Clinical Commander

Back to dossier
neuro.alzheimer.v1PRODUCTION
neuro.alzheimer.v1

Alzheimer Disease (outpatient + biomarker era)

neurologychronicadultgeriatric
Hard-required inputs
0 / 12
Care setting:

Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

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
2
Actions
0
Advance rule
Set
Advance when

AD clinical syndrome assigned (probable AD dementia / MCI due to AD / preclinical AD)

Patient inputs (18)

Age ≥65 typical sporadic AD; <65 = early-onset AD (consider APOE e4/e4 + dominant mutations) (NIA-AA 2011 PMID 21514250)

IADL impairment defines major NCD vs MCI; preserved IADL = MCI due to AD (Albert AAN MCI PMID 21514249)

Amnestic presentation is most common AD phenotype (McKhann NIA-AA 2011 PMID 21514250)

Depression mimics AD (pseudodementia); GDS preferred elderly; treat before assigning AD label (AAN 2018)

Anticholinergic / benzodiazepine / sedating burden reversibly worsens cognition; deprescribe per AGS Beers 2023

Insidious months-years onset characteristic of AD; rapid <1 y → CJD / autoimmune workup (route to symptom.dementia.v1 red-flag)

Hypothyroid mimic; reversible (AAN 2018)

B12 deficiency mimic; treat with IM if <200 pg/mL (AAN 2018)

Neurosyphilis is reversible dementia (AAN 2018)

HIV-associated neurocognitive disorder treatable with ART (AAN 2018)

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)

Delirium-superimposed-on-dementia common; CAM/4AT must be negative before chronic AD diagnosis (Inouye Lancet 2014)

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)

Confirms AD biology when CSF/blood unavailable; mandatory pre-donanemab tau-PET stratification (TRAILBLAZER-ALZ 2 PMID 37459141)

Biparietal/temporal hypometabolism supports AD vs FTD frontal pattern (NIA-AA 2018)

Caregiver Zarit ≥21 drives institutionalization risk; respite + APS referral (APA 2024)

MoCA <18 / FAST ≥4 / accident history → driving cessation discussion (AAN 2018; APA 2024)

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)

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (13)

13 need judgement
  • informationalseveresevere_ad_dementia
    Severe AD — MMSE <10, CDR 3, total dependence, mutism / immobility late, FAST 6-7 (NIA-AA 2011)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverearia_e_anti_amyloid_edema
    ARIA-E — vasogenic edema on FLAIR/T2 in mAb recipient; symptomatic (headache, visual change, confusion, seizure) OR asymptomatic surveillance finding (CLARITY-AD PMID 36449413)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverearia_h_microhemorrhage
    ARIA-H — new microhemorrhage (≤10 mm hypointensity on GRE/SWI) or superficial siderosis in mAb recipient (CLARITY-AD PMID 36449413)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverewandering_safety_risk
    Wandering — elopement risk; MedicAlert / GPS device / secured exits required
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatemild_ad_dementia
    Mild AD dementia — MMSE 21-26, CDR 1, IADL impairment, episodic memory predominant (NIA-AA 2011 PMID 21514250)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatemoderate_ad_dementia
    Moderate AD — MMSE 10-20, CDR 2, ADL impairment, language + executive decline (NIA-AA 2011)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateamyloid_pet_positive_mab_eligible
    Amyloid biomarker positive + CDR 0.5-1 + MMSE ≥22 + no anticoagulation + <5 microbleeds + no superficial siderosis → lecanemab or donanemab candidate (CLARITY-AD PMID 36449413; TRAILBLAZER-ALZ 2 PMID 37459141)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatebehavioral_neuropsychiatric_sx
    BPSD — apathy / agitation / psychosis / depression / aggression; non-pharm DICE FIRST per APA 2024
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatecaregiver_burden_severe
    Caregiver Zarit ≥21 → high burnout risk; institutionalization driver
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatedriving_safety_concern
    Driving concern — MoCA <18 / FAST ≥4 / accident / family report / on-road eval failure
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmildpreclinical_ad_biomarker_positive
    Preclinical AD — amyloid biomarker positive (CSF/blood/PET) but asymptomatic (NIA-AA 2018 PMID 29653606)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmildmci_due_to_ad
    MCI due to AD — amyloid biomarker positive + objective episodic memory deficit + preserved IADL (Albert AAN MCI PMID 21514249)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmildsundowning_evening_agitation
    Sundowning — evening agitation / confusion / pacing; circadian disruption
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

CONTEXTrequiredDrives screening
Loading…

Recommended regimen

Cholinesterase inhibitor + memantine ladder (AAN 2018; NICE 2024 dementia)
axis: ad_cognitive_enhancersstep 1 - Step 1 — Mild-to-moderate AD (MMSE 10-26) — start ChEI
Selected step "Step 1 — Mild-to-moderate AD (MMSE 10-26) — start ChEI" — Probable AD dementia mild-to-moderate per NIA-AA 2011 (McKhann PMID 21514250)
  • donepezil
    first line
    AChE_inhibitor
    5 mg PO QHS • PO • daily; titrate to 10 mg after 4-6 wk (max: 23 mg/day reserved for severe AD with caution)
    triggers: mild_to_severe_AD
    AAN 2018 PMID 29282327 modest symptomatic benefit; GI + bradycardia + sleep ADRs
    rxcui 997220
  • rivastigmine
    first line
    AChE_BuChE_inhibitor
    4.6 mg/24h patch • transdermal • daily; titrate to 9.5 then 13.3 mg/24h q4 wk (max: 13.3 mg/24h patch)
    triggers: donepezil_intolerant, PO_difficulty
    Patch reduces GI ADRs; FDA-approved for PDD/DLB overlap (McKeith 2017)
    rxcui 183379
  • galantamine
    second line
    AChE_inhibitor
    8 mg ER PO daily • PO • daily; titrate to 16 then 24 mg q4 wk (max: 24 mg/day)
    triggers: alternative_ChEI
    Weak nicotinic modulation (AAN 2018)
    rxcui 2690627

outpatient playbook — drug actions (8)

  1. 1. donepezil
    5 mg PO QHS → 10 mg • PO • daily
    trigger: Mild-moderate AD
    AAN 2018 first-line ChEI
  2. 2. rivastigmine patch
    4.6 → 9.5 → 13.3 mg/24h • transdermal • daily
    trigger: GI intolerance or PO difficulty
    Patch reduces GI ADRs
  3. 3. memantine
    5 mg titrate to 10 mg BID • PO • BID
    trigger: Moderate-severe (MMSE ≤14)
    AAN 2018 add-on
  4. 4. lecanemab
    10 mg/kg IV q2w × 18 mo • IV infusion • q2 wk
    trigger: Biomarker+ early AD + CDR 0.5-1 + MMSE ≥22 + safety screen passed
    CLARITY-AD PMID 36449413
  5. 5. donanemab
    700 mg × 3 then 1400 mg IV q4w • IV infusion • q4 wk to amyloid clearance
    trigger: Biomarker+ early AD + low/intermediate tau PET + safety screen passed
    TRAILBLAZER-ALZ 2 PMID 37459141
  6. 6. sertraline
    25-100 mg PO daily • PO • daily
    trigger: Depression / anxiety / agitation
    APA 2024
  7. 7. citalopram
    10-20 mg PO daily • PO • daily
    trigger: AD agitation (CitAD)
    CitAD PMID 24549548; QT-limited
  8. 8. pimavanserin
    34 mg PO daily • PO • daily
    trigger: AD psychosis (off-label)
    No D2 blockade (avoid motor worsening if DLB overlap)

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Insidious episodic memory decline + word-finding + IADL impact (NIA-AA 2011 McKhann PMID 21514250); Amnestic MCI — preserved IADL but objective episodic memory deficit (Albert AAN MCI PMID 21514249); CSF Aβ42/40 low OR amyloid-PET positive OR blood p-tau217 elevated (NIA-AA 2018 PMID 29653606).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Alzheimer Disease (outpatient + biomarker era)** (neuro.alzheimer.v1).
Phenotype framing: 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
Scope: 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)

No severity triggers fired against current inputs.

Plan

Regimen axis: **Cholinesterase inhibitor + memantine ladder (AAN 2018; NICE 2024 dementia)** — step "Step 1 — Mild-to-moderate AD (MMSE 10-26) — start ChEI".
1. donepezil 5 mg PO QHS PO daily; titrate to 10 mg after 4-6 wk (AChE_inhibitor, first line) — AAN 2018 PMID 29282327 modest symptomatic benefit; GI + bradycardia + sleep ADRs
2. rivastigmine 4.6 mg/24h patch transdermal daily; titrate to 9.5 then 13.3 mg/24h q4 wk (AChE_BuChE_inhibitor, first line) — Patch reduces GI ADRs; FDA-approved for PDD/DLB overlap (McKeith 2017)
3. galantamine 8 mg ER PO daily PO daily; titrate to 16 then 24 mg q4 wk (AChE_inhibitor, second line) — Weak nicotinic modulation (AAN 2018)

Setting playbook (outpatient) — Primary cognitive clinic — comprehensive AD management q3-6 mo: cognitive + functional assessment, biomarker review, mAb eligibility + ARIA monitoring, BPSD management, lifestyle (BP <130/80, statin, exercise, MIND diet), caregiver support, driving + advance directives
4. donepezil 5 mg PO QHS → 10 mg PO daily — Mild-moderate AD (AAN 2018 first-line ChEI)
5. rivastigmine patch 4.6 → 9.5 → 13.3 mg/24h transdermal daily — GI intolerance or PO difficulty (Patch reduces GI ADRs)
6. memantine 5 mg titrate to 10 mg BID PO BID — Moderate-severe (MMSE ≤14) (AAN 2018 add-on)
7. lecanemab 10 mg/kg IV q2w × 18 mo IV infusion q2 wk — Biomarker+ early AD + CDR 0.5-1 + MMSE ≥22 + safety screen passed (CLARITY-AD PMID 36449413)
8. donanemab 700 mg × 3 then 1400 mg IV q4w IV infusion q4 wk to amyloid clearance — Biomarker+ early AD + low/intermediate tau PET + safety screen passed (TRAILBLAZER-ALZ 2 PMID 37459141)
9. sertraline 25-100 mg PO daily PO daily — Depression / anxiety / agitation (APA 2024)
10. citalopram 10-20 mg PO daily PO daily — AD agitation (CitAD) (CitAD PMID 24549548; QT-limited)
11. pimavanserin 34 mg PO daily PO daily — AD psychosis (off-label) (No D2 blockade (avoid motor worsening if DLB overlap))

Non-pharmacologic actions:
- Non-pharm DICE for BPSD (APA 2024)
- Aerobic exercise 150 min/wk (FINGER signal)
- MIND / Mediterranean diet
- Cognitive engagement + social activity
- Hearing aids + glasses (Lancet 2024 dementia commission)
- Sleep hygiene + OSA workup if STOP-BANG ≥3
- BP control <130/80 (SPRINT-MIND PMID 30688979)
- Statin per ACC/AHA 2026
- Driving evaluation per state + functional capacity
- Caregiver education + support groups (Alzheimer Association)
- Advance directives + POLST + capacity assessment at moderate stage
- Vaccinations annual influenza + pneumococcal + COVID + RSV
- Annual neuro-psych battery if cognitive change
- Bone health (DEXA + vitamin D + calcium; fracture risk elevated)

AVOID / contraindication checks:
- ChEI_bradycardia_syncope_HR_baseline (AAN 2018)
- ChEI_GI_titrate_with_food (AAN 2018)
- ChEI_avoid_concurrent_anticholinergic (AGS Beers 2023)
- Memantine_renal_dose_adjust_eGFR_lt_30 (AAN 2018)
- ChEI_caution_in_severe_COPD_asthma (AAN 2018)

Monitoring

Regimen monitoring:
- MoCA or MMSE q6 to 12 mo (AAN 2018)
- HR at each visit for ChEI (AAN 2018)
- caregiver function review q3 mo (NICE 2024 dementia)
- BEERS deprescribe sweep q6 mo (AGS Beers 2023)

Setting (outpatient) monitoring:
- MoCA + functional review q3-6 mo
- ARIA MRI baseline + before infusions 5/7/14 on mAb
- Med titration + ChEI HR monitor
- Annual hearing + vision + sleep + driving
- Caregiver Zarit q3-6 mo

Follow-up plan: 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)
- Close-out criterion: Caregiver + advance care plan established

Monitoring phase: 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)

Disposition

Current setting: outpatient — Primary cognitive clinic — comprehensive AD management q3-6 mo: cognitive + functional assessment, biomarker review, mAb eligibility + ARIA monitoring, BPSD management, lifestyle (BP <130/80, statin, exercise, MIND diet), caregiver support, driving + advance directives

Disposition criteria:
- Continue indefinite cognitive clinic q3-6 mo
- Transition to palliative + hospice at FAST 7 (loss ambulation + ≤6 words/day + recurrent infections)

Escalation triggers (move to higher acuity):
- Acute delirium superimposed → ED + workup
- ARIA-E with neuro deficit on mAb → pause + urgent MRI + neurology
- Severe BPSD refractory to non-pharm + SSRI → consider time-limited antipsychotic with documented goal
- Behavioural crisis with safety risk → ED + geriatric psychiatry
- Caregiver burnout → respite + APS / home health intensification

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [SEVERE] Severe AD — MMSE <10, CDR 3, total dependence, mutism / immobility late, FAST 6-7 (NIA-AA 2011)
- [SEVERE] ARIA-E — vasogenic edema on FLAIR/T2 in mAb recipient; symptomatic (headache, visual change, confusion, seizure) OR asymptomatic surveillance finding (CLARITY-AD PMID 36449413)
- [SEVERE] ARIA-H — new microhemorrhage (≤10 mm hypointensity on GRE/SWI) or superficial siderosis in mAb recipient (CLARITY-AD PMID 36449413)

Citations

- NIA-AA 2018 research framework (Jack PMID 29653606) + NIA-AA 2011 clinical criteria (McKhann PMID 21514250) + AAN 2024 anti-amyloid mAb appropriate-use + APA 2024 BPSD + AGS Beers 2023 [PMID:29653606](https://pubmed.ncbi.nlm.nih.gov/29653606/)
- Cited evidence (PMID 36449413) [PMID:36449413](https://pubmed.ncbi.nlm.nih.gov/36449413/)
- Cited evidence (PMID 37459141) [PMID:37459141](https://pubmed.ncbi.nlm.nih.gov/37459141/)
- Cited evidence (PMID 21514249) [PMID:21514249](https://pubmed.ncbi.nlm.nih.gov/21514249/)
- Cited evidence (PMID 21514250) [PMID:21514250](https://pubmed.ncbi.nlm.nih.gov/21514250/)

Last reconciled with current guidelines: 2026-05-15.
References
  • NIA-AA 2018 research framework (Jack PMID 29653606) + NIA-AA 2011 clinical criteria (McKhann PMID 21514250) + AAN 2024 anti-amyloid mAb appropriate-use + APA 2024 BPSD + AGS Beers 2023 — PMID:29653606
  • Cited evidence (PMID 36449413) — PMID:36449413
  • Cited evidence (PMID 37459141) — PMID:37459141
  • Cited evidence (PMID 21514249) — PMID:21514249
  • Cited evidence (PMID 21514250) — PMID:21514250