Lifespan Changes Research Articles

Language change across the lifespan: The changing status of a local variant

Abstract Three major studies on pronunciation were conducted in Iceland over a period of 70 years, including collection of real-time data. One subgroup of participants was interviewed as children in the 1940s, again as adults in the 1980s, and once again in the 2010s. Another subgroup was interviewed twice. By reanalysing raw data on participants in the first study the author was able to compare them with subsequent studies and trace individual developments, and thus examine lifespan changes over a long period. This article focuses on 62 participants from the two subgroups (47 people born in 1927–1932, and 15 born in 1963–1970), all from north-eastern Iceland, and a regional variant called ‘hard speech’ (harðmæli), i.e., the use of aspirated rather than unaspirated intervocalic plosives, comparing it with another north-eastern variant, so-called ‘voiced pronunciation’ (raddaður framburður), i.e., the use of voiced rather than voiceless sonorants before /p,t,k/. This reanalysis of the data of these seminal studies not only corroborates earlier findings that pronunciation can and does change among adult individuals, it also suggests (a) that such lifespan changes are more likely to happen in the first 2–3 decades of adulthood; and (b) that while ‘hard speech’ is fading as a local variant it shows signs of strengthening among individual speakers over their lifetime. This development takes place concurrently with attitudinal changes towards ‘hard speech’, which has come to be perceived as ‘clear pronunciation’.

A systematic review on sustainable utilization of plastic waste in asphalt: assessing environmental and health impact, performance, and economic viability.

Increasing amount of plastic waste (PW) poses a global challenge that necessitates multifaceted strategies. Repurposing PW in asphalt pavement is a sustainable strategy with extensive benefits, but there are several challenges that need to be overcome. This systematic review aims to examine three significant aspects associated with plastic-modified asphalt: environmental and health considerations, performance and technical properties, and cost.-effectiveness and economic feasibility. The environmental and health impacts of using PW in asphalt were particularly focused on the release of carcinogenic compounds and harmful fumes like polyaromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs), microplastic pollution, and climate impact. Environmental challenges and potential health risks associated with the use of PW in asphalt production were analyzed and indicated. Afterwards, the effects of different plastic types on the fatigue and rutting resistance of asphalt pavement are investigated. While many types of PWs show potential for enhancing rutting and fatigue performance, conflicting results have been observed for certain plastics. Some PW types, such as polyvinyl chloride (PVC), polypropylene (PP), polystyrene (PS), low-density polyethylene (LDPE), and high-density polyethylene (HDPE), have been shown to yield inconsistent results. Lastly, factors that are recognized to have an impact on the cost-effectiveness of plastic-modified asphalt include the collection and processing costs, asphalt materials price and availability, incorporation method, and possible changes in the asphalt's lifespan. The findings of this review help researchers to identify current gaps and aid stakeholders in making informed decisions towards more environmentally friendly, high-performance, and economically viable approaches to asphalt production.

Systems biology approaches identify metabolic signatures of dietary lifespan and healthspan across species

Dietary restriction (DR) is a potent method to enhance lifespan and healthspan, but individual responses are influenced by genetic variations. Understanding how metabolism-related genetic differences impact longevity and healthspan are unclear. To investigate this, we used metabolites as markers to reveal how different genotypes respond to diet to influence longevity and healthspan traits. We analyzed data from Drosophila Genetic Reference Panel (DGRP) strains raised under AL and DR conditions, combining metabolomic, phenotypic, and genome-wide information. We employed two computational and complementary methods across species—random forest modeling within the DGRP as our primary analysis and Mendelian randomization in human cohorts as a secondary analysis. We pinpointed key traits with cross-species relevance as well as underlying heterogeneity and pleiotropy that influence lifespan and healthspan. Notably, orotate was linked to parental age at death in humans and blocked the DR lifespan extension in flies, while threonine supplementation extended lifespan, in a strain- and sex-specific manner. Thus, utilizing natural genetic variation data from flies and humans, we employed a systems biology approach to elucidate potential therapeutic pathways and metabolomic targets for diet-dependent changes in lifespan and healthspan.

Theoretical Study of the Wear of a Reduced-Diameter Wheel for Freight Wagons, Based on Its Diameter

This paper presents the development of a numerical analysis model designed to estimate the lifespan of reduced-diameter wheels used in freight wagons based on their diameter, under quasi-static conditions. These wheels are increasingly being used in combined transport applications, where they are installed in various bogie configurations and subjected to different operational environments. However, due to the unique characteristics of reduced-diameter wheels, their lifespan has been scarcely studied. To accurately build this model, an in-depth investigation of the rolling phenomenon was required, addressing key issues in the track–vehicle interaction and establishing relationships between these factors. After constructing the rail–wheel interaction model, it was applied to calculate the lifespan of wheels with standard, medium, and reduced diameters under identical conditions for comparison. This approach makes it possible to determine the lifespan of reduced-diameter wheels relative to standard ones, as well as to observe how lifespan changes with wheel diameter, and it is observed how lifespan diminishes non-linearly with decreasing diameters. The underlying reasons for this variation are explained through a comprehensive understanding of the rolling phenomenon, enabled by the full analysis.

Levels of Amyloid Beta (Aβ) Expression in the Caenorhabditis elegans Neurons Influence the Onset and Severity of Neuronally Mediated Phenotypes.

A characteristic feature of Alzheimer's disease (AD) is the formation of neuronal extracellular senile plaques composed of aggregates of fibrillar amyloid β (Aβ) peptides, with the Aβ1-42 peptide being the most abundant species. These Aβ peptides have been proposed to contribute to the pathophysiology of the disease; however, there are few tools available to test this hypothesis directly. In particular, there are no data that establish a dose-response relationship between Aβ peptide expression level and disease. We have generated a panel of transgenic Caenorhabditis elegans strains expressing the human Aβ1-42 peptide under the control of promoter regions of two pan-neuronal expressed genes, snb-1 and rgef-1. Phenotypic data show strong age-related defects in motility, subtle changes in chemotaxis, reduced median and maximum lifespan, changes in health span indicators, and impaired learning. The Aβ1-42 expression level of these strains differed as a function of promoter identity and transgene copy number, and the timing and severity of phenotypes mediated by Aβ1-42 were strongly positively correlated with expression level. The pan-neuronal expression of varying levels of human Aβ1-42 in a nematode model provides a new tool to investigate the in vivo toxicity of neuronal Aβ expression and the molecular and cellular mechanisms underlying AD progression in the absence of endogenous Aβ peptides. More importantly, it allows direct quantitative testing of the dose-response relationship between neuronal Aβ peptide expression and disease for the first time. These strains may also be used to develop screens for novel therapeutics to treat Alzheimer's disease.

Breaking boundaries: A new era in glycemic assessment for type 2 diabetes patients

BACKGROUND: Glycemic control is essential in managing type 2 diabetes mellitus (T2DM) to reduce the risk of complications, including diabetic nephropathy. Traditionally, glycated hemoglobin (HbA1c) has been the gold standard for assessing long-term glycemic control. However, glycated albumin (GA) has emerged as a potential alternative due to its shorter lifespan and reduced sensitivity to erythrocyte lifespan changes. AIMS AND OBJECTIVES: This study aimed to compare the efficacy of GA and HbA1c in evaluating glycemic control in stable T2DM patients, particularly regarding its implications for diabetic nephropathy and associated complications. METHODOLOGY: A comparative analysis was conducted between GA and HbA1c levels in a cohort of stable T2DM patients. The primary focus was on assessing the reliability and clinical applicability of GA as a marker for glycemic control, especially in cases where HbA1c might provide misleading results. RESULTS: The study findings indicated that GA could offer a valuable alternative for glycemic monitoring, especially in clinical scenarios where HbA1c might not accurately reflect glycemic status due to erythrocyte lifespan variations. The use of GA could enhance the precision of glycemic control assessment, thus potentially improving patient care. CONCLUSION: The results underscore the importance of incorporating GA in clinical practice as an adjunct to HbA1c, particularly in situations where HbA1c may be unreliable. GA provides a promising alternative for better management of glycemic control in T2DM patients, potentially impacting the management and progression of diabetic nephropathy.

Tongue strength and swallowing-related masseter activity and oropharyngeal timing across the lifespan

Purpose: This study examined lifespan changes in maximum tongue strength, swallowing time, and masseter activity during swallowing. It provides normative data with which to compare clinical assessments of orofacial myofunctional disorders (OMD) and oropharyngeal dysphagia (OPD). Method: 409 healthy participants without identified OMD or OPD (ages 5 – 79 years) provided instrumental measures of tongue strength and electromyographic measurements for oropharyngeal transit time and masseter activity during swallows of four boluses. Participants were placed in three broad age groups (5 – 15, 16 – 59, 60 – 79) for crosssectional analysis. Results: Differences were found between age groups for tongue strength, such that the youngest group had significantly lower anterior tongue strength than the other groups, and lower posterior tongue strength than the 16 – 59 age group. Anterior tongue strength was significantly greater for males than females; posterior tongue strength did not differ significantly between the sexes. The youngest group had longer oropharyngeal transit times than either of the two older groups for most boluses. Swallowing transit time decreased in duration across the age groups, from youngest to oldest, for the 2.5 cc pudding bolus. Both right and left masseters differed in activation among tasks and age groups. The oldest age group had consistently greater levels of activation of the right masseter, and all groups had greater activation for the cracker bolus. Spearman rank-order correlations largely confirmed the inferential statistics and provided evidence of a relationship between tongue weakness and increased oropharyngeal transit time. Conclusion: Maximum tongue pressure generation and oropharyngeal timing measures support a developmental hypothesis, with lower tongue strength and longer swallowing transit times for children ages 5 through 15. The smaller pudding bolus provided the greatest differentiation among the age groups, which may prove to be a functional indicator for clinical evaluation. These results are largely consistent with existing data for tongue strength and oropharyngeal swallowing transit times.

Sport and longevity: an observational study of international athletes.

The human lifespan is influenced by various factors, with physical activity being a significant contributor. Despite the clear benefit of exercise on health and longevity, the association between different types of sports and lifespan is yet to be considered. Accordingly, we aimed to study this association in a large international cohort of former athletes using a robust linear regression model. We collected data on athletes from public sources, accumulating a total of 95,210 observations, 95.5% of which were accounted for by males. The dataset represented athletes born between 1862 and 2002 from 183 countries across 44 sports disciplines. We calculated the change in lifespan by measuring the difference in age between athletes and the corresponding reference populations, while accounting for variations caused by sex, year of death, and country. The results revealed that various sports impacted lifespan differently, with male athletes being more likely to experience benefits from sports than female athletes. Among male athletes, pole vaulting and gymnastics were linked to the highest extension in lifespan (8.4years, 95% CI [6.8, 9.9] and 8.2years, 95% CI [7.4, 9], respectively), while volleyball and sumo wrestling were the most negatively associated with lifespan (- 5.4years, 95% CI [- 7, - 3.8]; - 9.8years, 95% CI [- 11, - 8.6], respectively). The association between lifespan and popular team sports in males was positive for cricket, rowing, baseball, water polo, Australian rules, hurling, lacrosse, field hockey, minimal for rugby, canoeing and kayaking, basketball, gridiron football, and football (soccer), and negative for handball and volleyball. Racquet sports (i.e., tennis and badminton) exhibited a consistent and positive association in both male and female athletes, as shown by an extended lifespan of up to 5.7years in males (95% CI [5, 6.5]) and 2.8years in females (95% CI [1.8, 3.9]). Although lacking conclusive evidence, we theorize that the observed results may be attributed to the aerobic and anaerobic characteristics of each sport, with mixed sports yielding the maximum benefits for the lifespan. While results from female athletes should be cautiously interpreted, our study highlights the complex interplay between sports and lifespan and contributes to the growing body of knowledge on the multifaceted relationship between physical activity and human longevity.

Maternal α-casein deficiency extends the lifespan of offspring and programmes their body composition.

Early nutrition has significant effects on physiological outcomes during adult life. We have analysed the effect of maternal α-casein (CSN1S1) deficiency on the physiological fate of dams and their offspring. α-casein deficiency reduces maternal milk protein concentration by more than 50% and attenuates the growth of pups to 27% (p < 0.001) of controls at the point of weaning. This is associated with a permanent reduction in adult body weight (- 31% at 25weeks). Offspring nursed by α-casein deficient dams showed a significantly increased lifespan (+ 20%, χ2: 10.6; p = 0.001). Liver transcriptome analysis of offspring nursed by α-casein deficient dams at weaning revealed gene expression patterns similar to those found in dwarf mice (reduced expression of somatotropic axis signalling genes, increased expression of xenobiotic metabolism genes). In adult mice, the expression of somatotropic axis genes returned to control levels. This demonstrates that, in contrast to dwarf mice, attenuation of the GH-IGF signalling axis in offspring nursed by α-casein deficient dams is transient, while the changes in body size and lifespan are permanent. Offspring nursed by α-casein deficient dams showed permanent changes in body composition. Absolute and relative adipose tissue weights (p < 0.05), the percentage of body fat (p < 0.001) as well as adipocyte size in epididymal white adipose tissue are all reduced. Serum leptin levels were 25% of those found in control mice (p < 0.001). Liver lipid content and lipid composition were significantly altered in response to postnatal nutrition. This demonstrates the nutrition in early life programmes adult lipid metabolism, body composition and lifespan.

Scarring In Utero: An Attempt to Validate With Data Unconfounded by Migration and Medical Care.

"Scarring in utero" posits that populations exposed to injurious stressors yield birth cohorts that live shorter lives than expected from history. This argument implies a positive historical association between period life expectancy (i.e., average age at death in year t) and cohort life expectancy (i.e., average lifespan of persons born in year t). Tests of the argument have not produced consistent results and appear confounded by autocorrelation, migration, and access to medical care. Here we test whether, as predicted by scarring in utero, sex-specific period and cohort life expectancy appear positively related among Swedes born from 1751 through 1800. If scarring has ever influenced longevity, we should detect signals of its effects in these cohorts because, unlike other populations with known life span, they aged in place and unlikely benefitted from increased access to efficacious medical care. We use Box-Jenkins methods to control autocorrelation and measure associations. Contrary to the scarring hypothesis, we find an inverse association between period and cohort life expectancy. Our findings imply that, among males, variation in injurious stress on the population predicted changes in cohort life span ranging from a gain of approximately 67 weeks to a loss of about 45 weeks of life and among females from a gain of approximately 68 weeks to a loss of about 38 weeks of life. Epidemiologists trying to understand and explain temporal variation in cohort life expectancy should view the scarring argument with greater skepticism than currently found in the literature.

Morphometric brain organization across the human lifespan reveals increased dispersion linked to cognitive performance.

The human brain is organized as segregation and integration units and follows complex developmental trajectories throughout life. The cortical manifold provides a new means of studying the brain's organization in a multidimensional connectivity gradient space. However, how the brain's morphometric organization changes across the human lifespan remains unclear. Here, leveraging structural magnetic resonance imaging scans from 1,790 healthy individuals aged 8 to 89 years, we investigated age-related global, within- and between-network dispersions to reveal the segregation and integration of brain networks from 3D manifolds based on morphometric similarity network (MSN), combining multiple features conceptualized as a "fingerprint" of an individual's brain. Developmental trajectories of global dispersion unfolded along patterns of molecular brain organization, such as acetylcholine receptor. Communities were increasingly dispersed with age, reflecting more disassortative morphometric similarity profiles within a community. Increasing within-network dispersion of primary motor and association cortices mediated the influence of age on the cognitive flexibility of executive functions. We also found that the secondary sensory cortices were decreasingly dispersed with the rest of the cortices during aging, possibly indicating a shift of secondary sensory cortices across the human lifespan from an extreme to a more central position in 3D manifolds. Together, our results reveal the age-related segregation and integration of MSN from the perspective of a multidimensional gradient space, providing new insights into lifespan changes in multiple morphometric features of the brain, as well as the influence of such changes on cognitive performance.

Lifespan effects in male UM-HET3 mice treated with sodium thiosulfate, 16-hydroxyestriol, and late-start canagliflozin.

Genetically heterogeneous UM-HET3 mice born in 2020 were used to test possible lifespan effects of alpha-ketoglutarate (AKG), 2,4-dinitrophenol (DNP), hydralazine (HYD), nebivolol (NEBI), 16α-hydroxyestriol (OH_Est), and sodium thiosulfate (THIO), and to evaluate the effects of canagliflozin (Cana) when started at 16 months of age. OH_Est produced a 15% increase (p = 0.0001) in median lifespan in males but led to a significant (7%) decline in female lifespan. Cana, started at 16 months, also led to a significant increase (14%, p = 0.004) in males and a significant decline (6%, p = 0.03) in females. Cana given to mice at 6 months led, as in our previous study, to an increase in male lifespan without any change in female lifespan, suggesting that this agent may lead to female-specific late-life harm. We found that blood levels of Cana were approximately 20-fold higher in aged females than in young males, suggesting a possible mechanism for the sex-specific disparities in its effects. NEBI was also found to produce a female-specific decline (4%, p = 0.03) in lifespan. None of the other tested drugs provided a lifespan benefit in either sex. These data bring to 7 the list of ITP-tested drugs that induce at least a 10% lifespan increase in one or both sexes, add a fourth drug with demonstrated mid-life benefits on lifespan, and provide a testable hypothesis that might explain the sexual dimorphism in lifespan effects of the SGLT2 inhibitor Cana.

Repair and Reuse or Recycle: What Is Best for Small WEEE in Australia?

The global and Australian trends indicate a steady increase in the generation of small waste electrical and electronic equipment (WEEE), constituting 30% of global WEEE in 2019 with an expected 90% increase in Australia over the next 25 years. Given this fact, identifying the most suitable circular economy strategy is vital in managing this waste stream. Hence, followed by a review of the literature, a model was developed to assess the suitability of repair, reuse, and recycling of small electrical and electronic equipment (EEE) by considering the lifespan and products put on the market (PoM) as critical variables. Findings indicate that solely repairing and reusing products, without reducing PoM small EEE, minimally affects short-term waste reduction. A synergistic approach, combining high product reuse with reduced PoM small EEE, is essential to decrease small WEEE generation significantly. Regardless of lifespan changes, the study indicates a proportional relationship between small WEEE generation rates and PoM small EEE changes, emphasising the need for a holistic strategy. Considering this, within stewardship schemes, the primary focus should initially lie on repairing and repurposing small EEE, with the potential for expansion into recycling once sufficient infrastructure and achievable recovery goals are established. Original equipment manufacturers (OEMs) must shoulder substantial accountability, with a firm commitment to extended producer responsibility (EPR) even for historical products. The initial rollout could target four specific categories: toys, food preparation equipment, vacuum cleaners, and household tools, with the scope widening to encompass all categories following successful implementation.

Combinatorial transcriptomic and genetic dissection of insulin/IGF-1 signaling-regulated longevity in Caenorhabditis elegans.

Classical genetic analysis is invaluable for understanding the genetic interactions underlying specific phenotypes, but requires laborious and subjective experiments to characterize polygenic and quantitative traits. Contrarily, transcriptomic analysis enables the simultaneous and objective identification of multiple genes whose expression changes are associated with specific phenotypes. Here, we conducted transcriptomic analysis of genes crucial for longevity using datasets with daf-2/insulin/IGF-1 receptor mutant Caenorhabditis elegans. Our analysis unraveled multiple epistatic relationships at the transcriptomic level, in addition to verifying genetically established interactions. Our combinatorial analysis also revealed transcriptomic changes associated with longevity conferred by daf-2 mutations. In particular, we demonstrated that the extent of lifespan changes caused by various mutant alleles of the longevity transcription factor daf-16/FOXO matched their effects on transcriptomic changes in daf-2 mutants. We identified specific aging-regulating signaling pathways and subsets of structural and functional RNA elements altered by different genes in daf-2 mutants. Lastly, we elucidated the functional cooperation between several longevity regulators, based on the combination of transcriptomic and molecular genetic analysis. These data suggest that different biological processes coordinately exert their effects on longevity in biological networks. Together our work demonstrates the utility of transcriptomic dissection analysis for identifying important genetic interactions for physiological processes, including aging and longevity.

Predictions about reward outcomes in rhesus monkeys.

Human infants and nonhuman animals respond to surprising events by looking longer at unexpected than expected situations. These looking responses provide core cognitive evidence that nonverbal minds make predictions about possible outcomes and detect when these predictions fail to match reality. We propose that this phenomenon has crucial parallels with the processes of reward prediction error, indexing the difference between expected and actual reward outcomes. Most work on reward prediction errors to date involves neurobiological techniques that cannot be implemented in many relevant populations, so we developed a novel behavioral task to assess monkeys' predictions about reward outcomes using looking time responses. In Study 1, we tested how semi-free-ranging monkeys (n = 210) responded to positive error (more rewards than expected), negative error (less rewards than expected), and a number control. We found that monkeys looked longer at a given reward when it was unexpectedly large or small, compared to when the same quantity was expected. In Study 2, we compared responses in the positive error condition in monkeys ranging from infancy to old age (n = 363), to assess lifespan changes in sensitivity to reward predictions. We found that adolescent monkeys showed heightened responses to unexpected rewards, similar to patterns seen in humans, but showed no changes during aging. These results suggest that monkeys' looking responses can be used to track their predictions about rewards, and that monkeys share some developmental signatures of reward sensitivity with humans, providing a new approach to access cognitive processes underlying reward-based decision making. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Changes in leaf lifespan, nitrogen resorption, and mean residence time of leaf nitrogen along a soil fertility gradient in an evergreen oak tree.

The ability of plants to retain nitrogen (N) for a long period of time is critical to their N use efficiency, growth, and fitness, particularly in infertile environments. The mean residence time of leaf N (MRTL) and its two determinants, leaf lifespan and N resorption efficiency (rN, the fraction of the total leaf N pool that is resorbed during leaf senescence), have been hypothesized to increase plastically with decreasing soil N fertility but this remains to be fully tested. To avoid confusion by random changes in these characteristics in a relatively narrow N fertility range, MRTL, leaf lifespan, and N resorption efficiency were measured in Quercus glauca over a broad N fertility range. In the high to moderate N fertility range, leaf lifespan and rN increased with decreasing N addition rate, and thus the MRTL increased. However, in the moderate to low N fertility range, leaf lifespan increased but rN decreased significantly, so MRTL decreased. The decrease in rN occurred because the senesced leaf N concentration was almost constant at the lower limit while the green leaf N concentration decreased in this range. The hump-shaped quadratic responses of MRTL and rN along the N fertility gradient suggest that incorrect conclusions about the response of these traits to N fertility variation may be drawn from experiments that include only a few fertility levels, and N recycling within leaf canopy alone cannot achieve efficient N use in infertile environments.

Lifespan estimates for 1d damped wave equation with zero moment initial data

In this manuscript, a sharp lifespan estimate of solutions to semilinear classical damped wave equation is investigated in one dimensional case when the Fourier 0th moment of sum of initial position and speed is 0. Especially, it is shown that the behavior of lifespan changes with p=3/2 with respect to the size of the initial data.

The integrated stress response protects against ER stress but is not required for altered translation and lifespan from dietary restriction in Caenorhabditis elegans.

The highly conserved integrated stress response (ISR) reduces and redirects mRNA translation in response to certain forms of stress and nutrient limitation. It is activated when kinases phosphorylate a key residue in the alpha subunit of eukaryotic translation initiation factor 2 (eIF2). General Control Nonderepressible-2 (GCN2) is activated to phosphorylate eIF2α by the presence of uncharged tRNA associated with nutrient scarcity, while protein kinase R-like ER kinase-1 (PERK) is activated during the ER unfolded protein response (UPRER). Here, we investigated the role of the ISR during nutrient limitation and ER stress with respect to changes in protein synthesis, translationally driven mRNA turnover, and survival in Caenorhabditis elegans. We found that, while GCN2 phosphorylates eIF2α when nutrients are restricted, the ability to phosphorylate eIF2α is not required for changes in translation, nonsense-mediated decay, or lifespan associated with dietary restriction (DR). Interestingly, loss of both GCN2 and PERK abolishes increased lifespan associated with dietary restriction, indicating the possibility of other substrates for these kinases. The ISR was not dispensable under ER stress conditions, as demonstrated by the requirement for PERK and eIF2α phosphorylation for decreased translation and wild type-like survival. Taken together, results indicate that the ISR is critical for ER stress and that other translation regulatory mechanisms are sufficient for increased lifespan under dietary restriction.

Blood‐brain barrier permeability measured with arterial spin labeling as potential cerebrovascular biomarker over the lifespan

AbstractBackgroundBlood‐brain barrier (BBB) dysfunction is considered a hallmark of Alzheimer’s disease (AD), making non‐invasive imaging of BBB with arterial spin labeling (ASL) MRI a potential imaging biomarker (BBB‐ASL). However, the normal BBB development over the lifespan is unknown. Here, we created population‐based BBB‐ASL permeability reference maps, and aimed to investigate associations between BBB‐ASL, chronological age, and biological cerebrovascular age – expressed as white matter hyperintensities (WMH) volume.MethodCognitively‐unimpaired (CU) participants were included from Center for Lifespan Changes in Brain and Cognition (LCBC) (n = 28, age 58.9±16.1y) and University of Singapore (n = 30, age 55.8±6.1y). The Singapore cohort is known to be vascularly compromised and thus expected to have early cerebrovascular pathology in the form of WMH. Multi‐echo, multi‐post‐labeling‐delay pseudo‐continuous ASL images were acquired at two identical Siemens 3T scanners and analyzed with ExploreASL. Gray matter (GM) BBB water time‐of‐exchange (Tex) was quantified with and without partial‐volume correction (PVC). For Singapore data, WMH were segmented on 3D FLAIR. Linear regression models were used to investigate associations of Tex with age and WMH volume, with and without covarying for sex and site.ResultBoth site population‐averages (Figure 1) show similar Tex patterns, with slightly higher posterior variability in the Singapore data. GM Tex was negatively associated with age (Figure 2A) irrespective of PVC, and after covarying for sex and site (Table 1). GM Tex was also negatively associated with WMH volume (β = ‐0.005, p = 0.012), although the association became non‐significant if both PVC and sex and site corrections were applied (β = ‐0.005, p = 0.068).ConclusionOur findings support the hypothesis of increased BBB permeability with aging and there are signs of association with increased cerebrovascular age assessed with WMH volume. We aim to further increase our sample size and also investigate associations with other AD biomarkers.

Blood‐brain barrier permeability measured with arterial spin labeling as potential cerebrovascular biomarker over the lifespan

AbstractBackgroundBlood‐brain barrier (BBB) dysfunction is considered a hallmark of Alzheimer’s disease (AD), making non‐invasive imaging of BBB with arterial spin labeling (ASL) MRI a potential imaging biomarker (BBB‐ASL). However, the normal BBB development over the lifespan is unknown. Here, we created population‐based BBB‐ASL permeability reference maps, and aimed to investigate associations between BBB‐ASL, chronological age, and biological cerebrovascular age – expressed as white matter hyperintensities (WMH) volume.MethodCognitively‐unimpaired (CU) participants were included from Center for Lifespan Changes in Brain and Cognition (LCBC) (n = 28, age 58.9±16.1y) and University of Singapore (n = 30, age 55.8±6.1y). The Singapore cohort is known to be vascularly compromised and thus expected to have early cerebrovascular pathology in the form of WMH. Multi‐echo, multi‐post‐labeling‐delay pseudo‐continuous ASL images were acquired at two identical Siemens 3T scanners and analyzed with ExploreASL. Gray matter (GM) BBB water time‐of‐exchange (Tex) was quantified with and without partial‐volume correction (PVC). For Singapore data, WMH were segmented on 3D FLAIR. Linear regression models were used to investigate associations of Tex with age and WMH volume, with and without covarying for sex and site.ResultBoth site population‐averages (Figure 1) show similar Tex patterns, with slightly higher posterior variability in the Singapore data. GM Tex was negatively associated with age (Figure 2A) irrespective of PVC, and after covarying for sex and site (Table 1). GM Tex was also negatively associated with WMH volume (ß = ‐0.005, p = 0.012), although the association became non‐significant if both PVC and sex and site corrections were applied (ß = ‐0.005, p = 0.068).ConclusionOur findings support the hypothesis of increased BBB permeability with aging and there are signs of association with increased cerebrovascular age assessed with WMH volume. We aim to further increase our sample size and also investigate associations with other AD biomarkers.