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Potential Fluid Biomarkers for the Diagnosis of Mild Cognitive Impairment.

ABSTRACT: Mild cognitive impairment (MCI) is characterized by a level of cognitive impairment that is lower than normal for a person's age, but a higher function than that that observed in a demented person. MCI represents a transitional state between normal aging and dementia disorders, especially Alzheimer's disease (AD). Much effort has been made towards determining the prognosis of a person with MCI who will convert to AD. It is now clear that cerebrospinal fluid (CSF) levels of A?40, A?42, total tau and phosphorylated tau are useful for predicting the risk of progression from MCI to AD. This review highlights the advantages of the current blood-based biomarkers in MCI, and discusses some of these challenges, with an emphasis on recent studies to provide an overview of the current state of MCI.

SUBMITTER: Giau VV

PROVIDER: S-EPMC6747411 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Potential Fluid Biomarkers for the Diagnosis of Mild Cognitive Impairment.

Giau Vo Van VV Bagyinszky Eva E An Seong Soo A SSA

International journal of molecular sciences 20190825 17

Mild cognitive impairment (MCI) is characterized by a level of cognitive impairment that is lower than normal for a person's age, but a higher function than that that observed in a demented person. MCI represents a transitional state between normal aging and dementia disorders, especially Alzheimer's disease (AD). Much effort has been made towards determining the prognosis of a person with MCI who will convert to AD. It is now clear that cerebrospinal fluid (CSF) levels of Aβ40, Aβ42, total tau ...[more]

PMID: 31450692

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Project description:To compare the effects of a 4-week high-saturated fat/high-glycemic index (HIGH) diet with a low-saturated fat/low-glycemic index (LOW) diet on insulin and lipid metabolism, cerebrospinal fluid (CSF) markers of Alzheimer disease, and cognition for healthy adults and adults with amnestic mild cognitive impairment (aMCI).Randomized controlled trial.Veterans Affairs Medical Center clinical research unit.Forty-nine older adults (20 healthy adults with a mean [SD] age of 69.3 [7.4] years and 29 adults with aMCI with a mean [SD] age of 67.6 [6.8] years).Participants received the HIGH diet (fat, 45% [saturated fat, > 25%]; carbohydrates, 35%-40% [glycemic index, > 70]; and protein, 15%-20%) or the LOW diet (fat, 25%; [saturated fat, < 7%]; carbohydrates, 55%-60% [glycemic index, < 55]; and protein, 15%-20%) for 4 weeks. Cognitive tests, an oral glucose tolerance test, and lumbar puncture were conducted at baseline and during the fourth week of the diet.The CSF concentrations of ?-amyloid (A?42 and A?40), tau protein, insulin, F2-isoprostanes, and apolipoprotein E, plasma lipids and insulin, and measures of cognition.For the aMCI group, the LOW diet increased CSF A?42 concentrations, contrary to the pathologic pattern of lowered CSF A?42 typically observed in Alzheimer disease. The LOW diet had the opposite effect for healthy adults, ie, decreasing CSF A?42, whereas the HIGH diet increased CSF A?42. The CSF apolipoprotein E concentration was increased by the LOW diet and decreased by the HIGH diet for both groups. For the aMCI group, the CSF insulin concentration increased with the LOW diet, but the HIGH diet lowered the CSF insulin concentration for healthy adults. The HIGH diet increased and the LOW diet decreased plasma lipids, insulin, and CSF F2-isoprostane concentrations. Delayed visual memory improved for both groups after completion of 4 weeks of the LOW diet.Our results suggest that diet may be a powerful environmental factor that modulates Alzheimer disease risk through its effects on central nervous system concentrations of A?42, lipoproteins, oxidative stress, and insulin.

Project description:Importance:Prior evidence suggests that racial differences exist in tau biomarkers in mild cognitive impairment (MCI) and Alzheimer disease (AD). Whether this reported disparity is associated with a differential level of neurodegeneration and disease stage or with underlying mechanisms separate from amyloid or tau is unclear. Objectives:To compare cerebrospinal fluid (CSF) biomarkers in African American and white individuals with normal cognition and MCI, to estimate race-based cutoffs for these biomarkers that maximize diagnostic discrimination between normal cognition and MCI, and to study the association of demographic characteristics, cognitive performance, and common vascular risk factors with these differences. Design, Setting, and Participants:This case-control study conducted from March 1, 2016, through January 31, 2019, included participants in the Brain Stress Hypertension and Aging Research Program cohort undergoing baseline assessment. Participants were 50 years or older and recruited from the Atlanta, Georgia, area. Exposures:Self-reported race and cognitive status categorized using modified Petersen criteria and clinical consensus diagnosis. Main Outcomes and Measures:Levels of ?-amyloid 1-42 (A?1-42), tau, and phosphorylated tau 181 (pTau181), the ratio of tau or pTau181 to A?1-42, and hippocampal volume on magnetic resonance imaging of the brain. Results:Data from 362 study participants were analyzed (mean [SD] age, 65.6 [7.9] years), of whom 152 (42.0%) were African American, 230 (63.5%) were women, and 189 (52.2%) had MCI. After adjustment for demographic characteristics and cognitive performance, lower mean (SE) levels were observed in African American vs white individuals with MCI for tau (52.40 [5.90] vs 78.98 [5.02] pg/mL; P?=?.001) and pTau181 (15.42 [2.06] vs 25.24 [1.75] pg/mL; P?=?.001) and a lower pTau181 to A?1-42 ratio (0.07 [0.02] vs 0.14 [0.01]; P?=?.003). There were no racial differences in the normal cognition group or in hippocampal volumes in the MCI group. Cutoffs for CSF biomarkers were higher for A?1-42 in African American relative to white individuals (208 [95% CI, 126-321] vs 197 [95% CI, 183-245] pg/mL) and lower for tau (51 [95% CI, 31-59] vs 59 [95% CI, 56-92] pg/mL) and pTau181 (12 [95% CI, 12-19] vs 20 [95% CI, 12-27] pg/mL) levels. Cutoffs for the pTau181 to A?1-42 ratio were 0.05 (95% CI, 0.03-0.12) for African American participants and 0.05 (95% CI, 0.05-0.13) for white participants. Conclusions and Relevance:This study found that African American individuals had lower levels of tau-based biomarkers that were not likely explained by the degree of disease stage or neurodegeneration reflected by hippocampal volumes. This study suggests that race is an important factor when interpreting CSF biomarkers, especially in the clinical diagnosis of prodromal AD. It appears that using the pTau181 to A?1-42 ratio may ameliorate these differences.

Project description:BackgroundMild cognitive impairment and cognitive impairment, no dementia, are emerging terms that encompass the clinical state between normal cognition and dementia in elderly people. Controversy surrounds their characterization, definition and application in clinical practice. In this article, we provide physicians with practical guidance on the definition, diagnosis and treatment of mild cognitive impairment and cognitive impairment, no dementia, based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, held in March 2006.MethodsWe developed evidence-based guidelines using systematic literature searches, with specific criteria for study selection and quality assessment, and a clear and transparent decision-making process. We selected studies published from January 1996 to December 2005 that had mild cognitive impairment or cognitive impairment, no dementia, as the outcome. Subsequent to the conference, we searched for additional articles published between January 2006 and January 2008. We graded the strength of evidence using the criteria of the Canadian Task Force on Preventive Health Care.ResultsWe identified 2483 articles, of which 314 were considered to be relevant and of good or fair quality. From a synthesis of the evidence in these studies, we made 16 recommendations. In brief, family physicians should be aware that most types of dementia are preceded by a recognizable phase of mild cognitive decline. They should be familiar with the concepts of mild cognitive impairment and of cognitive impairment, no dementia. Patients with these conditions should be closely monitored because of their increased risk for dementia. Leisure activities, cognitive stimulation and physical activity could be promoted as part of a healthy lifestyle in elderly people and those with mild cognitive impairment. Vascular risk factors should be treated optimally. No other specific therapies can yet be recommended.InterpretationPhysicians will increasingly see elderly patients with mild memory loss, and learning an approach to diagnosing states such as mild cognitive impairment is now warranted. Close monitoring for progression to dementia, promotion of a healthy lifestyle and treatment of vascular risk factors are recommended for the management of patients with mild cognitive impairment.

Dataset Information

Potential Fluid Biomarkers for the Diagnosis of Mild Cognitive Impairment.

Publications

Potential Fluid Biomarkers for the Diagnosis of Mild Cognitive Impairment.

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