Sex differences in cognitive decline among US adults

In the paper

“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”

What the sources say

• Partly supported

  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)

  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 sourceExperimental — accuracy not yet measured
• Disputed

  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.

  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 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [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

In the paper

“Declines in global cognition and executive function markedly raise the risk of death, dementia, and functional disability.39,40,41”

What the sources say

• ?Not checked — no full text of the sourcecites [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
• Partly supported

  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)

  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 sourceExperimental — accuracy not yet measured
• Partly supported

  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)

  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 sourceExperimental — accuracy not yet measured

In the paper

“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”

What the sources say

• Partly supported

  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)

  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 sourceExperimental — accuracy not yet measured
• Supported

  The Results report sex differences in blood-pressure trajectories, including systolic BP: women had faster age-related increases than men, and the difference persisted after adjustment for clinical covariates. This supports the attributed claim that systolic BP varies by sex. (LLM, conf=0.94)

  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

In the paper

“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”

What the sources say

• Supported

  The Results (Association between Predictors and Rate of Change) report that women with Alzheimer dementia declined faster than men on the MMSE, a measure of global cognition. The paper supports the AD part of the citing sentence; it does not study mild cognitive impairment. (LLM, conf=0.92)

  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
• Supported

  The Conclusions report that women with mild cognitive impairment declined faster than men on ADAS-Cog, a measure of cognitive performance. This source supports the MCI portion of the sentence; the separate reference to patients with AD is not attributed specifically to it. (LLM, conf=0.92)

  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

In the paper

“Recent studies suggest that women develop greater neurofibrillary degeneration, brain parenchymal loss, and cognitive decline.52,53,54”

What the sources say

• ?Not checked — no full text of the sourcecites [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
• Supported

  The Discussion states that females develop more neurofibrillary tangles and suffer greater AD-related loss of brain parenchyma and cognitive function. The Results also report higher Braak stages in females with AD, supporting the comparison with males. The claim’s tentative wording is consistent with the paper’s conclusion. (LLM, conf=0.94)

  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
• Partly supported

  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)

  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 sourceExperimental — accuracy not yet measured

In the paper

“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”

What the sources say

• ?Not checked — no full text of the sourcecites [1] Alzheimer's Association. 2020 Alzheimer's Disease facts and figures. Alzheimers Dement. 2020; 16(3): 391- 460. doi: 10.1002/alz.12068 source
• Partly supported

  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)

  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 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [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

In the paper

“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,”

What the sources say

• Supported

  The Abstract identifies participants in the Baltimore Longitudinal Study of Aging with mean baseline ages of 64.1–69.7 years. The Discussion reports faster decline for men on four measures; the Results identify visual memory as one of them, alongside the mental-status, perceptuomotor, and visuospatial measures described in the Abstract. The remaining eight of the twelve measures showed no significant sex difference in decline in the primary analyses. (LLM, conf=0.92)

  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

In the paper

“Previous studies31 have shown that women have higher initial scores on most types of cognitive tests except those measuring visuospatial ability.”

What the sources say

• Supported

  The Introduction reports prior studies finding higher average performance for women on reasoning, verbal ability, and memory tests, while men performed better on spatial tests. The Discussion describes generally higher baseline performance for women across cognitive domains, with a male advantage on tests with a visuospatial component. Page numbers were not available in our copy. (LLM, conf=0.88)

  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

In the paper

“Selective attrition of cognitively impaired participants could underestimate the rate of cognitive decline57 or not.58”

What the sources say

• ?Not checked — no full text of the sourcecites [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
• Supported

  The Discussion (page unavailable) supports the “or not” qualification: despite selective attrition, estimated cognitive change was similar for returning and nonreturning participants. The paper limits this finding to its moderately healthy adult sample and an assumption about missing data; it does not claim that attrition can never bias estimates. (LLM, conf=0.91)

  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

In the paper

“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”

What the sources say

• Supported

  The Abstract Results report a 13% decline in dementia incidence per decade, with a larger decline in men (24%) than women (8%). The Discussion describes this as a trend over the past 25 years in cohorts from Europe and the United States. (LLM, conf=0.94)

  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

In the paper

“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).”

In the paper

“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.”

In the paper

“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.”

In the paper

“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.”

In the paper

“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.”

In the paper

“We evaluated model assumptions by inspecting residual plots.”

In the paper

“memory decline is the clinical hallmark of AD, a common cause of dementia,1”

What the sources say

• ?Not checked — no full text of the sourcecites [1] Alzheimer's Association. 2020 Alzheimer's Disease facts and figures. Alzheimers Dement. 2020; 16(3): 391- 460. doi: 10.1002/alz.12068 source

In the paper

“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.”

In the paper

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

In the paper

“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”

What the sources say

• ?Not checked — no full text of the sourcecites [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

In the paper

“cognitive tests have been validated in Black and White participants20,21 and are consistent with the Vascular Cognitive Impairment Harmonization Standards.22”

What the sources say

• ?Not matched

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

  cites [20] Ferraro F. Minority and Cross-Cultural Aspects of Neuropsychological Assessment (Studies on Neuropsychology, Neurology and Cognition). Swets & Zeitlinger; 2002.
• ?Not checked — no full text of the sourcecites [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
• ?Not checked — no full text of the sourcecites [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

In the paper

“Diagnosis of the clinical syndrome of dementia/neurocognitive disorder requires cognitive decline by history and objective measurement.42”

What the sources say

• ?Not checked — no full text of the sourcecites [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

In the paper

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

In the paper

“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.”

In the paper

“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”

What the sources say

• ?Not checked — no full text of the sourcecites [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

In the paper

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

In the paper

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

In the paper

“By design, we did not adjust for baseline cognition.”

In the paper

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

In the paper

“We did not have information on participants’ instrumental activities of daily living, family history of dementia, and hormone replacement therapy use.”

In the paper

“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”

In the paper

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

In the paper

“We also did not study any particular age interval associated with greatest risk of sex-related cognitive decline.”

In the paper

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

In the paper

“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).”

In the paper

“We did not study incident dementia because some cohort studies lacked this information.”

In the paper

“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.”