{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chu WT"],"funding":["NIA NIH HHS","NINDS NIH HHS"],"pagination":["e700-e710"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8865892"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["98(7)"],"pubmed_abstract":["<h4>Background and objectives</h4>The goal of this work was to determine the relationship between diffusion microstructure and early changes in Alzheimer disease (AD) severity as assessed by clinical diagnosis, cognitive performance, dementia severity, and plasma concentrations of neurofilament light chain.<h4>Methods</h4>Diffusion MRI scans were collected on cognitively normal participants (CN) and patients with early mild cognitive impairment (EMCI), late mild cognitive impairment, and AD. Free water (FW) and FW-corrected fractional anisotropy were calculated in the locus coeruleus to transentorhinal cortex tract, 4 magnocellular regions of the basal forebrain (e.g., nucleus basalis of Meynert), entorhinal cortex, and hippocampus. All patients underwent a battery of cognitive assessments; neurofilament light chain levels were measured in plasma samples.<h4>Results</h4>FW was significantly higher in patients with EMCI compared to CN in the locus coeruleus to transentorhinal cortex tract, nucleus basalis of Meynert, and hippocampus (mean Cohen <i>d</i> = 0.54; <i>p</i> <sub>fdr</sub> < 0.05). FW was significantly higher in those with AD compared to CN in all the examined regions (mean Cohen <i>d</i> = 1.41; <i>p</i> <sub>fdr</sub> < 0.01). In addition, FW in the hippocampus, entorhinal cortex, nucleus basalis of Meynert, and locus coeruleus to transentorhinal cortex tract positively correlated with all 5 cognitive impairment metrics and neurofilament light chain levels (mean <i>r</i> <sup>2</sup> = 0.10; <i>p</i> <sub>fdr</sub> < 0.05).<h4>Discussion</h4>These results show that higher FW is associated with greater clinical diagnosis severity, cognitive impairment, and neurofilament light chain. They also suggest that FW elevation occurs in the locus coeruleus to transentorhinal cortex tract, nucleus basalis of Meynert, and hippocampus in the transition from CN to EMCI, while other basal forebrain regions and the entorhinal cortex are not affected until a later stage of AD. FW is a clinically relevant and noninvasive early marker of structural changes related to cognitive impairment."],"journal":["Neurology"],"pubmed_title":["Association of Cognitive Impairment With Free Water in the Nucleus Basalis of Meynert and Locus Coeruleus to Transentorhinal Cortex Tract."],"pmcid":["PMC8865892"],"funding_grant_id":["R01 NS058487","R01 NS023945","P30 AG066506","P50 AG047266","R01 NS052318","RF1 NS023945"],"pubmed_authors":["Vaillancourt DE","Zaborszky L","Coombes SA","DeKosky S","Adjouadi M","Loewenstein DA","Wang WE","Duara R","Chu WT","Golde TE"],"additional_accession":[]},"is_claimable":false,"name":"Association of Cognitive Impairment With Free Water in the Nucleus Basalis of Meynert and Locus Coeruleus to Transentorhinal Cortex Tract.","description":"<h4>Background and objectives</h4>The goal of this work was to determine the relationship between diffusion microstructure and early changes in Alzheimer disease (AD) severity as assessed by clinical diagnosis, cognitive performance, dementia severity, and plasma concentrations of neurofilament light chain.<h4>Methods</h4>Diffusion MRI scans were collected on cognitively normal participants (CN) and patients with early mild cognitive impairment (EMCI), late mild cognitive impairment, and AD. Free water (FW) and FW-corrected fractional anisotropy were calculated in the locus coeruleus to transentorhinal cortex tract, 4 magnocellular regions of the basal forebrain (e.g., nucleus basalis of Meynert), entorhinal cortex, and hippocampus. All patients underwent a battery of cognitive assessments; neurofilament light chain levels were measured in plasma samples.<h4>Results</h4>FW was significantly higher in patients with EMCI compared to CN in the locus coeruleus to transentorhinal cortex tract, nucleus basalis of Meynert, and hippocampus (mean Cohen <i>d</i> = 0.54; <i>p</i> <sub>fdr</sub> < 0.05). FW was significantly higher in those with AD compared to CN in all the examined regions (mean Cohen <i>d</i> = 1.41; <i>p</i> <sub>fdr</sub> < 0.01). In addition, FW in the hippocampus, entorhinal cortex, nucleus basalis of Meynert, and locus coeruleus to transentorhinal cortex tract positively correlated with all 5 cognitive impairment metrics and neurofilament light chain levels (mean <i>r</i> <sup>2</sup> = 0.10; <i>p</i> <sub>fdr</sub> < 0.05).<h4>Discussion</h4>These results show that higher FW is associated with greater clinical diagnosis severity, cognitive impairment, and neurofilament light chain. They also suggest that FW elevation occurs in the locus coeruleus to transentorhinal cortex tract, nucleus basalis of Meynert, and hippocampus in the transition from CN to EMCI, while other basal forebrain regions and the entorhinal cortex are not affected until a later stage of AD. FW is a clinically relevant and noninvasive early marker of structural changes related to cognitive impairment.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Feb","modification":"2025-05-18T12:29:43.683Z","creation":"2025-02-19T03:27:03.875Z"},"accession":"S-EPMC8865892","cross_references":{"pubmed":["34906980"],"doi":["10.1212/wnl.0000000000013206","10.1212/WNL.0000000000013206"]}}