Biology subjects

Waiter, G. D.

Publications and source records attributed to Waiter, G. D..

4 recordsLinked to original sources

bioRxiv2026

General cognitive function and the brain's structural connectome

General cognitive function ( g) reflects a broad capacity for flexible information processing, yet how brain-wide structural connectivity supports it remains unclear. In 38,824 individuals (26-84 years) across three cohorts, we show that g is supported by a widely distributed white matter network. Across streamline count, fractional anisotropy (FA), and mean diffusivity (MD), meta-analytic associations with g were widespread at global, nodal and edge levels, spanning all cerebral lobes and key subcortical structures and dependent on both inter- and intra-hemispheric connectivity, particularly ipsilateral long-range inter-lobar connections. White matter node-g associations spatially mirrored independent cortical morphometry-g associations, indicating convergence of grey and white matter contributions. Effect sizes increased with age: MD associations became more negative and FA more positive, especially in frontal regions. Edge-level findings replicated across cohorts and predicted g in a hold-out sample. These findings suggest g reflects a distributed structural communication backbone which becomes increasingly important with age.

neuroscience↗

bioRxiv2025

Machine learning identifies routine blood tests as accurate predictive measures of pollution-dependent poor cognitive function

BackgroundSeveral modifiable risk factors for dementia and related neurodegenerative diseases have been identified including education level, socio-economic status, and environmental exposures - however, how these population-level risks relate to individual risk remains elusive. To address this, we assess over 450 potential risk factors in one deeply clinically and demographically phenotyped cohort using random forest classifiers to determine predictive markers of poor cognitive function. This study aims to understand early risk factors for dementia by identifying predictors of poor cognitive performance amongst a comprehensive battery of imaging, blood, atmospheric pollutant and socio-economic measures. MethodsRandom forest modelling was used to determine significant predictors of poor cognitive performance in a cohort of 324 individuals (age 61.6 {+/-} 4.8 years; 150 males, 174 females) without extant neurological disease. 457 features were assessed including brain imaging measures of volume and iron deposition, blood measures of anaemia, inflammation, and heavy metal levels, social deprivation indicators and atmospheric pollution exposure. ResultsRoutinely assessed markers of anaemia including mean corpuscular haemoglobin concentration were identified as robust predictors of poor general cognition, where both extremes (low and high) were associated with poor cognitive performance. The strongest, most consistent predictors of poor cognitive performance were environmental measures of atmospheric pollution, in particular, lead, carbon monoxide, and particulate matter. Feature analysis demonstrated a significant negative relationship between low mean corpuscular haemoglobin concentration and high levels of atmospheric pollutants highlighting the potential of routinely assessed blood tests as a predictive measure of pollution-dependent cognitive functioning, at an individual level. ConclusionsTaken together, these data demonstrate how routine, inexpensive medical testing and local authority initiatives could help to identify and protect at-risk individuals. These findings highlight the potential to identify individuals for targeted, cost effective medical and social interventions to improve population cognitive health. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=66 SRC="FIGDIR/small/632396v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@1cda09org.highwire.dtl.DTLVardef@2e9243org.highwire.dtl.DTLVardef@1849bfcorg.highwire.dtl.DTLVardef@11cf9aa_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Associations between sex, systemic iron and inflammatory status and subcortical brain iron

Key PointsO_LIDifferences in subcortical brain iron levels were observed between males and females C_LIO_LIFemales exhibited more associations between brain iron and systemic markers for iron than males. C_LIO_LIMales exhibited more associations between brain iron and systemic markers for inflammation than females. C_LI BackgroundBrain iron is increased in several neurodegenerative diseases, with studies demonstrating relationships between increased subcortical iron and disease progression. However, the causes of increased brain iron remain unclear. This study investigates relationships between subcortical iron and systemic iron and inflammatory status to improve our understanding of brain iron accumulation. MethodsBrain MRI scans and blood plasma samples were collected from cognitively healthy females (n=176, mean age = 61.4 {+/-} 4.5 y, age range = 28 - 72 y) andmales (n=152, mean age = 62.0 {+/-} 5.1 y, age range = 32 - 74 y). Quantitative susceptibility mapping was used to quantify regional brain iron. To assess systemic iron, haematocrit, plasma ferritin and plasma soluble transferrin receptor (sTfR) were measured and total body iron index (TBI) was calculated. To assess systemic inflammation, C-reactive protein (CRP), Neutrophil/Lymphocyte ratio (NLR), plasma macrophage colony stimulating factor 1 (MCSF), plasma interleukin 6 (IL6) and plasma interleukin 1{beta} (IL1{beta}) were measured. ResultsFemales exhibited associations between TBI and iron levels in the left and right caudate and right pallidum. Females also exhibited associations between haematocrit and iron levels in the right pallidum and left putamen. However, in males, the only association between brain iron and iron status was a positive correlation between iron in the right caudate and ferritin. In males, positive associations were observed between CRP levels and iron in the right thalamus and between IL6 levels and iron in the right amygdala and right pallidum. Males also exhibited a negative association between IL6 levels and iron in the left caudate. Positive associations between iron in the left thalamus and NLR were observed in both sexes. ConclusionsThis study demonstrates differential relationships between systemic iron and inflammation markers and brain iron in females and males. These results suggest differing iron regulation mechanisms in older age between sexes which could lead towards an understanding of the differences in neurodegenerative disease prevalence in males and females.

neuroscience↗

bioRxiv2021

Local CpG density affects the trajectory of age-associated epigenetic changes

DNA methylation is an epigenetic mark associated with gene repression and genome stability. Its pattern in the genome is disrupted with age and these changes can be used to statistically predict age with epigenetic clocks. Rates of aging inferred from these clocks correlate with human health. However, the molecular mechanisms underpinning age-associated DNA methylation changes are unknown. Local DNA sequence plays a strong role in programming DNA methylation levels at individual loci independently of age, but its influence on age-associated DNA methylation changes is unknown. We analysed longitudinal human DNA methylation trajectories at 345,895 CpGs from 600 individuals aged between 67 and 80 to understand the factors responsible for age-associated epigenetic changes at individual CpGs in the genome. We show that changes in methylation with age are especially apparent at 8,322 low CpG density loci. Using SNP data from the same individuals we demonstrate that DNA methylation trajectories are affected by local sequence polymorphisms at 1,487 loci with low CpG density. More generally, we find that local CpG density is a strong determinant of a CpGs methylation trajectory and that CpGs located in low CpG density regions are particularly prone to change. Overall, our results demonstrate that local DNA sequence influences age-associated DNA methylation changes in humans in vivo. We suggest that this occurs because interactions between CpGs reinforce maintenance of methylation patterns in CpG dense regions.

genetics↗