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Cardiovascular interventions show therapeutic promise, hence may improve neurovascular coupling (NVC) and resting\u2010state functional connectivity (RSFC) hemodynamic responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>NVC and RSFC were recorded longitudinally in control and AD transgenic mice treated or not with simvastatin (SV) using optical imaging of intrinsic signals (OIS), together with memory testing.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>AD mice showed early decreases in NVC and bilateral connectivity (BC) in motor and cingulate cortex, and hypoconnectivity within the sensory\u2010motor network. Early default\u2010mode network (DMN) hyperconnectivity was followed by hypoconnectivity, together with a decreased BC in somatosensory (S) cortex. SV restored NVC, prevented aberrant DMN hyperconnectivity, improved BC of S, and preserved memory.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Our results indicate that OIS can detect early AD\u2010related changes in NVC and RSFC, and that a preventive cardiovascular strategy may bear therapeutic promise in at\u2010risk individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Optical imaging of intrinsic signals captures Alzheimer's disease (AD) progression and response to therapy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Neurovascular coupling (NVC) and resting\u2010state functional connectivity (RSFC) disruptions precede memory decline in AD transgenic mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Simvastatin prevented NVC and AD\u2010specific RSFC disruptions and protected memory.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This study supports translational value of hemodynamic signal in early AD detection.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70402","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T09:39:38Z","timestamp":1754041178000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Neurovascular coupling and functional connectivity changes through the Alzheimer's disease spectrum: Effects of simvastatin treatment"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8309-7068","authenticated-orcid":false,"given":"Aline R.","family":"Zimmer","sequence":"first","affiliation":[{"name":"Graduate Program in Pharmaceutical Science Federal University of Rio Grande do Sul (UFRGS)  Porto Alegre Brazil"},{"name":"Laboratory of Cerebrovascular Research Montreal Neurological Institute\u2010Hospital, McGill University  Montr\u00e9al Quebec Canad\u00e1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miled","family":"Bourourou","sequence":"additional","affiliation":[{"name":"Laboratory of Cerebrovascular Research Montreal Neurological Institute\u2010Hospital, McGill University  Montr\u00e9al Quebec Canad\u00e1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Lesage","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering Ecole Polytechnique de Montr\u00e9al  Montr\u00e9al Quebec Canad\u00e1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Hamel","sequence":"additional","affiliation":[{"name":"Laboratory of Cerebrovascular Research Montreal Neurological Institute\u2010Hospital, McGill University  Montr\u00e9al Quebec Canad\u00e1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2011.43"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2022.05.008"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313400"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.10.062"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11934"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.07.030"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20982383"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-080317-061725"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.48"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00954.2005"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-071013-014111"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2019.0630"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1117\/1.NPh.4.3.031208"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2021.117832"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2022.102977"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-020-00395-3"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2017.03.007"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq075"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0229541"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2019.20780"},{"key":"e_1_2_9_22_1","article-title":"Dementia risk reduction: why haven't the pharmacological risk reduction trials worked? 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