Importance: Dementia threatens the well-being of older adults, making efforts toward prevention of great importance.Objective: To evaluate the association of the Mediterranean–Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND) diet with the risk of dementia in 3 prospective studies and a meta-analysis.Design, Setting, and Participants: Cohort analyses included the Whitehall II study (WII), the Health and Retirement Study (HRS), and the Framingham Heart Study Offspring cohort (FOS), and the meta-analysis included 11 cohort studies. Participants were middle-aged and older women and men from WII in 2002 to 2004, HRS in 2013, and FOS in 1998 to 2001 without dementia at the study baseline. Data were analyzed from May 25 to September 1, 2022.Exposures: MIND diet score was measured using food frequency questionnaires, and scores ranged from 0 to 15, with a higher score indicating higher adherence to the MIND diet.Main Outcome and Measures: Incident all-cause dementia, with cohort-specific definitions.Results: Included in this study were 8358 participants (mean [SD] age, 62.2 [6.0] years; 5777 male [69.1%]) from WII, 6758 participants (mean [SD] age, 66.5 [10.4] years; 3965 female [58.7%]) from HRS, and 3020 participants (mean [SD] age, 64.2 [9.1] years; 1648 female [54.6%]) from FOS. The mean (SD) baseline MIND diet score was 8.3 (1.4) in WII, 7.1 (1.9) in HRS, and 8.1 (1.6) in FOS. Over 166 516 person-years, a total of 775 participants (220 in WII, 338 in HRS, and 217 in FOS) developed incident dementia. In the multivariable-adjusted Cox proportional hazard model, higher MIND diet score was associated with lower risk of dementia (pooled hazard ratio [HR] for every 3-point increment, 0.83; 95% CI, 0.72-0.95; P for trend = .01; I² = 0%). The associations were consistently observed in subgroups defined by sex, age, smoking status, and body mass index. In the meta-analysis of 11 cohort studies with 224 049 participants (5279 incident dementia cases), the highest tertile of MIND diet score was associated with lower risk of dementia compared with the lowest tertile (pooled HR, 0.83; 95% CI, 0.76-0.90; I² = 35%).Conclusions and Relevance: Results suggest that adherence to the MIND diet was associated with lower risk of incident dementia in middle-aged and older adults. Further studies are warranted to develop and refine the specific MIND diet for different populations.

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. 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. 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. 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 β-carotene, and a marginally significant linear inverse association was found for β-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. 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 β-amyloid deposition and fibril formation.

Air pollution is a risk factor for poor cognitive function, while a plant-based dietary pattern is associated with better cognitive function. We aimed to explore their interaction with cognitive function among older adults. We used a prospective cohort of old individuals, including 6525 participants of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), aged 65-110 years and with normal cognition at baseline. Air pollution measurement was derived using satellite-derived annual average fine particulate matter (PM_2.5) concentrations based on residential locations. Plant-based diet index (PDI) was calculated using survey responses to assess the dietary pattern. Repeated measures of the Mini-Mental State Examination (MMSE) were utilized to assess cognitive function. We applied the Cox proportional hazard regression to explore the associations and further stratified the analysis by PDI. During a median of 5·6-year follow-up, 1537 (23·6%) out of 6525 participants with normal cognition at baseline developed poor cognitive function (MMSE <18). Living in areas with the highest quintile of cumulative PM_2.5 was associated with a 46% increase in the risk of developing poor cognitive function (hazard ratio (HR): 1·46, 95% confidence interval (CI): 1·20, 1·77), compared to those living in areas with the lowest quintile. We observed a significant interaction between cumulative PM_2.5 and PDI (p-interaction: 0·04), with the corresponding associations of cumulative PM_2.5 being more pronounced among participants with lower PDI (HR: 1·68, 95% CI: 1·26, 2·24) than those with higher PDI (HR: 1·28, 95% CI: 0·98, 1·68). Plant-based dietary pattern may attenuate detrimental impacts of PM_2.5 on cognitive function among older adults. Adherence to the plant-based dietary pattern could be used to prevent adverse neurological effects caused by air pollution, especially in developing regions.

Importance: The effect of argatroban in patients with acute ischemic stroke (AIS) and early neurological deterioration (END) is unknown.Objective: To assess the efficacy of argatroban for END in AIS.Design, Setting, and Participants: This open-label, blinded–end point, randomized clinical trial was conducted from April 4, 2020, through July 31, 2022. The date of final follow-up was October 31, 2022. This was a multicenter trial. Eligible patients were adults with AIS who experienced END, which was defined as an increase of 2 or more points on the National Institutes of Health Stroke Scale within 48 hours from symptom onset. Patients who withdrew consent, experienced duplicate randomization, or were lost to follow-up were excluded from the study.Interventions: Patients were randomly assigned to the argatroban group and control group within 48 hours of symptom onset. Both groups received standard therapy based on guidelines, including oral mono or dual antiplatelet therapy. The argatroban group received intravenous argatroban for 7 days (continuous infusion at a dose of 60 mg per day for 2 days, followed by 20 mg per day for 5 days) in addition to standard therapy.Main Outcome and Measure: The primary end point was good functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 3.Results: A total of 628 patients (mean [SD] age, 65 [11.9] years; 400 male [63.7%]) were included in this study (argatroban group, 314 [50%] and control group, 314 [50%]). Of these, 18 withdrew consent, 1 had duplicate randomization, and 8 were lost to follow-up. A total of 601 patients with stroke were included in the intention-to-treat analysis. Finally, 564 patients were included in the per-protocol analysis as 6 participants in the argatroban group and 31 participants in the control group did not follow the complete protocol. The number of patients with good functional outcome at 90 days was 240 (80.5%) in the argatroban group and 222 (73.3%) in the control group (risk difference, 7.2%; 95% CI, 0.6%-14.0%; risk ratio, 1.10; 95% CI, 1.01-1.20; P = .04). The proportion of symptomatic intracranial hemorrhage was 3 of 317 (0.9%) in the argatroban group and 2 of 272 (0.7%) in the control group (P = .78).Conclusions and Relevance: Among patients with AIS with END, treatment with argatroban and antiplatelet therapy resulted in a better functional outcome at 90 days. This trial provided evidence to support the use of argatroban in reducing disability for patients with END.Trial Registration: ClinicalTrials.gov Identifier: NCT04275180