Molecular markers of neuropsychological functioning and Alzheimer's disease

Edwards, Melissa; Balldin, Valerie Hobson; Hall, James; O’Bryant, Sid

doi:10.1016/j.dadm.2014.11.001

Cited by 7 publications

(5 citation statements)

References 40 publications

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“…CRP is generally released by the body in response to acute injury, infection, or other inflammatory stimuli. Nonetheless, reduced levels of plasma and serum CRP have been observed in AD [56][57][58][59], in agreement with results on the present cohort previously obtained using immunoassays [12]. Herein, we additionally highlighted that decreased plasma level of CRP agreed with amyloid pathology CSF profile.…”

Section: Discussionsupporting

confidence: 92%

Plasma Proteomic Profiles of Cerebrospinal Fluid-Defined Alzheimer’s Disease Pathology in Older Adults

Dayon

Wojcik²,

Galindo

et al. 2017

JAD

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Section: Discussionsupporting

confidence: 92%

Plasma Proteomic Profiles of Cerebrospinal Fluid-Defined Alzheimer’s Disease Pathology in Older Adults

Dayon

Wojcik²,

Galindo

et al. 2017

JAD

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“…Proinflammatory cytokines, such as TNFα, have been implicated in the pathophysiology of dementia and depression. Past research studies have found higher concentrations of TNFα were found in depressed patients as compared to healthy controls (Dowlati et al ., 2010 ) and inflammation has been consistently linked to cognitive dysfunction, MCI, and AD in our prior work (O'Bryant et al ., 2014 ; Edwards et al ., 2015 ). However, studies examining the relationship between inflammatory markers, memory, and depression have been mixed.…”

Section: Discussionmentioning

confidence: 99%

“…Data from 381 participants from the Health and Aging Brain among Latino Elders (HABLE) study were analyzed (Edwards et al ., 2015 ; Johnson et al ., 2015a; Szerlip et al ., 2015 ). The HABLE study is an ongoing epidemiological study of cognitive aging among community-dwelling Mexican-American individuals.…”

Section: Methodsmentioning

confidence: 99%

“…Although these studies indicate little relationship, the pathophysiology of TNFα effecting cognition and mood suggests that a relationship may be found especially in populations where both depression and inflammatory diseases are prevalent, such as found for Mexican-Americans. In our work, inflammation was associated with diagnosis of MCI among Mexican-Americans (Edwards et al ., 2015 ). The current study sought to examine the additive impact of elevated inflammation to DepE on memory abilities and risk for MCI diagnosis among community-dwelling Mexican-American adults and elders.…”

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confidence: 99%

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Depression, inflammation, and memory loss among Mexican Americans: analysis of the HABLE cohort

Johnson

Edwards

Gamboa

et al. 2017

Int. Psychogeriatr.

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Background:This study explored the combined impact of depression and inflammation on memory functioning among Mexican-American adults and elders.Methods:Data were analyzed from 381 participants of the Health and Aging Brain study among Latino Elders (HABLE). Fasting serum samples were collected and assayed in duplicate using electrochemiluminesce on the SECTOR Imager 2400A from Meso Scale Discovery. Positive DepE (depression endophenotype) was codified as any score >1 on a five-point scale based on the GDS-30. Inflammation was determined by TNFα levels and categorized by tertiles (1st, 2nd, 3rd). WMS-III LMI and LMII as well as CERAD were utilized as measures of memory. ANOVAs examined group differences between positive DepE and inflammation tertiles with neuropsychological scale scores as outcome variables. Logistic regressions were used to examine level of inflammation and DepE positive status on the risk for MCI.Results:Positive DepE as well as higher inflammation were both independently found to be associated with lower memory scores. Among DepE positive, those who were high in inflammation (3rd tertile) were found to perform significantly worse on WMS-III LM I (F = 4.75, p = 0.003), WMS-III LM II (F = 8.18, p < 0.001), and CERAD List Learning (F = 17.37, p < 0.001) when compared to those low on inflammation (1st tertile). The combination of DepE positive and highest tertile of inflammation was associated with increased risk for MCI diagnosis (OR = 6.06; 95% CI = 3.9–11.2, p < 0.001).Conclusion:Presence of elevated inflammation and positive DepE scores increased risk for worse memory among Mexican-American older adults. Additionally, the combination of DepE and high inflammation was associated with increased risk for MCI diagnosis. This work suggests that depression and inflammation are independently associated with worse memory among Mexican-American adults and elders; however, the combination of both increases risk for poorer memory beyond either alone.

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“…Early detection of sporadic AD may require systematic attention to multiple modalities of biomarkers and risk factors, perhaps beyond (but including) the established neurobiological and clinical hallmarks of the disease (e.g., beta amyloid; Barnes and Yaffe, 2011 ). Accordingly, recent research has focused on testing panels, dosages, and interactions of multiple biomarkers, examining their synergistic, modifying, or complementary influences on phenotypes, pre-clinical trajectories or clinical status (Edwards et al, 2015 ; McFall et al, 2015a ; Iturria-Medina et al, 2016 ; Sapkota et al, 2017 ; Sapkota and Dixon, 2018 ). Arguably, identifying perturbations in profiles of biomarkers in asymptomatic periods of impairment or AD may provide a promising opportunity for developing precision or programmatic interventions that could delay or prevent clinical diagnosis (Imtiaz et al, 2014 ; Hampel et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Alzheimer’s Biomarkers From Multiple Modalities Selectively Discriminate Clinical Status: Relative Importance of Salivary Metabolomics Panels, Genetic, Lifestyle, Cognitive, Functional Health and Demographic Risk Markers

Sapkota

Huan

Tran

et al. 2018

Front. Aging Neurosci.

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Background: Among the neurodegenerative diseases of aging, sporadic Alzheimer’s disease (AD) is the most prevalent and perhaps the most feared. With virtually no success at finding pharmaceutical therapeutics for altering progressive AD after diagnosis, research attention is increasingly directed at discovering biological and other markers that detect AD risk in the long asymptomatic phase. Both early detection and precision preclinical intervention require systematic investigation of multiple modalities and combinations of AD-related biomarkers and risk factors. We extend recent unbiased metabolomics research that produced a set of metabolite biomarker panels tailored to the discrimination of cognitively normal (CN), cognitively impaired and AD patients. Specifically, we compare the prediction importance of these panels with five other sets of modifiable and non-modifiable AD risk factors (genetic, lifestyle, cognitive, functional health and bio-demographic) in three clinical groups.Method: The three groups were: CN (n = 35), mild cognitive impairment (MCI; n = 25), and AD (n = 22). In a series of three pairwise comparisons, we used machine learning technology random forest analysis (RFA) to test relative predictive importance of up to 19 risk biomarkers from the six AD risk domains.Results: The three RFA multimodal prediction analyses produced significant discriminating risk factors. First, discriminating AD from CN was the AD metabolite panel and two cognitive markers. Second, discriminating AD from MCI was the AD/MCI metabolite panel and two cognitive markers. Third, discriminating MCI from CN was the MCI metabolite panel and seven markers from four other risk modalities: genetic, lifestyle, cognition and functional health.Conclusions: Salivary metabolomics biomarker panels, supplemented by other risk markers, were robust predictors of: (1) clinical differences in impairment and dementia and even; (2) subtle differences between CN and MCI. For the latter, the metabolite panel was supplemented by biomarkers that were both modifiable (e.g., functional) and non-modifiable (e.g., genetic). Comparing, integrating and identifying important multi-modal predictors may lead to novel combinations of complex risk profiles potentially indicative of neuropathological changes in asymptomatic or preclinical AD.

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Molecular markers of neuropsychological functioning and Alzheimer's disease

Cited by 7 publications

References 40 publications

Plasma Proteomic Profiles of Cerebrospinal Fluid-Defined Alzheimer’s Disease Pathology in Older Adults

Plasma Proteomic Profiles of Cerebrospinal Fluid-Defined Alzheimer’s Disease Pathology in Older Adults

Depression, inflammation, and memory loss among Mexican Americans: analysis of the HABLE cohort

Alzheimer’s Biomarkers From Multiple Modalities Selectively Discriminate Clinical Status: Relative Importance of Salivary Metabolomics Panels, Genetic, Lifestyle, Cognitive, Functional Health and Demographic Risk Markers

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