Alzheimer's Disease¶

VERSION: 1.1 CREATED: January 27, 2026 REVISED: January 30, 2026 STATUS: Draft - Pending Review

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) 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 :: :: 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 :: :: 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 :: :: 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 :: :: 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 :: :: 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