Lesson 1Definitions and current diagnostic criteria (NIA-AA 2011/2018 research framework, IWG)Here we sum up the main rules doctors use to say if it is Alzheimer’s, like NIA-AA 2011, NIA-AA 2018 research rules, and IWG rules. We show changes in thinking towards body signs and what it means for clinic work or research.
Core elements of NIA-AA 2011 clinical criteriaNIA-AA 2018 biological definition and AT(N) useKey features of IWG diagnostic criteriaDifferences between clinical and research criteriaImplications for trial enrollment and labelingLesson 2When and how to combine biomarkers (CSF, blood, PET, MRI) to increase diagnostic certaintyWe look at ways to mix CSF, blood, MRI structure, and PET tests to be more sure of the diagnosis. We talk about matching and not matching results, order of tests, and mixing them with patient signs and sickness stage.
Principles of multimodal biomarker integrationCommon concordant and discordant result patternsSequential versus parallel testing strategiesAligning biomarker choice with disease stageCommunicating combined results to patientsLesson 3Molecular neuroimaging: amyloid PET and tau PET — indications, reading, quantitation, and regional patternsThis focuses on amyloid and tau PET scans, when to use them, reasons not to, and how to read. We discuss area patterns, numbers measure, problems, and how PET changes diagnosis and care choices.
Appropriate use criteria for amyloid PETTypical amyloid PET regional uptake patternsTau PET tracers and distribution in Alzheimer’sVisual reads versus quantitative PET measuresCommon artifacts and interpretive pitfallsLesson 4Structural and functional imaging: MRI (atrophy patterns, volumetry), FDG-PET — differential diagnostic utilityWe explain MRI structure and FDG-PET in Alzheimer’s and other sicknesses. We review shrink patterns and low energy use, number tools, and how scans help or question the thought diagnosis.
Medial temporal and parietal atrophy patternsVisual rating scales and volumetric quantificationFDG-PET hypometabolism in Alzheimer’s diseaseImaging clues to non-Alzheimer’s dementiasIntegrating MRI and FDG-PET with clinical dataLesson 5Practical algorithms for ordering tests given cost, availability, and patient comorbidity constraintsWe give step-by-step ways to choose tests when money, place to get them, and other sicknesses limit. We stress making plans fit the question, health place, patient wishes, without waste tests.
Initial cognitive workup before biomarker testingChoosing CSF versus blood biomarkersWhen to add amyloid or tau PET imagingAdapting algorithms to comorbidities and frailtyCost, insurance coverage, and health system limitsLesson 6Established fluid biomarkers: CSF Aβ42/40, total tau, phosphorylated tau assays — interpretation and limitationsWe detail known CSF tests Aβ42, Aβ42/40 ratio, total tau, phospho tau. We explain test types, cut points, usual Alzheimer’s signs, changes in tests, unclear areas, other causes of bad results.
CSF Aβ42 and Aβ42/40 ratio: biology and cutoffsTotal tau as a marker of neuronal injuryPhosphorylated tau isoforms and assay platformsInterpreting discordant or borderline CSF profilesNon-Alzheimer’s conditions affecting CSF markersLesson 7Blood-based biomarkers: plasma p-tau (181, 217), Aβ42/40, neurofilament light (NfL) — validity, thresholds, and preanalytical issuesWe cover blood tests like plasma p-tau181, p-tau217, Aβ42/40, NfL. We talk test trust, cut points, before test handling, how blood compares to CSF PET in places.
Biology and kinetics of plasma p-tau isoformsPlasma Aβ42/40 ratio and assay approachesNeurofilament light as a nonspecific injury markerPreanalytical factors affecting plasma biomarkersClinical scenarios suited to blood-based testingLesson 8Clinical phenotypes of Alzheimer’s disease and typical progression patternsWe describe usual and unusual ways Alzheimer’s shows, like memory loss, back brain, word loss, front brain types. We review how it goes on, daily work drop, link to test signs.
Typical amnestic late-onset Alzheimer’s presentationPosterior cortical atrophy and visuospatial deficitsLogopenic variant primary progressive aphasiaFrontal and behavioral-predominant Alzheimer’sLongitudinal progression and functional milestonesLesson 9Biomarker-based staging (AT(N) framework) and linking biomarkers to clinical stageWe bring in test staging with AT(N), linking amyloid, tau, nerve loss to clinic stage. We cover stage plans, usual paths, how AT(N) tells future and trial fit.
Conceptual basis of the AT(N) classificationMapping AT(N) profiles to clinical stagesLongitudinal change in AT(N) over the disease courseUsing AT(N) for prognosis and risk communicationLimitations and controversies of AT(N) stagingLesson 10Preanalytical, laboratory quality, and regulatory considerations for biomarker testingWe review before test handling, test check, quality for Alzheimer’s tests. We cover approval, rules paths, report ways for sure, useful test results in labs.
Sample collection tubes and timing requirementsCentrifugation, aliquoting, and storage conditionsInternal quality control and external proficiency testingRegulatory approval pathways and labeling limitsStandardized reporting formats and reference ranges
