was 7.9 (5.3-20.5) years. There were 11 775 (44.7%) men (median [interquartile range] age, 58 [51-66] years at first cognitive assessment; 2229 [18.9%] Black) and 14 313 women (median [interquartile range] age, 58 [51-67] years at first cognitive assessment; 3636 [25.4%] Black). Women had significantly higher baseline performance than men in global cognition (2.20 points higher; 95% CI, 2.04 to 2.35 points; P < .001), executive function (2.13 points higher; 95% CI, 1.98 to 2.29 points; P < .001), and memory (1.89 points higher; 95% CI, 1.72 to 2.06 points; P < .001). Compared with men, women had significantly faster declines in global cognition (-0.07 points/y faster; 95% CI, -0.08 to -0.05 points/y; P < .001) and executive function (-0.06 points/y faster; 95% CI, -0.07 to -0.05 points/y; P < .001). Men and women had similar declines in memory (-0.004 points/y faster; 95% CI, -0.023 to 0.014; P = .61). Conclusions and Relevance: The results of this cohort study suggest that women may have greater cognitive reserve but faster cognitive decline than men, which could contribute to sex differences in late-life dementia.

AI snapshot

Written from the paper’s full text.

TL;DR

In a pooled analysis of 26,088 US adults from 5 cohorts, women had higher baseline global cognition, executive function, and memory than men but faster declines in global cognition and executive function, not memory. The authors conclude women may have greater cognitive reserve but faster later-life cognitive decline.

Key findings

  • Among 26,088 participants (14,313 women, 11,775 men), women had higher baseline scores than men: global cognition +2.20 points (95% CI, 2.04-2.35), executive function +2.13 points (95% CI, 1.98-2.29), and memory +1.89 points (95% CI, 1.72-2.06); all P < .001.
  • Women had faster adjusted declines than men in global cognition (difference in slope −0.07 points/y; 95% CI, −0.08 to −0.05; P < .001) and executive function (−0.06 points/y; 95% CI, −0.07 to −0.05; P < .001), but not memory (−0.004 points/y; 95% CI, −0.023 to 0.014; P = .61).
  • The authors estimate that if causal, these differences correspond to 5 to 6 years of cognitive aging; women reached a 0.5-SD decline threshold 4.72 years faster for global cognition, 1.97 years faster for executive function, and 0.24 years faster for memory.
  • Sensitivity analyses including post-stroke observations, kidney function and myocardial infarction, APOE ε4, and within-cohort analyses showed similar results, with little heterogeneity across cohorts.

Methods

  • Pooled individual participant data from 5 prospective US cohorts (ARIC, CARDIA, CHS, FOS, NOMAS; 1971-2017); included adults without dementia or stroke at baseline and with at least 1 cognitive assessment and 1 blood pressure measurement, yielding 26,088 participants.
  • Cognitive tests were co-calibrated using item response theory into global cognition, memory, and executive function factor scores on a t-score metric (mean 50, SD 10) at first assessment; primary outcome was change in global cognition, with memory and executive function as secondary outcomes.
  • Linear mixed-effects models estimated sex differences in baseline and slope, including sex × follow-up time and covariates such as age, race, education, cohort, vascular risk factors, time-dependent cumulative mean systolic blood pressure, and hypertension treatment, with random intercepts and slopes; complete-case analysis excluded 693 of 26,781 participants (2.59%) with missing covariates.

Limitations

  • Stated: the study could not adjust for educational quality, literacy, other socioeconomic factors, or depressive symptoms; selective attrition could bias decline estimates; clinical impact was inferred by equating slopes with aging rather than directly measured; it did not study incident dementia, adjust for baseline cognition, or identify a specific age interval of greatest risk; secondary outcomes had smaller samples and fewer assessments; data were lacking on instrumental activities of daily living, family history of dementia, and hormone replacement therapy; possible immortal cohort bias and regression to the mean were noted; fixed cohort effects may produce conservative estimates.
  • Evident from the text: the observational cohort design cannot establish causality, and exclusion of participants reporting race other than Black or White and exclusion of Hispanic ethnicity from NOMAS limit generalizability; residual confounding by unmeasured factors remains possible.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1001/jamanetworkopen.2021.0169

Cites

65 of 65 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

23 of 45 cited sources checked · 13 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    Women demonstrate stronger verbal cognitive skills than men.

    “Studies have consistently found evidence of sex differences in baseline cognitive functioning with women demonstrating stronger verbal cognitive skills than men, but men demonstrating stronger visuospatial skills than women (eg, mental rotations).31,43”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [31] McCarrey AC, An Y, Kitner-Triolo MH, Ferrucci L, Resnick SM. Sex differences in cognitive trajectories in clinically normal older adults. Psychol Aging. 2016; 31(2): 166- 175. doi: 10.1037/pag0000070 26796792 PMC4783196 source
    • cites [43] Miller DI, Halpern DF. The new science of cognitive sex differences. Trends Cogn Sci. 2014; 18(1): 37- 45. doi: 10.1016/j.tics.2013.10.011 24246136 source
  • Premisecitation

    Systolic BP is a risk factor for cognitive decline.

    “We required participants to have 1 or more assessments of cognition and 1 or more measurements of blood pressure (BP) at or before the first measurement of cognition because BP is a risk factor for cognitive decline11,18 and varies by sex.18,19”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [11] Levine DA, Gross AL, Briceño EM,. Association between blood pressure and later-life cognition among Black and White individuals. JAMA Neurol. 2020; 77(7): 810- 819. doi: 10.1001/jamaneurol.2020.0568 32282019 PMC7154952 source
    • cites [18] Levine DA, Galecki AT, Langa KM,. Blood pressure and cognitive decline over 8 years in middle-aged and older Black and White Americans. Hypertension. 2019; 73(2): 310- 318. doi: 10.1161/HYPERTENSIONAHA.118.12062 30624986 PMC6450556 source
  • Premisecitation

    Men demonstrate stronger visuospatial skills than women.

    “Studies have consistently found evidence of sex differences in baseline cognitive functioning with women demonstrating stronger verbal cognitive skills than men, but men demonstrating stronger visuospatial skills than women (eg, mental rotations).31,43”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [31] McCarrey AC, An Y, Kitner-Triolo MH, Ferrucci L, Resnick SM. Sex differences in cognitive trajectories in clinically normal older adults. Psychol Aging. 2016; 31(2): 166- 175. doi: 10.1037/pag0000070 26796792 PMC4783196 source
    • cites [43] Miller DI, Halpern DF. The new science of cognitive sex differences. Trends Cogn Sci. 2014; 18(1): 37- 45. doi: 10.1016/j.tics.2013.10.011 24246136 source
  • Study design and conductown data

    The study could not adjust for educational quality, literacy, other socioeconomic factors, or depressive symptoms because not all cohorts had these data at or before the first cognitive assessment.

    “While we adjusted for educational years, we could not adjust for educational quality, literacy, other socioeconomic factors,10 or depressive symptoms, because not all cohorts had these data at or before the first cognitive assessment.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [10] Yaffe K, Falvey C, Harris TB,; Health ABC Study. Effect of socioeconomic disparities on incidence of dementia among biracial older adults: prospective study. BMJ. 2013; 347: f7051. doi: 10.1136/bmj.f7051 24355614 PMC3898154 source
  • Premisecitation

    Women have lower gray matter volume.

    “Women also appear to have lower gray matter volume,50”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [50] Gennatas ED, Avants BB, Wolf DH,. Age-related effects and sex differences in gray matter density, volume, mass, and cortical thickness from childhood to young adulthood. J Neurosci. 2017; 37(20): 5065- 5073. doi: 10.1523/JNEUROSCI.3550-16.2017 28432144 PMC5444192 source
  • Classified as probably not a substantial claim. 25
  • May combine two claims. 16
  • The quote only partly states this claim. 1

  • Classified as probably not a substantial claim.

    Premisecitation

    Clinically meaningful cognitive decline is defined as a decline in cognitive function of 0.5 or more SDs from baseline cognitive scores.

    “Experts have defined clinically meaningful cognitive decline as a decline in cognitive function of 0.5 or more SDs from baseline cognitive scores.36,37,38”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [36] Wolinsky FD, Unverzagt FW, Smith DM, Jones R, Stoddard A, Tennstedt SL. The ACTIVE cognitive training trial and health-related quality of life: protection that lasts for 5 years. J Gerontol A Biol Sci Med Sci. 2006; 61(12): 1324- 1329. doi: 10.1093/gerona/61.12.1324 17234829 source

      The HRQoL section defines a clinically relevant decline as a drop of 0.50 SD from baseline on an SF-36 health-related quality-of-life scale. It does not define that threshold for cognitive function or cognitive scores; page numbers are unavailable in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [37] Rossetti HC, Munro Cullum C, Hynan LS, Lacritz LH. The CERAD neuropsychologic battery total score and the progression of Alzheimer’s disease. Alzheimer Dis Assoc Disord. 2010; 24(2): 138- 142. doi: 10.1097/WAD.0b013e3181b76415 20505431 PMC2920638 source

      The Methods define meaningful cognitive change using a Reliable Change Index (RCI) based on test–retest data, not a decline of 0.5 or more standard deviations from baseline. The Discussion specifies a threshold of at least ±10.51 CERAD points under the RCI’s 90% confidence interval. The available passages do not give page numbers. (LLM, conf=0.86)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [38] Unger JM, van Belle G, Heyman A; Consortium to Establish a Registry for Alzheimer’s Disease. Cross-sectional versus longitudinal estimates of cognitive change in nondemented older people: a CERAD study. J Am Geriatr Soc. 1999; 47(5): 559- 563. doi: 10.1111/j.1532-5415.1999.tb02570.x 10323649 source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Declines in global cognition and executive function markedly raise the risk of death, dementia, and functional disability.

    “Declines in global cognition and executive function markedly raise the risk of death, dementia, and functional disability.39,40,41”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [39] Bennett HP, Corbett AJ, Gaden S, Grayson DA, Kril JJ, Broe GA. Subcortical vascular disease and functional decline: a 6-year predictor study. J Am Geriatr Soc. 2002; 50(12): 1969- 1977. doi: 10.1046/j.1532-5415.2002.50608.x 12473008 source
    • cites [40] Clark LJ, Gatz M, Zheng L, Chen Y-L, McCleary C, Mack WJ. Longitudinal verbal fluency in normal aging, preclinical, and prevalent Alzheimer’s disease. Am J Alzheimers Dis Other Demen. 2009; 24(6): 461- 468. doi: 10.1177/1533317509345154 19759254 PMC2824246 source

      The Results (page unavailable) report faster declines in verbal fluency among participants who subsequently developed Alzheimer’s disease than among cognitively normal participants, supporting a narrower link with dementia. The paper does not establish that declines in global cognition or executive function raise the risk of death or functional disability, nor does it quantify a marked increase in risk. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [41] Cosentino S, Scarmeas N, Albert SM, Stern Y. Verbal fluency predicts mortality in Alzheimer disease. Cogn Behav Neurol. 2006; 19(3): 123- 129. doi: 10.1097/01.wnn.0000213912.87642.3d 16957489 PMC2441850 source

      The Results (p. 1) link lower verbal fluency at Alzheimer disease diagnosis with higher mortality, supporting part of the executive-function and death claim. But the study examined scores at diagnosis, not cognitive declines; its mortality model found no significant association for global cognition (Table 3, p. 4). It did not assess the risk of developing dementia or functional disability. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Systolic BP varies by sex.

    “We required participants to have 1 or more assessments of cognition and 1 or more measurements of blood pressure (BP) at or before the first measurement of cognition because BP is a risk factor for cognitive decline11,18 and varies by sex.18,19”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [18] Levine DA, Galecki AT, Langa KM,. Blood pressure and cognitive decline over 8 years in middle-aged and older Black and White Americans. Hypertension. 2019; 73(2): 310- 318. doi: 10.1161/HYPERTENSIONAHA.118.12062 30624986 PMC6450556 source

      The Introduction (page unavailable) says men are more likely than women to have high blood pressure before age 50, with the disparity narrowing and reversing at older ages. That supports a sex difference in high blood pressure, but the passage does not establish that systolic blood pressure specifically varies by sex. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [19] Ji H, Kim A, Ebinger JE,. Sex differences in blood pressure trajectories over the life course. JAMA Cardiol. 2020; 5(3): 19- 26. doi: 10.1001/jamacardio.2019.5306 31940010 PMC6990675 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Our findings are consistent with studies showing that women with mild cognitive impairment or AD have faster decline in global cognition than men.

    “Our findings are consistent with studies showing that women with mild cognitive impairment or AD have faster decline in global cognition than men.32,33”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [32] Tschanz JT, Corcoran CD, Schwartz S,. Progression of cognitive, functional, and neuropsychiatric symptom domains in a population cohort with Alzheimer dementia: the Cache County Dementia Progression study. Am J Geriatr Psychiatry. 2011; 19(6): 532- 542. doi: 10.1097/JGP.0b013e3181faec23 21606896 PMC3101372 source
    • cites [33] Lin KA, Choudhury KR, Rathakrishnan BG, Marks DM, Petrella JR, Doraiswamy PM; Alzheimer’s Disease Neuroimaging Initiative. Marked gender differences in progression of mild cognitive impairment over 8 years. Alzheimers Dement (N Y). 2015; 1(2): 103- 110. doi: 10.1016/j.trci.2015.07.001 26451386 PMC4593067 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    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”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [52] Barnes LL, Wilson RS, Bienias JL, Schneider JA, Evans DA, Bennett DA. Sex differences in the clinical manifestations of Alzheimer disease pathology. Arch Gen Psychiatry. 2005; 62(6): 685- 691. doi: 10.1001/archpsyc.62.6.685 15939846 source
    • cites [53] Filon JR, Intorcia AJ, Sue LI,. Gender differences in Alzheimer Disease: brain atrophy, histopathology burden, and cognition. J Neuropathol Exp Neurol. 2016; 75(8): 748- 754. doi: 10.1093/jnen/nlw047 27297671 PMC7299435 source
    • cites [54] Liesinger AM, Graff-Radford NR, Duara R,. Sex and age interact to determine clinicopathologic differences in Alzheimer’s disease. Acta Neuropathol. 2018; 136(6): 873- 885. doi: 10.1007/s00401-018-1908-x 30219939 PMC6280837 source

      The Discussion (page unavailable) reports more severe hippocampal neurofibrillary tangles in women and cites neuroimaging findings of faster hippocampal atrophy. That supports a regional form of tissue loss, not greater brain-wide parenchymal loss. The Discussion and Results on clinical findings (pages unavailable) explicitly say that the rate of cognitive decline did not differ between women and men. (LLM, conf=0.91)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Women have a greater prevalence of Alzheimer disease than men, at least partly because women live longer.

    “It is known that women have a greater prevalence of Alzheimer disease (AD) than men, at least partly because women live longer.1,2,3”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [1] Alzheimer's Association. 2020 Alzheimer's Disease facts and figures. Alzheimers Dement. 2020; 16(3): 391- 460. doi: 10.1002/alz.12068 source
    • cites [2] Chêne G, Beiser A, Au R,. Gender and incidence of dementia in the Framingham Heart Study from mid-adult life. Alzheimers Dement. 2015; 11(3): 310- 320. doi: 10.1016/j.jalz.2013.10.005 24418058 PMC4092061 source

      The Results (§4.2; page unavailable) report a higher lifetime risk of AD in women than men. The Discussion (§5; page unavailable) suggests that women’s longer life expectancy partly explains that difference, alongside selective survival among men. The paper does not establish the claimed difference in AD prevalence specifically; its prevalence statement concerns dementia in the oldest-old. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [3] Hebert LE, Scherr PA, McCann JJ, Beckett LA, Evans DA. Is the risk of developing Alzheimer’s disease greater for women than for men? Am J Epidemiol. 2001; 153(2): 132- 136. doi: 10.1093/aje/153.2.132 11159157 source

  • May combine two claims.

    Premisecitation

    A 2016 study of older adults in Baltimore found that men had steeper rates of decline on 4 of 12 cognitive tests but no sex differences in declines on 8 of 12 cognitive tests.

    “A 2016 study31 of older adults in Baltimore (mean ages 64-70 years) found that men had steeper rates of decline on 4 of 12 cognitive tests (mental status [Mini Mental State Examination], perceptuomotor speed and integration, visual memory, and visuospatial ability) but no sex differences in declines on 8 of 12 cognitive tests (verbal learning and memory, object recognition and semantic retrieval,”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [31] McCarrey AC, An Y, Kitner-Triolo MH, Ferrucci L, Resnick SM. Sex differences in cognitive trajectories in clinically normal older adults. Psychol Aging. 2016; 31(2): 166- 175. doi: 10.1037/pag0000070 26796792 PMC4783196 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Previous studies have shown that women have higher initial scores on most types of cognitive tests except those measuring visuospatial ability.

    “Previous studies31 have shown that women have higher initial scores on most types of cognitive tests except those measuring visuospatial ability.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [31] McCarrey AC, An Y, Kitner-Triolo MH, Ferrucci L, Resnick SM. Sex differences in cognitive trajectories in clinically normal older adults. Psychol Aging. 2016; 31(2): 166- 175. doi: 10.1037/pag0000070 26796792 PMC4783196 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    Selective attrition of cognitively impaired participants could underestimate the rate of cognitive decline or not.

    “Selective attrition of cognitively impaired participants could underestimate the rate of cognitive decline57 or not.58”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [57] Euser SM, Schram MT, Hofman A, Westendorp RGJ, Breteler MMB. Measuring cognitive function with age: the influence of selection by health and survival. Epidemiology. 2008; 19(3): 440- 447. doi: 10.1097/EDE.0b013e31816a1d31 18414086 source
    • cites [58] Salthouse TA. Selectivity of attrition in longitudinal studies of cognitive functioning. J Gerontol B Psychol Sci Soc Sci. 2014; 69(4): 567- 574. doi: 10.1093/geronb/gbt046 23733858 PMC4049149 source

  • May combine two claims.

    Premisecitation

    Dementia incidence in Europe and the US has declined over the past 25 years, but declines were less in women than in men.

    “Evidence suggests that dementia incidence in Europe and the US has declined over the past 25 years, but declines were less in women than in men.61”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [61] Wolters FJ, Chibnik LB, Waziry R, Twenty-seven-year time trends in dementia incidence in Europe and the United States. Neurology. 2020; 95(5): e519- e531. doi: 10.1212/WNL.0000000000010022 32611641 PMC7455342 source

  • May combine two claims.

    Findingown data

    Results were similar in sensitivity analyses including post-stroke observations, adding kidney function and myocardial infarction, and adding APOE ε4.

    “Results were similar in analyses including participants’ cognitive observations after the time of incident stroke, adding glomerular filtration rate and history of myocardial infarction as covariates, and adding APOE ε4 and APOE ε4 × time variables as covariates (eTables 3-5 in the Supplement).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    Sex differences in cognitive decline were consistent across cohorts.

    “Our results of sex differences in cognitive decline were consistent across most cohorts.”
    • Also stated in: § Strengths and Limitations · plain
      “Our findings were consistent across cohorts.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Women in the study had faster declines in global cognition and executive function despite having higher initial levels of these measures.

    “However, evidence against this explanation is that women in our study had faster declines in global cognition and executive function despite having higher initial levels of these measures.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Women have greater cognitive reserve but faster cognitive decline than men, independent of sex differences in cardiovascular risk factors and educational years.

    “These findings suggest that women may have greater cognitive reserve but faster cognitive decline than men.”
    • Also stated in: § Discussion · hedged
      “Our results provide evidence suggesting that women have greater cognitive reserve but faster cognitive decline than men, independent of sex differences in cardiovascular risk factors and educational years.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The study performed a complete case analysis, excluding 693 of 26 781 (2.59%) participants with missing covariate values.

    “We performed a complete case analysis, excluding a small number of participants (693 of 26 781 [2.59%]) from the analytical data set that had missing values in covariates.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Missing covariate data are missing completely at random, so complete case analysis does not bias the results.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Model assumptions were evaluated by inspecting residual plots.

    “We evaluated model assumptions by inspecting residual plots.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Memory decline is the clinical hallmark of Alzheimer's disease, a common cause of dementia.

    “memory decline is the clinical hallmark of AD, a common cause of dementia,1”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Alzheimer's Association. 2020 Alzheimer's Disease facts and figures. Alzheimers Dement. 2020; 16(3): 391- 460. doi: 10.1002/alz.12068 source

  • May combine two claims.

    Study design and conductown data

    The study pooled 5 large, high-quality cohorts with longitudinal cognitive assessments and vascular risk factor measurements in a large number of Black and White individuals across young, middle-aged, and older ages.

    “By pooling 5 large, high-quality cohorts, we had longitudinal cognitive assessments and vascular risk factor measurements in a large number of Black and White individuals who were young, middle-aged, and older-aged to estimate cognitive trajectories in men and women.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Most participants completed 2 or more cognitive assessments (22 364 [85.7%]).

    “Most participants completed 2 or more cognitive assessments (22 364 participants [85.7%]).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Incident stroke alters the cognitive trajectory.

    “For each outcome, all available cognitive observations were used in the primary analysis except observations after the time of first cohort-adjudicated incident stroke during follow-up, because incident stroke alters the cognitive trajectory.17”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Levine DA, Galecki AT, Langa KM,. Trajectory of cognitive decline after incident stroke. JAMA. 2015; 314(1): 41- 51. doi: 10.1001/jama.2015.6968 26151265 PMC4655087 source

  • May combine two claims.

    Study design and conductcitation

    Cognitive tests have been validated in Black and White participants and are consistent with the Vascular Cognitive Impairment Harmonization Standards.

    “cognitive tests have been validated in Black and White participants20,21 and are consistent with the Vascular Cognitive Impairment Harmonization Standards.22”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [20] Ferraro F. Minority and Cross-Cultural Aspects of Neuropsychological Assessment (Studies on Neuropsychology, Neurology and Cognition). Swets & Zeitlinger; 2002.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [21] Lucas JA, Ivnik RJ, Smith GE,. Mayo’s older African Americans normative studies: norms for Boston Naming Test, controlled oral word association, category fluency, animal naming, token test, WRAT-3 reading, trail making test, stroop test, and judgment of line orientation. Clin Neuropsychol. 2005; 19(2): 243- 269. doi: 10.1080/13854040590945337 16019707 source
    • cites [22] Hachinski V, Iadecola C, Petersen RC,. National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke. 2006; 37(9): 2220- 2241. doi: 10.1161/01.STR.0000237236.88823.47 16917086 source

  • Classified as probably not a substantial claim.

    Premisecitation

    Diagnosis of the clinical syndrome of dementia/neurocognitive disorder requires cognitive decline by history and objective measurement.

    “Diagnosis of the clinical syndrome of dementia/neurocognitive disorder requires cognitive decline by history and objective measurement.42”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [42] Del Barrio V. Diagnostic and statistical manual of mental disorders. 5th ed. 2016. doi: 10.1016/B978-0-12-809324-5.05530-9 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The analysis followed a prespecified analysis plan.

    “Following a prespecified analysis plan, we compared participant characteristics by sex using a Wilcoxon rank sum test or χ2 test as appropriate.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Heterogeneity of the association of sex with cognitive decline between cohorts might have affected the statistical validity of the summary estimate in the pooled cohort.

    “Heterogeneity of the association of sex with cognitive decline between cohorts might have affected the statistical validity of the summary estimate of the effect in the pooled cohort.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    Estimating clinical impact by correlating with aging does not directly measure clinical impact, and clinically meaningful change might vary by age, educational quality, race, and baseline cognition.

    “Estimating the potential clinical impact of sex differences in cognitive decline by correlating it with decline due to aging is a common approach, but it does not directly measure clinical impact, and a clinically meaningful change might vary by an individual’s age, educational quality, race, and baseline cognition.59”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [59] Stein J, Luppa M, Luck T,. The assessment of changes in cognitive functioning: age-, education-, and gender-specific reliable change indices for older adults tested on the CERAD-NP battery: results of the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe). Am J Geriatr Psychiatry. 2012; 20(1): 84- 97. doi: 10.1097/JGP.0b013e318209dd08 22183013 source

  • Probably not a substantial claim: may not pass S2 (checkable).

    Study design and conductnone given

    It is valid to answer the research question quantifying sex differences in cognitive trajectories through study follow-up.

    “it is valid to answer the research question quantifying sex differences in cognitive trajectories through study follow-up.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: Participants' postmortem cognitive data are missing at random.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given

    Using a fixed effect for cohorts might have produced conservative estimates of sex effects on cognitive slopes.

    “Using a fixed effect for cohorts might have produced conservative estimates of sex effects on cognitive slopes.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The study did not adjust for baseline cognition by design.

    “By design, we did not adjust for baseline cognition.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Women may have greater need for serial cognitive assessment to allow for earlier detection of cognitive decline.

    “Women may also have greater need for serial cognitive assessment to allow for earlier detection of cognitive decline.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    The study did not have information on participants' instrumental activities of daily living, family history of dementia, and hormone replacement therapy use.

    “We did not have information on participants’ instrumental activities of daily living, family history of dementia, and hormone replacement therapy use.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Women have increased risk of dementia and disability compared with men.

    “Our findings suggest that women are at risk for delayed identification of cognitive decline, yet more rapid trajectory of decline, suggesting increased risk of dementia and disability compared with men, consistent with research showing that women with mild cognitive impairment or AD have faster cognitive decline than men.32,33”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Women have greater cognitive reserve but faster later-life cognitive decline than men.

    “These results suggest that women have greater cognitive reserve but faster later-life cognitive decline than men.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The study did not study any particular age interval associated with greatest risk of sex-related cognitive decline.

    “We also did not study any particular age interval associated with greatest risk of sex-related cognitive decline.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Women may have greater needs for caregiving and functional support resources, particularly given women's longer life expectancy compared with men.

    “Women may thus have greater needs for caregiving and functional support resources, particularly given women’s longer life expectancy compared with men.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Smaller sample size and fewer cognitive assessments might have reduced precision of estimates of cognitive decline in executive function and memory.

    “Smaller sample size and fewer cognitive assessments might have reduced precision of estimates of cognitive decline in executive function and memory (ie, the secondary outcomes).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The study did not study incident dementia because some cohort studies lacked this information.

    “We did not study incident dementia because some cohort studies lacked this information.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given

    Women might have had a greater likelihood of regressing to a lower value than men at follow-up because they had higher baseline cognitive function than men.

    “Women might have had a greater likelihood of regressing to a lower value than men at follow-up because they had higher baseline cognitive function than men.”
    Quote in the paperNot a substantial claim
37 of 37

  • The paper relies on this without support.

    Missing covariate data are missing completely at random, so complete case analysis does not bias the results.

    “We performed a complete case analysis, excluding a small number of participants (693 of 26 781 [2.59%]) from the analytical data set that had missing values in covariates.”

  • The authors state this as an assumption.

    Participants' postmortem cognitive data are missing at random.

    “the assumption that participants’ postmortem cognitive data are missing at random”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Executive-function decline is not equivalent to 5 to 6 years of aging

    Major

    The stated method compares the sex and age slope coefficients. Table 2 gives an executive-function sex difference of 0.06 points per year and an age effect of 0.028 points per year per 10 years of baseline age; their ratio corresponds to about 21 years of aging, not 5 to 6.

  • Global-cognition baseline score conflicts with the stated score scale

    Minor

    Table 1 reports a median baseline global-cognition score of 3, with an IQR of 2 to 5, although baseline cognitive scores are stated to have a mean of 50 and an SD of 10. The table values instead match the separately reported number of global-cognition assessments.

  • Executive-function confidence interval includes zero despite P < .001

    Minor

    The reported 95% confidence interval for the age-related change in executive-function slope runs from −0.034 to 0.022, crossing zero. That is inconsistent with the reported two-sided P value below .001.

3 of 3

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Ferraro, 2002, Minority and Cross-Cultural Aspects of Neuropsychological Assessment (Studies on Neuropsychology, Neurology and Cognition).
  2. Muthen, 2017, Mplus User’s Guide

Cited by

Sorted by citations

Related

Authors
Levine, D. A., Gross, A. L., Briceño, E. M., Tilton, N., Giordani, B. J., Sussman, J. B., Hayward, R. A., Burke, J. F., Hingtgen, S., Elkind, M. S. V., Manly, J. J., Gottesman, R. F., Gaskin, D. J., Sidney, S., Sacco, R. L., Tom, S. E., Wright, C. B., Yaffe, K., & Galecki, A. T.
Affiliations
  • University of Michigan (US)
  • Johns Hopkins University (US)
  • Columbia University (US)
  • Kaiser Permanente (US)
  • University of Miami (US)
  • National Institute of Neurological Disorders and Stroke (US)
  • University of California, San Francisco (US)
  • Cognitive Health Services Research Program, Department of Internal Medicine, University of Michigan, Ann Arbor
Corresponding author
Levine, Deborah A.
ORCID
Venue
JAMA Network Open
Publisher
American Medical Association (AMA)
Published
2021-02-25
Volume
4
Issue
2
Pages
e210169
ISSN
2574-3805 (ISSN-L)
DOI
10.1001/jamanetworkopen.2021.0169
PMC
PMC7907956
OpenAlex
W3130349791
Semantic Scholar
d6f141c296f99c0674780c9134c8ab6402b0d0b3
Cited by
440
References
65
Citations by year
2026: 69 · 2025: 125 · 2024: 85 · 2023: 83 · 2022: 58 · 2021: 20
FWCI
38.83
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • JAMA Network Open (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Funders
  • National Institutes of Health (5k01ag050699-05, 2p30ag024824-21)
  • National Institute on Aging (P30AG053760, K01-AG050699, K01AG050723, P30-AG024824, R01AG063887, RF1 AG054443, R01AG051827, P30AG066507)
  • National Institute of Neurological Disorders and Stroke (R01 NS029993, R01 NS102715, R37NS029993)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
Keywords
sex differences, cognitive decline, dementia risk, women, memory, executive function, global cognition, aging, Black women, racial disparities, cognitive aging, cohort studies, individual patient data meta-analysis, Framingham Offspring Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Northern Manhattan Study, Atherosclerosis Risk in Communities Study, middle-aged and older adults
MeSH terms
Aged, Female, Humans, Male, Memory, Middle Aged, Risk, Sex Factors, Time Factors, United States, Cohort Studies, Executive Function, Cognitive Reserve, Cognitive Dysfunction

About these checks

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-18.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-18.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review