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neuro.alzheimer.v1

Alzheimer Disease (outpatient + biomarker era)

neurologychronicadultgeriatricoutpatientinpatientmixed
Start encounter →Print handoutPRODUCTION

Phase C shard-3 neuro wave-9 (2026-05-15): authored at INTEGRATED — manifest stub forward-declared; PRODUCTION requires full manifest + RxNav validation. 13 severity_triggers: preclinical_AD / MCI_due_to_AD / mild_AD / moderate_AD / severe_AD / amyloid_PET_positive_mAb_eligible / ARIA-E / ARIA-H / behavioral_neuropsychiatric_sx / sundowning / wandering / caregiver_burden_severe / driving_concern. 5 setting playbooks: home (caregiver bundle + ARIA-E sentinel symptoms) → outpatient (primary cognitive clinic q3-6 mo + mAb infusion oversight) → ed (delirium-superimposed + ARIA-E rule-out) → icu (rare — ARIA-E with mass effect, autoimmune mimic, vent support) → inpatient (DSD workup + HELP bundle + pause mAb). 8 PMID evidence anchor: NIA-AA 2018 (29653606) + CLARITY-AD lecanemab (36449413) + TRAILBLAZER-ALZ 2 donanemab (37459141) + Albert AAN MCI (21514249) + McKhann NIA-AA 2011 (21514250) + FDA aducanumab historical (35542991 NEEDS_SOURCE_REVIEW) + Cummings clinical trial design (32695874 NEEDS_SOURCE_REVIEW) + CitAD citalopram (24549548). Schema-blocked: MoCA / MMSE / FAST / CDR / NPI / Zarit / APOE genotype slot / ARIA-E grading scale — not in clinical-tools-registry; surfaced in depth bundle as cross-shard tickets to registry maintainer. Critical safety: AVOID risperidone + typical antipsychotics if DLB overlap (McKeith 2017); citalopram max 20 mg in elderly (FDA QT); mAb requires pre-screen (anticoagulation, ≥4 microbleeds, superficial siderosis, recent stroke/TIA = block) + APOE pre-test counseling; ARIA-E with neuro deficit → PAUSE infusion + STAT MRI + neurology. Sibling differentiation routes to symptom.dementia.v1 (parent triage), neuro.delirium.v1 (DSD pivot), neuro.parkinson.v1 (parkinsonism mimic / PDD pivot) — all PRODUCTION-registered.

Entry points (8)

  • symptom
    Insidious episodic memory decline + word-finding + IADL impact (NIA-AA 2011 McKhann PMID 21514250)
    episodic_memory_decline
  • symptom
    Amnestic MCI — preserved IADL but objective episodic memory deficit (Albert AAN MCI PMID 21514249)
    mci_amnestic_pattern
  • lab_abnormality
    CSF Aβ42/40 low OR amyloid-PET positive OR blood p-tau217 elevated (NIA-AA 2018 PMID 29653606)
    amyloid_positive_biomarker
  • symptom
    Caregiver-corroborated cognitive decline ≥6 mo (NIA-AA 2011)
    caregiver_reported_cognitive_decline
  • history
    Family history early-onset AD (<65) — consider APP/PSEN1/PSEN2 dominant mutation
    family_history_early_onset_ad
  • symptom
    Posterior cortical atrophy variant — visuospatial / apraxia early; rule out Lewy body
    apraxia_visuospatial_decline
  • symptom
    Logopenic PPA — anomia + impaired repetition; often AD pathology (route to FTD engine for PPA differential)
    logopenic_aphasia
  • lab_abnormality
    MoCA <26 with corroborated functional change → AD workup pathway
    abnormal_moca_in_primary_care

Required inputs (18)

  • agerequired
    demographic • used at CONTEXT
    Age ≥65 typical sporadic AD; <65 = early-onset AD (consider APOE e4/e4 + dominant mutations) (NIA-AA 2011 PMID 21514250)
  • iadl_adl_functionrequired
    history • used at CONTEXT
    IADL impairment defines major NCD vs MCI; preserved IADL = MCI due to AD (Albert AAN MCI PMID 21514249)
  • symptom_onset_temporequired
    history • used at FRAME
    Insidious months-years onset characteristic of AD; rapid <1 y → CJD / autoimmune workup (route to symptom.dementia.v1 red-flag)
  • episodic_memory_complaintrequired
    history • used at CONTEXT
    Amnestic presentation is most common AD phenotype (McKhann NIA-AA 2011 PMID 21514250)
  • depression_screen_phq9_or_gdsrequired
    history • used at CONTEXT
    Depression mimics AD (pseudodementia); GDS preferred elderly; treat before assigning AD label (AAN 2018)
  • cam_4at_for_deliriumrequired
    history • used at RED_FLAGS
    Delirium-superimposed-on-dementia common; CAM/4AT must be negative before chronic AD diagnosis (Inouye Lancet 2014)
  • current_meds_anticholinergicrequired
    medication • used at CONTEXT
    Anticholinergic / benzodiazepine / sedating burden reversibly worsens cognition; deprescribe per AGS Beers 2023
  • tshrequired
    lab • used at INITIAL_WORKUP
    Hypothyroid mimic; reversible (AAN 2018)
  • b12required
    lab • used at INITIAL_WORKUP
    B12 deficiency mimic; treat with IM if <200 pg/mL (AAN 2018)
  • rpr_or_treponemalrequired
    lab • used at INITIAL_WORKUP
    Neurosyphilis is reversible dementia (AAN 2018)
  • hivrequired
    lab • used at INITIAL_WORKUP
    HIV-associated neurocognitive disorder treatable with ART (AAN 2018)
  • csf_amyloid_tau_or_blood_ptau217
    lab • used at BRANCHING_WORKUP
    Biomarker confirmation before anti-amyloid mAb; CSF Aβ42/40 low + p-tau181/217 elevated OR blood p-tau217 elevated OR amyloid-PET positive (NIA-AA 2018 PMID 29653606; CLARITY-AD PMID 36449413)
  • apoe_genotype_for_aria_risk
    lab • used at RISK_STRATIFICATION
    APOE e4/e4 homozygote ~3-4× ARIA-E/H risk on lecanemab/donanemab; influences shared-decision pre-mAb (AAN 2024 appropriate-use; CLARITY-AD van Dyck NEJM 2023 PMID 36449413)
  • mri_brainrequired
    imaging • used at INITIAL_WORKUP
    Hippocampal + medial-temporal atrophy supports AD; baseline microbleed + superficial siderosis count gates mAb eligibility (≥4 microbleeds OR superficial siderosis = block) (NIA-AA 2011; CLARITY-AD PMID 36449413)
  • amyloid_pet
    imaging • used at BRANCHING_WORKUP
    Confirms AD biology when CSF/blood unavailable; mandatory pre-donanemab tau-PET stratification (TRAILBLAZER-ALZ 2 PMID 37459141)
  • fdg_pet
    imaging • used at BRANCHING_WORKUP
    Biparietal/temporal hypometabolism supports AD vs FTD frontal pattern (NIA-AA 2018)
  • driving_safety
    history • used at MONITORING
    MoCA <18 / FAST ≥4 / accident history → driving cessation discussion (AAN 2018; APA 2024)
  • caregiver_burden_zarit
    history • used at FOLLOWUP
    Caregiver Zarit ≥21 drives institutionalization risk; respite + APS referral (APA 2024)

12-phase flow (12)

  1. 1FRAME
    Insidious-onset amnestic syndrome with biomarker confirmation (CSF / blood p-tau217 / amyloid-PET) meeting NIA-AA 2011 clinical + 2018 biomarker frameworks (McKhann PMID 21514250; NIA-AA 2018 PMID 29653606)
    inputs: symptom_onset_tempo, episodic_memory_complaint
    advance: AD clinical syndrome assigned (probable AD dementia / MCI due to AD / preclinical AD)
  2. 2ENTRY
    Cognitive complaint with corroboration → cognitive clinic referral; amnestic pattern + functional change → AD pathway
    inputs: age
    advance: AD pathway activated
  3. 3CONTEXT
    IADL/ADL, vascular RFs (for mixed pathology), depression screen, anticholinergic burden, sleep, hearing/vision (sensory deprivation worsens cognition — Lancet 2024 dementia commission)
    inputs: iadl_adl_function, depression_screen_phq9_or_gds, current_meds_anticholinergic
    advance: Full functional + medication context complete
  4. 4RED_FLAGS
    Delirium superimposed (CAM/4AT); rapid decline <1 y → route to symptom.dementia.v1 for CJD / autoimmune; behavioral crisis with safety risk; ARIA-E with neuro deficit on mAb → emergent MRI + pause infusion (CLARITY-AD PMID 36449413)
    inputs: symptom_onset_tempo, cam_4at_for_delirium
    actions: workup.delirium, workup.dementia
    advance: Delirium excluded + atypical / urgent etiologies routed
  5. 5INITIAL_WORKUP
    MoCA / MMSE; PHQ-9 or GDS; CBC, CMP, TSH, B12, folate, HIV, RPR; MRI brain (atrophy + baseline microbleeds for mAb candidacy) (AAN 2018 PMID 29282327; CLARITY-AD PMID 36449413)
    inputs: tsh, b12, rpr_or_treponemal, hiv, mri_brain
    actions: panel.cbc, panel.renal, panel.thyroid, panel.lft
    advance: Reversible mimics screened + structural + microbleed baseline done
  6. 6BRANCHING_WORKUP
    CSF Aβ42/40 + p-tau181/217 OR blood p-tau217 OR amyloid-PET; tau-PET for donanemab eligibility stratification (low vs intermediate tau); APOE genotype with pre-test counseling (NIA-AA 2018 PMID 29653606; TRAILBLAZER-ALZ 2 PMID 37459141)
    inputs: csf_amyloid_tau_or_blood_ptau217, amyloid_pet, apoe_genotype_for_aria_risk
    advance: Biomarker + APOE + tau status documented
  7. 7DIFFERENTIAL
    AD vs mixed AD-vascular (route to neuro.vascular-dementia.v1) vs FTD (route to neuro.frontotemporal-dementia.v1) vs DLB vs PDD (route to neuro.parkinson.v1 PDD trigger) vs reversible mimics — biomarker decoupling of clinical syndrome from biology per NIA-AA 2018
    advance: AD assigned with confidence
  8. 8RISK_STRATIFICATION
    CDR or FAST staging (preclinical → MCI → mild → moderate → severe); ARIA-E/H risk pre-mAb (APOE e4/e4, baseline microbleed count, superficial siderosis, anticoagulation); Zarit caregiver burden; driving safety (CLARITY-AD PMID 36449413)
    inputs: apoe_genotype_for_aria_risk
    advance: Stage + mAb candidacy + caregiver + driving risk evaluated
  9. 9TREATMENT
    Donepezil/rivastigmine/galantamine titrate for mild-moderate; memantine add for moderate-severe; lecanemab 10 mg/kg IV q2w (CLARITY-AD PMID 36449413) or donanemab Q4W (TRAILBLAZER-ALZ 2 PMID 37459141) for biomarker-confirmed early AD; BP <130/80 (SPRINT-MIND signal); statin; cognitive engagement; aerobic exercise 150 min/wk; non-pharm DICE for BPSD; citalopram (CitAD PMID 24549548) or pimavanserin (off-label) for agitation/psychosis; AVOID risperidone in DLB overlap
    inputs: csf_amyloid_tau_or_blood_ptau217
    advance: Tailored regimen + non-pharm + lifestyle plan documented
  10. 10DISPOSITION
    Outpatient cognitive clinic q3-6 mo; admit for delirium superimposed, ARIA-E with neuro deficit, behavioral crisis, suspected reversible mimic decompensation; ICU rarely (refractory ARIA-E with mass effect / status from autoimmune encephalitis mimic)
    advance: Disposition documented
  11. 11MONITORING
    Annual MoCA + function; ARIA MRI surveillance at baseline + before infusions 5/7/14 on mAb (CLARITY-AD PMID 36449413; TRAILBLAZER-ALZ 2 PMID 37459141); AGS Beers 2023 deprescribe q6 mo; antipsychotic taper q3 mo if used (APA 2024)
    inputs: driving_safety
    advance: Monitoring plan documented
  12. 12FOLLOWUP
    Caregiver education + dementia care navigator; driving cessation per MoCA / FAST trajectory; capacity assessment + advance directives / POLST; palliative referral at FAST 7 (NICE 2024 dementia; APA 2024)
    inputs: caregiver_burden_zarit
    advance: Caregiver + advance care plan established