Didac Vidal Pineiro

• Vidal-Pineiro, DIdac; Sørensen, Øystein, Strømstad, Maria; ...; Fjell, Anders M (2025). Vulnerability to memory decline in aging revealed by a mega-analysis of structural brain change. Nature Communications. ISSN 2041-1723. (Accepted). doi: 10.1101/2025.03.27.642988 (bioRxiv version).

• Fjell, Anders M; Rogeberg Ole J; Amlien, Inge K; ...; Vidal-Pineiro, Didac (2025). Reevaluating the Role of Education in Cognitive Decline and Brain Aging: Insights from Large-Scale Longitudinal Cohorts across 33 Countries. Nature Medicine, 31(9):2967-2976.  ISSN 1546-170X. 15(1).  doi: 10.1038/s41591-025-03828-y.

• Vidal-Pineiro, DIdac; Sørensen, Øystein, Strømstad, Maria; ...; Fjell, Anders M (2025). Reliability of structural brain change in cognitively healthy adult samples. Imaging Neuroscience, 22:3:imag_a_00547. ISSN 2837-6056. doi: 10.1162/imag_a_00547.

• Roe, James Michael; Vidal-Piñeiro, Didac; Sørensen, Øystein; ...; Wang, Yunpeng (2024). Brain change trajectories in healthy adults correlate with Alzheimer’s related genetic variation and memory decline across life. Nature Communications. ISSN 2041-1723. 15(1). doi: 10.1038/s41467-024-53548-z.

• Walhovd, Kristine B; Krogsrud, Stine Kleppe; Amlien, Inge; ...; Vidal-Pineiro, Didac. Fetal influence on the human brain through the lifespan. eLIFE. ISSN 2050-084X. 12. doi: 10.7554/eLife.86812.

• Vidal-Piñeiro, Didac; Wang, Yunpeng; Krogsrud, Stine Kleppe; ...; Fjell, Anders M (2021). Individual variations in ‘brain age’ relate to early-life factors more than to longitudinal brain change. eLIFE. ISSN 2050-084X. 10. doi: 10.7554/eLife.69995

• Mowinckel, Athanasia Monika & Vidal-Piñeiro, Didac (2020). Visualization of Brain Statistics With R Packages ggseg and ggseg3d. Advances in Methods and Practices in Psychological Science (AMPPS). ISSN 2515-2459. 3(4), p. 466–483. doi: 10.1177/2515245920928009.

• Xia, Lihua; Ren, Kang; Demetriou, Ina; Gurunandan, Kshipra; Meeker, Karin L. & Pineiro, Didac Vidal [Show all 8 contributors for this article] (2026). Bilingualism and cognitive aging in ethnically diverse older adults: cross-sectional and longitudinal evidence from Health and Aging Brain Study—Health Disparities. The journals of gerontology. Series B, Psychological sciences and social sciences. ISSN 1079-5014. 81(10), p. 1–10. doi: 10.1093/geronb/gbag150. Full text in Research Archive
• Walhovd, Kristine B; Bråthen, Anne Cecilie Sjøli; Øverbye, Knut Eiliv Ødegård; Kransberg, Jonas Moe; Sørensen, Øystein & Garrido, Pablo F. [Show all 19 contributors for this article] (2026). Feature-specific environmental contributions to human cortical architecture revealed by twin brainprints. Communications Biology. doi: 10.1038/s42003-026-10707-w. Full text in Research Archive Show summary

  Abstract How environmental variation shapes the human cerebral cortex remains incompletely understood. Here we compare cortical brainprints – individual profiles of regional cortical morphology – in 210 twins (age 16-78 years) to distinguish prenatal, adult naturalistic and experimentally induced environmental variation from genetic contributions. Monozygotic twins showed higher brainprint similarity than dizygotic twins, consistent with genetic effects. Lasting influences of early environment were evident in lower brainprint similarity in monozygotic twin-pairs with greater birthweight discordances, driven by surface area across the cortical ribbon. In contrast, within-pair 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. Relative brainprint similarity increased in monozygotic but diverged in dizygotic pairs following training. These findings show that distinct environmental influences acting at prenatal and adult stages are reflected in different features of the human cerebral cortex.

• Grødem, Edvard Olaf Sætersdal; Pineiro, Didac Vidal; Sørensen, Øystein; Bartrés-Faz, David; Brandmaier, Andreas M. & Cattaneo, Gabriele [Show all 20 contributors for this article] (2026). Stable individual differences dominate adult brain volume variation until later life. Imaging Neuroscience. 4. doi: 10.1162/IMAG.a.1242. Full text in Research Archive
• Morse, Rachel M.; Vaqué-Alcázar, Lídia; Cabello-Toscano, María; Solé-Padullés, Cristina; Mulet-Pons, Lídia & Trias, Juan Pablo Martin [Show all 12 contributors for this article] (2026). Modeling and evaluating longitudinal brain maintenance and cognitive reserve using episodic memory, brain structure, and functional connectivity in older adults. GeroScience. ISSN 2509-2715. doi: 10.1007/s11357-026-02157-3. Full text in Research Archive Show summary

  Cognitive reserve (CR) and brain maintenance (BM) reflect better than expected cognition despite brain pathology and minimal age-related brain changes that explain stable cognition, respectively. Despite being commonly used, joint quantification of these concepts has been limited; our aim is to derive longitudinal CR and BM measures and investigate CR’s relationship with education and functional connectivity. We analyzed longitudinal data from 451 participants (241 female, agemean = 68.5 years, follow-upmean = 4.2 years). From a hippocampus change-memory change regression, we modeled BM as memory stability relative to hippocampal stability and CR as better-than-expected memory stability relative to hippocampal atrophy. We examined whether education and resting-state functional connectivity (Default Mode, Executive Control and anterior Salience Network) (1) moderated the hippocampal-memory relationship using linear mixed effects models (LMEs), (2) moderated the hippocampus change-memory change relationship using linear regressions, and (3) were associated with our CR measure using LMEs. Analyses adjusted for demographics and MRI scanner/cohort, using false discovery rate (FDR) for multiple comparisons. From a significant hippocampus change-memory change relationship (β = 0.130, pFDR = 0.016, r2 = 0.282), we derived continuous CR and BM measures, providing subject-level estimates. Salience Network connectivity moderated the hippocampal-memory relationship (β = − 0.070, pFDR = 0.046, marginal r2 = 0.179). No variable moderated the hippocampus change-memory change relationship or correlated with our CR measure, consistent with the measure’s longitudinal definition. Our CR and BM measures refine phenotyping of aging trajectories. CR may be expressed through increased Salience Network connectivity, preserving memory level in the presence of hippocampal atrophy. Future work should delineate longitudinal CR mechanisms that decouple memory change from hippocampal atrophy.

• Pineiro, Didac Vidal; Sørensen, Øystein; Strømstad, Marie Lorentsen; Amlien, Inge; Baaré, William & Bartrés-Faz, David [Show all 74 contributors for this article] (2025). Vulnerability to memory decline in aging revealed by a mega-analysis of structural brain change. Nature Communications. 16(1). doi: 10.1038/s41467-025-66354-y. Full text in Research Archive Show summary

  Brain atrophy is a key factor behind episodic memory loss in aging, but the nature and ubiquity of this relationship remains poorly understood. This study leverages 13 longitudinal datasets, including 3737 cognitively healthy adults (10,343 MRI scans; 13,460 memory assessments), to determine whether brain change-memory change associations are more pronounced with age and genetic risk for Alzheimer’s Disease. Both factors are associated with accelerated brain decline, yet it remains unclear whethermemory loss is exacerbated beyond what atrophy alone would predict. Additionally, we assess whether memory decline aligns with a global pattern of atrophy or stems from distinct regional contributions. Our mega-analysis reveals a nonlinear relationship between memory decline and brain atrophy, primarily affecting individuals with above-average brain structural decline. The associations are stronger in the hippocampus but also spread across diverse cortical and subcortical regions. The associations strengthen with age, reachingmoderate associations in participants in their eighties. While APOE ε4 carriers exhibit steeper brain and memory loss, genetic risk has no effect on the change-change associations. These findings support the presence of common biological macrostructural substrates underlying memory function in older age which are vulnerable to multiple age-related factors, even in the absence of overt pathological changes.

• Fjell, Anders Martin; Røgeberg, Ole Jørgen; Sørensen, Øystein; Amlien, Inge; Bartrés-Faz, David & Brandmaier, Andreas M. [Show all 23 contributors for this article] (2025). Reevaluating the role of education on cognitive decline and brain aging in longitudinal cohorts across 33 Western countries. Nature Medicine. ISSN 1078-8956. 31, p. 2967–2976. doi: 10.1038/s41591-025-03828-y. Full text in Research Archive Show summary

  Why education is linked to higher cognitive function in aging is fiercely debated. Leading theories propose that education reduces brain decline in aging and enhances tolerance to brain pathology or that it does not affect cognitive decline but, rather, reflects higher early-life cognitive function. To test these theories, we analyzed 407,356 episodic memory scores from 170,795 participants older than 50 years, alongside 15,157 brain magnetic resonance imaging scans from 6,472 participants across 33 Western countries. More education was associated with better memory, larger intracranial volume and slightly larger volume of memory-sensitive brain regions. However, education did not protect against age-related decline or weakened effects of brain decline on cognition. The most parsimonious explanation for the results is that the associations reflect factors present early in life, including propensity of individuals with certain traits to pursue more education. Although education has numerous benefits, the notion that it provides protection against cognitive or brain decline is not supported. In a large cross-national study, education was linked to better memory and larger brain volumes but not to slower cognitive or brain decline with age, suggesting that the association reflects early-life factors rather than neuroprotective effects in aging.

• Ravndal, Anne; Fjell, Anders Martin; Vidal-Piñeiro, Didac; Sørensen, Øystein; Falch, Emilie Sogn & Kropiunig, Julia [Show all 21 contributors for this article] (2025). Sex differences in healthy brain aging are unlikely to explain higher Alzheimer’s disease prevalence in women. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 122(42). doi: 10.1073/pnas.2510486122. Full text in Research Archive Show summary

  As Alzheimer’s disease (AD) is diagnosed more frequently in women, understanding the role of sex has become a key priority in AD research. However, despite aging being the primary risk factor for AD, it remains unclear whether men and women differ in the extent of brain decline with age. Using 12,638 longitudinal brain MRIs from 4,726 participants aged 17 to 95 y across 14 cohorts, we examined sex differences in structural brain changes over time, controlling for differences in head size. Men showed greater cortical thickness (CT) decline in the cuneus, lingual, parahippocampal, and pericalcarine regions; surface area decline in the fusiform and postcentral regions; and in older adults, greater subcortical decline in the caudate, nucleus accumbens, putamen, and pallidum. In contrast, women only showed greater surface area decline in the banks of the superior temporal sulcus and greater ventricular expansion in older adults. These results suggest that sex differences in age-related brain decline are unlikely to contribute to the higher AD diagnosis prevalence in women, necessitating research into alternative explanations.

• Blakstad, Eirik G.; Sneve, Markus H.; Vidal-Pineiro, Didac; Walhovd, Kristine B.; Fjell, Anders M. & Grydeland, Håkon (2025). Memory-Related Default-Executive Coupling Across the Lifespan and Associations with Changes in Cognitive Control. BioRxiv. ISSN 0362-4331. doi: 10.1101/2025.09.02.673776. Full text in Research Archive Show summary

  Abstract Episodic memory and cognitive control declines in aging. The default-executive coupling hypothesis of aging (DECHA) suggests that a neural correlate of cognitive decline in aging is increased functional connectivity (FC) between lateral prefrontal areas and the default mode network. Here, in a lifespan sample (n=552, 6-81years), we tested FC between the left dorsolateral prefrontal cortex (dLPFC) and the default mode network (DMN) during the encoding and retrieval phases of an episodic memory fMRI task. We created two age groups based on evidence for episodic memory decline after 30 years: a youth group encompassing childhood, adolescence, and young adulthood (6-29 years) and an aging group (30-81 years). To test if the dLPFC-DMN FC was associated with changes in cognitive control, we used longitudinal change (up to 10 years) in a Stroop inhibition/switching task linked to the prefrontal cortex. Results showed (i) lower dLPFC and DMN connectivity with age in the youth group and higher connectivity in the aging group, and (ii) this FC was associated with an age-related increase in the inhibition task completion time, particularly in the aging group. However, dLPFC showed similar relationships with other networks, particularly salient attentional and control subnetworks, and despite decline in cognitive control associated with memory performance, memory-related FC between dLPFC and DMN did not. Although this link with memory performance remains unclear, the results using longitudinal cognitive data align with the DECHA mechanisms and extends the current proposal by indicating inverse relationships in development and the relevance of additional attentional and control network coupling.

• Vidal-Piñeiro, Didac; Sørensen, Øystein; Strømstad, Marie Lorentsen; Amlien, Inge; Anderson, Micael & Baaré, William F.C. [Show all 25 contributors for this article] (2025). Reliability of structural brain change in cognitively healthy adult samples. Imaging Neuroscience. 3, p. 1–25. doi: 10.1162/imag_a_00547. Full text in Research Archive Show summary

  In neuroimaging research, tracking individuals over time is key to understanding the interplay between brain changes and genetic, environmental, or cognitive factors across the lifespan. Yet, the extent to which we can estimate the individual trajectories of brain change over time with precision remains uncertain. In this study, we estimated the reliability of structural brain change in cognitively healthy adults from multiple samples and assessed the influence of follow-up time and number of observations. Estimates of cross-sectional measurement error and brain change variance were obtained using the longitudinal FreeSurfer processing stream. Our findings showed, on average, modest longitudinal reliability with 2 years of follow-up. Increasing the follow-up time was associated with a substantial increase in longitudinal reliability, while the impact of increasing the number of observations was comparatively minor. On average, 2-year follow-up studies require ≈2.7 and ≈4.0 times more individuals than designs with follow-ups of 4 and 6 years to achieve comparable statistical power. Subcortical volume exhibited higher longitudinal reliability than cortical area, thickness, and volume. The reliability estimates were comparable with those estimated from empirical data. The reliability estimates were affected by both the cohort’s age where younger adults had lower reliability of change and the preprocessing pipeline where the FreeSurfer’s longitudinal stream was notably superior than the cross-sectional stream. Suboptimal reliability inflated sample size requirements and compromised the ability to distinguish individual trajectories of brain aging. This study underscores the importance of long-term follow-ups and the need to consider reliability in longitudinal neuroimaging research.

• Grydeland, Håkon; Sneve, Markus Handal; Roe, James Michael; Raud, Liisa; Ness, Hedda Tvedten & Folvik, Line [Show all 12 contributors for this article] (2025). Network segregation during episodic memory shows age-invariant relations with memory performance from 7 to 82 years. Neurobiology of Aging. ISSN 0197-4580. 148, p. 1–15. doi: 10.1016/j.neurobiolaging.2025.01.004. Full text in Research Archive Show summary

  Lower episodic memory capability, as seen in development and aging compared with younger adulthood, may partly depend on lower brain network segregation. Here, our objective was twofold: (1) test this hypothesis using within- and between-network functional connectivity (FC) during episodic memory encoding and retrieval, in two independent samples (n = 734, age 7–82 years). (2) Assess associations with age and the ability to predict memory comparing task-general FC and memory-modulated FC. In a multiverse-inspired approach, we performed tests across multiple analytic choices. Results showed that relationships differed based on these analytic choices and were mainly present in the largest dataset,. Significant relationships indicated that (i) memory-modulated FC predicted memory performance and associated with memory in an age-invariant manner. (ii) In line with the so-called neural dedifferentiation view, task-general FC showed lower segregation with higher age in adults which was associated with worse memory performance. In development, although there were only weak signs of a neural differentiation, that is, gradually higher segregation with higher age, we observed similar lower segregation-worse memory relationships. This age-invariant relationships between FC and episodic memory suggest that network segregation is pivotal for memory across the healthy lifespan.

• Korbmacher, Max; Vidal-Piñeiro, Didac; Wang, Mengyun; Meer, Dennis van der; Wolfers, Thomas & Nakua, Hajer [Show all 10 contributors for this article] (2025). Cross-Sectional Brain Age Assessments Are Limited in Predicting Future Brain Change. Human Brain Mapping. ISSN 1065-9471. 46(6), p. 1–12. doi: 10.1002/hbm.70203. Full text in Research Archive Show summary

  The concept of brain age (BA) describes an integrative imaging marker of brain health, often suggested to reflect aging processes. However, the degree to which cross-sectional MRI features, including BA, reflect past, ongoing, and future brain changes across different tissue types from macro- to microstructure remains controversial. Here, we use multimodal imaging data of 39,325 UK Biobank participants, aged 44–82 years at baseline and 2,520 follow-ups within 1.12–6.90 years to examine BA changes and their relationship to anatomical brain changes. We find insufficient evidence to conclude that BA reflects the rate of brain aging. However, modality-specific differences in brain ages reflect the state of the brain, highlighting diffusion and multimodal MRI brain age as potentially useful cross-sectional markers.

• Fjell, Anders Martin; Sneve, Markus Handal; Amlien, Inge; Grydeland, Håkon; Mowinckel, Athanasia Monika & Vidal-Piñeiro, Didac [Show all 8 contributors for this article] (2025). Stable hippocampal correlates of high episodic memory function across adulthood. Scientific Reports. 15(1). doi: 10.1038/s41598-025-92278-0. Full text in Research Archive
• Capogna, Elettra; Sørensen, Øystein; Watne, Leiv; Roe, James Michael; Strømstad, Marie Lorentsen & Idland, Ane-Victoria [Show all 12 contributors for this article] (2025). Subtypes of brain change in aging and their associations with cognition and Alzheimer’s disease biomarkers. Neurobiology of Aging. ISSN 0197-4580. 147, p. 124–140. doi: 10.1016/j.neurobiolaging.2024.12.009. Full text in Research Archive Show summary

  Structural brain changes underlie cognitive changes and interindividual variability in cognition in older age. By using structural MRI data-driven clustering, we aimed to identify subgroups of cognitively unimpaired older adults based on brain change patterns and assess how changes in cortical thickness, surface area, and subcortical volume relate to cognitive change. We tested (1) which brain structural changes predict cognitive change (2) whether these are associated with core cerebrospinal fluid (CSF) Alzheimer’s disease biomarkers, and (3) the degree of overlap between clusters derived from different structural modalities in 1899 cognitively healthy older adults followed up to 16 years. We identified four groups for each brain feature, based on the degree of a main longitudinal component of decline. The minimal overlap between features suggested that each contributed uniquely and independently to structural brain changes in aging. Cognitive change and baseline cognition were associated with cortical area change, whereas higher baseline levels of phosphorylated tau and amyloid-β related to changes in subcortical volume. These results may contribute to a better understanding of different aging trajectories.

• Walhovd, Kristine B; Krogsrud, Stine Kleppe; Amlien, Inge; Sørensen, Øystein; Wang, Yunpeng & Bråthen, Anne Cecilie Sjøli [Show all 14 contributors for this article] (2024). Fetal influence on the human brain through the lifespan. eLIFE. 12. doi: 10.7554/eLife.86812. Full text in Research Archive
• Roe, James Michael; Vidal-Piñeiro, Didac; Sørensen, Øystein; Grydeland, Håkon; Leonardsen, Esten Høyland & Iakunchykova, Olena [Show all 35 contributors for this article] (2024). Brain change trajectories in healthy adults correlate with Alzheimer’s related genetic variation and memory decline across life. Nature Communications. 15(1). doi: 10.1038/s41467-024-53548-z. Full text in Research Archive Show summary

  Throughout adulthood and ageing our brains undergo structural loss in an average pattern resembling faster atrophy in Alzheimer’s disease (AD). Using a longitudinal adult lifespan sample (aged 30-89; 2–7 timepoints) and four polygenic scores for AD, we show that change in AD-sensitive brain features correlates with genetic AD-risk and memory decline in healthy adults. We first show genetic risk links with more brain loss than expected for age in early Braak regions, and find this extends beyond APOE genotype. Next, we run machine learning on AD-control data from the Alzheimer’s Disease Neuroimaging Initiative using brain change trajectories conditioned on age, to identify AD-sensitive features and model their change in healthy adults. Genetic AD-risk linked with multivariate change across many AD-sensitive features, and we show most individuals over age ~50 are on an accelerated trajectory of brain loss in AD-sensitive regions. Finally, high genetic risk adults with elevated brain change showed more memory decline through adulthood, compared to high genetic risk adults with less brain change. Our findings suggest quantitative AD risk factors are detectable in healthy individuals, via a shared pattern of ageing- and AD-related neurodegeneration that occurs along a continuum and tracks memory decline through adulthood.

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• Vidal-Piñeiro, Didac (2026). Brain structure across time and place: cohort and districts effects on neuroanatomy and its functional consequences in UK Biobank. doi: https:/www.lcbc.uio.no/english/origo-cogito/events/origocogito_conference_program.pdf. Full text in Research Archive
• Fjell, Anders Martin; Roe, James Michael & Vidal-Piñeiro, Didac (2026). Cortical thickness changes precede high levels of amyloid by at least 7 years-Article Metrics. Nature.com. doi: https:/www.nature.com/articles/s41593-026-02363-4. Full text in Research Archive
• Grødem, Edvard Olaf Sætersdal; Vidal-Piñeiro, Didac; Sørensen, Øystein; Garrido, Pablo F.; Nyberg, Lars Erik & Walhovd, Kristine B [Show all 8 contributors for this article] (2025). Distinguishing Lifelong Individual Differences from Divergent Aging Trajectories of Adult Brain Volumes. bioRxiv (preprint article). 2025.05.26.655710. doi: 10.1101/2025.05.26.655710. Full text in Research Archive
• Roe, James Michael; Grydeland, Håkon; Slivka, Maksim; Sørensen, Øystein; Grødem, Edvard Olaf Sætersdal & Walhovd, Kristine B [Show all 8 contributors for this article] (2025). Cortical thickness changes precede high levels of amyloid by at least seven years. bioRxiv (preprint article). doi: 10.1101/2025.08.14.670398. Full text in Research Archive
• Strømstad, Marie Lorentsen; Fjell, Anders Martin; Walhovd, Kristine B; Vidal-Piñeiro, Didac & Sørensen, Øystein (2024). Longitudinal association between structural brain change and episodic memory change. Full text in Research Archive

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