RESUMO
Accumulation of ß-amyloid (Aß) in the brain is associated with memory decline in healthy individuals as a prelude to Alzheimer's disease (AD). Genetic factors may moderate this decline. We examined the role of apolipoprotein E (É4 carrier[É4(+)], É4 non-carrier[É4(-)]) and brain-derived neurotrophic factor (BDNF(Val/Val), BDNF(Met)) in the extent to which they moderate Aß-related memory decline. Healthy adults (n=333, Mage=70 years) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent Aß neuroimaging. Neuropsychological assessments were conducted at baseline, 18-, 36- and 54-month follow-ups. Aß positron emission tomography neuroimaging was used to classify participants as Aß(-) or Aß(+). Relative to Aß(-)É4(-), Aß(+)É4(+) individuals showed significantly faster rates of cognitive decline over 54 months across all domains (d=0.40-1.22), while Aß(+)É4(-) individuals showed significantly faster decline only on verbal episodic memory (EM). There were no differences in rates of cognitive change between Aß(-)É4(-) and Aß(-)É4(+) groups. Among Aß(+) individuals, É4(+)/BDNF(Met) participants showed a significantly faster rate of decline on verbal and visual EM, and language over 54 months compared with É4(-)/BDNF(Val/Val) participants (d=0.90-1.02). At least two genetic loci affect the rate of Aß-related cognitive decline. Aß(+)É4(+)/BDNF(Met) individuals can expect to show clinically significant memory impairment after 3 years, whereas Aß(+)É4(+)/BDNF(Val/Val) individuals can expect a similar degree of impairment after 10 years. Little decline over 54 months was observed in the Aß(-) and Aß(+) É4(-) groups, irrespective of BDNF status. These data raise important prognostic issues in managing preclinical AD, and should be considered in designing secondary preventative clinical trials.
Assuntos
Doença de Alzheimer/complicações , Peptídeos beta-Amiloides/metabolismo , Apolipoproteínas E/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Transtornos Cognitivos , Polimorfismo de Nucleotídeo Único/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Compostos de Anilina/metabolismo , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/genética , Transtornos Cognitivos/metabolismo , Feminino , Seguimentos , Engenharia Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Escalas de Graduação Psiquiátrica , Tiazóis/metabolismoRESUMO
The aim of this paper was to investigate the association of three well-recognised dietary patterns with cognitive change over a 3-year period. Five hundred and twenty-seven healthy participants from the Australian Imaging, Biomarkers and Lifestyle study of ageing completed the Cancer Council of Victoria food frequency questionnaire at baseline and underwent a comprehensive neuropsychological assessment at baseline, 18 and 36 months follow-up. Individual neuropsychological test scores were used to construct composite scores for six cognitive domains and a global cognitive score. Based on self-reported consumption, scores for three dietary patterns, (1) Australian-style Mediterranean diet (AusMeDi), (2) western diet and (3) prudent diet were generated for each individual. Linear mixed model analyses were conducted to examine the relationship between diet scores and cognitive change in each cognitive domain and for the global score. Higher baseline adherence to the AusMeDi was associated with better performance in the executive function cognitive domain after 36 months in apolipoprotein E (APOE) É4 allele carriers (P<0.01). Higher baseline western diet adherence was associated with greater cognitive decline after 36 months in the visuospatial cognitive domain in APOE É4 allele non-carriers (P<0.01). All other results were not significant. Our findings in this well-characterised Australian cohort indicate that adherence to a healthy diet is important to reduce risk for cognitive decline, with the converse being true for the western diet. Executive function and visuospatial functioning appear to be particularly susceptible to the influence of diet.
Assuntos
Transtornos Cognitivos/epidemiologia , Dieta , Idoso , Envelhecimento/genética , Envelhecimento/psicologia , Apolipoproteína E4/genética , Austrália , Transtornos Cognitivos/genética , Estudos de Coortes , Função Executiva , Feminino , Seguimentos , Humanos , Modelos Lineares , Masculino , Testes Neuropsicológicos , Análise de Componente Principal , Inquéritos e QuestionáriosRESUMO
Lower hemoglobin is associated with cognitive impairment and Alzheimer's disease (AD). Since brain iron homeostasis is perturbed in AD, we investigated whether this is peripherally reflected in the hematological and related blood chemistry values from the Australian Imaging Biomarker and Lifestyle (AIBL) study (a community-based, cross-sectional cohort comprising 768 healthy controls (HC), 133 participants with mild cognitive impairment (MCI) and 211 participants with AD). We found that individuals with AD had significantly lower hemoglobin, mean cell hemoglobin concentrations, packed cell volume and higher erythrocyte sedimentation rates (adjusted for age, gender, APOE-É4 and site). In AD, plasma iron, transferrin, transferrin saturation and red cell folate levels exhibited a significant distortion of their customary relationship to hemoglobin levels. There was a strong association between anemia and AD (adjusted odds ratio (OR)=2.43, confidence interval (CI) (1.31, 4.54)). Moreover, AD emerged as a strong risk factor for anemia on step-down regression, even when controlling for all other available explanations for anemia (adjusted OR=3.41, 95% CI (1.68, 6.92)). These data indicated that AD is complicated by anemia, which may itself contribute to cognitive decline.
Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/complicações , Anemia/sangue , Anemia/complicações , Disfunção Cognitiva/sangue , Disfunção Cognitiva/complicações , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Estudos Transversais , Feminino , Ácido Fólico/sangue , Hemoglobinas/metabolismo , Humanos , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Transferrina/metabolismoRESUMO
Dementia is a global epidemic with Alzheimer's disease (AD) being the leading cause. Early identification of patients at risk of developing AD is now becoming an international priority. Neocortical Aß (extracellular ß-amyloid) burden (NAB), as assessed by positron emission tomography (PET), represents one such marker for early identification. These scans are expensive and are not widely available, thus, there is a need for cheaper and more widely accessible alternatives. Addressing this need, a blood biomarker-based signature having efficacy for the prediction of NAB and which can be easily adapted for population screening is described. Blood data (176 analytes measured in plasma) and Pittsburgh Compound B (PiB)-PET measurements from 273 participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were utilised. Univariate analysis was conducted to assess the difference of plasma measures between high and low NAB groups, and cross-validated machine-learning models were generated for predicting NAB. These models were applied to 817 non-imaged AIBL subjects and 82 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) for validation. Five analytes showed significant difference between subjects with high compared to low NAB. A machine-learning model (based on nine markers) achieved sensitivity and specificity of 80 and 82%, respectively, for predicting NAB. Validation using the ADNI cohort yielded similar results (sensitivity 79% and specificity 76%). These results show that a panel of blood-based biomarkers is able to accurately predict NAB, supporting the hypothesis for a relationship between a blood-based signature and Aß accumulation, therefore, providing a platform for developing a population-based screen.
Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Neocórtex/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Compostos de Anilina , Apolipoproteínas E/genética , Quimiocina CCL3/sangue , Estudos de Coortes , Proteínas Culina , Feminino , Humanos , Interleucina-17 , Masculino , Neocórtex/diagnóstico por imagem , Polipeptídeo Pancreático , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Curva ROC , TiazóisRESUMO
Testosterone and gonadotropins have been associated with cognitive decline in men and the modulation of ß amyloid (Aß) metabolism. The relatively few studies that have investigated whether changes in one or a combination of these hormones influence Aß levels have focused primarily on plasma Aß(1-40) and not on the more pathogenic Aß(1-42). Currently, no study has investigated whether these hormones are associated with an increase in brain amyloid deposition, ante mortem. Through the highly characterised Australian imaging, biomarkers and lifestyle study, we have determined the impact of these hormones on plasma Aß levels and brain amyloid burden (Pittsburgh compound B (PiB) retention). Spearman's rank correlation and linear regression analysis was carried out across the cohort and within subclassifications. Luteinizing hormone (LH) was the only variable shown, in the total cohort, to have a significant impact on plasma Aß(1-40) and Aß(1-42) levels (beta=0.163, P<0.001; beta=0.446, P<0.001). This held in subjective memory complainers (SMC) (Aß(1-40); beta=0.208, P=0.017; Aß(1-42); beta=0.215, P=0.017) but was absent in mild cognitive impairment (MCI) and Alzheimer's disease (AD) groups. In SMC, increased frequency of the APOE-É4 allele (beta=0.536, P<0.001) and increasing serum LH levels (beta=0.421, P=0.004) had a significant impact on PiB retention. Whereas in MCI, PiB retention was associated with increased APOE-É4 allele copy number (beta=0.674, P<0.001) and decreasing calculated free testosterone (beta=-0.303, P=0.043). These findings suggest a potential progressive involvement of LH and testosterone in the early preclinical stages of AD. Furthermore, these hormones should be considered while attempting to predict AD at these earliest stages of the disease.
Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Gonadotropinas/metabolismo , Fragmentos de Peptídeos/metabolismo , Testosterona/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Compostos de Anilina , Apolipoproteínas E/genética , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Estudos de Coortes , Humanos , Modelos Lineares , Masculino , Transtornos da Memória/diagnóstico por imagem , Transtornos da Memória/metabolismo , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Escalas de Graduação Psiquiátrica , Fatores de Risco , Estatísticas não Paramétricas , TiazóisRESUMO
Previous studies suggest physical activity improves cognition and lowers Alzheimer's disease (AD) risk. However, key AD pathogenic factors that are thought to be influenced by physical activity, particularly plasma amyloid-ß (Aß) and Aß brain load, have yet to be thoroughly investigated. The objective of this study was to determine if plasma Aß and amyloid brain deposition are associated with physical activity levels, and whether these associations differed between carriers and non-carriers of the apolipoprotein E (APOE) ε4 allele. Five-hundred and forty six cognitively intact participants (aged 60-95 years) from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) were included in these analyses. Habitual physical activity levels were measured using the International Physical Activity Questionnaire (IPAQ). Serum insulin, glucose, cholesterol and plasma Aß levels were measured in fasting blood samples. A subgroup (n=116) underwent (11)C-Pittsburgh compound B (PiB) positron emission tomography (PET) scanning to quantify brain amyloid load. Higher levels of physical activity were associated with higher high density lipoprotein (HDL) (P=0.037), and lower insulin (P<0.001), triglycerides (P=0.019) and Aß1-42/1-40 ratio (P=0.001). After stratification of the cohort based on APOE ε4 allele carriage, it was evident that only non-carriers received the benefit of reduced plasma Aß from physical activity. Conversely, lower levels of PiB SUVR (standardised uptake value ratio) were observed in higher exercising APOE ε4 carriers. Lower plasma Aß1-42/1-40 and brain amyloid was observed in those reporting higher levels of physical activity, consistent with the hypothesis that physical activity may be involved in the modulation of pathogenic changes associated with AD.
Assuntos
Envelhecimento/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Atividade Motora , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Alelos , Peptídeos beta-Amiloides/sangue , Apolipoproteína E4/genética , Biomarcadores/sangue , Biomarcadores/metabolismo , Glicemia , Colesterol/sangue , Feminino , Neuroimagem Funcional , Humanos , Insulina/sangue , Estilo de Vida , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The prognostic value of subjective memory complaints (SMCs) in the diagnosis of dementia of the Alzheimer's type is unclear. While some studies have found an association between SMCs and cognitive decline, many have found a stronger association with depression, which raises questions about their diagnostic utility. METHODS: We examined the cross-sectional association between SMC severity (as measured using the MAC-Q, a brief SMC questionnaire) and affect, memory, and Alzheimer's disease (AD) biomarkers (ß-amyloid deposition and the apolipoprotein E ε4 (APOEε4) allele) in healthy elderly controls (HC; M = 78.74 years, SD = 6.7) and individuals with mild cognitive impairment (MCI; M = 72.74 years, SD = 8.8). We analyzed a subset of individuals drawn from the Australian Imaging Biomarkers and Lifestyle (AIBL) Study of Aging. RESULTS: SMCs were more severe in MCI patients than in HCs. SMC severity was related to affective variables and the interaction between age and group membership (HC/MCI). Within the HC group, SMC severity was related to affective variables only, while severity correlated only with age in the MCI group. SMCs were not related to cognitive variables or AD biomarkers. CONCLUSION: SMCs were related to solely by poorer mood (greater depressive and anxious symptomatology) in the cognitively healthy elderly however mean levels were subclinical. This finding argues for the assessment of affective symptomatology in conjunction with cognitive assessment in elderly memory complainers. Future AIBL research will focus on assessing other AD biomarkers, such as brain atrophy and Aß plasma markers, in relation to complaint severity. Once our 36-month follow-up data are collected, we propose to assess whether SMCs can predict future cognitive decline.
Assuntos
Envelhecimento , Doença de Alzheimer/complicações , Biomarcadores/sangue , Memória , Afeto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Austrália , Estudos de Casos e Controles , Disfunção Cognitiva/diagnóstico , Estudos Transversais , Feminino , Avaliação Geriátrica/métodos , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Prognóstico , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: To assess whether consumption of lean red meat on three exercise training days per week can promote greater improvements than exercise alone in health-related quality of life (HR-QoL) in community-dwelling older adults. DESIGN: This study is a secondary analysis from a 6 month, two-arm, parallel randomized controlled trial conducted in 2014 and 2015. SETTING: Community-dwelling older adults living in metropolitan Melbourne, Australia. PARTICIPANTS: One hundred and fifty-four men and women aged ≥65 years. INTERVENTION: All participants were enrolled in a multi-component, resistance-based exercise program (3 d/week) and randomly allocated to either a group asked to consume lean red meat (2x80g cooked servings/day) on each of the three training days (Ex+Meat, n=77) or a control group asked to consume one serving of carbohydrates (1/2 cup rice/pasta or 1 medium potato; Ex+C, n=77). MEASUREMENTS: HR-QoL was assessed using the Short-Form (SF)-36 health survey. RESULTS: Overall 62% of the participants were female, the mean age was 70.7 years (range 65 to 84 years), approximately 67% of participants were classified as either overweight or obese, and the average number of chronic conditions was two. A total of 145 participants (94%) completed the study. Mean baseline HR-QoL scores were comparable to the mean for the Australian population [Global HR-QoL (mean ± SD): Ex+Meat, 49.99 ± 6.57; Ex+C, 50.49 ± 5.27]. General Linear Mixed Models examining within and between group changes over time revealed that after 6 months, there were no within-group changes in either Ex+Meat or Ex+C nor any between-group differences for any measure of HR-QoL, with the exception that the mental health subscale improved in Ex+C versus Ex+Meat [net difference for change, -2.32 (95% CI), -4.73, 0.09, P=0.048] after adjusting for relevant covariates and the physical function subscale improved in Ex+Meat relative to baseline [mean change (95% CI), 1.88 (0.37, 3.39), P=0.011]. CONCLUSION: A multi-component resistance-based training program performed with and without the provision of lean red meat in line with current Australian dietary guidelines on each of the three training days, did not improve HR-QoL in healthy community-dwelling older adults.
Assuntos
Carne Vermelha , Treinamento Resistido , Masculino , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Qualidade de Vida , Austrália , Exercício FísicoRESUMO
OBJECTIVES: Metabolic syndrome (MetS) represents a cluster of obesity and insulin resistance-related comorbidities. Abdominal obesity, hypertension, elevated triglyceride and glucose levels are components of MetS and may have a negative effect on cognitive function, but few cognitive studies have examined the combined risk severity. We sought to determine which specific cognitive abilities were associated with MetS in older adults at risk of cognitive decline. DESIGN: Cross-sectional study. PARTICIPANTS: 108 AIBL Active participants with memory complaints and at least one cardiovascular risk factor. MEASUREMENTS: Cardiovascular parameters and blood tests were obtained to assess metabolic syndrome criteria. The factors of MetS were standardized to obtain continuous z-scores. A battery of neuropsychological tests was used to evaluate cognitive function. RESULTS: Higher MetS z-scores were associated with poorer global cognition using ADAS-cog (adjusted standardized beta=0.26, SE 0.11, p<0.05) and higher Trail Making B scores (adjusted beta=0.23, SE 0.11, p<0.05). Higher MetS risk was related to lower cognitive performance. CONCLUSION: Combined risk due to multiple risk factors in MetS was related to lower global cognitive performance and executive function. A higher MetS risk burden may point to opportunities for cognitive testing in older adults as individuals may experience cognitive changes.
Assuntos
Doenças Cardiovasculares/etiologia , Cognição/fisiologia , Disfunção Cognitiva/etiologia , Síndrome Metabólica/complicações , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Extensive experimental and neuropathological evidence supports the general hypothesis that decline in the basal forebrain cholinergic system contributes significantly to age-related cognitive impairment. Postmortem studies suggest reductions in neuronal nicotinic acetylcholine receptors (nAChRs, particularly the alpha(4)beta(2) subtype) with aging. This study aimed to determine the distribution of alpha(4)beta(2)-subtype nAChRs in vivo by 2-FA PET in healthy subjects (aged 21-83) and to establish whether there is an age-related decline in nAChRs. Furthermore, the relationship between PET measures of 2-FA binding and neurobehavioral measures of cognitive function was investigated. All participants were nonsmokers and underwent extensive cognitive testing and a PET scan after injection of 2-FA (200 MBq). Brain regional 2-FA binding was assessed through a simplified estimation of distribution volume (DV(S)). As expected, increasing age was associated with poorer cognitive performance, particularly on tasks assessing episodic memory and attentional processes. No significant age-related differences in regional nAChR DV(S) were found. Furthermore, no significant correlations were found between cognitive measures and nAChR DV(S). These results are consistent with recent studies suggesting the stability of cholinergic markers during senescence. It is plausible that changes in alpha(4)beta(2) nAChRs do occur with advancing age, but are beyond detection by the clinical 2-FA PET approach adopted here. However, this approach may be appropriate for use in pathologies considered to undergo extensive nAChR loss such as Alzheimer's disease and Parkinson's disease.
Assuntos
Acetilcolina/metabolismo , Envelhecimento/metabolismo , Encéfalo/metabolismo , Transtornos Cognitivos/metabolismo , Transtornos da Memória/metabolismo , Receptores Nicotínicos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Azetidinas , Ligação Competitiva/efeitos dos fármacos , Ligação Competitiva/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/fisiopatologia , Feminino , Radioisótopos de Flúor , Humanos , Masculino , Transtornos da Memória/diagnóstico por imagem , Transtornos da Memória/fisiopatologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Receptores Nicotínicos/efeitos dos fármacos , Adulto JovemRESUMO
Control of parasitic gastroenteritis in cattle is typically based on group treatments with anthelmintics, complemented by grazing management, where feasible. However, the almost inevitable evolution of resistance in parasitic nematodes to anthelmintics over time necessitates a reappraisal of their use in order to reduce selection pressure. One such approach is targeted selective treatment (TST), in which only individual animals that will most benefit are treated, rather than whole groups of at-risk cattle. This study was designed to assess the feasibility of implementing TST on three commercial farms, two of which were organic. A total of 104 first-grazing season (FGS), weaned dairy calves were enrolled in the study; each was weighed at monthly intervals from the start of the grazing season using scales or weigh-bands. At the same time dung and blood samples were collected in order to measure faecal egg counts (FEC) and plasma pepsinogen, respectively. A pre-determined threshhold weight gain of 0.75kg/day was used to determine those animals that would be treated; the anthelmintic used was eprinomectin. No individual animal received more than one treatment during the grazing season and all treatments were given in July or August; five animals were not treated at all because their growth rates consistently exceeded the threshold. Mean daily live weight gain over the entire grazing season ranged between 0.69 and 0.82kg/day on the three farms. Neither FEC nor pepsinogen values were significantly associated with live weight gain. Implementation of TST at farm level requires regular (monthly) handling of the animals and the use of weigh scales or tape, but can be integrated into farm management practices. This study has shown that acceptable growth rates can be achieved in FGS cattle with modest levels of treatment and correspondingly less exposure of their nematode populations to anthelmintics, which should mitigate selection pressure for resistance by increasing the size of the refugia in both hosts and pasture.
Assuntos
Anti-Helmínticos/uso terapêutico , Doenças dos Bovinos/tratamento farmacológico , Gastroenterite/veterinária , Enteropatias Parasitárias/veterinária , Nematoides/efeitos dos fármacos , Infecções por Nematoides/veterinária , Animais , Bovinos , Doenças dos Bovinos/parasitologia , Indústria de Laticínios , Estudos de Viabilidade , Fezes/parasitologia , Feminino , Gastroenterite/tratamento farmacológico , Gastroenterite/parasitologia , Enteropatias Parasitárias/tratamento farmacológico , Ivermectina/análogos & derivados , Ivermectina/uso terapêutico , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/parasitologia , Contagem de Ovos de Parasitas/veterinária , Pepsinogênio A/sangue , Aumento de PesoRESUMO
During a 12-mo longitudinal study, bulk-tank milk was collected each month from organic (n = 17) and conventional (n = 19) dairy farms in the United Kingdom. All milk samples were analyzed for fatty acid (FA) content, with the farming system type, herd production level, and nutritional factors affecting the FA composition investigated by use of mixed model analyses. Models were constructed for saturated fatty acids, the ratio of polyunsaturated fatty acids (PUFA) to monounsaturated fatty acids, total n-3 FA, total n-6 FA, conjugated linoleic acid, and vaccenic acid. The ratio of n-6:n-3 FA in both organic and conventional milk was also compared. Organic milk had a higher proportion of PUFA to monounsaturated fatty acids and of n-3 FA than conventional milk, and contained a consistently lower n-6:n-3 FA ratio (which is considered beneficial) compared with conventional milk. There was no difference between organic and conventional milk with respect to the proportion of conjugated linoleic acid or vaccenic acid. A number of factors other than farming system were identified which affected milk FA content including month of year, herd average milk yield, breed type, use of a total mixed ration, and access to fresh grazing. Thus, organic dairy farms in the United Kingdom produce milk with a higher PUFA content, particularly n-3 FA, throughout the year. However, knowledge of the effects of season, access to fresh grazing, or use of specific silage types could be used by producers to enhance the content of beneficial FA in milk.
Assuntos
Ácidos Graxos/análise , Alimentos Orgânicos/análise , Leite/química , Ração Animal , Animais , Ácidos Graxos Monoinsaturados/análise , Ácidos Graxos Ômega-3/análise , Ácidos Graxos Ômega-6/análise , Ácidos Graxos Insaturados/análise , Ácidos Linoleicos Conjugados/análise , Ácidos Oleicos/análise , Estações do Ano , Reino UnidoRESUMO
The earliest detectable change in Alzheimer's disease (AD) is the buildup of amyloid plaque in the brain. Early detection of AD, prior to irreversible neurological damage, is important for the efficacy of current interventions as well as for the development of new treatments. Although PiB-PET imaging and CSF amyloid are the gold standards for early AD diagnosis, there are practical limitations for population screening. AD-related pathology occurs primarily in the brain, but some of the hallmarks of the disease have also been shown to occur in other tissues, including the retina, which is more accessible for imaging. Retinal vascular changes and degeneration have previously been reported in AD using optical coherence tomography and laser Doppler techniques. This report presents results from analysis of retinal photographs from AD and healthy control participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing. This is the first study to investigate retinal blood vessel changes with respect to amyloid plaque burden in the brain. We demonstrate relationships between retinal vascular parameters, neocortical brain amyloid plaque burden and AD. A number of RVPs were found to be different in AD. Two of these RVPs, venular branching asymmetry factor and arteriolar length-to-diameter ratio, were also higher in healthy individuals with high plaque burden (P = 0.01 and P = 0.02 respectively, after false discovery rate adjustment). Retinal photographic analysis shows potential as an adjunct for early detection of AD or monitoring of AD-progression or response to treatments.
Assuntos
Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Doenças Retinianas/complicações , Doenças Retinianas/diagnóstico , Idoso , Análise de Variância , Austrália , Biomarcadores , Encéfalo/diagnóstico por imagem , Estudos de Coortes , Progressão da Doença , Diagnóstico Precoce , Feminino , Humanos , Masculino , Fotografação/métodos , Placa Amiloide/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Reprodutibilidade dos Testes , Artéria Retiniana , Veia RetinianaRESUMO
OBJECTIVE: Given the recent and growing interest in the concepts of prodromal and presymptomatic Alzheimer disease, it is crucial to determine whether the presence of ß-amyloid (Aß) in the brain of asymptomatic elderly individuals is a pathologic condition associated with accelerated neuronal and synaptic loss. The aim of the present study was to assess whether Aß influences the rate of atrophy in cognitively normal elderly individuals. METHODS: Seventy-four healthy elderly individuals underwent an MRI scan and a 11C-Pittsburgh compound B (PiB) PET scan at baseline and a second MRI scan 18 months later. Voxel-wise analyses were performed using maps of annual rate of atrophy generated from the serial MRI scans, including comparison between individuals with high vs low neocortical PiB and correlation with baseline neocortical PiB. RESULTS: The rate of atrophy was significantly higher in the normal elderly individuals with high PiB compared with those with low PiB and was significantly correlated with baseline neocortical PiB, with the highest significance in the temporal neocortex and the posterior cingulate cortex. CONCLUSIONS: Our findings show that the presence of Aß in the brain, known to occur in about one-third of asymptomatic elderly individuals, is actually a pathologic state associated with accelerated atrophy. They also suggest that therapy aimed to reduce the neurodegenerative process should be commenced in presymptomatic individuals with high PiB.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Córtex Cerebral/patologia , Cognição/fisiologia , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina , Atrofia , Mapeamento Encefálico , Cerebelo/patologia , Córtex Cerebral/diagnóstico por imagem , Disfunção Cognitiva/patologia , Disfunção Cognitiva/psicologia , Progressão da Doença , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Neocórtex/patologia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , TiazóisRESUMO
Numerous studies have reported positive impacts of physical activity on cognitive function. However, the majority of these studies have utilised physical activity questionnaires or surveys, thus results may have been influenced by reporting biases. Through the objective measurement of routine levels of physical activity via actigraphy, we report a significant association between intensity, but not volume, of physical activity and cognitive functioning. A cohort of 217 participants (aged 60-89 years) wore an actigraphy unit for 7 consecutive days and underwent comprehensive neuropsychological assessment. The cohort was stratified into tertiles based on physical activity intensity. Compared with individuals in the lowest tertile of physical activity intensity, those in the highest tertile scored 9%, 9%, 6% and 21% higher on the digit span, digit symbol, Rey Complex Figure Test (RCFT) copy and Rey Figure Test 30-min recall test, respectively. Statistically, participants in the highest tertile of physical activity intensity performed significantly better on the following cognitive tasks: digit symbol, RCFT copy and verbal fluency test (all P<0.05). The results indicate that intensity rather than quantity of physical activity may be more important in the association between physical activity and cognitive function.
Assuntos
Cognição/fisiologia , Exercício Físico/fisiologia , Atividade Motora/fisiologia , Actigrafia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Exercício Físico/psicologia , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
The Mediterranean diet (MeDi), due to its correlation with a low morbidity and mortality for many chronic diseases, has been widely recognised as a healthy eating model. We aimed to investigate, in a cross-sectional study, the association between adherence to a MeDi and risk for Alzheimer's disease (AD) and mild cognitive impairment (MCI) in a large, elderly, Australian cohort. Subjects in the Australian Imaging, Biomarkers and Lifestyle Study of Ageing cohort (723 healthy controls (HC), 98 MCI and 149 AD participants) completed the Cancer Council of Victoria Food Frequency Questionnaire. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of AD and MCI status in multinominal logistic regression models that were adjusted for cohort age, sex, country of birth, education, apolipoprotein E genotype, total caloric intake, current smoking status, body mass index, history of diabetes, hypertension, angina, heart attack and stroke. There was a significant difference in adherence to the MeDi between HC and AD subjects (P < 0.001), and in adherence between HC and MCI subjects (P < 0.05). MeDi is associated with change in Mini-Mental State Examination score over an 18-month time period (P < 0.05) in HCs. We conclude that in this Australian cohort, AD and MCI participants had a lower adherence to the MeDi than HC participants.
Assuntos
Doença de Alzheimer/epidemiologia , Dieta Mediterrânea/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Idoso , Doença de Alzheimer/prevenção & controle , Austrália/epidemiologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/prevenção & controle , Estudos de Coortes , Estudos Transversais , Feminino , Seguimentos , Avaliação Geriátrica/métodos , Avaliação Geriátrica/estatística & dados numéricos , Humanos , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
A 12-month study was conducted to assess and monitor gastrointestinal tract nematodes and liver fluke in cohorts of cattle on a Scottish organic dairy farm. Various diagnostic markers for helminth parasites of cattle from different age groups were assessed monthly from April 2007 to March 2008. First season grazing stock were subjected to significant challenge from Ostertagia ostertagi nematodes as reflected in serum pepsinogen concentrations, which rose markedly in the second half of the grazing season. In addition, plasma albumin concentrations decreased and faecal egg counts (FEC) increased moderately, indicating exposure to both O ostertagi and probably Cooperia oncophora. Second season grazing animals had a peak FEC early in the grazing period, suggestive of a potential carry-over of Ostertagia species infection ('Type 2') during housing. All classes of cattle showed evidence of fluke (Fasciola hepatica) infection. Adult cow exposure to O ostertagi and fluke was estimated via the use of ELISA testing to detect antibodies to O ostertagi and F hepatica and the high levels detected suggested a significant exposure response. Despite low stocking densities and sympathetic grazing management, there was a significant challenge to all grazing stock from gastrointestinal nematodes and liver fluke.
Assuntos
Doenças dos Bovinos/diagnóstico , Indústria de Laticínios/métodos , Fasciolíase/veterinária , Enteropatias Parasitárias/veterinária , Agricultura Orgânica , Pepsinogênios/sangue , Animais , Biomarcadores/sangue , Bovinos , Doenças dos Bovinos/sangue , Estudos de Coortes , Fasciolíase/sangue , Fasciolíase/diagnóstico , Fezes/parasitologia , Feminino , Enteropatias Parasitárias/sangue , Enteropatias Parasitárias/diagnóstico , Contagem de Ovos de Parasitas/veterinária , Escócia , Estações do Ano , Albumina Sérica/metabolismoRESUMO
OBJECTIVE: There is mounting evidence for the contribution of apoE to the pathophysiology of Alzheimer disease (AD). Studies also indicate that plasma apoE levels may reflect disease status, suggesting that apoE is a potential AD biomarker. However, while some studies of apoE levels in plasma have presented correlations with AD pathology, others have not. Thus, there is a lack of consensus as to the suitability of plasma apoE as an AD biomarker. The major objective of this cross-sectional study was to investigate total plasma apoE as well as levels of the apoE4 form in a large, highly characterized cohort which included both healthy controls and participants with early-stage AD. METHODS: Total apoE and apoE4 were measured in 1,079 individuals drawn from the highly characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Total and isoform-specific plasma apoE levels were then compared with cerebral Aß load, as assessed by PET using Pittsburgh compound B (PiB). RESULTS: Total apoE and apoE4 levels were found to be significantly lower in patients with AD in the entire cohort, and decrease with Aß load in the PiB-PET subset. ApoE levels were significantly lower among ε4 homozygous individuals. In APOE ε3/ε4 heterozygote carriers, apoE4 levels decrease, indicating that apoE3 levels increase with disease. CONCLUSION: Analysis of cross-sectional data from the AIBL study indicates that plasma apoE levels are altered in AD and correlate with AD pathology level. The significance of these findings will be determined in the AIBL longitudinal study of aging.
Assuntos
Envelhecimento/metabolismo , Doença de Alzheimer/diagnóstico , Apolipoproteína E4/sangue , Apolipoproteínas E/sangue , Encéfalo/metabolismo , Transtornos Cognitivos/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Idoso , Envelhecimento/sangue , Envelhecimento/psicologia , Doença de Alzheimer/sangue , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina , Biomarcadores/sangue , Encéfalo/diagnóstico por imagem , Radioisótopos de Carbono , Transtornos Cognitivos/sangue , Transtornos Cognitivos/complicações , Transtornos Cognitivos/diagnóstico por imagem , Estudos Transversais , Heterozigoto , Homozigoto , Humanos , Fatores de Risco , TiazóisRESUMO
The strategies used and the results obtained in Orkney's bovine viral diarrhoea virus (BVDV) eradication programme over eight years (2001 to 2008) are presented and discussed. The venture was undertaken by local veterinary practices and the Orkney Livestock Association (OLA) with the financial support of the Orkney Islands Council. Participation is voluntary; the programme comprises screening of youngstock, a whole-herd test if required, elimination of persistently infected animals and strict biosecurity measures and/or vaccination. BVDV-free herds are certified, and certification is updated annually by retesting the youngstock. The programme aims to minimise economic losses, thereby increasing the competitiveness of the Orcadian cattle industry and to improve animal health and welfare by eliminating virus circulation. Information from databases of the Scottish Agricultural College, Biobest Laboratories and OLA show that despite a significant reduction in the overall prevalence of BVDV on Orkney during the initial stages of the eradication programme, there has been little progress made since 2006 and that some difficulties have been encountered, with herd BVDV breakdowns following initial eradication. These results highlight the need for continued motivation of farmers, strict application of biosecurity measures and/or systematic vaccination of all seronegative breeding animals.
Assuntos
Doença das Mucosas por Vírus da Diarreia Viral Bovina/prevenção & controle , Vacinação/veterinária , Criação de Animais Domésticos , Bem-Estar do Animal , Animais , Doença das Mucosas por Vírus da Diarreia Viral Bovina/economia , Bovinos , Análise Custo-Benefício , Indústria de Laticínios , Vírus da Diarreia Viral Bovina/isolamento & purificação , Eutanásia Animal , Feminino , Masculino , Programas de Rastreamento/veterinária , Reino Unido/epidemiologia , Vacinação/economiaRESUMO
OBJECTIVE: To investigate whether global and regional beta-amyloid (Abeta) burden as measured with 11C Pittsburgh compound B (PIB) PET is associated with hippocampal atrophy characterized using MRI in healthy controls and patients with amnestic mild cognitive impairment (aMCI) or Alzheimer disease (AD). METHODS: Ninety-two elderly healthy controls, 32 subjects with aMCI, and 35 patients with AD were imaged using 11C-PIB PET and MRI. Hippocampal volume was measured and PIB standardized uptake value ratio was extracted after partial volume correction within 41 regions of interest. Global, regional, and voxel-based correlations between PIB and hippocampal volume were computed for each group. RESULTS: In healthy control participants with elevated neocortex PIB retention, significant correlation was found between PIB retention in the inferior temporal region and hippocampal volume using both region-based and voxel-based approaches. No correlation was found in any other group. CONCLUSIONS: The strong correlation between hippocampal atrophy and beta-amyloid (Abeta) burden in the Pittsburgh compound B-positive healthy control group suggests that Abeta deposition in the inferior temporal neocortex is related to hippocampal synaptic and neuronal degeneration.