biostudies-literatureVerdi SAlzheimer's Association; Alzheimer's Drug Discovery FoundationH. Lundbeck A/SADNIDOD ADNILumosityAgence Nationale de la RechercheNIA NIH HHSAlzheimer's Drug Discovery FoundationCogstateJohnson & Johnson Pharmaceutical Research & Development LL.National Institutes of HealthAlzheimer&apos;s AssociationNational Health & Medical Research CouncilEli Lilly and CompanyNational Institute on AgingLaboratory for Neuro ImagingNovartis Pharmaceuticals CorporationEuroImmunNorthern California Institute for Research and EducationAlzheimer&apos;s Disease Neuroimaging InitiativeEU Joint Programme-Neurodegenerative Disease ResearchAraclon BiotechServierAlzheimer's AssociationNIH HHSItalian Ministry of Health (MoH)F. Hoffmann-La Roche Ltd.Janssen Alzheimer Immunotherapy Research & Development, LLC.Alzheimer's Therapeutic Research InstituteElan Pharmaceuticals, Inc.Fujirebio EuropeBristol-Myers Squibb CompanyMerck & Co., Inc. Meso Scale Diagnostics, LLCGenentech, Inc.GenentechF. Hoffmann-La RocheMedical Research Councilaegis of JPNDItalian Ministry of HealthBrain Research UKNIBIB NIH HHSPfizer Inc.UCLH Biomedical Research CentreEarly Detection of Alzheimer's Disease SubtypesDepartment of Health's National Institute for Health Research funded University College London Hospitals Biomedical Research CentreIXICO Ltd.GE HealthcareUniversity College London Hospitals Biomedical Research CentreCanadian Institutes of Health ResearchCereSpir, Inc.FujirebioVIDITransition TherapeuticsEisai IncorporatedAlzheimer&apos;s Drug Discovery FoundationTakeda Pharmaceutical CompanyFoundation for the National Institutes of HealthDutch Organization for Scientific ResearchBioClinicaEPSRC-funded UCL Centre for Doctoral Training in IntelligentUnited Kingdom, Medical Research CouncilNational Institute of Biomedical Imaging and BioengineeringAlzheimer's Research UKWeston Brain InstituteBritish Heart FoundationNational Research, Development and Innovation OfficePfizerNeurotrack TechnologiesUniversity of Southern CaliforniaZonMwBioClinica, Inc.AbbVieDepartment of Health's National Institute for Health ResearchCIHRPiramal ImagingNeuroRx ResearchBiogenLundbeckIntegrated Imaging in Healthcare6998-7012https://www.ebi.ac.uk/biostudies/studies/S-EPMC11633367biostudies-literatureUnknown20(10)<h4>Introduction</h4>Neuroanatomical normative modeling captures individual variability in Alzheimer's disease (AD). Here we used normative modeling to track individuals' disease progression in people with mild cognitive impairment (MCI) and patients with AD.<h4>Methods</h4>Cortical and subcortical normative models were generated using healthy controls (n ≈ 58k). These models were used to calculate regional z scores in 3233 T1-weighted magnetic resonance imaging time-series scans from 1181 participants. Regions with z scores < -1.96 were classified as outliers mapped on the brain and summarized by total outlier count (tOC).<h4>Results</h4>tOC increased in AD and in people with MCI who converted to AD and also correlated with multiple non-imaging markers. Moreover, a higher annual rate of change in tOC increased the risk of progression from MCI to AD. Brain outlier maps identified the hippocampus as having the highest rate of change.<h4>Discussion</h4>Individual patients' atrophy rates can be tracked by using regional outlier maps and tOC.<h4>Highlights</h4>Neuroanatomical normative modeling was applied to serial Alzheimer's disease (AD) magnetic resonance imaging (MRI) data for the first time. Deviation from the norm (outliers) of cortical thickness or brain volume was computed in 3233 scans. The number of brain-structure outliers increased over time in people with AD. Patterns of change in outliers varied markedly between individual patients with AD. People with mild cognitive impairment whose outliers increased over time had a higher risk of progression from AD.Alzheimer's & dementia : the journal of the Alzheimer's AssociationPersonalizing progressive changes to brain structure in Alzheimer's disease using normative modeling.PMC116333672019-2.1.7-ERA-NET-2020-000082019‐2.1.7‐ERA‐NET‐2020‐00008016.156.415EP/S021930/11191535MR/T046422/1U01 AG024904ANR-19-JPW2-000733051106ANR‐19‐JPW2‐000W81XWH-12-2-0012Alzheimer's Disease Neuroimaging InitiativeAltmann ARaket LLSchott JMCole JHFraza CTosun DMarquand AFVerdi SRutherford SfalsePersonalizing progressive changes to brain structure in Alzheimer's disease using normative modeling.<h4>Introduction</h4>Neuroanatomical normative modeling captures individual variability in Alzheimer's disease (AD). Here we used normative modeling to track individuals' disease progression in people with mild cognitive impairment (MCI) and patients with AD.<h4>Methods</h4>Cortical and subcortical normative models were generated using healthy controls (n ≈ 58k). These models were used to calculate regional z scores in 3233 T1-weighted magnetic resonance imaging time-series scans from 1181 participants. Regions with z scores < -1.96 were classified as outliers mapped on the brain and summarized by total outlier count (tOC).<h4>Results</h4>tOC increased in AD and in people with MCI who converted to AD and also correlated with multiple non-imaging markers. Moreover, a higher annual rate of change in tOC increased the risk of progression from MCI to AD. Brain outlier maps identified the hippocampus as having the highest rate of change.<h4>Discussion</h4>Individual patients' atrophy rates can be tracked by using regional outlier maps and tOC.<h4>Highlights</h4>Neuroanatomical normative modeling was applied to serial Alzheimer's disease (AD) magnetic resonance imaging (MRI) data for the first time. Deviation from the norm (outliers) of cortical thickness or brain volume was computed in 3233 scans. The number of brain-structure outliers increased over time in people with AD. Patterns of change in outliers varied markedly between individual patients with AD. People with mild cognitive impairment whose outliers increased over time had a higher risk of progression from AD.2024-01-01T00:00:00Z2024 Oct2025-04-22T13:11:21.047Z2025-04-06T00:34:52.843ZS-EPMC116333673923495610.1002/alz.14174