Biology subjects

Munoz Maniega, S.

Publications and source records attributed to Munoz Maniega, S..

8 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↗

bioRxiv2020

Birth weight is associated with brain tissue volumes seven decades later, but not with age-associated changes to brain structure

Birth weight, an indicator of fetal growth, is associated with cognitive outcomes in early life and risk of metabolic and cardiovascular disease across the life course. Cognitive ability in early life is predictive of cognitive ability in later life. Brain health in older age, defined by MRI features, is associated with cognitive performance. However, little is known about how variation in normal birth weight impacts on brain structure in later life. In a community dwelling cohort of participants in their early seventies we tested the hypothesis that birthweight is associated with the following MRI features: total brain (TB), grey matter (GM) and normal appearing white matter (NAWM) volumes; whiter matter hyperintensity (WMH) volume; a general factor of fractional anisotropy (gFA) and peak width skeletonised mean diffusivity (PSMD) across the white matter skeleton. We also investigated the associations of birthweight with cortical surface area, volume and thickness. Birthweight was positively associated with TB, GM and NAWM volumes in later life ({beta} [≥] 0.194), and with regional cortical surface area but not gFA, PSMD, WMH volume, or cortical volume or thickness. These positive relationships appear to be explained by larger intracranial volume rather than by age-related tissue atrophy, and are independent of body height and weight in adulthood. This suggests that larger birthweight is linked to increased brain tissue reserve in older life, rather than a resilience to age-related changes in brain structure, such as tissue atrophy or WMH volume. Significance StatementCognitive brain ageing carries a high personal, societal and financial cost and understanding its developmental origins is important for identifying possible preventative strategies. In a sample of older participants from the Lothian Birth Cohort 1936 we were able to explore the neurobiological correlates of birth weight, which is indicative of the fetal experience. We find that higher birth weight is related to larger brain tissue volumes in later life, but does not modify the trajectory of age-related change. This suggests that early life growth confers preserved differentiation, rather than differential preservation with regards to brain reserve. That these effects are detectable into later life indicates that this variable may be valuable biomarker in the epidemiology of ageing.

neuroscience↗

bioRxiv2019

Quantitative Measurements of Enlarged Perivascular Spaces in the Brain are Associated with Retinal Microvascular Parameters in Older Community-Dwelling Subjects

BackgroundPerivascular Spaces (PVS) become increasingly visible with advancing age on brain MRI, yet their relationship to morphological changes in the underlying microvessels remains poorly understood. Retinal and cerebral microvessels share morphological and physiological properties. We compared computationally-derived PVS morphologies with retinal vessel morphologies in older people. MethodsWe analysed data from community-dwelling individuals who underwent multimodal brain MRI and retinal fundus camera imaging at mean age 72.55 years (SD=0.71). We assessed centrum semiovale PVS computationally to determine PVS total volume and count, and mean per-subject individual PVS length, width and size. We analysed retinal images using the VAMPIRE software suite, obtaining the Central Retinal Artery and Vein Equivalents (CRVE and CRAE), Arteriole-to-Venule ratio (AVR), and fractal dimension (FD) of both eyes. We investigated associations using general linear models, adjusted for age, gender, and major vascular risk factors. ResultsIn 381 subjects with all measures, increasing total PVS volume and count were associated with decreased CRAE in the left eye (volume {beta}=-0.170, count {beta}=-0.184, p<0.001). No associations of PVS with CRVE were found. The PVS total volume, individual width and size increased with decreasing FD of the arterioles (a) and venules (v) of the left eye (total volume: FDa {beta}=-0.137, FDv {beta}=-0.139, p<0.01; width: FDa {beta}=-0.144, FDv {beta}=-0.158, p<0.01; size: FDa {beta}=-0.157, FDv {beta}=-0.162, p<0.01). ConclusionsIncrease in PVS number and size visible on MRI reflect arteriolar narrowing and lower retinal arteriole and venule branching complexity, both markers of impaired microvascular health. Computationally-derived PVS metrics may be an early indicator of failing vascular health and should be tested in longitudinal studies.

neuroscience↗

bioRxiv2019

Neurology-related protein biomarkers are associated with general fluid cognitive ability and brain volume in older age

Identifying the biological correlates of late life cognitive function is important if we are to ascertain biomarkers for, and develop treatments to help reduce, age-related cognitive decline. This study investigated the associations between plasma levels of 91 neurology-related proteins (Olink(R) Proteomics) and general fluid cognitive ability in the Lothian Birth Cohort 1936 (LBC1936, N=798), the Lothian Birth Cohort 1921 (LBC1921, N=165), and the INTERVAL BioResource, (N=4,451). In LBC1936, we also examined mediation of protein-cognitive ability associations by MRI-derived indices of brain structure. In the LBC1936, 22 of the proteins and the first principal component (PC) created from a PC analysis of the 91 proteins, were associated with general fluid cognitive ability ({beta} between -0.11 and -0.17, p<0.0029). Total brain volume partially mediated the association between 10 of these proteins and general fluid cognitive ability. Effect sizes for the 22 proteins, although smaller, were all in the same direction as in LBC1936 in an age-matched subsample of INTERVAL. Similar effect sizes were found for the majority of these 22 proteins in the older LBC1921. The associations were not replicated in a younger subset of INTERVAL. In conclusion, we identified plasma levels of a number of neurology-related proteins that were associated with general fluid cognitive ability in later life, some of which were mediated by brain volume.

neuroscience↗

bioRxiv2019

Polygenic architecture of human neuroanatomical diversity

We analysed the genomic architecture of neuroanatomical diversity using magnetic resonance imaging and single nucleotide polymorphism (SNP) data from >26,000 individuals from the UK Biobank project and 5 other projects that had previously participated in the ENIGMA consortium. Our results confirm the polygenic architecture of neuroanatomical diversity, with SNPs capturing from 40% to 54% of regional brain volume variance. Chromosomal length correlated with the amount of phenotypic variance captured, r[~]0.64 on average, suggesting that at a global scale causal variants are homogeneously distributed across the genome. At a local scale, SNPs within genes ([~]51%) captured [~]1.5 times more genetic variance than the rest; and SNPs with low minor allele frequency (MAF) captured less variance than the rest: the 40% of SNPs with MAF<5% captured <1/4th of the genetic variance. We also observed extensive pleiotropy across regions, with an average genetic correlation of rG[~]0.45. Genetic correlations were similar to phenotypic and environmental correlations, however, genetic correlations were often larger than phenotypic correlations for the left/right volumes of the same region. The heritability of differences in left/right volumes was generally not statistically significant, suggesting an important influence of environmental causes in the variability of brain asymmetry. Our code is available at https://github.com/neuroanatomy/genomic-architecture.

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bioRxiv2018

Spatial Gradient of Microstructural Changes in Normal-Appearing White Matter in Tracts Affected by White Matter Hyperintensities in Older Age

Brain white matter hyperintensities (WMH), common in older adults, may contribute to cortical disconnection and cognitive dysfunction. The presence of WMH within white matter (WM) tracts indicates underlying microstructural WM changes that may also affect the normal-appearing WM (NAWM) of a tract. We performed an exploratory study using diffusion magnetic resonance imaging of 52 healthy participants from the Lothian Birth Cohort 1936 (age 72.2 {+/-} 0.7 years) selected to include a range of WMH burden, to quantify microstructural changes of tracts intersecting WMH. We reconstructed tracts using automated tractography and identified intersections with WMH. Tissue volumes and water diffusion tensor parameters (mean diffusivity (MD) and fractional anisotropy (FA)) were established for tract-WMH and tract-NAWM. MD and FA were also measured for tract-NAWM at 2 mm incremental distances from the tract-WMH edge, and from the edge of nearby, non-intersecting, WMH. We observed microstructural changes in tract-WMH suggestive of tissue damage. Tract-NAWM also showed a spatial gradient of FA and MD abnormalities, which diminished with distance from the tract-WMH. Nearby WMH lesions, not directly crossed by the tract, also affected tract microstructure with a similar pattern. Additionally, both FA and MD changes in tract-NAWM were predicted by FA and MD changes respectively in tract-WMH. FA was also predicted by tract-WMH overlap volume, whereas MD was better predicted by whole-brain WMH load. These results suggest that tract-NAWM microstructure is affected by the pathological process underlying WMH, when WMH are either within or near to the tract. The changes in NAWM tract tissue may indicate future lesion progression and may play an important role in cognitive ageing.

neuroscience↗

bioRxiv2018

Brain peak width of skeletonised mean diffusivity (PSMD), processing speed, and other cognitive domains

It is suggested that the brain's peak width of skeletonised water mean diffusivity (PSMD) is a neuro-biomarker of processing speed, a crucial contributor to cognitive ageing. We tested whether PSMD is more strongly correlated with processing speed than with other cognitive domains, and more strongly than other structural brain MRI indices. Participants were 731 Lothian Birth Cohort 1936 members, mean age 73 years (SD=0.7); analytical sample was 656-680. Cognitive domains tested were: processing speed (5 tests), visuospatial (3), memory (3), and verbal (3). Brain-imaging variables included PSMD, white matter diffusion parameters and hyperintensity volumes, grey and white matter volumes, and perivascular spaces. PSMD was significantly associated with all processing speed tests; absolute standardised beta values were 0.11 to 0.23 (mean = 0.17). Other structural brain-imaging variables correlated as or more strongly. PSMD was significantly associated with processing speed (-0.27), visuospatial (-0.23), memory (-0.17), and general cognitive ability (-0.25). PSMD correlated with processing speed: but not more strongly than with other cognitive domains; and not more strongly than other brain-imaging measures.

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bioRxiv2017

Brain Structural Differences Between 73- And 92-Year Olds Matched For Childhood Intelligence, Social Background, And Intracranial Volume

Fully characterizing age differences in the brain is a key task for combatting ageing-related cognitive decline. Using propensity score matching on two independent, narrow-age cohorts, we used data on childhood cognitive ability, socioeconomic background, and intracranial volume to match participants at mean age 92 years (n = 42) to very similar participants at mean age 73 (n = 126). Examining a variety of global and regional structural neuroimaging variables, there were large differences in grey and white matter volumes, cortical surface area, cortical thickness, and white matter hyperintensity volume and spatial extent. In a mediation analysis, the total volume of white matter hyperintensities and total cortical surface area jointly mediated 24.9% of the relation between age and general cognitive ability (tissue volumes and cortical thickness were not significant mediators in this analysis). These findings provide an unusual and valuable perspective on neurostructural ageing, in which brains from the eighth and tenth decades of life differ widely despite the same cognitive, socio-economic, and brain-volumetric starting points.

neuroscience↗