Dataset Information

Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment.

ABSTRACT: Cerebral microbleeds (CMBs) are hypothesised to have an important yet unknown role in the dementia disease pathology. In this study we analysed increasing number of CMBs and their independent associations with routine cerebrospinal fluid (CSF) biomarkers in a continuum of cognitive impairment. A total of 1039 patients undergoing dementia investigation were analysed and underwent lumbar puncture, and an MRI scan. CSF samples were analysed for amyloid β (Aβ) 42, total tau (T-tau), tau phosphorylated at threonine 18 (P-tau) and CSF/serum albumin ratios. Increasing number of CMBs were independently associated with low Aβ42 levels, in the whole cohort, Alzheimer's disease and mild cognitive impairment (p < 0.05). CSF/serum albumin ratios were high with multiple CMBs (p < 0.001), reflecting accompanying blood-brain barrier dysfunction. T-tau and P-tau levels were lower in Alzheimer's patients with multiple CMBs when compared to zero CMBs, but did not change in the rest of the cohort. White matter hyperintensities were associated with low Aβ42 in the whole cohort and Alzheimer's disease (p < 0.05). Aβ42 is the routine CSF-biomarker mainly associated with CMBs in cognitive impairment, and there is an accumulative effect with increasing number of CMBs.

SUBMITTER: Shams S

PROVIDER: S-EPMC4794093 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment.

Shams Sara S Granberg Tobias T Martola Juha J Li Xiaozhen X Shams Mana M Fereshtehnejad Seyed-Mohammad SM Cavallin Lena L Aspelin Peter P Kristoffersen-Wiberg Maria M Wahlund Lars-Olof LO

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20150930 3

Cerebral microbleeds (CMBs) are hypothesised to have an important yet unknown role in the dementia disease pathology. In this study we analysed increasing number of CMBs and their independent associations with routine cerebrospinal fluid (CSF) biomarkers in a continuum of cognitive impairment. A total of 1039 patients undergoing dementia investigation were analysed and underwent lumbar puncture, and an MRI scan. CSF samples were analysed for amyloid β (Aβ) 42, total tau (T-tau), tau phosphorylat ...[more]

PMID: 26661151

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Project description:Lobar cerebral microbleeds (CMBs) in Alzheimer's disease (AD) are associated with cerebral amyloid angiopathy (CAA) due to vascular amyloid beta (Aβ) deposits. However, the relationship between lobar CMBs and clinical subtypes of AD remains unknown. Here, we enrolled patients with early- and late-onset amnestic dominant AD, logopenic variant of primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA) who were compatible with the AD criteria. We then examined the levels of cerebrospinal fluid (CSF) biomarkers [Aβ1-42, Aβ1-40, Aβ1-38, phosphorylated tau 181 (P-Tau), total tau (T-Tau), neurofilament light chain (NFL), and chitinase 3-like 1 protein (YKL-40)], analyzed the number and localization of CMBs, and measured the cerebral blood flow (CBF) volume by 99mTc-ethyl cysteinate dimer single photon emission computerized tomography (99mTc ECD-SPECT), as well as the mean cortical standard uptake value ratio by 11C-labeled Pittsburgh Compound B-positron emission tomography (11C PiB-PET). Lobar CMBs in lvPPA were distributed in the temporal, frontal, and parietal lobes with the left side predominance, while the CBF volume in lvPPA significantly decreased in the left temporal area, where the number of lobar CMBs and the CBF volumes showed a significant inversely correlation. The CSF levels of NFL in lvPPA were significantly higher compared to the other AD subtypes and non-demented subjects. The numbers of lobar CMBs significantly increased the CSF levels of NFL in the total AD patients, additionally, among AD subtypes, the CSF levels of NFL in lvPPA predominantly were higher by increasing number of lobar CMBs. On the other hand, the CSF levels of Aβ1-38, Aβ1-40, Aβ1-42, P-Tau, and T-Tau were lower by increasing number of lobar CMBs in the total AD patients. These findings may suggest that aberrant brain hypoperfusion in lvPPA was derived from the brain atrophy due to neurodegeneration, and possibly may involve the aberrant microcirculation causing by lobar CMBs and cerebrovascular injuries, with the left side dominance, consequently leading to a clinical phenotype of logopenic variant.

Project description:ObjectiveTo 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).DesignRandomized controlled trial.SettingVeterans Affairs Medical Center clinical research unit.ParticipantsForty-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).InterventionParticipants 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.Main outcome measuresThe CSF concentrations of β-amyloid (Aβ42 and Aβ40), tau protein, insulin, F2-isoprostanes, and apolipoprotein E, plasma lipids and insulin, and measures of cognition.ResultsFor the aMCI group, the LOW diet increased CSF Aβ42 concentrations, contrary to the pathologic pattern of lowered CSF Aβ42 typically observed in Alzheimer disease. The LOW diet had the opposite effect for healthy adults, ie, decreasing CSF Aβ42, whereas the HIGH diet increased CSF Aβ42. 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.ConclusionOur results suggest that diet may be a powerful environmental factor that modulates Alzheimer disease risk through its effects on central nervous system concentrations of Aβ42, lipoproteins, oxidative stress, and insulin.

Project description:BackgroundAlzheimer's disease (AD) biomarkers are emerging as critically important for disease detection and monitoring. Most biomarkers are obtained through invasive, resource-intense procedures. A cognitive marker, intra-individual cognitive variability (IICV) may provide an alternative or adjunct marker of disease risk for individuals unable or disinclined to undergo lumbar puncture.ObjectiveTo contrast risk of incident AD and mild cognitive impairment (MCI) associated with IICV to risk associated with well-established biomarkers: cerebrospinal fluid (CSF) phosphorylated tau protein (p-tau181) and amyloid-β 42 (Aβ42) peptide.MethodsDispersion in cognitive performance, IICV, was estimated with a published algorithm, and included Trail Making Test A and B, Rey Auditory Verbal Learning Test (RAVLT), and the American National Adult Reading Test (ANART). CSF biomarkers were expressed as a ratio: p-tau181/Aβ42, wherein high values signified pathognomonic profiles. Logistic regression models included longitudinal data from 349 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants who completed lumbar puncture. All subjects were cognitively healthy (n = 105) or diagnosed with MCI (n = 244) at baseline. We examined odds of conversion associated with baseline elevations in IICV and/or ratio of CSF p-tau181/Aβ42.ResultsWhen included in models alone or in combination with CSF p-tau181/Aβ42, one standard IICV unit higher was associated with an estimated odds ratio for incident AD or MCI of 2.81 (95% CI: 1.83-4.33) in the most inclusive sample, and an odds ratio of 3.41 (95% CI: 2.03-5.73) when restricted to participants with MCI. Iterative analyses suggested that IICV independently improved model fit even when individual index components were included in comparative models.ConclusionsThese analyses provide preliminary support for IICV as a marker of incident AD and MCI. This easily-disseminated, non-invasive marker compared favorably to well-established CSF biomarkers.

Dataset Information

Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment.

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Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment.

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