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Insulin-like growth factor 1 (IGF-1) is a peptide growth hormone crucial for neurogenesis and neuroprotection. Findings regarding potential involvement of IGF-1 in dementia have been conflicting, and the status of IGF-1 in clinical cohorts with Alzheimer\u2019s disease (AD) and concomitant cerebrovascular disease (CeVD) burden is unknown. A Singapore-based memory clinic cohort consisting of 46 non-cognitively impaired (NCI), 101 with cognitive impairment, no dementia (CIND) and 81 AD dementia subjects underwent plasma IGF-1 measurements and neuroimaging assessments for association analyses of peripheral IGF-1 with regional brain volumes, as well as with neuroimaging CeVD markers (lacunes, cerebral microbleeds, white matter hyperintensities). Plasma IGF-1 levels were significantly lower in AD compared to NCI and CIND participants (both p &lt; 0.001). Plasma IGF-1 was significantly associated with smaller hippocampal (p = 0.035), amygdala (p = 0.024), parietal lobe (p = 0.029), and frontal lobe (p = 0.002) volumes. In contrast, plasma IGF-1 did not associate with CeVD markers after covariate adjustments. Our findings suggest that plasma IGF-1 may be a blood-based biomarker for reduced brain volumes, while having no direct role in CeVD pathophysiology.<\/jats:p>","DOI":"10.3390\/biom16091248","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:27:46Z","timestamp":1787920066000},"page":"1248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Decreased Plasma IGF-1 Is Associated with Cortical Atrophy, but Not Concomitant Cerebrovascular Disease in Alzheimer\u2019s Dementia"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2117-3859","authenticated-orcid":false,"given":"Amelia T. 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T.","family":"Mok","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3593-6362","authenticated-orcid":false,"given":"Narayanaswamy","family":"Venketasubramanian","sequence":"additional","affiliation":[{"name":"Raffles Neuroscience Centre, Raffles Hospital, Singapore 188770, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Boon Yeow","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Medicine, St Luke\u2019s Hospital, Singapore 659674, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Ming Ann","family":"Sim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore"},{"name":"Memory Aging and Cognition Centre, National University Health System, Singapore 117600, Singapore"},{"name":"Department of Anaesthesia, National University Health System, Singapore 119074, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7685-1424","authenticated-orcid":false,"given":"Mitchell K. 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