Midlife Obesity Research Articles

Relationships between abdominal adipose tissue and neuroinflammation with diffusion basis spectrum imaging in midlife obesity.

This study investigated how obesity, BMI ≥ 30 kg/m2, abdominal adiposity, and systemic inflammation relate to neuroinflammation using diffusion basis spectrum imaging. We analyzed data from 98 cognitively normal midlife participants (meanage: 49.4 [SD 6.2] years; 34 males [34.7%]; 56 with obesity [57.1%]). Participants underwent brain and abdominal magnetic resonance imaging (MRI), blood tests, and amyloid positron emission tomography (PET) imaging. Abdominal visceral and subcutaneous adipose tissue (VAT and SAT, respectively) was segmented, and Centiloids were calculated. Diffusion basis spectrum imaging parameter maps were created using an in-house script, and tract-based spatial statistics assessed white matter differences in high versus low BMI values, VAT, SAT, insulin resistance, systemic inflammation, and Centiloids, with age and sex as covariates. Obesity, high VAT, and high SAT were linked to lower axial diffusivity, reduced fiber fraction, and increased restricted fraction in white matter. Obesity was additionally associated with higher hindered fraction and lower fractional anisotropy. Also, individuals with high C-reactive protein showed lower axial diffusivity. Higher restricted fraction correlated with continuous BMI and SAT particularly in male individuals, whereas VAT effects were similar in male and female individuals. The findings suggest that, at midlife, obesity and abdominal fat are associated with reduced brain axonal density and increased inflammation, with visceral fat playing a significant role in both sexes.

Childhood psychosocial adjustment and midlife obesity, diabetes and hypertension: prospective study from two birth cohorts.

Understanding how childhood psychosocial adjustment (CPA) influences later life health outcomes is crucial for developing interventions to mitigate the long-term risk of cardiometabolic diseases (CMDs). To investigate the association between CPA and incident CMDs in mid-life, and the mediating roles of educational attainment, smoking habits and depression during young adulthood. A prospective cohort study utilised data from the 1958 National Child Development Study (NCDS; 1958-2013) and the 1970 British Cohort Study (BCS70; 1970-2018), encompassing 22 012 participants assessed for CPA in childhood, who were subsequently evaluated for educational attainment, smoking habits and depression in young adulthood, followed by assessments for CMDs in mid-life. CPA was assessed using the Bristol Social Adjustment Guides in the NCDS and the Rutter Child Behaviour Scale in the BCS70, with higher scores indicating poorer psychosocial adjustment. The primary outcomes were the mid-life incidences of hypertension, diabetes and obesity. Compared with children in the lowest tertile for CPA scores, those in the middle tertile had an adjusted odds ratio for hypertension of 0.98 (95% CI 0.90-1.06), whereas those in the highest tertile had an odds ratio of 1.17 (95% CI 1.08-1.26). For diabetes, the corresponding odds ratios (95% CI) were 1.15 (0.98-1.35) and 1.39 (1.19-1.62). For obesity, the corresponding odds ratios (95% CI) were 1.08 (1.00-1.16) and 1.18 (1.09-1.27). These associations were partially mediated by educational attainment (2.4-13.9%) and depression during young adulthood (2.5-14.9%). Poorer CPA is correlated with the development of hypertension, diabetes and obesity in mid-life. Interventions aimed at improving CPA may help in reducing the burden of these diseases in later life.

Association of obesity indicators with cognitive function among US adults aged 60 years and older: Results from NHANES.

Midlife obesity is a significant risk factor for Alzheimer's disease, but the effects of obesity on cognitive function, either detrimental or beneficial, are controversial among older individuals. This study aims to assess this associations of body mass index (BMI) or waist circumference (WC) with cognitive function among United States older individuals. A cross-sectional research study was conducted utilizing data from the 2011 to 2014 National Health and Nutrition Examination Survey (NHANES). Initially, the study compared differences in cognitive function among the normal weight, overweight, and obese groups. Subsequently, we examined the relationships between BMI or WC and cognitive function using multivariate linear regression. Finally, structural equation models were constructed to assess the relationships among body shape, lifestyle, and cognitive function pathways. The study included 2254 individuals. Obese subjects had lower scores in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) word list learning tasks (CERAD-WL) (χ2=7.804, p=.020) and digit symbol substitution test (χ2=8.869, p=.012). The regression analysis showed that WC was negatively connected with the CERAD-WL score after adjusting for confounding factors (β=-.029, p=.045). Moreover, WC had a mediating effect on the path from lifestyle to cognition (CERAD-WL). However, there was no difference in the CERAD delayed recall score and the animal fluency test between the obese and the other groups. Obese older adults exhibited impaired cognitive abilities in terms of learning and working memory performance. The impact of lifestyle on cognition was mediated by obesity-related anthropometric indices. Sleep, physical activity, and diet influenced the degree of obesity, which subsequently determined cognitive function. Prioritizing weight management in elderly people is crucial for safeguarding cognitive function.

Temporal trends in population attributable fractions of modifiable risk factors for dementia: a time-series study of the English Longitudinal Study of Ageing (2004–2019)

BackgroundInterest in modifiable risk factors (MRFs) for dementia is high, given the personal, social, and economic impact of the disorder, especially in ageing societies such as the United Kingdom. Exploring the population attributable fraction (PAF) of dementia attributable to MRFs and how this may have changed over time remains unclear. Unravelling the temporal dynamics of MRFs is crucial for informing the development of evidence-based and effective public health policies. This investigation examined the temporal trajectories of MRFs for dementia in England.MethodsWe used data from the English Longitudinal Study of Ageing, a panel study over eight waves collected between 2004 and 2019 (76,904 interviews in total). We calculated the PAFs for twelve MRFs (including six early- to mid-life factors and six late-life factors), as recommended by the Lancet Commission, and the individual weighted PAFs (IW-PAFs) for each risk factor. Temporal trends were analysed to understand the changes in the overall PAF and IW-PAF over the study period. Subgroup analyses were conducted by sex and socioeconomic status (SES).ResultsThe overall PAF for dementia MRFs changed from 46.73% in 2004/2005 to 36.79% in 2018/2019, though this trend was not statistically significant. During 2004–2019, hypertension, with an average IW-PAF of 8.21%, was the primary modifiable determinant of dementia, followed by obesity (6.16%), social isolation (5.61%), hearing loss (4.81%), depression (4.72%), low education (4.63%), physical inactivity (3.26%), diabetes mellitus (2.49%), smoking (2.0%), excessive alcohol consumption (1.16%), air pollution (0.42%), and traumatic brain injury (TBI) (0.26%). During 2004–2019, only IW-PAFs of low education, social isolation, and smoking showed significant decreasing trends, while IW-PAFs of other factors either did not change significantly or increased (including TBI, diabetes mellitus, and air pollution). Upon sex-specific disaggregation, a higher overall PAF for MRFs was found among women, predominantly associated with later-life risk factors, most notably social isolation, depression, and physical inactivity. Additionally, hearing loss, classified as an early- to mid-life factor, played a supplementary role in the identified sex disparity. A comparable discrepancy was evident upon PAF evaluation by SES, with lower income groups experiencing a higher dementia risk, largely tied to later-life factors such as social isolation, physical inactivity, depression, and smoking. Early- to mid-life factors, in particular, low education and obesity, were also observed to contribute to the SES-associated divergence in dementia risk. Temporal PAF and IW-PAF trends, stratified by sex and SES, revealed that MRF PAF gaps across sex or SES categories have persisted or increased.ConclusionsIn England, there was little change over time in the proportion of dementia attributable to known modifiable risk factors. The observed trends underscore the continuing relevance of these risk factors and the need for targeted public health strategies to address them.

Childhood adiposity underlies numerous adult brain traits commonly attributed to midlife obesity.

Obese adults are often reported to have smaller brain volumes than their non-obese peers. Whether this represents evidence of accelerations in obesity-driven atrophy or is instead a legacy of developmental differences established earlier in the lifespan remains unclear. This study aimed to investigate whether early-life differences in adiposity explain differences in numerous adult brain traits commonly attributed to mid-life obesity. We utilised a two-sample lifecourse Mendelian randomization study in 37,501 adults recruited to UK Biobank (UKB) imaging centers from 2014, with secondary analyses in 6,996 children assessed in the Adolescent Brain Cognitive Development Study (ABCD) recruited from 2018. Exposures were genetic variants for childhood (266 variants) and adult (470 variants) adiposity derived from a GWAS of 407,741 UKB participants. Primary outcomes were adult total brain volume; grey matter volume, thickness, and surface area; white matter volume and hyperintensities; and hippocampus, amygdala, and thalamus volumes at mean age 55 in UKB. Secondary outcomes were equivalent childhood measures collected at mean age 10 in ABCD. In UKB, individuals who were genetically-predicted to have had higher levels of adiposity in childhood were found to have multiple smaller adult brain volumes relative to intracranial volume (e.g. z-score difference in normalised brain volume per category increase in adiposity [95%CI] = -0.20 [-0.28, -0.12]; p = 4 × 10-6). These effect sizes remained essentially unchanged after accounting for birthweight or current adult obesity in multivariable models, whereas most observed adult effects attenuated towards null (e.g. adult z-score [95%CI] for total volume = 0.06 [-0.05,0.17]; p = 0.3). Observational analyses in ABCD showed a similar pattern of changes already present in those with a high BMI by age 10 (z-score [95%CI] = -0.10 [-0.13, -0.07]; p = 8 × 10-13), with follow-up genetic risk score analyses providing some evidence for a causal effect already at this early age. Sensitivity analyses revealed that many of these effects were likely due to the persistence of larger head sizes established in those who gained excess weight in childhood (childhood z-score [95%CI] for intracranial volume = 0.14 [0.05,0.23]; p = 0.002), rather than smaller brain sizes per se. Our data suggest that persistence of early-life developmental differences across the lifecourse may underlie numerous neuroimaging traits commonly attributed to obesity-related atrophy in later life.

Loss of neuronal lysosomal acid lipase drives amyloid pathology in Alzheimer's disease.

Underlying drivers of late-onset Alzheimer's disease (LOAD) pathology remain unknown. However, multiple biologically diverse risk factors share a common pathological progression. To identify convergent molecular abnormalities that drive LOAD pathogenesis we compared two common midlife risk factors for LOAD, heavy alcohol use and obesity. This revealed that disrupted lipophagy is an underlying cause of LOAD pathogenesis. Both exposures reduced lysosomal flux, with a loss of neuronal lysosomal acid lipase (LAL). This resulted in neuronal lysosomal lipid (NLL) accumulation, which opposed Aβ localization to lysosomes. Neuronal LAL loss both preceded (with aging) and promoted (targeted knockdown) Aβ pathology and cognitive deficits in AD mice. The addition of recombinant LAL ex vivo and neuronal LAL overexpression in vivo prevented amyloid increases and improved cognition. In WT mice, neuronal LAL declined with aging and correlated negatively with entorhinal Aβ. In healthy human brain, LAL also declined with age, suggesting this contributes to the age-related vulnerability for AD. In human LOAD LAL was further reduced, correlated negatively with Aβ1-42, and occurred with polymerase pausing at the LAL gene. Together, this finds that the loss of neuronal LAL promotes NLL accumulation to impede degradation of Aβ in neuronal lysosomes to drive AD amyloid pathology.

Population attributable fractions of modifiable risk factors for dementia: a systematic review and meta-analysis

More than 57 million people have dementia worldwide. Evidence indicates a change in dementia prevalence and incidence in high-income countries, which is likely to be due to improved life-course population health. Identifying key modifiable risk factors for dementia is essential for informing risk reduction and prevention strategies. We therefore aimed to estimate the population attributable fraction (PAF) for dementia associated with modifiable risk factors. In this systematic review and meta-analysis, we searched Embase, MEDLINE, and PsycINFO, via Ovid, from database inception up to June 29, 2023, for population-derived or community-based studies and reviews reporting a PAF value for one or more modifiable risk factor for later-life dementia (prevalent or incident dementia in people aged ≥60 years), with no restrictions on dementia subtype, the sex or baseline age of participants, or the period of study. Articles were independently screened for inclusion by four authors, with disagreements resolved through consensus. Data including unweighted and weighted PAF values (weighted to account for communality or overlap in risk) were independently extracted into a predefined template by two authors and checked by two other authors. When five or more unique studies investigated a given risk factor or combination of the same factors, random-effects meta-analyses were used to calculate a pooled PAF percentage estimate for the factor or combination of factors. The review protocol was registered on PROSPERO, CRD42022323429. 4024 articles were identified, and 74 were included in our narrative synthesis. Overall, PAFs were reported for 61 modifiable risk factors, with sufficient data available for meta-analysis of 12 factors (n=48 studies). In meta-analyses, the highest pooled unweighted PAF values were estimated for low education (17·2% [95% CI 14·4-20·0], p<0·0001), hypertension (15·8% [14·7-17·1], p<0·0001), hearing loss (15·6% [10·3-20·9], p<0·0001), physical inactivity (15·2% [12·8-17·7], p<0·0001), and obesity (9·4% [7·3-11·7], p<0·0001). According to weighted PAF values, low education (9·3% [6·9-11·7], p<0·0001), physical inactivity (7·3% [3·9-11·2], p=0·0021), hearing loss (7·2% [5·2-9·7], p<0·0001), hypertension (7·1% [5·4-8·8], p<0·0001), and obesity (5·3% [3·2-7·4], p=0·0001) had the highest pooled estimates. When low education, midlife hypertension, midlife obesity, smoking, physical inactivity, depression, and diabetes were combined (Barnes and Yaffe seven-factor model; n=9 studies), the pooled unweighted and weighted PAF values were 55·0% (46·5-63·5; p<0·0001) and 32·0% (26·6-37·5; p<0·0001), respectively. The pooled PAF values for most individual risk factors were higher in low-income and middle-income countries (LMICs) versus high-income countries. Governments need to invest in a life-course approach to dementia prevention, including policies that enable quality education, health-promoting environments, and improved health. This investment is particularly important in LMICs, where the potential for prevention is high, but resources, infrastructure, budgets, and research focused on ageing and dementia are limited. UK Research and Innovation (Medical Research Council).

The impact of obesity on dementia

IntroductionDementia is a syndrome characterized by a gradual deterioration of cognitive functions, including memory, thinking, orientation, attention span, perception, judgment, and language abilities. Obesity influences its development. Materials and methodsThe following review of studies is based on recent scientific articles available in PubMed and Google Scholar databases.The most searched phrases included: "dementia", "obesity", "midlife",and "the relationship between obesity and the risk of dementia". ResultsLiterature review indicates the existence of a relationship between midlife obesity and later dementia. It has also been pointed out that the forecasts for the onset of obesity and dementia are alarmingly rising world wide.It is estimated that by the year 2050, we can expect a threefold increase in dementia cases.ConclusionThe results of the cited studies indicate that further research into the occurrence of obesity and its later association with dementia is necessary. Midlife obesity likely plays a significant role in the etiopathogenesis of dementia.

Brain Endothelial Senescence and Vascular Density in Mid-Life Obesity: Exploring Neurovascular Dysfunction and Cognitive Impairment

The obesity epidemic is a major health challenge in the United States, with more than 42% of American adults being obese. Growing evidence shows that mid-life obesity has detrimental effects on cerebrovasculature, and it compromises cerebral blood flow (CBF) regulation and promotes the pathogenesis of vascular cognitive impairment and dementia (VCID). The cerebral microcirculation and the "neurovascular unit" (NVU) play a key role in maintaining healthy brain function. Our previous studies have shown that obesity-induced NVU dysfunction impairs endothelium-mediated neurovascular coupling (NVC) and contributes to VCID. Although great advances have been made in the last decade, the cellular mechanisms underlying NVU dysfunction, CBF dysregulation and NVC impairment remain not clear and there are no available treatments. Cellular senescence is a typical cellular response that occurs in physiological and pathological conditions. In this context, we found that middle-life obesity promotes cellular senescence in the brain and in the vasculature. Moreover, senescence of cells within the NVU has been linked to cognitive impairment and neuro-vascular dysfunction. To provide proof-of-concept for our studies on obesity induced NVU senescence, we used the novel transgenic mouse model (p16-3MR mouse), which allows the visualization and selective elimination of senescent cells. We evaluated senescence through the expression of RFP (senescent marker) with flow cytometry and through the analysis of single cell transcriptomic. NVC and vascular density was measured with functional ultrasound imaging (ICONEUS) and cognitive function was tested with radial arm water maze test (RAWM). We found increased senescence in endothelial cells in high fat diet-fed (HFD; 60% kcal from fat) mice compared to ones fed with standard diet (SD; 10% kcal from fat). Moreover, we demonstrated the functional significance of senescent cells by treating older HFD-fed obese mice with the well-characterized, potent senolytic compound Navitoclax/ABT263, which selectively kills senescent cells. We found that in obese older mice NVC responses were significantly impaired and were rescued by senolytic treatment. HFD-fed mice had impaired learning plasticity in RAWM. Restoration of NVC responses by ABT263 treatment associated with significant cognitive benefit. Overall, our work is novel in that it will be the first to demonstrate that obesity-induced senescence is a critical contributing factor to the pathogenesis of VCID, providing insights into potential therapeutic interventions. NIH R03AG070479, K01AG073614, R21AG080775, American Heart Association, Hevolution/AFAR. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of xylo-oligosaccharide on gut microbiota, brain protein expression, and lipid profile induced by high-fat diet

Midlife overweight and obesity are risk factors of cognitive decline and Alzheimer' s disease (AD) in late life. In addition to increasing risk of obesity and cognitive dysfunction, diets rich in fats also contributes to an imbalance of gut microbiota. Xylo-oligosaccharides (XOS) are a kind of prebiotic with several biological advantages, and can selectively promote the growth of beneficial microorganisms in the gut. To explore whether XOS can alleviate cognitive decline induced by high-fat diet (HFD) through improving gut microbiota composition, mice were fed with normal control or 60% HFD for 9 weeks to induce obesity. After that, mice were supplemented with XOS (30 g or 60 g/kg-diet) or without, respectively, for 12 weeks. The results showed that XOS inhibited weight gain, decreased epidydimal fat weight, and improved fasting blood sugar and blood lipids in mice. Additionally, XOS elevated spatial learning and memory function, decreased amyloid plaques accumulation, increased brain-derived neurotrophic factor levels, and improved neuroinflammation status in hippocampus. Changes in glycerolipids metabolism-associated lipid compounds caused by HFD in hippocampus were reversed after XOS intervention. On the other hand, after XOS intervention, increase in immune-mediated bacteria, Faecalibacterium was observed. In conclusion, XOS improved gut dysbiosis and ameliorated spatial learning and memory dysfunction caused by HFD by decreasing cognitive decline-associated biomarkers and changing lipid composition in hippocampus.

Abstract P332: Metabolically Healthy Obesity is Associated With Higher Levels of Executive Function in Middle-Aged Adults: The Bogalusa Heart Study

Introduction: Obesity in midlife is associated with an increased risk of cognitive decline. It remains unclear if there is a difference in cognitive function between individuals with obesity and metabolic dysfunction (metabolically abnormal obesity - MAO) versus those with metabolically healthy obesity (MHO). We assessed the relationship between MHO (vs MAO) and cognitive function in mid-life among Black and White individuals in the Bogalusa Heart Study. Methods: The Bogalusa Heart Study is a longitudinal cohort exploring the natural history of cardiovascular disease among Black and White individuals in Bogalusa, Louisiana. This cross-sectional analysis included 659 participants with obesity, defined as BMI ≥ 30 kg/m 2 . Metabolic abnormality was defined as the presence of one or more of the following: systolic blood pressure ≥ 130 mm Hg, diastolic blood pressure ≥ 85 mm Hg, taking blood pressure lowering medication, triglycerides ≥ 150 mg/dL, HDL-C &lt; 40 mg/dL (men) or &lt; 50 mg/dL (women), taking lipid-lowering medication, fasting plasma glucose ≥ 100 mg/dL, or taking diabetes medication. Healthy metabolic status was defined as the absence of blood pressure, lipid, and glycemic abnormalities. Cognitive function was measured using a total of 9 neuropsychological tests assessing attention/information processing speed, executive function, and episodic memory. Linear regression models were used to determine the association between MHO and a demographically standardized global cognitive score and individual domain-based z-scores adjusting for smoking status and education. Results: Participants had a mean age of 47.8 ± 5.3 years, 42.7% self-identified as Black, and 64.1% were female. The prevalence of MHO was 9.9%. MHO was associated with higher levels of executive function compared with MAO (β=0.46; SE=0.19; p=0.0145). No significant differences were observed between MHO and MAO participants on global cognitive score, processing speed, or episodic memory. Conclusions: Our study found that MHO is associated with better levels of executive function in midlife. While additional studies are needed, these findings suggest that interventions that reduce metabolic abnormalities related to blood pressure, lipids, and glucose may reduce obesity-related decreases in executive function among middle-aged individuals with obesity.

Abstract P327: Examination of Cardiometabolic Health Status, Obesity, and Brain Health in Community-Dwelling Older Adults

Introduction: Mid-life and late-life obesity have been associated with changes in brain structure and function, though the exact nature of this dynamic relationship is not well understood. Purpose: To determine whether associations between measures of obesity and neuroimaging biomarkers are independent of cardiometabolic health status in older adults. Methods: Adults 55 and older were recruited into the Clinical Core of the Wake Forest Alzheimer’s Disease Research Center (ADRC) between 2016 and 2023 and underwent standard evaluation in accordance with the National Alzheimer’s Coordinating Center protocols. Body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) were measured to assess obesity. Cardiometabolic health was determined by the presence of impaired glucose tolerance (IGT) and hypertension (HTN). Brain MRI scans were conducted to assess cerebral blood flow (CBF) in white matter (WM) and gray matter (GM), WM microstructure using neurite orientation dispersion and density imaging (NODDI) of free water (FW), total brain volume (GM+WM), and temporal lobe cortical thickness. Linear regression was used to examine associations between anthropometric and neuroimaging measures, controlling for demographics (age, gender, race, education) in model 1 and demographics plus cardiometabolic health (HTN and IGT) in model 2. Results: A total of 647 Clinical Core participants with anthropometric, MRI, cardiometabolic, and demographic data available were analyzed. Mean age of participants was 70.1±8.2 years, 19% were African American, 48% had adjudicated cognitive impairment (35% mild cognitive impairment, 13% dementia), 76% had HTN, and 69% had IGT. BMI (p&lt;0.001), WC (p&lt;0.001), and WHR (p=0.006) were positively associated with WM CBF in models 1 and 2. BMI (p=0.039) was also positively associated with GM CBF in model 2. All three obesity measures were positively associated with NODDI FW in model 1: BMI (p=0.006), WC (p=0.007), and WHR (p=0.039), and WHR was negatively associated with total brain volume (p=0.043). However, these associations were attenuated after further adjustment. Cortical thickness was not significantly associated with obesity in any model. Conclusion: These results demonstrate that, among community-dwelling older adults, having higher BMI, WHR, and WC is associated with higher WM CBF even after adjusting for demographics, HTN and IGT, suggesting that obesity may be a risk factor for impaired brain perfusion in late life.

Associations of midlife fitness and obesity profiles with cognitive function

AbstractLow fitness and obesity at midlife are individually associated with later‐life decline in cognition and health. However, the relationship between profiles of midlife fitness and obesity with midlife cognition is unclear and was examined by this study. Participants from the third follow‐up of the Childhood Determinants of Adult Health study (2014–2019; aged 36–49 years) were assessed for obesity (body mass index [BMI]), cardiorespiratory (physical work capacity) and muscular fitness (isometric grip and leg strength), and these factors were entered into a latent profile analysis. Psychomotor‐attention, learning–working memory and global cognition composites were derived from z‐scores of individual CogState battery tests. Linear regression analyses examined associations between profiles of fitness and obesity with cognition, adjusting for age, sex, education, alcohol and smoking. Using data from 617 participants [44.4 ± 2.6 (mean ± SD) years, 52% female], we identified 5 mutually exclusive profiles of obesity and fitness. Relative to those with the lowest fitness and highest BMI (5% of sample), those with a profile of (1) highest muscular fitness and average BMI (9%), (2) average muscular fitness and BMI (61%) and (3) highest cardiorespiratory fitness (CRF) and below average BMI (7%) all exhibited better global cognition [at least 0.44 (0.12, 0.77) SD, 95% CI] and psychomotor‐attention performance [at least 0.59 (0.27, 0.91) SD, 95% CI]. Compared with low fitness and unhealthy BMI levels, possessing average or high muscular and CRF and a healthy BMI in midlife was associated with better cognitive performance. Enhancing fitness and reducing obesity in midlife could contribute to improved cognitive performance in middle age.

Childhood obesity and risk of Alzheimer's disease: a Mendelian randomization study.

Midlife obesity is a modifiable risk factor for Alzheimer's disease. However, the association between childhood obesity and Alzheimer's disease remains largely unknown. Therefore, we conducted a mendelian randomization analysis (MR) to assess the causal link between childhood obesity and Alzheimer's disease. Using summary statistics from publicly available genome-wide association studies (GWAS) database, we explored the genetic link between childhood obesity and Alzheimer's disease through a two-sample MR. The primary analysis employed the inverse-variance weighted (IVW) method. To complement our findings, we also employed MR-Egger, weighted median, simple model, and weighted model methods for MR estimates. Furthermore, we conducted Cochrane's Q-statistic test, Egger intercept test, and a leave-one-out sensitivity test to ensure the robustness and reliability of our results. The IVW analysis yielded non-significant results, indicating no significant genetic association between childhood obesity and Alzheimer's disease (OR = 0.958, 95% CI = 0.910-1.008, p = 0.095). Consistent with this, the results from MR-Egger, the weighted median, simple model, and weighted model approaches all supported these findings. Furthermore, we did not detect any signs of heterogeneity or pleiotropy, and our leave-one-out analysis confirmed that no single nucleotide polymorphisms had a substantial impact on the reliability of our results. The evidence from our MR analyses suggests that there is no causal effect of childhood obesity on the risk of Alzheimer's disease.

Sex-Specific Association of Body Mass Index with Hippocampal Subfield Volume and Cognitive Function in Non-Demented Chinese Older Adults.

Recent research suggests a possible association between midlife obesity and an increased risk of dementia in later life. However, the underlying mechanisms remain unclear. Little is known about the relationship between body mass index (BMI) and hippocampal subfield atrophy. In this study, we aimed to explore the associations between BMI and hippocampal subfield volumes and cognitive function in non-demented Chinese older adults. Hippocampal volumes were assessed using structural magnetic resonance imaging. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A total of 66 participants were included in the final analysis, with 35 females and 31 males. We observed a significant correlation between BMI and the hippocampal fissure volume in older females. In addition, there was a negative association between BMI and the RBANS total scale score, the coding score, and the story recall score, whereas no significant correlations were observed in older males. In conclusion, our findings revealed sex-specific associations between BMI and hippocampal subfield volumes and cognitive performance, providing valuable insights into the development of effective interventions for the early prevention of cognitive decline.

Motor difficulties from childhood to midlife: A 40-year cohort study

BackgroundThere are few studies of the persistence of childhood motor difficulties (MD) into adulthood. AimsTo investigate the association of childhood MD with motor skills and body mass index (BMI) in midlife. Methods and proceduresWe studied 324 adults aged 40 from a cohort born in 1971–1974. At age 9, they had undergone the Test of Motor Impairment, used to classify them into groups: childhood MD (cMD), borderline cMD (bcMD), or no cMD. At age 40, participants comprised 23 with cMD, 47 with bcMD, and 254 with no cMD. Participants completed motor tests of balance, manual dexterity, and visuomotor speed, followed by recording of their BMI. Outcomes and resultsAt age 40, the cMD group performed worse than the no-cMD group on all motor tests (p < .001–.008). The bcMD group had slower visuomotor speed than the no-cMD group (p = .025). The groups differed in BMI (p = .002). Having cMD was associated with obesity in midlife (p < .001). After adjusting for sex, childhood socioeconomic status, and BMI at age 9, both cMD and bcMD were associated with obesity in midlife (p = .015). Conclusions and implicationsChildhood MD are associated with poor motor skills, overweight, and obesity in midlife. This emphasises the importance of early intervention and follow-up when a child exhibits MD. What this paper addsThis prospective longitudinal study presents novel evidence that individuals with a history of comprehensively and objectively assessed childhood motor difficulties (MD) have worse motor skills and a higher risk of obesity in midlife than do those with no childhood MD. There is a growing literature on adults with developmental coordination disorder or a history of MD. There is, however, a scarcity of longitudinal studies of childhood MD that continue beyond early adulthood, into midlife. In a systematic search, we could identify only one longitudinal study of objectively measured childhood MD with a reassessment of motor skills in those same participants in adulthood, and no study with a reassessment after age 20. Furthermore, longitudinal studies of the association of comprehensively and objectively assessed childhood MD with BMI in midlife have been lacking.

The association between weight change patterns and obesity-related complex multimorbidity: evidence from NHANES.

Obesity is a major risk factor for non-communicable diseases (NCDs), which has been the leading cause of death nowadays. The aim of this study is to examine the association between total changes in body mass index (BMI) across adulthood and the risk of obesity-related complex multimorbidity in elderly, characterizing the capacity of BMI waves in predicting major chronic diseases. In this retrospective study, 15,520 participants were analyzed from the National Health and Nutrition Examination Survey (NHANES) from 1999 and 2018. BMI was categorized as obesity (≥30.0 kg/m²), overweight (25.0-29.9 kg/m²), normal weight (18.5-24.9 kg/m²), and underweight (<18.5 kg/m²). Odds ratios (ORs) with 95% confidence interval (CIs) for the relationship between BMI change patterns and major health outcomes included hypertension, cancer, chronic obstructive pulmonary disease, cardiovascular disease, and diabetes, and population attributable fractions (PAFs) of BMI were evaluated. In comparison with participants who remained non-obese, those who are stable obese showed the highest risks of developing at least one chronic disease in later life, with odds ratios of 2.76 (95% CI: 2.20 to 3.45) from age 25 years to 10 years before baseline, 2.90 (2.28 to 3.68) from age 25 years to baseline, and 2.49 (2.11 to 2.95) in the 10-year period before baseline. Moving from non-obese to obese weight-change pattern in all periods (from age 25 years to 10 years before baseline: OR = 1.82; 95% CI, 1.57 to 2.11; from age 25 years to baseline: OR = 1.87; 95% CI, 1.59 to 2.19; from 10 years before baseline to baseline: OR = 1.62; 95% CI, 1.26 to 2.08) and moving from obese to non-obese, the 10-year period before baseline (OR = 1.89; 95% CI, 1.39 to 2.57) was associated with increased risk of chronic diseases. Midlife obesity status can explain the 8.6% risk of occurrence of the chronic diseases in elderly. Maintaining a stable healthy weight and losing weight in early adulthood and midlife are important for better life quality during the aging process. More effective strategies and policies to reduce the prevalence of obesity are needed.

RISK AND PROTECTIVE FACTORS OF COGNITIVE FUNCTIONING AND DEMENTIA: COMPARING MEXICAN AND NON-MEXICAN HISPANICS

Abstract This study investigates the cognitive functioning of Hispanic individuals aged 65 and above, focusing on the unique risk and protective factors associated with dementia in Mexican Hispanics and non-Mexican Hispanics. The study utilizes data from the Harmonized Cognitive Assessment Protocol (HCAP) subsample of the Health and Retirement Study (HRS), comprising 388 Hispanic older individuals who participated in the HCAP in 2016 (traced back to 2000), allowing for a comprehensive examination of cognitive health within this population. Cognitive function was measured using the Mini-Mental State Examination (MMSE) score and to classify dementia. The findings reveal distinct patterns in cognitive functioning between Mexican Hispanic and non-Mexican Hispanic populations. Mexican Hispanic males exhibit lower MMSE scores across all age groups, while Mexican Hispanic females show slightly higher scores compared to non-Mexican Hispanic females. Education and wealth levels do not significantly affect cognitive scores in either group. Mexican Hispanics have lower odds of dementia compared to non-Mexican Hispanics, even when accounting for sociodemographic, midlife, and late-life characteristics. Both educational attainment and wealth emerge as protective factors against dementia for both groups. Additionally, midlife obesity, hearing loss, and later-life physical inactivity are identified as specific risk factors for dementia in Mexican Hispanics but have an insignificant impact on non-Mexican Hispanics. These findings have implications for targeted interventions and policies to promote cognitive well-being and address health disparities in older Hispanics. The aim is to improve the overall quality of life and achieve equitable healthcare outcomes.

Weight change patterns across adulthood in relation to osteoporosis and fracture among non-obese individuals.

Obesity is usually recognized as a protective factor to osteoporosis and osteoporotic fracture. However, it is still unclear whether historical weight status was associated with the risk of osteoporosis and fracture. The aim of this study was to investigate the relationship between weight change patterns across adulthood and the prevalence of osteoporosis and fracture. Data from the National Health and Nutrition Examination Survey (NHANES) with 8725 US adults aged ≥ 40 years were analyzed in this study. Weight change patterns were categorized as "stable non-obese," "obese with earlier weight gain," "obese with recent weight gain," and "revert to non-obese" based on the body mass index (BMI) at 25 years old, 10 years prior to baseline and at baseline. Body mineral density (BMD) was measured using dual x-ray absorptiometry (DXA), and osteoporosis was diagnosed based on the World Health Organization criteria. Self-reported occurrence of osteoporotic fractures were determined by questionnaires. Compared with subjects in "stable non-obese" group, obese with earlier weight gain were positively related to the increase of BMD in both genders, while elevated BMD was only observed in female of "obese with recent weight gain" group and in male of "revert to non-obese" group after multiple adjustment. Moreover, changing from the obesity to non-obesity in the 10 years period before baseline was associated with a 81.6% lower risk of osteoporosis (odds ratio (OR) 0.184, 95% confidence interval (CI) 0.037-0.914 (P = 0.039)) and a 69.8% lower risk of wrist fracture (OR 0.302, 95%CI 0.120-0.757 (P = 0.012)) in male, but not in female. Weight change from obesity in midlife to non-obesity in late adulthood was associated with a reduction in the risk of osteoporosis and wrist fracture in male. Our findings support the importance of investigating the mechanism of weight change in different life period.

Reducing Risk of ADRDs: Innovative Framework to Inform Behavior Change

AbstractBackgroundIn the United States alone, more than six million individuals are living with Alzheimer’s disease and related dementias (ADRDs), with minority groups disproportionately impacted. An estimated one‐third of ADRD cases is associated with eight modifiable risk factors: physical inactivity, smoking, depression, low education, diabetes, midlife obesity, midlife hypertension, and hearing loss. With the ADRD pandemic fast approaching, there is greater urgency to identify and adopt risk reduction behavior changes. Lifestyle interventions have shown efficacy in reducing risk for ADRDs and delaying the onset of symptoms. These interventions are often grounded in traditional theories of health behavior change; however, few intervention frameworks exist that combine constructs from multiple discrete theories, or incorporate concept of stigma, a powerful influence in setting the foundation of risk reduction behavior change.MethodsA review of the literature identified health behavior models from which risk reduction interventions are developed. Insights from these studies informed the development of a new framework to inform ADRD risk reduction interventions. This new framework seeks to leverage constructs from the Social Ecological Model (SEM), Health Belief Model (HBM), Transtheoretical Model (TTM), and the Health Stigma and Discrimination Framework (HSDF) to better inform and understand the factors that influence ADRD risk reduction behaviors.ResultThis framework contains several concepts that predict why individuals will take action to reduce risk of ADRDs: individual factors, social‐environmental factors, self and public stigma, and perceptions. Our model also includes stages of change to integrate processes and principles of change, offering a temporal dimension for understanding behavior change. This novel framework can be utilized to inform both individual and community‐level interventions.ConclusionThis new framework provides an innovative and alternative foundation for new ADRD risk reduction interventions. Applicable across a range of risk reduction behaviors, the model highlights the domains and pathways common across ADRD research and intervention implementation. This crosscutting approach will support a more efficient and effective response to addressing preventable risk factors for ADRDs, with the goal of application and realization. Further research is needed to assess the strengths and limitations of this framework in real‐world settings.