Mild Cognitive Impairment (MCI)

DIAGNOSIS: Mild Cognitive Impairment (MCI) ICD-10: G31.84 (Mild cognitive impairment), F06.7 (Mild neurocognitive disorder), R41.81 (Age-related cognitive decline)

CPT CODES: 85025 (CBC with differential), 80053 (CMP), 84443 (TSH), 82607 (Vitamin B12), 82746 (Folate), 83036 (HbA1c), 80061 (Fasting lipid panel), 82947 (Glucose, fasting), 86592 (RPR), 87389 (HIV-1/2 antigen/antibody), 82306 (Vitamin D, 25-OH), 83090 (Homocysteine), 85652 (ESR), 81003 (Urinalysis), 83921 (Methylmalonic acid), 83655 (Heavy metal panel: lead), 82525 (Copper), 86255 (Paraneoplastic antibody panel), 86235 (Anti-neuronal antibodies: NMDA-R, LGI1, CASPR2, GABA-B), 81401 (APOE genotyping), 81406 (Genetic testing: PSEN1, PSEN2, APP), 86618 (Lyme serology), 70551 (MRI Brain without contrast), 96116 (Mini-Mental State Examination), 70450 (CT Head non-contrast), 78816 (FDG-PET Brain), 78811 (Amyloid PET), 95810 (Sleep study, polysomnography), 95816 (EEG), 78607 (DaTscan), 83519 (CSF Amyloid-beta 1-42) SYNONYMS: MCI, amnestic MCI, non-amnestic MCI, pre-dementia, prodromal Alzheimer's, early cognitive decline, age-associated memory impairment (AAMI), cognitive impairment not dementia (CIND), mild neurocognitive disorder SCOPE: Outpatient-focused evaluation for MCI, identification of reversible causes, subtype classification (amnestic vs non-amnestic), risk factor modification, monitoring for progression, and symptomatic treatment. Includes guidance on disease-modifying therapy eligibility (anti-amyloid agents) and advance care planning.

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

STATUS: Approved

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

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SECTION A: ACTION ITEMS

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1. LABORATORY WORKUP

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

Test (CPT)	ED	HOSP	OPD	ICU	Rationale	Target Finding
CBC with differential (CPT 85025)	-	ROUTINE	ROUTINE	-	Anemia, infection, or malignancy contributing to cognitive changes	Normal
CMP (CPT 80053)	-	ROUTINE	ROUTINE	-	Hyponatremia, uremia, hypercalcemia, hepatic encephalopathy as reversible causes	Normal electrolytes, renal, hepatic function
TSH (CPT 84443)	-	ROUTINE	ROUTINE	-	Hypothyroidism is reversible cause of cognitive impairment	0.4-4.0 mIU/L
Vitamin B12 (CPT 82607)	-	ROUTINE	ROUTINE	-	Deficiency causes reversible cognitive impairment; common in elderly	>300 pg/mL (>400 pg/mL optimal for neurological function)
Folate (CPT 82746)	-	ROUTINE	ROUTINE	-	Deficiency contributes to cognitive impairment; check with B12	>3 ng/mL
HbA1c (CPT 83036)	-	ROUTINE	ROUTINE	-	Diabetes management affects cognition; vascular risk factor	<7% (individualize in elderly)
Fasting lipid panel (CPT 80061)	-	ROUTINE	ROUTINE	-	Vascular risk factor assessment; hyperlipidemia accelerates cognitive decline	LDL <100 mg/dL; <70 if established CVD
Glucose, fasting (CPT 82947)	-	ROUTINE	ROUTINE	-	Diabetes screening; glycemic control affects cognition	70-100 mg/dL

1B. Extended Workup (Second-line)

Test (CPT)	ED	HOSP	OPD	ICU	Rationale	Target Finding
RPR (CPT 86592)	-	ROUTINE	ROUTINE	-	Neurosyphilis is rare but treatable cause of cognitive impairment	Nonreactive
HIV-1/2 antigen/antibody (CPT 87389)	-	ROUTINE	ROUTINE	-	HIV-associated neurocognitive disorder; if risk factors present	Negative
Vitamin D, 25-OH (CPT 82306)	-	ROUTINE	ROUTINE	-	Deficiency associated with cognitive decline and dementia risk	>30 ng/mL
Homocysteine (CPT 83090)	-	ROUTINE	ROUTINE	-	Elevated levels associated with Alzheimer's disease and vascular cognitive impairment	<15 μmol/L
ESR (CPT 85652), CRP (CPT 86140)	-	ROUTINE	ROUTINE	-	Inflammatory or autoimmune causes; vasculitis screen	Normal
Urinalysis (CPT 81003)	-	ROUTINE	ROUTINE	-	UTI in elderly can present as cognitive changes; rule out reversible cause	Negative for infection
Methylmalonic acid (CPT 83921)	-	ROUTINE	ROUTINE	-	More sensitive than B12 level for functional B12 deficiency	<0.4 μmol/L

1C. Rare/Specialized (Refractory or Atypical)

Test (CPT)	ED	HOSP	OPD	ICU	Rationale	Target Finding
Heavy metal panel: lead (CPT 83655), mercury (CPT 83825), arsenic (CPT 82175)	-	-	EXT	-	Toxic exposure history; occupational risk	Normal
Copper (CPT 82525), Ceruloplasmin (CPT 82390)	-	-	EXT	-	Wilson's disease if age <50; hepatic symptoms	Normal
Paraneoplastic antibody panel (CPT 86255)	-	EXT	EXT	-	Autoimmune cognitive impairment; unexplained rapid progression	Negative
Anti-neuronal antibodies: NMDA-R, LGI1, CASPR2, GABA-B (CPT 86235)	-	EXT	EXT	-	Autoimmune encephalitis presenting as MCI	Negative
APOE genotyping (CPT 81401)	-	-	EXT	-	Risk stratification for AD progression; anti-amyloid therapy planning	Informational (APOE4 increases risk)
Genetic testing: PSEN1, PSEN2, APP (CPT 81406)	-	-	EXT	-	Familial early-onset AD (<65); family history of early-onset dementia	No pathogenic variants
Lyme serology (CPT 86618)	-	ROUTINE	ROUTINE	-	Endemic area; outdoor exposure; systemic symptoms	Negative

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2. DIAGNOSTIC IMAGING & STUDIES

2A. Essential/First-line

Study (CPT)	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
MRI Brain without contrast (CPT 70551)	-	ROUTINE	ROUTINE	-	At initial evaluation	Hippocampal volume, medial temporal atrophy (Scheltens scale), white matter disease burden, rule out structural causes (tumor, SDH, NPH)	MRI-incompatible devices
Neuropsychological testing, formal (CPT 96132, 96133)	-	-	ROUTINE	-	At diagnosis; gold standard for MCI characterization	Objective impairment 1-1.5 SD below age/education norms; preserved ADLs; characterize domain(s) affected	None
Mini-Mental State Examination (CPT 96116)	-	ROUTINE	ROUTINE	-	Screening; serial monitoring	24-30 (MCI often 24-27); <24 suggests dementia	None
Montreal Cognitive Assessment (CPT 96116)	-	ROUTINE	ROUTINE	-	More sensitive than MMSE for MCI	<26 abnormal; typically 18-25 in MCI	None

2B. Extended

Study (CPT)	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
CT Head non-contrast (CPT 70450)	-	ROUTINE	ROUTINE	-	If MRI contraindicated or unavailable	Rule out mass, hemorrhage, hydrocephalus	None
MRI Brain volumetrics (CPT 70551)	-	-	ROUTINE	-	Quantitative assessment; research/clinical trials	Hippocampal volume percentile for age; whole brain atrophy rate	MRI contraindications
FDG-PET Brain (CPT 78816)	-	-	ROUTINE	-	Differentiate underlying pathology when diagnosis uncertain	AD pattern: temporoparietal hypometabolism; FTD: frontal/temporal hypometabolism	None
Amyloid PET (CPT 78811)	-	-	ROUTINE	-	Diagnostic uncertainty; early-onset; anti-amyloid therapy eligibility	Positive confirms amyloid pathology (at risk for AD); negative makes AD unlikely	None
Sleep study, polysomnography (CPT 95810)	-	-	ROUTINE	-	Sleep apnea screening; sleep disturbance affecting cognition	AHI <5 normal; treat if elevated	None
EEG (CPT 95816)	-	ROUTINE	ROUTINE	-	Atypical features; concern for seizures or encephalopathy	Normal or mild nonspecific slowing in MCI	None

2C. Rare/Specialized

Study (CPT)	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
Tau PET (CPT 78811)	-	-	EXT	-	Research; disease staging; clinical trial eligibility	Pattern correlates with clinical syndrome; elevated tau predicts faster progression	None
DaTscan (CPT 78607)	-	-	EXT	-	MCI with parkinsonism; differentiate DLB prodrome	Reduced uptake suggests Lewy body pathology	Iodine hypersensitivity
SPECT perfusion (CPT 78607)	-	-	EXT	-	Alternative to PET if unavailable	Regional hypoperfusion patterns	None
MRI with SWI/GRE sequences (CPT 70551)	-	-	ROUTINE	-	Cerebral amyloid angiopathy; microbleed assessment	Lobar microbleeds suggest CAA; affects anti-amyloid eligibility	MRI contraindications

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LUMBAR PUNCTURE

Indication: Atypical presentation, early-onset (<65), diagnostic uncertainty, amyloid PET unavailable, anti-amyloid therapy eligibility assessment, clinical trial enrollment Timing: ROUTINE for biomarker-based diagnosis when indicated Volume Required: 10-15 mL (standard diagnostic); additional for research biomarkers

Study (CPT)	ED	HOSP	OPD	ICU	Rationale	Target Finding
Cell count, protein, glucose (CPT 89050, 89051)	-	ROUTINE	ROUTINE	-	Rule out infection, inflammation	WBC <5, protein <45 mg/dL, glucose >60% serum
CSF Amyloid-beta 1-42 (CPT 83519)	-	ROUTINE	ROUTINE	-	Low in Alzheimer's pathology; biomarker confirmation	Low Aβ42 (<600 pg/mL) suggests AD pathology
CSF total tau (CPT 83519)	-	ROUTINE	ROUTINE	-	Elevated in neurodegeneration; nonspecific	Mildly elevated in MCI due to AD; marked elevation suggests rapid progression
CSF phosphorylated tau 181 (CPT 83519)	-	ROUTINE	ROUTINE	-	Specific for AD pathology; predictor of progression	Elevated p-tau with low Aβ42 = high risk of AD progression
CSF Aβ42/Aβ40 ratio (CPT 83519)	-	ROUTINE	ROUTINE	-	More accurate than Aβ42 alone for amyloid status	<0.05-0.08 suggests amyloid positivity (assay-dependent)
CSF neurofilament light chain (CPT 83519)	-	-	ROUTINE	-	Nonspecific neurodegeneration marker; prognostic	Elevated suggests active neurodegeneration
VDRL (CPT 86592)	-	ROUTINE	ROUTINE	-	Neurosyphilis if RPR positive or high suspicion	Nonreactive

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

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3. TREATMENT

3A. Acute/Emergent

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Treat reversible causes	Various	Identified metabolic, nutritional, or infectious etiology	Per cause :: Various :: per etiology :: Correct hypothyroidism, replace B12/folate, treat infections, adjust medications	Depends on intervention	Cognitive reassessment 3-6 months after treatment	-	ROUTINE	ROUTINE	-
Thiamine	IV/PO	Suspected Wernicke's; alcoholism; malnutrition	500 mg :: IV :: TID :: 500 mg IV TID x 3 days if Wernicke suspected; then 100 mg PO daily maintenance	None	Clinical improvement	-	ROUTINE	ROUTINE	-
Vitamin B12	IM/PO	B12 deficiency (<300 pg/mL or elevated MMA)	1000 mcg :: IM :: daily :: 1000 mcg IM daily x 7d, then weekly x 4wk, then monthly; or high-dose oral 1000-2000 mcg daily	None	B12 level, MMA at 3 months; neurological improvement over months	-	ROUTINE	ROUTINE	-
Folate	PO	Folate deficiency	1 mg :: PO :: daily :: 1 mg PO daily; ensure B12 adequate before treating to avoid masking deficiency	None	Folate level at 3 months	-	ROUTINE	ROUTINE	-

3B. Symptomatic Treatments

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Donepezil	PO	MCI with high likelihood of AD pathology (amnestic MCI, positive biomarkers); modest symptomatic benefit	5 mg :: PO :: qHS :: Start 5 mg qHS x 4-6 weeks; may increase to 10 mg qHS; limited evidence in MCI but may offer modest benefit	Sick sinus syndrome; GI bleeding; severe COPD	Bradycardia, GI symptoms, vivid dreams; limited efficacy data in MCI	-	-	ROUTINE	-
Rivastigmine patch	TD	Alternative to donepezil; better GI tolerability; MCI with positive AD biomarkers	4.6 mg/24hr :: TD :: daily :: Start 4.6 mg/24hr; increase q4wk to 9.5 mg/24hr; limited evidence in MCI	Sick sinus syndrome; GI bleeding; severe COPD; severe hepatic impairment	Skin irritation, GI symptoms	-	-	EXT	-
Citalopram	PO	Depression contributing to cognitive symptoms (pseudodementia component)	10 mg :: PO :: daily :: Start 10 mg daily; max 20 mg in elderly due to QT risk	QT prolongation; concurrent QT-prolonging drugs	QTc at baseline and if dose >20 mg	-	ROUTINE	ROUTINE	-
Sertraline	PO	Depression; anxiety contributing to cognitive complaints	25 mg :: PO :: daily :: Start 25 mg daily; titrate by 25 mg q1-2wk; typical 50-100 mg	MAOIs; caution with bleeding risk	GI upset initially; reassess cognition after mood improves	-	ROUTINE	ROUTINE	-
Escitalopram	PO	Depression; anxiety with cognitive symptoms	5 mg :: PO :: daily :: Start 5 mg daily; increase to 10 mg after 1 week; max 10 mg in elderly	QT prolongation; MAOIs	QTc monitoring	-	ROUTINE	ROUTINE	-
Mirtazapine	PO	Depression with poor appetite, insomnia, and weight loss	7.5 mg :: PO :: qHS :: Start 7.5-15 mg qHS; may increase to 30 mg qHS	MAOIs	Weight gain (may be beneficial), sedation	-	ROUTINE	ROUTINE	-
Bupropion	PO	Depression with fatigue; avoid if seizure risk	150 mg :: PO :: daily :: Start 100 mg BID or 150 mg SR daily; increase after 1 week; max 300 mg/day	Seizure disorder; eating disorder; abrupt alcohol/benzo withdrawal	Seizure risk; may improve alertness	-	ROUTINE	ROUTINE	-
Trazodone	PO	Insomnia in MCI patients	25 mg :: PO :: qHS :: Start 25-50 mg qHS; titrate to effect; typical 50-100 mg qHS	Concurrent MAOIs; QT prolongation	Orthostatic hypotension, morning sedation	-	ROUTINE	ROUTINE	-
Melatonin	PO	Sleep disturbance; circadian rhythm support	1 mg :: PO :: qHS :: Start 1-3 mg qHS; may increase to 5 mg; take 30 min before bed	None	Daytime sedation; limited long-term data	-	ROUTINE	ROUTINE	-

3C. Cardiovascular Risk Factor Management

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Atorvastatin	PO	Hyperlipidemia; vascular risk reduction; may slow cognitive decline	10 mg :: PO :: daily :: Start 10-20 mg daily; titrate to LDL goal; target LDL <100 (or <70 if established CVD)	Active liver disease; pregnancy	LFTs at baseline; lipid panel q3-6mo initially	-	ROUTINE	ROUTINE	-
Rosuvastatin	PO	Hyperlipidemia; alternative statin	5 mg :: PO :: daily :: Start 5-10 mg daily; adjust to LDL goal	Active liver disease; severe renal impairment (dose adjust)	LFTs, lipid panel	-	ROUTINE	ROUTINE	-
Lisinopril	PO	Hypertension; target BP <130/80 for vascular protection	5 mg :: PO :: daily :: Start 5-10 mg daily; titrate q2wk to BP goal	Angioedema history; pregnancy; bilateral renal artery stenosis	K+, Cr, BP; cough	-	ROUTINE	ROUTINE	-
Amlodipine	PO	Hypertension; especially if ACE-I intolerant	2.5 mg :: PO :: daily :: Start 2.5-5 mg daily; increase q2wk; max 10 mg	Severe aortic stenosis	Peripheral edema, BP	-	ROUTINE	ROUTINE	-
Losartan	PO	Hypertension; alternative if ACE-I intolerant	25 mg :: PO :: daily :: Start 25-50 mg daily; titrate to BP goal; max 100 mg	Angioedema history; pregnancy; bilateral renal artery stenosis	K+, Cr, BP	-	ROUTINE	ROUTINE	-
Metformin	PO	Type 2 diabetes; potential neuroprotective effects	500 mg :: PO :: daily :: Start 500 mg daily with meal; increase by 500 mg weekly; max 2000 mg/day	eGFR <30; risk of lactic acidosis	HbA1c q3mo; B12 annually (metformin reduces absorption)	-	ROUTINE	ROUTINE	-
Aspirin (low-dose)	PO	Secondary prevention if established CVD; not for primary prevention in MCI	81 mg :: PO :: daily :: 81 mg daily; only if established CVD or high vascular risk	Active bleeding; aspirin allergy; high bleeding risk	GI symptoms; bleeding	-	ROUTINE	ROUTINE	-

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

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Lecanemab (Leqembi)	IV	MCI due to AD with confirmed amyloid pathology (positive amyloid PET or CSF biomarkers)	10 mg/kg :: IV :: q2wk :: 10 mg/kg IV every 2 weeks; infuse over 1 hour; continue as long as benefit maintained	Amyloid PET or CSF confirming amyloid positivity; MRI baseline (within 1 year); APOE genotyping recommended; informed consent for ARIA risk	>4 microbleeds on MRI; superficial siderosis; anticoagulation (increased ARIA risk); recent stroke/TIA	MRI at baseline, weeks 14, 52, 78; monitor for ARIA-E/H symptoms (headache, confusion, vision changes)	-	-	ROUTINE	-
Donanemab (Kisunla)	IV	MCI due to AD with confirmed amyloid and intermediate/high tau pathology	700 mg :: IV :: q4wk :: 700 mg q4wk x 3 doses, then 1400 mg q4wk until amyloid cleared (PET-guided discontinuation)	Amyloid PET positive; tau PET intermediate/high; MRI baseline; APOE genotyping	APOE4 homozygotes have higher ARIA risk; >4 microbleeds; anticoagulation	MRI at baseline, weeks 16, 24, 52, 76; amyloid PET to guide discontinuation	-	-	EXT	-

ARIA Monitoring Notes: - ARIA-E (edema): Usually asymptomatic; may cause headache, confusion, visual disturbances - ARIA-H (hemorrhage): Microbleeds, superficial siderosis - Hold infusion for symptomatic ARIA; resume after resolution per protocol - APOE4 homozygotes have higher ARIA risk; requires detailed informed consent discussion - MCI patients with positive biomarkers are eligible for these treatments (FDA approved for early AD including MCI stage)

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4. OTHER RECOMMENDATIONS

4A. Referrals & Consults

Recommendation	ED	HOSP	OPD	ICU
Neurology/Cognitive neurology for MCI subtype characterization, biomarker interpretation, and treatment planning	-	ROUTINE	ROUTINE	-
Neuropsychology for comprehensive cognitive testing to establish baseline, characterize affected domains, and distinguish MCI subtypes	-	-	ROUTINE	-
Geriatrics for comprehensive geriatric assessment, polypharmacy review, and functional optimization	-	ROUTINE	ROUTINE	-
Occupational therapy for cognitive strategies, compensatory techniques, and home safety evaluation	-	-	ROUTINE	-
Occupational therapy driving evaluation to assess fitness to drive given cognitive impairment	-	-	ROUTINE	-
Social work for community resources, support services, and early care planning guidance	-	ROUTINE	ROUTINE	-
Speech therapy for communication strategies if language domain affected (non-amnestic MCI)	-	-	ROUTINE	-
Sleep medicine for sleep apnea evaluation if symptoms present (snoring, daytime sleepiness, witnessed apneas)	-	-	ROUTINE	-
Psychiatry for depression evaluation if significant mood symptoms confounding cognitive assessment	-	ROUTINE	ROUTINE	-
Genetics counseling if early-onset (<65), family history of early-onset dementia, or considering genetic testing	-	-	ROUTINE	-
Clinical trial referral for eligible patients interested in research studies targeting MCI and early AD	-	-	ROUTINE	-
Elder law attorney for advance directives, healthcare proxy, and financial planning while patient has full capacity	-	-	ROUTINE	-
PCP follow-up for cardiovascular risk factor management and coordination of vascular prevention	-	ROUTINE	ROUTINE	-

4B. Patient Instructions

Recommendation	ED	HOSP	OPD
Return if sudden confusion worsens or new neurological symptoms develop which may indicate stroke or other acute process	-	ROUTINE	ROUTINE
Complete advance directives and establish healthcare proxy NOW while you have full capacity to make decisions	-	ROUTINE	ROUTINE
Consider long-term care preferences, financial planning, and legal arrangements with family while fully competent	-	ROUTINE	ROUTINE
Discuss driving safety with physician; formal driving evaluation recommended as MCI may affect reaction time and judgment	-	ROUTINE	ROUTINE
Use memory aids (calendars, smartphone reminders, pill organizers, written lists) to compensate for memory difficulties	-	ROUTINE	ROUTINE
Keep a consistent daily routine which helps with memory and reduces confusion	-	ROUTINE	ROUTINE
Take all medications as prescribed; bring medication list to all appointments	-	ROUTINE	ROUTINE
Return for follow-up cognitive testing every 6-12 months to monitor for progression	-	-	ROUTINE
Report new memory concerns, personality changes, or functional difficulties to physician promptly	-	ROUTINE	ROUTINE
Avoid anticholinergic medications (diphenhydramine, PM sleep aids) as they can worsen cognition	-	ROUTINE	ROUTINE

4C. Lifestyle & Prevention

Recommendation	ED	HOSP	OPD
Engage in regular aerobic exercise (150 minutes/week moderate intensity) which may slow cognitive decline and improve brain health	-	ROUTINE	ROUTINE
Follow Mediterranean or MIND diet emphasizing vegetables, berries, fish, nuts, whole grains, and olive oil to reduce dementia risk	-	ROUTINE	ROUTINE
Participate in cognitively stimulating activities (reading, puzzles, learning new skills, social engagement) to build cognitive reserve	-	ROUTINE	ROUTINE
Maintain active social connections and relationships as social isolation is a modifiable dementia risk factor	-	ROUTINE	ROUTINE
Achieve adequate sleep (7-8 hours nightly) and treat sleep disorders (CPAP for sleep apnea) as poor sleep accelerates cognitive decline	-	ROUTINE	ROUTINE
Cardiovascular risk factor control with target BP <130/80, HbA1c <7%, LDL <100 to reduce vascular contribution to cognitive decline	-	ROUTINE	ROUTINE
Address hearing loss with hearing aids as untreated hearing loss is a modifiable risk factor for cognitive decline	-	-	ROUTINE
Limit alcohol to maximum 1 drink daily as excess alcohol accelerates brain atrophy and cognitive decline	-	ROUTINE	ROUTINE
Smoking cessation to reduce vascular risk and improve overall brain health	-	ROUTINE	ROUTINE
Manage stress through relaxation techniques, mindfulness, or counseling as chronic stress impairs cognition	-	ROUTINE	ROUTINE
Review all medications with physician to identify and discontinue drugs that impair cognition (anticholinergics, benzodiazepines, opioids)	-	ROUTINE	ROUTINE

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SECTION B: REFERENCE

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5. DIFFERENTIAL DIAGNOSIS

Alternative Diagnosis	Key Distinguishing Features	Tests to Differentiate
Normal aging	Subjective memory concerns without objective impairment; no functional decline; normal neuropsych testing	Neuropsychological testing within 1 SD of norms
Subjective cognitive decline	Memory complaints but normal objective testing; may be earliest preclinical stage	Neuropsychological testing normal; monitor annually
Depression (pseudodementia)	Prominent mood symptoms; often aware of and distressed by deficits; improves with antidepressants	GDS, PHQ-9; trial of antidepressant; reassess cognition
Medication-induced cognitive impairment	Temporal relationship to medication initiation; improvement with discontinuation	Medication review; trial discontinuation of suspect agents
Sleep apnea-related cognitive impairment	Excessive daytime sleepiness; snoring; morning headaches; reversible with CPAP	Polysomnography; cognitive reassessment after CPAP
Alzheimer's disease (dementia stage)	Functional impairment in ADLs (not just IADLs); more severe cognitive deficits	Functional assessment; neuropsychological testing
Vascular cognitive impairment	Stepwise decline; focal findings; executive dysfunction prominent; significant white matter disease	MRI with confluent white matter disease; vascular risk factors
Dementia with Lewy bodies (prodromal)	Visual hallucinations; REM sleep behavior disorder; parkinsonism; fluctuating cognition	DaTscan; clinical features; sleep study for RBD
Frontotemporal dementia (prodromal)	Behavioral/personality changes; disinhibition; apathy; language variants; typically <65	FDG-PET frontal/temporal hypometabolism; neuropsychological profile
Thyroid dysfunction	Fatigue, weight changes, cold/heat intolerance; reversible with treatment	TSH, free T4; reassess after treatment
Vitamin B12 deficiency	Peripheral neuropathy; macrocytic anemia; reversible with replacement	B12, MMA; improvement with supplementation

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6. MONITORING PARAMETERS

Parameter	Frequency	Target/Threshold	Action if Abnormal	ED	HOSP	OPD	ICU
MoCA or MMSE	Every 6-12 months	Stable or <2 point decline/year	Decline >3 points or reaching dementia threshold warrants reassessment; consider biomarker workup if not done	-	ROUTINE	ROUTINE	-
Full neuropsychological testing	Every 1-2 years or if significant change	Stable across domains	Decline suggests progression to dementia; adjust care plan	-	-	ROUTINE	-
IADL/ADL function (FAQ, Lawton)	Every 6-12 months	Preserved basic ADLs (defines MCI vs dementia)	Functional decline suggests progression to dementia; increase supports	-	ROUTINE	ROUTINE	-
Depression screening (GDS, PHQ-9)	Annually or if symptoms	No significant depression	Treat depression; reassess cognition after treatment	-	ROUTINE	ROUTINE	-
Blood pressure	Each visit	<130/80 mmHg	Optimize antihypertensive therapy	-	ROUTINE	ROUTINE	-
HbA1c (if diabetic)	Every 3-6 months	<7% (individualized)	Optimize glycemic control	-	ROUTINE	ROUTINE	-
Lipid panel	Annually	LDL <100 mg/dL	Optimize statin therapy	-	ROUTINE	ROUTINE	-
Vitamin B12	Annually	>300 pg/mL	Supplement if low	-	-	ROUTINE	-
TSH	Annually	0.4-4.0 mIU/L	Treat thyroid dysfunction	-	-	ROUTINE	-
MRI (ARIA monitoring if on anti-amyloid)	Per protocol (baseline, weeks 14, 52, 78 for lecanemab)	No ARIA-E or ARIA-H	Hold infusion per protocol; resume after resolution	-	-	ROUTINE	-
Driving safety	Annually or with decline	Safe to drive	Recommend driving cessation or OT driving evaluation	-	-	ROUTINE	-
Weight	Each visit	Stable	Nutritional assessment if declining	-	ROUTINE	ROUTINE	-
Caregiver/family concerns	Each visit	No new concerns	Investigate reported changes; adjust care plan	-	ROUTINE	ROUTINE	-

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7. DISPOSITION CRITERIA

Disposition	Criteria
Outpatient management (most MCI)	Stable MCI; reversible causes addressed; care plan established; follow-up arranged
Admit to floor	Acute delirium requiring workup; safety concerns at home; caregiver crisis
Outpatient neurology follow-up	Every 6-12 months for cognitive monitoring; sooner if concerns
Outpatient neuropsychology	At diagnosis for baseline; repeat in 1-2 years or if significant change
Referral to memory care program	Progressive decline; need for specialized multidisciplinary management
Clinical trial referral	Eligible patient interested in research; positive biomarkers; early stage

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8. EVIDENCE & REFERENCES

Recommendation	Evidence Level	Source
MCI diagnostic criteria and subtypes	Class I, Level A	Petersen et al. Arch Neurol 2004; Albert et al. Alzheimers Dement 2011
Neuropsychological testing for MCI diagnosis	Class I, Level A	AAN Practice Parameter 2018
CSF biomarkers for AD pathology	Class I, Level A	Hansson et al. Lancet Neurol 2018
Amyloid PET for AD diagnosis in MCI	Class I, Level A	Johnson et al. Alzheimers Dement 2013
Cholinesterase inhibitors limited benefit in MCI	Class I, Level B	Petersen et al. NEJM 2005; Russ & Morling, Cochrane 2012
Lecanemab slows decline in MCI due to AD	Class I, Level A	van Dyck et al. NEJM 2023 (Clarity AD)
Donanemab slows decline in early AD	Class I, Level A	Sims et al. JAMA 2023 (TRAILBLAZER-ALZ 2)
Physical exercise may slow cognitive decline	Class II, Level B	Livingston et al. Lancet 2020 (Lancet Commission on Dementia)
Mediterranean/MIND diet reduces dementia risk	Class II, Level B	Morris et al. Alzheimers Dement 2015
Cardiovascular risk factor control protects cognition	Class I, Level A	Ngandu et al. Lancet 2015 (FINGER trial)
Sleep apnea treatment improves cognition	Class II, Level B	Osorio et al. Neurology 2015
MCI progression rate to dementia (~10-15%/year)	Epidemiological	Mitchell & Shiri-Feshki, Acta Psychiatr Scand 2009
Hearing loss as modifiable dementia risk factor	Class II, Level B	Lin et al. Arch Neurol 2011
Modifiable risk factors for dementia prevention	Class II, Level A	Livingston et al. Lancet 2024 (Lancet Commission Update)

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CHANGE LOG

v1.1 (January 30, 2026) - Standardized lab tables (1A/1B/1C) to Test (CPT) | ED | HOSP | OPD | ICU | Rationale | Target Finding format - Standardized imaging tables (2A/2B/2C) to Study (CPT) | ED | HOSP | OPD | ICU | Timing | Target Finding | Contraindications format - Standardized LP table to Study (CPT) | ED | HOSP | OPD | ICU | Rationale | Target Finding format - Added inline CPT codes to all laboratory, imaging, and LP studies - Fixed structured dosing first fields across all treatment sections (3A/3B/3C/3D) - Expanded "Same as donepezil" cross-reference in rivastigmine contraindications - Expanded "Same as lisinopril" cross-reference in losartan contraindications - Added additional ICD-10 codes (F06.7, R41.81) - Added clinical synonyms - Added VERSION/CREATED/REVISED header block

v1.0 (January 27, 2026) - Initial template creation - Outpatient-focused plan for MCI diagnosis and monitoring - Includes MCI subtypes (amnestic vs non-amnestic) - Comprehensive reversible causes workup - Structured dosing format for order sentence generation - Anti-amyloid therapy eligibility guidance (lecanemab, donanemab) - Cardiovascular risk factor management section - Driving assessment and advance care planning recommendations - Serial cognitive monitoring protocol

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APPENDIX A: MCI Subtypes and Prognosis

Classification

Subtype	Characteristics	Progression Risk
Amnestic MCI - Single Domain	Memory impairment only; preserved other domains	Higher risk for Alzheimer's disease
Amnestic MCI - Multi-Domain	Memory + other cognitive domains impaired	Higher risk for AD or vascular dementia
Non-Amnestic MCI - Single Domain	Impairment in one non-memory domain (executive, language, visuospatial)	May progress to FTD, DLB, or vascular dementia
Non-Amnestic MCI - Multi-Domain	Multiple non-memory domains impaired	Variable; may progress to non-AD dementias

Biomarker-Based Staging (NIA-AA Research Framework)

Stage	Clinical	Amyloid	Tau	Neurodegeneration
A-/T-/N-	Cognitively normal	-	-	-
A+/T-/N-	Preclinical AD	+	-	-
A+/T+/N-	Preclinical AD	+	+	-
A+/T+/N+	MCI or Dementia due to AD	+	+	+

A = Amyloid, T = Tau, N = Neurodegeneration (atrophy, FDG-PET hypometabolism)

Progression Risk Factors

• Higher risk: Amnestic subtype, positive amyloid biomarkers, APOE4 carrier, greater hippocampal atrophy
• Lower risk: Negative amyloid biomarkers, identifiable reversible cause, younger age, non-amnestic subtype

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APPENDIX B: Anti-Amyloid Therapy Eligibility Checklist

Lecanemab (Leqembi) Eligibility

Inclusion Criteria: - [ ] MCI due to AD OR mild AD dementia - [ ] Confirmed amyloid pathology (positive amyloid PET OR CSF Aβ42/40 ratio consistent with AD) - [ ] MMSE typically 22-30 or MoCA 18-26 - [ ] Reliable caregiver/study partner

Exclusion Criteria: - [ ] >4 microbleeds on MRI - [ ] Any superficial siderosis - [ ] Prior macrohemorrhage - [ ] Current anticoagulation (relative; increases ARIA risk) - [ ] Recent stroke or TIA (<12 months)

Pre-Treatment Workup: - [ ] MRI brain within 1 year (assess for microbleeds, rule out other pathology) - [ ] Amyloid PET or CSF biomarkers confirming amyloid positivity - [ ] APOE genotyping (recommended for risk counseling) - [ ] Baseline cognitive testing (MMSE, MoCA, or CDR) - [ ] Informed consent including ARIA risk discussion

Monitoring Schedule: - MRI: Baseline, Week 14, Week 52, Week 78 (and with new symptoms) - Clinical assessment for ARIA symptoms each infusion

ARIA Symptom Recognition

ARIA-E (Edema)	ARIA-H (Hemorrhage)
Headache	Often asymptomatic
Confusion/disorientation	Headache
Visual disturbances	Focal neurological symptoms
Nausea/vomiting	If large hemorrhage
Gait instability

Most ARIA is asymptomatic and detected on scheduled MRI monitoring