Lipids constitute the bulk of the dry mass of the brain and have been associated with healthy function as well as the most common pathological conditions of the brain. Demographic factors, genetics, and lifestyles are the major factors that influence lipid metabolism and are also the key components of lipid disruption in Alzheimer's disease (AD). Additionally, the most common genetic risk factor of AD, APOE 4 genotype, is involved in lipid transport and metabolism. We propose that lipids are at the center of Alzheimer's disease pathology based on their involvement in the blood-brain barrier function, amyloid precursor protein (APP) processing, myelination, membrane remodeling, receptor signaling, inflammation, oxidation, and energy balance. Under healthy conditions, lipid homeostasis bestows a balanced cellular environment that enables the proper functioning of brain cells. However, under pathological conditions, dyshomeostasis of brain lipid composition can result in disturbed BBB, abnormal processing of APP, dysfunction in endocytosis/exocytosis/autophagocytosis, altered myelination, disturbed signaling, unbalanced energy metabolism, and enhanced inflammation. These lipid disturbances may contribute to abnormalities in brain function that are the hallmark of AD. The wide variance of lipid disturbances associated with brain function suggest that AD pathology may present as a complex interaction between several metabolic pathways that are augmented by risk factors such as age, genetics, and lifestyles. Herewith, we examine factors that influence brain lipid composition, review the association of lipids with all known facets of AD pathology, and offer pointers for potential therapies that target lipid pathways.
Objective: To demonstrate differences in cardiovascular structure and function between diabetic and nondiabetic older adults. To investigate associations between acyl-carnitines and cardiovascular function as indexed by imaging measurements. Methods: A community-based cohort of older adults without cardiovascular disease underwent current cardiovascular imaging and metabolomics acyl-carnitines profiling based on current and archived sera obtained fifteen years prior to examination. Results: A total of 933 participants (women 56%, n=521) with a mean age 63±13 years were studied. Old diabetics compared to old non-diabetics had lower myocardial relaxation (0.8±0.2 vs 0.9±0.3, p=0.0039); lower left atrial conduit strain (12±4.3 vs 14±4.1, p=0.045), lower left atrial conduit strain rate (-1.2±0.4 vs -1.3±0.5, p=0.042) and lower ratio of left atrial conduit strain to left atrial booster strain (0.5±0.2 vs 0.7±0.3, p=0.0029). Higher levels of archived short chain acyl-carnitine were associated with present-day impairments in myocardial relaxation (C5:1; OR 1.03, p=0.011), worse left atrial conduit strain function (C5:1; OR 1.03, p=0.037). Increases in hydroxylated acylcarnitines were associated with worse left atrial conduit strain [(C4-OH; OR 1.05, p=0.0017), (C16:2-OH; OR 1.18, p=0.037)]. Current, archived and changes in long chain acyl-carnitines were associated with cardiovascular functions [(C16; OR 1.02, p=0.002), (C20:3; OR 1.01, p=0.014), (C14:3; OR 1.12, p=0.033), (C18:1; OR 1.01, p=0.018), (C18:2; OR 1.01, p=0.028), (C20:4; OR 1.10, p=0.038)] (all p<0.05). Conclusion: Older diabetic adults had significant impairments in left ventricular myocardial relaxation and left atrial strain, compared to older non-diabetic adults. Short chain and long chain, di-carboxyl and hydroxylated acyl-carnitines were associated with these cardiovascular functional differences.1Medium and long-chain carnitines C8,
A Spirituality Interest Group (SIG) was set up in in the School of Nursing and Midwifery, Trinity College Dublin, Republic of Ireland (ROI), in March 2013. This paper reports on some of the journey and requirements involved in developing the group. It highlights the essential work of establishing agreed understandings in an objective way in order for the group to move forward with action. These agreed understandings have contributed to the group's success. Outlining the group's journey in arriving at agreements may be of use to others considering creating similar groups. One key action taken to determine the suitability of the group's aims and terms of reference was the distribution of a Survey Monkey to group members (n = 28) in 2014. One early meeting of the group discussed future goals and direction using the responses of this anonymous survey. This paper reports on the results of the survey regarding the establishment of the SIG and the development of a shared understanding of spiritual care among the members. There is consensus in the group that the spiritual care required by clients receiving healthcare ought to be an integrated effort across the healthcare team. However, there is an acceptance that spirituality and spiritual care are not always clearly understood concepts in practice. By developing shared or at least accepted understandings of spirituality and spiritual care, SIG hopes to be able to underpin both research and practice with solid foundational conceptual understanding, and in the process also to meet essential prerequisites for achieving the group's aims.
Background The adverse consequences of diabetes mellitus on cardiovascular health is well-established. However, few studies have studied the impact of diabetes on ageing. In our previous investigations, we identified distinct patterns of myocardial ageing among older adults otherwise asymptomatic for clinical cardiovascular disease. In this analysis, we hypothesize that glycated hemoglobin (HbA1c) may be differentially associated with these distinct signatures of myocardial ageing, thereby providing greater precision towards future preventative trials. Methods We performed extensive cardiovascular examinations on a cohort of asymptomatic aged community adults. Transthoracic echocardiography measured left ventricular structure and function. LV filling pressure was measured as the ratio between early mitral inflow velocity and mitral annular early diastolic velocity. Longitudinal left atrial (LA) strain comprising reservoir strain (ɛs), conduit strain (ɛe) and booster strain (ɛa) and their corresponding peak strain rates (SRs, SRe, SRa) were measured using cardiac magnetic resonance (CMR) feature tracking technique. Blood sampling for biomarkers were performed simultaneously with cardiovascular examinations. Results Among n=515 community adults in sinus rhythm and without cardiovascular disease [mean age 73±4 years, 255 (50%) females], 116 (23%) had diabetes. Age (73 vs 73 years) and heart rate (72 vs 75 beats per minute) were similar between diabetic and non-diabetic older adults. Diabetic older adults are mostly male (59% vs 48%, p=0.046), had larger body mass indices (24 vs 23 kg/m2, p=0.027), and greater burdens of hypertension (81% vs 41%, p<0.0001) and dyslipidemia (79% vs 43%, p<0.0001), compared to non-diabetic older adults. Diabetics had worse LV myocardial relaxation [(ratio of peak velocity flow in early diastole E (m/s) to peak velocity flow in late diastole by atrial contraction A (m/s), 0.8±0.2 vs 0.9±0.3, p=0.031), worse LV filling pressures (10.9±3.1 vs 10.1±3.3, p=0.022), reductions in LA global strain (−33±17 vs −28±9.7, p=0.016), LA conduit strain ɛe (12±4.3 vs 14±4.1, p=0.045), increases in SRe (−1.2±0.4 vs −1.3±0.5, p=0.042) and reductions in SRe: SRa ratio (0.5±0.2 vs 0.7±0.3, p=0.0059) compared to non-diabetics. Based on multivariate analysis, HbA1c was independently associated with LV myocardial relaxation (β=−0.08 (−0.1, −0.03), p=0.002), LA conduit strain (β=−0.9, (−1.6, −0.1), p=0.025), LA conduit strain rate (β=0.1, (0.04, 0.2), p=0.005), strongly associated with LA global strain (β=3.0, (0.9, 5.1), p=0.006), but not associated with LV filling pressure (β=0.5 (−0.04, 1.0), p=NS). Conclusion Our detailed examinations revealed distinct associations between glycated hemoglobin and myocardial functions that additionally varied in magnitude. As a contemporary biomarker, glycated hemoglobin may be useful for stratifying risks associated with myocardial ageing, particularly in ageing-related left atrial myopathies. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): National Medical Research Council of Singapore; Singhealth Foundation
Although fatty acid oxidation is associated with Alzheimer's disease (AD) pathology, no links have been established between brain lipids and excreted oxidized products. We hypothesize that oxidation of brain polyunsaturated fatty acids (PUFA) can generate dicarboxylic acids (DCA) excreted in urine by AD subjects at different rates compared with cognitively healthy (CH) subjects. Furthermore, this trend can be extended to differentiate CH subjects with normal cerebrospinal fluid (CSF) Aβ42/tau ratios (CH‐NAT) and CH subjects with pathological CSF Aβ42/tau ratios (CH‐PAT).Subjects > 70 years were classified as CH (n=64) or AD (n=26) after neuropsychological assessment. CSF Aβ42 and Tau levels were determined using an ELISA‐based method and a logistic regression of Aβ42/tau ratios used to classify CH‐NAT and CH‐PAT. CSF was fractionated and PUFA levels quantified in supernatant fluid (SF), nanoparticles (NP), and unesterified fatty acid (UFA). DCA was derivatized to pentafluorobenzyl ester, and quantified using gas chromatography and isotope dilution negative ion chemical ionization mass spectrometry. PUFA data is expressed as a percentage of fatty acids detected in CSF fractions while DCA is calculated as a percentage of 7 DCAs (C4–C10) in urine. Links between urinary DCAs and CSF PUFAs were determined using Spearman's ranked correlation.C10 DCA negatively correlated with 6 of 8 PUFAs in SF from CH and also negatively correlated with C20:3n‐3 and C22:6n‐3 in SF from CH‐NAT. In contrast, C9 DCA negatively correlated with 7 of 8 PUFAs in SF from AD. C6 and C8 DCAs positively correlated with SF C18:3n‐3 and C20:3n‐3 in AD, respectively, while C6 DCA negatively correlated with SF C18:2n‐6 from CH‐NAT. C4 DCA negatively correlated with C18:2n‐6, C20:4n‐6, and C22:6n‐3 in SF from CH‐PAT, while C7 DCA positively correlated with C20:4n‐6 in SF from CH‐PAT. In the NP fraction of CH, C4 DCA positively correlated with C20:2n‐6, C20:3n‐3, C20:5n‐3, and C22:5n‐3 PUFAs, while C8 DCA negatively correlated with C20:5n‐3. Only C9 DCA positively correlated with C20:4n‐6 in AD NP fractions. Interestingly, no correlations were found in the NP fraction from CH‐NAT. However, C8 DCA negatively correlated with NP C20:3n‐3, C20:5n‐3, and C22:5n‐3 and C4 DCA positively correlated with NP C20:5n‐3 from CH‐PAT. For UFA of CH, C6 DCA negatively correlated with C20:2n‐6, C20:3n‐3, and C22:6n‐3, while C5 and C7 DCAs positively correlated with homo‐γ‐C20:3n‐6 and C18:2n‐6, respectively. For UFA of CH‐NAT, C4 DCA positively correlated with homo‐γ‐C20:3n‐6, C5 and C8 DCAs negatively correlated with homo‐γ‐C20:3n‐6, and C7 DCA negatively correlated with C18:2n‐6. C5 DCA positively correlated with C18:2n‐6 in UFA from CH‐PAT. C8 DCA positively correlated with unesterified C22:6n‐3, while C9 DCA negatively correlated with unesterified C20:5n‐3 in AD subjects.Differential correlation of urinary DCAs with CSF PUFAs in clinical groups suggests a link with AD pathology. PUFAs and DCAs that segregate CH‐NAT from CH‐PAT are potential biomarkers of early AD.Support or Funding InformationL.K. Whittier and the Helen Posthuma FoundationsThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.