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
AI snapshot
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).
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
33 Own result · 11 Own method · 6 Partly supported · 6 Own interpretation · 3 Supported · 2 No basis given · 1 Supported so far · 1 Sources not found · 1 Not checked yet · 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)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
plainn = 34- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plainn = 9- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably 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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“103 clinically normal individuals from the Alzheimer’s Disease Neuroimaging Initiative (age range, 63–94 years; 55 women [51%])”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Abstract > DESIGN, SETTING AND PARTICIPANTS
Reported 51 · recomputed 53.398058
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Abstract > RESULTS
“The mean (SD) age of all individuals was 74.2 (7.6) years”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Methods > Participants
“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”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Methods > Aβ Positron Emission Tomography
“4-hour dynamic acquisition of 69 volumes”
§ Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults > Methods > Aβ Positron Emission Tomography
“(12 × 15 seconds, 57 × 60 seconds)”
Citations
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · cited 2×
“ForHABS, the timebetween the first tauPETscanand theclosestAβPETscanwasamedian (interquartile range)of54 (14-135) days (maximum,3.”
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP
Lewis, J., Dickson, D. W., Lin, W.-L., Chisholm, L., Corral, A., Jones, G., Yen, S.-H., Sahara, N., Skipper, L., Yager, D., et al. (2001) · Science · doi:10.1126/science.1058189 · Cited by 1,611
Midlife cardiovascular risk factors and risk of dementia in late life
Whitmer, R. A., Sidney, S., Selby, J., Johnston, S. C., & Yaffe, K. (2005) · Neurology · doi:10.1212/01.wnl.0000149519.47454.f2 · Cited by 1,238
PET Imaging of Tau Deposition in the Aging Human Brain
Schöll, M., Lockhart, S. N., Schonhaut, D. R., O’Neil, J. P., Janabi, M., Ossenkoppele, R., Baker, S. L., Vogel, J. W., Faria, J., Schwimmer, H. D., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.028 · Cited by 1,214
Clinical epidemiology of Alzheimer’s disease: assessing sex and gender differences
Mielke, M., Vemuri, P., & Rocca, W. (2014) · Clinical Epidemiology · doi:10.2147/clep.s37929 · Cited by 1,021
Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging
Rowe, C. C., Ellis, K. A., Rimajova, M., Bourgeat, P., Pike, K. E., Jones, G., Fripp, J., Tochon-Danguy, H., Morandeau, L., O'Keefe, G., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.04.007 · Cited by 986
Self-citationTau positron emission tomographic imaging in aging and early Alzheimer disease
Johnson, K. A., Schultz, A., Betensky, R. A., Becker, J. A., Sepulcre, J., Rentz, D., Mormino, E., Chhatwal, J., Amariglio, R., Papp, K., et al. (2016) · Annals of Neurology · doi:10.1002/ana.24546 · Cited by 986
Self-citationCorrection for partial volume effects in PET: principle and validation.
ROUSSET, O. G., Ma, Y., & Evans, A. C. (1998) · PubMed · Cited by 919
Sex modifies the APOE ‐related risk of developing Alzheimer disease
Altmann, A., Tian, L., Henderson, V. W., Greicius, M. D., & Alzheimer's Disease Neuroimaging Initiative Investigators (2014) · Annals of Neurology · doi:10.1002/ana.24135 · Cited by 891
Cited by
Sorted by citations
Scheltens, P., De Strooper, B., Kivipelto, M., Holstege, H., Chételat, G., Teunissen, C. E., Cummings, J., & van der Flier, W. M. (2021) · The Lancet · doi:10.1016/s0140-6736(20)32205-4 · Cited by 5,465
Sex and gender: modifiers of health, disease, and medicine
Mauvais-Jarvis, F., Bairey Merz, N., Barnes, P. J., Brinton, R. D., Carrero, J.-J., DeMeo, D. L., De Vries, G. J., Epperson, C. N., Govindan, R., Klein, S. L., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)31561-0 · Cited by 2,001
Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C.-C., & Bu, G. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0228-7 · Cited by 1,425
Spread of pathological tau proteins through communicating neurons in human Alzheimer’s disease
Vogel, J. W., Iturria‐Medina, Y., Strandberg, O. T., Smith, R. A., Levitis, E., Evans, A. C., Hansson, O., Initiative, A. D. N., Weiner, M. W., Aisen, P., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15701-2 · Cited by 537
Self-citationSuárez‐Calvet, M., Karikari, T. K., Ashton, N. J., Lantero Rodríguez, J., Milà‐Alomà, M., Gispert, J. D., Salvadó, G., Minguillon, C., Fauria, K., Shekari, M., et al. (2020) · EMBO Molecular Medicine · doi:10.15252/emmm.202012921 · Cited by 401
Mechanisms of sex differences in Alzheimer’s disease
Lopez-Lee, C., Torres, E. R. S., Carling, G., & Gan, L. (2024) · Neuron · doi:10.1016/j.neuron.2024.01.024 · Cited by 376
Bellaver, B., Povala, G., Ferreira, P. C. L., Ferrari-Souza, J. P., Leffa, D. T., Lussier, F. Z., Benedet, A. L., Ashton, N. J., Triana-Baltzer, G., Kolb, H. C., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02380-x · Cited by 319
Self-citationAPOE2: protective mechanism and therapeutic implications for Alzheimer’s disease
Li, Z., Shue, F., Zhao, N., Shinohara, M., & Bu, G. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00413-4 · Cited by 306
Association of Apolipoprotein E ε4 With Medial Temporal Tau Independent of Amyloid-β
Therriault, J., Benedet, A. L., Pascoal, T. A., Mathotaarachchi, S., Chamoun, M., Savard, M., Thomas, E., Kang, M. S., Lussier, F., Tissot, C., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2019.4421 · Cited by 256
Sex and gender differences in cognitive resilience to aging and Alzheimer's disease
Arenaza‐Urquijo, E. M., Boyle, R., Casaletto, K., Anstey, K. J., Vila‐Castelar, C., Colverson, A., Palpatzis, E., Eissman, J. M., Kheng Siang Ng, T., Raghavan, S., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13844 · Cited by 223
Self-citationMielke, M. M., Aggarwal, N. T., Vila‐Castelar, C., Agarwal, P., Arenaza‐Urquijo, E. M., Brett, B., Brugulat‐Serrat, A., DuBose, L. E., Eikelboom, W. S., Flatt, J., et al. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12662 · Cited by 198
Veitch, D. P., Weiner, M. W., Aisen, P. S., Beckett, L. A., DeCarli, C., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Landau, S. M., et al. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12422 · Cited by 184
Self-citationA second X chromosome contributes to resilience in a mouse model of Alzheimer’s disease
Davis, E. J., Broestl, L., Abdulai-Saiku, S., Worden, K., Bonham, L. W., Miñones-Moyano, E., Moreno, A. J., Wang, D., Chang, K., Williams, G., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aaz5677 · Cited by 176
Sex-driven modifiers of Alzheimer risk
Rahman, A., Schelbaum, E., Hoffman, K., Diaz, I., Hristov, H., Andrews, R. D., Jett, S., Jackson, H. C., Lee, A., Sarva, H., et al. (2020) · Neurology · doi:10.1212/wnl.0000000000009781 · Cited by 163
Ossenkoppele, R., Lyoo, C. H., Jester-Broms, J., Sudre, C. H., Cho, H., Ryu, Y. H., Choi, J. Y., Smith, R., Strandberg, O., Palmqvist, S., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2019.5154 · Cited by 161
Ferretti, M. T., Martínková, J., Biskup, E. M., Benke, T., Gialdini, G., Nedelská, Z., Rauen, K., Mantua, V., Religa, D., Hort, J., et al. (2020) · European Journal of Neurology · doi:10.1111/ene.14174 · Cited by 152
Sex differences in neuropsychiatric symptoms in Alzheimer’s disease dementia: a meta-analysis
Eikelboom, W. S., Pan, M., Ossenkoppele, R., Coesmans, M., Gatchel, J. R., Ismail, Z., Lanctôt, K. L., Fischer, C. E., Mortby, M. E., van den Berg, E., et al. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-00991-z · Cited by 154
X-linked ubiquitin-specific peptidase 11 increases tauopathy vulnerability in women
Yan, Y., Wang, X., Chaput, D., Shin, M.-K., Koh, Y., Gan, L., Pieper, A. A., Woo, J.-A. A., & Kang, D. E. (2022) · Cell · doi:10.1016/j.cell.2022.09.002 · Cited by 144
Coughlan, G., Betthauser, T. J., Boyle, R. T., Koscik, R. L., Klinger, H. M., Chibnik, L. B., Jonaitis, E. M., Yau, W. W., Wenzel, A., Christian, B. T., et al. (2023) · JAMA Neurology · doi:10.1001/jamaneurol.2023.0455 · Cited by 136
Self-citationThe accumulation rate of tau aggregates is higher in females and younger amyloid-positive subjects
Smith, R. A., Strandberg, O. T., Mattsson, N., Leuzy, A., Palmqvist, S., Pontecorvo, M. J., Devous, M. D., Ossenkoppele, R., & Hansson, O. (2020) · Brain · doi:10.1093/brain/awaa327 · Cited by 141
Protective genes and pathways in Alzheimer’s disease: moving towards precision interventions
Seto, M., Weiner, R. L., Dumitrescu, L., & Hohman, T. J. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00452-5 · Cited by 135
Self-citationSex Mediates Relationships Between Regional Tau Pathology and Cognitive Decline
Buckley, R. F., Scott, M. R., Jacobs, H. I. L., Schultz, A. P., Properzi, M. J., Amariglio, R. E., Hohman, T. J., Mayblyum, D. V., Rubinstein, Z. B., Manning, L. K., et al. (2020) · Annals of Neurology · doi:10.1002/ana.25878 · Cited by 137
Self-citationSex differences in Alzheimer’s-related Tau biomarkers and a mediating effect of testosterone
Sundermann, E. E., Panizzon, M. S., Chen, X., Andrews, M., Galasko, D. R., Banks, S. J., & Initiative, A. D. N. (2020) · Biology of Sex Differences · doi:10.1186/s13293-020-00310-x · Cited by 110
Sexual Dimorphism in the 3xTg-AD Mouse Model and Its Impact on Pre-Clinical Research
Dennison, J. L., Ricciardi, N. R., Lohse, I., Volmar, C., & Wahlestedt, C. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201014 · Cited by 107
Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study
Buckley, R. F., O’Donnell, A., McGrath, E. R., Jacobs, H. I. L., Lois, C., Satizábal, C. L., Ghosh, S., Rubinstein, Z. B., Murabito, J. M., Sperling, R. A., et al. (2022) · Annals of Neurology · doi:10.1002/ana.26382 · Cited by 101
Self-citationLocal Sleep and Alzheimer’s Disease Pathophysiology
Mander, B. A. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.525970 · Cited by 97
Dubal, D. B. (2020) · Handbook of clinical neurology · doi:10.1016/b978-0-444-64123-6.00018-7 · Cited by 92
Sex and Gender Differences in Neurodegenerative Diseases: Challenges for Therapeutic Opportunities
Bianco, A., Antonacci, Y., & Liguori, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076354 · Cited by 90
Sex-specific effects of microglial activation on Alzheimer’s disease proteinopathy in older adults
Casaletto, K. B., Nichols, E., Aslanyan, V., Simone, S. M., Rabin, J. S., Joie, R. L., Brickman, A. M., Dams-O’Connor, K., Palta, P., Kumar, R. G., et al. (2022) · Brain · doi:10.1093/brain/awac257 · Cited by 92
Self-citationSex Differences in the Gut-Brain Axis: Implications for Mental Health
Holingue, C., Budavari, A. C., Rodriguez, K. M., Zisman, C. R., Windheim, G., & Fallin, M. D. (2020) · Current Psychiatry Reports · doi:10.1007/s11920-020-01202-y · Cited by 85
Gamache, J., Yun, Y., & Chiba-Falek, O. (2020) · Disease Models & Mechanisms · doi:10.1242/dmm.045211 · Cited by 84
Tau PET and multimodal brain imaging in patients at risk for chronic traumatic encephalopathy
Lesman‐Segev, O. H., Joie, R. L., Stephens, M. L., Sonni, I., Tsai, R. M., Bourakova, V., Visani, A. V., Edwards, L., O’Neil, J. P., Baker, S. L., et al. (2019) · NeuroImage Clinical · doi:10.1016/j.nicl.2019.102025 · Cited by 83
Women can bear a bigger burden: ante- and post-mortem evidence for reserve in the face of tau
Digma, L. A., Madsen, J. R., Rissman, R. A., Jacobs, D. M., Brewer, J. B., Banks, S. J., Initiative, A. D. N., Weiner, M. W., Aisen, P. S. S., Petersen, R. C., et al. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa025 · Cited by 80
Self-citationLatest advances in cerebrospinal fluid and blood biomarkers of Alzheimer’s disease
Milà‐Alomà, M., Suárez‐Calvet, M., & Molinuevo, J. L. (2019) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756286419888819 · Cited by 81
APOE effects on regional tau in preclinical Alzheimer’s disease
Young, C. B., Johns, E., Kennedy, G., Belloy, M. E., Insel, P. S., Greicius, M. D., Sperling, R. A., Johnson, K. A., Poston, K. L., Mormino, E. C., et al. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00590-4 · Cited by 80
Self-citationNicoletti, A. S. Q., Baschi, R., Cicero, C. E., Iacono, S., Re, V. L., Luca, A., Schirò, G., & Monastero, R. (2023) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2023.111821 · Cited by 79
Ramanan, V. K., Castillo, A. M., Knopman, D. S., Graff‐Radford, J., Lowe, V. J., Petersen, R. C., Jack, C. R., Mielke, M. M., & Vemuri, P. (2019) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.13909 · Cited by 74
Demarest, T. G., Varma, V. R., Estrada, D. J., Babbar, M., Basu, S., Mahajan, U. V., Moaddel, R., Croteau, D. L., Thambisetty, M., Mattson, M. P., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02152-8 · Cited by 74
Udeh-Momoh, C., & Watermeyer, T. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101459 · Cited by 67
ApoE4 and Connectivity-Mediated Spreading of Tau Pathology at Lower Amyloid Levels
Steward, A., Biel, D., Dewenter, A., Roemer, S., Wagner, F., Dehsarvi, A., Rathore, S., Otero Svaldi, D., Higgins, I., Brendel, M., et al. (2023) · JAMA Neurology · doi:10.1001/jamaneurol.2023.4038 · Cited by 67
Farrell, M. E., Papp, K. V., Buckley, R. F., Jacobs, H. I. L., Schultz, A. P., Properzi, M. J., Vannini, P., Hanseeuw, B. J., Rentz, D. M., Johnson, K. A., et al. (2022) · Neurology · doi:10.1212/wnl.0000000000200137 · Cited by 64
Self-citationIulita, M. F., Bejanin, A., Vilaplana, E., Carmona-Iragui, M., Benejam, B., Videla, L., Barroeta, I., Fernández, S., Altuna, M., Pegueroles, J., et al. (2023) · Brain Communications · doi:10.1093/braincomms/fcad074 · Cited by 68
Sex differences in longitudinal tau-PET in preclinical Alzheimer disease: a meta-analysis
Coughlan, G. T., Klinger, H. M., Boyle, R., Betthauser, T. J., Binette, A. P., Christenson, L., Chadwick, T., Hansson, O., Harrison, T. M., Healy, B., et al. (2025) · JAMA Neurology · doi:10.1001/jamaneurol.2025.0013 · Cited by 69
Self-citationFrequency and Clinical Outcomes Associated With Tau Positron Emission Tomography Positivity
Moscoso, A., Heeman, F., Raghavan, S., Costoya‐Sánchez, A., van Essen, M., Mainta, I., Camacho, V., Fonseca, O. D. R., Silva‐Rodríguez, J., Perissinotti, A., et al. (2025) · JAMA · doi:10.1001/jama.2025.7817 · Cited by 74
Self-citationLiu, M., Paranjpe, M. D., Zhou, X., Duy, P. Q., Goyal, M. S., Benzinger, T. L. S., Lu, J., Wang, R., & Zhou, Y. (2019) · Theranostics · doi:10.7150/thno.35366 · Cited by 67
Tau pathology in cognitively normal older adults
Ziontz, J., Bilgel, M., Shafer, A. T., Moghekar, A., Elkins, W., Helphrey, J. H., Gómez, G., June, D., McDonald, M. A., Dannals, R. F., et al. (2019) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2019.07.007 · Cited by 67
Tissot, C., Therriault, J., Pascoal, T. A., Chamoun, M., Lussier, F. Z., Savard, M., Mathotaarachchi, S. S., Benedet, A. L., Thomas, E. M., Parsons, M., et al. (2021) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12154 · Cited by 63
Cumplido‐Mayoral, I., García-Prat, M., Operto, G., Falcón, C., Shekari, M., Cacciaglia, R., Milà‐Alomà, M., Lorenzini, L., Ingala, S., Wink, A. M., et al. (2023) · eLife · doi:10.7554/elife.81067 · Cited by 74
The complex pathway between amyloid β and cognition: implications for therapy
Jagust, W. J., Teunissen, C. E., & DeCarli, C. S. (2023) · The Lancet Neurology · doi:10.1016/s1474-4422(23)00128-x · Cited by 69
Challenges and Advancements in the Health-Related Quality of Life of Older People
Rony, M. K. K., Parvin, M. R., Wahiduzzaman, M., Akter, K., & Ullah, M. (2024) · Advances in Public Health · doi:10.1155/2024/8839631 · Cited by 63
Edwards, L., Joie, R. L., Iaccarino, L., Strom, A., Baker, S. L., Casaletto, K. B., Cobigo, Y., Grant, H. E., Kim, M., Kramer, J. H., et al. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.04.003 · Cited by 65
Shaw, C., Hayes-Larson, E., Glymour, M. M., Dufouil, C., Hohman, T. J., Whitmer, R. A., Kobayashi, L. C., Brookmeyer, R., & Mayeda, E. R. (2021) · JAMA Network Open · doi:10.1001/jamanetworkopen.2021.1001 · Cited by 60
Self-citationSex modifies APOE ε4 dose effect on brain tau deposition in cognitively impaired individuals
Yan, S., Zheng, C., Paranjpe, M. D., Li, Y., Li, W., Wang, X., Benzinger, T. L. S., Lu, J., & Zhou, Y. (2021) · Brain · doi:10.1093/brain/awab160 · Cited by 61
Biofluid Biomarkers of Alzheimer’s Disease: Progress, Problems, and Perspectives
Huang, S., Wang, Y., & Guo, J. (2022) · Neuroscience Bulletin · doi:10.1007/s12264-022-00836-7 · Cited by 63
Mander, B. A., Dave, A., Lui, K. K., Sprecher, K. E., Berisha, D. E., Chappel-Farley, M. G., Chen, I. Y., Riedner, B. A., Heston, M. B., Suridjan, I., et al. (2022) · SLEEP · doi:10.1093/sleep/zsac135 · Cited by 62
Determinants of cognitive and brain resilience to tau pathology: a longitudinal analysis
Bocancea, D. I., Svenningsson, A. L., van Loenhoud, A. C., Groot, C., Barkhof, F., Strandberg, O. T., Smith, R. A., Initiative, A. D. N., Weiner, M. W., Aisen, P., et al. (2023) · Brain · doi:10.1093/brain/awad100 · Cited by 59
Proportion of Women and Reporting of Outcomes by Sex in Clinical Trials for Alzheimer Disease
Martínková, J., Quevenco, F., Karcher, H., Ferrari, A., Sandset, E. C., Szoeke, C. E. I., Hort, J., Schmidt, R., Chadha, A. S., & Ferretti, M. T. (2021) · JAMA Network Open · doi:10.1001/jamanetworkopen.2021.24124 · Cited by 65
Belonwu, S., Li, Y., Bunis, D. G., Rao, A. A., Solsberg, C. W., Tang, A., Fragiadakis, G. K., Dubal, D. B., Oskotsky, T., & Sirota, M. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02591-8 · Cited by 55
Menopause hormone therapy significantly alters pathophysiological biomarkers of Alzheimer's disease
Depypere, H. T., Vergallo, A., Lemercier, P., Lista, S., Benedet, A. L., Ashton, N. J., Cavedo, E., Zetterberg, H., Blennow, K., Vanmechelen, E., et al. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12759 · Cited by 61
Ossenkoppele, R., Coomans, E. M., Apostolova, L. G., Baker, S. L., Barthel, H., Beach, T. G., Benzinger, T. L. S., Betthauser, T. J., Bischof, G. N., Bottlaender, M., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-02000-6 · Cited by 60
Self-citationWisch, J. K., Meeker, K. L., Gordon, B. A., Flores, S. E., Dincer, A., Grant, E., Benzinger, T. L. S., Morris, J. C., & Ances, B. M. (2020) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000393 · Cited by 56
Boerwinkle, A. H., Gordon, B. A., Wisch, J., Flores, S., Henson, R. L., Butt, O. H., McKay, N., Chen, C. D., Benzinger, T. L. S., Fagan, A. M., et al. (2023) · The Lancet Neurology · doi:10.1016/s1474-4422(22)00408-2 · Cited by 55
Self-citationBiechele, G., Franzmeier, N., Blume, T., Ewers, M., Medina-Luque, J., Eckenweber, F., Sacher, C., Beyer, L., Ruch, F., Lindner, S., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-02046-2 · Cited by 53
White matter hyperintensities are associated with subthreshold amyloid accumulation
Moscoso, A., Rey-Bretal, D., Silva-Rodríguez, J., Aldrey, J. M., Cortés, J., Pías-Peleteiro, J., Ruibal, Á., & Aguiar, P. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.116944 · Cited by 49
“Amyloid-related tau pathology has been found to be higher in females (Buckley et al., 2019); however, to the best of our knowledge, neither differences in amyloid burden, particularly in the subthreshold regime, nor potential biological mechanisms have been reported before.”
Boccalini, C., Peretti, D. E., Scheffler, M., Mu, L., Griffa, A., Dardel, N. T., Allali, G., Prior, J. O., Ashton, N. J., Zetterberg, H., et al. (2025) · Alzheimer s Research & Therapy · doi:10.1186/s13195-025-01684-z · Cited by 55
Sex differences in Alzheimer’s disease: metabolic reprogramming and therapeutic intervention
Demetrius, L., Eckert, A., & Grimm, A. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.09.004 · Cited by 52
Wang, Y., Therriault, J., Servaes, S., Tissot, C., Rahmouni, N., Macedo, A. C., Arias, J. F., Mathotaarachchi, S. S., Benedet, A. L., Stevenson, J., et al. (2023) · Brain · doi:10.1093/brain/awad397 · Cited by 54
Therriault, J., Pascoal, T. A., Savard, M., Benedet, A. L., Chamoun, M., Tissot, C., Lussier, F. Z., Kang, M. S., Thomas, E. M., Terada, T., et al. (2020) · Neurology · doi:10.1212/wnl.0000000000011081 · Cited by 53
The impact of demographic, clinical, genetic, and imaging variables on tau PET status
Ossenkoppele, R., Leuzy, A., Cho, H., Sudre, C. H., Strandberg, O. T., Smith, R. A., Palmqvist, S., Mattsson, N., Olsson, T., Jögi, J., et al. (2020) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-020-05099-w · Cited by 53
Bollack, A., Pemberton, H., Collij, L. E., Markiewicz, P. J., Cash, D. M., Farrar, G., & Barkhof, F. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13158 · Cited by 51
Mishra, A., Wang, Y., Yin, F., Vitali, F., Rodgers, K. E., Soto, M., Mosconi, L., Wang, T., & Brinton, R. D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101542 · Cited by 48
Sex influences the effects of APOE genotype and Alzheimer’s diagnosis on neuropathology and memory
Duarte‐Guterman, P., Albert, A., Barha, C. K., Galea, L. A. M., & Initiative, O. B. O. T. A. D. N. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2021.105248 · Cited by 48
Sex differences in off-target binding using tau positron emission tomography
Smith, R. A., Strandberg, O. T., Leuzy, A., Betthauser, T. J., Johnson, S. C., Pereira, J. B., & Hansson, O. (2021) · NeuroImage Clinical · doi:10.1016/j.nicl.2021.102708 · Cited by 46
Egroo, M. V., van Hooren, R. W. E., & Jacobs, H. I. L. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-021-00902-8 · Cited by 52
Self-citationWolters, E. E., Dodich, A., Boccardi, M., Corre, J., Drzezga, A. E., Hansson, O., Nordberg, A. K., Frisoni, G. B., Garibotto, V., & Ossenkoppele, R. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-020-05118-w · Cited by 48
Saloner, R., VandeVrede, L. A., Asken, B. M., Paolillo, E. W., Gontrum, E. Q., Wolf, A. A., Lario‐Lago, A., Milà‐Alomà, M., Triana‐Baltzer, G., Kolb, H. C., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13454 · Cited by 49
Parkinson disease clinical subtypes: key features & clinical milestones
Campbell, M. C., Myers, P. S., Weigand, A. J., Foster, E. R., Cairns, N. J., Jackson, J. J., Lessov‐Schlaggar, C. N., & Perlmutter, J. S. (2020) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51102 · Cited by 44
Interactions between vascular burden and amyloid-β pathology on trajectories of tau accumulation
Coomans, E. M., van Westen, D., Binette, A. P., Strandberg, O. T., Spotorno, N., Serrano, G. E., Beach, T. G., Palmqvist, S., Stomrud, E., Ossenkoppele, R., et al. (2023) · Brain · doi:10.1093/brain/awad317 · Cited by 47
The sex-specific interaction of the microbiome in neurodegenerative diseases
Cox, L. M., Abou‐El‐Hassan, H., Maghzi, A. H., Vincentini, J., & Weiner, H. L. (2019) · Brain Research · doi:10.1016/j.brainres.2019.146385 · Cited by 44
Marongiu, R. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00242 · Cited by 47
Disappearing metabolic youthfulness in the cognitively impaired female brain
Beheshti, I., Nugent, S., Potvin, O., & Duchesne, S. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.01.026 · Cited by 40
Sex differences in default mode network connectivity in healthy aging adults
Ficek, B., Horien, C. L., Ju, S., Xu, W., Li, N., Lacadie, C., Shen, X., Scheinost, D., Constable, R. T., & Fredericks, C. A. (2022) · Cerebral Cortex · doi:10.1093/cercor/bhac491 · Cited by 46
Cai, Y. Q., Du, J., Li, A., Zhu, Y., Xu, L., Sun, K., Ma, S., Guo, T., & Initiative, A. D. N. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01178-w · Cited by 41
Sass, D., Guedes, V. A., Smith, E. G., Vorn, R., Devoto, C., Edwards, K. A., Mithani, S., Hentig, J., Lai, C., Wagner, C., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.746491 · Cited by 44
Association of CD14 with incident dementia and markers of brain aging and injury
Pase, M. P., Himali, J. J., Beiser, A., DeCarli, C. S., McGrath, E. R., Satizábal, C. L., Aparicio, H. J., Adams, H. H. H., Reiner, A. P., Longstreth, W. T., et al. (2019) · Neurology · doi:10.1212/wnl.0000000000008682 · Cited by 39
Pereira, J. B., Harrison, T. M., Joie, R. L., Baker, S. L., & Jagust, W. J. (2020) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-019-04669-x · Cited by 40
Subramaniapillai, S., Rajagopal, S., Snytte, J., Otto, A. R., Einstein, G., & Rajah, M. N. (2021) · NeuroImage Clinical · doi:10.1016/j.nicl.2021.102620 · Cited by 44
A Call to Action to Address Sex Differences in Alzheimer Disease Clinical Trials
Buckley, R. F., Gong, J., & Woodward, M. (2023) · JAMA Neurology · doi:10.1001/jamaneurol.2023.1059 · Cited by 38
Self-citationCieri, F., Zhuang, X., Cordes, D., Kaplan, N., Cummings, J. L., Caldwell, J., & Initiative, A. D. N. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-00973-1 · Cited by 41
Emrani, S., & Sundermann, E. E. (2025) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2025.101184 · Cited by 53
Interactive rather than independent effect of APOE and sex potentiates tau deposition in women
Wang, Y., Pascoal, T. A., Therriault, J., Kang, M. S., Benedet, A. L., Savard, M., Tissot, C., Lussier, F. Z., Arias, J. F., Mathotaarachchi, S. S., et al. (2021) · Brain Communications · doi:10.1093/braincomms/fcab126 · Cited by 37
Alzheimer disease seen through the lens of sex and gender
Castro‐Aldrete, L., Einsiedler, M., Martínková, J., Depypere, H. T., Ang, T. F. A., Mielke, M. M., Sindi, S., Eyre, H. A., Au, R., Dimech, A. S., et al. (2025) · Nature Reviews Neurology · doi:10.1038/s41582-025-01071-0 · Cited by 46
Lim, Y. Y., Maruff, P. T., Barthélemy, N. R., Goate, A., Hassenstab, J. J., Sato, C., Fagan, A. M., Benzinger, T. L. S., Xiong, C., Cruchaga, C., et al. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2021.5181 · Cited by 34
Self-citationSex differences in Alzheimer’s disease: plasma MMP-9 and markers of disease severity
Tsiknia, A. A., Sundermann, E. E., Reas, E. T., Edland, S. D., Brewer, J. B., Galasko, D. R., Banks, S. J., & Initiative, A. D. N. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-01106-4 · Cited by 39
In vivo network models identify sex differences in the spread of tau pathology across the brain
Shokouhi, S., Taylor, W. D., Albert, K., Kang, H., Newhouse, P. A., & Initiative, T. A. D. N. (2020) · Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring · doi:10.1002/dad2.12016 · Cited by 35
Microglial heterogeneity in aging and Alzheimer's disease: Is sex relevant?
Delage, C. I., Šimončičová, E., & Tremblay, M. (2021) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2021.03.006 · Cited by 36
Vila‐Castelar, C., Chen, Y., Langella, S., Lopera, F. J., Zetterberg, H., Hansson, O., Dage, J. L., Janelidzde, S., Su, Y., Chen, K., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13314 · Cited by 35
Sex differences in in vivo tau neuropathology in a multiethnic sample of late middle-aged adults
Palta, P., Rippon, B., Tahmi, M., Pardo, M., Johnson, A. S., Tomljanovic, Z., He, H., Laing, K. K., Razlighi, Q. R., Teresi, J. A., et al. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.03.007 · Cited by 33
Scene memory and hippocampal volume in middle-aged women with early hormone loss
Gervais, N. J., Gravelsins, L. L., Brown, A., Reuben, R. B., Karkaby, L., Baker‐Sullivan, E., Mendoza, L., Lauzon, C., Almey, A., Foulkes, W. D., et al. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.05.003 · Cited by 32
Misiura, M. B., Butts, B., Hammerschlag, B. L., Munkombwe, C., Bird, A., Fyffe, M., Hemphill, A., Dotson, V. M., & Wharton, W. (2023) · Neurotherapeutics · doi:10.1007/s13311-023-01408-x · Cited by 35
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.
A language model drew the claims from the paper on 2026-10-18, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-18 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (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
