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Cardiovasc. Transl. Res."],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Obesity is a major risk factor for metabolic dysfunction and cognitive decline, yet the influence of age of onset and sex on neurovascular outcomes remains unclear. We examined how the age at initiation and duration of diet-induced obesity influence metabolism, cognition, and cerebrovascular perfusion in male and female mice. A high-fat diet increased body weight and impaired glucose regulation, particularly in females. Obesity selectively impaired recognition memory while sparing spatial working memory. Cerebrovascular effects were region- and age-specific. Early- and mid-life obesity produced localized perfusion changes despite preserved global cortical blood flow. In contrast, early-life obesity was associated with reduced cortical perfusion and decreased hippocampal vascular complexity, including fewer branch points and smaller vessel diameters. These alterations parallel recognition memory deficits, suggesting a vascular mechanism linking early metabolic stress to cognitive impairment. Together, our findings identify early-life obesity as a critical window of vulnerability for long-term neurovascular and cognitive dysfunction.<\/jats:p>","DOI":"10.1007\/s12265-026-10806-3","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:49:48Z","timestamp":1785941388000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Timing and Duration of Prediabetic Metabolic Dysfunction Differentially Impact Cerebral Perfusion, Vascular Structure, and Behavior"],"prefix":"10.1007","volume":"19","author":[{"given":"Annika","family":"Matthiesen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"DiLucia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riley","family":"Feagle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadie","family":"Lofton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catrina","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0873-6015","authenticated-orcid":false,"given":"Adviye","family":"Ergul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"issue":"8","key":"10806_CR1","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1001\/jama.2025.12923","volume":"334","author":"LD Baker","year":"2025","unstructured":"Baker LD, et al. <article-title update=\u201cadded\u201d>Structured vs self-guided multidomain lifestyle interventions for global cognitive function. 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Johnson VA Medical Center Research and Development Committee (NURD-010\u201321\u00a0F, ACORP 712).","order":1,"name":"Ethics","label":"Animal Studies","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Human Subjects\/Informed Consent","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The perfusion patterns observed in this study parallel those in (1) Alzheimer\u2019s disease, which predominantly affects women and is associated with reduced parietal and temporal perfusion [\n                      \n                      ,\n                      \n                      ], and (2) dementia with Lewy bodies, which disproportionately affects men and correlates with occipital hypoperfusion [\n                      \n                      ,\n                      \n                      ]. While risk prognostication for dementia sub-variants is beyond the scope of this study, these similarities highlight the utility of perfusion imaging and sex-specific analyses when investigating cognitive pathologies.","order":3,"name":"Ethics","label":"Clinical Relevance","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"AE serves as an editor for this journal but was recused from the peer-review process and all editorial decisions for this manuscript; no other conflicts are declared.","order":4,"name":"Ethics","label":"Conflict of interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"98"}}