Late-life Risk Research Articles

On the importance of birth weight in relation to disease risk in later life.

On the importance of birth weight in relation to disease risk in later life.

Association between gestational weight gain and chronic disease risks in later life

To assess the association between gestational weight gain (GWG) and the risk of developing chronic diseases in later life, this historical cohort study of 318 non-overweight women was conducted between April 2017 and November 2020 at a hospital in Tokyo. Data about GWG in the last pregnancy and the development of any chronic diseases of the subjects were retrieved from the women’s Maternal and Child Health Handbooks and through a questionnaire survey, respectively. The outcomes were chronic diseases, such as diabetes mellitus (DM), hypertension, hyperlipidemia, and being overweight (body mass index [BMI] ≥ 25 kg/m2). Association between GWG and outcomes were assessed using a logistic regression analysis.There were significant positive linear associations between GWG and the risks of developing DM, hypertension, and being overweight (P = 0.013, 0.050, and 0.017, respectively). After adjusting for later-life BMI, a significant association between GWG and DM (P = 0.025) remained, but the association between GWG and hypertension disappeared. GWG was significantly associated with DM, hypertension, and being overweight later in life. Although the association between GWG and DM was partially independent of BMI later in life, the association between GWG and hypertension was influenced by being overweight later in life.

Relationship of weight change patterns from young to middle adulthood with incident rheumatoid arthritis and osteoarthritis: a retrospective cohort study.

The relationship between weight change patterns and arthritis onset, specifically rheumatoid arthritis (RA) and osteoarthritis (OA), is unclear. We examined the association between weight changes from young adulthood to midlife and arthritis onset. Using data from NHANES 1999-2018, participants with self-reported arthritis were selected. Age at diagnosis determined arthritis onset. Weight change patterns were based on BMI at age 25 and 10 years before the survey. Patterns were categorized as stable non-obese, non-obese to obese, obese to non-obese, and stable obese. Cox regression models and restricted cubic spline (RCS) analysis were employed, calculating hazard ratios (HRs) and 95% confidence intervals (CIs) considering covariates. Out of 20,859 participants (male 11,017, 52.82%), 4922 developed arthritis over a mean 8.66-year follow-up. Compared to stable non-obese individuals, the HRs for arthritis were 1.55 (95% CI=1.45 to 1.66, P < 0.0001) for non-obese to obese and 1.74 (95% CI=1.56 to 1.95, P < 0.0001) for stable obese. Those gaining 10-20kg had a HR of 1.33 (95% CI=1.22 to 1.46, P < 0.0001), and gains >20kg had a HR of 1.56 (95% CI=1.42 to 1.71, P < 0.0001), compared to stable weight (change within 2.5kg). Identical results observed for OA and RA. RCS showed a nonlinear relationship between weight change and arthritis (all P < 0.01). Stable obesity and weight gain during adulthood increase arthritis risk. Maintaining a non-obese weight throughout adult years might reduce arthritis risk in later life.

RPTOR Is an Alzheimer's Disease Susceptibility Gene Associated with the Risk Factors Body Mass Index and Infectious Encephalitis.

In comparison to persons who did not have viral encephalitis, people with viral encephalitis had a later-life risk of Alzheimer's disease (AD) that was 31 times higher. In a previous study, we were able to confirm the association of viral encephalitis with AD and suggest that West Nile Virus infection is a significant AD risk factor. A genome wide association study (GWAS) with UK Biobank data revealed that the gene RAR Related Orphan Receptor B (RORB) is significantly associated with viral encephalitis. To use data from the 8 PheWeb datasets to try to identify genes other than RORB that might be involved in both infectious encephalitis and AD. PheWeb includes data from UKBB and 5 other databanks. We used UK Biobank data to examine gene expression and phenotypic expression. PheWeb identified additional genes associated with both infectious encephalitis and AD. RPTOR, a gene associated with the mTOR pathway, emerges as significant. Analyses of UK Biobank data reveal the impact of RPTOR on AD risk, with carriers of the minor allele A exhibiting decreased prevalence in subjects under age 55. Further analysis demonstrates that RPTOR genotypes influence body mass index (BMI) in subjects of all ages, with carriers of the minor allele A having lower BMI. Logistic regression analyses confirm the association between reduced BMI and increased AD risk, along with the established factor of age. RPTOR may represent an AD gene, though mTOR's role in AD and BMI is complex. Nevertheless, RPTOR and mTOR could represent potential therapeutic targets for AD.

SOCIAL ISOLATION AND RISK OF DEMENTIA: DO RACE, ETHNICITY, AND GENDER MATTER?

Abstract Social isolation has emerged as a significant predictor of dementia risk in later life. However, our understanding of how this association may vary across race-ethnicity and gender remains limited. To address this gap, we used longitudinal data from the Health and Retirement Study (2000-2016) to examine the link between social isolation and dementia risk among older adults, separately for non-Hispanic Whites, non-Hispanic Blacks, and Hispanics. We also explored gender variations in this association within each racial-ethnic group. Our results indicate that social isolation increases the risk of dementia for both non-Hispanic Whites and Blacks, even after controlling for basic sociodemographic characteristics. However, social isolation does not appear to be a significant predictor of dementia risk among Hispanics, suggesting that cultural and social factors may play a key role in the association between social isolation and dementia risk across racial/ethnic groups. Further, we found few significant gender variations in the association between social isolation and dementia, except for a stronger effect of severe isolation among Black men compared to Black women. Economic resources and health-related factors were identified as significant mediators of the relationship between social isolation and dementia risk for both non-Hispanic Whites and Blacks. Our study highlights the importance of addressing social isolation as a potential risk factor for dementia among older adults, particularly for those in vulnerable groups. The findings underscore the need for targeted interventions to reduce social isolation and promote social engagement in diverse communities to mitigate dementia risk.

EARLY-LIFE CIRCUMSTANCES AND RACIAL DISPARITIES IN COGNITION AMONG US OLDER ADULTS

Abstract There are marked racial disparities in cognitive outcomes between non-Hispanic Black (Black) and non-Hispanic White (White) older adults in the US. Existing studies concentrate on exploring mid-life to late-life risk factors, yet the early-life circumstances through which the racial gaps may arise remain under-explored. Using a wide spectrum of early-life factors assembled from the Health and Retirement Study, including demographics, SES, health, trauma, family relationships, and genetics, we investigated how racial gaps in cognitive score and cognitive impairment among older Americans were tied to racial differences in early-life circumstances. 9,015 (7,381 White, 1,634 Black) Americans aged 50 and older were included in the analysis. Using Blinder-Oaxaca-Decomposition, we showed that Black participants generally had less favorable early-life circumstances than White participants, especially in early-life residence, education level, quality and experience. We demonstrated that overall, differences in early-life circumstances explained up to 61.9% of the racial gaps in cognitive score, and 80.9% of the racial gaps in cognitive impairment between White and Black participants. Disentangling racial gaps by individual factors, we found that differences in the level and quality of education contributed the most. Years of education and school racial segregation respectively accounted for 22.7-24.8% and 26.0%-42.8% of the gaps in cognitive outcomes. Early-life educational experience and place of birth/residence additionally contributed to the disparities. However, childhood trauma, health, and genetic factors were not significant contributors. These findings suggest that exposure to less favorable early-life circumstances is associated with clinically meaningful and statistically significant racial gaps in cognition, which warrants targeted interventions.

Early-life risk factors, accelerated biological aging and the late-life risk of mortality and morbidity.

Early-life exposure increases health risks throughout an individual's lifetime. Biological aging is influenced by early-life risks as a key process of disease development, but whether early-life risks could accelerate biological aging and elevate late-life mortality and morbidity risks remains unknown. Knowledge is also limited on the potential moderating role of healthy lifestyle. We investigate associations of three early-life risks around birth, breastfeeding, maternal smoking and birth weight, with biological aging of 202 580 UK Biobank participants (54.9 ± 8.1 years old). Biological aging was quantified as KDM-BA, PhenoAge and frailty. Moderate alcohol intake, no current smoking, healthy diet, BMI <30 kg/m2 and regular physical activity were considered as healthy lifestyles. Mortality and morbidity data were retrieved from health records. Individual early-life risk factors were robustly associated with accelerated biological aging. A one-unit increase in the 'early-life risk score' integrating the three factors was associated with 0.060 (SE=0.0019) and 0.036-unit (SE = 0.0027) increase in z-scored KDM-BA acceleration and PhenoAge acceleration, respectively, and with 22.3% higher odds (95% CI: 1.185-1.262) of frailty. Increased chronological age and healthy lifestyles could mitigate the accelerations of KDM-BA and PhenoAge, respectively. Associations of early-life risk score with late-life mortality and morbidity were mediated by biological aging (proportions: 5.66-43.12%). KDM-BA and PhenoAge accelerations could significantly mediate the impact on most outcomes except anxiety, and frailty could not mediate the impact on T2D. Biological aging could capture and mediate the late-life health risks stemming from the early-life risks, and could be potentially targeted for healthy longevity promotion.

Low- and High-Density Lipoprotein Cholesterol and Dementia Risk Over 17 Years of Follow-up Among Members of a Large Health Care Plan.

The associations of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) with dementia risk in later life may be complex, and few studies have sufficient data to model nonlinearities or adequately adjust for statin use. We evaluated the observational associations of HDL-C and LDL-C with incident dementia in a large and well-characterized cohort with linked survey and electronic health record (EHR) data. Kaiser Permanente Northern California health plan members aged 55 years and older who completed a health behavior survey between 2002 and 2007, had no history of dementia before the survey, and had laboratory measurements of cholesterol within 2 years after survey completion were followed up through December 2020 for incident dementia (Alzheimer disease-related dementia [ADRD]; Alzheimer disease, vascular dementia, and/or nonspecific dementia) based on ICD-9 or ICD-10 codes in EHRs. We used Cox models for incident dementia with follow-up time beginning 2 years postsurvey (after cholesterol measurement) and censoring at end of membership, death, or end of study period. We evaluated nonlinearities using B-splines, adjusted for demographic, clinical, and survey confounders, and tested for effect modification by baseline age or prior statin use. A total of 184,367 participants [mean age at survey = 69.5 years, mean HDL-C = 53.7 mg/dL (SD = 15.0), mean LDL-C = 108 mg/dL (SD = 30.6)] were included. Higher and lower HDL-C values were associated with elevated ADRD risk compared with the middle quantile: HDL-C in the lowest quintile was associated with an HR of 1.07 (95% CI 1.03-1.11), and HDL-C in the highest quintile was associated with an HR of 1.15 (95% CI 1.11-1.20). LDL-C was not associated with dementia risk overall, but statin use qualitatively modified the association. Higher LDL-C was associated with a slightly greater risk of ADRD for statin users (53% of the sample, HR per 10 mg/dL increase = 1.01, 95% CI 1.01-1.02) and a lower risk for nonusers (HR per 10 mg/dL increase = 0.98; 95% CI 0.97-0.99). There was evidence for effect modification by age with linear HDL-C (p = 0.003) but not LDL-C (p = 0.59). Both low and high levels of HDL-C were associated with elevated dementia risk. The association between LDL-C and dementia risk was modest.

Effects of PROtein enriched MEDiterranean Diet and EXercise on nutritional status and cognition in adults at risk of undernutrition and cognitive decline: the PROMED-EX Randomised Controlled Trial.

IntroductionUndernutrition leading to unplanned weight loss is common in older age and has been linked to increased dementia risk in later life. Weight loss can precede dementia by a decade...

Prenatal Exposure to Multiple Endocrine-Disrupting Chemicals and Childhood BMI Trajectories in the INMA Cohort Study.

Prenatal exposure to endocrine-disrupting chemicals (EDCs) may disrupt normal fetal and postnatal growth. Studies have mainly focused on individual aspects of growth at specific time points using single chemical exposure models. However, humans are exposed to multiple EDCs simultaneously, and growth is a dynamic process. The objective of this study was to evaluate the associations between prenatal exposure to EDCs and children's body mass index (BMI) growth trajectories using single exposure and mixture modeling approaches. Using data from the INfancia y Medio Ambiente (INMA) Spanish birth cohort (), prenatal exposure to persistent chemicals [hexachlorobenzene (HCB), 4-4'-dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCB-138, -150, and -180), 4 perfluoroalkyl substances (PFAS)] and nonpersistent chemicals (8 phthalate metabolites, 7 phenols) was assessed using blood and spot urine concentrations. BMI growth trajectories were calculated from birth to 9 years of age using latent class growth analysis. Multinomial regression was used to assess associations for single exposures, and Bayesian weighted quantile sum (BWQS) regression was used to evaluate the EDC mixture's association with child growth trajectories. In single exposure models exposure to HCB, DDE, PCBs, and perfluorononanoic acid (PFNA) were associated with increased risk of belonging to a trajectory of lower birth size followed by accelerated BMI gain by 19%-32%, compared with a trajectory of average birth size and subsequent slower BMI gain [e.g., relative risk ratio (RRR) per doubling in DDE (95% CI: 1.05, 1.35); RRR for (95% CI: 1.05, 1.66)]. HCB and DDE exposure were also associated with higher probability of belonging to a trajectory of higher birth size and accelerated BMI gain. Results from the BWQS regression showed the mixture was positively associated with increased odds of belonging to a BMI trajectory of lower birth size and accelerated BMI gain (odds ratio per 1-quantile increase of the ; credible interval: 1.03, 2.61), with HCB, DDE, and PCBs contributing the most. This study provides evidence that prenatal EDC exposure, particularly persistent EDCs, may lead to BMI trajectories in childhood characterized by accelerated BMI gain. Given that accelerated growth is linked to a higher disease risk in later life, continued research is important. https://doi.org/10.1289/EHP11103.

Childhood Adversity and Passive Suicidal Ideation in Later Life in the United States: Does Religious Attendance Matter?

This study examines whether adverse childhood experiences are associated with passive suicidal ideation in later life and whether religious attendance moderates this association among U.S. older adults. To this end, logistic regression analyses were conducted using data from the 2016 Health and Retirement Study. The results show that poor childhood health, lack of parental affection, and childhood trauma are all positively associated with passive suicidal ideation in later life. However, religious attendance modifies the association between childhood health and passive suicidal ideation. For instance, poor childhood health is associated with greater odds of passive suicidal ideation only for older adults who never attend religious services, while this is not the case for those who attend religious services. Yet, the associations of parental affection and childhood trauma with passive suicidal ideation do not appear to differ by religious attendance. We discuss the theoretical implications of these findings for views about childhood adversity, religion, and suicide risk in later life.

RORB, an Alzheimer’s disease susceptibility gene, is associated with viral encephalitis, an Alzheimer’s disease risk factor

BackgroundViral encephalitis increases later-life risk of Alzheimer’s disease (AD) by a factor of 31. MethodsTo further evaluate this finding, we examined the relationship of West Nile virus (WNV) to Alzheimer’s disease in 50 US states. In addition, we performed a genome wide association study (GWAS) of viral encephalitis cases in UK Biobank (UKBB) to see if encephalitis genes might be related to AD. ResultsWNV was significantly associated with deaths from Alzheimer’s disease in 50 US states (r = 0.806, p < 0.001). One gene, RORB-AS1, was most significantly related on GWAS to viral encephalitis. RORB-AS1 (RORB Antisense RNA 1) is an RNA gene. Diseases associated with RORB-AS1 include childhood epilepsy and idiopathic generalized epilepsy. The closely related RORB (Related Orphan Receptor B) is a marker of selectively AD vulnerable excitatory neurons in the entorhinal cortex; these neurons are depleted and susceptible to neurofibrillary inclusions during AD progression. RORB variants significantly decreased the risk of AD, independent of the significant effects of epilepsy, age, and years of education. The total effect size of variant RORB on AD prevalence is small, 0.19%, probably the reason RORB has not turned up on genome wide association studies of AD. But the decrease in effect size on AD, no variant versus varian is larger 0.20–0.16%. To produce the 31-fold increase in AD risk associated with viral encephalitis, non-variant RORB may need to interact with encephalitis virus. LimitationsA weakness in our correlative analysis is possible confounding by the ecological fallacy (or ecological inference fallacy), a logical fallacy in the interpretation of statistical data where inferences about the nature of individuals are derived from inference for the group to which those individuals belong. In this case, inferences about individuals are being drawn from the characteristics of U.S. states where they reside, rather than from the individuals themselves. A weakness in our GWAS is that UK Biobank had only 18 cases of viral encephalitis and none of these had AD. Conclusiondata presented here confirm the association of viral encephalitis with AD and suggest that WNV infection is a significant AD risk factor. In addition, GWAS suggests that the gene RORB, an AD vulnerability factor, is significantly related to viral encephalitis. Future prospects: A human WNV vaccine could reduce Alzheimer’s disease morbidity and mortality.

Abstract P203: Microvascular Imaging As Early Predictor For Cardiac Dysfunction After Preeclampsia

Preeclampsia (PE), the most common pregnancy disease, is the main cause for maternal and fetal mortality and morbidity worldwide. The disease is characterized by a sudden increase in blood pressure in combination with signs of end organ damage, e.g. proteinuria and the underlying mechanisms are poorly understood. Immune dysregulation and endothelial dysfunction are important pathomechanisms leading to PE, we hypothesize that anti-angiogenesis and dysregulation of microvascular perfusion postpartum lead to the increased cardiovascular risk in later life. In addition, we will test if the examination of retinal vessels can be used as a diagnostic window for early risk prediction of cardiovascular alterations. In a well-established transgenic rat model for PE, we performed speckle tracking echocardiography, immunostaining, RNA sequencing and small vessel imaging by micro-computed tomography of the heart and the eyes in former preeclamptic rats (PEpp) and healthy controls (WTpp). A reduction of cardiac vessels (AUC 0-200 μm: WTpp 77.19±4.64 vs. PEpp 62.59±2.72) in combination with an increase of small vessels in the retina (AUC 0-50 μm: WTpp 52.89±1.47 vs. PEpp 59.54±1.09) is shown postpartum. Data from echocardiography (Global longitudinal strain: WTpp -22.03±2.47 % vs. PEpp -14.50±1.80 %) and histological staining (CD31: WTpp 292.7±30.9 per fov vs. PEpp 219.0±10.5 per fov) support the hypothesis of persistent cardiovascular alterations after PE. Performing RNAseq, 65 genes were found to be permanently altered in the left ventricle of the heart of preeclamptic rats compared to 4 genes in controls. In the retinal tissue, 39 genes in PEpp and no genes in WTpp were identified postpartum compared to never pregnant animals (adjusted p-value &lt; 0.05,

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.

Insights into the pathological basis of dementia from population-based neuropathology studies.

The epidemiological neuropathology perspective of population and community-based studies allows unbiased assessment of the prevalence of various pathologies and their relationships to late-life dementia. In addition, this approach provides complementary insights to conventional case-control studies, which tend to be more representative of a younger clinical cohort. The Cognitive Function and Ageing Study (CFAS) is a longitudinal study of cognitive impairment and frailty in the general United Kingdom population. In this review, we provide an overview of the major findings from CFAS, alongside other studies, which have demonstrated a high prevalence of pathology in the ageing brain, particularly Alzheimer's disease neuropathological change and vascular pathology. Increasing burdens of these pathologies are the major correlates of dementia, especially neurofibrillary tangles, but there is substantial overlap in pathology between those with and without dementia, particularly at intermediate burdens of pathology and also at the oldest ages. Furthermore, additional pathologies such as limbic-predominant age-related TDP-43 encephalopathy, ageing-related tau astrogliopathy and primary age-related tauopathies contribute to late-life dementia. Findings from ageing population-representative studies have implications for the understanding of dementia pathology in the community. The high prevalence of pathology and variable relationship to dementia status has implications for disease definition and indicate a role for modulating factors on cognitive outcome. The complexity of late-life dementia, with mixed pathologies, indicates a need for a better understanding of these processes across the life-course to direct the best research for reducing risk in later life of avoidable clinical dementia syndromes.

Proteomics analysis of plasma from middle-aged adults identifies protein markers of dementia risk in later life.

A diverse set of biological processes have been implicated in the pathophysiology of Alzheimer's disease (AD) and related dementias. However, there is limited understanding of the peripheral biological mechanisms relevant in the earliest phases of the disease. Here, we used a large-scale proteomics platform to examine the association of 4877 plasma proteins with 25-year dementia risk in 10,981 middle-aged adults. We found 32 dementia-associated plasma proteins that were involved in proteostasis, immunity, synaptic function, and extracellular matrix organization. We then replicated the association between 15 of these proteins and clinically relevant neurocognitive outcomes in two independent cohorts. We demonstrated that 12 of these 32 dementia-associated proteins were associated with cerebrospinal fluid (CSF) biomarkers of AD, neurodegeneration, or neuroinflammation. We found that eight of these candidate protein markers were abnormally expressed in human postmortem brain tissue from patients with AD, although some of the proteins that were most strongly associated with dementia risk, such as GDF15, were not detected in these brain tissue samples. Using network analyses, we found a protein signature for dementia risk that was characterized by dysregulation of specific immune and proteostasis/autophagy pathways in adults in midlife ~20 years before dementia onset, as well as abnormal coagulation and complement signaling ~10 years before dementia onset. Bidirectional two-sample Mendelian randomization genetically validated nine of our candidate proteins as markers of AD in midlife and inferred causality of SERPINA3 in AD pathogenesis. Last, we prioritized a set of candidate markers for AD and dementia risk prediction in midlife.

Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section delivery

BackgroundMost interactions between the host and its microbiota occur at the gut barrier, and primary colonizers are essential in the gut barrier maturation in the early life. The mother–offspring transmission of microorganisms is the most important factor influencing microbial colonization in mammals, and C-section delivery (CSD) is an important disruptive factor of this transfer. Recently, the deregulation of symbiotic host-microbe interactions in early life has been shown to alter the maturation of the immune system, predisposing the host to gut barrier dysfunction and inflammation. The main goal of this study is to decipher the role of the early-life gut microbiota-barrier alterations and its links with later-life risks of intestinal inflammation in a murine model of CSD.ResultsThe higher sensitivity to chemically induced inflammation in CSD mice is related to excessive exposure to a too diverse microbiota too early in life. This early microbial stimulus has short-term consequences on the host homeostasis. It switches the pup’s immune response to an inflammatory context and alters the epithelium structure and the mucus-producing cells, disrupting gut homeostasis. This presence of a too diverse microbiota in the very early life involves a disproportionate short-chain fatty acids ratio and an excessive antigen exposure across the vulnerable gut barrier in the first days of life, before the gut closure. Besides, as shown by microbiota transfer experiments, the microbiota is causal in the high sensitivity of CSD mice to chemical-induced colitis and in most of the phenotypical parameters found altered in early life. Finally, supplementation with lactobacilli, the main bacterial group impacted by CSD in mice, reverts the higher sensitivity to inflammation in ex-germ-free mice colonized by CSD pups’ microbiota.ConclusionsEarly-life gut microbiota-host crosstalk alterations related to CSD could be the linchpin behind the phenotypic effects that lead to increased susceptibility to an induced inflammation later in life in mice.BBJL6KRzb7pAFtZtZ-zX7MVideo

TYPE 2 DIABETES IN YOUNG ADULTS: PREVALENCE AND RISK FACTOR CONTROL IN A TERTIARY DIABETES CENTRE

Objective: The prevalence of type 2 diabetes (T2DM) is increasing in younger adults. Diagnosis at young age translates into increased lifetime complications risk and number of years of life lost. Despite this, clinical guidelines advocate risk-factor management based on 10-year rather than lifetime risk, and there are no specific treatment targets for young adults as this group is under-represented in outcome studies. We reviewed prescribing; risk-factor management; glycaemic control; and follow-up arrangements in people with T2DM aged 18-30 living in North-East Glasgow. Design and method: We used the Scottish Care Information – Diabetes Collaboration (Sci-Diabetes) registry to identify all individuals with T2DM aged 18-30 years and collected data from online medical records. Results: We identified a cohort of 74 (70% female) individuals. Mean age at diagnosis was 23 years. Social deprivation was high (mean SIMD 1.7). Mean HbA1c was 60.4 (range 32 – 119) mmol/mol with 35 (47%) requiring more than 1 glucose-lowering medication and 7 were (9%) insulin-treated. Mean BMI was 35kg/m2 and 55 (74%) individuals were clinically obese. Dietetic review was documented in 30 (45%), GLP-1 analogues were prescribed to 18 (24%). Blood pressure (mean 125/82; range 100-168/60-101) mmHg was above target in 16 (22%) individuals. Only 8 (10%) and 4 (5%) people were on anti-hypertensive and lipid-lowering drugs respectively. Pregnancy advice had been given in 39 (75%) of female patients. Seventeen (22%) individuals were lost to follow-up. Conclusions: Follow-up and risk-factor control are inconsistent in this high-risk group. Service innovation is urgently required to ensure young adults with T2DM are offered appropriate and accessible follow-up in order to minimise cardiovascular risk in later life.

Assessing the impacts of smoking cessation and resumption on back pain risk in later life.

This study aimed to assess the impacts of smoking cessation and resumption over 4 years on the risk of back pain at the 6-year follow-up among older adults in England. We analysed 6467 men and women aged ≥50 years in the English Longitudinal Study of Aging. Self-reported smoking status, assessed in waves 4 (2008-2009) and 6 (2012-2013), was used as exposure for the study, whereas self-reported back pain of moderate or severe intensity, assessed in wave 7 (2014-2015), was used as the outcome. A targeted minimum loss-based estimator was used with longitudinal modified treatment policies to adjust for baseline and time-varying covariates. Regarding the estimation of the effects of changes in smoking status on the risk of back pain, during the follow-up, individuals who resumed smoking within 4 years had a higher risk of back pain than those who avoided smoking for over 4 years, and the relative risk (RR) (95% confidence interval [CI]) was 1.536 (1.214-1.942). Regarding the estimation of effects of smoking cessation on the risk of back pain, smoking cessation over 4 years was associated with a significantly lower risk of back pain, as indicated by the originally observed data, and the RR (95% CI) was 0.955 (0.912-0.999). Older adults who avoided smoking for over 4 years had a lower risk of back pain. However, those who resumed smoking within 4 years had a higher risk of back pain. Older adults who avoided smoking for over 4 years had a lower risk of back pain. However, those who resumed smoking within 4 years had a higher risk of back pain. Our study data suggest the importance of maintaining smoking cessation to reduce the risk of back pain in the older population.

Resting-state MRI functional connectivity as a neural correlate of multidomain lifestyle adherence in older adults at risk for Alzheimer’s disease

Prior research has demonstrated the importance of a healthy lifestyle to protect brain health and diminish dementia risk in later life. While a multidomain lifestyle provides an ecological perspective to voluntary engagement, its association with brain health is still under-investigated. Therefore, understanding the neural mechanisms underlying multidomain lifestyle engagement, particularly in older adults at risk for Alzheimer’s disease (AD), gives valuable insights into providing lifestyle advice and intervention for those in need. The current study included 139 healthy older adults with familial risk for AD from the Prevent-AD longitudinal aging cohort. Self-reported exercise engagement, cognitive activity engagement, healthy diet adherence, and social activity engagement were included to examine potential phenotypes of an individual’s lifestyle adherence. Two adherence profiles were discovered using data-driven clustering methodology [i.e., Adherence to healthy lifestyle (AL) group and Non-adherence to healthy lifestyle group]. Resting-state functional connectivity matrices and grey matter brain features obtained from magnetic resonance imaging were used to classify the two groups using a support vector machine (SVM). The SVM classifier was 75% accurate in separating groups. The features that show consistently high importance to the classification model were functional connectivity mainly between nodes located in different prior-defined functional networks. Most nodes were located in the default mode network, dorsal attention network, and visual network. Our results provide preliminary evidence of neurobiological characteristics underlying multidomain healthy lifestyle choices.