Lesson 1Definitions and current diagnostic criteria (NIA-AA 2011/2018 research framework, IWG)Summarises key diagnostic standards for Alzheimer’s disease, including NIA-AA 2011, NIA-AA 2018 research framework, and IWG criteria. Highlights shifts towards biological definitions and their meaning for clinic use versus 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 certaintyLooks at ways to mix CSF, blood, structural MRI, and PET markers to boost diagnosis confidence. Discusses matching and mismatching patterns, test order, and blending results with clinical signs and disease 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 patternsFocuses on amyloid and tau PET scans, including when to use, what not to, and reading rules. Discusses area-specific uptake patterns, measurement tools, pitfalls, and how PET affects 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 utilityExplains structural MRI and FDG-PET findings in Alzheimer’s and other conditions. Reviews typical shrinkage and low activity patterns, measurement tools, and how scans confirm or question a suspected 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 constraintsGives step-by-step guides for picking marker tests considering cost, access, and patient health issues. Stresses matching plans to the clinical need, local setup, and patient wishes while skipping needless 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 limitationsDetails proven CSF markers Aβ42, Aβ42/40 ratio, total tau, and phosphorylated tau. Explains test methods, cut-off points, typical Alzheimer’s patterns, plus test variations, unclear zones, and other causes of odd 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 issuesCovers blood markers like plasma p-tau181, p-tau217, Aβ42/40, and neurofilament light. Discusses test reliability, cut-offs, sample handling, and how blood tests stack up against CSF and PET in various 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 patternsDescribes common and unusual clinical types of Alzheimer’s, like memory loss, posterior cortical, speech issues, and frontal types. Reviews progression paths, daily function drop, and link to marker profiles.
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 stageIntroduces marker-based staging with AT(N) framework, connecting amyloid, tau, and nerve damage markers to clinical stage. Covers staging plans, usual paths, and how AT(N) guides outlook 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 testingReviews sample handling, test validation, and quality checks for Alzheimer’s markers. Covers lab approvals, rules, and reporting standards for reliable, useful test results across 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
