Thrombopoietin is associated with δ's intercept, and only in Non‐Hispanic Whites

Royall, Donald R.; Palmer, Raymond F.

doi:10.1016/j.dadm.2016.02.003

Cited by 19 publications

(32 citation statements)

References 32 publications

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“…Change in δ scores is strongly associated with change in dementia severity, as measured by CDR [2,3]. Additionally, Koppara et al.…”

Section: Discussionmentioning

confidence: 98%

“…This dEQ homolog has previously been reported to have acceptable factor determinacy by Grice's method [18], to be factor equivalent across ethnicity in this sample with respect to all indicator loadings and several residuals, to be strongly associated with its IADL target (r = 0.89, P < .001), and to correlate strongly with CDR‐SB (r = 0.99, P < .001). The dEQ composite accurately distinguished NC from AD (area under the receiver operating characteristic curve [AUC] = 0.95; 95% confidence interval [CI] = 0.94–0.96) [3].…”

Section: Methodsmentioning

confidence: 99%

“…dEQ's construction and validation in this sample has been previously described [3]. Briefly, dEQ's cognitive indicators included the Controlled Oral Word Association [15], Logical Memory II [16], the Digit Span Test [16], and Wechsler Memory Scale Visual Reproduction I [16].…”

Section: Deq's Construction and Validationmentioning

confidence: 99%

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δ scores predict mild cognitive impairment and Alzheimer's disease conversions from nondemented states

Royall

Palmer²

2017

Alz & Dem Diag Ass & Dis Mo

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IntroductionWe tested the latent variable “δ” (for “dementia”)'s ability to predict conversion to “mild cognitive impairment” (MCI) and Alzheimer's disease (AD).MethodsAn ethnicity equivalent d homolog (“dEQ”) was constructed in n = 1113 Mexican- American (MA) and n = 1958 non-Hispanic white (NHW) participants in the Texas Alzheimer's Research and Care Consortium. “Normal Controls” (NC) (n = 1276) and MCI cases (n = 611) were followed annually for up to 6 years [m = 4.7(0.6)].Results22.0% (n = 281) of NC converted to “MCI” or “AD”. 17.3%( n = 106) of MCI converted to “AD.” Independently of covariates, each quintile increase in the dEQ scores of NC increased the odds of conversion by 52%. Each quintile increase in the dEQ scores of MCI cases increased the odds of conversion to AD almost three-fold.DiscussionBaseline δ scores predict MCI and AD conversions from nondemented states in MA and NHW.

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“…Change in δ scores is strongly associated with change in dementia severity, as measured by CDR [2,3]. Additionally, Koppara et al.…”

Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

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δ scores predict mild cognitive impairment and Alzheimer's disease conversions from nondemented states

Royall

Palmer²

2017

Alz & Dem Diag Ass & Dis Mo

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“…SEM can also address the temporal associations among δ‐related biomarkers. For example, we have shown that THPO, which partially mediates gender's association with δ, is associated with δ's intercept (i.e., in a latent growth curve model) but not its slope [10]. Thus, that serum protein may initiate prospective changes in dementia severity as measured by δ without prosecuting them.…”

Section: Discussionmentioning

confidence: 99%

“…The TARCC has a substantial number of MA participants. MA ethnicity has pronounced effects on serum protein biomarkers in the TARCC [9,10,29]. There are no racial distinctions in the TARCC, and no reported racial effects on plasma protein biomarkers in the ADNI.…”

Section: Methodsmentioning

confidence: 99%

Blood‐based protein predictors of dementia severity as measured by δ: Replication across biofluids and cohorts

Bishnoi

Pavlik

Massman

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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Introduction Dementia severity can be empirically described by the latent dementia phenotype “δ” and its various composite “homologs”. We have explored δ's blood‐based protein biomarkers in the Texas Alzheimer's Research and Care Consortium (TARCC) study. However, it would be convenient to replicate those associations in the Alzheimer's Disease Neuroimaging Initiative (ADNI). To this end, we recently engineered a δ homolog from observed cognitive performance measures common to both projects (i.e., “dT2A”). Methods We used nine rationally chosen peripheral blood‐based protein biomarkers as indicators of a latent variable “INFLAMMATION”. We then associated that construct with dT2A in structural equation models adjusted for age, gender, depressive symptoms, and apolipoprotein E (APOE) ε4 allelic burden. Significant factor loadings and INFLAMMATION's association with dT2A were confirmed in random splits of TARCC's relatively large sample, and across biofluids in the ADNI. Results Nine proteins measured in serum (TARCC) or plasma (ADNI) explained ≅10% of dT2A's variance in both samples, independently of age, APOE, education, and gender. All loaded significantly on INFLAMMATION, and positively or negatively, depending on their known roles are PRO‐ or ANTI‐inflammatory proteins, respectively. The parameters of interest were confirmed across random 50% splits of the TARCC's sample, and replicated across biofluids in the ADNI. Discussion These results suggest that SEM can be used to replicate biomarker findings across samples and biofluids, and that a substantial fraction of dementia's variance is attributable to peripheral blood‐based protein levels.

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Statin use moderates APOE's and CRP's associations with dementia and is associated with lesser dementia severity in ε4 carriers

Royall,

Palmer

2023

Alzheimer's & Dementia

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INTRODUCTIONWe tested the effect of statins on C‐reactive protein (CRP) and apolipoprotein E (APOE)'s associations with dementia severity.METHODSA total of 1725 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI) were assigned from 12‐month follow‐up data into the following groups: (1) ε4 (–)/statin (–), (2) ε4 (–)/statin (+), (3) ε4 (+)/statin (–), and (4) ε4 (+)/statin (+). Dementia severity was assessed by a δ homolog: “dHABS.” A mediation model was stratified on statin use and moderation effects tested by a chi‐square difference.RESULTSPlasma CRP level decreased with ε4 allelic dose. Statins had no effect on the dHABS d‐score in non‐carriers but were associated with better scores in carriers. Treated carriers did not have more severe dementia than non‐carriers. Statin use moderated the mutual adjusted effects of APOE and CRP. CRP was not a mediator of APOE's effect.DISCUSSIONStatins may provide a protective effect on the dementia severity of ε4 carriers.Highlights δ is a dementia‐specific phenotype related to general intelligence “g” and is assessed via a “d‐score.” Apolipoprotein E (APOE) and plasma C‐reactive protein (CRP) are independently associated with δ. Plasma CRP decreases with ε4 allelic dose. Statins were associated with better (less demented) d‐scores in ε4 carriers but had no effect in non‐ε4 carriers. Treated ε4 carriers did not have more severe dementia than non‐carriers. Statin use moderated the effects of APOE and CRP on δ. CRP was not a mediator of APOE's effect on δ.

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Thrombopoietin is associated with δ's intercept, and only in Non‐Hispanic Whites

Cited by 19 publications

References 32 publications

δ scores predict mild cognitive impairment and Alzheimer's disease conversions from nondemented states

δ scores predict mild cognitive impairment and Alzheimer's disease conversions from nondemented states

Blood‐based protein predictors of dementia severity as measured by δ: Replication across biofluids and cohorts

Statin use moderates APOE's and CRP's associations with dementia and is associated with lesser dementia severity in ε4 carriers

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