Midlife Risk Research Articles

Genomics and Biomarkers in older Latinos: Challenges and Opportunities

AbstractThere are fundamental knowledge gaps about normal aging, cognitive decline, and the roles of Alzheimer’s Disease (AD) biomarkers in the Latino population. Previous studies report, ethno‐racial differences in amyloid (A), tau (T), and neurodegeneration (N) biomarkers and genetics of AD. However, most studies including Latino populations consider those as a monolithic group while ignoring the genetic and environmental diversity of this group. Latinos are racially and ethnically diverse, and often reflect a mix of culture, environment, and genetic ancestries drawn from African, Amerindian, and European backgrounds. Research suggest that Latinos are both less likely to carry an APOE‐ε4 allele and have less of a risk for AD due to the ε4 allele than White non‐Latinos. Further, epidemiology, biomarker, and neuroimaging data suggest that vascular risk factors are prevalent in Latinos and may increase risk in midlife, thus impacting dementia rates later in life. The interaction of genetic and environmental factors in the development and progression of AD is complex in Latinos due to the influence of different levels of education, acculturation, socioeconomic conditions, immigration, language proficiency, and bilingualism, among others. In this session, the US Consortium of Aging, Dementia & Latino Studies (CADLAS) Genomics and Biomarkers Special Interest Group (SIG) will discuss recent developments, current challenges and opportunities in this area of research. The SIG was created in 2022 with the main goal of promoting collaborations among investigators to accelerate research and discovery of biomarkers and new diagnostics that work for US Latino populations. Research priorities include validation of biomarkers of proteinopathies and neurodegeneration, as well as vascular contributions to cognitive impairment and dementias, and development of novel and most sensitive biomarkers. Explorations of the unique genomic ancestry of diverse Latinos will also be considered as they are likely to provide new insights into cognitive decline and dementia in this population.

FC36: Social determinants of modifiable dementia risk in Maori and Non-Maori: Results of the New Zealand Health, Work and Retirement study

Background:Dementia risk varies along the social gradient, which needs to be considered in risk reduction and prevention strategies. Revealing links of social determinants of health (SDOH) and modifiable health and lifestyle factors for dementia holds clues towards maximizing dementia risk reduction opportunities, especially for vulnerable populations. Therefore, the aim was to investigate associations of SDOH and a dementia risk score in Indigenous Māori and Non-Māori (mainly European descent) in midlife and early late-life.Method:A subsample of the New Zealand Health, Work and Retirement study completed standardized face-to-face cognitive assessments (adapted ‘Kiwi’ Addenbrooke’s Cognitive Examination/ACE-R) in 2010. We computed the Lifestyle for Brain Health (LIBRA) dementia risk score, comprising 8 risk factors (low/moderate alcohol consumption, heart disease, physical inactivity, chronic kidney disease, diabetes, smoking, hypertension, depression). Higher scores indicate higher dementia risk/poorer lifestyle (range= -1;+9.2). First, we assessed associations of LIBRA and cognition. Second, we performed adjusted regression analysis for area-based (socioeconomic deprivation, health care access, neighbourhood safety) and individual SDOH (education, employment status, net income, social loneliness) with LIBRA stratified for Māori and Non-Māori.Results:In 918 participants (age: M= 62.9 years, SD= 6.7, range= 48-75; females= 52.8%; Māori= 26.2%), a higher LIBRA score (M= 1.8, SD= 1.6, observed range= -1; +7.4) was associated with lower cognitive functioning (b= -0.30, 95%CI= [-0.48;-0.11], p= .002) and cognitive impairment (OR= 1.41, 95%CI= [1.10;1.81], p= .007), adjusted for age, sex, education, ethnicity and area-based socio- economic deprivation. Higher area-based socio-economic deprivation was associated with higher LIBRA in Māori (b= .10, 95%CI= [0.02;0.18], p= .020), but not in Non-Māori (b= 0.01, 95%CI= [- .03;0.05], p= .677). Employment status and lower neighbourhood safety were associated with higher LIBRA in Non-Māori only. Health care access difficulties and social loneliness were associated with higher LIBRA in both populations, while education and net income were not.Conclusion:SODH are differentially associated with dementia risk in midlife and early late-life New Zealanders. Area-based socioeconomic deprivation was linked to dementia risk in Indigenous Māori, but not in Non-Māori. This points to systematic inequities in dementia risk, which require equity- focused policy-based public health approaches to risk reduction.

Social determinants of modifiable dementia risk in Māori and Non‐Māori: Results of the New Zealand Health, Work and Retirement study

AbstractBackgroundDementia risk varies along the social gradient, which needs to be considered in risk reduction and prevention strategies. Revealing links of social determinants of health (SDOH) and modifiable health and lifestyle factors for dementia holds clues towards maximizing dementia risk reduction opportunities, especially for vulnerable populations. Therefore, the aim was to investigate associations of SDOH and a dementia risk score in Indigenous Māori and Non‐Māori (mainly European descent) in midlife and early late‐life.MethodA subsample of the New Zealand Health, Work and Retirement study completed standardized face‐to‐face cognitive assessments (adapted ‘Kiwi’ Addenbrooke’s Cognitive Examination/ACE‐R) in 2010. We computed the Lifestyle for Brain Health (LIBRA) dementia risk score, comprising 8 risk factors (low/moderate alcohol consumption, heart disease, physical inactivity, chronic kidney disease, diabetes, smoking, hypertension, depression). Higher scores indicate higher dementia risk/poorer lifestyle (range = ‐1;+9.2). First, we assessed associations of LIBRA and cognition. Second, we performed adjusted regression analysis for area‐based (socioeconomic deprivation, health care access, neighborhood safety) and individual SDOH (education, employment status, net income, social loneliness) with LIBRA stratified for Māori and Non‐Māori.ResultsIn 918 participants (age: M = 62.9 years, SD = 6.7, range = 48‐75; females = 52.8%; Māori = 26.2%), a higher LIBRA score (M = 1.8, SD = 1.6, observed range = ‐1; +7.4) was associated with lower cognitive functioning (b = ‐0.30, 95%CI = [‐0.48;‐0.11], p = .002) and cognitive impairment (OR = 1.41, 95%CI = [1.10;1.81], p = .007), adjusted for age, sex, education, ethnicity and area‐based socio‐economic deprivation. Higher area‐based socio‐economic deprivation was associated with higher LIBRA in Māori (b = .10, 95%CI = [0.02;0.18], p = .020), but not in Non‐Māori (b = 0.01, 95%CI = [‐.03;0.05], p = .677). Employment status and lower neighborhood safety were associated with higher LIBRA in Non‐Māori only. Health care access difficulties and social loneliness were associated with higher LIBRA in both populations, while education and net income were not.ConclusionSODH are differentially associated with dementia risk in midlife and early late‐life New Zealanders. Area‐based socioeconomic deprivation was linked to dementia risk in Indigenous Māori, but not in Non‐Māori. This points to systematic inequities in dementia risk, which require equity‐focused policy‐based public health approaches to risk reduction.

Involuntary tobacco smoke exposures from conception to 18 years increase midlife cardiometabolic disease risk: a 40-year longitudinal study.

Few population studies have sufficient follow-up period to examine early-life exposures with later life diseases. A critical question is whether involuntary exposure to tobacco smoke from conception to adulthood increases the risk of cardiometabolic diseases (CMD) in midlife. In the Collaborative Perinatal Project, serum-validated maternal smoking during pregnancy (MSP) was assessed in the 1960s. At a mean age of 39 years, 1623 offspring were followed-up for the age at first physician-diagnoses of any CMDs, including diabetes, heart disease, hypertension, or hyperlipidemia. Detailed information on their exposure to environmental tobacco smoke (ETS) in childhood and adolescence was collected with a validated questionnaire. Cox regression was used to examine associations of in utero exposure to MSP and exposure to ETS from birth to 18 years with lifetime incidence of CMD, adjusting for potential confounders. We calculated midlife cumulative incidences of hyperlipidemia (25.2%), hypertension (14.9%), diabetes (3.9%), and heart disease (1.5%). Lifetime risk of hypertension increased by the 2nd -trimester exposure to MSP (adjusted hazard ratio: 1.29, 95% confidence interval: 1.01-1.65), ETS in childhood (1.11, 0.99-1.23) and adolescence (1.22, 1.04-1.44). Lifetime risk of diabetes increased by joint exposures to MSP and ETS in childhood (1.23, 1.01-1.50) or adolescence (1.47, 1.02-2.10). These associations were stronger in males than females, in never-daily smokers than lifetime ever smokers. In conclusion, early-life involuntary exposure to tobacco smoke increases midlife risk of hypertension and diabetes in midlife.

Impact of midlife intake of flavonoid‐rich fruits on dementia risk in the Framingham Heart Study

AbstractBackgroundConsumption of foods with high flavonoid content may be protective against dementia in older adults, but it is unclear whether this relationship is consistent earlier in life. We investigated the relationship between consumption of flavonoid‐rich fruits in midlife and risk of dementia, including Alzheimer’s disease (AD).Method1,642 participants from the Framingham Heart Study Offspring cohort who were aged 45‐59 years and did not have prevalent dementia at Exam 5 (1991‐1995), and had a valid food frequency questionnaire data were included. Intake of 12 fruit items with high flavonoid content or are important contributors to overall flavonoid intake at Exam 5 were examined. Total fruit intake was calculated by summing intake of each fruit item. Diagnoses of all‐cause dementia and AD dementia were adjudicated by a multi‐disciplinary consensus committee through 2019. Cox models were used to evaluate the association between higher intake (>30th percentile) versus lower intake (≤30th percentile) of total fruit consumption, as well for each fruit item, and incident dementia, adjusting for demographic, behavior and lifestyle, dietary, genetic, and clinical factors.ResultThe sample was, on average, 52 years of age, 53% female, and had 14 years of education, with an average follow up time of 24 years in the study. Higher intake of total fruits was associated with decreased risk of all‐cause dementia (HR = 0.56; 95% CI = 0.32 – 0.98), but not with AD dementia. Decreased risk of all‐cause dementia was associated with higher intake of apples or pears (HR = 0.47; 95% CI = 0.27 – 0.81), and oranges (HR = 0.55; 95% CI = 0.32 – 0.95). Higher intakes of apples or pears (HR = 0.50; 95% CI = 0.25 – 1.00), and oranges (HR = 0.43; 95% CI = 0.22 – 0.85), were also associated with decreased risk of AD dementia. Sex modified the association between total fruit intake in midlife and dementia risk (HRfemale = 0.46; 95% CI = 0.21 – 0.97; HRmale = 0.65; 95% CI = 0.27 – 1.60).ConclusionGreater consumption of flavonoid‐rich fruits in midlife, particularly apples or pears, as well as oranges, were significantly associated with reduced dementia risk.

P140: Midlife diet and risk of dementia/mild cognitive impairment

The Japan Public Health Center-based prospective (JPHC) Study is a large population-based cohort. Midlife dietary intake was assessed on two occasions: in the years 1995 and 2000 (aged 45-64 in 1995). In 2014-2015, approximately 1300 participants from Saku district in Nagano prefecture completed a mental health screening including later life depression and cognitive decline (i.e., mild cognitive impairment (MCI) and dementia). We used logistic regression analyses to calculate odds ratios (ORs) for MCI and dementia. Based on this survey, we found the following characteristics of midlife diet, which may be useful information to prevent cognitive decline/dementia.1.High-density lipoprotein cholesterol (HDL-C) and later cognitive decline (Svensson et al. Transl Psychiatry, 2019): Midlife high-density lipoprotein cholesterol (HDL-C) is a measure which could help identify individuals at reduced risk of developing age-related cognitive decline. Compared to the lowest HDL-C quartile, the highest HDL-C quartile was significantly inversely associated with MCI. High HDL-C (quartiles 2-4) was inversely associated with dementia compared to low HDL-C (quartile 1).2.Dietary fish and n-3 polyunsaturated fatty acid (PUFA) and later cognitive decline (Nozaki et al. J Alzheimers Dis, 2021): Higher intake of fish, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) in midlife significantly reduced risks of dementia.3.Intake of soy and the isoflavone and later cognitive decline (Svensson et al. J Alzheimers Dis, 2021): Compared to the lowest dietary quartile of energy-adjusted isoflavone genistein intake, the highest quartile was significantly associated with late-life cognitive impairment.4.Cancer/diabetes and later cognitive decline (Sadahiro et al. Psychiatry Clin Neurosci, 2019): Comorbid cancer and diabetes from midlife may increase the risk of MCI or dementia in later life. In addition to the increased dementia risk associated with diabetes on the basis of insulin resistance, cancer and cancer therapies may also interfere with cognitive function via insulin resistance.

Cardiovascular Disease and Alzheimer's Disease: The Heart-Brain Axis.

Cardiovascular disease (CVD) remains one of the leading causes of morbidity and mortality in aging adults across the United States. Prior studies indicate that the presence of atherosclerosis, the pathogenic basis of CVD, is linked with dementias. Alzheimer's disease (AD) and AD-related dementias are a major public health challenge in the United States. Recent studies indicate that ≈3.7 million Americans ≥65 years of age had clinical AD in 2017, with projected increases to 9.3 million by 2060. Treatment options for AD remain limited. Development of disease-modifying therapies are challenging due, in part, to the long preclinical window of AD. The preclinical incubation period of AD starts in midlife, providing a critical window for identification and optimization of AD risk factors. Studies link AD with CVD risk factors such as hypertension, inflammation, and dyslipidemia. Both AD and CVD are progressive diseases with decades-long development periods. CVD can clinically manifest several years earlier than AD, making CVD and its risk factors a potential predictor of future AD. The current review focuses on the state of literature on molecular and metabolic pathways modulating the heart-brain axis underlying the potential association of midlife CVD risk factors and their effect on AD and related dementias. Further, we explore potential CVD/dementia preventive strategies during the window of opportunity in midlife and the future of research in the field in the multiomics and novel biomarker use era.

Cohort profile: the longitudinal National Growth and Health Study (NGHS) of black and white girls from Northern California tracking how behavioural and psychosocial risk factors predict cardiovascular risk and biological ageing in midlife and in offspring

PurposeThe National Heart, Lung and Blood Institute Growth and Health Study (NGHS) prospectively collected anthropometric, biospecimens, clinical, health behaviour and psychosocial measures associated with cardiovascular disease from childhood to young...

A lifecourse Mendelian randomization study uncovers age-dependent effects of adiposity on asthma risk

Evaluating the long-term consequences of childhood lifestyle factors on asthma risk can be exceptionally challenging in epidemiology given that cases are typically diagnosed at various timepoints throughout the lifecourse. In this study, we used human genetic data to evaluate the effects of childhood and adulthood adiposity on risk of pediatric (n= 13,962 cases) and adult-onset asthma (n= 26,582 cases) with a common set of controls (n= 300,671) using a technique known as lifecourse Mendelian randomization. We found that childhood adiposity directly increases risk of pediatric asthma (OR= 1.20, 95% CI= 1.03-1.37, p=0.03), but limited evidence that it has an effect on adult-onset asthma after accounting for adiposity during adulthood (OR= 1.05, 95% CI= 0.93-1.17, p= 0.39). Conversely, there was strong evidence that adulthood adiposity increases asthma risk in midlife (OR= 1.37, 95% CI= 1.28-1.46, P= 7×10-12). These findings suggest that childhood and adulthood adiposity are independent risk factors for asthma at each of their corresponding timepoints in the lifecourse.

Physical illness and changes in spousal depression: a register study on Finnish middle-aged couples

Abstract Background Physical health decline may affect family members’ mental health by causing distress and, in case of functional impairments, need to provide care. We examined how diseases common in midlife but with different disease progression and level of impairment are associated with short-term and long-term changes in spousal depression. Methods We used Finnish total population register data from 2000-2019 to identify 91,849 men and 70,836 women aged 30-70 that experienced onset of severe diseases without cognitive impairment (myocardial infarction, prostate cancer, breast cancer), conditions with sudden onset and immediate impairment (stroke, traumatic brain injury) or progressive conditions with increasing impairment (Parkinson's disease, multiple sclerosis, dementia) while living with a spouse. We measured depression with antidepressant purchases and used fixed-effects linear probability models to examine spouses’ depression trajectories before and after onset of spousal disease Results Preliminary findings show that the onset of any type of spousal illness is associated with an increase in depression. Among men this increase is similar in magnitude irrespective of the type of spouse's illness, whereas among women the increase is smaller if the spouse is diagnosed with a disease without cognitive impairment. When the spouse is diagnosed with a progressive condition, female spouses’ depression increases more gradually, whereas a large immediate increase in depression follows sudden onset conditions. One year after diagnosis there are little changes in spousal depression. Conclusions Diseases common in midlife increase spouse's risk of depression around the time of diagnosis, and the effect appears persistent. Adequate support should thus be available to family members from the start of physical illness. When planning support to female spouses, the male spouse's cognitive impairment and associated care needs should be carefully evaluated. Key messages • Diseases common in midlife increase spouse's depression risk around the time of diagnosis, and the effect appears persistent. Support to spouses should be available from the start of illness. • Cognitive impairment of the male spouse seems to increase female spouse's depression particularly strongly, suggesting that caregiving help could be especially beneficial for women.

Midlife cardiovascular health factors as predictors of retirement age, work-loss years, and years spent in retirement among older businessmen

Cardiovascular disease (CVD) is one of the leading causes of premature retirement. However, the relationship between CVD risk factors and workforce participation is not well known. We studied the relationship between midlife CVD risk, age at retirement, work-loss years, and survival in retirement. Middle-aged Finnish men (initial n = 3490, mean age = 47.8 years) were assessed for CVD risk factors and general health in the 1970s. They worked as business executives and provided information on their retirement status in the year 2000. Survival was followed up to the 9th decade of life with a follow-up of up to 44 years. Work-loss years were calculated as death or retirement occurring at age ≤ 65 years. Smoking, body mass index, and alcohol use were used as covariates, excluding models of CVD risk, which were adjusted for alcohol use only. Higher risk of 10-year fatal CVD was associated with 0.32 more years (relative risk < 1 vs. 1, covariate-adjusted β = 0.32, 95% CI = 0.13, 0.53) of work-loss. Higher risk of 5-year incident (covariate-adjusted time-constant HR = 1.32, 95% CI = 1.19, 1.47) and 10-year fatal (covariate-adjusted time-dependent HR = 1.55, 95% CI = 1.30, 1.85) CVD in midlife were associated with fewer years spent in retirement. Poorer self-rated health and physical fitness and higher levels of triglycerides were associated with increased hazard of earlier retirement, more work-loss years, and fewer years spent in retirement. Poorer health and greater midlife CVD risk may be associated with earlier exit from the workforce and fewer years spent in retirement. Management of CVD risk in midlife may support people to work longer.

Mid-Life Vascular Risk and Rate of Physical Function Decline Among Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study.

Physical function and its decline in older age may be connected to treatable vascular risk factors in mid-life. This study aimed to evaluate whether these factors affect the underlying rate of decline. This prospective cohort included 5 481 older adults aged 67-91 in the Atherosclerosis Risk in Communities Study (mean [standard deviation {SD}] age = 75.8 [5.0], 58% women, 21% Black race) without a history of stroke. The main outcome was the rate of Short Physical Performance Battery (SPPB) decline over a median late-life follow-up of 4.8 years. Primary mid-life (aged 45-64) exposures were Visit 1 hypertension (>140/90 mm Hg or treatment), diabetes (>126 mg/dL or treatment), high cholesterol (>240 mg/dL or treatment), and smoking, and number of decades of vascular risk exposure across Visits 1-4. The average adjusted rate of SPPB decline (points per 5 years) for older adults was -0.79 (confidence interval [CI]: -0.87, 0.71) and was accelerated by mid-life hypertension (+57% decline vs normotension: additional decline of -0.47, 95% CI: -0.64, -0.30), diabetes (+73% decline vs no diabetes: additional decline of -0.67, 95% CI: -1.09, -0.24), elevated systolic blood pressure (+17% decline per SD: -0.16, 95% CI: -0.23, -0.10), and elevated fasting blood glucose (+16% decline per SD: -0.015, 95% CI: -0.24, -0.06). Each decade greater mid-life exposure to hypertension (+32% decline: -0.93, 95% CI: -1.25, -0.61) and diabetes (+35% decline: -1.03, 95% CI: -1.68, -0.38) was associated with faster SPPB decline. Mid-life control of blood pressure and diabetes may offset aging-related functional decline.

Childhood Maltreatment and Dementia Risk Factors in Midlife: A Prospective Investigation.

Previous studies have linked childhood adversities to dementia risk, yet most studies are cross-sectional in design and utilize retrospective self-reports to assess childhood experiences. These design characteristics make it difficult to establish temporal order and draw firm conclusions. Using a longitudinal design, we sought to determine whether childhood maltreatment predicts dementia risk factors in middle adulthood. Data have been obtained from a prospective cohort design study of children with documented cases of childhood maltreatment (ages 0-11 years at case identification) and demographically matched controls who were followed up and interviewed in middle adulthood. Outcomes were assessed through a medical examination and interview, and 807 of the cases that included blood collection at mean age 41. Dementia risk were investigated using 11 potentially modifiable risk factors. Compared to controls, individuals with histories of childhood maltreatment had a higher risk of low educational attainment, low social contact, smoking, and clinical depression, and a higher total number of dementia risk factors. In general, childhood maltreatment predicted a higher risk of dementia for females, males, and Black and White participants. Black maltreated participants had a greater risk for traumatic brain injury compared to Black controls. Physical abuse, sexual abuse, and neglect, each predicted a higher number of dementia risk factors in mid-life. These findings provide evidence that childhood maltreatment increases the risk for dementia in mid-life and has a demonstrable impact lasting over 30 years. Reducing the prevalence of mid-life dementia risk factors could reduce the risk of later-life dementia.

Inflammatory proteins are associated with mortality in a middle-aged diverse cohort.

Recent data indicate a decline in overall longevity in the United States. Even prior to the COVID-19 pandemic, an increase in midlife mortality rates had been reported. Life expectancy disparities have persisted in the United States for racial and ethnic groups and for individuals living at low socioeconomic status. These continued trends in mortality indicate the importance of examining biomarkers of mortality at midlife in at-risk populations. Circulating levels of cytokines and inflammatory markers reflect systemic chronic inflammation, which is a well-known driver of many age-related diseases. In this study, we examined the relationship of nine different inflammatory proteins with mortality in a middle-aged socioeconomically diverse cohort of African-American and White men and women (n=1122; mean age=47.8 years). We found significant differences in inflammatory-related protein serum levels between African-American and White middle-aged adults. E-selectin and fibrinogen were significantly higher in African-American adults. IFN-γ, TNF-α trimer, monocyte chemoattractant protein-1 (MCP-1), soluble receptor for advanced glycation end-products (sRAGE) and P-selectin were significantly higher in White participants compared to African-American participants. Higher levels of E-selectin, MCP-1 and P-selectin were associated with a higher mortality risk. Furthermore, there was a significant interaction between sex and IL-6 with mortality. IL-6 levels were associated with an increased risk of mortality, an association that was significantly greater in women than men. In addition, White participants with high levels of sRAGE had significantly higher survival probability than White participants with low levels of sRAGE, while African-American participants had similar survival probabilities across sRAGE levels. These results suggest that circulating inflammatory markers can be utilized as indicators of midlife mortality risk in a socioeconomically diverse cohort of African-American and White individuals.

Associations of blood pressure trajectories in early life with target organ damage in midlife : a 30-year cohort study.

Hypertension is a pivotal factor in cardiovascular risk. However, the association of longitudinal blood pressure (BP) trajectories in the early life and cardiovascular risk assessed by target organ damage (TOD) in adulthood is poorly reported. The objective of this study was to identify the association between systolic BP, diastolic BP, and mean atrial pressure (MAP) trajectories early in life with a single or multiple TOD in later life. We identified BP trajectories from 6 to 45 year-old using group-based trajectory models among 2430 individuals in the Hanzhong Adolescent Hypertension Study and examined the relationship between BP trajectories and cardiovascular risk in later life. Four discrete long-term systolic BP, diastolic BP, and MAP trajectories were identified, namely, low stable, moderate stable, high stable (low increasing), and moderate increasing groups, based on the BP levels at baseline and in the 30-year follow-up. The carotid intima-media thickness were higher in persistently high or increasing trajectories in comparison to the low stable group. Individuals with deteriorative trajectories during early life were at an increased risk of suffering from a single TOD, including left ventricular hypertrophy (LVH) and carotid atherosclerosis (CA) in middle age (36-49 years old). Moreover, higher BP trajectories were correlated with the presence of combined TODs load stage which were assessed by CA, LVH, arteriosclerosis and subclinical renal damage (SRD). Higher longitudinal BP trajectories early in life were associated with increased cardiovascular risk in midlife, and identifying BP trajectories in early life can help screen individuals with TOD later. LVH, left Ventricular Hypertrophy; CA, carotid atherosclerosis; SRD, subclinical renal damage; TOD, target organ damage.

New horizons in hearing conditions.

Hearing conditions such as hearing loss, tinnitus and hyperacusis are highly prevalent in the population and can severely impact communication and quality of life. Hearing is affected by multiple factors, including heredity, noise exposure, age, sex, ear disorders and lifestyle factors. Globally, hearing loss affects over 80% of adults aged 80years and older, is often experienced in combination with other long-term health conditions and is a mid-life risk factor for dementia. To form a themed collection, we searched Age and Ageing for articles on hearing conditions published from 2000 onwards. This resulted in 22 articles included within the collection. They examined a range of important topics related to hearing healthcare and research, including noise-induced hearing loss, health service quality and safety, psychological and psychosocial consequences of hearing loss and co-morbidities of hearing loss. All articles reported on hearing loss; there were no published articles with a primary focus on other hearing conditions such as tinnitus or hyperacusis, on the health of older people from the Deaf community or on users of Cochlear implants, suggesting key gaps in knowledge and targets for future research. This New Horizons article highlights novel directions in research and practice and takes a forward look at how research into hearing conditions may develop in years to come. It highlights opportunities for the growth of patient-centred research and hearing healthcare supported by the better integration of health and care services as well as cross-speciality working to include common co-morbid health conditions.

Childhood attention-deficit hyperactivity disorder problems and mid-life cardiovascular risk: prospective population cohort study.

It is well-known that childhood attention-deficit hyperactivity disorder (ADHD) is associated with later adverse mental health and social outcomes. Patient-based studies suggest that ADHD may be associated with later cardiovascular disease (CVD) but the focus of preventive interventions is unclear. It is unknown whether ADHD leads to established cardiovascular risk factors because so few cohort studies measure ADHD and also follow up to an age where CVD risk is evident. To examine associations between childhood ADHD problems and directly measured CVD risk factors at ages 44/45 years in a UK population-based cohort study (National Child Development Study) of individuals born in 1958. Childhood ADHD problems were defined by elevated ratings on both the parent Rutter A scale and a teacher-rated questionnaire at age 7 years. Outcomes were known cardiovascular risk factors (blood pressure, lipid measurements, body mass index and smoking) at the age 44/45 biomedical assessment. Of the 8016 individuals assessed both during childhood and at the biomedical assessment 3.0% were categorised as having childhood ADHD problems. ADHD problems were associated with higher body mass index (B = 0.92 kg/m2, s.d. = 0.27-1.56), systolic (3.5 mmHg, s.d. = 1.4-5.6) and diastolic (2.2 mmHg, s.d. = 0.8-3.6) blood pressure, triglyceride levels (0.24 mol/l, s.d. = 0.02-0.46) and being a current smoker (odds ratio OR = 1.6, s.d. = 1.2-2.1) but not with LDL cholesterol. Childhood ADHD problems predicted multiple cardiovascular risk factors by mid-life. These findings, when taken together with previously observed associations with cardiovascular disease in registries, suggest that individuals with ADHD could benefit from cardiovascular risk monitoring, given these risk factors are modifiable with timely intervention.

Cardiometabolic risk and bone mineral density in midlife and elderly women

Cardiometabolic risk and bone mineral density in midlife and elderly women

Educational Attainment and Dementia: Mediation by Mid-Life Vascular Risk Factors.

Lower education is associated with higher burden of vascular risk factors in mid-life and higher risk of dementia in late life. We aim to understand the causal mechanism through which vascular risk factors potentially mediate the relationship between education and dementia. In a cohort of 13,368 Black and White older adults in the Atherosclerosis Risk in Communities Study, we assessed the relationship between education (grade school, high school without graduation, high school graduate or equivalent, college, graduate/professional school) and dementia among all participants and among those with incident stroke. Cox models were adjusted for age, race-center (a variable stratified by race and field center), sex, apolipoprotein E (APOE) ε4 genotype, and family history of cardiovascular disease. Causal mediation models assessed mediation by mid-life systolic blood pressure, fasting blood glucose, body mass index, and smoking. More education was associated with 8 to 44% lower risk of dementia compared to grade school-level education in a dose-response pattern, while the relationship between education and post-stroke dementia was not statistically significant. Up to 25% of the association between education and dementia was mediated through mid-life vascular risk factors, with a smaller percentage mediated for lower levels of education. A substantial proportion of the relationship between education and dementia was mediated through mid-life vascular risk factors. However, risk factor modification is unlikely to fully address the large educational disparities in dementia risk. Prevention efforts must also address disparities in socioeconomic resources leading to divergent early-life education and other structural determinants of mid-life vascular risk factors. ANN NEUROL 2023;94:13-26.

Life’s Simple 7 and the Risk of Dementia among Women (P2-5.030)

<h3>Objective:</h3> To determine if higher scores on the American Heart Association (AHA) Life’s Simple 7 in midlife are associated with a decreased risk of dementia among women. <h3>Background:</h3> A growing body of research underscores the need to examine midlife risk factors for dementia, as dementia pathology often begins decades before diagnosis. <h3>Design/Methods:</h3> The study population included women enrolled in the Women’s Health Study who had available risk factor information needed to calculate the AHA Life’s Simple 7 at baseline (1992–1994) and approximately ten years later (2004) and were fully covered by fee-for-service Medicare for all eligible person-months. Women received one point for each component of the AHA Life’s Simple 7 (smoking status, diet, physical activity, body mass index, diabetes, blood cholesterol, and blood pressure) for which they had ideal cardiovascular health. We used fee-for-service Medicare data (available from 2011 through 2018) and validated lists of ICD-9 and ICD-10 codes to identify dementia diagnoses. We used logistic regression to examine the association between the score, modeled as a continuous variable, and dementia diagnosis adjusted for age and socioeconomic status at baseline. <h3>Results:</h3> 13,720 women were eligible for these analyses and 1771 (12.9%) dementia cases were observed. The mean age (standard deviation (SD)) was 54.2 (6.6) years at baseline. The average AHA Life’s Simple 7 score at baseline was 4.3 (SD=1.3) and after ten years of follow-up was 4.2 (SD=1.3). Higher AHA Life’s Simple 7 score as measured at baseline (odds ratio per one unit change in score=0.94, 95% CI: 0.90–0.98) was associated with a decreased risk of dementia. This effect was similar for the AHA Life’s Simple 7 score as measured after ten years of follow-up (OR=0.95, 95% CI: 0.91–1.00). <h3>Conclusions:</h3> Better cardiovascular health in midlife was associated with a decreased risk of dementia in late life among women. <b>Disclosure:</b> Dr. Rist has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association. The institution of Dr. Rist has received research support from National Institutes of Health. The institution of Dr. Rist has received research support from Biogen, Inc. The institution of Dr. Rist has received research support from Brigham and Women’s Hospital. Melinda Power, PhD has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. I-Min Lee has nothing to disclose. Julie E. Buring has nothing to disclose.