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Cited by 373Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsMedical Imaging Techniques and Applications

Sex Differences in the Association of Global Amyloid and Regional Tau Deposition Measured by Positron Emission Tomography in Clinically Normal Older Adults

Open access
Buckley, Rachel F., Mormino, Elizabeth C., Rabin, Jennifer S., Hohman, Timothy J., Landau, Susan, Hanseeuw, Bernard J., Jacobs, Heidi I. L., Papp, Kathryn V. +13 more·2019·JAMA Neurology
DOI 10.1001/jamaneurol.2018.4693PMC PMC6515599
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Abstract

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.

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

Crossref · 10.1001/jamaneurol.2018.4693

Cites

50 of 50 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

24 of 27 cited sources checked · 16 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Sex differences in Aβ burden alone have not been reported in older adults.

    “Sex differences in Aβ burden alone have not been reported in older adults,11–13”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [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

      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)

      Experimental — accuracy not yet measured
    • cites [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
    • cites [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
  • Premisecitation

    Sex differences may be more likely to appear downstream after the onset of Aβ accumulation.

    “supporting the notion that sex differences may be more likely to appear downstream after the onset of Aβ accumulation.5,10”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [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

      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)

      Experimental — accuracy not yet measured
    • cites [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
  • Premisecitation

    Mounting evidence suggests that women are at heightened risk for exhibiting Alzheimer disease pathophysiology.

    “although mounting evidence suggests that women are at heightened risk for exhibiting AD pathophysiology.5–8”
    Quote in the paperSubstantial claim3 of 4 sources checked
    • cites [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
    • cites [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
    • cites [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
    • cites [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
  • Premisecitation

    In clinically normal older adults and individuals with mild cognitive impairment, higher cerebrospinal fluid tau levels have been observed in female APOE ε4 carriers compared with male carriers.

    “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.”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [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
    • cites [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 (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)

      Experimental — accuracy not yet measured
    • cites [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
  • Premisecitation

    The cross-sectional association between regional tau PET and global Aβ PET is well-characterized.

    “we examined the influence of sex to modify the well-characterized cross-sectional association between regional tau PET and global Aβ PET.14–16”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [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
    • cites [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 source

      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)

      Experimental — accuracy not yet measured
    • cites [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
  • Classified as probably not a substantial claim. 16
  • May combine two claims. 12

  • Classified as probably not a substantial claim.

    Premisecitation

    Sex differences exist in brain morphology.

    “As sex differences exist in brain morphology,33”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [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

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

    Premisecitation

    APOE ε4 is highly associated with Aβ.

    “given that APOE ε4 is highly associated with Aβ,45”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [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

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

    Findingown data

    Women exhibited higher scores on logical memory delayed recall in the HABS clinically normal group.

    “Women exhibited higher scores on logical memory delayed recall in the HABS clinically normal group (Table 1)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In ADNI, a sex × APOE ε4 interaction was found with the tau meta-ROI (β = −0.30; 95% CI, −0.58 to −0.02; P = .04), whereby the association between APOE ε4 and tau retention was stronger among women compared with men.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Neither cohort showed significant interactions of sex × Aβ or sex × APOE on either extratemporal ROI.

    “Neither cohort showed significant interactions of sex × Aβ or sex × APOE on either extratemporal ROI.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There was no sex-Aβ interaction on either inferior temporal tau or the tau meta-ROI in HABS.

    “There was no sex-Aβ interaction on either IT tau or the meta-ROI.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    No sex differences were found in demographics in the ADNI clinically normal group.

    “however, no sex differences were found in demographics in the ADNI clinically normal group.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    HABS and ADNI clinically normal individuals did not differ by age, sex, Aβ+ status, or APOE ε4 status.

    “but did not differ by age, sex, Aβ+ status, or APOE ε4 status.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Clinically normal men in the ADNI group showed lower dynamic range for Aβ and lower inferior temporal tau retention compared with women.

    “Clinically normal men in the ADNI group, for instance, showed lower dynamic range for Aβ and lower IT tau retention compared with women.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The 10% sex difference in entorhinal cortex tau was hit within the Aβ cut-off in ADNI but far above the established cutoff in HABS.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    The ADNI clinically normal group were older, exhibited lower memory performance, and had greater dynamic range in tau SUVrs than the HABS clinically normal cohort.

    “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”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    Separate analyses including APOE were run because of missing APOE genotype data.

    “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).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In a 2018 meta-analysis of multiple independent cohorts with CSF data, Hohman and colleagues found greater CSF total and phosphorylated tau in female APOE ε4 carriers than male carriers, with findings driven by abnormal levels of β-amyloid.

    “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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Hohman and colleagues10

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

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

    Study design and conductown data

    Sex × Aβ × APOE interactions were not included as a stand-alone analysis owing to low statistical power; they were included as an exploratory meta-analysis estimate.

    “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.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Post hoc analyses using robust linear regression examined the influence of outliers.

    “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.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The study covaried for scan interval in analyses because some participants had a delay of longer than a year between tau and Aβ scans.

    “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.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Hierarchical linear regressions adjusted for age and delay between tau and Aβ scans.

    “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).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The interaction was dependent on partial volume correction for the NCs from both cohorts, suggesting that partial volume adjustment facilitates detection of this association at lower levels of tau.

    “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.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    We did not have statistical power to robustly assess the issue of survival bias.

    “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.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    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.

    “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.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    A strength of this study is the replication of our findings across 2 independent studies of aging with Aβ and tau PET.

    “A strength of this study is the replication of our findings across 2 independent studies of aging with Aβ and tau PET.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    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.

    “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.”
    Quote in the paperSubstantial claim

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

    Interpretationcitation

    Animal and cellular models of AD support a female-specific vulnerability to AD pathophysiology.

    “Together, these animal and cellular models of AD support a female-specific vulnerability to AD pathophysiology.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    These cohorts are convenience samples and involve recruitment and sampling biases that may result in a lack of generalizability of findings.

    “However, these cohorts are convenience samples and involve recruitment and sampling biases that may result in a lack of generalizability of findings.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Animal models of AD have often reported sex differences in Aβ and tau deposition.

    “Animal models of AD have often reported sex differences in Aβ and tau deposition.”
    Quote in the paperNot a substantial claim
25 of 25

  • 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.”
1 of 1

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

    Minor

    The 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

  • Overall mean age is below both cohort mean ages

    Minor

    The 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.

  • Stated PET acquisition duration conflicts with volume timings

    Minor

    The specified volumes total 12 × 15 + 57 × 60 = 3720 seconds, or 62 minutes, rather than four hours.

3 of 3

Cites

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Related

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
Venue
JAMA Neurology
Publisher
American Medical Association (AMA)
Published
2019-05-01
Volume
76
Issue
5
Pages
542
ISSN
2168-6149 (ISSN-L)
DOI
10.1001/jamaneurol.2018.4693
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
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
  • Health Sciences › Medicine › Physiology › 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

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