Dataset Information

Diet Effects on Cerebrospinal Fluid Amino Acids Levels in Adults with Normal Cognition and Mild Cognitive Impairment.

ABSTRACT:

Background

Exploration of cerebrospinal fluid (CSF) amino acids and the impact of dietary intake on central levels may provide a comprehensive understanding of the metabolic component of Alzheimer's disease.

Objective

The objective of this exploratory study was to investigate the effects of two diets with varied nutrient compositions on change in CSF amino acids levels in adults with mild cognitive impairment (MCI) and normal cognition (NC). Secondary objectives were to assess the correlations between the change in CSF amino acids and change in Alzheimer's disease biomarkers.

Methods

In a randomized, parallel, controlled feeding trial, adults (NC, n = 20; MCI, n = 29) consumed a high saturated fat (SFA)/glycemic index (GI) diet [HIGH] or a low SFA/GI diet [LOW] for 4 weeks. Lumbar punctures were performed at baseline and 4 weeks.

Results

CSF valine increased and arginine decreased after the HIGH compared to the LOW diet in MCI (ps = 0.03 and 0.04). This pattern was more prominent in MCI versus NC (diet by diagnosis interaction ps = 0.05 and 0.09), as was an increase in isoleucine after the HIGH diet (p = 0.05). Changes in CSF amino acids were correlated with changes in Alzheimer's disease CSF biomarkers Aβ42, total tau, and p-Tau 181, with distinct patterns in the relationships by diet intervention and cognitive status.

Conclusion

Dietary intake affects CSF amino acid levels and the response to diet is differentially affected by cognitive status.

SUBMITTER: Russin KJ

PROVIDER: S-EPMC8673538 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

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:Cognitive function is not generally associated with diet, and there is debate over that association. Moreover, little is known about such associations with the specific cognitive domains and subtypes of mild cognitive impairment (MCI). We analyzed data of 4309 Chinese adults aged 55 and over from the Community-based Cohort Study on Nervous System Diseases from 2018-2019. Dietary habits were assessed at inclusion using a validated semi-quantitative food frequency questionnaire. Cognitive function of the participants was measured by using the Montreal Cognitive Assessment. Analyses were performed using multiple logistic regression and quantile regression with adjustment for socio-demographic, lifestyle, and health-related factors. Compared with normal cognition participants, those with a worse cognition state were characterized as being an older age and lower economic level. After adjustment for potential factors, participants with higher consumption of rice, legumes, fresh vegetables, fresh fruit, pork, poultry, fish, and nuts tended to have higher scores of global cognitive function and domains, and to have lower odds of MCI, while those with higher consumption levels of wheat and eggs had worse cognition, compared with the corresponding bottom consumption level of each food. Participants with a medium consumption level of beef or mutton had 57% (OR: 1.57, 95%CI: 1.07-2.32) higher odds of aMCI-SD, whereas they had 50% (OR: 0.50, 95%CI: 0.34-0.73) lower odds of naMCI-MD. Similarly, the highest consumption level of dairy was positively associated with the odds of aMCI-SD (OR:1.51, 95%CI:1.00-2.29), but inversely linked to the odds of naMCI-SD (OR: 0.60, 95%CI: 0.38-0.93) and naMCI-MD (OR: 0.49, 95%CI: 0.29-0.82). Most diet global cognitive benefits were observed to be associated with the preexisting higher consumption of rice, legumes, fresh vegetables, fresh fruit, meat, and nuts. In addition, the heterogeneity of associations between the consumption of certain foods and MCI subtypes was observed among Chinese adults aged over 55 years. These cross-sectional observations require validation in prospective studies.

Project description:BackgroundPhase-contrast magnetic resonance imaging (PC-MRI) enables quantification of cerebrospinal fluid (CSF) flow and total cerebral blood (tCBF) flow and may be of value for the etiological diagnosis of neurodegenerative diseases. This investigation aimed to study CSF flow and intracerebral vascular flow in patients with Alzheimer's disease (AD) and patients with amnesic mild cognitive impairment (a-MCI) and to compare the results with patients with idiopathic normal pressure hydrocephalus (NPH) and with healthy elderly volunteers (HEV).MethodsTen a-MCI and 9 mild AD patients were identified in a comprehensive neurological and neuropsychological assessment. They underwent brain MRI; PC-MRI pulse sequence was performed with the following parameters: two views per segment; flip angle: 25° for vascular flow and 20° for CSF flow; field-of-view (FOV): 14 × 14 mm²; matrix: 256 × 128; slice thickness: 5 mm; with one excitation for exams on the 3 T machine, and 2 excitations for the 1.5 T machine exams. Velocity (encoding) sensitization was set to 80 cm/s for the vessels at the cervical level, 10 or 20 cm/s for the aqueduct and 5 cm/s for the cervical subarachnoid space (SAS). Dynamic flow images were analyzed with in-house processing software. The patients' results were compared with those obtained for HEVs (n = 12), and for NPH patients (n = 13), using multivariate analysis.ResultsArterial tCBF and the calculated pulsatility index were significantly greater in a-MCI patients than in HEVs. In contrast, vascular parameters were lower in NPH patients. Cervical CSF flow analysis yielded similar values for all four populations. Aqueductal CSF stroke volumes (in μl per cardiac cycle) were similar in HEVs (34 ± 17) and AD patients (39 ± 18). In contrast, the aqueductal CSF was hyperdynamic in a-MCI patients (73 ± 33) and even more so in NPH patients (167 ± 89).ConclusionOur preliminary data show that a-MCI patients present with high systolic arterial peak flows, which are associated with higher mean total cerebral arterial flows. Aqueductal CSF oscillations are within normal range in AD and higher than normal in NPH. This study provides an original dynamic vision of cerebral neurodegenerative diseases, consistent with the vascular theory for AD, and supporting primary flow disturbances different from those observed in NPH.

Project description:BACKGROUND:Alzheimer'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. OBJECTIVE:To 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-? 42 (A?42) peptide. METHODS:Dispersion 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/A?42, 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/A?42. RESULTS:When included in models alone or in combination with CSF p-tau181/A?42, 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. CONCLUSIONS:These 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.

Project description:BackgroundLeukotriene receptor antagonists (LTRAs) alleviate Alzheimer's disease (AD) pathology and improve cognition in animal models; however, clinical evidence is limited. This study aimed to explore the associations between the use of LTRAs (montelukast or zafirlukast) and cognitive performance in people with normal cognition, mild cognitive impairment (MCI), or AD dementia. We hypothesized that LTRA use would be associated with better cognitive performance over time.MethodsThis longitudinal observational study used data from the National Alzheimer's Coordinating Center. Within groups of participants with normal cognition, MCI, or AD dementia, LTRA users were matched 1:3 to non-users using propensity score matching. Cognitive domains including immediate and delayed memory (Wechsler Memory Scale Revised-Logical Memory IA and IIA), psychomotor processing speed (Digit Symbol Substitution Test), and language (animal naming, vegetable naming, and Boston Naming Test) were compared between users and non-users in mixed-effects linear or Poisson regression models.ResultsIn AD dementia, LTRA use was associated with a slower decline in psychomotor processing speed, as measured by the Digit Symbol Substitution Test (Β = 1.466 [0.253, 2.678] symbols/year, n = 442), and language, as measured by animal naming (Β = 0.541 [0.215, 0.866] animals/year, n = 566), vegetable naming (B = 0.309 [0.056, 0.561] vegetables/year, n = 565), and the Boston Naming Test (B = 0.529 [0.005, 1.053] items/year, n = 561). Effect sizes were small but persisted after controlling for a 10% false discovery rate. LTRA use was not associated with changes in memory performance in AD, nor was it associated with changes in cognitive performance in people with normal cognition or MCI. In a post hoc analysis, LTRA use was associated with a slower decline in clinical progression in MCI (B = -0.200 [-0.380, -0.019] points/year, n = 800) and AD dementia (B = -0.321 [-0.597, -0.046] points/year, n = 604) as measured by CDR Sum of Boxes.ConclusionsThe use of LTRAs was associated with preserved function in non-amnestic cognitive domains in AD dementia. The role of leukotrienes and their receptors in cognitive decline warrants further investigation and the leukotriene pathway may represent a target for AD treatment.

Project description:Recent evidence indicates that measures from cerebrospinal fluid, MRI scans and cognitive testing obtained from cognitively normal individuals can be used to predict likelihood of progression to mild cognitive impairment several years later, for groups of individuals. However, it remains unclear whether these measures are useful for predicting likelihood of progression for an individual. The increasing focus on early intervention in clinical trials for Alzheimer's disease emphasizes the importance of improving the ability to identify which cognitively normal individuals are more likely to progress over time, thus allowing researchers to efficiently screen participants, as well as determine the efficacy of any treatment intervention. The goal of this study was to determine which measures, obtained when individuals were cognitively normal, predict on an individual basis, the onset of clinical symptoms associated with a diagnosis of mild cognitive impairment due to Alzheimer's disease. Cognitively normal participants (n = 224, mean baseline age = 57 years) were evaluated with a range of measures, including: cerebrospinal fluid amyloid-? and phosphorylated-tau, hippocampal and entorhinal cortex volume, cognitive tests scores and APOE genotype. They were then followed to determine which individuals developed mild cognitive impairment over time (mean follow-up = 11 years). The primary outcome was progression from normal cognition to the onset of clinical symptoms of mild cognitive impairment due to Alzheimer's disease at 5 years post-baseline. Time-dependent receiver operating characteristic analyses examined the sensitivity and specificity of individual measures, and combinations of measures, as predictors of the outcome. Six measures, in combination, were the most parsimonious predictors of transition to mild cognitive impairment 5 years after baseline (area under the curve = 0.85; sensitivity = 0.80, specificity = 0.75). The addition of variables from each domain significantly improved the accuracy of prediction. The incremental accuracy of prediction achieved by adding individual measures or sets of measures successively to one another was also examined, as might be done when enrolling individuals in a clinical trial. The results indicate that biomarkers obtained when individuals are cognitively normal can be used to predict which individuals are likely to develop clinical symptoms at 5 years post-baseline. As a number of the measures included in the study could also be used as subject selection criteria in a clinical trial, the findings also provide information about measures that would be useful for screening in a clinical trial aimed at individuals with preclinical Alzheimer's disease.