{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Shirzadi Z"],"funding":["NIBIB NIH HHS","NIA NIH HHS","NCRR NIH HHS"],"pagination":["869-873"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11266366"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(4)"],"pubmed_abstract":["<h4>Background</h4>Increased white matter hyperintensity (WMH) volume visible on MRI is a common finding in Alzheimer's disease (AD). We hypothesized that WMH in preclinical AD is associated with the presence of advanced vessel amyloidosis manifested as microhemorrhages (MCH).<h4>Objectives</h4>1) To assess the relationship between baseline WMH volume and baseline MCH. 2) To assess the relationship between longitudinal WMH accumulation and last MRI MCH during the double-blind phase of the A4 trial.<h4>Design</h4>A multicenter, randomized, double-blind, placebo-controlled, Phase 3 study comparing solanezumab with placebo given as infusions once every 4 weeks over 4.5 years in subjects with preclinical AD, defined as having evidence of elevated brain amyloid before the stage of clinically evident cognitive impairment, with an optional open-label extension period.<h4>Setting</h4>Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study.<h4>Participants</h4>A sample of 1157 cognitively unimpaired older adults (mean age = 71.9 years [SD = 4.8 years], 59% women, 59% APOE ε4 carriers).<h4>Measurements</h4>A linear regression model was used to assess the impact of baseline MCH amount (0, 1, 2+) on WMH volume. A linear mixed-effects model was used to assess the impact of last MRI MCH on longitudinal WMH. All models were corrected for age, sex, grey matter volume, cortical amyloid PET, APOE ε4 status, and treatment group.<h4>Results</h4>Baseline WMH volume was greater in individuals with more than one MCH compared to those with no MCH (t=4.8, p<0.001). The longitudinal increase in WMH amongst individuals with one (t=2.3, p=0.025) and more than one MCH (t=6.7, p<0.001) at the last MRI was greater than those with no MCH.<h4>Conclusion</h4>These results indicate a strong association between WMH and MCH, a common manifestation of cerebral amyloid angiopathy and ARIA-H. These results suggest that increased WMH volume may represent an early sign of vessel amyloidosis, likely prior to the emergence of MCH."],"journal":["The journal of prevention of Alzheimer's disease"],"pubmed_title":["Greater White Matter Hyperintensity Volume Is Associated with the Number of Microhemorrhages in Preclinical Alzheimer's Disease."],"pmcid":["PMC11266366"],"funding_grant_id":["S10 RR023401","P41 EB015896","P01 AG036694","K23 AG084868","S10 RR021110","S10 RR023043"],"pubmed_authors":["Aisen P","Chhatwal JP","Schultz AP","Ernstrom K","Brickman AM","Jack CR","Rafii MS","Properzi M","Raman R","Donohue MC","Wang S","Greenberg SM","Shirzadi Z","Sperling RA","Yau WW","Yaari R"],"additional_accession":[]},"is_claimable":false,"name":"Greater White Matter Hyperintensity Volume Is Associated with the Number of Microhemorrhages in Preclinical Alzheimer's Disease.","description":"<h4>Background</h4>Increased white matter hyperintensity (WMH) volume visible on MRI is a common finding in Alzheimer's disease (AD). We hypothesized that WMH in preclinical AD is associated with the presence of advanced vessel amyloidosis manifested as microhemorrhages (MCH).<h4>Objectives</h4>1) To assess the relationship between baseline WMH volume and baseline MCH. 2) To assess the relationship between longitudinal WMH accumulation and last MRI MCH during the double-blind phase of the A4 trial.<h4>Design</h4>A multicenter, randomized, double-blind, placebo-controlled, Phase 3 study comparing solanezumab with placebo given as infusions once every 4 weeks over 4.5 years in subjects with preclinical AD, defined as having evidence of elevated brain amyloid before the stage of clinically evident cognitive impairment, with an optional open-label extension period.<h4>Setting</h4>Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study.<h4>Participants</h4>A sample of 1157 cognitively unimpaired older adults (mean age = 71.9 years [SD = 4.8 years], 59% women, 59% APOE ε4 carriers).<h4>Measurements</h4>A linear regression model was used to assess the impact of baseline MCH amount (0, 1, 2+) on WMH volume. A linear mixed-effects model was used to assess the impact of last MRI MCH on longitudinal WMH. All models were corrected for age, sex, grey matter volume, cortical amyloid PET, APOE ε4 status, and treatment group.<h4>Results</h4>Baseline WMH volume was greater in individuals with more than one MCH compared to those with no MCH (t=4.8, p<0.001). The longitudinal increase in WMH amongst individuals with one (t=2.3, p=0.025) and more than one MCH (t=6.7, p<0.001) at the last MRI was greater than those with no MCH.<h4>Conclusion</h4>These results indicate a strong association between WMH and MCH, a common manifestation of cerebral amyloid angiopathy and ARIA-H. These results suggest that increased WMH volume may represent an early sign of vessel amyloidosis, likely prior to the emergence of MCH.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024","modification":"2026-03-27T16:50:35.706Z","creation":"2025-08-27T03:10:58.664Z"},"accession":"S-EPMC11266366","cross_references":{"pubmed":["39044495"],"doi":["10.14283/jpad.2024.139"]}}