Dataset Information

Association of Plasma Transferrin With Cognitive Decline in Patients With Mild Cognitive Impairment and Alzheimer's Disease.

ABSTRACT: Objective: The objective of this study was to examine whether plasma transferrin levels are associated with longitudinal changes in cognitive performance in older individuals with normal cognition (CN), mild cognitive impairment (MCI), and mild Alzheimer's disease (AD). Methods: At baseline, there were a total of 358 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, including 58 older individuals with CN, 198 older individuals with MCI, and 102 patients with AD. Linear mixed models were utilized to examine the associations of plasma transferrin levels with changes in cognitive performance over time after adjustment of several potential covariates. The Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) were used to examine the global cognition of participants. Results: First, no significant differences in the plasma transferrin levels were observed across three diagnostic groups. Second, in the cross-sectional analyses, the baseline plasma transferrin levels were negatively associated with the MMSE scores in the CN group, but not in the MCI or the AD group. Third, in the longitudinal analyses, we found that a higher plasma transferrin was associated with a steeper cognitive decline in the MCI and AD groups, but not in the CN group. Conclusion: Higher plasma transferrin levels were associated with a steeper cognitive decline in participants with MCI and AD.

SUBMITTER: Guan J

PROVIDER: S-EPMC7080847 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association of Plasma Transferrin With Cognitive Decline in Patients With Mild Cognitive Impairment and Alzheimer's Disease.

Guan Jingjing J Wang Peng P Lu Liping L Zhao Guanan G

Frontiers in aging neuroscience 20200312

<b>Objective</b>: The objective of this study was to examine whether plasma transferrin levels are associated with longitudinal changes in cognitive performance in older individuals with normal cognition (CN), mild cognitive impairment (MCI), and mild Alzheimer's disease (AD). <b>Methods</b>: At baseline, there were a total of 358 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, including 58 older individuals with CN, 198 older individuals with MCI, and 102 patien ...[more]

PMID: 32226377

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Project description:Plasma-based biomarkers present a promising approach in the research and clinical practice of Alzheimer's disease as they are inexpensive, accessible and minimally invasive. In particular, prognostic biomarkers of cognitive decline may aid in planning and management of clinical care. Although recent studies have demonstrated the prognostic utility of plasma biomarkers of Alzheimer pathology or neurodegeneration, such as pTau-181 and NF-L, whether other plasma biomarkers can further improve prediction of cognitive decline is undetermined. We conducted an observational cohort study to determine the prognostic utility of plasma biomarkers in predicting progression to dementia for individuals presenting with mild cognitive impairment due to probable Alzheimer's disease. We used the Olink™ Proximity Extension Assay technology to measure the level of 460 circulating proteins in banked plasma samples of all participants. We used a discovery data set comprised 60 individuals with mild cognitive impairment (30 progressors and 30 stable) and a validation data set consisting of 21 stable and 21 progressors. We developed a machine learning model to distinguish progressors from stable and used 44 proteins with significantly different plasma levels in progressors versus stable along with age, sex, education and baseline cognition as candidate features. A model with age, education, APOE genotype, baseline cognition, plasma pTau-181 and 12 plasma Olink protein biomarker levels was able to distinguish progressors from stable with 86.7% accuracy (mean area under the curve = 0.88). In the validation data set, the model accuracy was 78.6%. The Olink proteins selected by the model included those associated with vascular injury and neuroinflammation (e.g. IL-8, IL-17A, TIMP-4, MMP7). In addition, to compare these prognostic biomarkers to those that are altered in Alzheimer's disease or other types of dementia relative to controls, we analyzed samples from 20 individuals with Alzheimer, 30 with non-Alzheimer dementias and 34 with normal cognition. The proteins NF-L and PTP-1B were significantly higher in both Alzheimer and non-Alzheimer dementias compared with cognitively normal individuals. Interestingly, the prognostic markers of decline at the mild cognitive impairment stage did not overlap with those that differed between dementia and control cases. In summary, our findings suggest that plasma biomarkers of inflammation and vascular injury are associated with cognitive decline. Developing a plasma biomarker profile could aid in prognostic deliberations and identify individuals at higher risk of dementia in clinical practice.

Project description:In this paper, we explore the utility of resting-state EEG measures as potential biomarkers for the detection and assessment of cognitive decline in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Neurophysiological biomarkers of AD derived from EEG and FDG-PET, once characterized and validated, would expand the set of existing diagnostic molecular biomarkers of AD pathology with associated biomarkers of disease progression and neural dysfunction. Since symptoms of AD often begin to appear later in life, successful identification of EEG-based biomarkers must account for age-related neurophysiological changes that occur even in healthy individuals. To this end, we collected EEG data from individuals with AD (n = 26), MCI (n = 53), and cognitively normal healthy controls stratified by age into three groups: 18-40 (n = 129), 40-60 (n = 62) and 60-90 (= 55) years old. For each participant, we computed power spectral density at each channel and spectral coherence between pairs of channels. Compared to age matched controls, in the AD group, we found increases in both spectral power and coherence at the slower frequencies (Delta, Theta). A smaller but significant increase in power of slow frequencies was observed for the MCI group, localized to temporal areas. These effects on slow frequency spectral power opposed that of normal aging observed by a decrease in the power of slow frequencies in our control groups. The AD group showed a significant decrease in the spectral power and coherence in the Alpha band consistent with the same effect in normal aging. However, the MCI group did not show any significant change in the Alpha band. Overall, Theta to Alpha ratio (TAR) provided the largest and most significant differences between the AD group and controls. However, differences in the MCI group remained small and localized. We proposed a novel method to quantify these small differences between Theta and Alpha bands' power using empirically derived distributions of spectral power across the time domain as opposed to averaging power across time. We defined Power Distribution Distance Measure (PDDM) as a distance measure between probability distribution functions (pdf) of Theta and Alpha power. Compared to average TAR, using PDDF enhanced the statistical significance, the effect size, and the spatial distribution of significant effects in the MCI group. We designed classifiers for differentiating individual MCI and AD participants from age-matched controls. The classification performance measured by the area under ROC curve after cross-validation were AUC = 0.85 and AUC = 0.6, for AD and MCI classifiers, respectively. Posterior probability of AD, TAR, and the proposed PDDM measure were all significantly correlated with MMSE score and neuropsychological tests in the AD group.

Dataset Information

Association of Plasma Transferrin With Cognitive Decline in Patients With Mild Cognitive Impairment and Alzheimer's Disease.

Publications

Association of Plasma Transferrin With Cognitive Decline in Patients With Mild Cognitive Impairment and Alzheimer's Disease.

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