When Age Tips the Balance: a Dual Mechanism Affecting Hemispheric Specialization for Language.

Aging engenders neuroadaptations, generally reducing specificity and selectivity in functional brain responses. Our investigation delves into the functional specialization of brain hemispheres within language-related networks across adulthood. In a cohort of 728 healthy adults spanning ages 18 to 88, we modeled the trajectories of inter-hemispheric asymmetry concerning the principal functional gradient across 37 homotopic regions of interest (hROIs) of an extensive language network, known as the Language-and-Memory Network. Our findings reveal that over two-thirds of Language-and-Memory Network hROIs undergo asymmetry changes with age, falling into two main clusters. The first cluster evolves from left-sided specialization to right-sided tendencies, while the second cluster transitions from right-sided asymmetry to left-hemisphere dominance. These reversed asymmetry shifts manifest around midlife, occurring after age 50, and are associated with poorer language production performance. Our results provide valuable insights into the influence of functional brain asymmetries on language proficiency and present a dynamic perspective on brain plasticity during the typical aging process.

Role of Emotion Reactivity to Predict Facial Emotion Recognition Changes with Aging.

Emotional intelligence includes an assortment of factors related to emotion function. Such factors involve emotion recognition (in this case via facial expression), emotion trait, reactivity, and regulation. We aimed to investigate how the subjective appraisals of emotional intelligence (i.e. trait, reactivity, and regulation) are associated with objective emotion recognition accuracy, and how these associations differ between young and older adults. Data were extracted from the CamCAN dataset (189 adults: 57 young/118 older) from assessments measuring these emotion constructs. Using linear regression models, we found that greater negative reactivity was associated with better emotion recognition accuracy among older adults, though the pattern was opposite for young adults with the greatest difference in disgust and surprise recognition. Positive reactivity and depression level predicted surprise recognition, with the associations significantly differing between the age groups. The present findings suggest the level to which older and young adults react to emotional stimuli differentially predicts their ability to correctly identify facial emotion expressions. Older adults with higher negative reactivity may be able to integrate their negative emotions effectively in order to recognize other's negative emotions more accurately. Alternatively, young adults may experience interference from negative reactivity, lowering their ability to recognize other's negative emotions.

Resting state network connectivity alterations in HIV: Parallels with aging.

The increasing incidence of age-related comorbidities in people with HIV (PWH) has led to accelerated aging theories. Functional neuroimaging research, including functional connectivity (FC) using resting-state functional magnetic resonance imaging (rs-fMRI), has identified neural aberrations related to HIV infection. Yet little is known about the relationship between aging and resting-state FC in PWH. This study included 86 virally suppressed PWH and 99 demographically matched controls spanning 22-72 years old who underwent rs-fMRI. The independent and interactive effects of HIV and aging on FC were investigated both within- and between-network using a 7-network atlas. The relationship between HIV-related cognitive deficits and FC was also examined. We also conducted network-based statistical analyses using a brain anatomical atlas (n = 512 regions) to ensure similar results across independent approaches. We found independent effects of age and HIV in between-network FC. The age-related increases in FC were widespread, while PWH displayed further increases above and beyond aging, particularly between-network FC of the default-mode and executive control networks. The results were overall similar using the regional approach. Since both HIV infection and aging are associated with independent increases in between-network FC, HIV infection may be associated with a reorganization of the major brain networks and their functional interactions in a manner similar to aging.

Developmental differences in functional organization of multispectral networks.

Assessing brain connectivity during rest has become a widely used approach to identify changes in functional brain organization during development. Generally, previous works have demonstrated that brain activity shifts from more local to more distributed processing from childhood into adolescence. However, the majority of those works have been based on functional magnetic resonance imaging measures, whereas multispectral functional connectivity, as measured using magnetoencephalography (MEG), has been far less characterized. In our study, we examined spontaneous cortical activity during eyes-closed rest using MEG in 101 typically developing youth (9-15 years old; 51 females, 50 males). Multispectral MEG images were computed, and connectivity was estimated in the canonical delta, theta, alpha, beta, and gamma bands using the imaginary part of the phase coherence, which was computed between 200 brain regions defined by the Schaefer cortical atlas. Delta and alpha connectivity matrices formed more communities as a function of increasing age. Connectivity weights predominantly decreased with age in both frequency bands; delta-band differences largely implicated limbic cortical regions and alpha band differences in attention and cognitive networks. These results are consistent with previous work, indicating the functional organization of the brain becomes more segregated across development, and highlight spectral specificity across different canonical networks.

Changes of creative ability and underlying brain network connectivity throughout the lifespan.

Creativity, or divergent thinking, is essential to and supported by cognitive functions necessary for everyday tasks. The current study investigates divergent thinking and its neural mechanisms from adolescence to late adulthood. To do this, 180 healthy participants completed a creativity task called the egg task including 86 adolescents (mean age (SD) = 13.62 (1.98)), 52 young adults (24.92 (3.60), and 42 older adults (62.84 (7.02)). Additionally, a subsample of 111 participants completed a resting-state fMRI scan. After investigating the impact of age on different divergent thinking metrics, we investigated the impact of age on the association between divergent thinking and resting-state functional connectivity within and between major resting-state brain networks associated with creative thinking: the DMN, ECN, and SN. Adolescents tended to be less creative than both young and older adults in divergent thinking scores related to expansion creativity, and not in persistent creativity, while young and older adults performed relatively similar. We found that adolescents' functional integrity of the executive control network (ECN) was positively associated with expansion creativity, which was significantly different from the negative association in both the young and older adults. These results suggest that creative performance and supporting brain networks change throughout the lifespan.

Altered longitudinal trajectory of default mode network connectivity in healthy youth with subclinical depressive and posttraumatic stress symptoms.

The default mode network (DMN) plays a crucial role in internal self-processing, rumination, and social functions. Disruptions to DMN connectivity have been linked with early adversity and the emergence of psychopathology in adolescence and early adulthood. Herein, we investigate how subclinical psychiatric symptoms can impact DMN functional connectivity during the pubertal transition. Resting-state fMRI data were collected annually from 190 typically-developing youth (9-15 years-old) at three timepoints and within-network DMN connectivity was computed. We used latent growth curve modeling to determine how self-reported depressive and posttraumatic stress symptoms predicted rates of change in DMN connectivity over the three-year period. In the baseline model without predictors, we found no systematic changes in DMN connectivity over time. However, significant modulation emerged after adding psychopathology predictors; greater depressive symptomatology was associated with significant decreases in connectivity over time, whereas posttraumatic stress symptoms were associated with significant increases in connectivity over time. Follow-up analyses revealed that these effects were driven by connectivity changes involving the dorsal medial prefrontal cortex subnetwork. In conclusion, these data suggest that subclinical depressive and posttraumatic symptoms alter the trajectory of DMN connectivity, which may indicate that this network is a nexus of clinical significance in mental health disorders.

Changing role of the amygdala in affective and cognitive traits between early and late adulthood.

Introduction: Healthy aging is typically associated with cognitive decline and lower negative affect. Previous studies have reported a significant and opposite role of the amygdala in relation to cognitive and affective processing in early adulthood. However, it remains unclear how aging impacts such relationships. Methods: Seventy-seven healthy participants including 40 young (mean age = 26.1 years) and 37 older (mean age = 61.8 years) adults completed a functional MRI Affective Stroop (AS) paradigm, a cognitive battery, and the state-trait anxiety inventory. The AS fMRI paradigm included "task trials," where participants saw a positively, negatively or neutrally valenced distractor image, followed by a numerical display, followed by another distractor image. We extracted signal in both amygdalas during the AS Task and compared it across all conditions and age group. We further conducted moderation analyses to investigate the impact of aging on the relationship between amygdala activation and anxiety or cognitive variables, respectively. Results: At the behavioral level, older participants showed lower trait anxiety than the younger adults (p = 0.002). While overall slower during the AS task, older adults achieved comparable accuracy during the AS task, relative to the younger adults. At the brain level, we revealed a significant interaction between age group and trial types in amygdala activation (F = 4.9, p = 0.03), with the older group showing stronger activation during the most complex trials compared to the passive view trials. We further found that age significantly modulated the relationship between anxiety and the left amygdala activation during negative stimuli, where the younger adults showed a positive association while the older adults showed a negative association. Age also significantly modulated the relationship between verbal fluency and left amygdala activation during incongruent versus view trials, with the younger adults showing a negative association and the older adults showing a positive association. Discussion: The current study suggests that the role of the amygdala on both emotional processing and cognitive traits changes between early and late adulthood.

Neurocognitive Endophenotypes for Eating Disorders: A Preliminary High-Risk Family Study.

Eating disorders (EDs) are psychiatric disorders with a neurobiological basis. ED-specific neuropsychological and brain characteristics have been identified, but often in individuals in the acute phase or recovered from EDs, precluding an understanding of whether they are correlates and scars of EDs vs. predisposing factors. Although familial high-risk (FHR) studies are available across other disorders, this study design has not been used in EDs. We carried out the first FMH study in EDs, investigating healthy offspring of women with EDs and controls. We preliminarily aimed to investigate ED-related neurocognitive and brain markers that could point to predisposing factors for ED. Sixteen girls at FHR for EDs and twenty control girls (age range: 8−15), completed neuropsychological tests assessing executive functions. Girls also underwent a resting-state fMRI scan to quantify functional connectivity (FC) within resting-state networks. Girls at FHR for EDs performed worse on a cognitive flexibility task compared with controls (F = 5.53, p = 0.02). Moreover, they showed different FC compared with controls in several resting-state networks (p < 0.05 FDR-corrected). Differences identified in cognitive flexibility and in FC are in line with those identified in individuals with EDs, strongly pointing to a role as potential endophenotypes of EDs.

Assessing the relationship between maternal risk for attention deficit hyperactivity disorder and functional connectivity in their biological toddlers.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with increased risk for poor educational attainment and compromised social integration. Currently, clinical diagnosis rarely occurs before school-age, despite behavioral signs of ADHD in very early childhood. There is no known brain biomarker for ADHD risk in children ages 2-3 years-old. METHODS: The current study aimed to investigate the functional connectivity (FC) associated with ADHD risk in 70 children aged 2.5 and 3.5 years via functional near-infrared spectroscopy (fNIRS) in bilateral frontal and parietal cortices; regions involved in attentional and goal-directed cognition. Children were instructed to passively watch videos for approximately 5 min. Risk for ADHD in each child was assessed via maternal symptoms of ADHD, and brain data was evaluated for FC. RESULTS: Higher risk for maternal ADHD was associated with lower FC in a left-sided parieto-frontal network. Further, the interaction between sex and risk for ADHD was significant, where FC reduction in a widespread bilateral parieto-frontal network was associated with higher risk in male, but not female, participants. CONCLUSIONS: These findings suggest functional organization differences in the parietal-frontal network in toddlers at risk for ADHD; potentially advancing the understanding of the neural mechanisms underlying the development of ADHD.

Link between fluid/crystallized intelligence and global/local visual abilities across adulthood.

Human visual processing involves the extraction of both global and local information from a visual stimulus. Such processing may be related to cognitive abilities, which is likely going to change over time as we age. We aimed to investigate the impact of healthy aging on the association between visual global vs local processing and intelligence. In this context, we collected behavioral data during a visual search task in 103 adults (50 younger/53 older). We extracted three metrics reflecting global advantage (faster global than local processing), and visual interference in detecting either local or global features (based on interfering visual distractors). We found that older, but not younger, adults with higher levels of fluid and crystallized intelligence showed stronger signs of global advantage and interference effects during local processing, respectively. The present findings also provide promising clues regarding how participants consider and process their visual world in healthy aging.

Longitudinal Assessments of Neurocognitive Performance and Brain Structure Associated With Initiation of Tobacco Use in Children, 2016 to 2021.

Importance: The landscape of tobacco use is changing. However, information about the association between early-age tobacco use and cognitive performances is limited, especially for emerging tobacco products such as electronic cigarettes (e-cigarettes). Objective: To assess the association between early-age initiation of tobacco use and cognitive performances measured by the National Institutes of Health (NIH) Toolbox Cognitive Battery and to examine whether initiation is associated with differences in brain morphometry. Design, Setting, and Participants: This observational cohort study examined the longitudinal associations of initiation of tobacco use with neurocognition using multivariate linear mixed models. Children aged 9 to 10 years from 21 US sites were enrolled in wave 1 (October 1, 2016, to October 31, 2018 [n = 11 729]) and the 2-year follow-up (August 1, 2018, to January 31, 2021 [n = 10 081]) of the Adolescent Brain Cognitive Development (ABCD) Study. Exposures: Ever use (vs none) of any tobacco products at wave 1, including e-cigarettes, cigarettes, cigars, smokeless tobacco, hookah, pipes, and nicotine replacement. Main Outcomes and Measures: Neurocognition measured by the NIH Toolbox Cognition Battery and morphometric measures of brain structure and region of interest analysis for the cortex from structural magnetic resonance imaging. Results: Among 11 729 participants at wave 1 (mean [SE] age, 9.9 [0.6] years; 47.9% girls and 52.1% boys; 20.3% Hispanic; 14.9% non-Hispanic Black; and 52.1% non-Hispanic White), 116 children reported ever use of tobacco products. Controlling for confounders, tobacco ever users vs nonusers exhibited lower scores in the Picture Vocabulary Tests at wave 1 (b [SE] = -2.9 [0.6]; P < .001) and 2-year follow-up (b [SE] = -3.0 [0.7]; P < .001). The crystalized cognition composite score was lower among tobacco ever users than nonusers both at wave 1 (b [SE] = -2.4 [0.5]; P < .001) and 2-year follow-up (b [SE] = -2.7 [0.8]; P = .005). In structural magnetic resonance imaging, the whole-brain measures in cortical area and volume were significantly lower among tobacco users than nonusers, including cortical area (b [SE] = -5014.8 [1739.8] mm2; P = .004) at wave 1 and cortical volume at wave 1 (b [SE] = -174 621.0 [5857.7] mm3; P = .003) and follow-up (b [SE] = -21 790.8 [7043.9] mm3; P = .002). Further region of interest analysis revealed smaller cortical area and volume in multiple regions across frontal, parietal, and temporal lobes at both waves. Conclusions and Relevance: In this cohort study, initiating tobacco use in late childhood was associated with inferior cognitive performance and reduced brain structure with sustained effects at 2-year follow-up. These findings suggest that youths vulnerable to e-cigarettes and tobacco products should be treated as a priority population in tobacco prevention.

Evidence of discontinuity between psychosis-risk and non-clinical samples in the neuroanatomical correlates of social function.

Objective: Social dysfunction is a major feature of clinical-high-risk states for psychosis (CHR-P). Prior research has identified a neuroanatomical pattern associated with impaired social function outcome in CHR-P. The aim of the current study was to test whether social dysfunction in CHR-P is neurobiologically distinct or in a continuum with the lower end of the normal distribution of individual differences in social functioning. Methods: We used a machine learning classifier to test for the presence of a previously validated brain structural pattern associated with impaired social outcome in CHR-P (CHR-outcome-neurosignature) in the neuroimaging profiles of individuals from two non-clinical samples (total n = 1763) and examined its association with social function, psychopathology and cognition. Results: Although the CHR-outcome-neurosignature could be detected in a subset of the non-clinical samples, it was not associated was adverse social outcomes or higher psychopathology levels. However, participants whose neuroanatomical profiles were highly aligned with the CHR-outcome-neurosignature manifested subtle disadvantage in fluid (PFDR = 0.004) and crystallized intelligence (PFDR = 0.01), cognitive flexibility (PFDR = 0.02), inhibitory control (PFDR = 0.01), working memory (PFDR = 0.0005), and processing speed (PFDR = 0.04). Conclusions: We provide evidence of divergence in brain structural underpinnings of social dysfunction derived from a psychosis-risk enriched population when applied to non-clinical samples. This approach appears promising in identifying brain mechanisms bound to psychosis through comparisons of patient populations to non-clinical samples with the same neuroanatomical profiles.

Initial evidence of abnormal brain plasticity in anorexia nervosa: an ultra-high field study.

Anorexia Nervosa has been associated with white matter abnormalities implicating subcortical abnormal myelination. Extending these findings to intracortical myelin has been challenging but ultra-high field neuroimaging offers new methodological opportunities. To test the integrity of intracortical myelin in AN we used 7 T neuroimaging to acquire T1-weighted images optimized for intracortical myelin from seven females with AN (age range: 18-33) and 11 healthy females (age range: 23-32). Intracortical T1 values (inverse index of myelin concentration) were extracted from 148 cortical regions at ten depth-levels across the cortical ribbon. Across all cortical regions, these levels were averaged to generate estimates of total intracortical myelin concentration and were clustered using principal component analyses into two clusters; the outer cluster comprised T1 values across depth-levels ranging from the CSF boundary to the middle of the cortical regions and the inner cluster comprised T1 values across depth-levels ranging from the middle of the cortical regions to the gray/white matter boundary. Individuals with AN exhibited higher T1 values (i.e., decreased intracortical myelin concentration) in all three metrics. It remains to be established if these abnormalities result from undernutrition or specific lipid nutritional imbalances, or are trait markers; and whether they may contribute to neurobiological deficits seen in AN.

The forest, the trees, and the leaves across adulthood: Age-related changes on a visual search task containing three-level hierarchical stimuli.

Selecting relevant visual information in complex scenes by processing either global information or local parts helps us act efficiently within our environment and achieve goals. A global advantage (faster global than local processing) and global interference (global processing interferes with local processing) comprise an evidentiary global precedence phenomenon in early adulthood. However, the impact of healthy aging on this phenomenon remains unclear. As such, we collected behavioral data during a visual search task, including three-levels hierarchical stimuli (i.e., global, intermediate, and local levels) with several hierarchical distractors, in 50 healthy adults (26 younger (mean age: 26 years) and 24 older (mean age: 62 years)). Results revealed that processing information presented at the global and intermediate levels was independent of age. Conversely, older adults were slower for local processing compared to the younger adults, suggesting lower efficiency to deal with visual distractors during detail-oriented visual search. Although healthy older adults continued exhibiting a global precedence phenomenon, they were disproportionately less efficient during local aspects of information processing, especially when multiple visual information was displayed. Our results could have important implications for many life situations by suggesting that visual information processing is impacted by healthy aging, even with similar visual stimuli objectively presented.

Multivariate patterns of brain-behavior associations across the adult lifespan.

The nature of brain-behavior covariations with increasing age is poorly understood. In the current study, we used a multivariate approach to investigate the covariation between behavioral-health variables and brain features across adulthood. We recruited healthy adults aged 20-73 years-old (29 younger, mean age = 25.6 years; 30 older, mean age = 62.5 years), and collected structural and functional MRI (s/fMRI) during a resting-state and three tasks. From the sMRI, we extracted cortical thickness and subcortical volumes; from the fMRI, we extracted activation peaks and functional network connectivity (FNC) for each task. We conducted canonical correlation analyses between behavioral-health variables and the sMRI, or the fMRI variables, across all participants. We found significant covariations for both types of neuroimaging phenotypes (ps = 0.0004) across all individuals, with cognitive capacity and age being the largest opposite contributors. We further identified different variables contributing to the models across phenotypes and age groups. Particularly, we found behavior was associated with different neuroimaging patterns between the younger and older groups. Higher cognitive capacity was supported by activation and FNC within the executive networks in the younger adults, while it was supported by the visual networks' FNC in the older adults. This study highlights how the brain-behavior covariations vary across adulthood and provides further support that cognitive performance relies on regional recruitment that differs between older and younger individuals.

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.

Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder.

First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.

Greater male than female variability in regional brain structure across the lifespan.

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years.

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.

Person-Based Similarity Index for Cognition and Its Neural Correlates in Late Adulthood: Implications for Cognitive Reserve.

Healthy aging is typically associated with some level of cognitive decline, but there is substantial variation in such decline among older adults. The mechanisms behind such heterogeneity remain unclear but some have suggested a role for cognitive reserve. In this work, we propose the "person-based similarity index" for cognition (PBSI-Cog) as a proxy for cognitive reserve in older adults, and use the metric to quantify similarity between the cognitive profiles of healthy older and younger participants. In the current study, we computed this metric in 237 healthy older adults (55-88 years) using a reference group of 156 younger adults (18-39 years) taken from the Cambridge Center for Ageing and Neuroscience dataset. Our key findings revealed that PBSI-Cog scores in older adults were: 1) negatively associated with age (rho = -0.25, P = 10-4) and positively associated with higher education (t = 2.4, P = 0.02), 2) largely explained by fluid intelligence and executive function, and 3) predicted more by functional connectivity between lower- and higher-order resting-state networks than brain structural morphometry or education. Particularly, we found that higher segregation between the sensorimotor and executive networks predicted higher PBSI-Cog scores. Our results support the notion that brain network functional organization may underly variability in cognitive reserve in late adulthood.