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BACKGROUND: It remains unclear whether cognitive reserve can attenuate dementia risk among people with different genetic predispositions. AIMS: We aimed to examine the association between cognitive reserve and dementia, and further to explore whether and to what extent cognitive reserve may modify the risk effect of genetic factors on dementia. METHOD: Within the UK Biobank, 210 631 dementia-free participants aged ≥60 years were followed to detect incident dementia. Dementia was ascertained through medical and death records. A composite cognitive reserve indicator encompassing education, occupation and multiple cognitively loaded activities was created using latent class analysis, categorised as low, moderate and high level. Polygenic risk scores for Alzheimer's disease were constructed to evaluate genetic risk for dementia, categorised by tertiles (high, moderate and low). Data were analysed using Cox models and Laplace regression. RESULTS: In multi-adjusted Cox models, the hazard ratio (HR) of dementia was 0.66 (95% confidence interval (CI) 0.61-0.70) for high cognitive reserve compared with low cognitive reserve. In Laplace regression, participants with high cognitive reserve developed dementia 1.62 (95% CI 1.35-1.88) years later than those with low cognitive reserve. In stratified analysis by genetic risk, high cognitive reserve was related to more than 30% lower dementia risk compared with low cognitive reserve in each stratum. There was an additive interaction between low cognitive reserve and high genetic risk on dementia (attributable proportion 0.24, 95% CI 0.17-0.31). CONCLUSIONS: High cognitive reserve is associated with reduced risk of dementia and may delay dementia onset. Genetic risk for dementia may be mitigated by high cognitive reserve. Our findings underscore the importance of enhancing cognitive reserve in dementia prevention.
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Reserva Cognitiva , Demência , Herança Multifatorial , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Demência/genética , Demência/epidemiologia , Predisposição Genética para Doença , Modelos de Riscos Proporcionais , Fatores de Risco , Biobanco do Reino Unido , Reino Unido/epidemiologiaRESUMO
INTRODUCTION: The associations of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with brain structural changes are unclear. METHODS: Among 26,466 UK Biobank participants, a 15-point MIND score was calculated from 24-hour diet recalls from 2009 to 2012. We assessed its associations with 17 magnetic-resonance-derived brain volumetric markers and their longitudinal changes and explored whether genetic factors modify the associations. RESULTS: Higher MIND adherence was associated with larger volumes of thalamus, putamen, pallidum, hippocampus, and accumbens (beta per 3-unit increment ranging from 0.024 to 0.033) and lower white matter hyperintensities (P-trends < 0.05), regardless of genetic predispositions of Alzheimer's disease. MIND score was not associated with their longitudinal changes (P > 0.05) over a median of 2.2 years among participants with repeated imaging assessments (N = 2963), but was associated with slower atrophy in putamen (beta: 0.026, P-trend = 0.044) and pallidum (beta: 0.030, P-trend = 0.033) among APOE ε4 non-carriers (N = 654). DISCUSSION: The MIND diet showed beneficial associations with certain brain imaging markers, and its associations with long-term brain structural changes warrants future investigation. HIGHLIGHTS: Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet was significantly associated with higher volumes and larger gray matter volumes in certain brain regions in UK adults, and the associations were not modified by genetic factors. No significant associations were observed between MIND diet and longitudinal changes in the investigated brain structural markers over a median of 2.2 years. Higher MIND score was significantly associated with slower atrophy in the putamen and pallidum among APOE ε4 non-carriers.
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Doença de Alzheimer , Dieta Mediterrânea , Adulto , Humanos , Apolipoproteína E4 , Doença de Alzheimer/genética , Substância Cinzenta , AtrofiaRESUMO
INTRODUCTION: Apolipoprotein E4 (APOE4) carriers' tendency toward hypercholesterolemia may contribute to Alzheimer's disease (AD) risk through oxysterols, which traverse the blood-brain barrier. METHODS: Relationships between baseline plasma oxysterols, APOE status, serum lipids, and cognitive impairment risk were examined in 328 postmenopausal women from the Women's Health Initiative Memory Study. Women were followed for 25 years or until incident dementia or cognitive impairment. RESULTS: Levels of 24(S)-hydroxycholesterol (24-OHC), 27-hydroxycholesterol (27-OHC), and 24-OHC/27-OHC ratio did not differ by APOE status (p's > 0.05). Higher 24-OHC and 27-OHC were associated with higher total, low density lipoprotein (LDL), non-high density lipoprotein (HDL), remnant, LDL/HDL, and total/HDL cholesterol and triglycerides (p's < 0.05). Higher 24-OHC/27-OHC was associated with greater dementia risk (hazard ratio = 1.51, 95% confidence interval:1.02-2.22), which interaction analyses revealed as significant for APOE3 and APOE4+, but not APOE2+ carriers. DISCUSSION: Less favorable lipid profiles were associated with higher oxysterol levels. A higher ratio of 24-OHC/27-OHC may contribute to dementia risk in APOE3 and APOE4+ carriers.
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Demência , Lipídeos , Oxisteróis , Humanos , Feminino , Demência/sangue , Idoso , Oxisteróis/sangue , Lipídeos/sangue , Hidroxicolesteróis/sangue , Apolipoproteína E4/genética , Fatores de Risco , Pessoa de Meia-Idade , Pós-Menopausa/sangueRESUMO
BACKGROUND: Whether a low-inflammatory diet relates to type 2 diabetes risk remains unclear. We examined the association between a low-inflammatory diet and risk of type 2 diabetes among normoglycemic and prediabetic participants. We also explored whether a low-inflammatory diet modifies genetic risk for type 2 diabetes. METHODS: Among 142,271 diabetes-free UK Biobank participants (aged 39-72 years), 126,203 were normoglycemic and 16,068 were prediabetic at baseline. Participants were followed for up to 15 years to detect incident type 2 diabetes. At baseline, dietary intake was assessed with a 24-h dietary record. An inflammatory diet index (IDI) was generated based on high-sensitivity C-reactive protein levels and was a weighted sum of 34 food groups (16 anti-inflammatory and 18 pro-inflammatory). Participants were grouped into tertiles corresponding to inflammatory level (low, moderate, and high) based on IDI scores. Prediabetes at baseline was defined as HbA1c 5.7-6.4% in diabetes-free participants. Incident type 2 diabetes and age of onset were ascertained according to the earliest recorded date of type 2 diabetes in the Primary Care and Hospital inpatient data. A diabetes-related genetic risk score (GRS) was calculated using 424 single-nucleotide polymorphisms. Data were analyzed using Cox regression and Laplace regression. RESULTS: During follow-up (median 8.40 years, interquartile range 6.89 to 11.02 years), 3348 (2.4%) participants in the normoglycemia group and 2496 (15.5%) in the prediabetes group developed type 2 diabetes. Type 2 diabetes risk was lower in normoglycemic (hazard ratio [HR] = 0.71, 95% confidence interval [CI] 0.65, 0.78) and prediabetic (HR = 0.81, 95% CI 0.73, 0.89) participants with low IDI scores compared to those with high IDI scores. A low-inflammatory diet may prolong type 2 diabetes onset by 2.20 (95% CI 1.67, 2.72) years among participants with normoglycemia and 1.11 (95% CI 0.59, 1.63) years among participants with prediabetes. In joint effect analyses, normoglycemic or prediabetes participants with low genetic predisposition to type 2 diabetes and low IDI scores had a significant 74% (HR = 0.26, 95% CI 0.21, 0.32) or 51% (HR = 0.49, 95% CI 0.40, 0.59) reduction in type 2 diabetes risk compared to those with high genetic risk plus high IDI scores. There were significant additive and multiplicative interactions between IDI and GRS in relation to type 2 diabetes risk in the normoglycemia group. CONCLUSIONS: A low-inflammatory diet is associated with a decreased risk of type 2 diabetes and may delay type 2 diabetes onset among participants with normal blood glucose or prediabetes. A low-inflammatory diet might significantly mitigate the risk of genetic factors on type 2 diabetes development.
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Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Humanos , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/genética , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Incidência , Glicemia/metabolismo , Fatores de Risco , DietaRESUMO
INTRODUCTION: Whether apolipoprotein E's (APOE's) involvement in lipid metabolism contributes to Alzheimer's disease (AD) risk remains unknown. METHODS: Incident probable dementia and cognitive impairment (probable dementia+mild cognitive impairment) were analyzed in relation to baseline serum lipids (total, low-density lipoprotein [LDL], high-density lipoprotein [HDL], non-HDL cholesterol, total-to-HDL, LDL-to-HDL, remnant cholesterol, and triglycerides) using Mendelian randomization in 5358 postmenopausal women from the Women's Health Initiative Memory Study. We also examined associations of baseline dietary cholesterol and fat with lipids based on APOE status. RESULTS: After an average of 11.13 years, less favorable lipid levels related to greater dementia and cognitive impairment risk. Dementia (odds ratio [OR] = 3.13; 95% confidence interval [CI]: 2.31 to 4.24) and cognitive impairment (OR = 2.38; 95% CI: 1.85 to 3.06) risk were greatest in relation to higher remnant cholesterol levels. Greater cholesterol consumption related to poorer lipids in APOE4+ compared to APOE3 carriers. DISCUSSION: APOE4+ carriers consuming more cholesterol had less favorable lipids, which were associated with greater dementia and cognitive impairment risk. HIGHLIGHTS: Less favorable serum lipids were associated with higher dementia incidence. Mendelian randomization findings suggest causality between lipids and dementia. Lipid levels in older women may be clinical indicators of dementia risk. APOE4 carriers had poorest lipid profiles in relation to cholesterol consumption. APOE risk for dementia may be modifiable through lipid management.
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Colesterol na Dieta , Demência , Idoso , Feminino , Humanos , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Colesterol , Demência/epidemiologia , Demência/genética , Genótipo , Fatores de Risco , TriglicerídeosRESUMO
BACKGROUND: Although age at menopause has been linked to mortality, the association between the entire reproductive lifespan and mortality remains unclear. OBJECTIVE: This study aimed to examine to what extent life-course reproductive duration is associated with all-cause mortality and explore the role of a healthy lifestyle and familial background in such an association. STUDY DESIGN: A total of 11,669 women (mean age, 63.54 years) from the Swedish Twin Registry were followed for up to 19 years. Information on reproductive duration (the interval between ages at menarche and menopause) and lifestyle factors (including smoking, alcohol consumption, and physical activity; divided into unfavorable/intermediate/favorable) was collected on the basis of a structured questionnaire. Survival status was obtained from the Sweden Cause of Death Register. The data were analyzed using generalized estimating equation models, Laplace regression, and conditional logistic regression. RESULTS: In the generalized estimating equation model, compared with those with ≤34 reproductive years, the odds ratio (95% confidence interval) of all-cause mortality was 0.79 (0.68-0.90) for those with ≥40 reproductive years, which prolonged survival time by 0.84 (0.24-1.43) years. Women with ≥40 reproductive years plus a favorable lifestyle (odds ratio, 0.28; 95% confidence interval, 0.23-0.35) were at a lower risk of all-cause mortality than those with <40 reproductive years plus an unfavorable lifestyle. An additive interaction between ≥40 reproductive years and a favorable lifestyle on all-cause mortality was observed (attributable proportion, 0.584; 95% confidence interval, 0.016-1.151). The odds ratios in conditional logistic regression and generalized estimating equation models did not differ significantly (P=.67). CONCLUSION: A longer reproductive lifespan is associated with reduced all-cause mortality and prolongs survival by 0.84 years. A favorable lifestyle may amplify the beneficial effect of longer reproductive lifespan on mortality. Familial background does not account for the observed association.
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OBJECTIVE: This study is based on long-term follow-up of participants in a randomized double-blind sham surgery-controlled trial (1995-1999) designed to determine the effectiveness of implantation of human embryonic mesencephalic tissue containing dopamine neuron precursors into the brains of patients with advanced Parkinson's disease (PD). We investigated differences between long-term survivors and nonsurvivors at baseline in order to contribute to information regarding optimal patient selection for upcoming stem cell trials. METHOD: Forty participants were randomly assigned to receive either neural implantation or sham surgery. Thirty-four patients who ultimately received the implant were followed periodically with the most recent assessment occurring in 2015-2016. Demographic information, neurological measures, positron emission tomography (PET) imaging, neuropsychological assessments, and a personality assessment were included in the current analyses. T-tests were used to compare survivors and nonsurvivors. Logistic regression analyses examined predictors of survivorship. RESULTS: Five of six survivors were female. They were younger than nonsurvivors (p = .03) and more neuropsychologically "intact" across a broad range of cognitive areas (significance levels ranged from <.001 to .045). There were no differences between survivors and nonsurvivors off medications at baseline on neurological or PET assessments. Survivors reported more "Openness to Experience" (p = .004) than nonsurvivors. Using empirically derived predictor variables, results of logistic regression analyses indicated that Animal Naming (cognitive task) and Openness to Experience (personality variable) were the strongest predictors of survivorship. CONCLUSIONS: Variables to consider when selecting participants for future cell-based therapies include being "intact" neuropsychologically, level of Openness to Experience, younger age, and inclusion of women.
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Encéfalo , Sobreviventes , Colorado , Método Duplo-Cego , Feminino , Humanos , Masculino , Testes NeuropsicológicosRESUMO
BACKGROUND: This article aimed to develop and validate a simple-to-use nomogram to predict 15-year disability-free survival among older adults. METHODS: A cohort of 1878 disability-free participants aged ≥60 was followed for 15 years. Participants were randomly divided into a training cohort for nomogram development (n = 1314 [70 %]) and validation cohort to confirm the model's performance (n = 564 [30 %]). Information on socio-demographic, lifestyle factors, the Life Satisfaction Index A (LSI-A), chronic diseases, and Mini-Mental State Examination (MMSE) score, and biomarkers were collected through interviews, clinical and neuropsychological examinations, and medical records. Disability-free survival was defined as survival in the absence of dementia and physical disability, and the composite endpoint is first occurrence of events of death, dementia and physical disability. We developed a nomogram summing the number of risk points corresponding to weighted covariates to predict disability-free survival. Validation of the nomogram using C statistic, calibration plots, and Kaplan-Meier curves. RESULTS: In the multivariate-adjusted model, factors associated with composite end point were younger age, high MMSE (hazard ratio [HR], 0.93; [95 % CI, 0.87-0.99]), high LSI-A (0.78, [0.64-0.97]), non-smoking (0.74, [0.59-0.94]), engagement in physical leisure activity (0.62, [0.48-0.78]), and absence of chronic diseases (0.78, [0.66-0.91]). Incorporating these 6 factors, the nomogram achieved C-statistics of 0.78 (95 % CI, 0.75-0.81) and 0.77 (95 % CI, 0.74-0.80) in predicting disability-free survival in the training and validation cohorts, respectively, and had good calibration curves. CONCLUSION: The nomogram was able to predict long-term of disability-free survival and performed well on internal validation, and may be considered for use in effective surveillance, promote, management of clinical and public health ageing.
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OBJECTIVES: The association of the dietary inflammatory potential with cancer risk remains uncertain. We examined the relationship of the dietary inflammatory potential with risk of overall and site-specific cancers and explored its sex and age differences. DESIGN: A community-based longitudinal study. SETTING: Participants from the UK Biobank completed baseline surveys during 2006-2010 and were followed for up to 15 years to detect incident cancer. PARTICIPANTS: 170,899 cancer-free participants with dietary data available (mean age: 55.73 ± 7.95, 54.10% female). MEASUREMENTS: At baseline, dietary intake was assessed with a 24-h dietary record for up to 5 times. The inflammatory diet index (IDI) was calculated to assess the dietary inflammatory potential as a weighted sum of 31 food groups (including 14 anti-inflammatory and 17 pro-inflammatory) based on plasma high-sensitivity C-reactive protein (hsCRP) levels, and tertiled as low (indicating low-inflammatory diet), moderate, and high IDI (as reference). Overall and site-specific cancers were ascertained via linkage to routine hospital admission, cancer registry, and death certificate data. Data were analyzed using Cox regression and Laplace regression. RESULTS: During the follow-up (median 10.32 years, interquartile range: 9.95-11.14 years), 18,884 (11.05%) participants developed cancer. In multi-adjusted Cox regression, low IDI scores were associated with decreased risk of rectal cancer (hazard ratio [95% confidence interval, CI] 0.76 [0.61, 0.94]), thyroid cancer [0.45 (0.27, 0.74)], lung cancer [0.73 (0.61, 0.88)]. However, the association between IDI score and the risk of overall cancer was not significant. Laplace regression analysis showed that 10th percentile differences (95% CIs) of cancer onset time for participants with low IDI scores was prolonged by 1.29 (0.32, 2.27), 1.44 (0.58, 2.30), and 2.62 (0.98, 4.27) years for rectal cancer, thyroid cancer, and lung cancer, respectively, compared to those with high IDI scores. Stratified analysis revealed that low IDI scores were associated with a lower risk of rectal cancer (p interaction between IDI score and sex = 0.035) and lung cancer in males, but not in females, and with a reduced risk of thyroid cancer in females, but not in males. Moreover, low IDI scores were associated with a reduced risk of rectal cancer and lung cancer in the participants aged ≥60 years, but not in those <60 years, and with a reduced risk of thyroid cancer in those aged ≥60 years and <60 years. CONCLUSIONS: A low-inflammatory diet is associated with decreased risk and prolonged onset time of rectal cancer and lung cancer, especially among males and individuals aged ≥60 years, and thyroid cancer among females.
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Dieta , Inflamação , Neoplasias , Humanos , Masculino , Feminino , Estudos Longitudinais , Pessoa de Meia-Idade , Reino Unido/epidemiologia , Neoplasias/epidemiologia , Dieta/estatística & dados numéricos , Dieta/efeitos adversos , Fatores de Risco , Idoso , Bancos de Espécimes Biológicos , Proteína C-Reativa/análise , Adulto , Modelos de Riscos Proporcionais , Registros de Dieta , Neoplasias Pulmonares/epidemiologia , Incidência , Neoplasias da Glândula Tireoide/epidemiologia , Biobanco do Reino UnidoRESUMO
Importance: Inflammation has been proposed as a mechanism linking cardiometabolic diseases (CMDs) to increased risk of dementia. However, whether an anti-inflammatory diet can support brain and cognitive health among people with CMDs is unclear. Objective: To examine CMD status and dietary inflammatory potential in association with dementia risk and brain magnetic resonance imaging (MRI) measures using joint effect analysis. Design, Setting, and Participants: The UK Biobank is an ongoing community-based cohort study with baseline assessments conducted between March 13, 2006, and October 1, 2010. The present study included 84â¯342 dementia-free older adults (≥60 years), who were followed up until January 20, 2022 (maximum, 15 years). A subsample (n = 8917) underwent brain MRI scans between May 2, 2014, and March 13, 2020. Exposures: Baseline CMDs (including type 2 diabetes, heart disease, and stroke) were ascertained from medical records. Dietary Inflammatory Index scores (anti-inflammatory [≤-1.5 points], neutral [>-1.5 to <0.5 points], or proinflammatory [≥0.5 points]) were calculated from participants' average intake of 31 nutrients, assessed up to 5 times using the Oxford WebQ, a web-based, 24-hour dietary assessment. Main Outcomes and Measures: Incident dementia was identified through linkage to medical records. Regional brain volumes were collected from brain MRI scans. Results: The study included 84â¯342 participants (mean [SD] age, 64.1 [2.9] years; 43â¯220 [51.2%] female). At baseline, 14â¯079 (16.7%) had at least 1 CMD. Over a median follow-up of 12.4 (IQR, 11.8-13.1) years, 1559 individuals (1.9%) developed dementia. With the use of joint effect analysis, the hazard ratio of dementia was 2.38 (95% CI, 1.93-2.93) for people with CMDs and a proinflammatory diet and 1.65 (95% CI, 1.36-2.00) for those with CMDs and an anti-inflammatory diet (reference: CMD-free, anti-inflammatory diet). Dementia risk was 31% lower (hazard ratio, 0.69; 95% CI, 0.55-0.88; P = .003) among people with CMDs and an anti-inflammatory diet. On brain MRI, participants with CMDs and an anti-inflammatory diet compared with a proinflammatory diet additionally had significantly larger gray matter volume (ß = -0.15; 95% CI, -0.24 to -0.06 vs ß = -0.27; 95% CI, -0.38 to -0.16) and smaller white matter hyperintensity volume (ß = 0.05; 95% CI, -0.04 to 0.14 vs ß = 0.16; 95% CI, 0.05-0.27). Conclusions and Relevance: In this cohort study, people with CMDs and an anti-inflammatory compared with proinflammatory diet had a significantly lower hazard ratio of dementia, larger gray matter volume, and smaller white matter hyperintensity volume.
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Demência , Dieta , Inflamação , Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Demência/epidemiologia , Idoso , Pessoa de Meia-Idade , Estudos de Coortes , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Reino Unido/epidemiologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologiaRESUMO
BACKGROUND & AIMS: Evidence on the association between dietary inflammation and longevity is limited. We aimed to examine the association of a low-inflammatory diet with mortality and longevity, and to explore whether cardiometabolic diseases (CMDs) and lifestyle factors may play a role in this association. METHODS: Within the UK Biobank, 188,443 participants aged 39-72 years (mean 56.07) were followed for up to 16 years to detect survival status from the death registry. At baseline, dietary intake was assessed with a 24-h dietary record. An inflammatory diet index (IDI) was calculated as weighted sum of 31 food groups (including 14 anti-inflammatory and 17 pro-inflammatory) based on plasma high-sensitivity C-reactive protein levels, and tertiled as low, moderate, and high IDI scores. Baseline lifestyle beyond diet was assessed by summing the number of healthy lifestyle factors (i.e., never smoking, regular physical activity, and normal BMI) and categorized as unfavorable (≤1) and favorable (≥2). Presence of CMDs was defined as having any one of type 2 diabetes, ischemic heart disease, atrial fibrillation, heart failure, and stroke. Data were analyzed using Cox regression, Laplace regression, and generalized structural equation modelling. RESULTS: During the follow-up (median 9.79 years, interquartile range: 9.68-10.57 years), 9178 (4.9%) participants died. In multi-adjusted Cox regression models, a low-inflammatory diet (i.e. low IDI score) was associated with lower risk of all-cause mortality [hazard ratio (HR) = 0.82, 95% confidence interval (CI): 0.78 to 0.86]. Laplace regression analysis showed that the multi-adjusted 10th percentile difference (10th PD, 95% CI) of death time was delayed by 0.80 (0.55, 1.06; P < 0.001) years for participants with a low IDI score compared to those with a high IDI score. In mediation analysis, 21.48% of the association between IDI and mortality was mediated by CMDs. In joint effect analysis, participants with a low IDI score and favorable lifestyle had a 42% lower risk of death (HR = 0.58, 95% CI: 0.54, 0.62) compared to those with a high IDI score and unfavorable lifestyle. There was a significant additive interaction between low IDI score and favorable lifestyle on decreased mortality. CONCLUSIONS: A low-inflammatory diet is associated with a lower risk of death and could prolong survival time. CMDs may partially mediate the IDI-mortality association. A favorable lifestyle beyond diet may augment the positive effect of a low-inflammatory diet on longevity.
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Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Adulto , Humanos , Fatores de Risco , Dieta , Estilo de VidaRESUMO
BACKGROUND AND OBJECTIVES: Cardiovascular health (CVH) has been associated with cognitive decline and dementia, but the extent to which CVH affects brain health remains unclear. We investigated the association of CVH, assessed using Life's Essential 8 (LE8), with neuroimaging-based brain age and brain-predicted age difference (brain-PAD). METHODS: This longitudinal community-based study was based on UK Biobank participants aged 40-69 years who were free from dementia and other neurologic diseases at baseline. LE8 score at baseline was assessed with 8 measures and tertiled as low, moderate, and high CVH. Structural and functional brain MRI scans were performed approximately 9 years after baseline, and 1,079 measures from 6 neuroimaging modalities were used to model brain age. A Least Absolute Shrinkage and Selection Operator regression model was trained in 4,355 healthy participants and then used to calculate brain age and brain-PAD in the whole population. Data were analyzed using linear regression models. RESULTS: The study included 32,646 participants (mean age at baseline 54.74 years; 53.44% female; mean LE8 score: 71.90). In multivariable-adjusted linear regression, higher LE8 score was associated with younger brain age (ß [95% CI] -0.037 [-0.043 to -0.031]) and more negative brain-PAD (ß [95% CI] -0.043 [-0.048 to -0.038]) (brain looks younger for chronological age). Compared with high CVH, low/moderate CVH was associated with older brain age (ß [95% CI] 1.030 [0.852-1.208]/0.475 [0.303-0.647]) and increased brain-PAD (ß [95% CI] 1.193 [1.029-1.357]/0.528 [0.370-0.686]). The associations between low CVH and older brain age/brain-PAD remained similar and significant in both middle-aged (ß [95% CI] 1.199 [0.992-1.405]/1.351 [1.159-1.542]) and older adults (ß [95% CI] 0.764 [0.417-1.110]/0.948 [0.632-1.263]). DISCUSSION: Low CVH is associated with older brain age and greater brain-PAD, even among middle-aged adults. Our findings suggest that optimizing CVH could support brain health. The main limitation of our study is that the study sample was healthier than the general population, thus caution is required when generalizing our findings to other populations.
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Envelhecimento , Encéfalo , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Humanos , Pessoa de Meia-Idade , Feminino , Masculino , Idoso , Encéfalo/diagnóstico por imagem , Adulto , Estudos Longitudinais , Envelhecimento/fisiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/diagnóstico por imagem , Neuroimagem/métodos , Reino Unido/epidemiologiaRESUMO
Importance: Avoiding high protein intake in older adults with chronic kidney disease (CKD) may reduce the risk of kidney function decline, but whether it can be suboptimal for survival is not well known. Objective: To estimate the associations of total, animal, and plant protein intake with all-cause mortality in older adults with mild or moderate CKD and compare the results to those of older persons without CKD. Design, Setting, and Participants: Data from 3 cohorts (Study on Cardiovascular Health, Nutrition and Frailty in Older Adults in Spain 1 and 2 and the Swedish National Study on Aging and Care in Kungsholmen [in Sweden]) composed of community-dwelling adults 60 years or older were used. Participants were recruited between March 2001 and June 2017 and followed up for mortality from December 2021 to January 2024. Those with no information on diet or mortality, with CKD stages 4 or 5, or undergoing kidney replacement therapy and kidney transplant recipients were excluded. Data were originally analyzed from June 2023 to February 2024 and reanalyzed in May 2024. Exposures: Cumulative protein intake, estimated via validated dietary histories and food frequency questionnaires. Main Outcomes and Measures: The study outcome was 10-year all-cause mortality, ascertained with national death registers. Chronic kidney disease was ascertained according to estimated glomerular filtration rates, urine albumin excretion, and diagnoses from medical records. Results: The study sample consisted of 8543 participants and 14 399 observations. Of the 4789 observations with CKD stages 1 to 3, 2726 (56.9%) corresponded to female sex, and mean (SD) age was 78.0 (7.2) years. During the follow-up period, 1468 deaths were recorded. Higher total protein intake was associated with lower mortality among participants with CKD; adjusted hazard ratio (HR) for 1.00 vs 0.80 g/kg/d was 0.88 (95% CI, 0.79-0.98); for 1.20 vs 0.80 g/kg/d, 0.79 (95% CI, 0.66-0.95); and for 1.40 vs 0.80 g/kg/d, 0.73 (95% CI, 0.57-0.92). Associations with mortality were comparable for plant and animal protein (HRs, 0.80 [95% CI, 0.65-0.98] and 0.88 [95% CI, 0.81-0.95] per 0.20-g/kg/d increment, respectively) and for total protein intake in participants younger than 75 years vs 75 years or older (HRs, 0.94 [95% CI, 0.85-1.04] and 0.91 [95% CI, 0.85-0.98] per 0.20-g/kg/d increment in total protein intake, respectively). However, the hazards were lower among participants without CKD than in those with CKD (HRs, 0.85 [95% CI, 0.79-0.92] and 0.92 [95% CI, 0.86-0.98] per 0.20-g/kg/d increment, respectively; P = .02 for interaction). Conclusions and Relevance: In this multicohort study of older adults, higher intake of total, animal, and plant protein was associated with lower mortality in participants with CKD. Associations were stronger in those without CKD, suggesting that the benefits of proteins may outweigh the downsides in older adults with mild or moderate CKD.
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Proteínas Alimentares , Insuficiência Renal Crônica , Humanos , Idoso , Masculino , Feminino , Insuficiência Renal Crônica/mortalidade , Suécia/epidemiologia , Proteínas Alimentares/administração & dosagem , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Espanha/epidemiologia , Estudos de Coortes , Causas de MorteRESUMO
BACKGROUND: The pattern of olfactory identification change in the early phases of dementing disorders is unclear. We aimed to assess olfactory identification trajectories preceding incident mild cognitive impairment (MCI) and dementia and explore the role of brain pathologies in these trajectories. METHODS: Within the Rush Memory and Aging Project, 1318 dementia-free older adults were followed annually for up to 11 years. Olfactory identification was assessed using the Brief Smell Identification Test annually. Of 900 cognitively intact participants, incident MCI and dementia were diagnosed following standard criteria. Over follow-up, 518 participants died and underwent brain autopsies for neuropathological assessment. Data were analyzed using mixed-effect models with backward timescales. FINDINGS: Compared to participants who remained cognitively intact, olfactory identification declined faster among those who developed MCI (ß -0.09 [95% CI -0.13, -0.05]), leading to a significantly lower olfactory identification starting from five years preceding MCI diagnosis (mean difference at year -5: -0.39 [-0.71, -0.07]). Among participants with incident MCI, olfactory identification declined faster in those who developed dementia compared to those who did not (ß -0.19 [-0.36, -0.01]), leading to a significantly lower olfactory identification starting from three years preceding dementia diagnosis (mean difference at year -3: -0.95 [-1.67, -0.23]). A faster decline in olfactory identification was associated with higher burdens of global Alzheimer's disease pathology, neurofibrillary tangles, and amyloid beta load. INTERPRETATION: Olfactory identification declined faster preceding dementia disorders and Alzheimer's pathology may underlie these faster declines. FUNDING: This study was funded by the National Institutes of Health (R01AG17917) and Swedish Research Council (2021-01647).
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Estados Unidos , Humanos , Idoso , Olfato , Estudos Longitudinais , Peptídeos beta-Amiloides , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologiaRESUMO
BACKGROUND: APOEÉ4 allele confers greatest genetic risk for Alzheimer's disease (AD), yet mechanisms underlying this risk remain elusive. APOE is involved in lipid metabolism, and literature suggest relationships between high total cholesterol, APOE, and AD. Further investigation is needed to elucidate the potential role of total cholesterol in AD risk. OBJECTIVE: To investigate the relationship between total cholesterol and APOE-related AD risk in the Alzheimer's Disease Neuroimaging Initiative. METHODS: Participants (Nâ=â1,534) were classified as controls (cognitively normal; Nâ=â404), early mild cognitive impairment (MCI; Nâ=â294), late MCI (Nâ=â539), or AD (Nâ=â297). Total cholesterol levels were compared across APOE genotype and diagnosis. Mendelian randomization was performed to examine causality between total cholesterol and AD risk using APOE as a genetic instrument. RESULTS: Total cholesterol was higher in APOE4+ compared to APOE3 and APOE2+ (psâ<â0.04) carriers. Those with AD and late MCI (psâ<â0.001) had higher total cholesterol than the control group. Comparing APOE4+ to APOE3 carriers, the predicted odds ratios per mg/dL greater total cholesterol were 1.11 for MCI (95% confidence interval, 1.04-7.32), 1.05 for early MCI (1.01-3.22), 1.13 for late MCI (1.05-11.70), 1.21 for AD (1.09-54.05), and 1.13 for composite dementia (MCI or AD; 1.06-11.59) (psâ<â0.05, F-statistics > 10). CONCLUSION: Higher total cholesterol may be a significant contributor to AD risk, particularly in APOE4 carriers who, based on existing literature, tend to have impaired cholesterol metabolism. Our findings highlight a possible mechanism by which APOE confers AD risk and indicate potential for AD risk modification through maintenance of healthy total cholesterol levels.