Biology subjects

Garrido, P. F.

Publications and source records attributed to Garrido, P. F..

4 recordsLinked to original sources

bioRxiv2026

Punctuated memory change: The temporal dynamics and brain basis of memory stability in aging

Are there individuals who resist episodic memory decline into older age? Analyzing 728,000 memory tests from 80,000 participants with at least 4 assessments, we introduce a simulation-calibrated framework to identify genuine memory stability. Across cohorts and models, [~]10% of adults [≥]70 years showed stable performance over a decade. In an MRI subgroup (n{approx}2,000), stable performers exhibited lower rates of brain atrophy across widespread regions, anchoring cognitive stability in structural brain maintenance. However, stability was often transient rather than trait-like: many individuals followed trajectories with extended plateaus of stable performance punctuated by episodes of accelerated decline. Accordingly, 54% showed at least one period of observed stability, averaging 10 years, whereas only 0.4% upheld stable performance over 24 years under the strictest definition. These findings are consistent with a complex-systems model of cognitive aging in which decline often reflects critical transitions rather than continuous erosion.

neuroscience↗

bioRxiv2025

Cortical thickness changes precede high levels of amyloid by at least seven years

Alzheimers disease (AD) is now defined based on its underlying brain pathology1, with the presence of amyloid (A{beta}) plaques at high enough levels sufficient to warrant a diagnosis in the absence of cognitive symptoms. High levels of PET-detectable A{beta} are widely thought to be the first imaging marker, with structural brain changes detectable on MRI scans thought to occur later. We combined 4570 longitudinal MRIs and 1684 A{beta} PET scans from three cognitively healthy cohorts to test the difference in cortical thickness and its change between those that subsequently converted to be A{beta}-positive or stayed A{beta}-negative, using MRIs acquired exclusively in the years before conversion. We found those that subsequently developed elevated A{beta} levels show both thicker cortex and less cortical thinning, even when the last MRI used to estimate their thickness trajectories was acquired at least seven years before conversion. Many effects remained when accounting for quantitative A{beta} levels, suggesting some cortical thickness effects may be partly independent of A{beta}. Differences in cortical thickness and its change between converters and A{beta}-negative individuals showed moderate alignment with patterns of A{beta} deposition, and the timing of thickness changes tracked the temporal progression of A{beta} accumulation. Thus, if amyloid is AD1, we show that high levels of PET-detectable amyloid are not the first imaging marker of AD, as cortical thickness changes can be traced years before pathological amyloid. This has implications for understanding the sequence of events leading up to the earliest stages of AD.

neuroscience↗

bioRxiv2025

Distinguishing Lifelong Individual Differences from Divergent Aging Trajectories of Adult Brain Volumes

Individual differences in the volumes of brain structures are often linked to various conditions, including Alzheimers disease, schizophrenia, and overall brain health. However, it remains unclear to what extent these differences reflect individual levels present from young adulthood or diverging aging trajectories from later ages. In this study, we analyze the aging dynamics of the volumes of six brain structures based on magnetic resonance imaging (MRI) scans from a large cross-cohort longitudinal sample of cognitively healthy adults (n = 8,311 with 18,520 MRIs, ages from 18 to 97 years). From general assumptions about structural brain dynamics and measurement noise, a stochastic dynamical model was fitted to the data to estimate both the variability and persistence of structural changes across adulthood. Using this model, we calculated how much of the variance of volumetric differences between individuals can be attributed to stable levels from young adulthood versus systematic changes at older ages, as well as the theoretical sensitivity of longitudinal studies to detect individual differences in change. The findings were as follows: 1) Before age 60 years, inter-individual differences in neuroanatomical volumes almost exclusively reflect stable differences between individuals, while the influence from systematic differences in rate-of-change increases thereafter; up to 50 % of the variation being due to differences in change at 80 years. In contrast, ventricular volume reflects differences in change from early adulthood. 2) Current brain-age models are unlikely to be sensitive to detect differences in aging trajectories. 3) Imaging studies have low reliability in detecting inter-individual brain changes before age 60. After 60 years, the study reliability increases sharply with longer intervals between scans and more modestly with additional intermediate observations. In conclusion, our results reinforce the view that it is critical to distinguish stable early-adulthood levels from systematic differences in change when studying adult brain aging.

neuroscience↗

bioRxiv2025

How and when can environmental influences change cerebral cortex? An experimental training study of twins with birth weight differences

How environmental variation shapes the human cerebral cortex remains incompletely understood. We compared cortical brainprints based in 210 twins (71 MZ and 34 DZ pairs, age 16-78 years) to distinguish prenatal, adult naturalistic and experimentally induced environmental variation from genetic contributions. Genetic effects were reflected in higher brainprint similarity within monozygotic (MZ) than dizygotic (DZ) pairs. Early environmental contributions were evident in lower brainprint similarity in MZ twin pairs with larger birthweight discordances, driven by area across the cortical ribbon. Later within-pair environmental differences in adult weight and lifestyle had minimal influence. Still, a 10-week virtual-reality navigation intervention revealed training-induced changes in the gray-white interface, with curvature and area changes supported by microstructural reconfigurations. In support of gene-environment interactions, relative brainprint similarity increased in MZ but diverged in DZ pairs following training. The results demonstrate that in adulthood, early life environmental difference persistently contributes to make the cortical architecture of genetically identical twins deviate. Environmental influence in adulthood in the form of training can still affect similarity of twin brainprints at the grey-white-matter boundary. These findings show that distinct environmental influences at prenatal and adult stage are differentially expressed across cortical features within a genetically informed framework.

neuroscience↗