Browsing by Subject "Cognitive reserve"

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    Design and Harmonization Approach for the Multi-Institutional Neurocognitive Discovery Study (MINDS) of Adult Congenital Heart Disease (ACHD) Neuroimaging Ancillary Study: A Technical Note
    (MDPI, 2023-09-06) Panigrahy, Ashok; Schmithorst, Vanessa; Ceschin, Rafael; Lee, Vince; Beluk, Nancy; Wallace, Julia; Wheaton, Olivia; Chenevert, Thomas; Qiu, Deqiang; Lee, James N.; Nencka, Andrew; Gagoski, Borjan; Berman, Jeffrey I.; Yuan, Weihong; Macgowan, Christopher; Coatsworth, James; Fleysher, Lazar; Cannistraci, Christopher; Sleeper, Lynn A.; Hoskoppal, Arvind; Silversides, Candice; Radhakrishnan, Rupa; Markham, Larry; Rhodes, John F.; Dugan, Lauryn M.; Brown, Nicole; Ermis, Peter; Fuller, Stephanie; Cotts, Timothy Brett; Rodriguez, Fred Henry; Lindsay, Ian; Beers, Sue; Aizenstein, Howard; Bellinger, David C.; Newburger, Jane W.; Glass Umfleet, Laura; Cohen, Scott; Zaidi, Ali; Gurvitz, Michelle; Pediatric Heart Network MINDS Neuroimaging Ancillary Study Investigators; Radiology and Imaging Sciences, School of Medicine
    Dramatic advances in the management of congenital heart disease (CHD) have improved survival to adulthood from less than 10% in the 1960s to over 90% in the current era, such that adult CHD (ACHD) patients now outnumber their pediatric counterparts. ACHD patients demonstrate domain-specific neurocognitive deficits associated with reduced quality of life that include deficits in educational attainment and social interaction. Our hypothesis is that ACHD patients exhibit vascular brain injury and structural/physiological brain alterations that are predictive of specific neurocognitive deficits modified by behavioral and environmental enrichment proxies of cognitive reserve (e.g., level of education and lifestyle/social habits). This technical note describes an ancillary study to the National Heart, Lung, and Blood Institute (NHLBI)-funded Pediatric Heart Network (PHN) “Multi-Institutional Neurocognitive Discovery Study (MINDS) in Adult Congenital Heart Disease (ACHD)”. Leveraging clinical, neuropsychological, and biospecimen data from the parent study, our study will provide structural–physiological correlates of neurocognitive outcomes, representing the first multi-center neuroimaging initiative to be performed in ACHD patients. Limitations of the study include recruitment challenges inherent to an ancillary study, implantable cardiac devices, and harmonization of neuroimaging biomarkers. Results from this research will help shape the care of ACHD patients and further our understanding of the interplay between brain injury and cognitive reserve.
  • Thumbnail Image
    Item
    Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer's disease
    (Springer, 2024-08-05) Jury‑Garfe, Nur; Redding‑Ochoa, Javier; You, Yanwen; Martínez, Pablo; Karahan, Hande; Chimal‑Juárez, Enrique; Johnson, Travis S.; Zhang, Jie; Resnick, Susan; Kim, Jungsu; Troncoso, Juan C.; Lasagna‑Reeves, Cristian A.; Medical and Molecular Genetics, School of Medicine
    Asymptomatic Alzheimer's disease (AsymAD) describes the status of individuals with preserved cognition but identifiable Alzheimer's disease (AD) brain pathology (i.e., beta-amyloid (Aβ) deposits, neuritic plaques, and neurofibrillary tangles) at autopsy. In this study, we investigated the postmortem brains of a cohort of AsymAD subjects to gain insight into the mechanisms underlying resilience to AD pathology and cognitive decline. Our results showed that AsymAD cases exhibit enrichment in core plaques, decreased filamentous plaque accumulation, and increased plaque-surrounding microglia. Less pathological tau aggregation in dystrophic neurites was found in AsymAD brains than in AD brains, and tau seeding activity was comparable to that in healthy brains. We used spatial transcriptomics to characterize the plaque niche further and revealed autophagy, endocytosis, and phagocytosis as the pathways associated with the genes upregulated in the AsymAD plaque niche. Furthermore, the levels of ARP2 and CAP1, which are actin-based motility proteins that participate in the dynamics of actin filaments to allow cell motility, were increased in the microglia surrounding amyloid plaques in AsymAD cases. Our findings suggest that the amyloid-plaque microenvironment in AsymAD cases is characterized by the presence of microglia with highly efficient actin-based cell motility mechanisms and decreased tau seeding compared with that in AD brains. These two mechanisms can potentially protect against the toxic cascade initiated by Aβ, preserving brain health, and slowing AD pathology progression.
  • Thumbnail Image
    Item
    Enhanced microglial dynamics and paucity of tau seeding in the amyloid plaque microenvironment contributes to cognitive resilience in Alzheimer’s disease
    (bioRxiv, 2023-07-28) Jury-Garfe, Nur; You, Yanwen; Martínez, Pablo; Redding-Ochoa, Javier; Karahan, Hande; Johnson, Travis S.; Zhan, Jie; Kim, Jungsu; Troncoso, Juan C.; Lasagna-Reeves, Cristian A.; Anatomy, Cell Biology and Physiology, School of Medicine
    Asymptomatic Alzheimer’s disease (AsymAD) describes the status of subjects with preserved cognition but with identifiable Alzheimer’s disease (AD) brain pathology (i.e. Aβ-amyloid deposits, neuritic plaques, and neurofibrillary tangles) at autopsy. In this study, we investigated the postmortem brains of a cohort of AsymAD cases to gain insight into the underlying mechanisms of resilience to AD pathology and cognitive decline. Our results showed that AsymAD cases exhibit an enrichment of core plaques and decreased filamentous plaque accumulation, as well as an increase in microglia surrounding this last type. In AsymAD cases we found less pathological tau aggregation in dystrophic neurites compared to AD and tau seeding activity comparable to healthy control subjects. We used spatial transcriptomics to further characterize the plaque niche and found autophagy, endocytosis, and phagocytosis within the top upregulated pathways in the AsymAD plaque niche, but not in AD. Furthermore, we found ARP2, an actin-based motility protein crucial to initiate the formation of new actin filaments, increased within microglia in the proximity of amyloid plaques in AsymAD. Our findings support that the amyloid-plaque microenvironment in AsymAD cases is characterized by microglia with highly efficient actin-based cell motility mechanisms and decreased tau seeding compared to AD. These two mechanisms can potentially provide protection against the toxic cascade initiated by Aβ that preserves brain health and slows down the progression of AD pathology.
  • Thumbnail Image
    Item
    Social Enrichment on the Job: Complex Work with People Improves Episodic Memory, Promotes Brain Reserve, and Reduces the Risk of Dementia
    (Wiley, 2023) Coleman, Max E.; Roessler, Meghan E. H.; Peng, Siyun; Roth, Adam R.; Risacher, Shannon L.; Saykin, Andrew J.; Apostolova, Liana G.; Perry, Brea L.; Radiology and Imaging Sciences, School of Medicine
    Individuals with more complex jobs experience better cognitive function in old age and a lower risk of dementia, yet complexity has multiple dimensions. Drawing on the Social Networks in Alzheimer Disease study, we examine the association between occupational complexity and cognition in a sample of older adults (N = 355). A standard deviation (SD) increase in complex work with people is associated with a 9% to 12% reduction in the probability of mild cognitive impairment or dementia, a 0.14-0.19 SD increase in episodic memory, and a 0.18-0.25 SD increase in brain reserve, defined as the gap (residual) between global cognitive function and magnetic resonance imaging (MRI) indicators of brain atrophy. In contrast, complexity with data or things is rarely associated with cognitive outcomes. We discuss the clinical and methodological implications of these findings, including the need to complement data-centered activities (e.g., Sudoku puzzles) with person-centered interventions that increase social complexity.
  • Thumbnail Image
    Item
    Social Networks and Cognitive Function: An Evaluation of Social Bridging and Bonding Mechanisms
    (Oxford University Press, 2022) Perry, Brea L.; McConnell, William R.; Peng, Siyun; Roth, Adam R.; Coleman, Max; Manchella, Mohit; Roessler, Meghann; Francis, Heather; Sheean, Hope; Apostolova, Liana A.; Radiology and Imaging Sciences, School of Medicine
    Background and objectives: Social connectedness has been linked prospectively to cognitive aging, but there is little agreement about the social mechanisms driving this relationship. This study evaluated 9 measures of social connectedness, focusing on 2 forms of social enrichment-access to an expansive and diverse set of loosely connected individuals (i.e., social bridging) and integration in a supportive network of close ties (i.e., social bonding). Research design and methods: This study used egocentric network and cognitive data from 311 older adults in the Social Networks in Alzheimer Disease study. Linear regressions were used to estimate the association between social connectedness and global cognitive function, episodic memory, and executive function. Results: Measures indicative of social bridging (larger network size, lower density, presence of weak ties, and proportion of non-kin) were consistently associated with better cognitive outcomes, while measures of social bonding (close ties, multiplex support, higher frequency of contact, better relationship quality, and being married) largely produced null effects. Discussion and implications: These findings suggest that the protective benefits of social connectedness for cognitive function and memory may operate primarily through a cognitive reserve mechanism that is driven by irregular contact with a larger and more diverse group of peripheral others.
  • Thumbnail Image
    Item
    Social Networks and Cognitive Reserve: Network Structure Moderates the Association Between Amygdalar Volume and Cognitive Outcomes
    (Oxford University Press, 2022) Perry, Brea L.; Roth, Adam R.; Peng, Siyun; Risacher, Shannon L.; Saykin, Andrew J.; Apostolova, Liana G.; Radiology and Imaging Sciences, School of Medicine
    Objectives: The cognitive reserve hypothesis has been proposed as a key mechanism explaining the link between social networks and cognitive function but has rarely been empirically tested using neuroimaging data. This study examines whether social network attributes moderate the association between amygdalar volume and cognitive function. Methods: Data were from the Social Networks in Alzheimer Disease study (N = 154) and Indiana Alzheimer's Disease Research Center. Social networks were measured using the PhenX Social Network Battery. Regional data from magnetic resonance imaging (amygdalar volume [AV]) were analyzed using FreeSurfer software. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and consensus diagnosis. Linear regression analyses were conducted to test the moderating role of social networks on the association between AV and cognitive function. Results: Participants with greater ability to span multiple social roles and subgroups within their networks scored higher on the MoCA after adjusting for sociodemographic variables, depression, frequency of contact, and AV. Social networks moderated the association between AV and cognitive function. Discussion: Among participants who engaged in diverse and loosely connected social networks, the expected adverse cognitive effects of brain volume in regions implicated in socioemotional processing were attenuated. These findings suggest that cognitive stimulation achieved through social interaction with a diverse array of social relationships across multiple contexts may help promote cognitive reserve.