Association of cognitive reserve with the risk of dementia in the UK Biobank: role of polygenic factors.

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.

Association between psychosocial working conditions and well-being before retirement: a community-based study.

Psychosocial working conditions have been linked to mental health outcomes, but their association with well-being is poorly studied. We aimed to investigate the association between psychosocial working conditions and well-being before retirement, and to explore the role of gender and leisure activities in the association. From the Swedish National Study on Aging and Care in Kungsholmen, 598 community dwellers aged 60-65 years were included in the cross-sectional study. Lifelong occupational history was obtained through an interview. Job demands and job control in the longest-held occupation were graded with job exposure matrices. Psychosocial working conditions were classified into high strain (high demands, low control), low strain (low demands, high control), passive job (low demands, low control), and active job (high demands, high control). Well-being was assessed with the 10-item version of positive and negative affect schedule, and scored using confirmatory factor analysis. Engagement in leisure activities was categorized as low, moderate, and high. Data were analyzed using linear regression. Both high job control and high job demands were dose-dependently associated with higher well-being. Overall, compared to active jobs, passive jobs were associated with lower well-being (ß -0.19, 95% CI -0.35 to -0.02, P = 0.028). Passive (ß -0.28, 95% CI -0.51 to -0.04, P = 0.020) and high strain (ß -0.31, 95% CI -0.52 to -0.10, P = 0.004) jobs were associated with lower well-being in men, but not in women. The association between passive jobs and well-being was attenuated by high leisure activities, while the association between high strain and well-being was magnified by low leisure activities. In conclusion, negative psychosocial working conditions are associated with poor well-being, especially in men. Leisure activities may modulate the association. Our study highlights that promoting favorable working conditions can be a target to improve well-being among employees and active participation in leisure activities is encouraged to cope with work-related stress for better well-being.

High lifelong cognitive reserve prolongs disability-free survival: The role of cognitive function.

INTRODUCTION: The association between cognitive reserve (CR) and survival with independence is unknown. We examined whether lifelong CR accumulation is associated with disability-free survival and explored the extent to which cognitive function mediates this association. METHODS: Within the Rush Memory and Aging Project, 1633 dementia- and disability-free participants were followed annually for up to 22 years. Lifelong CR including education, early-/mid-/late-life cognitive activities, and late-life social activity was assessed and tertiled. RESULTS: CR score was dose-dependently associated with disability/death (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.93-0.99). Compared to low CR, the HR (95% CI) of disability/death was 0.82 (0.70-0.95) for high CR. The median disability-free survival time was prolonged by 0.99 (95% CI 0.28-1.71) years for participants with high CR. Cognitive function mediated 35.7% of the association between CR and disability-free survival. DISCUSSION: High lifelong CR was associated with prolonged disability-free survival. Cognitive function mediates about one-third of this association. Our findings underscore the importance of CR for healthy aging.

Association of life-course traumatic brain injury with dementia risk: A nationwide twin study.

INTRODUCTION: The impact of life-course traumatic brain injury (TBI) on dementia is unclear. METHODS: Within the Swedish Twin Registry (STR), 35,312 dementia-free twins were followed for up to 18 years. TBI history was identified via medical records. Data were analyzed using generalized estimating equation (GEE) and conditional logistic regression. RESULTS: In multi-adjusted GEE models, the odds ratio (OR, 95% confidence interval [CI]) of dementia was 1.27 (1.03-1.57) for TBI at any age, 1.55 (1.04-2.31) for TBI at 50 to 59 years, and 1.67 (1.12-2.49) for TBI at 60 to 69 years. Cardiometabolic diseases (CMDs) increased dementia risk associated with TBI at age 50 to 69 years. The ORs in GEE and conditional logistic regression did not differ significantly (P = .37). DISCUSSION: TBI, especially between ages 50 and 69 years, is associated with an increased risk of dementia, and this is exacerbated among people with CMDs. Genetic and early-life environmental factors may not account for the TBI-dementia association.

Association of impaired kidney function with dementia and brain pathologies: A community-based cohort study.

INTRODUCTION: The relationship between impaired kidney function (KF), dementia, and brain pathologies remains unclear. METHODS: A total of 1354 dementia- and kidney disease-free participants including 895 with normal and 459 with impaired KF were followed from 2002 until 2020 (median [interquartile range]: 5 [2-9]) to detect incident dementia. KF was assessed at baseline and categorized as normal or impaired. Over the follow-up, 453 participants died and underwent autopsies for neuropathological assessment. RESULTS: Compared to those with normal KF, the hazard ratios (95% confidence intervals [CIs]) of those with impaired KF was 1.48 (1.15, 1.90)/1.44 (1.10, 1.88) for dementia/Alzheimer's dementia. Furthermore, impaired KF was related to a significantly higher burden of cerebral amyloid angiopathy (CAA; odds ratio = 1.96, 95% CI: 1.17, 3.30), but not to other brain pathologies. DISCUSSION: Impaired KF is associated with an increased risk of dementia and Alzheimer's dementia. CAA may underlie, in part, this association. HIGHLIGHTS: Impaired kidney function (KF) was associated with higher dementia and Alzheimer's dementia risk. Impaired KF anticipated dementia and Alzheimer's dementia onset by more than 1.5 years. Impaired KF was significantly related to a higher burden of cerebral amyloid angiopathy (CAA) but not to other brain pathologies.

Association of life-course reproductive duration with mortality: a population-based twin cohort study.

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.

Injurious falls before, during and after dementia diagnosis: a population-based study.

BACKGROUND: the timing of incident injurious falls at different stages of dementia diagnosis is unclear. OBJECTIVES: to identify when the occurrence of injurious falls begins to increase among individuals who are going to develop dementia, to explore the time point at which people living with dementia are at highest risk of injurious falls and to ascertain differences in fall-related factors pre- and post-dementia diagnosis. DESIGN: this study included 2,707 participants with incident dementia and 2,707 1:1 matched (i.e. same birth year and sex) controls without dementia. METHODS: dementia diagnosis and date of onset were identified from the National Patient Registry (NPR) and the Swedish Cause of Death Register following international criteria. Information on injurious falls and history of chronic disease was obtained from the NPR. Data were analysed using conditional Poisson regression and generalized estimating equation models. RESULTS: compared with controls, the incidence of injurious falls among participants with dementia started to increase beginning 4 years pre-diagnosis (incidence rate ratio [IRR] 1.70, 95% confidence interval [CI] 1.30-2.22), reaching a peak (IRR 3.73, 95% CI 3.16-4.41) in the year of dementia diagnosis. Heavy drinking, physically active and cardiometabolic diseases (CMDs) were associated with incident falls among those with dementia. CONCLUSION: people with dementia have a higher incidence of injurious falls beginning 4 years leading up to diagnosis and peaking during the year of diagnosis. Older age, female, heavy drinking, physically active and CMDs may predict injurious falls among people with dementia.

Research Progress of H2S Donors Conjugate Drugs Based on ADTOH.

H2S is an endogenous gas signaling molecule and its multiple biological effects have been demonstrated. The abnormal level of H2S is closely related to the occurrence and development of many diseases, and H2S donors has important pharmacological implications. In recent years, H2S donors represented by ADTOH (5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione) are often used to synthesize new 'conjugate' compounds that can release H2S and parent drugs. These hybrids retain the pharmacological activity of the parent drugs and H2S and have a synergistic effect. ADTOH and parent drug hybrids have become one of the important strategies for the development of H2S donor conjugate drugs. This review summarizes molecular hybrids between ADTOH and clinical drugs to provide new ideas for the study of H2S donor drug design.

Association of life-course depression with the risk of dementia in late life: A nationwide twin study.

INTRODUCTION: Whether depression is a prodromal phase or risk factor for dementia is under debate. We aimed to unveil the nature of depression-dementia association by looking into the time window of depression occurrence. METHODS: Dementia-free twins (n = 41,727) from the Swedish Twin Registry were followed-up for 18 years. Data were analyzed using generalized estimating equation (GEE) for all individuals and conditional logistic regression for co-twin matched pairs. RESULTS: In the GEE model, multi-adjusted odds ratios (ORs; 95% confidence intervals [CIs]) of dementia were 1.46 (1.09-1.95) for mid-life, 2.16 (1.82-2.56) for late-life, 2.24 (1.49-3.36) for mid- to late-life, and 2.65 (1.17-5.98) for lifelong depression. The ORs in conditional logistic regression and in GEE did not differ significantly (P = 0.60). Education ≥8 years attenuated dementia risk associated with mid-life depression. DISCUSSION: Not only late-life depression, but also mid-life depression is associated with dementia. Genetic and early-life environmental factors could not account for this association. Education ≥8 years might buffer the impact of mid-life depression on dementia.

Housefly Pupae-Derived Antioxidant Peptides Exerting Neuroprotective Effects on Hydrogen Peroxide-Induced Oxidative Damage in PC12 Cells.

In this study, two antioxidant peptides were identified and characterized from the alcalase-hydrolysate of housefly (Musca domestica L.) pupae guided by ABTS cation radical scavenging activity. Peptides sequences were identified as DFTPVCTTELGR (DR12, 1338.48 Da) and ARFEELCSDLFR (AR12, 1485.66 Da) using nano-liquid chromatography-tandem mass spectrometry (LC-MS/MS). Both DR12 and AR12 exert strong ABTS cation radical scavenging ability with EC50 values of 0.39 and 0.35 mM, respectively. Moreover, AR12 can effectively protect PC12 cells from oxidative damage induced by hydrogen peroxide (H2O2) by decreasing intracellular reactive oxygen species (ROS) and malonaldehyde (MDA), recovering cellular mitochondrial membrane potential (MMP), and increasing the activity of intracellular superoxide dismutase (SOD). Stability tests suggest that AR12 is competent for the challenge of heating, acid, alkali or simulated gastrointestinal (GI) digestion and exhibits great activity to remove ABTS cation radical. DR12 shows a great stability against heating, but its antioxidative ability declines after being treated with acid, alkali or simulated GI digestion. In general, both DR12 and AR12 identified from housefly pupae hydrolysate stand a chance of being potential antioxidants or precursors to antioxidants and AR12 might be applied in the field of neuroprotection.

Identification of a PDE4-Specific Pocket for the Design of Selective Inhibitors.

Inhibitors of phosphodiesterases (PDEs) have been widely studied as therapeutics for the treatment of human diseases, but improvement of inhibitor selectivity is still desirable for the enhancement of inhibitor potency. Here, we report identification of a water-containing subpocket as a PDE4-specific pocket for inhibitor binding. We designed against the pocket and synthesized two enantiomers of PDE4 inhibitor Zl-n-91. The ( S)-Zl-n-91 enantiomer showed IC50 values of 12 and 20 nM for the catalytic domains of PDE4D2 and PDE4B2B, respectively, selectivity several thousand-fold greater than those of other PDE families, and potent neuroprotection activities. Crystal structures of the PDE4D2 catalytic domain in complex with each Zl-n-91 enantiomer revealed that ( S)-Zl-n-91 but not ( R)-Zl-n-91 formed a hydrogen bond with the bound water in the pocket, thus explaining its higher affinity. The structural superposition between the PDE families revealed that this water-containing subpocket is unique to PDE4 and thus valuable for the design of PDE4 selective inhibitors.

Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats.

Endothelial dysfunction, characterized by impairment of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) bioavailability, has been implicated in diabetic cardiovascular pathogenesis. In this study, low-molecular-weight fucoidan (LMWF), which has multiple biological activities including anti-inflammatory and anti-oxidative properties, was investigated for its protective effect against endothelial dysfunction in Goto-Kakizaki type 2 diabetic rats. LMWF (50, 100, or 200 mg/kg/day) or probucol (100 mg/kg/day) were given to diabetic rats for 12 weeks. Basal blood pressure, acetylcholine- or flow-mediated relaxation of mesenteric and paw arteries, endothelium-dependent dilation of aorta, eNOS phosphorylation, and NO production were measured using laser Doppler flowmetry, force myograph, hematoxylin and eosin staining, western blot analysis, and an NO assay. We found that LMWF robustly ameliorated the basal hypertension and impairment of endothelium-dependent relaxation in the aorta, as well as mesenteric and paw arteries in diabetic rats. In addition, the reduction in eNOS phosphorylation at Ser1177, eNOS expression, and NO production because of diabetes were partially reversed by LMWF treatment. However, probucol, a lipid-modifying drug with antioxidant properties, displayed only mild effects. Moreover, LMWF induced, in a dose-dependent manner, endothelium-dependent vasodilation and eNOS phosphorylation at Ser1177 in normal aorta, and also promoted Ser1177 phosphorylation and NO synthesis in primary cultured vasoendothelial cells. Thus, these data demonstrate for the first time that fucoidan protects vasoendothelial function and reduces basal blood pressure in type 2 diabetes rats via, at least in part, preservation of eNOS function. Fucoidan is therefore a potential candidate drug for protection of endothelium in diabetic cardiovascular complications.

[Identification of marine-derived shell TCM by near infrared spectroscopy].

The identification of five marine-derived shell traditional Chinese medicine (TCM) recorded in the Chinese Pharmacopoeia were studied. Using near infrared technology (NIR) combined with principal component analysis (PCA) methods, Ostreae Concha, Haliotidis Concha, and Margaritifera Concha could be efficiently distinguished from Meretricis Concha together with Arcae Concha. In the first principal components, Ostreae Concha exhibited obvious differences with high loadings in 4 236, 5 263, 7 142 cm(-1) concerning to the contents of CaCO3 and H2O in the samples. Arcae Concha and Meretricis Concha displayed significant differences with others in the second principal components, which can be illustrated by high loadings in 5 000 -4 430 cm(-1) areas. It is indicated that the second principal components might be related to organics which contained NH and CH groups, for example proteins. Meanwhile, our data showed a correlation between the function of these shell TCM and their distribution in the PCA plot. These results suggested that organic components in marine-derived shell TCM could not be neglected for their quality control.

Procyanidine alleviates bisphenol A-induced apoptosis in TM3 cells via the Nrf2 signaling pathway.

Contaminated foods are a major source of bisphenol A (BPA) and are widely used in food packaging. Prolonged exposure to BPA can cause reproductive dysfunction in humans. Procyanidine (PC) is a potent natural antioxidant; however, the exact mechanism by which PC mitigates Leydig cell damage caused by BPA is unknown. In this study, the protective effect of PC against BPA-induced TM3 cell damage was investigated, and the underlying mechanism was assessed. PC treatment attenuates BPA-induced TM3 cell damage by suppressing oxidative stress and inhibiting TM3 apoptosis. In addition, PC upregulates the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant target genes. Treatment with the NRF2 inhibitor ML385 reversed the PC-induced upregulation of the mRNA expression of these genes. Overall, PC may mitigate BPA-induced cell damage by activating the Nrf2 signaling pathway, suggesting that PC supplementation may alleviate BPA toxicity in TM3 cells.

Vertical porous aerogel based on polypyrrole and bimetallic modified ß-cyclodextrin polymer-chitosan for efficient solar evaporation.

Solar-driven interfacial evaporation (SDIE) stands out as a prospective technology for freshwater production, playing a significant role in mitigating global water scarcity. Herein, a cyclodextrin polymer/chitosan composite aerogel (PPy-La/Al@CDP-CS) with vertically aligned channels was prepared as a solar evaporator for efficient solar steam generation. The vertically aligned pore structure, achieved through directional freezing assisted by liquid nitrogen, not only improves water transport during evaporation but also enhances light absorption through multiple reflections of sunlight within the pores. The polypyrrole particles sprayed on the surface of the aerogel acted as a light-absorbing layer, resulting in an impressive absorbance of 98.15 % under wetting conditions. The aerogel has an evaporation rate of 1.85 kg m-2 h-1 under 1 kW m-2 irradiation. Notably, the vertical pore structure of the aerogel allows it to exhibit excellent evaporation performance and salt resistance even in highly concentrated salt solutions. Furthermore, this aerogel is an excellent solar-driven interfacial evaporator for purifying seawater and fluoride-containing wastewater. This photothermal aerogel has the advantages of excellent performance, low cost, and environmental friendliness, and thus this work provides a new approach to the design and fabrication of solar photothermal materials for water treatment.

Influence of cognitive reserve on risk of depression and subsequent dementia: A large community-based longitudinal study.

BACKGROUND: Cognitive reserve (CR) has been linked to dementia, yet its influence on the risk of depression and related outcomes remains unknown. We aimed to examine the association of CR with depression and subsequent dementia or death, and to assess the extent to which CR is related to depression-free survival. METHODS: Within the UK Biobank, 436,232 participants free of depression and dementia were followed. A comprehensive CR indicator (low, moderate, and high) was created using latent class analysis based on information on education, occupation, mentally passive sedentary behavior, social connection, confiding with others, and leisure activities. Depression, dementia, and survival status were ascertained through self-reported medical history and/or linkages to medical records. Data were analyzed using multi-state Markov model and Laplace regression. RESULTS: Over a median follow-up of 12.96 years, 16,560 individuals developed depression (including 617 with subsequent dementia) and 28,655 died. In multivariable multi-state models, compared with low CR, high CR was associated with lower risk of depression (hazard ratio 0.53 [95% confidence interval 0.51-0.56]) and lower risk of post-depression dementia (0.55 [0.34-0.88]) or death (0.69 [0.55-0.88]) in middle-aged adults (aged <60 years). In Laplace regression, the depression-free survival time was prolonged by 2.77 (2.58-2.96) years in participants with high compared to low CR. CONCLUSIONS: High CR is associated with lower risks of depression and subsequent transitions to dementia and death, particularly in middle age. High CR may prolong depression-free survival. Our findings highlight the importance of enhancing CR in the prevention and prognosis of depression.

Association of cardiometabolic multimorbidity with risk of late-life depression: a nationwide twin study.

BACKGROUND: Cardiometabolic diseases (CMDs) including heart disease, stroke, and type 2 diabetes have been individually linked to depression. However, their combined impact on depression risk is unclear. We aimed to examine the association between cardiometabolic multimorbidity and depression and explore the role of genetic background in this association. METHODS: Within the Swedish Twin Registry, 40,080 depression-free individuals (mean age 60 years) were followed for 18 years. Cardiometabolic multimorbidity was defined as having ≥2 CMDs. CMDs and depression were ascertained based on the National Patient Register. Cox regression was used to estimate the CMD-depression association in a classical cohort study design and a matched co-twin design involving 176 twin pairs. By comparing the associations between monozygotic and dizygotic co-twins, the contribution of genetic background was estimated. RESULTS: At baseline, 4809 (12.0%) participants had one CMD and 969 (2.4%) had ≥2 CMDs. Over the follow-up period, 1361 participants developed depression. In the classical cohort design, the multi-adjusted hazard ratios (95% confidence interval [CIs]) of depression were 1.52 (1.31-1.76) for those with one CMD and 1.83 (1.29-2.58) for those with ≥2 CMDs. CMDs had a greater risk effect on depression if they developed in mid-life (<60 years) as opposed to late life (≥60 years). In matched co-twin analysis, the CMD-depression association was significant among dizygotic twins (HR = 1.63, 95% CI, 1.02-2.59) but not monozygotic twins (HR = 0.90, 95% CI, 0.32-2.51). CONCLUSIONS: Cardiometabolic multimorbidity is associated with an elevated risk of depression. Genetic factors may contribute to the association between CMDs and depression.

Association of a low-inflammatory diet with survival among adults: The role of cardiometabolic diseases and lifestyle.

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.

Relation of Cognitive Reserve Indicator to Heart Disease and Cardiac Structure and Function: A Large Community-Based Longitudinal Study.

BACKGROUND: High cognitive reserve (CR) has been related to lower dementia risk, but its association with heart disease (HD) is unknown. We aimed to explore the relation of CR to HD and cardiac structure and function. METHODS AND RESULTS: Within the UK Biobank, 349 907 HD-free participants were followed up. A composite CR indicator involving education/occupation attainment/television viewing time/confiding frequency/social connection frequency/variety of leisure activities was generated, and further categorized into low/moderate/high levels. Incident HD, including coronary HD, cardiac arrhythmia, and heart failure, was ascertained on the basis of medical records. During the follow-up, a subsample (n=31 182) underwent cardiac magnetic resonance imaging to assess ventricular structure and function. Data were analyzed using Cox regression, Laplace regression, and linear regression. Compared with low CR, the hazard ratio and 95% CI of any HD for high CR was 0.78 (0.75-0.80) (including 0.68 [0.66-0.71] for coronary HD, 0.91 [0.87-0.95] for cardiac arrhythmia, and 0.63 [0.58-0.68] for heart failure). Furthermore, high CR was associated with delayed HD onset by 1.59 (95% CI, 1.37-1.82) years compared with low CR. In cardiac magnetic resonance imaging data analysis, compared with low CR, high CR was associated with larger left ventricular end-diastolic volume (ß, 0.13 [95% CI, 0.09-0.17]), left ventricular end-systolic volume (ß, 0.05 [95% CI, 0.01-0.10]), left ventricular stroke volume (ß, 0.16 [95% CI, 0.12-0.21]), and left ventricular ejection fraction (ß, 0.08 [95% CI, 0.03-0.13]). CONCLUSIONS: High CR is associated with favorable HD health. Our findings suggest that the beneficial effect of CR is not limited to dementia but also HD.

High cognitive reserve attenuates the risk of dementia associated with cardiometabolic diseases.

BACKGROUND: Cardiometabolic diseases (CMDs) including type 2 diabetes, heart disease, and stroke have been linked to a higher risk of dementia. We examined whether high levels of cognitive reserve (CR) can attenuate the increased dementia risk and brain pathologies associated with CMDs. METHODS: Within the UK Biobank, 216,178 dementia-free participants aged ≥ 60 were followed for up to 15 years. Baseline CMDs and incident dementia were ascertained from medical records, medication use, and medical history. Latent class analysis was used to generate an indicator of CR (low, moderate, and high) based on education, occupational attainment, confiding in others, social contact, leisure activities, and television watching time. A subsample (n = 13,663) underwent brain MRI scans during follow-up. Volumes of total gray matter (GMV), hippocampus (HV), and white matter hyperintensities (WMHV) were ascertained, as well as mean diffusivity (MD) and fractional anisotropy (FA) in white matter tracts. RESULTS: At baseline, 43,402 (20.1%) participants had at least one CMD. Over a mean follow-up of 11.7 years, 6,600 (3.1%) developed dementia. The presence of CMDs was associated with 57% increased risk of dementia (HR 1.57 [95% CI 1.48, 1.67]). In joint effect analysis, the HRs of dementia for people with CMDs and moderate-to-high CR and low CR were 1.78 [1.66, 1.91] and 2.13 [1.97, 2.30]), respectively (reference: CMD-free, moderate-to-high CR). Dementia risk was 17% lower (HR 0.83 [0.77, 0.91], p < 0.001) among people with CMDs and moderate-to-high compared to low CR. On brain MRI, CMDs were associated with smaller GMV (ß -0.18 [-0.22, -0.13]) and HV (ß -0.13 [-0.18, -0.08]) as well as significantly larger WMHV (ß 0.06 [0.02, 0.11]) and MD (ß 0.08 [0.02, 0.13]). People with CMDs and moderate-to-high compared to low CR had significantly larger GMV and HV, but no differences in WMHV, MD, or FA. CONCLUSIONS: Among people with CMDs, having a higher level of CR was associated with lower dementia risk and larger gray matter and hippocampal volumes. The results highlight a mentally and socially active life as a modifiable factor that may support cognitive and brain health among people with CMDs.