A systematic review of diet and medication use among centenarians and near-centenarians worldwide.

Centenarians represent a phenomenon of successful aging. This systematic review aimed to understand lifestyles and health practices, focusing on diet and medication use for healthy longevity in community-based adults 95 years or over. Medline, CINAHL, Scopus, and gray literature were searched from 1 January 2000 to 10 December 2022. Study quality was assessed using the Modified Newcastle-Ottawa Scale (mNOS). Pooled prevalence [%; 95% confidence interval] for categorical variables and pooled mean for continuous variables were estimated for demographics, weight status, lifestyle factors, medications, and health conditions. Of 3392 records screened, 34 studies were included in the review, and 71% (24/34) met the 6/8 criteria in mNOS. Centenarians/near-centenarians' ages ranged from 95 to 118 years, with 75% (71-78%) female and 78% (68-88%) living in rural areas. They had an overall healthy lifestyle: current smoking (7%; 5-9%), drinking (23%; 17-30%), normal weight (52%; 42-61%), overweight (14%; 8-20%), physical activity (23%; 20-26%), and sleep satisfaction (68%; 65-72%). Diet averaged 59.6% carbohydrate, 18.5% protein, and 29.3% fat; over 60% consumed a diverse diet, and < 20% preferred salty food, contributing to lower mortality risks and functional decline. About half used antihypertensives (49%; 14-84%) or other cardiovascular drugs (48%; 24-71%), with an average of 4.6 medications. Common health issues included impaired basic activities of daily living (54%; 33-74%), hypertension (43%; 21-65%), and dementia (41%; 23-59%). The findings of this systemic review underscore the pivotal role of dietary practice and weight management in healthcare strategies to promote healthy ageing. It also recognises rural living styles and sleep hygiene as potential factors contributing to healthy longevity.

The contribution of cumulative blood pressure load to dementia, cognitive function and mortality in older adults.

BACKGROUND: Few studies evaluated the contribution of long-term elevated blood pressure (BP) towards dementia and deaths. We examined the association between cumulative BP (cBP) load and dementia, cognitive decline, all-cause and cardiovascular deaths in older Australians. We also explored whether seated versus standing BP were associated with these outcomes. METHODS: The Sydney Memory and Aging Study included 1037 community-dwelling individuals aged 70-90 years, recruited from Sydney, Australia. Baseline data was collected in 2005-2007 and the cohort was followed for seven waves until 2021. cSBP load was calculated as the area under the curve (AUC) for SBP ≥140 mmHg divided by the AUC for all SBP values. Cumulative diastolic BP (cDBP) and pulse pressure (cPP) load were calculated using thresholds of 90 mmHg and 60 mmHg. Cox and mixed linear models were used to assess associations. RESULTS: Of 527 participants with both seated and standing BP data (47.7% men, median age 77), 152 (28.8%) developed dementia over a mean follow-up of 10.5 years. Higher cPP load was associated with a higher risk of all-cause deaths, and cSBP load was associated with a higher risk of cardiovascular deaths in multivariate models (P for trend < 0.05). Associations between cPP load, dementia and cognitive decline lost statistical significance after adjustment for age. Differences between sitting and standing BP load were not associated with the outcomes. CONCLUSION: Long-term cPP load was associated with a higher risk of all-cause deaths and cSBP load associated with a higher risk of cardiovascular deaths in older Australians.

Functional neurological disorder clinics in Australasia: A binational survey.

BACKGROUND: Functional neurological symptom disorder (FND) is characterised by neurological symptoms that are incompatible with recognised neurological or medical conditions. The condition is common in neurology clinics and causes significant morbidity, though timely access to specialist care is difficult. We sought to characterise the availability and clinical practice of specialist FND clinics across Australia and New Zealand. METHODS: Clinicians or coordinators involved in running specialist FND clinics were identified through clinical contacts with further recruitment by snowball sampling and contacting patient organisations. All clinics completed a survey about details of service delivery, including clinical model, referral sources, criteria, demand, staffing, interventions, clinical data collection, and funding. RESULTS: We identified 16 clinics across Australia and New Zealand. Of these, 12 were in capital cities and four were in regional centres. Three of these focused on paediatric patients and 13 focused on adults. Clinics varied in their clinical model, referral sources, criteria, staffing, interventions, data collection, and funding. Most clinics reported challenges related to coping with demand and obtaining adequate funding. CONCLUSION: FND clinics in Australia and New Zealand appear to be concentrated predominantly in metropolitan areas and vary considerably in their referral sources, clinical data collection, and models of care. Reported challenges in meeting demand indicate a need for greater resources. The heterogeneity across clinics suggests a need to harmonise clinical standards to facilitate access to evidence-based care.

The protocol for an observational Australian cohort study of CADASIL: The AusCADASIL study.

Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic condition with a broad phenotypic presentation. This study aims to establish the first Australian cohort of individuals affected by CADASIL (AusCADASIL) and examine its clinical features and longitudinal course, and to investigate neuroimaging and blood biomarkers to assist in early diagnosis and identify disease progression. Methods: Participants will be recruited from six study centres across Australia for an observational study of CADASIL. We aim to recruit 150 participants with diagnosed CADASIL, family history of CADASIL or suspected CADASIL symptoms, and 150 cognitively normal NOTCH3 negative individuals as controls. Participants will complete: 1) online questionnaires on medical and family history, mental health, and wellbeing; 2) neuropsychological evaluation; 3) neurological examination and brain MRI; 4) ocular examination and 5) blood sample donation. Participants will have annual follow-up for 4 years to assess their progression and will be asked to invite a study partner to corroborate their self-reported cognitive and functional abilities.Primary outcomes include cognitive function and neuroimaging abnormalities. Secondary outcomes include investigation of genetics and blood and ocular biomarkers. Data from the cohort will contribute to an international consortium, and cohort participants will be invited to access future treatment/health intervention trials. Discussion: AusCADASIL will be the first study of an Australian cohort of individuals with CADASIL. The study will identify common pathogenic variants in this cohort, and characterise the pattern of clinical presentation and longitudinal progression, including imaging features, blood and ocular biomarkers and cognitive profile.

Brain-Derived Neurotrophic Factor Val66Met is Associated with Variation in Cortical Structure in Healthy Aging Subjects.

Aging is associated with progressive brain atrophy and declines in learning and memory, often attributed to hippocampal or cortical deterioration. The role of brain-derived neurotrophic factor (BDNF) in modulating the structural and functional changes in the brain and visual system, particularly in relation to BDNF Val66Met polymorphism, remains underexplored. In this present cross-sectional observational study, we aimed to assess the effects of BDNF polymorphism on brain structural integrity, cognitive function, and visual pathway alterations. A total of 108 older individuals with no evidence of dementia and a mean (SD) age of 67.3 (9.1) years were recruited from the Optic Nerve Decline and Cognitive Change (ONDCC) study cohort. The BDNF Met allele carriage had a significant association with lower entorhinal cortex volume (6.7% lower compared to the Val/Val genotype, P = 0.02) and posterior cingulate volume (3.2% lower than the Val/Val group, P = 0.03), after adjusting for confounding factors including age, sex and estimated total intracranial volumes (eTIV). No significant associations were identified between the BDNF Val66Met genotype and other brain volumetric or diffusion measures, cognitive performances, or vision parameters except for temporal retinal nerve fibre layer thickness. Small but significant correlations were found between visual structural and functional, cognitive, and brain morphological metrics. Our findings suggest that carriage of BDNF Val66Met polymorphism is associated with lower entorhinal cortex and posterior cingulate volumes and may be involved in modulating the cortical morphology along the aging process.

Genetics of environmental sensitivity to psychiatric and neurodevelopmental phenotypes: evidence from GWAS of monozygotic twins.

Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes. However, environmental sensitivity genetic variants have proven challenging to detect. GWAS of monozygotic twin differences is a family-based variance analysis method, which is more robust to systemic biases that impact population-based methods. We combined data from up to 21,792 monozygotic twins (10,896 pairs) from 11 studies to conduct the largest GWAS meta-analysis of monozygotic phenotypic differences in children and adolescents/adults for seven psychiatric and neurodevelopmental phenotypes: attention deficit hyperactivity disorder (ADHD) symptoms, autistic traits, anxiety and depression symptoms, psychotic-like experiences, neuroticism, and wellbeing. The SNP-heritability of variance in these phenotypes were estimated (h2: 0% to 18%), but were imprecise. We identified a total of 13 genome-wide significant associations (SNP, gene, and gene-set), including genes related to stress-reactivity for depression, growth factor-related genes for autistic traits and catecholamine uptake-related genes for psychotic-like experiences. Monozygotic twins are an important new source of evidence about the genetics of environmental sensitivity.

Associations between fruit and vegetable intakes and incident depression in middle-aged and older adults from 10 diverse international longitudinal cohorts.

BACKGROUND: Emerging observational evidence supports a role for higher fruit and vegetable intake in protecting against the development of depression. However, there is a scarcity of research in older adults or in low- to middle-income countries (LMICs). METHODS: Participants were 7801 community-based adults (mean age 68.6 ± 8.0 years, 55.8 % female) without depression, from 10 diverse cohorts, including four cohorts from LMICs. Fruit and vegetable intake was self-reported via comprehensive food frequency questionnaire, short food questionnaire or diet history. Depressive symptoms were assessed using validated measures, and depression defined applying validated cut-offs. The associations between baseline fruit and vegetable intakes and incident depression over a follow-up period of three to nine years were examined using Cox regression. Analyses were performed by cohort with results meta-analysed. RESULTS: There were 1630 cases of incident depression (21 % of participants) over 40,258 person-years of follow-up. Higher intake of fruit was associated with a lower risk of incident depression (HR 0.87, 95%CI [0.77, 0.99], I2 = 4 %). No association was found between vegetable intake and incident depression (HR 0.93, 95%CI [0.84, 1.04], I2 = 0 %). LIMITATIONS: Diverse measures used across the different cohorts and the modest sample size of our study compared with prior studies may have prevented an association being detected for vegetable intake. CONCLUSIONS: Our study supports a role for fruit, but not vegetable intake in protecting against depression. Research investigating different types of fruits and vegetables using standardised measures in larger cohorts of older adults from low- and middle-income countries is warranted.

Longitudinal alcohol-related brain changes in older adults: The Sydney Memory and Ageing Study.

Increases in harmful drinking among older adults indicate the need for a more thorough understanding of the relationship between later-life alcohol use and brain health. The current study investigated the relationships between alcohol use and progressive grey and white matter changes in older adults using longitudinal data. A total of 530 participants (aged 70 to 90 years; 46.0% male) were included. Brain outcomes assessed over 6 years included total grey and white matter volume, as well as volume of the hippocampus, thalamus, amygdala, corpus callosum, orbitofrontal cortex and insula. White matter integrity was also investigated. Average alcohol use across the study period was the main exposure of interest. Past-year binge drinking and reduction in drinking from pre-baseline were additional exposures of interest. Within the context of low-level average drinking (averaging 11.7 g per day), higher average amount of alcohol consumed was associated with less atrophy in the left (B = 7.50, pFDR = 0.010) and right (B = 5.98, pFDR = 0.004) thalamus. Past-year binge-drinking was associated with poorer white matter integrity (B = -0.013, pFDR = 0.024). Consuming alcohol more heavily in the past was associated with greater atrophy in anterior (B = -12.73, pFDR = 0.048) and posterior (B = -17.88, pFDR = 0.004) callosal volumes over time. Across alcohol exposures and neuroimaging markers, no other relationships were statistically significant. Within the context of low-level drinking, very few relationships between alcohol use and brain macrostructure were identified. Meanwhile, heavier drinking was negatively associated with white matter integrity.

Exploring the link between brain topological resilience and cognitive performance in the context of aging and vascular risk factors: A cross-ethnicity population-based study.

Brain aging is typically associated with a significant decline in cognitive performance. Vascular risk factors (VRF) and subsequent atherosclerosis (AS) play a major role in this process. Brain resilience reflects the brain's ability to withstand external perturbations, but the relationship of brain resilience with cognition during the aging process remains unclear. Here, we investigated how brain topological resilience (BTR) is associated with cognitive performance in the face of aging and vascular risk factors. We used data from two cross-ethnicity community cohorts, PolyvasculaR Evaluation for Cognitive Impairment and Vascular Events (PRECISE, n = 2220) and Sydney Memory and Ageing Study (MAS, n = 246). We conducted an attack simulation on brain structural networks based on k-shell decomposition and node degree centrality. BTR was defined based on changes in the size of the largest subgroup of the network during the simulation process. Subsequently, we explored the negative correlations of BTR with age, VRF, and AS, and its positive correlation with cognitive performance. Furthermore, using structural equation modeling (SEM), we constructed path models to analyze the directional dependencies among these variables, demonstrating that aging, AS, and VRF affect cognition by disrupting BTR. Our results also indicated the specificity of this metric, independent of brain volume. Overall, these findings underscore the supportive role of BTR on cognition during aging and highlight its potential application as an imaging marker for objective assessment of brain cognitive performance.

Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications.

BACKGROUND: Type 2 diabetes (T2D) susceptibility is influenced by genetic and environmental factors. Previous findings suggest DNA methylation as a potential mechanism in T2D pathogenesis and progression. METHODS: We profiled DNA methylation in 248 blood samples from participants of European ancestry from 7 twin cohorts using a methylation sequencing platform targeting regulatory genomic regions encompassing 2,048,698 CpG sites. FINDINGS: We find and replicate 3 previously unreported T2D differentially methylated CpG positions (T2D-DMPs) at FDR 5% in RGL3, NGB and OTX2, and 20 signals at FDR 25%, of which 14 replicated. Integrating genetic variation and T2D-discordant monozygotic twin analyses, we identify both genetic-based and genetic-independent T2D-DMPs. The signals annotate to genes with established GWAS and EWAS links to T2D and its complications, including blood pressure (RGL3) and eye disease (OTX2). INTERPRETATION: The results help to improve our understanding of T2D disease pathogenesis and progression and may provide biomarkers for its complications. FUNDING: Funding acknowledgements for each cohort can be found in the Supplementary Note.

Brain structural covariances in the ageing brain in the UK Biobank.

The morphologic properties of brain regions co-vary or correlate with each other. Here we investigated the structural covariances of cortical thickness and subcortical volumes in the ageing brain, along with their associations with age and cognition, using cross-sectional data from the UK Biobank (N = 42,075, aged 45-83 years, 53% female). As the structural covariance should be estimated in a group of participants, all participants were divided into 84 non-overlapping, equal-sized age groups ranging from the youngest to the oldest. We examined 84 cortical thickness covariances and subcortical covariances. Our findings include: (1) there were significant differences in the variability of structural covariance in the ageing process, including an increased variance, and a decreased entropy. (2) significant enrichment in pairwise correlations between brain regions within the occipital lobe was observed in all age groups; (3) structural covariance in older age, especially after the age of around 64, was significantly different from that in the youngest group (median age 48 years); (4) sixty-two of the total 528 pairs of cortical thickness correlations and 10 of the total 21 pairs of subcortical volume correlations showed significant associations with age. These trends varied, with some correlations strengthening, some weakening, and some reversing in direction with advancing age. Additionally, as ageing was associated with cognitive decline, most of the correlations with cognition displayed an opposite trend compared to age associated patterns of correlations.

Heritability of Gene Expression Measured from Peripheral Blood in Older Adults.

The contributions of genetic variation and the environment to gene expression may change across the lifespan. However, few studies have investigated the heritability of blood gene expression in older adults. The current study therefore aimed to investigate this question in a community sample of older adults. A total of 246 adults (71 MZ and 52 DZ twins, 69.91% females; mean age-75.79 ± 5.44) were studied. Peripheral blood gene expression was assessed using Illumina microarrays. A heritability analysis was performed using structural equation modelling. There were 5269 probes (19.9%) from 4603 unique genes (23.9%) (total 26,537 probes from 19,256 genes) that were significantly heritable (mean h2 = 0.40). A pathway analysis of the top 10% of significant genes showed enrichment for the immune response and ageing-associated genes. In a comparison with two other gene expression twin heritability studies using adults from across the lifespan, there were 38 out of 9479 overlapping genes that were significantly heritable. In conclusion, our study found ~24% of the available genes for analysis were heritable in older adults, with only a small number common across studies that used samples from across adulthood, indicating the importance of examining gene expression in older age groups.

Age and Sex Differences in the Genetic Architecture of Measures of Subjective Health: Relationships With Physical Health, Depressive Symptoms, and Episodic Memory.

OBJECTIVES: Subjective health (SH) is not just an indicator of physical health, but also reflects active cognitive processing of information about one's own health and has been associated with emotional health measures, such as neuroticism and depression. Behavior genetic approaches investigate the genetic architecture of SH, that is, genetic and environmental influences on individual differences in SH and associations with potential components such as physical, cognitive, and emotional health. Previous twin analyses have been limited by sex, sample size, age range, and focus on single covariates. METHODS: The current analysis used data from 24,173 adults ranging in age from 40 to 90 years from the international Interplay of Genes and Environment across Multiple Studies consortium to investigate the genetic architecture of 3 measures of SH: self-rated health, health compared to others, and impact of health on activities. Independent pathways model of SH included physical health, depressive symptoms, and episodic memory, with age, sex, and country included as covariates. RESULTS: Most or all of the genetic variance for SH measures were shared with physical health, depressive symptoms, and episodic memory. Genetic architecture of SH differed across measures, age groups (40-65, 66-90), and sexes. Age comparisons indicated stronger correlations with all 3 covariates in older adults, often resulting from greater shared genetic variance. DISCUSSION: The predictive value of SH has been amply demonstrated. The higher genetic contributions to associations between SH and its components in older adults support the increasing conceptualization with age of SH as an intuitive summation of one's vital reserve.

Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: The COSMIC consortium.

INTRODUCTION: White matter hyperintensities (WMHs) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well documented in populations of different ethnicities and/or from different geographical regions. METHODS: We investigated how WMHs were associated with vascular risk factors and cognition in both Whites and Asians, using data from five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1946). WMH volumes (whole brain, periventricular, and deep) were quantified with UBO Detector and harmonized using the ComBat model. We also harmonized various vascular risk factors and scores for global cognition and individual cognitive domains. RESULTS: Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake, and insufficient physical activity. Hypertension and stroke had stronger associations with WMH volumes in Whites than in Asians. No associations between WMH volumes and cognitive performance were found after correction for multiple testing. CONCLUSION: The current study highlights ethnic differences in the contributions of vascular risk factors to WMHs.

Fluid biomarkers of the neurovascular unit in cerebrovascular disease and vascular cognitive disorders: A systematic review and meta-analysis.

Background: The disruption of the neurovascular unit (NVU), which maintains the integrity of the blood brain barrier (BBB), has been identified as a critical mechanism in the development of cerebrovascular and neurodegenerative disorders. However, the understanding of the pathophysiological mechanisms linking NVU dysfunction to the disorders is incomplete, and reliable blood biomarkers to measure NVU dysfunction are yet to be established. This systematic review and meta-analysis aimed to identify biomarkers associated with BBB dysfunction in large vessel disease, small vessel disease (SVD) and vascular cognitive disorders (VCD). Methods: A literature search was conducted in PubMed, EMBASE, Scopus and PsychINFO to identify blood biomarkers related to dysfunction of the NVU in disorders with vascular pathologies published until 20 November 2023. Studies that assayed one or more specific markers in human serum or plasma were included. Quality of studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Effects were pooled and methodological heterogeneity examined using the random effects model. Results: A total of 112 studies were included in this review. Where study numbers allowed, biomarkers were analysed using random effect meta-analysis for VCD (1 biomarker; 5 studies) and cerebrovascular disorders, including stroke and SVD (9 biomarkers; 29 studies) while all remaining biomarkers (n = 17 biomarkers; 78 studies) were examined through qualitative analysis. Results of the meta-analysis revealed that cerebrospinal fluid/serum albumin quotient (Q-Alb) reliably differentiates VCD patients from healthy controls (MD = 2.77; 95 % CI = 1.97-3.57; p < 0.0001) while commonly measured biomarkers of endothelial dysfunction (VEGF, VCAM-1, ICAM-1, vWF and E-selectin) and neuronal injury (NfL) were significantly elevated in vascular pathologies. A qualitative assessment of non-meta-analysed biomarkers revealed NSE, NfL, vWF, ICAM-1, VCAM-1, lipocalin-2, MMP-2 and MMP-9 levels to be upregulated in VCD, although these findings were not consistently replicated. Conclusions: This review identifies several promising biomarkers of NVU dysfunction which require further validation. A panel of biomarkers representing multiple pathophysiological pathways may offer greater discriminative power in distinguishing possible disease mechanisms of VCD.

Association of Blood Pressure With Brain Ages: A Cohort Study of Gray and White Matter Aging Discrepancy in Mid-to-Older Adults From UK Biobank.

BACKGROUND: Gray matter (GM) and white matter (WM) impairments are both associated with raised blood pressure (BP), although whether elevated BP is differentially associated with the GM and WM aging process remains inadequately examined. METHODS: We included 37 327 participants with diffusion-weighted imaging (DWI) and 39 630 participants with T1-weighted scans from UK Biobank. BP was classified into 4 categories: normal BP, high-normal BP, grade 1, and grade 2 hypertension. Brain age gaps (BAGs) for GM (BAGGM) and WM (BAGWM) were derived from diffusion-weighted imaging and T1 scans separately using 3-dimensional-convolutional neural network deep learning techniques. RESULTS: There was an increase in both BAGGM and BAGWM with raised BP (P<0.05). BAGWM was significantly larger than BAGGM at high-normal BP (0.195 years older; P=0.006), grade 1 hypertension (0.174 years older; P=0.004), and grade 2 hypertension (0.510 years older; P<0.001), but not for normal BP. Mediation analysis revealed that the association between hypertension and cognitive decline was primarily mediated by WM impairment. Mendelian randomization analysis suggested a causal relationship between hypertension and WM aging acceleration (unstandardized B, 1.780; P=0.016) but not for GM (P>0.05). Sliding-window analysis indicated the association between hypertension and brain aging acceleration was moderated by chronological age, showing stronger correlations in midlife but weaker associations in the older age. CONCLUSIONS: Compared with GM, WM was more vulnerable to raised BP. Our study provided compelling evidence that concerted efforts should be directed towards WM damage in individuals with hypertension in clinical practice.

White matter brain age as a biomarker of cerebrovascular burden in the ageing brain.

As the brain ages, it almost invariably accumulates vascular pathology, which differentially affects the cerebral white matter. A rich body of research has investigated the link between vascular risk factors and the brain. One of the less studied questions is that among various modifiable vascular risk factors, which is the most debilitating one for white matter health? A white matter specific brain age was developed to evaluate the overall white matter health from diffusion weighted imaging, using a three-dimensional convolutional neural network deep learning model in both cross-sectional UK biobank participants (n = 37,327) and a longitudinal subset (n = 1409). White matter brain age gap (WMBAG) was the difference between the white matter age and the chronological age. Participants with one, two, and three or more vascular risk factors, compared to those without any, showed an elevated WMBAG of 0.54, 1.23, and 1.94 years, respectively. Diabetes was most strongly associated with an increased WMBAG (1.39 years, p < 0.001) among all risk factors followed by hypertension (0.87 years, p < 0.001) and smoking (0.69 years, p < 0.001). Baseline WMBAG was associated significantly with processing speed, executive and global cognition. Significant associations of diabetes and hypertension with poor processing speed and executive function were found to be mediated through the WMBAG. White matter specific brain age can be successfully targeted for the examination of the most relevant risk factors and cognition, and for tracking an individual's cerebrovascular ageing process. It also provides clinical basis for the better management of specific risk factors.

Disrupted pattern of rich-club organization in structural brain network from prediabetes to diabetes: A population-based study.

The network nature of the brain is gradually becoming a consensus in the neuroscience field. A set of highly connected regions in the brain network called "rich-club" are crucial high efficiency communication hubs in the brain. The abnormal rich-club organization can reflect underlying abnormal brain function and metabolism, which receives increasing attention. Diabetes is one of the risk factors for neurological diseases, and most individuals with prediabetes will develop overt diabetes within their lifetime. However, the gradual impact of hyperglycemia on brain structures, including rich-club organization, remains unclear. We hypothesized that the brain follows a special disrupted pattern of rich-club organization in prediabetes and diabetes. We used cross-sectional baseline data from the population-based PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study, which included 2218 participants with a mean age of 61.3 ± 6.6 years and 54.1% females comprising 1205 prediabetes, 504 diabetes, and 509 normal control subjects. The rich-club organization and network properties of the structural networks derived from diffusion tensor imaging data were investigated using a graph theory approach. Linear mixed models were used to assess associations between rich-club organization disruptions and the subjects' glucose status. Based on the graphical analysis methods, we observed the disrupted pattern of rich-club organization was from peripheral regions mainly located in frontal areas to rich-club regions mainly located in subcortical areas from prediabetes to diabetes. The rich-club organization disruptions were associated with elevated glucose levels. These findings provided more details of the process by which hyperglycemia affects the brain, contributing to a better understanding of the potential neurological consequences. Furthermore, the disrupted pattern observed in rich-club organization may serve as a potential neuroimaging marker for early detection and monitoring of neurological disorders in individuals with prediabetes or diabetes.