Abstract Background Cognitive dispersion index (CDI), a measure of intraindividual variability across neuropsychological tests, is considered a sensitive marker of prodromic stages of Alzheimer’s Disease (Halliday et al. J. Intell 2018;6(1):12). CDI has been negatively associated with cognitive reserve (CR), another factor that influences the risk of dementia (Stern et al. Alzh&Dement 2020;16(9):1305‐1311). Nevertheless, how these two elements interact with each other and are linked with cognition and brain state (e.g., functional connectivity), remains unclear. Our aim was to investigate whether CDI has a differential influence on cognitive performance (CP) and on resting‐state functional connectivity (rsFC) as a function of CR level, in a healthy middle‐aged sample. Method Five hundred forty‐four healthy volunteers (aged 53.11±7.10 years; 269 female) from the Barcelona Brain Health Initiative cohort (BBHI, https://bbhi.cat/en), were stratified by CR (median = 14) into High CR (HCR, N = 230) and Low CR (LCR, N = 314) using the cognitive reserve questionnaire (CRQ; Rami et al. Rev Neurol 2011;52(4):195‐201). CDI was extracted by intraindividual standard deviation method (Costa et al. Clinic Neuropsychol 2019;33(2):369‐389) and CP was calculated as a global cognition composite score including episodic memory, speed of processing and executive function tests. Functional magnetic resonance imaging (fMRI) was acquired, and measures of rsFC within networks were computed through Shirer atlas (Shirer et al. Cerebral Cortex 2012;22(1):158‐165). Statistical analyses were based on univariate ANCOVA GLMs, and partial correlations adjusted by age and gender. Result Though no significant group interaction was found, a negative correlation between CDI and CP was identified for the HCR group (r = ‐0.170,p = 0.010; Fig.1A). On fMRI there was a significant group difference (HCR vs. LCR) in the association between CDI and rsFC in anterior salience network (aSN: F = 5.005,p = 0.026), where only HCR participants showed a significant negative association between CDI and aSN rsFC values (r = ‐0.187,p = 0.010; Fig.1B&C). Conclusion Our findings suggested that CDI has a clearly measurable effect on HCR participants, both in terms of its effect on CP and on rsFC. These results highlight the value of considering CDI measurements when performing neuropsychological assessments in middle‐aged individuals, particularly in those with high CR estimates.

Cognitive reserve

10.1002/alz.064479

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Estimulación cerebral no invasiva combinada con neuroimagen: Hacia una medicina de precisión en el tratamiento de las adicciones

Adicciones (2023)

Kilian Abellaneda‐Pérez Laia Miquel Pilar Lusilla-Palacios Antoni Gual

10.20882/adicciones.1923

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Characterizing the Molecular Architecture of Cortical Regions Associated with High Educational Attainment in Older Individuals

Journal of Neuroscience (2019)

David Bartrés‐Faz Gabriel González‐Escamilla Lídia Vaqué‐Alcázar Kilian Abellaneda‐Pérez Cinta Valls‐Pedret

Neuroimaging investigations have revealed interindividual variations in anatomy, metabolism, activity, and connectivity of specific cortical association areas through which years of education (YoE), as a common proxy of cognitive reserve, may operate in the face of age- or pathology-associated brain changes. However, the associated molecular properties of YoE-related brain regions and the biological pathways involved remain poorly understood. In the present study we first identified brain areas that showed an association between cortical thickness and YoE among 122 cognitively healthy older human individuals (87 female). We subsequently characterized molecular properties of these regions by studying brain-wide microarray measurements of regional gene expression. In accordance with previous studies, we observed that YoE were associated with higher cortical thickness in medial prefrontal, anterior cingulate, and orbitofrontal areas. Compared with the rest of the cortex, these regions exhibited a distinct gene expression profile characterized by relative upregulation of gene sets implicated in ionotropic and metabotropic neurotransmission as well as activation of immune response. Our genome-wide expression profile analysis of YoE-related brain regions points to distinct molecular pathways that may underlie a higher capacity for plastic changes in response to lifetime intellectual enrichment and potentially also a higher resilience to age-related pathologic brain changes. SIGNIFICANCE STATEMENT We combined a neuroimaging-based analysis with a transcriptome-wide gene expression approach to investigate the molecular-functional properties of cortical regions associated with educational attainment, as a commonly used proxy for cognitive reserve, in older individuals. The strongest association with education was observed in specific areas of the medial prefrontal cortex, and these areas exhibited a distinct gene expression profile characterized by relative upregulation of gene sets implicated in neurotransmission and immune responses. These findings complement previous neuroimaging studies in the field and point to novel biological pathways that may mediate the beneficial effects of high educational attainment on adaptability to cope with, or prevent, age-related brain changes. The identified genes and pathways now warrant further exploration in mechanistic studies.

Orbitofrontal cortex

Human brain

10.1523/jneurosci.2370-18.2019

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Combining non‐invasive brain stimulation with functional magnetic resonance imaging to investigate the neural substrates of cognitive aging

Journal of Neuroscience Research (2019)

Kilian Abellaneda‐Pérez Lídia Vaqué‐Alcázar Cristina Solé‐Padullés David Bartrés‐Faz

Abstract As aging population is increasing, new methodologies to apprehend and enhance the mechanisms related to optimal brain function in advancing age become urgent. This review describes how the combined use of non‐invasive brain stimulation (NIBS) with functional magnetic resonance imaging (fMRI) provides novel experimental data on the putative neurophysiological mechanisms underlying inter‐individual differences in cognitive status among older adults, also further illuminating our understanding of theoretical models proposed within the cognitive neuroscience of aging literature. In addition, it explores published evidence of how this combined procedure entails the capacity to modify the activity and connectivity of specific brain networks in older adults, potentially leading to improvements in cognitive function and other measures reflecting mental health status. Although additional research is needed, combining NIBS with fMRI might provide innovative understanding of how fundamental brain plasticity mechanisms operate in advancing age, a knowledge that may be eventually used to refine more individually tailored approaches to promote brain health in aged populations.

Brain Aging

Brain stimulation

Neurophysiology

Brain Function

Aging brain

10.1002/jnr.24514

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[P3–351]: STRUCTURAL AND FUNCTIONAL CORRELATES OF BRAIN MAINTENANCE DURING A WORKING MEMORY TASK

Alzheimer s & Dementia (2017)

Lídia Vaqué‐Alcázar Roser Sala‐Llonch Kilian Abellaneda‐Pérez Cinta Valls‐Pedret Emilio Ros

Despite the well-described cognitive decline in normal aging (Fjell A, et al., ProgNeurobiol. 2014 Jun;117:20–40.), some elders maintain a preserved functioning. These subjects -brain maintainers- achieve a successful cognitive aging presumably because they do not experience significant declines neither at a neurochemical level, nor in terms of functional or structural brain measures (Nyberg L, et al., TrendsCognSci. 2012 May;16(5):292–305). We aimed to characterize the functional and structural changes of an aged group showing working memory function maintenance during 2-years follow-up, as compared to those showing some level of cognitive decline (non-maintainer). Forty-eight subjects (mean age: 70.54±2.98; 31 females) were further classified into two groups according to N-back task scores (Fig1A), namely brain maintainers (BM) and non-maintainers (NM). BM (n=14) were defined as those exhibiting baseline performance above the group mean and not showing decline. At the two time-points, we acquired magnetic resonance imaging (MRI) in a 3T Siemens scanner: T1-weighted 3D MPRAGE and functional MRI (fMRI)-EPI scans during the N-back task. We performed a Cortical Thickness (CTh) analysis with the FreeSurfer suite (https://surfer.nmr.mgh.harvard.edu/) to evaluate the structural integrity. FMRI scans were analysed using FEAT-FSL software (http://fsl.fmrib.ox.ac.uk/fsl/), statistical significance was set at p<0.05 and z>2.3 (cluster wise corrected). In both modalities we tested whether the groups had different patterns of change across time. Groups differ in years of education, BM are higher educated than NM (t=2.294, p=0.026). The behavioral results are shown in Fig 1B. As regards the neuroimaging findings, a time x group interaction was detected. NM exhibit higher activation at the second time-point compared to baseline not observed in BM (Fig 2). Finally, both groups displayed significant grey matter atrophy, but a greater CTh reduction was detected in NM compared to BM (Fig 3). Present findings provide first evidence of the functional and structural brain correlates underlying maintenance of working memory in aging. While maintainers remained performing better than non-maintainers at follow-up, only the latter group recruited greater brain regions during a cognitive demanding task, which suggests unsuccessful attempted compensation. Finally, patterns of brain atrophy paralleled the cognitive profile as it was more pronounced in the non-maintainer group. (A) Subjects performed a letter N-back task with different memory loads (0-back, 1-back, 2-back, 3-back) inside the MR scan at the two time-points. (B) Cognitive performance measured by hits on 3-back load. There were significant differences between groups, BM had better scores compared to NM for the baseline (t=4.391, p<0.001) and follow-up (t=6.874, p<0.001). Results of the fMRI analyses. (A) Significant activity maps, and (B) BOLD signal values at the ROI in maintainers and non-maintainers separated by baseline and follow-up measures. We used a GLM design to evaluate BOLD activity in the highest loads compared to the lowest loads (3-back > 2-back > 1-back > 0-back). We found a time x group interaction in the sense that NM exhibit increases in brain activity at the second time- point compared to baseline that were not observed in BM, who showed an intermediate level of activity at both time-points. Only non-maintainers show significant differences between the first and second time point (t=2.288, p=0.029). Results of the longitudinal CTh analysis. (p<0.05, corrected) showing reductions in thickness between timepoints for the two groups. (A) The maintainer group exhibit CTh decrease over time in parahippocampal region (RH) and superior parietal (LH). (B) Non-maintainer group present CTh reduction in areas as: superior temporal, inferior parietal (RH) and medial orbitofrontal, superior temporal, rostral middle frontal, fusiform, posterior cingulate, inferior parietal, precuneus, postcentral and lateraloccipital (LH), among others.

10.1016/j.jalz.2017.06.1567

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