10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Age‐related changes in cerebrovascular health and their effects on neural function and cognition: A comprehensive review

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The process of aging includes changes in cellular biology that affect local interactions between cells and their environments and eventually propagate to systemic levels. In the brain, where neurons critically depend on an efficient and dynamic supply of oxygen and glucose, age‐related changes in the complex interaction between the brain parenchyma and the cerebrovasculature have effects on health and functioning that negatively impact cognition and play a role in pathology. Thus, cerebrovascular health is considered one of the main mechanisms by which a healthy lifestyle, such as habitual cardiorespiratory exercise and a healthful diet, could lead to improved cognitive outcomes with aging. This review aims at detailing how the physiology of the cerebral vascular system changes with age and how these changes lead to differential trajectories of cognitive maintenance or decline. This provides a framework for generating specific mechanistic hypotheses about the efficacy of proposed interventions and lifestyle covariates that contribute to enhanced cognitive well‐being. Finally, we discuss the methodological implications of age‐related changes in the cerebral vasculature for human cognitive neuroscience research and propose directions for future experiments aimed at investigating age‐related changes in the relationship between physiology and cognitive mechanisms.

          Impact Statement

          In this comprehensive review, we discuss, in detail, the physiology of how the cerebrovasculature can change with age and how these changes lead to differences in cognitive outcomes. The review provides a framework for generating mechanistic hypotheses about the efficacy of proposed interventions and lifestyle covariates that contribute to enhanced cognitive well‐being in aging and discusses methodological issues in human cognitive aging research related to cerebrovascular physiology.

          Related collections

          Most cited references456

          • Record: found
          • Abstract: found
          • Article: not found

          Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

          Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty - which affect clinical manifestations, prognosis, and response to treatment - and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Complement and microglia mediate early synapse loss in Alzheimer mouse models.

            Synapse loss in Alzheimer's disease (AD) correlates with cognitive decline. Involvement of microglia and complement in AD has been attributed to neuroinflammation, prominent late in disease. Here we show in mouse models that complement and microglia mediate synaptic loss early in AD. C1q, the initiating protein of the classical complement cascade, is increased and associated with synapses before overt plaque deposition. Inhibition of C1q, C3, or the microglial complement receptor CR3 reduces the number of phagocytic microglia, as well as the extent of early synapse loss. C1q is necessary for the toxic effects of soluble β-amyloid (Aβ) oligomers on synapses and hippocampal long-term potentiation. Finally, microglia in adult brains engulf synaptic material in a CR3-dependent process when exposed to soluble Aβ oligomers. Together, these findings suggest that the complement-dependent pathway and microglia that prune excess synapses in development are inappropriately activated and mediate synapse loss in AD.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

              The blood-brain barrier (BBB) is a continuous endothelial membrane within brain microvessels that has sealed cell-to-cell contacts and is sheathed by mural vascular cells and perivascular astrocyte end-feet. The BBB protects neurons from factors present in the systemic circulation and maintains the highly regulated CNS internal milieu, which is required for proper synaptic and neuronal functioning. BBB disruption allows influx into the brain of neurotoxic blood-derived debris, cells and microbial pathogens and is associated with inflammatory and immune responses, which can initiate multiple pathways of neurodegeneration. This Review discusses neuroimaging studies in the living human brain and post-mortem tissue as well as biomarker studies demonstrating BBB breakdown in Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, multiple sclerosis, HIV-1-associated dementia and chronic traumatic encephalopathy. The pathogenic mechanisms by which BBB breakdown leads to neuronal injury, synaptic dysfunction, loss of neuronal connectivity and neurodegeneration are described. The importance of a healthy BBB for therapeutic drug delivery and the adverse effects of disease-initiated, pathological BBB breakdown in relation to brain delivery of neuropharmaceuticals are briefly discussed. Finally, future directions, gaps in the field and opportunities to control the course of neurological diseases by targeting the BBB are presented.
                Bookmark

                Author and article information

                Contributors
                bzimme5@illinois.edu , mfabiani@illinois.edu
                mfabiani@illinois.edu
                Journal
                Psychophysiology
                Psychophysiology
                10.1111/(ISSN)1469-8986
                PSYP
                Psychophysiology
                John Wiley and Sons Inc. (Hoboken )
                0048-5772
                1540-5958
                16 March 2021
                July 2021
                : 58
                : 7 , Aging and Cerebrovascular Health: Structural, Functional, Cognitive, and Methodological Implications ( doiID: 10.1111/psyp.v58.7 )
                : e13796
                Affiliations
                [ 1 ] Beckman Institute for Advanced Science and Technology University of Illinois at Urbana‐Champaign Urbana IL USA
                [ 2 ] School of Behavioral and Brain Sciences University of Texas at Dallas Richardson TX USA
                [ 3 ] Department of Psychiatry University of Texas Southwestern Medical Center Dallas TX USA
                [ 4 ] Department of Psychology University of Illinois at Urbana‐Champaign Champaign IL USA
                [ 5 ] Neuroscience Program University of Illinois at Urbana‐Champaign Champaign IL USA
                Author notes
                [*] [* ] Correspondence

                Benjamin Zimmerman and Monica Fabiani, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana‐Champaign, Urbana, IL, USA.

                Email: bzimme5@ 123456illinois.edu (B. Z.) and mfabiani@ 123456illinois.edu (M. F.)

                Author information
                https://orcid.org/0000-0003-2570-8198
                https://orcid.org/0000-0003-3634-7463
                https://orcid.org/0000-0002-7579-2773
                Article
                PSYP13796
                10.1111/psyp.13796
                8244108
                33728712
                720df9a0-1cca-4493-9402-c4a2c9eaf711
                © 2021 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 11 January 2021
                : 06 November 2020
                : 08 February 2021
                Page count
                Figures: 7, Tables: 1, Pages: 40, Words: 31998
                Funding
                Funded by: National Institute on Aging , open-funder-registry 10.13039/100000049;
                Award ID: R01AG047972
                Award ID: R01AG059878
                Award ID: RF1AG062666
                Funded by: Arnold and Mabel Beckman Foundation , open-funder-registry 10.13039/100000997;
                Categories
                Special Issue Title: Aging and Cerebrovascular Health: Structural, Functional, Cognitive, and Methodological Implications
                Introductory Review
                Custom metadata
                2.0
                July 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:30.06.2021

                Neurology
                aging,cerebrovascular health,cerebrovascular reactivity,cognitive aging,dementia,neurovascular coupling

                Comments

                Comment on this article