ABSTRACT
Objectives: Summarise theory informed educational interventions for improving bowel cancer awareness and screening. Methods: A search was conducted in PubMed, EMBASE, Web of Science and CINAHL. English studies from 2016 to 2022 which implemented community-based bowel cancer awareness and/or screening education interventions for adults in Organisation for Economic Co-operation and Development countries were included. Results: Sixty-two studies were included, 32 measured both screening and awareness (24 measured screening only, 6 measured awareness only). Education interventions were grouped and summarised in five education types: lay community health education/counselling (n = 28), education material (n = 5), health professional education/counselling (n = 10), mass media (n = 5) and other (n = 19). Other included education interventions which did not fit into the four types previously mentioned. Six studies tested more than one education type. Each type within these studies were reported/summarised separately within the appropriate education type. Lay educators resulted in improved awareness and screening. Brochures were effective education materials for screening and combined with lay educators resulted in increased awareness. State-wide mass media campaigns significantly improved screening uptake for up to 2-months post-campaign. Fear and loss-framed messaging improved screening intentions compared to humour or gain-based messaging. Decision aids had limited improvements in awareness. Facebook campaign and telephone counselling had limited improvements in screening. Conclusions: Lay community health educators, brochures, and mass media campaigns occurring multiple times a year may be effective interventions in improving screening and/or awareness. Such approaches should be considered when developing community education. Education interventions should include multiple components suggested above to maximise improvements of awareness and screening.
ABSTRACT
The diet quality of rural Australians is under researched. Characterising disparities in diet quality between rural and urban populations may inform targeted interventions in at- risk groups. A cross-sectional study aimed to determine the relationship between diet quality, rurality and sociodemographic characteristics in a sample of Australian adults. Participants were recruited at rural and regional events between 2017 and 2020, in New South Wales, Australia. Diet quality was measured using the Healthy Eating Quiz or Australian Eating Survey to generate an Australian Recommended Food Score (ARFS). ARFS was compared by rurality and sociodemographic characteristics using multivariate regression. Participants (n = 247; 53% female) had a mean ± SD ARFS of 34.5 ± 9.0. There was no significant effect of rurality on ARFS (ß-coefficient = -0.4; 95%CI -3.0, 2.3). Compared to participants aged 18-30 years, higher ARFS was evident for those aged 31-50 (ß = 5.4; 95%CI 0.3, 10.4), 51-70 (ß = 4.4; 95%CI 0.3, 8.5) and >71 years (ß = 6.5; 95% CI 1.6-11.4). Compared to those living alone, participants living with a partner (ß = 5.2; 95%CI 2.0, 8.4) and families with children (ß = 5.6; 95%CI 1.4, 9.8) had significantly higher ARFS. ARFS was significantly lower with each additional self-reported chronic health condition (ß = -1.4; 95%CI -2.3, -0.4). Our results indicate that diet quality as defined by the ARFS was classified as 'getting there' and that age, living arrangements and chronic health conditions, but not rurality, influenced diet quality in a sample of Australian adults.
Subject(s)
Diet, Healthy/statistics & numerical data , Rural Population/statistics & numerical data , Urban Population/statistics & numerical data , Adolescent , Adult , Age Factors , Aged , Chronic Disease , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , New South Wales , Regression Analysis , Residence Characteristics/statistics & numerical data , Young AdultABSTRACT
Lack of physical activity is a risk factor for dementia, however, the utility of interventional physical activity programs as a protective measure against brain atrophy and cognitive decline is uncertain. Here we present the effect of a randomized controlled trial of a 24-month physical activity intervention on global and regional brain atrophy as characterized by longitudinal voxel-based morphometry with T1-weighted MRI images. The study sample consisted of 98 participants at risk of dementia, with mild cognitive impairment or subjective memory complaints, and having at least one vascular risk factor for dementia, randomized into an exercise group and a control group. Between 0 and 24 months, there was no significant difference detected between groups in the rate of change in global, or regional brain volumes.
Subject(s)
Cognitive Dysfunction , Dementia , Aged , Atrophy/pathology , Brain/diagnostic imaging , Brain/pathology , Cognition , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/pathology , Dementia/diagnostic imaging , Dementia/pathology , Exercise , Humans , Magnetic Resonance ImagingABSTRACT
White matter (WM) microstructure is a sensitive marker to distinguish individuals at risk of Alzheimer's disease. The association of objective physical fitness (PF) measures and WM microstructure has not been explored and mixed results reported with physical activity (PA). Longitudinal studies of WM with PA and PF measures have had limited investigation. This study explored the relationship between objective PF measures over 24-months with "normal-appearing" WM microstructure. Data acquired on magnetic resonance imaging was used to measure "normal-appearing" WM microstructure at baseline and 24-months. Clinical variables such as cognitive and blood-based measures were collected longitudinally. Also, as part of the randomized controlled trial of a PA, extensive measures of PA and fitness were obtained over the 24 months. Bilateral corticospinal tracts (CST) and the corpus callosum showed a significant association between PF performance over 24-months and baseline WM microstructural measures. There was no significant longitudinal effect of the intervention or PF performance over 24-months. Baseline WM microstructural measures were significantly associated with PF performance over 24-months in this cohort of participants with vascular risk factors and at risk of Alzheimer's disease with distinctive patterns for each PF test.
ABSTRACT
BACKGROUND: There is a paucity of information on the role of microvascular and inflammatory biomarkers in cognitive dysfunction. OBJECTIVE: This study sought to evaluate the relationships between established and a number of peripheral biomarkers on cognitive patterns in 108 older adults with memory complaints. METHODS: Participants in the AIBL Active study aged 60 years and older with at least one vascular risk factor and memory complaints completed a neuropsychological test battery and provided cross-sectional health data. Linear regression models adjusted for covariates examined associations between cognitive performance and a panel of vascular risk factors (Framingham cardiovascular scores, hs-CRP, homocysteine, fasting glucose, LDL-cholesterol) and peripheral biomarkers (TNF-α, BDNF, VCAM-1, ICAM-1, PAI-1, CD40L). RESULTS: Higher fasting glucose and homocysteine levels were independent factors associated with poorer performance in Trail Making Test (TMT) B (adjusted ß=â0.40±0.10 and 0.43±0.09, respectively). Increasing homocysteine levels were weakly associated with poorer global cognition and delayed recall (adjusted ß=â0.23±0.10 and -0.20±0.10 respectively). Increasing Framingham cardiovascular scores were related to poorer performance in TMT B (ß â=â0.42±0.19). There was early evidence of associations between increasing plasma TNF-α and poorer TMT B (adjusted ß â=â0.21±0.10) and between increasing BDNF and better global cognition (ß=â-0.20±0.09). CONCLUSION: This study provides evidence to support the associations between vascular risk factors (Framingham scores, fasting glucose, and homocysteine) and poorer cognitive functions. Additionally, we measured several peripheral biomarkers to further investigate their associations with cognition. The relationship between TNF-α, BDNF, and cognitive performance in various domains may offer new insights into potential mechanisms in vascular cognitive impairment.
Subject(s)
Cognition , Cognitive Dysfunction/epidemiology , Heart Disease Risk Factors , Aged , Aged, 80 and over , Australia/epidemiology , Biomarkers , Cognitive Dysfunction/diagnosis , Cross-Sectional Studies , Executive Function , Female , Humans , Inflammation/pathology , Inflammation Mediators/analysis , Male , Memory , Mental Status and Dementia Tests , Microcirculation , Middle Aged , Psychomotor Performance , Risk Factors , Trail Making TestABSTRACT
White matter hyperintensities (WMHs) are a risk factor for cognitive decline. Physical activity (PA) is associated with lower WMH. Whether long-term exposure to PA programs has beneficial effects on WMH progression in older adults with memory complaints and comorbid conditions has had limited exploration. This study explored whether a 24-month moderate-intensity PA intervention can delay the progression of WMH and hippocampus loss in older adults at risk for cognitive decline. Data acquired on magnetic resonance imaging were used to measure the progression of WMH and hippocampus loss. The results of this study showed no effect of intervention on either the primary outcome measure "WMH" or the secondary outcome measure "hippocampal volume." In addition, neither beta amyloid status nor the adherence to the intervention had any effect on the outcome. In this cohort of subjective memory complaints and mild cognitive impairment participants with vascular risk factors, there was no effect of long-term moderate-intensity PA on WMH or hippocampal loss.
Subject(s)
Brain/diagnostic imaging , Brain/pathology , Exercise/physiology , Negative Results , Preventive Health Services/methods , Program Evaluation , Aged , Aged, 80 and over , Alzheimer Disease/prevention & control , Cognitive Dysfunction/prevention & control , Female , Humans , Magnetic Resonance Imaging , Male , Positron-Emission Tomography , Risk , Time FactorsABSTRACT
Studies of the brains of Alzheimer's disease (AD) patients have revealed key neuropathological features, such as the deposition of aggregates of insoluble amyloid-ß (Aß) peptides and neurofibrillary tangles (NFTs). These pathological protein deposits, including Aß peptides (which form senile plaques) and hyperphosphorylated tau (which aggregates into NFTs), have been assumed to be 'the cause of AD'. Aß has been extensively targeted to develop an effective disease-modifying therapy, but with limited clinical success. Emerging therapies are also now targeting further pathological processes in AD, including neuroinflammation. This review focuses on the inflammatory and oxidative stress-related changes that occur in AD, and discusses some emerging anti-inflammatory natural products and phytomedicines. Many of the promising compounds are cytokine-suppressive anti-inflammatory drugs (CSAIDs), which target the proinflammatory AP1 and nuclear factor-κB signalling pathways and inhibit the expression of many proinflammatory cytokines, such as interleukin (IL)-1, IL-6, tumour necrosis factor-α, or nitric oxide produced by inducible nitric oxide synthase. However, many of these phytomedicines have not been tested in rigorous clinical trials in AD patients. It is not yet clear if the active compounds reach an effective concentration in the brain (due to limited bioavailability) or if they can slow down AD progression in long-term trials. The authors suggest that it is crucial for both the pharmacological and complementary medicine industries to conduct and fund those studies to significantly advance the field.
Subject(s)
Alzheimer Disease/drug therapy , Anti-Inflammatory Agents/therapeutic use , Biological Products/therapeutic use , Oxidative Stress/drug effects , Alzheimer Disease/immunology , Alzheimer Disease/metabolism , Clinical Trials as Topic , Cytokines/metabolism , Glycation End Products, Advanced/metabolism , Humans , Inflammation , NF-kappa B/metabolism , Oxidative Stress/immunologyABSTRACT
Increasingly, evidence is accumulating pointing at a protective role of a healthy diet at decreasing the risk of Alzheimer's disease. To test the effectiveness of nutritional components, the following food-derived compounds: curcumin alone (curcumin), curcumin combined with (-)epigallocatechin-3-gallate (EGCG), docosahexaenoic acid (DHA) and α-lipoic acid (ALA) (curcuminâ¯+â¯EDA), or a combination of EGCG, DHA and ALA (EDA) were assessed in male Tg2576 transgenic mice on amyloid plaque load, amyloid levels (Aß40/Aß42, but not oligomers due to tissue limitations), microglial activation and memory using the contextual and cued fear conditioning test. The combination diet EDA, resulted in the strongest reduction of amyloid plaque load in both the cortical (pâ¯<â¯.0001) and hippocampal (pâ¯<â¯.0001) areas of the Tg2576 mouse brain, along with lower Aß40/Aß42 levels in the frontal cortex (pâ¯=â¯.000129 and pâ¯=â¯.000039, respectively) and Aß42 levels in the temporal lobe (pâ¯=â¯.000082). A curcumin only diet was shown to lower amyloid plaque load (pâ¯=â¯.028), but when combined with EGCG, DHA and ALA did not result in further decreases in amyloid plaque load. The EDA combination group showed the most prominent decrease in microglial activation (number of microglia around plaques: pâ¯<â¯.05 and pâ¯<â¯.0001, respectively, for the cortex and hippocampus). Analysing the hippocampal associated contextual fear conditioning revealed that both the curcumin+EDA (pâ¯<â¯.0001) and EDA groups (pâ¯=â¯.001) spent increased time on freezing compared to the control group. In addition, the curcumin+EDA group showed a significant increase in time spent freezing compared with the curcumin only group. In the amygdala associated cued test, all mice demonstrated the ability to associate the conditioned stimulus with the unconditioned stimulus as evidenced by a significant increase in freezing behaviour in response to the presentation of the cue (pâ¯<â¯.0001). Post-hoc analysis showed that only curcumin+EDA (pâ¯<â¯.0001) and EDA groups (pâ¯<â¯.0001) developed a significant increase in freezing during the cue presentation. The results from this study show that the combination of EGCG, DHA and ALA (EDA) appeared to have the most potent anti-inflammatory and neuroprotective effect. Our results also demonstrate that interactions between nutraceutical products might result in counterproductive outcomes, highlighting the fact that manufacturers of nutraceuticals containing multiple compounds should be careful not to claim additive or synergistic effects of their combination products in vivo without having tested it in animal models and/or human clinical trials.
Subject(s)
Alzheimer Disease , Diet, Healthy , Dietary Supplements , Inflammation , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Animals , Antioxidants/administration & dosage , Curcumin/administration & dosage , Disease Models, Animal , Docosahexaenoic Acids/administration & dosage , Male , Mice , Mice, Transgenic , Neuroprotective Agents/administration & dosage , Plaque, Amyloid/pathology , Thioctic Acid/administration & dosageABSTRACT
BACKGROUND: Previous studies have demonstrated that physical activity (PA) interventions can improve physical and cognitive outcomes in older adults, but most have been relatively short in duration (<1 year) with a few having specifically targeting individuals at risk of developing Alzheimer's disease. OBJECTIVE: To examine adherence and physical health outcomes in a 24-month home-based PA intervention in older adults at risk of Alzheimer's disease. METHODS: Participants 60 years and older with mild cognitive impairment (MCI) or subjective memory complaints (SMC) with at least 1 cerebrovascular risk factor recruited from The Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL) were randomized to a PA or control group (nâ=â106). The control group continued with their usual lifestyle. The PA group received a 24-month home-based program with a target of 150 minutes/week of moderate PA and a behavioral intervention. Retention (participants remaining) and PA adherence (PA group only, percent PA completed to the PA prescribed) were determined at 6, 12, 18, and 24 months. Assessments at baseline, 6, 12, and 24 months included, PA; fitness; body composition and fat distribution. Key outcome measures were PA adherence and PA. RESULTS: The 24-month retention rate (97.2%) and the median PA adherence 91.67% (Q1-Q3, 81.96, 100.00) were excellent. In the long-term the intervention group achieved significantly better improvements in PA levels, leg strength, fat mass and fat distribution compared to the control. CONCLUSION: This study demonstrates that in this target group, long-term PA adherence is achievable and has physical health benefits.
Subject(s)
Aging/psychology , Alzheimer Disease/prevention & control , Cognitive Dysfunction/prevention & control , Exercise/psychology , Life Style , Patient Compliance , Aged , Alzheimer Disease/psychology , Cognitive Dysfunction/psychology , Female , Humans , Male , Middle AgedABSTRACT
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by deposition of amyloid plaques and neurofibrillary tangles, as well as microglial and astroglial activation, and, finally, leading to neuronal dysfunction and death. Current treatments for AD primarily focus on enhancement of cholinergic transmission. However, these treatments are only symptomatic, and no disease-modifying drug is available for the treatment of AD patients. This review will provide an overview of the antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects of a variety of nutraceuticals including curcumin, apigenin, docosahexaenoic acid, epigallocatechin gallate, α-lipoic acid and resveratrol and their potential for AD prevention and treatment. We suggest that therapeutic use of these compounds might lead to a safe strategy to delay the onset of AD or slow down its progression. The continuing investigation of the potential of these substances is necessary as they are promising compounds to yield a possible remedy for this pervasive disease.
Subject(s)
Alzheimer Disease/drug therapy , Alzheimer Disease/pathology , Antioxidants/therapeutic use , Biological Products/therapeutic use , Neuroprotective Agents/therapeutic use , Alzheimer Disease/metabolism , Animals , Antioxidants/isolation & purification , Biological Products/isolation & purification , Chronic Disease , Curcumin/isolation & purification , Curcumin/therapeutic use , Fish Oils/isolation & purification , Fish Oils/therapeutic use , Humans , Inflammation/metabolism , Inflammation/pathology , Inflammation/prevention & control , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Neurodegenerative Diseases/prevention & control , Neurofibrillary Tangles/drug effects , Neurofibrillary Tangles/metabolism , Neurofibrillary Tangles/pathology , Neuroprotective Agents/isolation & purification , Randomized Controlled Trials as Topic/methods , Resveratrol , Stilbenes/isolation & purification , Stilbenes/therapeutic useABSTRACT
BACKGROUND: To evaluate a new semi-automated segmentation method for calculating hippocampal volumes and to compare results with standard software tools in a cohort of people with subjective memory complaints (SMC) and mild cognitive impairment (MCI). METHODS: Data from 58 participants, 39 with SMC (17 male, 22 female, mean age 72.6) and 19 with MCI (6 male, 13 female, mean age 74.3), were analyzed. For each participant, T1-weighted images were acquired using an MPRAGE sequence on a 3 Tesla MRI system. Hippocampal volumes (left, right, and total) were calculated with a new, age appropriate registration template, based on older people and using the advanced software tool ANTs (Advanced Normalization Tools). The results were compared with manual tracing (seen as the reference standard) and two widely accepted automated software tools (FSL, FreeSurfer). RESULTS: The hippocampal volumes, calculated by using the age appropriate registration template were significantly (P < 0.05) more accurate (mean volume accuracy more than 90%) than those obtained with FreeSurfer and FSL (both less than 70%). Dice coefficients for the hippocampal segmentations with the new template method (75.3%) were slightly, but significantly (P < 0.05) higher than those from FreeSurfer (72.4%). CONCLUSION: These results suggest that an age appropriate registration template might be a more accurate alternative to calculate hippocampal volumes when manual segmentation is not feasible.
Subject(s)
Aging/pathology , Cognitive Dysfunction/pathology , Hippocampus/pathology , Image Interpretation, Computer-Assisted/methods , Memory Disorders/pathology , Subtraction Technique , Aged , Cognitive Dysfunction/complications , Female , Humans , Image Enhancement/methods , Male , Memory Disorders/complications , Pattern Recognition, Automated/methods , Reproducibility of Results , Sensitivity and Specificity , SoftwareABSTRACT
BACKGROUND: Recent evidence suggests that exercise plays a role in cognition and that the posterior cingulate cortex (PCC) can be divided into dorsal and ventral subregions based on distinct connectivity patterns. AIMS: To examine the effect of physical activity and division of the PCC on brain functional connectivity measures in subjective memory complainers (SMC) carrying the epsilon 4 allele of apolipoprotein E (APOE ε4) allele. METHOD: Participants were 22 SMC carrying the APOE ε4 allele (ε4+; mean age 72.18 years) and 58 SMC non-carriers (ε4-; mean age 72.79 years). Connectivity of four dorsal and ventral seeds was examined. Relationships between PCC connectivity and physical activity measures were explored. RESULTS: ε4+ individuals showed increased connectivity between the dorsal PCC and dorsolateral prefrontal cortex, and the ventral PCC and supplementary motor area (SMA). Greater levels of physical activity correlated with the magnitude of ventral PCC-SMA connectivity. CONCLUSIONS: The results provide the first evidence that ε4+ individuals at increased risk of cognitive decline show distinct alterations in dorsal and ventral PCC functional connectivity. DECLARATION OF INTEREST: D.A. has served on scientific advisory boards for Novartis, Eli Lilly, Janssen, Prana and Pfizer, and as Editor-in-Chief for International Psychogeriatrics; received speaker honoraria from Pfizer and Lundbeck, and research support from Eli Lilly, GlaxoSmithKline, Forest Laboratories, Novartis, and CSIRO. C.L.M. has received consulting fees from Eli Lilly and Prana Biotechnology, and has stock ownership in Prana Biotechnology. C.C.R. has received consultancy payments from Roche and Piramal, and research support from Avid Radiopharmaceuticals, Eli Lilly, GE Healthcare, Piramal and Navidea for amyloid imaging. C.S. has provided clinical consultancy and been on scientific advisory committees for the Australian CSIRO, Alzheimer's Australia, University of Melbourne and other relationships, which are subject to confidentiality clauses; she has been a named Chief Investigator on investigator-driven collaborative research projects in partnership with Pfizer, Merck, Piramal, Bayer and GE Healthcare. Her research programme has received support from the National Health and Medical Research Council Alzheimer's Association, Collier Trust, Scobie and Claire McKinnon Foundation, JO and JR Wicking Trust, Shepherd Foundation, Brain Foundation, Mason Foundation, Ramaciotti Foundation, Alzheimer's Australia and the Royal Australian College of Physicians. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.
ABSTRACT
Apolipoprotein E (ApoE) is important in facilitating the transport of lipids (cholesterol, phospholipids, and sulfatides) and plays a fundamental role in normal lipid metabolism. High cholesterol levels increases the risk of developing Alzheimer's disease. In this study, we investigated the effects of a high-fat high cholesterol (HFHC) diet on brain lipid profiles in 95 young and aged APOE ε3 and ε4 knock-in mice to determine whether diet leads to altered brain levels of a number of glycerophospholipids, sphingolipids, cholesterol precursors, cholesterol, cholesterol oxidation products, and cholesterol esters. The results in this study revealed significant changes in lipid levels. The HFHC-enriched diet influenced the levels of cholesterol esters. A sharp increase in cholesterol ester levels, particularly in the aged APOE ε4 diet-enriched group, might be suggestive of abnormal acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT) activity and/or levels. Age exerts appreciable effects on the brain lipidome, especially with regard to polar lipid species.
Subject(s)
Aging/metabolism , Apolipoprotein E3/genetics , Apolipoprotein E3/physiology , Apolipoprotein E4/genetics , Apolipoprotein E4/physiology , Brain/metabolism , Cholesterol, Dietary/administration & dosage , Diet, High-Fat/adverse effects , Genotype , Lipid Metabolism/genetics , Animals , Cholesterol Esters/metabolism , Gene Knock-In Techniques , Male , Mass Spectrometry , Mice , Mice, Transgenic , Sterol O-Acyltransferase/metabolism , Sulfoglycosphingolipids/metabolismABSTRACT
BACKGROUND: Older adults free of dementia but with subjective memory complaints (SMC) or mild cognitive impairment (MCI) are considered at increased risk of cognitive decline. Vascular risk factors (VRF), including hypertension, heart disease, smoking, hypercholesterolemia and lack of physical activity (PA) have been identified as modifiable risk factors contributing to cognitive decline, and white matter hyperintensities (WMH) are associated with VRF, SMC and cognitive impairment. Findings from a growing number of clinical trials with older adults are providing strong evidence for the benefits of physical activity for maintaining cognitive function, but few studies are investigating these benefits in high-risk populations. The aim of AIBL Active is to determine whether a 24-month physical activity program can delay the progression of white matter changes on magnetic resonance imaging (MRI). METHODS/DESIGN: This single-blind randomized controlled trial (RCT) is offered to 156 participants, aged 60 and older, in the Melbourne arm of the Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL). Participants must have SMC with or without MCI and at least one VRF. The PA intervention is a modification of the intervention previously trialed in older adults with SMC and MCI (Fitness for the Ageing Brain Study). It comprises 24 months of moderate, home-based PA (150 minutes per week) and a behavioral intervention package. The primary outcome measure will be change in WMH after 24 months on MRI. Cognition, quality of life, functional fitness, level of physical activity, plasma biomarkers for cerebrovascular disease and amyloid positron emission tomography (PET) imaging comprise secondary measures. DISCUSSION: Currently, there is no effective pharmacological treatment available to delay cognitive decline and dementia in older adults at risk. Should our findings show that physical activity can slow down the progression of WMH, this RCT would provide an important proof of concept. Since imbedded in AIBL this RCT will also be able to investigate the interaction between vascular and Alzheimer's disease pathologies. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12611000612910.
Subject(s)
Brain/pathology , Cognitive Dysfunction , Disease Progression , Exercise Therapy/methods , Magnetic Resonance Imaging/methods , Memory Disorders , Adult , Aged , Brain/physiopathology , Cognitive Behavioral Therapy/methods , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/prevention & control , Cognitive Dysfunction/therapy , Exercise Therapy/standards , Female , Geriatric Assessment , Humans , Magnetic Resonance Imaging/instrumentation , Male , Memory Disorders/pathology , Memory Disorders/physiopathology , Memory Disorders/therapy , Middle Aged , Single-Blind Method , Treatment OutcomeABSTRACT
AIM: The purpose of this research was to use metabolomics to investigate the cystic phenotype in the Lewis polycystic kidney rat. METHODS: Spot urine samples were collected from four male Lewis control and five male Lewis polycystic kidney rats aged 5 weeks, before kidney function was significantly impaired. Metabolites were extracted from urine and analysed using gas chromatography-mass spectrometry. Principal component analysis was used to determine key metabolites contributing to the variance observed between sample groups. RESULTS: With the development of a metabolomics method to analyse Lewis and Lewis polycystic kidney rat urine, 2-ketoglutaric acid, allantoin, uric acid and hippuric acid were identified as potential biomarkers of cystic disease in the rat model. CONCLUSION: The findings of this study demonstrate the potential of metabolomics to further investigate kidney disease.
Subject(s)
Metabolomics , Polycystic Kidney Diseases/urine , Allantoin/urine , Animals , Biomarkers/urine , Disease Models, Animal , Gas Chromatography-Mass Spectrometry , Hippurates/urine , Ketoglutaric Acids/urine , Male , Metabolomics/methods , Phenotype , Principal Component Analysis , Rats , Rats, Inbred Lew , Uric Acid/urine , UrinalysisABSTRACT
The epsilon4 allele of apolipoprotein E (APOE) is currently the major genetic risk factor identified for Alzheimer's disease (AD). Previous in vivo data from our laboratory has demonstrated that amyloid-beta (Abeta) is rapidly removed from the plasma by the liver and kidney and that the rate of its clearance is affected by ApoE in C57BL/6J and APOE-/- mice. To expand upon these findings, we assessed the peripheral clearance of human synthetic Abeta42 in APOE epsilon2, epsilon3, and epsilon4 knock-in and APOE knock-out mice injected with lipidated recombinant apoE2, E3, and E4 protein. Our results show that APOE does influence the rate at which the mice are able to clear Abeta42 from their bloodstream. Both APOE epsilon4 mice and APOE knock-out mice treated with lipidated recombinant apoE4 demonstrated increased retention of plasma Abeta42 over time compared to APOE epsilon2/APOE knock-out rE2 and APOE epsilon3/APOE knock-out rE3 mice. These findings suggest that the peripheral clearance of Abeta42 is significantly altered by APOE genotype. Given that APOE epsilon4 is a risk factor for AD, then these novel findings provide some insight into the role of ApoE isoforms on the peripheral clearance of Abeta which may impact on clearance from the brain.
Subject(s)
Alzheimer Disease/metabolism , Amyloid beta-Peptides/pharmacokinetics , Apolipoprotein E2/genetics , Apolipoprotein E3/genetics , Apolipoprotein E4/genetics , Peptide Fragments/pharmacokinetics , Alzheimer Disease/genetics , Amyloid beta-Peptides/blood , Animals , Apolipoprotein E2/pharmacology , Apolipoprotein E3/pharmacology , Apolipoprotein E4/pharmacology , Brain/metabolism , Gene Knock-In Techniques , Genotype , Humans , Mice , Mice, 129 Strain , Mice, Inbred C57BL , Mice, Knockout , Peptide Fragments/blood , Recombinant Proteins/genetics , Recombinant Proteins/pharmacology , Tissue DistributionABSTRACT
It is known that apolipoprotein E (ApoE) is essential for normal lipid metabolism. ApoE is the major apolipoprotein in the central nervous system and plays a key role in neurobiology by mediating the transport of cholesterol, phospholipids, and sulfatides. We therefore examined APOE epsilon2, epsilon3, and epsilon4 knock-in mice, using electrospray ionization mass spectrometry to determine if APOE genotype or age leads to altered levels in the brain of a number of glycerophospholipids (phosphatidylinositol, PI; phosphatidylethanolamine, PE; phosphatidic acid, PA, phosphatidylserine, PS; phosphatidylcholine, PC), sphingolipids (sphingomyelin, SM; ceramide, Cer), cholesterol, and triacylglycerols. We observed slight changes within individual PI, PE, PC, Cer, and SM lipid levels in APOE epsilon2 and epsilon4 mice compared to APOE epsilon3 mice. However, overall, we did not observe any major effects in APOE epsilon4 knock-in mice for the levels of the glycerophospholipids measured, as compared to APOE epsilon2 and epsilon3 mice. Our findings indicate that variations in ApoE isoforms do not per se affect bulk lipid homeostasis in the brain. These findings indicate that APOE epsilon4 is not associated with disturbances in brain sterol or sphingolipids in the absence of environmental factors.
Subject(s)
Apolipoproteins E/genetics , Brain/metabolism , Lipids/blood , Plasma/metabolism , Age Factors , Animals , Apolipoprotein E2 , Apolipoprotein E3 , Apolipoprotein E4 , Humans , Male , Mice , Mice, Transgenic , Spectrometry, Mass, Electrospray Ionization/methodsABSTRACT
Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting millions of people worldwide. Apart from age, the major risk factor identified so far for the sporadic form of AD is possession of the epsilon4 allele of apolipoprotein E (APOE), which is also a risk factor for coronary artery disease (CAD). Other apolipoproteins known to play an important role in CAD such as apolipoprotein B are now gaining attention for their role in AD as well. AD and CAD share other risk factors, such as altered cholesterol levels, particularly high levels of low density lipoproteins together with low levels of high density lipoproteins. Statins--drugs that have been used to lower cholesterol levels in CAD, have been shown to protect against AD, although the protective mechanism(s) involved are still under debate. Enzymatic production of the beta amyloid peptide, the peptide thought to play a major role in AD pathogenesis, is affected by membrane cholesterol levels. In addition, polymorphisms in several proteins and enzymes involved in cholesterol and lipoprotein transport and metabolism have been linked to risk of AD. Taken together, these findings provide strong evidence that changes in cholesterol metabolism are intimately involved in AD pathogenic processes. This paper reviews cholesterol metabolism and transport, as well as those aspects of cholesterol metabolism that have been linked with AD.
Subject(s)
Alzheimer Disease/etiology , Alzheimer Disease/metabolism , Biological Transport/physiology , Cholesterol/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Animals , Apolipoproteins/metabolism , Biological Transport/drug effects , Brain/metabolism , Brain/pathology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Models, Biological , Receptors, LDL/physiologySubject(s)
Carbohydrates/chemistry , Diet, Atherogenic , Dietary Fats/metabolism , Lipoproteins, LDL/metabolism , Proteins/metabolism , Animal Feed , Animals , Aorta/metabolism , Cholesterol/metabolism , Cytokines/metabolism , Guinea Pigs , Inflammation , Male , Models, Biological , Models, StatisticalABSTRACT
Carbohydrate-restricted diets (CRDs) promote weight loss, reductions in plasma triacylglycerol (TAG) levels, and increases in high-density lipoprotein cholesterol (HDL-C) levels but may cause undesirable low-density lipoprotein cholesterol (LDL-C) responses in some people. The objective of the present study was to determine the effect of adding soluble fiber to a CRD on plasma LDL-C and other traditionally measured markers of cardiovascular disease. Using a parallel-arm, double-blind, placebo-controlled design, 30 overweight and obese men (body mass index, 25-35 kg/m(2)) were randomly assigned to supplement a CRD with soluble fiber (Konjac-mannan, 3g/d) (n = 15) or placebo (n = 15). Plasma lipids, anthropometrics, body composition, blood pressure, and nutrient intake were evaluated at baseline and at 6 and 12 weeks. Compliance was excellent as assessed by 7-day weighed dietary records and ketonuria. Both groups experienced decreases in (P < .01) body weight, percent body fat, systolic blood pressure, waist circumference, and plasma glucose levels. After 12 weeks, HDL-C and TAG improved significantly in the fiber (10% and -34%) and placebo (14%, -43%) groups. LDL-C decreased by 17.6% (P < .01) at week 6 and 14.1% (P < .01) at week 12 in the fiber group. Conversely, LDL-C reductions were significant in the placebo group only after 12 weeks (-6.0%, P < .05). We conclude that although clearly effective at lowering LDL-C, adding soluble fiber to a CRD during active and significant weight loss provides no additional benefits to the diet alone. Furthermore, a CRD led to clinically important positive alterations in cardiovascular disease risk factors.