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BACKGROUND: Findings from observational studies suggest that dietary patterns may offer protective benefits against cognitive decline, but data from clinical trials are limited. The Mediterranean-DASH Intervention for Neurodegenerative Delay, known as the MIND diet, is a hybrid of the Mediterranean diet and the DASH (Dietary Approaches to Stop Hypertension) diet, with modifications to include foods that have been putatively associated with a decreased risk of dementia. METHODS: We performed a two-site, randomized, controlled trial involving older adults without cognitive impairment but with a family history of dementia, a body-mass index (the weight in kilograms divided by the square of the height in meters) greater than 25, and a suboptimal diet, as determined by means of a 14-item questionnaire, to test the cognitive effects of the MIND diet with mild caloric restriction as compared with a control diet with mild caloric restriction. We assigned the participants in a 1:1 ratio to follow the intervention or the control diet for 3 years. All the participants received counseling regarding adherence to their assigned diet plus support to promote weight loss. The primary end point was the change from baseline in a global cognition score and four cognitive domain scores, all of which were derived from a 12-test battery. The raw scores from each test were converted to z scores, which were averaged across all tests to create the global cognition score and across component tests to create the four domain scores; higher scores indicate better cognitive performance. The secondary outcome was the change from baseline in magnetic resonance imaging (MRI)-derived measures of brain characteristics in a nonrandom sample of participants. RESULTS: A total of 1929 persons underwent screening, and 604 were enrolled; 301 were assigned to the MIND-diet group and 303 to the control-diet group. The trial was completed by 93.4% of the participants. From baseline to year 3, improvements in global cognition scores were observed in both groups, with increases of 0.205 standardized units in the MIND-diet group and 0.170 standardized units in the control-diet group (mean difference, 0.035 standardized units; 95% confidence interval, -0.022 to 0.092; P = 0.23). Changes in white-matter hyperintensities, hippocampal volumes, and total gray- and white-matter volumes on MRI were similar in the two groups. CONCLUSIONS: Among cognitively unimpaired participants with a family history of dementia, changes in cognition and brain MRI outcomes from baseline to year 3 did not differ significantly between those who followed the MIND diet and those who followed the control diet with mild caloric restriction. (Funded by the National Institute on Aging; ClinicalTrials.gov number, NCT02817074.).
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Disfunção Cognitiva , Demência , Dieta Mediterrânea , Idoso , Idoso de 80 Anos ou mais , Humanos , Encéfalo/diagnóstico por imagem , Cognição , Disfunção Cognitiva/prevenção & controle , Demência/prevenção & controle , Dieta Hipossódica , Restrição CalóricaRESUMO
INTRODUCTION: The U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER) is conducted to confirm and expand the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in Americans. METHODS: U.S. POINTER was planned as a 2-year randomized controlled trial of two lifestyle interventions in 2000 older adults at risk for dementia due to well-established factors. The primary outcome is a global cognition composite that permits harmonization with FINGER. RESULTS: U.S. POINTER is centrally coordinated and conducted at five clinical sites (ClinicalTrials.gov: NCT03688126). Outcomes assessments are completed at baseline and every 6 months. Both interventions focus on exercise, diet, cognitive/social stimulation, and cardiovascular health, but differ in intensity and accountability. The study partners with a worldwide network of similar trials for harmonization of methods and data sharing. DISCUSSION: U.S. POINTER is testing a potentially sustainable intervention to support brain health and Alzheimer's prevention for Americans. Impact is strengthened by the targeted participant diversity and expanded scientific scope through ancillary studies.
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Disfunção Cognitiva , Humanos , Idoso , Disfunção Cognitiva/psicologia , Estilo de Vida , Cognição , Exercício Físico , EncéfaloRESUMO
OBJECTIVE: The objective of this study was to examine the association between caffeine intake and cognitive impairment. Caffeine-neuropathology correlations and interactions with lifestyle and genetic factors impacting caffeine metabolism and response were also tested. METHODS: We included 888 participants aged 59+ years from the Rush Memory and Aging Project (MAP) and 303,887 participants aged 55+ years from the UK Biobank (UKB). MAP participants took part in annual cognitive testing. Diagnosis of dementia was based on clinical neurological examination and standardized criteria. A subset provided postmortem tissue for neuropathologic evaluation for common age-related diseases (eg, Alzheimer's disease [AD], Lewy bodies, and vascular). For UKB, dementia was determined by linked hospital and death records. Self-reported caffeine intake was estimated using food-frequency questionnaires in both cohorts. Cox proportional hazard ratio (HR), regression, and mixed models were used to examine associations of caffeine intake with incident dementia, cognitive decline, and neuropathology. RESULTS: In MAP, compared to ≤100 mg/day, caffeine intake >100 mg/day was associated with a significantly higher HR (95% confidence interval [CI]) of all-cause (HR = 1.35, 95% CI = 1.03-1.76) and AD (HR = 1.41, 95% CI = 1.07-1.85) dementia. Caffeine intake was not associated with cognitive decline. In UKB, compared to ≤100 mg/day, the HRs (95% CI) of all-cause dementia for consuming 100 ≤ 200, 200 ≤ 300, 300 ≤ 400, and > 400 mg/day were 0.83 (95% CI = 0.72-0.94), 0.74 (95% CI = 0.64-0.85), 0.74 (95% CI = 0.64-0.85), and 0.92 (95% CI = 0.79-1.08), respectively. Similar results were observed for Alzheimer's dementia. In MAP, caffeine intake was inversely associated with postmortem Lewy bodies but no other age-related pathologies. Caffeine intake >100 mg/day was associated with lower neocortical type Lewy bodies (odds ratio (95%CI): 0.40 (95% CI = 0.21-0.75). INTERPRETATION: Caffeine intake was inconsistently associated with clinical dementia; potentially explained by cohort differences in underlying dementia etiology. Lewy bodies may link caffeine to lower risk in some persons. ANN NEUROL 2022;91:834-846.
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Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/patologia , Cafeína/efeitos adversos , Disfunção Cognitiva/etiologia , Humanos , Corpos de Lewy/patologia , Testes NeuropsicológicosRESUMO
Cortical iron has been shown to be elevated in Alzheimer's disease (AD), but the impact of the directly measured iron on the clinical syndrome has not been assessed. We investigated the association between post-mortem iron levels with the clinical and pathological diagnosis of AD, its severity, and the rate of cognitive decline in the 12 years prior to death in subjects from the Memory and Aging Project (n = 209). Iron was elevated (ß [SE] = 9.7 [2.6]; P = 3.0 × 10-4) in the inferior temporal cortex only in subjects who were diagnosed with clinical AD during life and had a diagnosis of AD confirmed post-mortem by standardized criteria. Although iron was weakly associated with the extent of proteinopathy in tissue with AD neuropathology, it was strongly associated with the rate of cognitive decline (e.g., global cognition: ß [SE] = -0.040 [0.005], P = 1.6 × 10-14). Thus, cortical iron might act to propel cognitive deterioration upon the underlying proteinopathy of AD, possibly by inducing oxidative stress or ferroptotic cell death, or may be related to an inflammatory response.
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Doença de Alzheimer/complicações , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Disfunção Cognitiva/complicações , Disfunção Cognitiva/metabolismo , Ferro/metabolismo , Idoso de 80 Anos ou mais , Cognição , Feminino , Ferroptose , Humanos , Masculino , Estresse OxidativoRESUMO
OBJECTIVE: This paper is a proposal for an update of the iron hypothesis of Alzheimer's disease (AD), based on large-scale emerging evidence. BACKGROUND: Iron featured historically early in AD research efforts for its involvement in the amyloid and tau proteinopathies, APP processing, genetics, and one clinical trial, yet iron neurochemistry remains peripheral in mainstream AD research. Much of the effort investigating iron in AD has focused on the potential for iron to provoke the onset of disease, by promoting proteinopathy though increased protein expression, phosphorylation, and aggregation. NEW/UPDATED HYPOTHESIS: We provide new evidence from a large post mortem cohort that brain iron levels within the normal range were associated with accelerated ante mortem disease progression in cases with underlying proteinopathic neuropathology. These results corroborate recent findings that argue for an additional downstream role for iron as an effector of neurodegeneration, acting independently of tau or amyloid pathologies. We hypothesize that the level of tissue iron is a trait that dictates the probability of neurodegeneration in AD by ferroptosis, a regulated cell death pathway that is initiated by signals such as glutathione depletion and lipid peroxidation. MAJOR CHALLENGES FOR THE HYPOTHESIS: While clinical biomarkers of ferroptosis are still in discovery, the demonstration of additional ferroptotic correlates (genetic or biomarker derived) of disease progression is required to test this hypothesis. The genes implicated in familial AD are not known to influence ferroptosis, although recent reports on APP mutations and apolipoprotein E allele (APOE) have shown impact on cellular iron retention. Familial AD mutations will need to be tested for their impact on ferroptotic vulnerability. Ultimately, this hypothesis will be substantiated, or otherwise, by a clinical trial of an anti-ferroptotic/iron compound in AD patients. LINKAGE TO OTHER MAJOR THEORIES: Iron has historically been linked to the amyloid and tau proteinopathies of AD. Tau, APP, and apoE have been implicated in physiological iron homeostasis in the brain. Iron is biochemically the origin of most chemical radicals generated in biochemistry and thus closely associated with the oxidative stress theory of AD. Iron accumulation is also a well-established consequence of aging and inflammation, which are major theories of disease pathogenesis.
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Doença de Alzheimer/patologia , Amiloide/metabolismo , Encéfalo/patologia , Ferro/metabolismo , Proteínas tau/metabolismo , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas E/genética , Estudos de Coortes , Feminino , Humanos , Masculino , FosforilaçãoRESUMO
INTRODUCTION: It is unclear whether eating Western diet food components offsets the Mediterranean diet's (MedDiet) potential benefits on cognitive decline. METHODS: The study includes 5001 Chicago Health and Aging Project participants (63% African American, 36% males, 74 ± 6.0 years old), with food frequency questionnaires and ≥ two cognitive assessments over 6.3 ± 2.8 years of follow-up. Mixed-effects models were adjusted for age, sex, education, race, cognitive activities, physical activity, and total calories. RESULTS: Stratified analysis showed a significant effect of higher MedDiet on cognitive decline only with a low Western diet score (highest vs lowest MedDiet tertile: ß = 0.020, P = .002; p trend = 0.002) and not with a high Western diet score (highest vs lowest MedDiet tertile: ß = 0.010, P = .11; p trend = 0.09). CONCLUSION: This prospective study found that high consumption of Western diet components attenuates benefits of the MedDiet on cognition.
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Negro ou Afro-Americano/estatística & dados numéricos , Disfunção Cognitiva/prevenção & controle , Dieta Mediterrânea/etnologia , Dieta Ocidental/etnologia , Idoso , Envelhecimento/fisiologia , Chicago , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Non-pharmacological treatments (NPTs) have the potential to improve meaningful outcomes for older people at risk of, or living with dementia, but research often lacks methodological rigor and continues to produce mixed results. METHODS: In the current position paper, experts in NPT research have specified treatment targets, aims, and ingredients using an umbrella framework, the Rehabilitation Treatment Specification System. RESULTS: Experts provided a snapshot and an authoritative summary of the evidence for different NPTs based on the best synthesis efforts, identified main gaps in knowledge and relevant barriers, and provided directions for future research. Experts in trial methodology provide best practice principles and recommendations for those working in this area, underscoring the importance of prespecified protocols. DISCUSSION: We conclude that the evidence strongly supports various NPTs in relation to their primary targets, and discuss opportunities and challenges associated with a unifying theoretical framework to guide future efforts in this area.
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Envelhecimento/fisiologia , Demência , Terapia Cognitivo-Comportamental , Demência/reabilitação , Demência/terapia , Exercício Físico , Humanos , Meditação , MusicoterapiaRESUMO
BACKGROUND: Coffee and tea are the major contributors of caffeine in the diet. Evidence points to the premise that caffeine may benefit cognition. OBJECTIVE: We examined the associations of habitual regular coffee or tea and caffeine intake with cognitive function whilst additionally accounting for genetic variation in caffeine metabolism. METHODS: We included white participants aged 37-73 y from the UK Biobank who provided biological samples and completed touchscreen questionnaires regarding sociodemographic factors, medical history, lifestyle, and diet. Habitual caffeine-containing coffee and tea intake was self-reported in cups/day and used to estimate caffeine intake. Between 97,369 and 445,786 participants with data also completed ≥1 of 7 self-administered cognitive functioning tests using a touchscreen system (2006-2010) or on home computers (2014). Multivariable regressions were used to examine the association between coffee, tea, or caffeine intake and cognition test scores. We also tested interactions between coffee, tea, or caffeine intake and a genetic-based caffeine-metabolism score (CMS) on cognitive function. RESULTS: After multivariable adjustment, reaction time, Pairs Matching, Trail Making test B, and symbol digit substitution, performance significantly decreased with consumption of 1 or more cups of coffee (all tests P-trend < 0.0001). Tea consumption was associated with poor performance on all tests (P-trend < 0.0001). No statistically significant CMS × tea, CMS × coffee, or CMS × caffeine interactions were observed. CONCLUSIONS: Our findings, based on the participants of the UK Biobank, provide little support for habitual consumption of regular coffee or tea and caffeine in improving cognitive function. On the contrary, we observed decrements in performance with intakes of these beverages which may be a result of confounding. Whether habitual caffeine intake affects cognitive function therefore remains to be tested.
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Apolipoproteínas E/genética , Cafeína/administração & dosagem , Coffea , Cognição/efeitos dos fármacos , Variação Genética , Chá , Adulto , Idoso , Bancos de Espécimes Biológicos , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Reino UnidoRESUMO
Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.
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Doença de Alzheimer/etnologia , Doença de Alzheimer/epidemiologia , Etnicidade , Disparidades em Assistência à Saúde , Grupos Raciais , Idoso , Biomarcadores , Pesquisa Biomédica , HumanosRESUMO
Fish are a primary source of long-chain omega-3 fatty acids, which may help delay cognitive aging. We pooled participants from the French Three-City study and 4 US cohorts (Nurses' Health Study, Women's Health Study, Chicago Health and Aging Project, and Rush Memory and Aging Project) for whom diet and cognitive data were available (n = 23,688 white persons, aged ≥65 years, 88% female, baseline year range of 1992-1999, and median follow-up range of 3.9-9.1 years) to investigate the relationship of fish intake to cognitive decline and examine interactions with genes related to Alzheimer disease. We estimated cohort-specific associations between fish and change in composite scores of global cognition and episodic memory using linear mixed models, and we pooled results using inverse-variance weighted meta-analysis. In multivariate analyses, higher fish intake was associated with slower decline in both global cognition and memory (P for trend ≤ 0.031). Consuming ≥4 servings/week versus <1 serving/week of fish was associated with a lower rate of memory decline: 0.018 (95% confidence interval: 0.004, 0.032) standard units, an effect estimate equivalent to that found for 4 years of age. For global cognition, no comparisons of higher versus low fish intake reached statistical significance. In this meta-analysis, higher fish intake was associated with a lower rate of memory decline. We found no evidence of effect modification by genes associated with Alzheimer disease.
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Doença de Alzheimer/genética , Cognição , Peixes , Memória Episódica , Alimentos Marinhos , Idoso , Idoso de 80 Anos ou mais , Animais , Apolipoproteína E4/genética , Estudos de Coortes , Dieta , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
IMPORTANCE: Seafood consumption is promoted for its many health benefits even though its contamination by mercury, a known neurotoxin, is a growing concern. OBJECTIVE: To determine whether seafood consumption is correlated with increased brain mercury levels and also whether seafood consumption or brain mercury levels are correlated with brain neuropathologies. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analyses of deceased participants in the Memory and Aging Project clinical neuropathological cohort study, 2004-2013. Participants resided in Chicago retirement communities and subsidized housing. The study included 286 autopsied brains of 554 deceased participants (51.6%). The mean (SD) age at death was 89.9 (6.1) years, 67% (193) were women, and the mean (SD) educational attainment was 14.6 (2.7) years. EXPOSURES: Seafood intake was first measured by a food frequency questionnaire at a mean of 4.5 years before death. MAIN OUTCOMES AND MEASURES: Dementia-related pathologies assessed were Alzheimer disease, Lewy bodies, and the number of macroinfarcts and microinfarcts. Dietary consumption of seafood and n-3 fatty acids was annually assessed by a food frequency questionnaire in the years before death. Tissue concentrations of mercury and selenium were measured using instrumental neutron activation analyses. RESULTS: Among the 286 autopsied brains of 544 participants, brain mercury levels were positively correlated with the number of seafood meals consumed per week (ρ = 0.16; P = .02). In models adjusted for age, sex, education, and total energy intake, seafood consumption (≥ 1 meal[s]/week) was significantly correlated with less Alzheimer disease pathology including lower density of neuritic plaques (ß = -0.69 score units [95% CI, -1.34 to -0.04]), less severe and widespread neurofibrillary tangles (ß = -0.77 score units [95% CI, -1.52 to -0.02]), and lower neuropathologically defined Alzheimer disease (ß = -0.53 score units [95% CI, -0.96 to -0.10]) but only among apolipoprotein E (APOE ε4) carriers. Higher intake levels of α-linolenic acid (18:3 n-3) were correlated with lower odds of cerebral macroinfarctions (odds ratio for tertiles 3 vs 1, 0.51 [95% CI, 0.27 to 0.94]). Fish oil supplementation had no statistically significant correlation with any neuropathologic marker. Higher brain concentrations of mercury were not significantly correlated with increased levels of brain neuropathology. CONCLUSIONS AND RELEVANCE: In cross-sectional analyses, moderate seafood consumption was correlated with lesser Alzheimer disease neuropathology. Although seafood consumption was also correlated with higher brain levels of mercury, these levels were not correlated with brain neuropathology.
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Doença de Alzheimer/patologia , Química Encefálica , Ácidos Graxos Ômega-3/administração & dosagem , Mercúrio/análise , Alimentos Marinhos/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Apolipoproteína E4/análise , Autopsia , Cerebelo/química , Cerebelo/patologia , Estudos Transversais , Registros de Dieta , Escolaridade , Feminino , Lobo Frontal/química , Lobo Frontal/patologia , Humanos , Masculino , Selênio/análise , Lobo Temporal/química , Lobo Temporal/patologiaRESUMO
INTRODUCTION: In a previous study, higher concordance to the MIND diet, a hybrid Mediterranean-Dietary Approaches to Stop Hypertension diet, was associated with slower cognitive decline. In this study we related these three dietary patterns to incident Alzheimer's disease (AD). METHODS: We investigated the diet-AD relations in a prospective study of 923 participants, ages 58 to 98 years, followed on average 4.5 years. Diet was assessed by a semiquantitative food frequency questionnaire. RESULTS: In adjusted proportional hazards models, the second (hazards ratio or HR = 0.65, 95% confidence interval or CI 0.44, 0.98) and highest tertiles (HR = 0.47, 95% CI 0.26, 0.76) of MIND diet scores had lower rates of AD versus tertile 1, whereas only the third tertiles of the DASH (HR = 0.61, 95% CI 0.38, 0.97) and Mediterranean (HR = 0.46, 95% CI 0.26, 0.79) diets were associated with lower AD rates. DISCUSSION: High adherence to all three diets may reduce AD risk. Moderate adherence to the MIND diet may also decrease AD risk.
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Doença de Alzheimer/dietoterapia , Doença de Alzheimer/epidemiologia , Dieta Mediterrânea , Idoso de 80 Anos ou mais , Doença de Alzheimer/fisiopatologia , Chicago/epidemiologia , Transtornos Cognitivos/dietoterapia , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/fisiopatologia , Progressão da Doença , Feminino , Humanos , Incidência , Masculino , Cooperação do Paciente , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de SobrevidaRESUMO
INTRODUCTION: The Mediterranean and dash diets have been shown to slow cognitive decline; however, neither diet is specific to the nutrition literature on dementia prevention. METHODS: We devised the Mediterranean-Dietary Approach to Systolic Hypertension (DASH) diet intervention for neurodegenerative delay (MIND) diet score that specifically captures dietary components shown to be neuroprotective and related it to change in cognition over an average 4.7 years among 960 participants of the Memory and Aging Project. RESULTS: In adjusted mixed models, the MIND score was positively associated with slower decline in global cognitive score (ß = 0.0092; P < .0001) and with each of five cognitive domains. The difference in decline rates for being in the top tertile of MIND diet scores versus the lowest was equivalent to being 7.5 years younger in age. DISCUSSION: The study findings suggest that the MIND diet substantially slows cognitive decline with age. Replication of these findings in a dietary intervention trial would be required to verify its relevance to brain health.
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Envelhecimento/psicologia , Transtornos Cognitivos/dietoterapia , Transtornos Cognitivos/epidemiologia , Dieta Mediterrânea , Idoso de 80 Anos ou mais , Chicago/epidemiologia , Transtornos Cognitivos/prevenção & controle , Inquéritos sobre Dietas , Progressão da Doença , Feminino , Humanos , Modelos Lineares , Masculino , Estudos Prospectivos , Testes PsicológicosRESUMO
Randomized trials of α-tocopherol supplements on cognitive decline are negative, whereas studies of dietary tocopherols have shown benefit. We investigated these inconsistencies by analyzing the relations of α- and γ-tocopherol brain concentrations to Alzheimer's disease (AD) neuropathology among 115 deceased participants of the prospective Rush Memory and Aging Project. Associations of amyloid load and neurofibrillary tangle severity with brain tocopherol concentrations were examined in separate adjusted linear regression models. γ-Tocopherol concentrations were associated with lower amyloid load (ß = -2.10, P = .002) and lower neurofibrillary tangle severity (ß = -1.16, P = .02). Concentrations of α-tocopherol were not associated with AD neuropathology, except as modified by γ-tocopherol: high α-tocopherol was associated with higher amyloid load when γ-tocopherol levels were low and with lower amyloid levels when γ-tocopherol levels were high (P for interaction = 0.03). Brain concentrations of γ- and α-tocopherols may be associated with AD neuropathology in interrelated, complex ways. Randomized trials should consider the contribution of γ-tocopherol.
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Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Encéfalo/metabolismo , Emaranhados Neurofibrilares/patologia , Placa Amiloide/patologia , alfa-Tocoferol/metabolismo , gama-Tocoferol/metabolismo , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Envelhecimento/patologia , Estudos de Coortes , Feminino , Humanos , MasculinoRESUMO
Adherence to Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) may lower the risk of dementia by impacting immunity and cholesterol, which are pathways also implicated by genome-wide association studies of Alzheimer's Dementia (AD). We examined whether adherence to the MIND diet could modify the association of genetic risk for AD with incident dementia. We used three ongoing US cohorts: Chicago Health and Aging Project (CHAP, n = 2449), Rush Memory and Aging Project (MAP, n = 725), and Women's Health Initiative Memory Study (WHIMS, n = 5308). Diagnosis of dementia was based on clinical neurological examination and standardized criteria. Repeated measures of global cognitive function were available in MAP and CHAP. Self-reported adherence to MIND was estimated using food-frequency questionnaires. Global and pathway-specific genetic scores (GS) for AD were derived. Cox proportional hazard, logistic regression, and mixed models were used to examine associations of MIND, GS, and GS-MIND interactions with incident dementia and cognitive decline. Higher adherence to MIND and lower GS were associated with a lower risk of dementia in MAP and WHIMS and a slower rate of cognitive decline in MAP (p < 0.05). MIND or GS were not associated with incident dementia or cognitive decline in CHAP. No gene−diet interaction was replicated across cohorts. Genetic risk and MIND adherence are independently associated with dementia among older US men and women.
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Doença de Alzheimer , Dieta Mediterrânea , Abordagens Dietéticas para Conter a Hipertensão , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Doença de Alzheimer/prevenção & controle , Dieta Mediterrânea/psicologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Estudos ProspectivosRESUMO
BACKGROUND: Depression is common in older adults and more prevalent in those with cognitive impairment, vascular risk factors, or stroke. Nonpharmacologic strategies to reduce depression, such as diet, may be effective; however, few studies have investigated the relation. METHODS: A total of 709 participants (23.3% men, mean age 80.4), from an observational prospective cohort study were assessed annually for an average of 6.53 years of follow-up. Participants with missing or invalid baseline dietary evaluations or fewer than two depression assessments were excluded. Depressive symptoms were assessed with a 10-item version of the Center for Epidemiologic Studies Depression scale. High burden of depressive symptoms was defined as the presence of four or more depressive symptoms. Diet scores were computed using a validated food frequency questionnaire for the Dietary Approaches to Stop Hypertension (DASH) diet, Mediterranean diet, Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, and Western diets. Diet scores were modeled in tertiles. A generalized estimating equation (GEE) model was performed for the longitudinal analysis of depression as a binary outcome. RESULTS: Participants in the highest tertile of the DASH (ß = -0.10, confidence interval [CI]: -0.20, -0.0064) and MIND (ß = -0.12, CI: -0.23, -0.0092) diet scores had lower rates of depressive symptoms over time when compared to those in the respective lowest tertiles. The Western diet was positively associated with depressive symptoms over time (ß = 0.093, p-trend = .05). CONCLUSIONS: Diet may be effective in reducing depressive symptoms in older adults. A diet intervention trial may be needed to determine the optimal nutritional components for prevention of late onset depression.
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Depressão/diagnóstico , Depressão/prevenção & controle , Dieta Mediterrânea , Abordagens Dietéticas para Conter a Hipertensão , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Fatores de TempoRESUMO
BACKGROUND: Studies have reported a protective relation to cognitive decline with long-term intake of total and individual dietary carotenoids. However, the underlying mechanisms have not yet been clearly established in humans. OBJECTIVES: To evaluate the prospective association between intakes of total and individual carotenoids and risk of incident Alzheimer dementia (AD) and explore the underlying neuropathological basis. METHODS: Among 927 participants from the Rush Memory and Aging Project who were free from AD at baseline and were followed up for a mean of 7 y, we estimated HRs for AD using Cox proportional hazards models by intakes of energy-adjusted carotenoids. Brain AD neuropathology was assessed in postmortem brain autopsies among 508 deceased participants. We used linear regression to assess the association of carotenoid intake with AD-related neuropathology. RESULTS: Higher intake of total carotenoids was associated with substantially lower hazard of AD after controlling for age, sex, education, ApoE-ε4, participation in cognitively stimulating activities, and physical activity level. Comparing the top and bottom quintiles (median intake: 24.8 compared with 6.7 mg/d) of total carotenoids, the multivariate HR (95% CI) was 0.52 (0.33, 0.81), P-trend < 0.01. A similar association was observed for lutein-zeaxanthin, a weaker linear inverse association was observed for ß-carotene, and a marginally significant linear inverse association was found for ß-cryptoxanthin. Among the deceased participants, consumers of higher total carotenoids (top compared with bottom tertile, 18.2 compared with 8.2 mg/d) had less global AD pathology (b: -0.10; SE = 0.04; P-trend = 0.01). For individual carotenoids, lutein-zeaxanthin and lycopene were inversely associated with brain global pathology, whereas lutein-zeaxanthin showed additional inverse associations with AD diagnostic score, neuritic plaque severity, and neurofibrillary tangle density and severity. CONCLUSIONS: Our findings support a beneficial role of total carotenoid consumption, in particular lutein/zeaxanthin, on AD incidence that may be related to the inhibition of brain ß-amyloid deposition and fibril formation.
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Alzheimer's dementia (AD) is the sixth leading cause of death in the U.S., with an estimated $305 billion cost of care in 2020. Currently there are no cures or therapies to ameliorate the disease progression and symptoms. Growing evidence links a diet characterized by high antioxidant components with benefits to cognitive function, which is indicative of the preventative potential of dietary inteventions. The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) study is a 3-year, multicenter, randomized controlled trial to test the effects of the MIND diet on cognitive function in 604 individuals at risk for AD. Men and women ages 65 to 84 years were recruited. Eligible participants were randomized to either the MIND diet with mild caloric restriction or their usual diet with mild caloric restriction. Cognitive assessments, medical history, blood pressure, anthropometric measurements, and blood and urine sample collections will be taken at baseline and follow-up visits. MRI scans will be completed on approximately half of the enrolled participants at the start and end of the study. Unique features of the MIND study include: 1) a dietary pattern, rather than single nutrient or food, tested in an at-risk population; 2) foods featured as key components of the MIND diet (i.e. extra-virgin olive oil, blueberries, and nuts) provided for participants; and 3) MRI scans of brain structure and volume that may provide potential mechanistic evidence on the effects of the diet. Results from the study will be crucial to the development of dietary guidelines for the prevention of AD.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Dieta Mediterrânea , Abordagens Dietéticas para Conter a Hipertensão , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/prevenção & controle , Cognição , Disfunção Cognitiva/prevenção & controle , Feminino , Humanos , MasculinoRESUMO
Clinical evidence points to the premise that caffeine may benefit cognition, but whether these findings extend to real life settings and amidst factors that impact caffeine metabolism is unclear. The aim of this study was to investigate the impact of recent caffeine drinking on cognitive ability while additionally accounting for lifestyle and genetic factors that impact caffeine metabolism. We included up to 434,900 UK Biobank participants aged 37-73 years, recruited in 2006-2010, who provided biological samples and completed touchscreen questionnaires regarding sociodemographic factors, medical history, lifestyle, and diet. Recent caffeine drinking (yes/no in the last hour) was recorded during a physical assessment. Participants completed at least one of four self-administered cognitive function tests using the touchscreen system: prospective memory (PM), pairs matching (Pairs), fluid intelligence (FI), and reaction time (RT). Multivariable regressions were used to examine the association between recent caffeine drinking and cognition test scores. We also tested interactions between recent caffeine drinking and a genetic caffeine-metabolism score (CMS) on cognitive function. Among white participants, recent caffeine drinking was associated with higher performance on RT but lower performance on FI, Pairs, and PM (p ≤ 0.004). Similar directions of associations for FI (p = 0.09), Pairs (p = 0.03), and PM (p = 0.34) were observed among non-white participants. No significant and consistent effect modification by age, sex, smoking, test time, habitual caffeine intake, or CMS was observed. Caffeine consumed shortly before tasks requiring shorter reaction times may improve task performance. Potential impairments in memory and reasoning tasks with recent caffeine drinking warrant further study.
Assuntos
Bancos de Espécimes Biológicos , Cafeína/administração & dosagem , Cognição/efeitos dos fármacos , Adulto , Idoso , Cafeína/metabolismo , Café , Dieta , Feminino , Genótipo , Humanos , Estilo de Vida , Masculino , Memória Episódica , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tempo de Reação/efeitos dos fármacos , Inquéritos e Questionários , Fatores de Tempo , Reino UnidoRESUMO
BACKGROUND: Higher vitamin E intake has been widely related to lower risks of cognitive decline and dementia. Animal models suggest that this relationship might be (partially) explained by the protection of vitamin E against presynaptic protein oxidation. OBJECTIVE: In this cross-sectional study, we aimed to examine the associations between brain tocopherols and presynaptic protein levels in elderly humans. METHODS: We examined associations of α- and γ-tocopherol brain levels with presynaptic protein levels in 113 deceased participants (age 88.5±6.0 years, 45 (40%) female) from the prospective Memory and Aging project. Three distinct presynaptic proteins, a SNARE protein composite, a synaptotagmin synaptophysin composite and the protein-protein interaction between synaptosomal-associated protein 25 (SNAP-25), and syntaxin were measured in two cortical brain regions. Linear regression models assessed associations of brain tocopherols with presynaptic protein levels. RESULTS: Higher brain γ-tocopherol levels were associated with higher levels of the SNARE protein composite, complexin-I, complexin-II, the synaptotagmin synaptophysin composite, and septin-5 in the midfrontal cortex (B(SE)â=â0.272 to 0.412 (0.084 to 0.091), pâ<â0.001 to 0.003). When additionally adjusted for global Alzheimer's disease pathology, cerebral infarcts, and Lewy body disease pathology, these associations remained largely similar. No associations were found between α-tocopherol and presynaptic protein levels. CONCLUSION: In this cross-sectional study, we found higher brain γ-tocopherol levels were associated with presynaptic protein levels in the midfrontal cortex. These results are consistent with a proposed role of vitamin E to maintain presynaptic protein levels.