Skip to content

Alzheimer's Disease

VERSION: 1.1 CREATED: January 27, 2026 REVISED: January 30, 2026 STATUS: Approved

DIAGNOSIS: Alzheimer's Disease ICD-10: G30.9 (Alzheimer's disease, unspecified), G30.0 (Early-onset AD), G30.1 (Late-onset AD), F02.80 (Dementia in AD without behavioral disturbance), F02.81 (Dementia in AD with behavioral disturbance), G30.8 (Other Alzheimer's disease)

CPT CODES: 85025 (CBC with differential), 80048 (BMP), 84443 (TSH), 82607 (Vitamin B12), 82746 (Folate), 80076 (Hepatic panel (AST, ALT, albumin)), 82310 (Calcium), 81003 (Urinalysis), 83036 (Hemoglobin A1c), 80061 (Lipid panel), 83090 (Homocysteine), 82306 (Vitamin D, 25-hydroxy), 86592 (RPR), 87389 (HIV testing), 85652 (ESR), 81401 (APOE genotyping), 81406 (Genetic panel (PSEN1, PSEN2, APP)), 82525 (Copper), 86255 (Paraneoplastic antibody panel), 70551 (MRI Brain without contrast), 70450 (CT Head non-contrast), 78816 (Amyloid PET), 95816 (EEG), 95810 (Sleep study (polysomnography)), 78607 (DaTscan (ioflupane I-123)), 89051 (Cell count, protein, glucose), 83519 (CSF Aβ42 (amyloid beta 1-42)) CLINICAL SYNONYMS: Alzheimer's disease, Alzheimer disease, AD, senile dementia of Alzheimer type, SDAT, presenile dementia, Alzheimer's dementia, dementia of the Alzheimer type, DAT, early-onset Alzheimer's, late-onset Alzheimer's, EOAD, LOAD, amyloid-related dementia, Alzheimer's-type dementia SCOPE: Diagnosis confirmation using NIA-AA criteria, biomarker assessment, pharmacologic treatment with cholinesterase inhibitors and memantine, anti-amyloid disease-modifying therapies, BPSD management, safety planning, and caregiver support. Primarily outpatient-focused with coverage for ED and hospital presentations.

PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting

SECTION A: ACTION ITEMS

1. LABORATORY WORKUP

1A. Essential/Core Labs (Reversible Causes Screen)

Test ED HOSP OPD ICU Rationale Target Finding
CBC with differential (CPT 85025) STAT STAT ROUTINE - Rule out infection, anemia, malignancy contributing to cognitive impairment Normal
BMP (CPT 80048) STAT STAT ROUTINE - Metabolic causes of confusion (hyponatremia, uremia, hypoglycemia) Normal electrolytes, renal function
TSH (CPT 84443) URGENT ROUTINE ROUTINE - Hypothyroidism is reversible cause of cognitive impairment 0.4-4.0 mIU/L
Vitamin B12 (CPT 82607) URGENT ROUTINE ROUTINE - B12 deficiency causes reversible cognitive decline >300 pg/mL (>400 optimal)
Folate (CPT 82746) - ROUTINE ROUTINE - Deficiency contributes to cognitive impairment >3 ng/mL
Hepatic panel (AST, ALT, albumin) (CPT 80076) - ROUTINE ROUTINE - Hepatic encephalopathy; nutritional status Normal
Calcium (CPT 82310) STAT ROUTINE ROUTINE - Hypercalcemia causes confusion 8.5-10.5 mg/dL
Urinalysis (CPT 81003) STAT STAT ROUTINE - UTI common cause of acute confusion in elderly Negative for infection

1B. Extended Workup (Second-line)

Test ED HOSP OPD ICU Rationale Target Finding
Hemoglobin A1c (CPT 83036) - ROUTINE ROUTINE - Diabetes affects cognition and vascular risk <7.0%
Lipid panel (CPT 80061) - ROUTINE ROUTINE - Vascular risk factor modification LDL <100 mg/dL
Homocysteine (CPT 83090) - ROUTINE ROUTINE - Elevated levels associated with AD and vascular disease <15 μmol/L
Vitamin D, 25-hydroxy (CPT 82306) - ROUTINE ROUTINE - Deficiency associated with cognitive decline >30 ng/mL
RPR (CPT 86592) or VDRL - ROUTINE ROUTINE - Neurosyphilis is treatable cause Nonreactive
HIV testing (CPT 87389) - ROUTINE ROUTINE - HIV-associated neurocognitive disorder if risk factors Negative
ESR (CPT 85652) / CRP (CPT 86140) - ROUTINE ROUTINE - Inflammatory or autoimmune causes Normal

1C. Rare/Specialized (Refractory or Atypical)

Test ED HOSP OPD ICU Rationale Target Finding
APOE genotyping (CPT 81401) - - ROUTINE - Risk stratification; ARIA risk assessment for anti-amyloid therapy APOE ε4 status
Genetic panel (PSEN1, PSEN2, APP) (CPT 81406) - - EXT - Early-onset AD (<65) with family history No pathogenic mutation (AD diagnosis still valid)
Heavy metal panel (lead, mercury) (CPT 83655, 83825) - - EXT - History of occupational exposure Normal
Copper (CPT 82525), ceruloplasmin (CPT 82390) - EXT EXT - Wilson disease if age <50 with movement disorder Normal
Paraneoplastic antibody panel (CPT 86255) - EXT EXT - Rapid progression; cancer history Negative
Anti-neuronal antibodies (NMDA-R, LGI1, CASPR2) (CPT 86255) - EXT EXT - Atypical presentation; rapid progression Negative

2. DIAGNOSTIC IMAGING & STUDIES

2A. Essential/First-line

Study ED HOSP OPD ICU Timing Target Finding Contraindications
MRI Brain without contrast (CPT 70551) URGENT ROUTINE ROUTINE - At initial evaluation Hippocampal and medial temporal atrophy; rule out structural causes (tumor, SDH, NPH, stroke) MRI-incompatible devices, severe claustrophobia
CT Head non-contrast (CPT 70450) STAT STAT ROUTINE - If MRI unavailable or contraindicated Rule out mass, hemorrhage, hydrocephalus None

2B. Extended

Study ED HOSP OPD ICU Timing Target Finding Contraindications
Amyloid PET (CPT 78816) - - ROUTINE - Diagnostic uncertainty; anti-amyloid therapy eligibility Positive amyloid deposition confirms AD pathology None
FDG-PET Brain (CPT 78816) - - ROUTINE - Differentiate AD from FTD; atypical presentations AD: bilateral temporoparietal hypometabolism None
Tau PET (flortaucipir) (CPT 78816) - - EXT - Staging AD; donanemab eligibility Elevated tau correlates with disease stage None
MRI Brain volumetrics (CPT 70551) - - ROUTINE - Baseline for anti-amyloid monitoring; track progression Quantify hippocampal and whole brain atrophy MRI contraindications
MRI with SWI/GRE sequences (CPT 70551) - ROUTINE ROUTINE - Pre-treatment for anti-amyloid (microbleed assessment) Count microbleeds (<4 eligible for therapy) MRI contraindications
EEG (CPT 95816) URGENT ROUTINE ROUTINE - Seizures, encephalopathy, or rapid decline Diffuse slowing typical in AD; rule out CJD None
Sleep study (polysomnography) (CPT 95810) - - ROUTINE - Sleep apnea contributing to cognition; RBD evaluation Assess AHI; REM without atonia suggests DLB None

2C. Rare/Specialized

Study ED HOSP OPD ICU Timing Target Finding Contraindications
DaTscan (ioflupane I-123) (CPT 78607) - - EXT - Differentiate DLB/PDD from AD Reduced uptake: DLB; Normal: AD Iodine hypersensitivity
SPECT (perfusion) (CPT 78607) - - EXT - Alternative to PET if unavailable Regional hypoperfusion patterns None
Whole body PET-CT (CPT 78816) - EXT EXT - Paraneoplastic workup if suspected Rule out occult malignancy None

LUMBAR PUNCTURE

Indication: Diagnostic confirmation with CSF biomarkers; clinical trial eligibility; atypical presentation; rapid progression; young-onset (<65) Timing: ROUTINE for biomarker confirmation; URGENT if autoimmune or infectious etiology suspected Volume Required: 10-15 mL standard; additional for research biomarkers

Study ED HOSP OPD ICU Rationale Target Finding
Cell count, protein, glucose (CPT 89051) URGENT ROUTINE ROUTINE - Rule out infection, inflammation WBC <5, protein <45 mg/dL, glucose >60% serum
CSF Aβ42 (amyloid beta 1-42) (CPT 83519) - ROUTINE ROUTINE - Reduced in AD due to brain amyloid deposition <600 pg/mL suggests AD pathology
CSF Aβ42/Aβ40 ratio (CPT 83519) - ROUTINE ROUTINE - More accurate than Aβ42 alone <0.05-0.08 suggests AD (assay-dependent)
CSF total tau (t-tau) (CPT 83519) - ROUTINE ROUTINE - Elevated in neurodegeneration >400 pg/mL suggests neuronal injury
CSF phosphorylated tau (p-tau181 or p-tau217) (CPT 83519) - ROUTINE ROUTINE - Specific for AD pathology; best discriminator Elevated p-tau181 >60 pg/mL or p-tau217 >20 pg/mL
CSF NfL (neurofilament light) (CPT 83519) - ROUTINE ROUTINE - Non-specific marker of neuronal damage Elevated suggests active neurodegeneration
14-3-3 protein (CPT 83519) - ROUTINE ROUTINE - Rapid progression; suspected CJD Negative (positive suggests CJD)
RT-QuIC - ROUTINE EXT - Prion disease confirmation if suspected Negative
Autoimmune encephalitis panel (CPT 86255) - EXT EXT - Atypical presentation; subacute onset Negative

Special Handling: CSF biomarkers require polypropylene tubes; freeze within 1 hour; send to qualified reference lab Contraindications: Coagulopathy (INR >1.5, platelets <50k); posterior fossa mass; skin infection at puncture site

3. TREATMENT

3A. Acute/Emergent

Treatment Route Indication Dosing Contraindications Monitoring ED HOSP OPD ICU
Treat reversible causes Various Identified metabolic or infectious etiology Per specific cause :: Various :: per etiology :: Correct hyponatremia slowly, treat UTI, replace B12, treat hypothyroidism Depends on intervention Cognitive reassessment after treatment STAT STAT ROUTINE -
Thiamine IV/PO Suspected Wernicke's; alcoholism; malnutrition 500 mg IV TID x 3 days; 100 mg PO daily :: IV/PO :: TID x 3d then daily :: 500 mg IV TID x 3 days if Wernicke suspected; then 100 mg PO daily maintenance None Clinical improvement in confusion STAT STAT ROUTINE -
Vitamin B12 IM/PO B12 deficiency (<300 pg/mL) 1000 mcg IM daily x 7d; 1000 mcg IM weekly x 4wk; 1000 mcg IM monthly :: IM/PO :: daily x 7d then weekly then monthly :: 1000 mcg IM daily x 7d, then weekly x 4wk, then monthly; or high-dose oral 1000-2000 mcg daily None B12 level at 2 months; cognitive improvement over months - ROUTINE ROUTINE -

3B. Cholinesterase Inhibitors (Cognitive Enhancement)

Treatment Route Indication Dosing Contraindications Monitoring ED HOSP OPD ICU
Donepezil (Aricept) PO Mild, moderate, or severe AD (first-line) 5 mg :: PO :: qHS :: Start 5 mg qHS x 4-6 weeks; if tolerated, increase to 10 mg qHS; 23 mg available for moderate-severe AD after stable on 10 mg Sick sinus syndrome; second/third degree heart block without pacemaker; active GI bleeding; severe COPD Heart rate; GI symptoms (nausea, diarrhea); vivid dreams; muscle cramps - ROUTINE ROUTINE -
Rivastigmine oral (Exelon) PO Mild-moderate AD; may be better for attention/executive symptoms 1.5 mg :: PO :: BID :: Start 1.5 mg BID with meals; increase by 1.5 mg BID every 2 weeks; target 6 mg BID Sick sinus syndrome; second/third degree heart block; active GI bleeding; severe hepatic impairment GI symptoms (most common); weight loss; bradycardia - ROUTINE ROUTINE -
Rivastigmine patch (Exelon Patch) TD Mild-moderate AD; better GI tolerability than oral 4.6 mg/24hr :: TD :: daily :: Start 4.6 mg/24hr patch; increase every 4 weeks; target 9.5-13.3 mg/24hr; apply to clean, hairless skin Sick sinus syndrome; second/third degree heart block; active GI bleeding Skin irritation (rotate sites); GI symptoms less than oral - ROUTINE ROUTINE -
Galantamine (Razadyne) PO Mild-moderate AD; dual mechanism (AChE inhibitor + nicotinic modulator) 4 mg :: PO :: BID :: Start 4 mg BID with meals x 4 weeks; increase to 8 mg BID x 4 weeks; target 8-12 mg BID Sick sinus syndrome; second/third degree heart block; severe renal impairment (CrCl <9); severe hepatic impairment GI symptoms; bradycardia; weight loss - ROUTINE ROUTINE -
Galantamine ER (Razadyne ER) PO Once-daily alternative for adherence 8 mg :: PO :: daily :: Start 8 mg daily with breakfast x 4 weeks; increase by 8 mg every 4 weeks; target 16-24 mg daily Sick sinus syndrome; second/third degree heart block; severe renal impairment (CrCl <9); severe hepatic impairment GI symptoms; bradycardia; weight loss - ROUTINE ROUTINE -

3C. NMDA Receptor Antagonist

Treatment Route Indication Dosing Contraindications Monitoring ED HOSP OPD ICU
Memantine (Namenda) PO Moderate-severe AD; add to cholinesterase inhibitor 5 mg :: PO :: daily :: Start 5 mg daily x 1 week; increase by 5 mg/week: 5 mg BID, then 5 mg/10 mg, then 10 mg BID Severe renal impairment (reduce dose if CrCl 5-29: max 5 mg BID) Confusion, dizziness, constipation, headache - ROUTINE ROUTINE -
Memantine XR (Namenda XR) PO Once-daily option for adherence 7 mg :: PO :: daily :: Start 7 mg daily; increase by 7 mg/week; target 28 mg daily Severe renal impairment (reduce dose if CrCl 5-29: max 14 mg daily) Confusion, dizziness, constipation, headache - ROUTINE ROUTINE -
Memantine/Donepezil (Namzaric) PO Combination for moderate-severe AD already on both 28/10 mg :: PO :: qHS :: One capsule (28 mg memantine XR + 10 mg donepezil) once daily at bedtime; must be stable on both drugs first Severe renal impairment; sick sinus syndrome; second/third degree heart block Confusion, dizziness, GI symptoms, vivid dreams - - ROUTINE -

3D. Disease-Modifying Therapies (Anti-Amyloid)

Treatment Route Indication Dosing Pre-Treatment Requirements Contraindications Monitoring ED HOSP OPD ICU
Lecanemab (Leqembi) IV Early AD (MCI or mild dementia) with confirmed amyloid pathology 10 mg/kg IV q2wk :: IV :: q2wk :: 10 mg/kg IV every 2 weeks; infuse over approximately 1 hour Amyloid PET positive OR CSF biomarkers confirming amyloid; MRI within 1 year (assess microbleeds); APOE genotyping strongly recommended; informed consent for ARIA risk >4 cerebral microbleeds; superficial siderosis; recent macrohemorrhage; concurrent anticoagulation (relative); APOE ε4/ε4 (higher ARIA risk - not absolute CI) MRI: baseline, weeks 7, 14, 52, 78 (ARIA monitoring); clinical assessment for ARIA symptoms (headache, confusion, visual changes) - - ROUTINE -
Donanemab (Kisunla) IV Early AD (MCI or mild dementia) with confirmed amyloid AND intermediate/high tau pathology 700 mg IV q4wk x 3; then 1400 mg IV q4wk :: IV :: q4wk :: 700 mg IV every 4 weeks x 3 doses, then 1400 mg IV every 4 weeks until amyloid clearance (by PET); discontinue when PET negative Amyloid PET positive; Tau PET showing intermediate or high tau levels; MRI baseline; APOE genotyping (higher ARIA in ε4/ε4) Same as lecanemab; higher ARIA risk in APOE ε4 homozygotes MRI: baseline, weeks 12, 24, 52, 76 (ARIA monitoring); repeat amyloid PET to assess clearance - - EXT -
~~Aducanumab (Aduhelm)~~ IV DISCONTINUED — Biogen halted Aduhelm commercialization January 2024; no longer available N/A N/A N/A N/A - - - -

ARIA Monitoring Protocol: - ARIA-E (edema): Sulcal effusion and/or cortical edema on FLAIR MRI; usually asymptomatic but may cause headache, confusion, visual disturbance - ARIA-H (hemorrhage): Microbleeds and/or superficial siderosis on GRE/SWI - Management: Hold infusion for symptomatic ARIA or significant imaging findings; resume per protocol after resolution (typically 4-12 weeks) - APOE ε4 risk: Homozygotes have ~35% ARIA risk with lecanemab vs ~10% for non-carriers; requires shared decision-making

3E. Behavioral and Psychological Symptoms of Dementia (BPSD)

Treatment Route Indication Dosing Contraindications Monitoring ED HOSP OPD ICU
Citalopram PO Depression; mild-moderate agitation 10 mg :: PO :: daily :: Start 10 mg daily; max 20 mg in elderly due to QT prolongation risk QT prolongation; concurrent QT-prolonging drugs; severe hepatic impairment ECG at baseline if cardiac risk; QTc monitoring if >20 mg - ROUTINE ROUTINE -
Sertraline (Zoloft) PO Depression; anxiety 25 mg :: PO :: daily :: Start 25 mg daily; increase by 25 mg every 1-2 weeks; typical dose 50-100 mg daily MAOIs; uncontrolled seizures (lowers threshold slightly) GI symptoms initially; bleeding risk with anticoagulants - ROUTINE ROUTINE -
Mirtazapine (Remeron) PO Depression with poor appetite, insomnia, and weight loss 7.5 mg :: PO :: qHS :: Start 7.5-15 mg qHS; may increase to 30-45 mg qHS; lower doses more sedating MAOIs; angle-closure glaucoma Weight gain (often desired); sedation; hyperlipidemia - ROUTINE ROUTINE -
Trazodone PO Insomnia; sundowning; mild agitation 25 mg :: PO :: qHS :: Start 25-50 mg qHS; titrate by 25-50 mg every 3-5 days; typical 50-150 mg qHS for sleep Concurrent MAOIs; significant QT prolongation Orthostatic hypotension (fall risk); priapism (rare); QTc - ROUTINE ROUTINE -
Melatonin PO Sleep disturbance; circadian rhythm dysfunction 3 mg :: PO :: qHS :: Start 3 mg qHS, 30 min before bed; may increase to 6-9 mg if needed None significant Daytime drowsiness; minimal side effects - ROUTINE ROUTINE -
Brexpiprazole (Rexulti) PO Agitation in AD (FDA approved 2023) 0.5 mg :: PO :: daily :: Start 0.5 mg daily x 1 week; increase to 1 mg daily x 1 week; target 2-3 mg daily Black box: increased mortality in dementia (but FDA approved for this use) Weight, metabolic parameters, EPS, falls - ROUTINE ROUTINE -
Quetiapine (Seroquel) PO Severe agitation/psychosis when non-pharmacologic fails 12.5 mg :: PO :: qHS :: Start 12.5-25 mg qHS; titrate slowly (25 mg increments); keep dose as low as possible Black box: increased mortality in dementia; Parkinson's (less risk than other antipsychotics) Metabolic effects; sedation; falls; QTc - EXT ROUTINE -
Risperidone (Risperdal) PO Severe aggression/psychosis (short-term only) 0.25 mg :: PO :: BID :: Start 0.25 mg BID; increase by 0.25 mg BID weekly; max 1 mg BID; limit to 6-12 weeks Black box: increased mortality and CVA in dementia EPS, metabolic effects, stroke risk, prolactin - EXT ROUTINE -
Haloperidol IM/IV/PO Acute severe agitation in delirium-crisis only (not chronic use) 0.5 mg :: IM :: q4-6h PRN :: 0.5-2 mg IM/IV q4-6h PRN; short-term acute use only; avoid chronic use QT prolongation; Parkinson's disease; DLB (avoid) QTc; EPS; akathisia STAT EXT - -

Non-Pharmacologic Approaches (First-Line for BPSD): - Identify and treat underlying causes (pain, infection, constipation) - Environmental modifications (reduce noise, adequate lighting) - Music therapy, art therapy, pet therapy - Structured activities and consistent routines - Caregiver education on redirection and validation techniques

4. OTHER RECOMMENDATIONS

4A. Referrals & Consults

Recommendation ED HOSP OPD ICU
Neurology/Cognitive neurology for diagnosis confirmation, biomarker interpretation, and treatment planning - ROUTINE ROUTINE -
Neuropsychology for formal cognitive testing (MoCA insufficient) to establish baseline and track progression - - ROUTINE -
Geriatric psychiatry for BPSD management and capacity evaluation when decision-making ability questioned - ROUTINE ROUTINE -
Occupational therapy for ADL assessment, cognitive strategies, and home safety evaluation - ROUTINE ROUTINE -
Speech therapy for communication strategies and swallowing evaluation if dysphagia develops - ROUTINE ROUTINE -
Social work for caregiver support resources, community services, and long-term care planning - ROUTINE ROUTINE -
Palliative care for advanced AD symptom management and goals of care discussions - ROUTINE ROUTINE -
Elder law attorney for advance directives, healthcare proxy, and financial planning while capacity exists - - ROUTINE -
Genetics counseling for early-onset AD (<65) families or those considering predictive testing - - ROUTINE -
Driving rehabilitation specialist for formal on-road driving evaluation when ability is questioned - - ROUTINE -
Infusion center coordination for anti-amyloid therapy administration and ARIA monitoring - - ROUTINE -

4B. Patient Instructions

Recommendation ED HOSP OPD
Return immediately if sudden worsening of confusion which may indicate stroke, infection, or medication toxicity STAT STAT ROUTINE
If on anti-amyloid therapy (lecanemab, donanemab): return immediately for new headache, visual changes, confusion, or unsteadiness (possible ARIA) - - ROUTINE
Complete advance directives (living will, healthcare proxy, POLST) while patient has capacity to document preferences for future care - ROUTINE ROUTINE
Designate financial power of attorney and consider trust arrangements early while patient can participate - ROUTINE ROUTINE
Do not drive until cleared by physician or formal driving evaluation; report diagnosis to DMV per state requirements - ROUTINE ROUTINE
Use pill organizers, alarms, or caregiver supervision to ensure medication adherence - ROUTINE ROUTINE
Wear medical alert bracelet with diagnosis and emergency contact in case of wandering - ROUTINE ROUTINE
Keep environment safe: remove throw rugs, install grab bars, secure stove knobs, lock away dangerous items - ROUTINE ROUTINE
Maintain consistent daily routines which help with orientation and reduce anxiety - ROUTINE ROUTINE

4C. Lifestyle & Prevention

Recommendation ED HOSP OPD
Regular aerobic exercise (150 min/week moderate intensity) may slow cognitive decline and improve mood - ROUTINE ROUTINE
Mediterranean or MIND diet emphasizing vegetables, berries, fish, whole grains, nuts, and olive oil - ROUTINE ROUTINE
Cognitive stimulation through reading, puzzles, music, social activities to support cognitive reserve - ROUTINE ROUTINE
Adequate sleep (7-8 hours); treat sleep apnea aggressively as it worsens cognition - ROUTINE ROUTINE
Social engagement and meaningful activities to reduce isolation and support emotional well-being - ROUTINE ROUTINE
Cardiovascular risk factor control: BP <130/80, A1c <7%, LDL <100 to reduce vascular contribution - ROUTINE ROUTINE
Hearing aids for hearing loss which is a modifiable dementia risk factor (Lancet Commission) - - ROUTINE
Limit alcohol to ≤1 drink daily; excess alcohol accelerates cognitive decline - ROUTINE ROUTINE
Smoking cessation to reduce vascular damage and improve overall brain health - ROUTINE ROUTINE
Caregiver respite services to prevent burnout; Alzheimer's Association support groups - ROUTINE ROUTINE

SECTION B: REFERENCE

5. DIFFERENTIAL DIAGNOSIS

Alternative Diagnosis Key Distinguishing Features Tests to Differentiate
Mild Cognitive Impairment (MCI) Cognitive decline without functional impairment; may progress to AD Serial cognitive testing; preserved ADLs
Vascular dementia Stepwise decline; focal neurologic findings; executive dysfunction prominent; vascular risk factors MRI shows significant WM disease, strategic infarcts
Dementia with Lewy bodies (DLB) Visual hallucinations; parkinsonism; REM sleep behavior disorder; fluctuating cognition DaTscan reduced; clinical criteria
Frontotemporal dementia (behavioral variant) Personality/behavior changes; disinhibition; apathy; hyperorality; often <65 years FDG-PET frontal hypometabolism; genetics
Primary progressive aphasia Language dysfunction predominates (word-finding, comprehension, grammar) Neuropsych pattern; FDG-PET language regions
Parkinson's disease dementia Parkinsonism precedes dementia by >1 year; different from DLB timing Clinical history; DaTscan
Normal pressure hydrocephalus (NPH) Triad: gait disturbance, urinary incontinence, dementia; gait earliest MRI ventriculomegaly; large-volume LP with gait improvement
Depression (pseudodementia) Prominent mood symptoms; often aware of deficits; improves with treatment GDS, PHQ-9; antidepressant trial
Creutzfeldt-Jakob disease (CJD) Rapid progression (weeks-months); myoclonus; ataxia; pyramidal signs EEG (periodic sharp waves); MRI DWI ribboning; CSF RT-QuIC
Autoimmune encephalitis Subacute onset; psychiatric features; seizures; often younger Autoantibody panel; MRI limbic changes
Medication-induced cognitive impairment Anticholinergics, benzodiazepines, opioids Medication reconciliation; improvement with discontinuation

6. MONITORING PARAMETERS

Parameter Frequency Target/Threshold Action if Abnormal ED HOSP OPD ICU
Cognitive testing (MoCA or MMSE) Every 6-12 months Establish baseline; track trajectory Adjust staging; modify treatment; increase support - ROUTINE ROUTINE -
Functional status (ADL/IADL, FAQ) Every 6-12 months Document for staging and care planning Increase caregiver support; consider placement - ROUTINE ROUTINE -
Neuropsychiatric Inventory (NPI) Each visit Monitor BPSD Non-pharmacologic interventions; consider medications - ROUTINE ROUTINE -
Weight Each visit Stable; monitor for malnutrition Nutritional consult; assess swallowing - ROUTINE ROUTINE -
MRI Brain (ARIA monitoring) Per protocol if on anti-amyloid No ARIA-E or ARIA-H Hold infusion; follow protocol for resumption - - ROUTINE -
Caregiver burden (Zarit Burden Interview) Every 6-12 months Early identification of burnout Support resources; respite care; social work - - ROUTINE -
Driving status Each visit Safe for patient and community Formal driving evaluation; report to DMV if unsafe - - ROUTINE -
ECG (if on donepezil or citalopram) Baseline; with dose changes Normal QTc (<470 ms men, <480 ms women) Reduce dose or switch medication - ROUTINE ROUTINE -
Amyloid PET (if on donanemab) Annually until clearance Amyloid negative Discontinue donanemab when cleared - - EXT -
Fall risk assessment Each visit Minimize fall risk PT referral; home safety; assistive devices - ROUTINE ROUTINE -

7. DISPOSITION CRITERIA

Disposition Criteria
Discharge home Stable cognition; safe environment; adequate caregiver support; outpatient follow-up arranged; reversible causes treated
Admit to floor Acute delirium requiring workup; behavioral crisis unsafe for home; aspiration pneumonia; falls with injury
Admit to psychiatry Severe behavioral disturbance requiring specialized psychiatric management; danger to self or others
Long-term care/Memory care Progressive decline; caregiver unable to manage safely; wandering; 24-hour supervision needed
Hospice End-stage AD; limited responsiveness; recurrent aspiration; weight loss; goals focused on comfort
Outpatient follow-up Neurology every 3-6 months early disease; every 6-12 months stable; more frequent if on anti-amyloid therapy

8. EVIDENCE & REFERENCES

Recommendation Evidence Level Source
NIA-AA diagnostic criteria for AD Class I, Level A Jack et al. Alzheimers Dement 2018
CSF biomarkers (Aβ42, t-tau, p-tau) accurate for AD Class I, Level A Hansson et al. Lancet Neurol 2018
Donepezil efficacy in mild-moderate AD Class I, Level A Birks & Harvey. Cochrane 2018
Rivastigmine efficacy in AD Class I, Level A Birks et al. Cochrane 2015
Galantamine efficacy in AD Class I, Level A Loy & Schneider. Cochrane 2006
Memantine efficacy in moderate-severe AD Class I, Level A Reisberg et al. NEJM 2003
Combination therapy (ChEI + memantine) Class I, Level A Tariot et al. JAMA 2004
Lecanemab slows cognitive decline in early AD Class I, Level A van Dyck et al. NEJM 2023 (Clarity AD)
Donanemab slows cognitive decline Class I, Level A Sims et al. JAMA 2023 (TRAILBLAZER-ALZ 2)
Brexpiprazole for agitation in AD Class I, Level A Grossberg et al. NEJM 2024
Antipsychotic mortality risk in dementia Class I, Level A Schneider et al. JAMA 2005
Mediterranean diet reduces dementia risk Class II, Level B Scarmeas et al. Ann Neurol 2006
Physical exercise may slow cognitive decline Class II, Level B Livingston et al. Lancet 2020
APOE genotyping for ARIA risk stratification Class II, Level B Sperling et al. JAMA Neurol 2024
Citalopram for agitation in AD (CitAD) Class II, Level B Porsteinsson et al. JAMA 2014
Hearing aid use reduces dementia risk Class II, Level B Lin et al. JAMA Intern Med 2023
Driving assessment in dementia Class III, Level C Iverson et al. Neurology 2010

CHANGE LOG

v1.1 (January 30, 2026) - Reformatted lab tables (1A/1B/1C/LP) to match approved plan column order (venues after test name) - Reformatted imaging tables (2A/2B/2C) to match approved plan column order - Added CPT codes to all labs, imaging, and procedures - Added clinical synonyms and expanded ICD-10 codes - Cleaned structured dosing: starting dose only in first field across all treatment rows - Removed cross-references ("Same as donepezil", "Same as immediate release") — each row now self-contained - Annotated Aducanumab (Aduhelm) as discontinued (January 2024) - Added VERSION/CREATED/REVISED header block

v1.0 (January 27, 2026) - Initial template creation - NIA-AA diagnostic criteria framework - Comprehensive biomarker workup (CSF, PET) - Complete cholinesterase inhibitor coverage (donepezil, rivastigmine, galantamine) - Memantine for moderate-severe AD - Anti-amyloid DMTs (lecanemab, donanemab, aducanumab) with ARIA monitoring - Brexpiprazole (FDA-approved 2023 for AD agitation) - BPSD management with non-pharmacologic and pharmacologic approaches - Structured dosing format for order sentence generation - Driving assessment and safety planning - Caregiver support recommendations

APPENDIX A: NIA-AA Diagnostic Framework (2018)

ATN Classification System

The NIA-AA research framework uses biomarkers to define AD biologically:

Biomarker Category Method
A (Amyloid) CSF Aβ42 low, Aβ42/Aβ40 ratio low, OR amyloid PET positive CSF assay or PET
T (Tau) CSF p-tau elevated OR tau PET positive CSF assay or PET
N (Neurodegeneration) CSF t-tau elevated, FDG-PET hypometabolism, OR MRI atrophy CSF, PET, or MRI

Clinical Staging

Stage Biomarkers Cognition Function
Preclinical AD A+ (with or without T+, N+) Normal Normal
MCI due to AD A+ T+ (N variable) Impaired (1-1.5 SD below mean) Preserved
Mild AD dementia A+ T+ N+ Impaired Mild functional decline
Moderate AD dementia A+ T+ N+ Moderate impairment Needs assistance with ADLs
Severe AD dementia A+ T+ N+ Severe impairment Dependent for basic ADLs

APPENDIX B: Anti-Amyloid Therapy Eligibility Checklist

Lecanemab (Leqembi) Eligibility

Inclusion Criteria: - [ ] MCI or mild AD dementia (MMSE typically 22-30) - [ ] Amyloid-positive (PET or CSF biomarkers) - [ ] Age typically 50-90 (clinical trial range) - [ ] Stable cardiac, renal, hepatic function - [ ] Able to complete MRI monitoring schedule

Exclusion Criteria: - [ ] >4 microbleeds on MRI - [ ] Superficial siderosis - [ ] Macrohemorrhage history - [ ] Concurrent anticoagulation (relative; discuss risk) - [ ] Uncontrolled hypertension - [ ] Moderate-severe AD dementia

Pre-Treatment Workup: - [ ] Amyloid PET OR CSF biomarkers confirming A+ - [ ] MRI Brain with SWI/GRE (microbleed count) - [ ] APOE genotyping (risk stratification, not required) - [ ] CBC, BMP, LFTs - [ ] Detailed informed consent (ARIA risk discussion)

ARIA Monitoring Schedule (Lecanemab)

Timepoint MRI Required Notes
Baseline Yes Document microbleeds, WM changes
Week 7 Yes Early ARIA detection
Week 14 Yes Before dose continuation
Week 52 Yes Annual monitoring
Week 78 Yes Continued monitoring
As needed Yes If symptoms suggestive of ARIA

APPENDIX C: ARIA Management Algorithm

ARIA-E (Edema)

ARIA-E Detected on MRI
           │
           ▼
    Symptomatic?
    ┌───────┴───────┐
   YES             NO
    │               │
    ▼               ▼
HOLD infusion    HOLD infusion
Reassess weekly  Repeat MRI in 4 weeks
    │               │
    ▼               ▼
If resolved AND   If resolved →
asymptomatic →    Resume therapy
Resume therapy

ARIA-H (Hemorrhage - New Microbleeds)

New Microbleeds Action
1-4 new Consider continuing with close monitoring
5-9 new Hold; repeat MRI in 4 weeks
>9 new or macrohemorrhage Discontinue permanently

APPENDIX D: Driving Assessment in Alzheimer's Disease

Red Flags Requiring Immediate Driving Cessation

  • Getting lost in familiar areas
  • Involvement in at-fault accidents
  • Traffic violations
  • Impaired visuospatial skills (clock drawing failure)
  • CDR ≥1 (mild dementia)

Assessment Tools

Tool Description
CDR (Clinical Dementia Rating) CDR ≥1 suggests high-risk driver
Trail Making Test B >180 seconds suggests impaired executive function
Clock Drawing Test Errors suggest visuospatial impairment
MMSE/MoCA Not sufficient alone for driving decisions
On-road driving evaluation Gold standard; refer to OT driving specialist

Documentation Requirements

  • Document driving discussion at each visit
  • Note patient and family concerns
  • Record any incidents or near-misses
  • Follow state reporting requirements (varies by jurisdiction)
  • Provide written recommendation if cessation advised