Systemic determinants of brain health in ageing

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Systemic determinants of brain health in ageing
  • World Health Organization. Optimizing brain health across the life course: WHO position paper (WHO, 2022).

  • Bassetti, C. L. A. et al. The European Academy of Neurology Brain Health Strategy: one brain, one life, one approach. Eur. J. Neurol. 29, 2559–2566 (2022).

    Article 
    PubMed 

    Google Scholar 

  • GBD 2019 Dementia Forecasting Collaborators. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health 7, e105–e125 (2022).

    Article 

    Google Scholar 

  • Cahill, S. WHO’s global action plan on the public health response to dementia: some challenges and opportunities. Aging Ment. Health 24, 197–199 (2020).

    Article 
    PubMed 

    Google Scholar 

  • Ross, C. A. & Poirier, M. A. Protein aggregation and neurodegenerative disease. Nat. Med. 10, S10–S17 (2004).

    Article 
    PubMed 

    Google Scholar 

  • van Dyck, C. H. et al. Lecanemab in early Alzheimer’s disease. N. Engl. J. Med. 388, 9–21 (2023).

    Article 
    PubMed 

    Google Scholar 

  • Mintun, M. A. et al. Donanemab in early Alzheimer’s disease. N. Engl. J. Med. 384, 1691–1704 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Livingston, G. et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet 396, 413–446 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ely, E. W., Siegel, M. D. & Inouye, S. K. Delirium in the intensive care unit: an under-recognized syndrome of organ dysfunction. Semin. Respir. Crit. Care Med. 22, 115–126 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wolters, F. J. et al. Coronary heart disease, heart failure, and the risk of dementia: a systematic review and meta-analysis. Alzheimers Dement. 14, 1493–1504 (2018).

    Article 
    PubMed 

    Google Scholar 

  • Tang, X. et al. Association of kidney function and brain health: a systematic review and meta-analysis of cohort studies. Ageing Res. Rev. 82, 101762 (2022).

    Article 
    PubMed 

    Google Scholar 

  • Pathan, S. S. et al. Association of lung function with cognitive decline and dementia: the Atherosclerosis Risk in Communities (ARIC) Study. Eur. J. Neurol. 18, 888–898 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Guay-Gagnon, M. et al. Sleep apnea and the risk of dementia: a systematic review and meta-analysis. J. Sleep Res. 31, e13589 (2022).

    Article 
    PubMed 

    Google Scholar 

  • Yuan, S. et al. Digestive system diseases, genetic risk, and incident dementia: a prospective cohort study. Am. J. Prev. Med. 66, 516–525 (2024).

    Article 
    PubMed 

    Google Scholar 

  • Parikh, N. S. et al. Association of liver fibrosis with cognitive test performance and brain imaging parameters in the UK Biobank study. Alzheimers Dement. 19, 1518–1528 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Xue, M. et al. Diabetes mellitus and risks of cognitive impairment and dementia: a systematic review and meta-analysis of 144 prospective studies. Ageing Res. Rev. 55, 100944 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Gorelick, P. B. et al. Defining optimal brain health in adults: a presidential advisory from the American Heart Association/American Stroke Association. Stroke 48, e284–e303 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Johansen, M. C. et al. Association between acute myocardial infarction and cognition. JAMA Neurol. 80, 723–731 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Xie, W., Zheng, F., Yan, L. & Zhong, B. Cognitive decline before and after incident coronary events. J. Am. Coll. Cardiol. 73, 3041–3050 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Greaves, D. et al. Cognitive outcomes following coronary artery bypass grafting: a systematic review and meta-analysis of 91,829 patients. Int. J. Cardiol. 289, 43–49 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Selnes, O. A. et al. Cognition 6 years after surgical or medical therapy for coronary artery disease. Ann. Neurol. 63, 581–590 (2008).

    Article 
    PubMed 

    Google Scholar 

  • Vishwanath, S. et al. Cognitive decline and risk of dementia in individuals with heart failure: a systematic review and meta-analysis. J. Card. Fail. 28, 1337–1348 (2022).

    Article 
    PubMed 

    Google Scholar 

  • Kamel, H. et al. Atrial cardiopathy and the risk of ischemic stroke in the CHS (Cardiovascular Health Study). Stroke 49, 980–986 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kamel, H. et al. Association between left atrial abnormality on ECG and vascular brain injury on MRI in the Cardiovascular Health Study. Stroke 46, 711–716 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Johansen, M. C. et al. Risk of dementia associated with atrial cardiopathy: the ARIC study. J. Am. Heart Assoc. 11, e025646 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Johansen, M. C. et al. Associations of echocardiography markers and vascular brain lesions: the ARIC Study. J. Am. Heart Assoc. 7, e008992 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yoshida, Y. et al. Subclinical left ventricular systolic dysfunction and incident stroke in the elderly: long-term findings from cardiovascular abnormalities and brain lesions. Eur. Heart J. Cardiovasc. Imaging 24, 522–531 (2023).

    Article 
    PubMed 

    Google Scholar 

  • Debette, S., Schilling, S., Duperron, M. G., Larsson, S. C. & Markus, H. S. Clinical significance of magnetic resonance imaging markers of vascular brain injury: a systematic review and meta-analysis. JAMA Neurol. 76, 81–94 (2018).

    Article 
    PubMed Central 

    Google Scholar 

  • Mejia-Renteria, H. et al. Coronary microvascular dysfunction is associated with impaired cognitive function: the Cerebral-Coronary Connection study (C3 study). Eur. Heart J. 44, 113–125 (2023).

    Article 
    PubMed 

    Google Scholar 

  • Levin, A. & Stevens, P. E. Summary of KDIGO 2012 CKD guideline: behind the scenes, need for guidance, and a framework for moving forward. Kidney Int. 85, 49–61 (2014).

    Article 
    PubMed 

    Google Scholar 

  • GBD Chronic Kidney Disease Collaboration. Collaboration. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 395, 709–733 (2020).

    Article 

    Google Scholar 

  • Trocchi, P., Girndt, M., Scheidt-Nave, C., Markau, S. & Stang, A. Impact of the estimation equation for GFR on population-based prevalence estimates of kidney dysfunction. BMC Nephrol. 18, 341 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kar, S., Paglialunga, S. & Islam, R. Cystatin C is a more reliable biomarker for determining eGFR to support drug development studies. J. Clin. Pharmacol. 58, 1239–1247 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Scheppach, J. B. et al. Albuminuria and estimated GFR as risk factors for dementia in midlife and older age: findings from the ARIC study. Am. J. Kidney Dis. 76, 775–783 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Nam, G. E. et al. Chronic renal dysfunction, proteinuria, and risk of Parkinson’s disease in the elderly. Mov. Disord. 34, 1184–1191 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Scheppach, J. B. et al. Association of kidney function measures with signs of neurodegeneration and small vessel disease on brain magnetic resonance imaging: the atherosclerosis risk in communities (ARIC) study. Am. J. Kidney Dis. 81, 261–269.e1 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sedaghat, S. et al. The association of kidney function with plasma amyloid-β levels and brain amyloid deposition. J. Alzheimers Dis. 92, 229–239 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Janelidze, S., Barthelemy, N. R., He, Y., Bateman, R. J. & Hansson, O. Mitigating the associations of kidney dysfunction with blood biomarkers of Alzheimer disease by using phosphorylated tau to total tau ratios. JAMA Neurol. 80, 516–522 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Lutsey, P. L. et al. Impaired lung function, lung disease, and risk of incident dementia. Am. J. Respir. Crit. Care Med. 199, 1385–1396 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Xiao, T. et al. Lung function impairment and the risk of incident dementia: the Rotterdam study. J. Alzheimers Dis. 82, 621–630 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Peng, Y. H. et al. Adult asthma increases dementia risk: a nationwide cohort study. J. Epidemiol. Community Health 69, 123–128 (2015).

    Article 
    PubMed 

    Google Scholar 

  • Frenzel, S. et al. Associations of pulmonary function with MRI brain volumes: a coordinated multi-study analysis. J. Alzheimers Dis. 90, 1073–1083 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zhang, B. et al. Inflammatory bowel disease is associated with higher dementia risk: a nationwide longitudinal study. Gut 70, 85–91 (2021).

    Article 
    PubMed 

    Google Scholar 

  • Gau, S. Y., Lai, J. N., Yip, H. T., Wu, M. C. & Wei, J. C. Higher dementia risk in people with gastroesophageal reflux disease: a real-world evidence. Front. Aging Neurosci. 14, 830729 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chen, C. H., Lin, C. L. & Kao, C. H. Irritable bowel syndrome is associated with an increased risk of dementia: a nationwide population-based study. PLoS ONE 11, e0144589 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Cryan, J. F. et al. The microbiota-gut-brain axis. Physiol. Rev. 99, 1877–2013 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Adewuyi, E. O., O’Brien, E. K., Nyholt, D. R., Porter, T. & Laws, S. M. A large-scale genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer’s disease and gastrointestinal tract disorders. Commun. Biol. 5, 691 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Vogt, N. M. et al. Gut microbiome alterations in Alzheimer’s disease. Sci. Rep. 7, 13537 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Seo, D. O. et al. ApoE isoform- and microbiota-dependent progression of neurodegeneration in a mouse model of tauopathy. Science 379, eadd1236 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dodiya, H. B. et al. Synergistic depletion of gut microbial consortia, but not individual antibiotics, reduces amyloidosis in APPPS1-21 Alzheimer’s transgenic mice. Sci. Rep. 10, 8183 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Warnecke, T., Schafer, K. H., Claus, I., Del Tredici, K. & Jost, W. H. Gastrointestinal involvement in Parkinson’s disease: pathophysiology, diagnosis, and management. NPJ Parkinsons Dis. 8, 31 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hu, W. et al. Autonomic symptoms are predictive of dementia with Lewy bodies. Parkinsonism Relat. Disord. 95, 1–4 (2022).

    Article 
    PubMed 

    Google Scholar 

  • Doi, H. et al. Gastrointestinal function in dementia with Lewy bodies: a comparison with Parkinson disease. Clin. Auton. Res. 29, 633–638 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Camacho, M. et al. Early constipation predicts faster dementia onset in Parkinson’s disease. NPJ Parkinsons Dis. 7, 45 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Braak, H. et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol. Aging 24, 197–211 (2003).

    Article 
    PubMed 

    Google Scholar 

  • Matteoni, C. A. et al. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 116, 1413–1419 (1999).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sanyal, A. J. Past, present and future perspectives in nonalcoholic fatty liver disease. Nat. Rev. Gastroenterol. Hepatol. 16, 377–386 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Harris, R., Harman, D. J., Card, T. R., Aithal, G. P. & Guha, I. N. Prevalence of clinically significant liver disease within the general population, as defined by non-invasive markers of liver fibrosis: a systematic review. Lancet Gastroenterol. Hepatol. 2, 288–297 (2017).

    Article 
    PubMed 

    Google Scholar 

  • Allwright, M. et al. Ranking the risk factors for Alzheimer’s disease; findings from the UK Biobank study. Aging Brain 3, 100081 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Xiao, T., van Kleef, L. A., Ikram, M. K., de Knegt, R. J. & Ikram, M. A. Association of nonalcoholic fatty liver disease and fibrosis with incident dementia and cognition: the Rotterdam study. Neurology 99, e565–e573 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Shang, Y. et al. Non-alcoholic fatty liver disease does not increase dementia risk although histology data might improve risk prediction. JHEP Rep. 3, 100218 (2021).

    Article 
    PubMed 

    Google Scholar 

  • Weinstein, G. et al. Nonalcoholic fatty liver disease, liver fibrosis, and structural brain imaging: the Cross-Cohort Collaboration. Eur. J. Neurol. 31, e16048 (2024).

    Article 
    PubMed 

    Google Scholar 

  • Parikh, N. S. et al. Association between liver fibrosis and incident dementia in the UK Biobank study. Eur. J. Neurol. 29, 2622–2630 (2022).

    Article 
    PubMed 

    Google Scholar 

  • Weinstein, G. et al. Non-alcoholic fatty liver disease, liver fibrosis, and regional amyloid-β and tau pathology in middle-aged adults: the Framingham study. J. Alzheimers Dis. 86, 1371–1383 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Jeong, S. M. et al. Favorable impact of non-alcoholic fatty liver disease on the cerebral white matter hyperintensity in a neurologically healthy population. Eur. J. Neurol. 26, 1471–1478 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Jang, H. et al. Non-alcoholic fatty liver disease and cerebral small vessel disease in Korean cognitively normal individuals. Sci. Rep. 9, 1814 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Petta, S. et al. The presence of white matter lesions is associated with the fibrosis severity of nonalcoholic fatty liver disease. Medicine 95, e3446 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yan, M. et al. Gut liver brain axis in diseases: the implications for therapeutic interventions. Signal. Transduct. Target. Ther. 8, 443 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hiller-Sturmhofel, S. & Bartke, A. The endocrine system: an overview. Alcohol Health Res. World 22, 153–164 (1998).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Biessels, G. J. & Despa, F. Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications. Nat. Rev. Endocrinol. 14, 591–604 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Crane, P. K. et al. Glucose levels and risk of dementia. N. Engl. J. Med. 369, 540–548 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Moran, C. et al. Glycemic control over multiple decades and dementia risk in people with type 2 diabetes. JAMA Neurol. 80, 597–604 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gottesman, R. F. et al. Association between midlife vascular risk factors and estimated brain amyloid deposition. JAMA 317, 1443–1450 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Moran, C. et al. Type 2 diabetes mellitus and biomarkers of neurodegeneration. Neurology 85, 1123–1130 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Abner, E. L. et al. Diabetes is associated with cerebrovascular but not Alzheimer’s disease neuropathology. Alzheimers Dement. 12, 882–889 (2016).

    Article 
    PubMed 

    Google Scholar 

  • Dos Santos Matioli, M. N. P. et al. Diabetes is not associated with Alzheimer’s disease neuropathology. J. Alzheimers Dis. 60, 1035–1043 (2017).

    Article 
    PubMed 

    Google Scholar 

  • Takenoshita, N. et al. Amyloid and tau positron emission tomography in suggested diabetesrelated dementia. Curr. Alzheimer Res. 15, 1062–1069 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Priest, C. & Tontonoz, P. Inter-organ cross-talk in metabolic syndrome. Nat. Metab. 1, 1177–1188 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Davidson, T. L. & Stevenson, R. J. Vulnerability of the hippocampus to insults: links to blood-brain barrier dysfunction. Int. J. Mol. Sci. 25, 1991 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Raz, L. et al. Hypoxia promotes tau hyperphosphorylation with associated neuropathology in vascular dysfunction. Neurobiol. Dis. 126, 124–136 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bailey, D. M. et al. Hypoxemia increases blood-brain barrier permeability during extreme apnea in humans. J. Cereb. Blood Flow Metab. 42, 1120–1135 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wardlaw, J. M., Smith, C. & Dichgans, M. Small vessel disease: mechanisms and clinical implications. Lancet Neurol. 18, 684–696 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Ding, H. et al. Hypercapnia exacerbates the disruption of the blood-brain barrier by inducing interleukin-1β overproduction in the blood of hypoxemic adult rats. Int. J. Mol. Med. 46, 762–772 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yang, W. et al. Effects of acute systemic hypoxia and hypercapnia on brain damage in a rat model of hypoxia-ischemia. PLoS ONE 11, e0167359 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Dodd, J. W., Getov, S. V. & Jones, P. W. Cognitive function in COPD. Eur. Respir. J. 35, 913–922 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Shim, T. S. et al. Cerebral metabolic abnormalities in COPD patients detected by localized proton magnetic resonance spectroscopy. Chest 120, 1506–1513 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Li, H. et al. Abnormal intrinsic functional hubs and connectivity in stable patients with COPD: a resting-state MRI study. Brain Imaging Behav. 14, 573–585 (2020).

    Article 
    PubMed 

    Google Scholar 

  • King, P. T. Inflammation in chronic obstructive pulmonary disease and its role in cardiovascular disease and lung cancer. Clin. Transl. Med. 4, 68 (2015).

    Article 
    PubMed 

    Google Scholar 

  • Rajendran, P. et al. The vascular endothelium and human diseases. Int. J. Biol. Sci. 9, 1057–1069 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Iadecola, C. The pathobiology of vascular dementia. Neuron 80, 844–866 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Schaeffer, S. & Iadecola, C. Revisiting the neurovascular unit. Nat. Neurosci. 24, 1198–1209 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wei, H. et al. Vascular endothelial cells: a fundamental approach for brain waste clearance. Brain 146, 1299–1315 (2023).

    Article 
    PubMed 

    Google Scholar 

  • Iadecola, C. et al. The neurovasculome: key roles in brain health and cognitive impairment: a scientific statement from the American Heart Association/ American Stroke Association. Stroke 54, e251–e271 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Katusic, Z. S., d’Uscio, L. V. & He, T. Emerging roles of endothelial nitric oxide in preservation of cognitive health. Stroke 54, 686–696 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Nasiri-Ansari, N. et al. Endothelial cell dysfunction and nonalcoholic fatty liver disease (NAFLD): a concise review. Cells 11, 2511 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Xu, S. et al. Endothelial dysfunction in atherosclerotic cardiovascular diseases and beyond: from mechanism to pharmacotherapies. Pharmacol. Rev. 73, 924–967 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Roumeliotis, S., Mallamaci, F. & Zoccali, C. Endothelial dysfunction in chronic kidney disease, from biology to clinical outcomes: a 2020 update. J. Clin. Med. 9, 2359 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Gallo, G. & Savoia, C. New insights into endothelial dysfunction in cardiometabolic diseases: potential mechanisms and clinical implications. Int. J. Mol. Sci. 25, 2973 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Badji, A., Cohen-Adad, J. & Girouard, H. Relationship between arterial stiffness index, pulse pressure, and magnetic resonance imaging markers of white matter integrity: a UK Biobank study. Front. Aging Neurosci. 14, 856782 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zanoli, L. et al. Vascular consequences of inflammation: a position statement from the ESH Working Group on Vascular Structure and Function and the ARTERY Society. J. Hypertension 38, 1682–1698 (2020).

    Article 
    CAS 

    Google Scholar 

  • Wilkinson, I. B., Franklin, S. S. & Cockcroft, J. R. Nitric oxide and the regulation of large artery stiffness: from physiology to pharmacology. Hypertension 44, 112–116 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Lacolley, P., Regnault, V. & Laurent, S. Mechanisms of arterial stiffening: from mechanotransduction to epigenetics. Arterioscler. Thromb. Vasc. Biol. 40, 1055–1062 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Arai, K. & Lo, E. H. Wiring and plumbing: oligodendrocyte precursors and angiogenesis in the oligovascular niche. J. Cereb. Blood Flow Metab. 41, 2132–2133 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Yousef, H. et al. Aged blood impairs hippocampal neural precursor activity and activates microglia via brain endothelial cell VCAM1. Nat. Med. 25, 988–1000 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Toya, T. et al. Impact of peripheral microvascular endothelial dysfunction on white matter hyperintensity. J. Am. Heart Assoc. 10, e021066 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Khatri, M. et al. Chronic kidney disease is associated with white matter hyperintensity volume: the Northern Manhattan Study (NOMAS). Stroke 38, 3121–3126 (2007).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Moroni, F. et al. Cardiovascular disease and brain health: focus on white matter hyperintensities. Int. J. Cardiol. Heart Vasc. 19, 63–69 (2018).

    PubMed 
    PubMed Central 

    Google Scholar 

  • Dight, J., Zhao, J., Styke, C., Khosrotehrani, K. & Patel, J. Resident vascular endothelial progenitor definition and function: the age of reckoning. Angiogenesis 25, 15–33 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Han, Y. & Kim, S. Y. Endothelial senescence in vascular diseases: current understanding and future opportunities in senotherapeutics. Exp. Mol. Med. 55, 1–12 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Faraco, G. et al. Dietary salt promotes cognitive impairment through tau phosphorylation. Nature 574, 686–690 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kresge, H. A. et al. Subclinical compromise in cardiac strain relates to lower cognitive performances in older adults. J. Am. Heart Assoc. 7, e007562 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Moore, E. E. & Jefferson, A. L. Impact of cardiovascular hemodynamics on cognitive aging. Atheroscler. Thromb. Vasc. Biol. 41, 1255–1264 (2021).

    Article 
    CAS 

    Google Scholar 

  • van Osch, M. J. P. et al. Human brain clearance imaging: pathways taken by magnetic resonance imaging contrast agents after administration in cerebrospinal fluid and blood. NMR Biomed. 37, e5159 (2024).

    Article 
    PubMed 

    Google Scholar 

  • Agarwal, N. et al. Current understanding of the anatomy, physiology, and magnetic resonance imaging of neurofluids: update from the 2022 “ISMRM Imaging Neurofluids Study group” workshop in Rome. J. Magn. Reson. Imaging 59, 431–449 (2024).

    Article 
    PubMed 

    Google Scholar 

  • Licastro, E. et al. Glymphatic and lymphatic communication with systemic responses during physiological and pathological conditions in the central nervous system. Commun. Biol. 7, 229 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rego, S., Sanchez, G. & Da Mesquita, S. Current views on meningeal lymphatics and immunity in aging and Alzheimer’s disease. Mol. Neurodegener. 18, 55 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Moonen, J. E. F. et al. Contributions of amyloid beta and cerebral small vessel disease in clinical decline. Alzheimers Dement. 20, 1868–1880 (2024).

    Article 
    PubMed 

    Google Scholar 

  • Pacholko, A. & Iadecola, C. Hypertension, neurodegeneration, and cognitive decline. Hypertension 81, 991–1007 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Coomans, E. M. et al. Interactions between vascular burden and amyloid-β pathology on trajectories of tau accumulation. Brain 147, 949–960 (2024).

    Article 
    PubMed 

    Google Scholar 

  • Yau, W. W. et al. Tau mediates synergistic influence of vascular risk and Aβ on cognitive decline. Ann. Neurol. 92, 745–755 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Nho, K. et al. Altered bile acid profile in mild cognitive impairment and Alzheimer’s disease: relationship to neuroimaging and CSF biomarkers. Alzheimers Dement. 15, 232–244 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Nho, K. et al. Association of altered liver enzymes with alzheimer disease diagnosis, cognition, neuroimaging measures, and cerebrospinal fluid biomarkers. JAMA Netw. Open 2, e197978 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Myers, S. J., Jimenez-Ruiz, A., Sposato, L. A. & Whitehead, S. N. Atrial cardiopathy and cognitive impairment. Front. Aging Neurosci. 14, 914360 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Roberts, K. F. et al. Amyloid-β efflux from the central nervous system into the plasma. Ann. Neurol. 76, 837–844 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tian, D. Y. et al. Physiological clearance of amyloid-beta by the kidney and its therapeutic potential for Alzheimer’s disease. Mol. Psychiatry 26, 6074–6082 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Xiang, Y. et al. Physiological amyloid-beta clearance in the periphery and its therapeutic potential for Alzheimer’s disease. Acta Neuropathol. 130, 487–499 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Liu, Y. H. et al. Association between serum amyloid-beta and renal functions: implications for roles of kidney in amyloid-beta clearance. Mol. Neurobiol. 52, 115–119 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Wang, Y.-R. et al. Associations between hepatic functions and plasma amyloid-beta levels — implications for the capacity of liver in peripheral amyloid-beta clearance. Mol. Neurobiol. 54, 2338–2344 (2016).

    Article 
    PubMed 

    Google Scholar 

  • Cheng, Y. et al. Physiological β-amyloid clearance by the liver and its therapeutic potential for Alzheimer’s disease. Acta Neuropathol. 145, 717–731 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Chen, Y., Strickland, M. R., Soranno, A. & Holtzman, D. M. Apolipoprotein E: structural insights and links to Alzheimer disease pathogenesis. Neuron 109, 205–221 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Nascimento, J. C. R. et al. Impact of apolipoprotein E genetic polymorphisms on liver disease: an essential review. Ann. Hepatol. 19, 24–30 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Liu, C. C. et al. Peripheral apoE4 enhances Alzheimer’s pathology and impairs cognition by compromising cerebrovascular function. Nat. Neurosci. 25, 1020–1033 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ehtezazi, T., Rahman, K., Davies, R. & Leach, A. G. The pathological effects of circulating hydrophobic bile acids in Alzheimer’s disease. J. Alzheimers Dis. Rep. 7, 173–211 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Horowitz, A. M. et al. Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain. Science 369, 167–173 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Shi, M. et al. CNS tau efflux via exosomes is likely increased in Parkinson disease but not in Alzheimer disease. Alzheimers Dement. 12, 1125–1131 (2016).

    Article 
    PubMed 

    Google Scholar 

  • Tarasoff-Conway, J. M. et al. Clearance systems in the brain-implications for Alzheimer disease. Nat. Rev. Neurol. 11, 457–470 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, J. et al. Physiological clearance of tau in the periphery and its therapeutic potential for tauopathies. Acta Neuropathol. 136, 525–536 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Mielke, M. M. et al. Performance of plasma phosphorylated tau 181 and 217 in the community. Nat. Med. 28, 1398–1405 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Semmler, A. et al. Sepsis causes neuroinflammation and concomitant decrease of cerebral metabolism. J. Neuroinflammation 5, 38 (2008).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Rankin, L. C. & Artis, D. Beyond host defense: emerging functions of the immune system in regulating complex tissue physiology. Cell 173, 554–567 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Rock, K. L., Latz, E., Ontiveros, F. & Kono, H. The sterile inflammatory response. Annu. Rev. Immunol. 28, 321–342 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • van Eeden, S. F. & Sin, D. D. Chronic obstructive pulmonary disease: a chronic systemic inflammatory disease. Respiration 75, 224–238 (2008).

    Article 
    PubMed 

    Google Scholar 

  • Benakis, C. et al. The microbiome-gut-brain axis in acute and chronic brain diseases. Curr. Opin. Neurobiol. 61, 1–9 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Chen, L. et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 9, 7204–7218 (2018).

    Article 
    PubMed 

    Google Scholar 

  • Furman, D. et al. Chronic inflammation in the etiology of disease across the life span. Nat. Med. 25, 1822–1832 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Venereau, E., Ceriotti, C. & Bianchi, M. E. DAMPs from cell death to new life. Front. Immunol. 6, 422 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Zindel, J. & Kubes, P. DAMPs, PAMPs, and LAMPs in immunity and sterile inflammation. Annu. Rev. Pathol. 15, 493–518 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Oudijk, E. J., Lammers, J. W. & Koenderman, L. Systemic inflammation in chronic obstructive pulmonary disease. Eur. Respir. J. Suppl. 46, 5s–13s (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Brezzo, G., Simpson, J., Ameen-Ali, K. E., Berwick, J. & Martin, C. Acute effects of systemic inflammation upon the neuro-glial-vascular unit and cerebrovascular function. Brain Behav. Immun. Health 5, 100074 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Pober, J. S. & Sessa, W. C. Evolving functions of endothelial cells in inflammation. Nat. Rev. Immunol. 7, 803–815 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Amersfoort, J., Eelen, G. & Carmeliet, P. Immunomodulation by endothelial cells — partnering up with the immune system? Nat. Rev. Immunol. 22, 576–588 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Chen, B. R., Kozberg, M. G., Bouchard, M. B., Shaik, M. A. & Hillman, E. M. A critical role for the vascular endothelium in functional neurovascular coupling in the brain. J. Am. Heart Assoc. 3, e000787 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Smith, B. C., Tinkey, R. A., Shaw, B. C. & Williams, J. L. Targetability of the neurovascular unit in inflammatory diseases of the central nervous system. Immunol. Rev. 311, 39–49 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tarantini, S., Tran, C. H. T., Gordon, G. R., Ungvari, Z. & Csiszar, A. Impaired neurovascular coupling in aging and Alzheimer’s disease: contribution of astrocyte dysfunction and endothelial impairment to cognitive decline. Exp. Gerontol. 94, 52–58 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Iadecola, C. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron 96, 17–42 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Banks, W. A., Kastin, A. J. & Broadwell, R. D. Passage of cytokines across the blood-brain barrier. Neuroimmunomodulation 2, 241–248 (1995).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Sama, M. A. et al. Interleukin-1β-dependent signaling between astrocytes and neurons depends critically on astrocytic calcineurin/NFAT activity. J. Biol. Chem. 283, 21953–21964 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Xie, D. et al. IL-1β induces hypomyelination in the periventricular white matter through inhibition of oligodendrocyte progenitor cell maturation via FYN/MEK/ERK signaling pathway in septic neonatal rats. Glia 64, 583–602 (2016).

    Article 
    PubMed 

    Google Scholar 

  • Zelenay, S. & Reis e Sousa, C. Adaptive immunity after cell death. Trends Immunol. 34, 329–335 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Cramer, J. V., Benakis, C. & Liesz, A. T cells in the post-ischemic brain: troopers or paramedics? J. Neuroimmunol. 326, 33–37 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Kunzli, M. & Masopust, D. CD4+ T cell memory. Nat. Immunol. 24, 903–914 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Netea, M. G. et al. Trained immunity: a program of innate immune memory in health and disease. Science 352, aaf1098 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • van Zeventer, I. A. et al. Prevalence, predictors, and outcomes of clonal hematopoiesis in individuals aged >/=80 years. Blood Adv. 5, 2115–2122 (2021).

    Article 
    PubMed 

    Google Scholar 

  • Avagyan, S. & Zon, L. I. Clonal hematopoiesis and inflammation — the perpetual cycle. Trends Cell Biol. 33, 695–707 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Bouzid, H. et al. Clonal hematopoiesis is associated with protection from Alzheimer’s disease. Nat. Med. 29, 1662–1670 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Santisteban, M. M. et al. Meningeal interleukin-17-producing T cells mediate cognitive impairment in a mouse model of salt-sensitive hypertension. Nat. Neurosci. 27, 63–77 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Uekawa, K. et al. Border-associated macrophages promote cerebral amyloid angiopathy and cognitive impairment through vascular oxidative stress. Mol. Neurodegener. 18, 73 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Schonhoff, A. M. et al. Border-associated macrophages mediate the neuroinflammatory response in an alpha-synuclein model of Parkinson disease. Nat. Commun. 14, 3754 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Mildenberger, W., Stifter, S. A. & Greter, M. Diversity and function of brain-associated macrophages. Curr. Opin. Immunol. 76, 102181 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • De Maeyer, R. P. H. & Chambers, E. S. The impact of ageing on monocytes and macrophages. Immunol. Lett. 230, 1–10 (2021).

    Article 
    PubMed 

    Google Scholar 

  • Franceschi, C. & Campisi, J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J. Gerontol. A Biol. Sci. Med. Sci. 69, S4–9 (2014).

    Article 
    PubMed 

    Google Scholar 

  • Huber, J. D., Campos, C. R., Mark, K. S. & Davis, T. P. Alterations in blood-brain barrier ICAM-1 expression and brain microglial activation after λ-carrageenan-induced inflammatory pain. Am. J. Physiol. Heart Circ. Physiol. 290, H732–H740 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Purchiaroni, F. et al. The role of intestinal microbiota and the immune system. Eur. Rev. Med. Pharmacol. Sci. 17, 323–333 (2013).

    CAS 
    PubMed 

    Google Scholar 

  • Lynch, S. V., Ng, S. C., Shanahan, F. & Tilg, H. Translating the gut microbiome: ready for the clinic? Nat. Rev. Gastroenterol. Hepatol. 16, 656–661 (2019).

    Article 
    PubMed 

    Google Scholar 

  • Violi, F., Castellani, V., Menichelli, D., Pignatelli, P. & Pastori, D. Gut barrier dysfunction and endotoxemia in heart failure: a dangerous connubium? Am. Heart J. 264, 40–48 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hufnagl, K., Pali-Scholl, I., Roth-Walter, F. & Jensen-Jarolim, E. Dysbiosis of the gut and lung microbiome has a role in asthma. Semin. Immunopathol. 42, 75–93 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wieland, A., Frank, D. N., Harnke, B. & Bambha, K. Systematic review: microbial dysbiosis and nonalcoholic fatty liver disease. Alimentary Pharmacol. Ther. 42, 1051–1063 (2015).

    Article 
    CAS 

    Google Scholar 

  • Sharma, S. & Tripathi, P. Gut microbiome and type 2 diabetes: where we are and where to go? J. Nutr. Biochem. 63, 101–108 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Hosang, L. et al. The lung microbiome regulates brain autoimmunity. Nature 603, 138–144 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Colombo, A. V. et al. Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition. eLife 10, e59826 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Aho, V. T. E. et al. Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson’s disease. Mol. Neurodegener. 16, 6 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Ho, L. et al. Protective roles of intestinal microbiota derived short chain fatty acids in Alzheimer’s disease-type beta-amyloid neuropathological mechanisms. Expert Rev. Neurother. 18, 83–90 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Han, Y. et al. Vagus nerve and underlying impact on the gut microbiota-brain axis in behavior and neurodegenerative diseases. J. Inflamm. Res. 15, 6213–6230 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Tan, A. H., Lim, S. Y. & Lang, A. E. The microbiome-gut-brain axis in Parkinson disease — from basic research to the clinic. Nat. Rev. Neurol. 18, 476–495 (2022).

    Article 
    PubMed 

    Google Scholar 

  • Svensson, E. et al. Vagotomy and subsequent risk of Parkinson’s disease. Ann. Neurol. 78, 522–529 (2015).

    Article 
    PubMed 

    Google Scholar 

  • Kim, S. et al. Transneuronal propagation of pathologic α-synuclein from the gut to the brain models Parkinson’s disease. Neuron 103, 627–641.e7 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kjelvik, G. et al. Public knowledge about dementia risk reduction in Norway. BMC Public Health 22, 2046 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • De Krom, F. J. W. et al. Awareness of dementia risk reduction among current and future healthcare professionals: a survey study. J. Public Health Res. 10, 1961 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Harkness, K. et al. Cognitive function and self-care management in older patients with heart failure. Eur. J. Cardiovasc. Nurs. 13, 277–284 (2014).

    Article 
    PubMed 

    Google Scholar 

  • van Nieuwkerk, A. C. et al. Cognitive impairment in patients with cardiac disease: implications for clinical practice. Stroke 54, 2181–2191 (2023).

    Article 
    PubMed 

    Google Scholar 

  • Wong, M. D., Shapiro, M. F., Boscardin, W. J. & Ettner, S. L. Contribution of major diseases to disparities in mortality. N. Engl. J. Med. 347, 1585–1592 (2002).

    Article 
    PubMed 

    Google Scholar 

  • Barthelemy, N. R. et al. Highly accurate blood test for Alzheimer’s disease is similar or superior to clinical cerebrospinal fluid tests. Nat. Med. 30, 1085–1095 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Okuzumi, A. et al. Propagative α-synuclein seeds as serum biomarkers for synucleinopathies. Nat. Med. 29, 1448–1455 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wolters, F. J. et al. Twenty-seven-year time trends in dementia incidence in Europe and the United States: the Alzheimer cohorts consortium. Neurology 95, e519–e531 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Wang, L. et al. Trends in prevalence of diabetes and control of risk factors in diabetes among US adults, 1999-2018. JAMA 326, 1–13 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • An, E. et al. Stress-resilience impacts psychological wellbeing as evidenced by brain–gut microbiome interactions. Nat. Ment. Health 2, 935–950 (2024).

    Article 

    Google Scholar 

  • Oh, H. S. et al. Organ aging signatures in the plasma proteome track health and disease. Nature 624, 164–172 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Whitlock, E. L. et al. Association of coronary artery bypass grafting vs percutaneous coronary intervention with memory decline in older adults undergoing coronary revascularization. JAMA 325, 1955–1964 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Kalantarian, S., Stern, T. A., Mansour, M. & Ruskin, J. N. Cognitive impairment associated with atrial fibrillation: a meta-analysis. Ann. Intern. Med. 158, 338–346 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Johansen, M. C. et al. Risk of dementia associated with atrial cardiopathy: the ARIC study. JAHA 11, e025646 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Hort, J. et al. EFNS guidelines for the diagnosis and management of Alzheimer’s disease. Eur. J. Neurol. 17, 1236–1248 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Johansen, M. C. et al. Associations between left ventricular structure, function, and cerebral amyloid: the ARIC-PET study. Stroke 50, 3622–3624 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  • Sible, I. J., Nation, D. A. & Alzheimer’s Disease Neuroimaging Initiative. Visit-to-visit blood pressure variability and longitudinal tau accumulation in older adults. Hypertension 79, 629–637 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Biessels, G. J., Nobili, F., Teunissen, C. E., Simo, R. & Scheltens, P. Understanding multifactorial brain changes in type 2 diabetes: a biomarker perspective. Lancet Neurol. 19, 699–710 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar 

  • Nelson, P. T. et al. Human cerebral neuropathology of type 2 diabetes mellitus. Biochim. Biophys. Acta 1792, 454–469 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar 

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