{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:33:04Z","timestamp":1791844384553,"version":"4.3.4"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging"],"abstract":"<jats:p>Loneliness, the subjective perception of inadequate social connection, is increasingly recognized as a significant and modifiable determinant of health with implications extending beyond psychosocial well-being to cardiovascular and cognitive outcomes. A growing body of evidence links loneliness to increased risk of cardiovascular disease, cognitive decline, and dementia; however, these domains have often been studied in parallel. This review advances a brain\u2013heart axis framework to integrate these literature, conceptualizing loneliness as a chronic psychosocial stressor that contributes to cognitive aging through interconnected neuroendocrine, autonomic, inflammatory, and vascular pathways. Loneliness is associated with sustained activation of stress-responsive systems, including the hypothalamic\u2013pituitary\u2013adrenal axis and sympathetic nervous system, leading to cumulative physiological burden, or allostatic load. These processes contribute to endothelial dysfunction, vascular injury, and increased risk of cardiovascular conditions, which in turn impair cerebral perfusion and promote neurodegeneration. In parallel, loneliness is associated with neurobiological effects, including hippocampal atrophy, neuroinflammation, and reduced cognitive reserve. Behavioral and psychological pathways further amplify these effects. This paper synthesizes epidemiologic, mechanistic, and clinical evidence to propose a multi-pathway model linking loneliness to cognitive aging through neurobiological and cardiovascular-mediated mechanisms, alongside behavioral and coping processes. Translational implications are discussed, positioning loneliness as a clinically actionable risk marker to support prevention and promote cognitive resilience in aging populations.<\/jats:p>","DOI":"10.3389\/fragi.2026.1856056","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:41:41Z","timestamp":1779169301000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Loneliness and cognitive aging: a brain-heart axis perspective on a modifiable risk"],"prefix":"10.3389","volume":"7","author":[{"given":"Alison","family":"Warren","sequence":"first","affiliation":[{"name":"Department of Clinical Research and Leadership, George Washington University School of Medicine and Health Sciences","place":["Washington, DC, United States"]},{"name":"Frame-Corr Laboratory","place":["Washington, DC, United States"]},{"name":"Department of Continuing Education, Harvard University Extension School","place":["Cambridge, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"B1","unstructured":"Care coordination\n          \n          \n          2025"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1002\/alz.12327","article-title":"Associations of loneliness with risk of Alzheimer\u2019s disease dementia in the Framingham Heart Study","volume":"17","author":"Akhter\u2010Khan","year":"2021","journal-title":"Alzheimers Dement."},{"key":"B3","doi-asserted-by":"publisher","first-page":"12871","DOI":"10.1038\/s41598-024-63528-4","article-title":"The impact of social isolation and loneliness on cardiovascular disease risk factors: a systematic review, meta-analysis, and bibliometric investigation","volume":"14","author":"Albasheer","year":"2024","journal-title":"Sci. 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