biostudies-literatureLi QH. Lundbeck A/SLumosityChongqing Natural Science Fund Key ProjectNIA NIH HHSAlzheimer's Drug Discovery FoundationCogstateNational Institutes of HealthAlzheimer&apos;s AssociationNational Institute on AgingEli Lilly and CompanyNovartis Pharmaceuticals CorporationEuroImmunAlzheimer&apos;s Disease Neuroimaging InitiativeAraclon BiotechServierAlzheimer's AssociationNIH HHSBristol-Myers SquibbF. Hoffmann-La Roche Ltd.Elan Pharmaceuticals, Inc.Fujirebio EuropeDepartment of DefenseBristol-Myers Squibb CompanyGenentech, Inc.GenentechF. Hoffmann-La RocheJanssen Alzheimer Immunotherapy Research & Development, LLCPfizer Inc.NIBIB NIH HHSIXICO Ltd.Meso Scale Diagnostics, LLCEisai Inc.GE HealthcareMerckCereSpir, Inc.FujirebioTransition TherapeuticsMerck & Co., Inc.Takeda Pharmaceutical CompanyAlzheimer&apos;s Drug Discovery FoundationBioClinicaNational Institute of Biomedical Imaging and BioengineeringJohnson & Johnson Pharmaceutical Research & Development LLCPfizerChongqing Natural Science Fund General ProgramNeurotrack TechnologiesAbbVieBioClinica, Inc.Piramal ImagingAlzheimer's Disease Neuroimaging InitiativeNeuroRx ResearchKuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical UniversityBiogenU.S. Department of DefenseLundbeck4891-4902https://www.ebi.ac.uk/biostudies/studies/S-EPMC11247680biostudies-literatureUnknown20(7)<h4>Introduction</h4>Long-term blood pressure variability (BPV) and plasma neurofilament light (pNfL) have been identified as potential biomarkers for Alzheimer's disease (AD) and cerebral small vessel disease (CSVD). However, the relationship between BPV, pNfL, and their association with the comorbidity of AD and CSVD remains unknown.<h4>Methods</h4>Participants with normal cognition and mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study were included in the data analysis. Linear mixed-effects regression models and causal mediation analyses were conducted to investigate the relationship among BPV, pNfL, comorbidity-related brain structural changes (hippocampal atrophy and white matter hyperintensities [WMH]), and cognitive function.<h4>Results</h4>BPV was associated with pNfL, volumes of hippocampus and WMH, and cognition. pNfL mediated the effects of BPV on brain structural changes and cognition.<h4>Discussion</h4>Our findings suggest a potential role of BPV and pNfL in the mechanism of comorbidity between AD and CSVD, underscoring the importance of BPV intervention in the general population.<h4>Highlights</h4>Individuals with both Alzheimer's disease (AD) and cerebral small vessel disease (CSVD) pathologies had elevated blood pressure variability (BPV) and plasma neurofilament light (pNfL). The association between different components of BPV and brain structural changes may vary. BPV was associated with pNfL levels independent of average blood pressure. pNfL mediated the effects of BPV on comorbidity-related brain structural changes and cognitive performance.Alzheimer's & dementia : the journal of the Alzheimer's AssociationPotential role of blood pressure variability and plasma neurofilament light in the mechanism of comorbidity between Alzheimer's disease and cerebral small vessel disease.PMC11247680W81XWH‐12‐2‐0012cstc2019jcyj-zdxmX0029U01 AG024904W81XWH-12-2-0012CSTB2023NSCQ-MSX0198Liao ZLi XAlzheimer's Disease Neuroimaging InitiativeSu SLi JFeng YLi QJia MZhan JfalsePotential role of blood pressure variability and plasma neurofilament light in the mechanism of comorbidity between Alzheimer's disease and cerebral small vessel disease.<h4>Introduction</h4>Long-term blood pressure variability (BPV) and plasma neurofilament light (pNfL) have been identified as potential biomarkers for Alzheimer's disease (AD) and cerebral small vessel disease (CSVD). However, the relationship between BPV, pNfL, and their association with the comorbidity of AD and CSVD remains unknown.<h4>Methods</h4>Participants with normal cognition and mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study were included in the data analysis. Linear mixed-effects regression models and causal mediation analyses were conducted to investigate the relationship among BPV, pNfL, comorbidity-related brain structural changes (hippocampal atrophy and white matter hyperintensities [WMH]), and cognitive function.<h4>Results</h4>BPV was associated with pNfL, volumes of hippocampus and WMH, and cognition. pNfL mediated the effects of BPV on brain structural changes and cognition.<h4>Discussion</h4>Our findings suggest a potential role of BPV and pNfL in the mechanism of comorbidity between AD and CSVD, underscoring the importance of BPV intervention in the general population.<h4>Highlights</h4>Individuals with both Alzheimer's disease (AD) and cerebral small vessel disease (CSVD) pathologies had elevated blood pressure variability (BPV) and plasma neurofilament light (pNfL). The association between different components of BPV and brain structural changes may vary. BPV was associated with pNfL levels independent of average blood pressure. pNfL mediated the effects of BPV on comorbidity-related brain structural changes and cognitive performance.2024-01-01T00:00:00Z2024 Jul2025-04-26T14:10:02.849Z2025-04-06T14:29:51.235ZS-EPMC112476803889592110.1002/alz.14056