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Cited by 7Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCerebrovascular and genetic disorders

Amyloid-PET and White Matter Hyperintensities Have Independent Effects on Baseline Cognitive Function and Synergistic Effects on Longitudinal Executive Function

Open access
Ali, Doaa G., Abner, Erin L., Bahrani, Ahmed A., El Khouli, Riham, Gold, Brian T., Jiang, Yang, Wilcock, Donna M., Jicha, Gregory A.·2023·Brain Sciences
DOI 10.3390/brainsci13020218PMC PMC9953773
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Abstract

Co-occurrence of beta amyloid (Aβ) and white matter hyperintensities (WMHs) increase the risk of dementia and both are considered biomarkers of preclinical dementia. Moderation and mediation modeling were used to define the interplay between global and regional Aβ and WMHs measures in relation to executive function (EF) and memory composite scores outcomes at baseline and after approximately 2 years across a sample of 714 clinically normal participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI 2). The moderation regression analysis showed additive effects of Aβ and WMHs over baseline memory and EF scores (p = 0.401 and 0.061, respectively) and synergistic effects over follow-up EF (p < 0.05). Through mediation analysis, the data presented demonstrate that WMHs effects, mediated by global and regional amyloid burden, are responsible for baseline cognitive performance deficits in memory and EF. These findings suggest that Aβ and WMHs contribute to baseline cognition independently while WMHs volumes exert effects on baseline cognitive performance directly and through influences on Aβ accumulation.

AI snapshot

Written from the paper’s full text.

TL;DR

In 714 clinically normal ADNI 2 participants, amyloid-PET burden and white matter hyperintensities showed independent associations with baseline memory and executive function, plus a synergistic interaction for longitudinal executive function. Mediation analyses suggested WMH effects on baseline cognition were partly mediated by global and regional amyloid burden.

Key findings

  • Moderation analyses found no significant global Aβ×WMH interaction for baseline memory (p = 0.401) or baseline executive function (p = 0.061), but a significant interaction for follow-up executive function (p = 0.036); regional follow-up EF interactions were significant for frontal Aβ (p = 0.033) and cingulate Aβ (p = 0.024).
  • Follow-up memory showed no significant Aβ×WMH interaction (p = 0.937), and regional Aβ×WMH interactions with baseline memory were also nonsignificant (frontal p = 0.360, parietal p = 0.353, cingulate p = 0.411).
  • Mediation analysis showed global Aβ mediated the relationship between WMHs and baseline EF (indirect effect a × b = −0.045; 95% CI −0.09, −0.01) and baseline memory (CI −0.01, −0.006); frontal and parietal Aβ also mediated baseline EF and memory, while cingulate Aβ did not.
  • Follow-up mediation was not significant: global Aβ indirect effects crossed zero for follow-up EF (a × b = −0.015; CI −0.045, 0.009) and follow-up memory (CI −0.031, 0.002). WMH volumes correlated weakly with global Aβ (r = 0.162), frontal Aβ (r = 0.155), cingulate Aβ (r = 0.130), and parietal Aβ (r = 0.177).

Methods

  • Used ADNI 2 data from 714 clinically normal participants (326 women, 388 men; mean age 73.13 ± 7.4 years; education 16.3 ± 2.6 years) with MMSE ≥ 26, complete demographics/ApoE, baseline and approximately 2-year EF and memory composites, florbetapir PET, and T2 FLAIR WMH quantification.
  • WMHs were quantified via 4-tissue segmentation; florbetapir SUVr was calculated globally and in frontal, parietal, and cingulate regions; cognition used ADNI-EF and ADNI-Memory composites.
  • Moderation regressions used Hayes’ PROCESS model 1, and mediation models used model 4 with 5,000 bootstrap samples; covariates included age, sex, education, ApoE, and total intracranial volume, with longitudinal models also adjusting for baseline cognition and time between tests.

Limitations

  • The paper states possible selection bias because ADNI excludes participants with significant cerebrovascular disease, limiting generalizability; it also notes the sample is relatively small for moderation analyses and the follow-up period is relatively short.
  • The paper states further studies are needed in participants with higher CSVD burden, including lacunes, small subcortical infarctions, microinfarcts, and microbleeds, and with longer follow-up across MCI and early dementia stages.
  • Evident from the text: the mediation models assume a causal ordering from WMH to Aβ deposition to cognition, but the observational design cannot establish causality; the sample is also highly educated and relatively homogeneous.

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

Integrity signals

Registry

Crossref · 10.3390/brainsci13020218

Cites

52 of 52 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

16 of 21 cited sources checked · 3 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    WMHs often occur prior to the presence of amyloid-β plaques in preclinical AD.

    “findings from previous studies have also shown that WMHs often occur prior to the presence of amyloid-β plaques in preclinical AD [19,20,21]”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [19] Lee, 2016, White matter hyperintensities are a core feature of Alzheimer’s disease: Evidence from the dominantly inherited Alzheimer network, Ann. Neurol. source

      The Results and Discussion (page not available in our copy) place global WMH increases after detectable CSF amyloid abnormalities, with posterior WMH increases occurring at about the same time—not before. The study does not directly establish when amyloid-β plaques first appear, so its biomarker findings do not support the claimed plaque sequence. (LLM, conf=0.77)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [20] Sotero, 2016, Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis, Nat. Commun. source

      The Results (Multifactorial biomarker ordering in LOAD progression) place vascular dysregulation before Aβ deposition. But the Discussion says the analysis did not evaluate white-matter alterations, so it does not establish that WMHs specifically precede amyloid plaques in preclinical AD or that this often occurs. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [21] Moscoso, 2020, White matter hyperintensities are associated with subthreshold amyloid accumulation, Neuroimage source
  • Premisecitation

    The majority of published studies have emphasized the spatial heterogeneity of WMHs but have left the potential heterogeneous influences of regional Aβ deposition relatively unexplored.

    “The majority of published studies have emphasized the spatial heterogeneity of WMHs [25,26], but have left the potential heterogeneous influences of regional Aβ deposition relatively unexplored.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [25] Sudre, 2021, Brain amyloid and vascular risk are related to distinct white matter hyperintensity patterns, J. Cereb. Blood Flow Metab. source

      The Introduction and Discussion > Interpretation describe prior studies of regional WMH patterns, and this paper itself examines WMH distribution. They support the citation as an example of work on spatial heterogeneity, but do not establish that a majority of published studies emphasized it. The citation is attached to that first clause, not the subsequent claim about regional Aβ deposition. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [26] Weaver, 2019, Cerebral amyloid burden is associated with white matter hyperintensity location in specific posterior white matter regions, Neurobiol. Aging source

      The Introduction describes prior studies of differing WMH locations across conditions, supporting the citation’s point that spatial heterogeneity has received attention. It does not establish that a majority of published studies emphasized this topic. Its discussion of limited amyloid-related research concerns overall amyloid burden and WMH location, not specifically the heterogeneous influences of regional Aβ deposition. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Premisecitation

    Co-occurrence of beta amyloid (Aβ) and white matter hyperintensities (WMHs) increases the risk of dementia.

    “Co-occurrence of beta amyloid (Aβ) (a hallmark pathologic feature of AD) and white matter hyperintensities (WMHs) (reflecting CSVD burden) increase the risk of dementia [5].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [5] Iadecola, 2010, The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia, Acta Neuropathol. source

      In “Does the vascular pathology worsen the cognitive dysfunction in AD?” (page unavailable), the review says ischemic white matter lesions alongside AD pathology are associated with greater cognitive impact and more severe dementia. It does not specifically identify those lesions as MRI-defined WMHs or establish that co-occurring Aβ and WMHs increase the risk of developing dementia. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
  • Interpretationcitation

    The relation between regional Aβ burden and WMHs' effect on future EF change might be explained by WMHs' impacts on connectivity within the executive control and default mode networks.

    “These data suggest that this relation might be explained by WMHs’ impacts on connectivity within the executive control, and default mode networks [44].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [44] Lin, 2020, The effect of amyloid deposition on longitudinal resting-state functional connectivity in cognitively normal older adults, Alzheimers Res. Ther. source

      The Results (page unavailable) link amyloid, connectivity, and executive function, while the Introduction discusses amyloid-related default mode connectivity. They do not show that WMHs affect connectivity within the executive control or default mode networks, or that such an effect explains future executive-function change. In Table 2, the time-by-WMH interaction for the connectivity measured was not significant. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Interpretationown data

    Executive function performance is dependent on both intact white matter pathway connectivity and pathologic integrity of the cortical regions themselves.

    “Indeed, the present findings support the hypothesis that executive function performance is dependent on both intact white matter pathway connectivity, as well as pathologic integrity of the cortical regions themselves [12,45,46]”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [12] Kim, 2015, Clinical effect of white matter network disruption related to amyloid and small vessel disease, Neurology source
    • cites [45] Wang, 2020, The effect of white matter signal abnormalities on default mode network connectivity in mild cognitive impairment, Hum. Brain Mapp. source

      The Introduction (page unavailable) says functional connectivity depends on intact white matter pathways and cortical structural integrity. The Results (page unavailable) associate medial prefrontal connectivity with executive-function test performance. The paper does not establish that executive performance itself depends on both structural factors, so the claim extends its connectivity finding to performance. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [46] Kumar, 2020, Differential Effects of Confluent and Nonconfluent White Matter Hyperintensities on Functional Connectivity in Mild Cognitive Impairment, Brain Connect. source
  • Classified as probably not a substantial claim. 14
  • May combine two claims. 9

  • Classified as probably not a substantial claim.

    Premisecitation

    The relationship between WMHs and Aβ is strongly determined by the spatial distribution of the two pathologies.

    “evidence from recent studies has suggested that the relationship between WMHs and Aβ is strongly determined by the spatial distribution of the two pathologies [24]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [24] Lorenzini, 2022, Regional associations of white matter hyperintensities and early cortical amyloid pathology, Brain Commun. source

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

    Premisecitation

    WMHs in all cortical regions (frontal, occipital, parietal and temporal) are associated with deficits in executive function scores.

    “Previous studies investigating the impact of regional distribution of WMHs on executive function (EF) found that WMHs in all cortical regions (frontal areas, occipital, parietal and temporal) are associated with deficits in EF scores [15,16,17]”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [15] Sudre, 2020, Patterns of white matter hyperintensities associated with cognition in middle-aged cognitively healthy individuals, Brain Imaging Behav. source
    • cites [16] Bougacha, 2020, White matter hyperintensities across the adult lifespan: Relation to age, Aβ load, and cognition, Alzheimers Res. Ther. source

      The Results section (“Associations between WMH and cognition”; page unavailable) links frontal WMH to worse executive-function performance. Parietal and occipital associations did not survive correction for multiple comparisons, and Table 4 shows no significant temporal association. The claim therefore overstates the evidence by saying the association holds in all four regions. (LLM, conf=0.92)

      Experimental — accuracy not yet measured
    • cites [17] Tullberg, 2004, White matter lesions impair frontal lobe function regardless of their location, Neurology source

      The Results (Executive function; page unavailable) associate frontal, parietal and occipital WMHs with lower executive scores in nondemented subjects, but report no significant relationship in demented subjects. They do not establish a separate temporal-region association, and the orbitofrontal association was not significant. The claim omits these limits. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    WMHs and Aβ are key drivers of cognitive decline in healthy older adults and both are considered biomarkers of preclinical dementia.

    “WMHs and Aβ are also key drivers of cognitive decline in healthy older adults, and both are considered biomarkers of preclinical dementia [6,7].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [6] Vemuri, 2015, Vascular and amyloid pathologies are independent predictors of cognitive decline in normal elderly, Brain source

      The Discussion (page not provided) reports that cerebrovascular and amyloid pathologies had additive, similarly sized effects on cognitive decline in cognitively normal older adults. The Imaging biomarkers methods (page not provided) use WMHs as part of the vascular measure, alongside infarcts, and amyloid PET as the amyloid measure. The paper does not establish that WMHs and Aβ are both considered biomarkers of preclinical dementia. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [7] Hedden, 2012, Cognitive profile of amyloid burden and white matter hyperintensities in cognitively normal older adults, J. Neurosci. source

      The Discussion (page not provided) reports associations between amyloid burden and memory and between WMHs and executive function in cognitively normal older adults. It describes these effects as small and notes that substantial age-related differences in cognition remain unexplained, so the cross-sectional findings do not establish that either is a key driver of decline. The Abstract calls both potential early indicators of age-related neurological disorders, but does not establish both as biomarkers of preclinical dementia. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

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

    Premisecitation

    In cognitively normal participants with low WMH volumes, memory performance underwent low to no changes independent of amyloid burden.

    “One previous study showed that CN participants with low WMH volumes underwent low to no changes in memory performance, independent of amyloid burden [11].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [11] Han, 2020, Association of vascular brain injury, neurodegeneration, amyloid, and cognitive trajectory, Neurology source

  • May combine two claims.

    Interpretationown data

    WMHs play an important role as a risk factor for future memory decline even if they may not affect baseline memory performance at the stage of pAD.

    “These findings emphasize the important role of WMHs as a risk factor for future memory decline even if they may not affect baseline memory performance at the stage of pAD [11,49].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [11] Han, 2020, Association of vascular brain injury, neurodegeneration, amyloid, and cognitive trajectory, Neurology source

      The Results section (page not available) reports that WMH volume was associated with later episodic-memory trajectories, while no brain measure was associated with baseline episodic memory. However, the study examined cognitively normal individuals, not people at the pAD stage, so it does not establish the claim for that population. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [49] Kumar, 2022, APOE4 and Confluent White Matter Hyperintensities Have a Synergistic Effect on Episodic Memory Impairment in Prodromal Dementia, J. Alzheimer’s Dis. source

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

    Premisecitation

    In demented participants, the association between WMH volumes and both EF and memory function was significant, but the relationship between memory and WMHs was not detected in cognitively normal participants.

    “findings from another study have demonstrated that the association between WMH volumes and both EF and memory function were significant in demented participants, but that the relationship between memory and WMHs was not detected in CN participants, such as those included in the present study [43].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [43] Carmichael, 2012, MRI predictors of cognitive change in a diverse and carefully characterized elderly population, Neurobiol. Aging source

      The Discussion reports an association of greater WMH volume with poorer episodic memory and executive function in the heterogeneous cohort. The Results also report models adjusted for clinical diagnosis, but do not establish that both associations were significant specifically in demented participants or that the WMH–memory association was absent in cognitively normal participants. The cited subgroup contrast is therefore unsupported. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    Neither global nor regional Aβ SUVr mediates the relationship between WMHs and follow-up cognitive (EF and memory) scores.

    “Results demonstrated that neither global Aβ SUVr (see Figure 2C,D) nor regional Aβ SUVr mediates these associations as the CI for the indirect effect was crossing the zero and did not reach statistical significance.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: WMH is causally related to Aβ deposition, which is in turn causally related to cognitive (ADNI-EF or ADNI-Memory) scores.

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

    Findingown data

    The Pearson correlation between parietal Aβ and WMH volumes was 0.177.

    “Finally, in Figure 3D the Pearson correlation between parietal Aβ and WMH volumes was 0.177.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Aβ burden was the only predictor of follow-up EF performance and baseline memory performance.

    “but that Aβ burden was the only predictor of follow-up EF performance and baseline memory performance (See Supplementary Tables S1 and S2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Aβ and WMHs have independent effects on baseline cognitive performance and a synergistic interaction on future EF performance.

    “The present results indicate that there is an independent effect of both Aβ and WMHs on cognitive performance at baseline and a synergistic interaction between these baseline biomarkers of pathology on future EF performance.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    A total of 53 participants were excluded from the longitudinal analysis due to missing data required for the analysis.

    “A total of 53 participants were excluded from the longitudinal analysis on the basis of missing data required for the analysis.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Age, sex, education, ApoE and total intracranial volumes were entered as covariates in all analyses.

    “Age (continuous values), sex (indicator variable), education (continuous values), ApoE (dummy indicator variable) and total intracranial volumes (continuous values) were entered as covariates in all analyses.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    WMH accumulation appears to increase Aβ deposition, which in turn influences cognition longitudinally.

    “Thus, WMH accumulation appears to increase Aβ deposition which in turn influences cognition longitudinally.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: WMH is causally related to Aβ deposition, which is in turn causally related to cognitive (ADNI-EF or ADNI-Memory) scores.

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

    Study design and conductown data

    The present study used ADNI data allowing analysis in a large sample of relatively homogeneous CN participants that have been classified extensively for the presence of pAD and CSVD.

    “Strengths of the present study include the use of ADNI data allowing analysis in a large sample of relatively homogeneous CN participants that have been classified extensively for the presence of pAD and CSVD.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Mediation models used 5000 bootstrap samples to calculate bias-corrected 95% confidence intervals.

    “Significance was tested using 5000 bootstrap samples to calculate bias-corrected 95% confidence intervals.”
    Quote in the paperSubstantial claim

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

    Interpretationreasoning

    The synergistic effect on follow-up EF but not memory may be related to the population studied, as ADNI participants are largely well-educated and ADNI excludes participants with severe CSVD.

    “This finding may be related to the population studied as ADNI participants are largely well-educated and ADNI excludes participants with severe CSVD.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: ADNI participants are largely well-educated and ADNI excludes participants with severe CSVD.

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

    Study design and conductown data

    Excluded participants did not differ significantly from included participants in age, sex, education, ApoE or baseline MMSE scores.

    “Excluded participants did not differ significantly from these included in the analysis in regards to age, sex, education, ApoE or baseline MMSE scores (data not shown).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The present study used both mediation and moderation analyses in studying the relation between cognitive function and the effects of the two primary drivers of dementia in the population (Aβ and WMHs) within discrete brain regions.

    “An additional strength is the use of both mediation and moderation analyses in studying the relation between cognitive function and the effects of the two primary drivers of dementia in the population (Aβ and WMHs) within discrete brain regions.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Longitudinal analyses controlled for baseline ADNI cognitive scores and time following baseline scan acquisitions and cognitive testing.

    “Longitudinal analyses examined the association of the interaction between baseline Aβ burden and WMHs with mean follow-up cognitive (ADNI-EF or ADNI-Memory) scores after controlling for baseline ADNI cognitive scores and time following the baseline scan acquisitions and cognitive testing.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Longitudinal outcome analyses may be limited by the relatively short follow-up period in the ADNI 2 participants studied.

    “Longitudinal outcome analyses may also be limited by the relatively short follow-up period in the ADNI 2 participants studied.”
    Quote in the paperNot a substantial claim
20 of 20

  • The authors state this as an assumption.

    WMH is causally related to Aβ deposition, which is in turn causally related to cognitive (ADNI-EF or ADNI-Memory) scores.

    “Assuming that WMH is causally related to Aβ deposition, which is in turn causally related to cognitive (ADNI-EF or ADNI-Memory) scores, mediation models were built to estimate the relationship between WMH (independent variable) and cognitive function (dependent variable) and Aβ (mediator variable).”

  • The paper relies on this without support.

    ADNI participants are largely well-educated and ADNI excludes participants with severe CSVD.

    “This finding may be related to the population studied as ADNI participants are largely well-educated and ADNI excludes participants with severe CSVD.”
2 of 2

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.

  • Baseline memory association of WMHs is reported inconsistently

    Major

    The discussion says Aβ burden was the only predictor of baseline memory performance, but the conclusion says both Aβ burden and WMH volumes had independent associations with baseline memory scores.

  • Longitudinal mediation claim conflicts with the reported results

    Major

    The discussion describes WMH-related Aβ deposition as influencing cognition longitudinally, but the longitudinal mediation analysis reports no significant indirect effect through global or regional Aβ.

2 of 2

Cites

Flagged first, then by citations

2 of the 54 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Gibbons, 2012, Composite measures of executive function and memory: ADNI_EF and ADNI_Mem, Alzheimer’s Dis. Neuroimaging Initiat., 6, 517

Cited by

Sorted by citations

Related

Authors
Ali, D. G., Abner, E. L., Bahrani, A. A., El Khouli, R., Gold, B. T., Jiang, Y., Wilcock, D. M., & Jicha, G. A.
Affiliations
  • University of Kentucky (US)
  • Department of Radiology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA
Corresponding author
Ali, Doaa G.
ORCID
Venue
Brain Sciences
Publisher
MDPI AG
Published
2023-01-28
Volume
13
Issue
2
Pages
218
ISSN
2076-3425 (ISSN-L)
DOI
10.3390/brainsci13020218
PMC
PMC9953773
OpenAlex
W4318476835
Semantic Scholar
7057ca17c97570e073119bcaacc6fa1221e3ea17
Cited by
7
References
54
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2023: 1
FWCI
1.26
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Sciences (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
NIH P30 AG072946 , Robert T. &amp; Nyles Y. McCowan and the B. Wayne Hughes Memorial Fund. (P30 AG072946)
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 › Neurology › Cerebrovascular and genetic disorders
Keywords
amyloid PET, amyloid-beta, white matter hyperintensities, executive function, memory, preclinical dementia, dementia biomarkers, baseline cognitive function, longitudinal cognitive change, Alzheimer's disease, mediating and moderating effects

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

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