The DOI matches its Crossref record; 50 of the 54 references it cites were found in a registry or an index; 24 of the 27 sources its claims cite were checked for support.
Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults
Open accessAbstract
Importance: Mounting evidence suggests that sex differences exist in the pathologic trajectory of Alzheimer disease. Previous literature shows elevated levels of cerebrospinal fluid tau in women compared with men as a function of apolipoprotein E (APOE) ε4 status and β-amyloid (Aβ). What remains unclear is the association of sex with regional tau deposition in clinically normal individuals. Objective: To examine sex differences in the cross-sectional association between Aβ and regional tau deposition as measured with positron emission tomography (PET). Design, Setting and Participants: This is a study of 2 cross-sectional, convenience-sampled cohorts of clinically normal individuals who received tau and Aβ PET scans. Data were collected between January 2016 and February 2018 from 193 clinically normal individuals from the Harvard Aging Brain Study (age range, 55-92 years; 118 women [61%]) who underwent carbon 11-labeled Pittsburgh Compound B and flortaucipir F18 PET and 103 clinically normal individuals from the Alzheimer's Disease Neuroimaging Initiative (age range, 63-94 years; 55 women [51%]) who underwent florbetapir and flortaucipir F 18 PET. Main Outcomes and Measures: A main association of sex with regional tau in the entorhinal cortices, inferior temporal lobe, and a meta-region of interest, which was a composite of regions in the temporal lobe. Associations between sex and global Aβ as well as sex and APOE ε4 on these regions after controlling for age were also examined. Results: The mean (SD) age of all individuals was 74.2 (7.6) years (81 APOE ε4 carriers [31%]; 89 individuals [30%] with high Aβ). There was no clear association of sex with regional tau that was replicated across studies. However, in both cohorts, clinically normal women exhibited higher entorhinal cortical tau than men (meta-analytic estimate: β [male] = -0.11 [0.05]; 95% CI, -0.21 to -0.02; P = .02), which was associated with individuals with higher Aβ burden. A sex by APOE ε4 interaction was not associated with regional tau (meta-analytic estimate: β [male, APOE ε4+] = -0.15 [0.09]; 95% CI, -0.32 to 0.01; P = .07). Conclusions and Relevance: Early tau deposition was elevated in women compared with men in individuals on the Alzheimer disease trajectory. These findings lend support to a growing body of literature that highlights a biological underpinning for sex differences in Alzheimer disease risk.
Overview
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Written from the paper’s full text.
TL;DR
In two clinically normal older-adult cohorts, women showed higher entorhinal cortical tau than men, particularly among individuals with higher global amyloid burden, although sex differences were not consistently replicated across all regional tau measures. The findings suggest early tau deposition may be elevated in women on the Alzheimer disease trajectory.
Key findings
- There was no clear association of sex with regional tau that replicated across studies, but clinically normal women exhibited higher entorhinal cortical tau than men in both cohorts (meta-analytic estimate: β [male] = −0.11 [0.05]; 95% CI, −0.21 to −0.02; P = .02).
- The sex difference in entorhinal tau was associated with higher Aβ burden: meta-analytic sex × Aβ interaction β (male, Aβ+) = −0.19 (0.06); 95% CI, −0.32 to −0.07; P = .002.
- A sex × APOE ε4 interaction was not significantly associated with regional tau (meta-analytic estimate: β [male, APOE ε4+] = −0.15 [0.09]; 95% CI, −0.32 to 0.01; P = .07).
- In ADNI only, a sex × APOE ε4 interaction was found for the tau meta-ROI (β = −0.30; 95% CI, −0.58 to −0.02; P = .04), with a stronger APOE ε4–tau association among women than men.
Methods
- Cross-sectional study of two convenience-sampled clinically normal cohorts: 193 individuals from the Harvard Aging Brain Study (HABS; age range, 55–92 years; 118 women [61%]) and 103 from the Alzheimer’s Disease Neuroimaging Initiative (ADNI; age range, 63–94 years; 55 women [51%]).
- Participants received tau PET with [18F]flortaucipir and Aβ PET ([11C]PiB in HABS; [18F]florbetapir in ADNI); tau regions included entorhinal cortex, inferior temporal cortex, a temporal meta-ROI, and extratemporal precuneus and superior parietal regions.
- Hierarchical linear regressions examined sex, Aβ, and APOE ε4 associations with regional tau after adjusting for age and scan interval, followed by fixed-effect meta-analysis of standardized coefficients across cohorts.
Limitations
- The paper states that both cohorts are convenience samples with recruitment and sampling biases that may limit generalizability; it also notes possible sex-specific partial volume effects, though no association of gray matter volume with the findings was found.
- The paper states that exploratory analyses of sex × entorhinal tau on cognitive decline were null and should be interpreted cautiously because of limited power and follow-up; it also notes unresolved survival bias and limited power to examine APOE and 3-way interactions.
- Evident from the text: the cross-sectional design cannot establish temporal or causal ordering, and APOE genotype data were missing for some participants (n = 34 in HABS; n = 7 in ADNI).
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Claims the paper makes
24 of 27 cited sources checked · 16 supported · 0 flagged · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Sex differences in Aβ burden alone have not been reported in older adults,11–13”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Abstract > CONCLUSIONS AND RELEVANCE
What the sources say
- Partly supportedcites [11] Altmann A, Tian L, Henderson VW, Greicius MD; Alzheimer’s Disease Neuroimaging Initiative Investigators. Sex modifies the APOE-related risk of developing Alzheimer disease. Ann Neurol. 2014; 75 (4): 563– 573. doi: 10.1002/ana.24135 24623176 PMC4117990 sourceExperimental — accuracy not yet measured
The Discussion reports similar beta-amyloid levels in men and women with MCI and a pronounced APOE4 effect on beta-amyloid in healthy older adults of both sexes. However, the Results (CSF Biomarkers; page not provided) report a nominal sex-by-APOE4 interaction for CSF Aβ in healthy controls that did not survive correction for multiple tests. These findings support the absence of a robust difference in this study, but not the broader assertion that sex differences in Aβ burden have never been reported in older adults. (LLM, conf=0.82)
- Supportedcites [12] Mielke MM, Wiste HJ, Weigand SD, Indicators of amyloid burden in a population-based study of cognitively normal elderly. Neurology. 2012; 79(15): 1570– 1577.doi: 10.1212/WNL.0b013e31826e2696 22972644 PMC3475629 source
The Results (Table 2) report no detectable difference in amyloid burden by sex among cognitively normal older adults: the male-versus-female odds ratio for PiB positivity was 1.01 at both thresholds, with p values of 0.97 and 0.98. This supports the claim that sex differences in Aβ burden were not reported in this population. (LLM, conf=0.87)
- Supportedcites [13] Morris JC, Roe CM, Xiong C, APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Ann Neurol. 2010; 67(1): 122– 131. doi: 10.1002/ana.21843 20186853 PMC2830375 source
In Results > Adjusted analyses (page unavailable), the paper reports that sex was not significantly associated with mean cortical binding potential, a measure of cerebral Aβ burden, among nondemented individuals. This supports the cited statement for the population studied; it does not establish that no other study has reported a sex difference. (LLM, conf=0.86)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“supporting the notion that sex differences may be more likely to appear downstream after the onset of Aβ accumulation.5,10”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Abstract > CONCLUSIONS AND RELEVANCE
What the sources say
- Partly supportedcites [5] Vest RS, Pike CJ. Gender, sex steroid hormones, and Alzheimer’s disease. Horm Behav. 2013; 63 (2): 301– 307. doi: 10.1016/j.yhbeh.2012.04.006 22554955 PMC3413783 sourceExperimental — accuracy not yet measured
The ‘Females, menopause, and risk of AD’ section reports sex differences in Aβ accumulation, neuropathology, and behavioral performance in transgenic mice. It does not establish that sex differences are more likely to emerge only downstream of the onset of Aβ accumulation; it reports differences in Aβ accumulation itself. (LLM, conf=0.78)
- Supportedcites [10] Hohman TJ, Dumitrescu L, Barnes LL,; Alzheimer’s Disease Genetics Consortium and the Alzheimer’s Disease Neuroimaging Initiative. Sex-specific association of Apolipoprotein E with cerebrospinal fluid levels of tau. JAMA Neurol. 2018; 75(8): 989– 998. doi: 10.1001/jamaneurol.2018.0821 29801024 PMC6142927 source
The Discussion reports that the sex difference in the APOE–CSF tau association was driven by amyloid-positive individuals, while no sex difference was observed for biomarkers of amyloidosis. It suggests sex-specific risk for downstream neurodegeneration in the presence of amyloidosis, supporting the citing sentence’s tentative wording. The paper’s cross-sectional data do not establish the temporal sequence. (LLM, conf=0.88)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“although mounting evidence suggests that women are at heightened risk for exhibiting AD pathophysiology.5–8”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Abstract > CONCLUSIONS AND RELEVANCE
What the sources say
- Supportedcites [5] Vest RS, Pike CJ. Gender, sex steroid hormones, and Alzheimer’s disease. Horm Behav. 2013; 63 (2): 301– 307. doi: 10.1016/j.yhbeh.2012.04.006 22554955 PMC3413783 source
In “Females, menopause, and risk of AD,” the review reports evidence that AD pathology is greater in women than in men and describes increased vulnerability of the female brain to AD pathogenesis. This supports the citing sentence’s hedged claim. (LLM, conf=0.93)
- Supportedcites [6] Mosconi L, Berti V, Quinn C, Sex differences in Alzheimer risk: brain imaging of endocrine vs chronologic aging. Neurology. 2017; 89(13): 1382– 1390. 28855400 PMC5652968 source
The Discussion reports that, relative to age-matched men, women undergoing menopause showed imaging markers indicative of Alzheimer disease risk, including increased amyloid accumulation, reduced glucose metabolism, and brain tissue loss. The Abstract likewise reports increased indicators of an Alzheimer disease endophenotype in perimenopausal and postmenopausal women. These findings support the citing sentence’s hedged claim, though the study concerns women in those endocrine transition stages rather than all women. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [7] Laws KR, Irvine K, Gale TM. Sex differences in Alzheimer’s disease. CurrOpin Psychiatry. 2018; 31 (2): 133– 139. doi: 10.1097/YC0.0000000000000401 29324460 source
- Supportedcites [8] Fisher DW, Bennett DA, Dong H. Sexual dimorphism in predisposition to Alzheimer’s disease. Neurobiol Aging. 2018; 70: 308– 324. doi: 10.1016/j.neurobiolaging.2018.04.004 29754747 PMC6368179 source
The Conclusion says that growing evidence suggests a true increase in AD risk for women, alongside proposed biological mechanisms. The section on sex-specific brain changes and biomarkers reports faster atrophy in women in several studies and describes an observed increase in pathophysiology. The claim's cautious wording matches the review's qualifications. (LLM, conf=0.91)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In clinically normal older adults9,10 and individuals with mild cognitive impairment,11 higher cerebrospinal fluid (CSF) tau levels have been observed in female apolipoprotein E (APOE) ε4 carriers compared with male carriers.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Abstract > CONCLUSIONS AND RELEVANCE
What the sources say
- Supportedcites [9] Damoiseaux JS, Seeley WW, Zhou J,; Alzheimer’s Disease Neuroimaging Initiative. Gender modulates the APOE ε4 effect in healthy older adults: convergent evidence from functional brain connectivity and spinal fluid tau levels. J Neurosci. 2012; 32(24): 8254– 8262. doi: 10.1523/JNEUROSCI.0305-12.2012 22699906 PMC3394933 source
The Results (ADNI cerebrospinal fluid) report higher mean CSF total tau in female than male APOE ε4 carriers among 93 healthy older controls (99 versus 72 pg/ml). The female–male comparison was not statistically significant (p=0.144). This source is cited for the clinically normal older-adult group, not the mild cognitive impairment group. (LLM, conf=0.90)
- Partly supportedcites [10] Hohman TJ, Dumitrescu L, Barnes LL,; Alzheimer’s Disease Genetics Consortium and the Alzheimer’s Disease Neuroimaging Initiative. Sex-specific association of Apolipoprotein E with cerebrospinal fluid levels of tau. JAMA Neurol. 2018; 75(8): 989– 998. doi: 10.1001/jamaneurol.2018.0821 29801024 PMC6142927 sourceExperimental — accuracy not yet measured
The Results (Sex × APOE Interactions) report a stronger association between APOE ε4 and CSF tau in females than in males. The Materials and Methods say an included cohort contained people with mild cognitive impairment, but the reported result is pooled rather than specific to that group. Post hoc Results also indicate that the sex difference was observed in amyloid-positive, not amyloid-negative, individuals. (LLM, conf=0.83)
- Supportedcites [11] Altmann A, Tian L, Henderson VW, Greicius MD; Alzheimer’s Disease Neuroimaging Initiative Investigators. Sex modifies the APOE-related risk of developing Alzheimer disease. Ann Neurol. 2014; 75 (4): 563– 573. doi: 10.1002/ana.24135 24623176 PMC4117990 source
Citation 11 is attached to the mild cognitive impairment (MCI) group, not the clinically normal older adults. The Results (CSF Biomarkers) report a significant APOE ε4-by-sex interaction for CSF tau in MCI, with a more AD-like pattern in female carriers; the Discussion states that APOE ε4 increased total tau more in women than in men. (LLM, conf=0.92)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“we examined the influence of sex to modify the well-characterized cross-sectional association between regional tau PET and global Aβ PET.14–16”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Abstract > CONCLUSIONS AND RELEVANCE
What the sources say
- Supportedcites [14] Johnson KA, Schultz A, Betensky RA, Tau positron emission tomographic imaging in aging and early Alzheimer disease. Ann Neurol. 2016; 79 (1): 110– 119. doi: 10.1002/ana.24546 26505746 PMC4738026 source
The Results section ('18F T807 and PiB binding in relation to clinical status and to each other'; page unavailable) reports an association between regional inferior temporal tau PET binding and mean cortical Aβ PET retention in both clinically normal and MCI/AD groups. This directly supports the cited cross-sectional association. (LLM, conf=0.92)
- Partly supportedcites [15] Brier MR, Gordon B, Friedrichsen K, Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease. Sci Transl Med. 2016; 8(338): 338ra66. doi: 10.1126/scitranslmed.aaf2362 PMC5267531 27169802 sourceExperimental — accuracy not yet measured
The Results section ('PET tau and Aβ, in distinct topographies, are strongly correlated'; page unavailable) reports a strong cross-sectional association between regional tau PET and Aβ PET topographies. It does not establish the specifically claimed association with a global Aβ PET measure; its Aβ measure in that analysis is a weighted regional topography. (LLM, conf=0.85)
- Supportedcites [16] Maass A, Landau S, Baker SL,; Alzheimer’s Disease Neuroimaging Initiative. Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer’s disease. Neuroimage. 2017; 157: 448– 463. doi: 10.1016/j.neuroimage.2017.05.058 28587897 PMC5814575 source
The Results section (page not provided) reports significant positive cross-sectional associations between all tau PET measures, including regional measures, and Aβ in both cohorts. The PET methods section (page not provided) describes Aβ PET measures averaged across cortical regions, supporting the claim’s reference to global Aβ PET. (LLM, conf=0.93)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Female APOE ε4 carriers with abnormal levels of CSF Aβ also exhibit higher CSF tau than male carriers.10”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Discussion
What the sources say
- Supportedcites [10] Hohman TJ, Dumitrescu L, Barnes LL,; Alzheimer’s Disease Genetics Consortium and the Alzheimer’s Disease Neuroimaging Initiative. Sex-specific association of Apolipoprotein E with cerebrospinal fluid levels of tau. JAMA Neurol. 2018; 75(8): 989– 998. doi: 10.1001/jamaneurol.2018.0821 29801024 PMC6142927 source
The Results (page not provided) report a stronger association between APOE-ε4 and CSF tau in females than males, with the sex difference present among amyloid-positive individuals. The Discussion likewise says the difference was driven by amyloid-positive individuals. (LLM, conf=0.90)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Epidemiologic studies show sex differences in clinical risk are largely discernable within the context of APOE ε4,11,42,43 particularly between the ages of 65 to 75 years compared with APOE ε4 clinically normal male carriers.44”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Discussion
What the sources say
- Partly supportedcites [11] Altmann A, Tian L, Henderson VW, Greicius MD; Alzheimer’s Disease Neuroimaging Initiative Investigators. Sex modifies the APOE-related risk of developing Alzheimer disease. Ann Neurol. 2014; 75 (4): 563– 573. doi: 10.1002/ana.24135 24623176 PMC4117990 sourceExperimental — accuracy not yet measured
The Results (Clinical Conversion Risks; page unavailable) report a stronger APOE ε4–associated risk of conversion in clinically normal older women than in men, supporting the sex-difference point. They do not identify ages 65–75 as a particularly pronounced interval, and their reported risk estimates compare carriers with non-carriers within each sex rather than directly comparing female carriers with male carriers. (LLM, conf=0.84)
- Partly supportedcites [42] Beydoun MA, Boueiz A, Abougergi MS, Sex differences in the association of the apolipoprotein E epsilon 4 allele with incidence of dementia, cognitive impairment, and decline. Neurobiol Aging. 2012; 33 (4): 720– 731. doi: 10.1016/j.neurobiolaging.2010.05.017 20619505 PMC2974952 sourceExperimental — accuracy not yet measured
The Results and Discussion (pages unavailable) report stronger APOE ε4 associations with some cognitive outcomes in women than men, although the sex difference in dementia risk was not statistically significant. The Results also note higher dementia incidence among carriers by age 75, but do not establish a sex difference specifically at ages 65–75 or a comparison with clinically normal male carriers. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [43] Farrer LA, Cupples LA, Haines JL,; APOE and Alzheimer Disease Meta Analysis Consortium. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis. JAMA. 1997; 278(16): 1349– 1356. doi: 10.1001/jama.1997.03550160069041 9343467 source
- Supportedcites [44] Neu SC, Pa J, Kukull W, Apolipoprotein E genotype and sex risk factors for Alzheimer disease: a meta-analysis. JAMA Neurol. 2017; 74(10): 1178– 1189. doi: 10.1001/jamaneurol.2017.2188 28846757 PMC5759346 source
The Results report that APOE ε3/ε4 women aged 65–75 had greater Alzheimer disease risk than men with the same genotype. The Methods describe the case-control analyses using clinically normal participants, supporting the clinical-risk context of the comparison. (LLM, conf=0.91)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Minimal,6 if any,11,12,36 sex differences have been found cross sectionally in levels of global Aβ burden in clinically normal older adults”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Discussion
What the sources say
- Could not verifycites [6] Mosconi L, Berti V, Quinn C, Sex differences in Alzheimer risk: brain imaging of endocrine vs chronologic aging. Neurology. 2017; 89(13): 1382– 1390. 28855400 PMC5652968 sourceExperimental — accuracy not yet measured
The Results (Participants section; page unavailable) report significant sex differences in PiB uptake in specific brain regions, not global Aβ burden. The study examined cognitively normal adults aged 40–60, so its cross-sectional findings do not establish whether global Aβ burden differs minimally, if at all, between sexes in clinically normal older adults. I searched the indexed copy for global amyloid burden and sex differences. (LLM, conf=0.75)
- Partly supportedcites [11] Altmann A, Tian L, Henderson VW, Greicius MD; Alzheimer’s Disease Neuroimaging Initiative Investigators. Sex modifies the APOE-related risk of developing Alzheimer disease. Ann Neurol. 2014; 75 (4): 563– 573. doi: 10.1002/ana.24135 24623176 PMC4117990 sourceExperimental — accuracy not yet measured
The Results (CSF Biomarkers; page unavailable) found no statistically significant APOE4-by-sex interaction in CSF Aβ levels among healthy controls after correction for multiple testing, which supports the cited word “minimal.” The paper measured CSF Aβ and tested an APOE4-by-sex interaction; it did not establish minimal sex differences in global Aβ burden. (LLM, conf=0.82)
- Supportedcites [12] Mielke MM, Wiste HJ, Weigand SD, Indicators of amyloid burden in a population-based study of cognitively normal elderly. Neurology. 2012; 79(15): 1570– 1577.doi: 10.1212/WNL.0b013e31826e2696 22972644 PMC3475629 source
The Results (Table 2) show virtually identical odds of exceeding either cortical PiB-PET amyloid threshold for men and women (OR 1.01 at both thresholds). The Imaging methods describe a retention ratio combining cortical regions; the study assessed amyloid positivity rather than comparing continuous burden values. (LLM, conf=0.91)
- Supportedcites [36] Buckley RF, Mormino EC, Amariglio RE,; Alzheimer’s Disease Neuroimaging Initiative; Australian Imaging, Biomarker and Lifestyle study of ageing; Harvard Aging Brain Study. Sex, amyloid, and APOE ε4 and risk of cognitive decline in preclinical Alzheimer’s disease: Findings from three well-characterized cohorts. Alzheimers Dement. 2018; 14(9): 1193– 1203.doi: 10.1016/j.jalz.2018.04.010 29803541 PMC6131023 source
The Results (§3.2) report no significant sex difference in median Aβ burden or Aβ status. The Discussion (§4) likewise states that sex was not associated with baseline Aβ burden in the study’s clinically normal older adults. (LLM, conf=0.93)
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Could not verify
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This was a significantly better-fitting model than the main effects-only model (model 1 vs model 3 log likelihood ratio: 4.42, P = .04).”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Results > Interactive Association Between Sex and Aβ With Tau
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and remained significant with robust linear regression (robust F = 5.55, P = .02).”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Results > Interactive Association Between Sex and Aβ With Tau
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Probably not a substantial claim. 16
- It may state two separate claims as one. 12
Every source the paper cites for this claim was checked and supports it.
In the paper
“As sex differences exist in brain morphology,33”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Methods > Tau Positron Emission Tomography
What the sources say
- Supportedcites [33] Ritchie SJ, Cox SR, Shen X, Sex differences in the adult human brain: evidence from 5,216 UK Biobank participants. Cereb Cortex. 2018; 28(8): 2959– 2975. doi: 10.1093/cercor/bhy109 29771288 PMC6041980 source
The Discussion reports sex differences in brain volume, surface area, and cortical thickness among more than 5,000 UK Biobank participants. It also notes substantial overlap between males and females, which does not negate the broad claim that morphological differences exist. (LLM, conf=0.95)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“given that APOE ε4 is highly associated with Aβ,45”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Discussion
What the sources say
- Supportedcites [45] Lim YY, Mormino EC; Alzheimer’s Disease Neuroimaging Initiative. APOE genotype and early β-amyloid accumulation in older adults without dementia. Neurology. 2017; 89(10): 1028– 1034. doi: 10.1212/WNL.0000000000004336 28794245 PMC5589795 source
The Results passage reports that APOE ε4 carriers were much more likely to be classified as Aβ-positive at baseline than ε3 carriers (72.9% versus 30.6%). The introductory passage also describes ε4 as consistently linked to abnormal Aβ aggregation. These passages support the broad association claimed; the supplied copy does not give page numbers for them. (LLM, conf=0.93)
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Women exhibited higher scores on logical memory delayed recall in the HABS clinically normal group (Table 1)”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Results > Cohort and Sex Differences in Demographics
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For the ADNI clinically normal group, a sex × APOE ε4 interaction term was found with the tau meta-ROI (β = −0.30; 95% CI, −0.58 to −0.02; P = .04; model 4), whereby the association between APOE ε4 and tau retention was stronger among women compared with men.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Results > Interactive Association Between Sex and APOE With Tau
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Neither cohort showed significant interactions of sex × Aβ or sex × APOE on either extratemporal ROI.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Results > Specificity of Sex Differences in the Temporal Region
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was no sex-Aβ interaction on either IT tau or the meta-ROI.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Results > Interactive Association Between Sex and Aβ With Tau
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“however, no sex differences were found in demographics in the ADNI clinically normal group.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Results > Cohort and Sex Differences in Demographics
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“but did not differ by age, sex, Aβ+ status, or APOE ε4 status.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Results > Cohort and Sex Differences in Demographics
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Clinically normal men in the ADNI group, for instance, showed lower dynamic range for Aβ and lower IT tau retention compared with women.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Discussion
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This is highlighted by the 10% sex difference in EC tau; although the ADNI clinically normal group hit this difference within the Aβ cut-off, the HABS clinically normal cohort exhibited this difference far above their established cutoff.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Discussion > Strengths and Limitations
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“since the ADNI clinically normal group were older than the HABS clinically normal cohort, exhibited lower memory performance, and had greater dynamic range in tau SUVrs”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Discussion > Strengths and Limitations
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“There were some missing data for APOE genotype (n = 34 for HABS; n = 7 for ADNI), and as such, we ran separate analyses including main associations of APOE (model 2).”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Methods > Statistical Analysis
Strength:plain· not yet calibratedn = 34Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Ina 2018 meta-analysis of multiple independent cohorts with CSF data, Hohman and colleagues10 found greater CSF total and phosphorylated tau in female APOE ε4 carriers than male carriers, with findings driven by abnormal levels of β-amyloid (Aβ).”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Abstract > CONCLUSIONS AND RELEVANCE
What the sources say
- Not matchedcites Hohman and colleagues10
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We did not include sex × Aβ × APOE interactions as a stand-alone analysis in the current study owing to low statistical power; however, we included it as an exploratory meta-analysis estimate.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Methods > Statistical Analysis
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We conducted post hoc analyses examining the influence of outliers using robust linear regression (using M estimation with Huber with the rlm package) on findings of interest.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Methods > Statistical Analysis
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Some participants had a duration delay of longer than a year between scans (HABS: n = 9; ADNI: n = 9 clinically normal individuals), and as such, we covaried for scan interval in our analyses.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Methods > Participants
Strength:plain· not yet calibratedn = 9Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A series of hierarchical linear regressions were conducted to examine the influence of sex on the association between tau and Aβ, after adjusting for age and delay between tau and Aβ scans (model 1).”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Methods > Statistical Analysis
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, this interaction was dependent on PVC for the NCs from both cohorts, suggesting that partial volume adjustment facilitates detection of this association at lower levels of tau.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We did not have statistical power to robustly assess this issue, and so the association of survival will need to be explored with larger cohorts.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, we predominantly focused on temporal ROIs, although we did find some preliminary evidence of main effects of sex on an extratemporal region of the brain.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Discussion > Strengths and Limitations
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A strength of this study is the replication of our findings across 2 independent studies of aging with Aβ and tau PET.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Discussion > Strengths and Limitations
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Owing to issues of power and limited follow-up neuropsychological observations post-tau scan in both cohorts, these preliminary null findings should be approached with caution.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Discussion > Strengths and Limitations
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these animal and cellular models of AD support a female-specific vulnerability to AD pathophysiology.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Discussion
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“However, these cohorts are convenience samples and involve recruitment and sampling biases that may result in a lack of generalizability of findings.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Discussion > Strengths and Limitations
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Animal models of AD have often reported sex differences in Aβ and tau deposition.”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Discussion
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper relies on this without support.
The association of sex with regional tau deposition in clinically normal individuals remains unclear, and studies have yet to fully explore this notion.
“What remains unclear is the association of sex with regional tau deposition in clinically normal individuals.”
“To our knowledge, studies have yet to fully explore this notion,8 with little attention paid to elucidating sex differences in regional tau deposition in the context of Aβ burden and APOE ε4.”
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.
ADNI percentage of women is incorrect in the abstract
MinorThe abstract reports 55 women among 103 ADNI participants as 51%; that fraction is 53.4%, consistent with the 53% reported in Methods.
Reported 51 · recomputed 53.398058
“103 clinically normal individuals from the Alzheimer’s Disease Neuroimaging Initiative (age range, 63–94 years; 55 women [51%])”
Overall mean age is below both cohort mean ages
MinorThe reported overall mean age of 74.2 years cannot be below both cohort means, 74.3 and 75.6 years, when those cohorts comprise the study population.
“The mean (SD) age of all individuals was 74.2 (7.6) years”
“mean [SD] age, 74.3 (8.0) years; 118 women [62%]). For ADNI, we included 103 individuals who were classified as clinically normal (global clinical dementia rating score, 0; mean [SD] age, 75.6 (6.3) years”
Stated PET acquisition duration conflicts with volume timings
MinorThe specified volumes total 12 × 15 + 57 × 60 = 3720 seconds, or 62 minutes, rather than four hours.
“4-hour dynamic acquisition of 69 volumes”
“(12 × 15 seconds, 57 × 60 seconds)”
Citations
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Items 101–200 of 373
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Polygenic Effect on Tau Pathology Progression in Alzheimer's Disease
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Self-citationSex‐ and region‐dependent neuroinflammation in Alzheimer's disease
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Age- and Sex-Associated Glucose Metabolism Decline in a Mouse Model of Alzheimer’s Disease
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Sex Differences in P-Tau217, Tau Aggregation, and Cognitive Decline
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Self-citationLiterature Overview of the Relation Between Psoriasis and Alzheimer
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Metadata
- Authors
- Buckley, R. F., Mormino, E. C., Rabin, J. S., Hohman, T. J., Landau, S., Hanseeuw, B. J., Jacobs, H. I. L., Papp, K. V., Amariglio, R. E., Properzi, M. J., Schultz, A. P., Kirn, D., Scott, M. R., Hedden, T., Farrell, M., Price, J., Chhatwal, J., Rentz, D. M., Villemagne, V. L., Johnson, K. A., & Sperling, R. A.
- Affiliations
- Brigham and Women's Hospital (US)
- Stanford University (US)
- Harvard University (US)
- Vanderbilt University (US)
- University of California, Berkeley (US)
- Cliniques Universitaires Saint-Luc (BE)
- Austin Hospital (AU)
- Corresponding author
- Sperling, Reisa A.
- ORCID
- Buckley, Rachel F.
- Mormino, Elizabeth C.
- Rabin, Jennifer S.
- Hohman, Timothy J.
- Hanseeuw, Bernard J.
- Jacobs, Heidi I. L.
- Papp, Kathryn V.
- Amariglio, Rebecca E.
- Properzi, Michael J.
- Schultz, Aaron P.
- Scott, Matthew R.
- Hedden, Trey
- Farrell, Michelle
- Price, Julie
- Chhatwal, Jasmeer
- Rentz, Dorene M.
- Villemagne, Victor L.
- Johnson, Keith A.
- Sperling, Reisa A.
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2019-05-01
- Volume
- 76
- Issue
- 5
- Pages
- 542
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC6515599
- OpenAlex
- W2913192031
- Semantic Scholar
- 7b6811fdb97945fde9c6476aca67038bda3fbac8
- Cited by
- 373
- References
- 54
- Citations by year
- 2026: 58 · 2025: 71 · 2024: 37 · 2023: 61 · 2022: 44 · 2021: 47 · 2020: 42 · 2019: 13
- FWCI
- 25.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Neurology (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- Massachusetts General Hospital
- Vanderbilt University
- Vanderbilt University Medical Center
- Universiteit Maastricht
- Centre d'Imagerie BioMédicale
- National Institutes of Health (5k01ag049164-06, 5r21ag059941-02, 5k01ag051718-05, 5p30ag062421-07)
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital
- National Institute on Aging (P30-AG062421, R21-AG059941, R01AG059716, K24 AG035007, R01 AG046396, K01-AG049164), K99AG061238, K01‐AG051718, P01AG036694, R00AG061238)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- sex differences, Alzheimer's disease, amyloid-beta, APOE ε4, entorhinal cortex, Pittsburgh compound B, flortaucipir, florbetapir, amyloid PET, tau PET, neurodegeneration biomarkers, temporal lobe, brain aging
- MeSH terms
- Aged, Aged, 80 and over, Aniline Compounds, Brain, Carbolines, Contrast Media, Cross-Sectional Studies, Ethylene Glycols, Female, Humans, Male, Middle Aged, Sex Factors, Temporal Lobe, Thiazoles, Amyloid beta-Peptides, tau Proteins, Entorhinal Cortex, Positron-Emission Tomography, Apolipoprotein E4, Healthy Volunteers
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.
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