Development and validation of risk index for cognitive decline using blood-derived markers

Nettiksimmons, Jasmine; Ayonayon, Hilsa N.; Harris, Tamara B.; Phillips, Caroline; Rosano, Caterina; Satterfield, Suzanne; Yaffe, Kristine

doi:10.1212/wnl.0000000000001263

Cited by 11 publications

(6 citation statements)

References 37 publications

(31 reference statements)

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“…Therefore, low plasma KB levels may be a potential biomarker for AD pathology in individuals with preclinical sporadic AD or reversible CF. A cummulative risk index, including blood-derived markers ApoE ε4 and Aβ42/40, telomere length, blood glucose, cystatin, C-reactive protein, interleukin (IL)-6 and albumin ( 39 ), may provide valuable predictive information regarding future cognitive trajectories independent of age and baseline cognitive status. It is a question worthy of further research whether this same risk index could also predict CF.…”

Section: Resultsmentioning

confidence: 99%

Potential fluid biomarkers for pathological brain changes in Alzheimer's disease: Implication for the screening of cognitive frailty

Ruan

Sancarlo

Greco

et al. 2016

Molecular Medicine Reports

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Cognitive frailty (CF) overlaps with early neuropathological alterations associated with aging-related major neurocognitive disorders, including Alzheimer's disease (AD). Fluid biomarkers for these pathological brain alterations allow for early diagnosis in the preclinical stages of AD, and for objective prognostic assessments in clinical intervention trials. These biomarkers may also be helpful in the screening of CF. The present study reviewed the literature and identified systematic reviews of cohort studies and other authoritative reports. The selection criteria for potentially suitable fluid biomarkers included: i) Frequent use in studies of fluid-derived markers and ii) evidence of novel measurement techniques for fluid-derived markers. The present study focused on studies that assessed these biomarkers in AD, mild cognitive impairment and non-AD demented subjects. At present, widely used fluid biomarkers include cerebrospinal fluid (CSF), total tau, phosphorylated tau and amyloid-β levels. With the development of novel measurement techniques and improvements in understanding regarding the mechanisms underlying aging-related major neurocognitive disorders, numerous novel biomarkers associated with various aspects of AD neuropathology are being explored. These include specific measurements of Aβ oligomer or monomer forms, tau proteins in the peripheral plasma and CSF, and novel markers of synaptic dysfunction, neuronal damage and apoptosis, neuronal activity alteration, neuroinflammation, blood brain barrier dysfunction, oxidative stress, metabolites, mitochondrial function and aberrant lipid metabolism. The proposed panels of fluid biomarkers may be useful in the early diagnosis of AD, prediction of the progression of AD from preclinical stages to the dementia stage, and the differentiation of AD from non-AD dementia. In combination with physical frailty, the present study surmised that these biomarkers may also be used as biomarkers for CF, thus contribute to discovering causes and informing interventions for cognitive impairment in individuals with CF.

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Section: Resultsmentioning

confidence: 99%

Potential fluid biomarkers for pathological brain changes in Alzheimer's disease: Implication for the screening of cognitive frailty

Ruan

Sancarlo

Greco

et al. 2016

Molecular Medicine Reports

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“…Insulin resistance and raised inflammatory cytokines are associated with subsequent cardiovascular disease events, and possibly with impaired cognitive function. (31–34)…”

Section: Discussionmentioning

confidence: 99%

Comparison of Associations of DXA and CT Visceral Adipose Tissue Measures With Insulin Resistance, Lipid Levels, and Inflammatory Markers

Schousboe

Langsetmo

Schwartz

et al. 2017

Journal of Clinical Densitometry

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Background Visceral adipose tissue (VAT) measured by computed tomography (CT) is related to insulin resistance, lipids, and serum inflammatory markers. Our objective was to compare the strength of the associations of visceral adipose tissue (VAT) measured with dual energy x-ray absorptiometry (DXA-VAT) and computed tomography (CT-VAT) with insulin resistance, serum lipids, and serum markers of inflammation. Methodology For 1,117 men age 65 and older enrolled in the Study of Osteoporotic Fractures in Men (MrOS), the cross-sectional associations of DXA-VAT and CT-VAT with Homeostasis Model Assessment of insulin resistance (homa2ir), C-reactive protein (CRP), and HDL cholesterol were estimated with regression models, and compared using a Hausmann test. Results Adjusted for age and body mass index (BMI), DXA-VAT was moderately associated with homa2ir (effect size 0.38, 95% C.I. 0.28 to 0.47) and modestly associated with HDL cholesterol (DXA effect size −0.29, 95% C.I. −0.38 to −0.21). These associations were significantly greater than for CT-VAT with homa2ir (0.30, 95% C.I. 0.24 to 0.37; p-value for effect size difference 0.03) and CT-VAT with HDL cholesterol (-0.22, 95% C.I. −0.29 to −0.15; p-value for difference 0.005). Neither DXA-VAT nor CT-VAT were associated with CRP after adjustment for age and BMI (DXA-VAT effect size 0.14, 95% C.I. −0.04 to 0.32; CT-VAT effect size 0.08, 95% C.I. −0.08 to 0.25; p-value for difference 0.35). Conclusion DXA-VAT has similar or greater associations with insulin resistance, and HDL cholesterol as does CT-VAT in older men, confirming the concurrent validity of DXA-VAT. Investigations of how well DXA measurements of VAT predict incident cardiovascular disease events are warranted.

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“…One study used a panel of 4 plasma biomarkers to predict the progression through early-stage AD, but this panel demonstrated a sensitivity (true positive rate) of only 74% [ 16 ]. A longitudinal study of cognitive decline in older adults used a panel of 8 blood-based markers, including APOE, plasma amyloid β 42/40 ratio, telomere length, serum glucose, cystatin C, C-reactive protein (CRP), interleukin-6 (IL-6), and albumin [ 17 ]. After 11 years of follow-up, the 5 blood-based markers that correlated best with cognitive decline were APOE (present/absent), cystatin C, serum glucose, CRP, and IL-6.…”

Section: Introductionmentioning

confidence: 99%

Distinguishing Alzheimer’s Disease Patients and Biochemical Phenotype Analysis Using a Novel Serum Profiling Platform: Potential Involvement of the VWF/ADAMTS13 Axis

et al. 2021

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It is important to develop minimally invasive biomarker platforms to help in the identification and monitoring of patients with Alzheimer’s disease (AD). Assisting in the understanding of biochemical mechanisms as well as identifying potential novel biomarkers and therapeutic targets would be an added benefit of such platforms. This study utilizes a simplified and novel serum profiling platform, using mass spectrometry (MS), to help distinguish AD patient groups (mild and moderate) and controls, as well as to aid in understanding of biochemical phenotypes and possible disease development. A comparison of discriminating sera mass peaks between AD patients and control individuals was performed using leave one [serum sample] out cross validation (LOOCV) combined with a novel peak classification valuation (PCV) procedure. LOOCV/PCV was able to distinguish significant sera mass peak differences between a group of mild AD patients and control individuals with a p value of 10−13. This value became non-significant (p = 0.09) when the same sera samples were randomly allocated between the two groups and reanalyzed by LOOCV/PCV. This is indicative of physiological group differences in the original true-pathology binary group comparison. Similarities and differences between AD patients and traumatic brain injury (TBI) patients were also discernable using this novel LOOCV/PCV platform. MS/MS peptide analysis was performed on serum mass peaks comparing mild AD patients with control individuals. Bioinformatics analysis suggested that cell pathways/biochemical phenotypes affected in AD include those involving neuronal cell death, vasculature, neurogenesis, and AD/dementia/amyloidosis. Inflammation, autoimmunity, autophagy, and blood–brain barrier pathways also appear to be relevant to AD. An impaired VWF/ADAMTS13 vasculature axis with connections to F8 (factor VIII) and LRP1 and NOTCH1 was indicated and is proposed to be important in AD development.

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Development and validation of risk index for cognitive decline using blood-derived markers

Cited by 11 publications

References 37 publications

Potential fluid biomarkers for pathological brain changes in Alzheimer's disease: Implication for the screening of cognitive frailty

Potential fluid biomarkers for pathological brain changes in Alzheimer's disease: Implication for the screening of cognitive frailty

Comparison of Associations of DXA and CT Visceral Adipose Tissue Measures With Insulin Resistance, Lipid Levels, and Inflammatory Markers

Distinguishing Alzheimer’s Disease Patients and Biochemical Phenotype Analysis Using a Novel Serum Profiling Platform: Potential Involvement of the VWF/ADAMTS13 Axis

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