Frontotemporal Dementia¶
DIAGNOSIS: Frontotemporal Dementia (FTD) ICD-10: G31.09 (Frontotemporal dementia, unspecified); G31.0 (Frontotemporal dementia); F02.80 (Dementia in FTD without behavioral disturbance); F02.81 (Dementia in FTD with behavioral disturbance); G31.01 (Pick's disease) SYNONYMS: Pick's disease, frontotemporal lobar degeneration, FTLD, behavioral variant frontotemporal dementia, bvFTD, primary progressive aphasia, PPA, semantic dementia, progressive nonfluent aphasia, FTD-MND, FTD-ALS, Pick complex, frontotemporal neurocognitive disorder SCOPE: Diagnosis and management of frontotemporal lobar degeneration syndromes including behavioral variant FTD (bvFTD), semantic variant primary progressive aphasia (svPPA), nonfluent/agrammatic variant PPA (nfvPPA), FTD with motor neuron disease (FTD-ALS), and genetic forms (C9orf72, MAPT, GRN). Covers diagnostic evaluation, symptomatic treatment, behavioral management, genetic counseling, safety planning, and caregiver support. Primarily outpatient-focused with coverage for ED and hospital presentations of behavioral crises.
VERSION: 1.1 CREATED: January 27, 2026 REVISED: January 30, 2026 STATUS: Draft - Pending Review
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 behavioral changes | Normal |
| BMP (Na, K, BUN, Cr, glucose) (CPT 80048) | STAT | STAT | ROUTINE | - | Metabolic causes of behavioral disturbance (hyponatremia, uremia, hypoglycemia) | Normal electrolytes, renal function |
| TSH (CPT 84443) | URGENT | ROUTINE | ROUTINE | - | Hypothyroidism can cause apathy; hyperthyroidism can cause behavioral changes | 0.4-4.0 mIU/L |
| Vitamin B12 (CPT 82607) | URGENT | ROUTINE | ROUTINE | - | B12 deficiency causes neuropsychiatric symptoms and 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, ammonia) (CPT 80076) | STAT | ROUTINE | ROUTINE | - | Hepatic encephalopathy; nutritional status; liver function for medications | Normal |
| Calcium (CPT 82310) | STAT | ROUTINE | ROUTINE | - | Hypercalcemia causes neuropsychiatric symptoms | 8.5-10.5 mg/dL |
| Urinalysis (CPT 81001) | STAT | STAT | ROUTINE | - | UTI common cause of acute behavioral changes in elderly | Negative for infection |
1B. Extended Workup (Second-line)¶
| Test | ED | HOSP | OPD | ICU | Rationale | Target Finding |
|---|---|---|---|---|---|---|
| RPR or VDRL (CPT 86592) | - | ROUTINE | ROUTINE | - | Neurosyphilis is treatable cause of behavioral and cognitive changes | Nonreactive |
| HIV testing (CPT 87389) | - | ROUTINE | ROUTINE | - | HIV-associated neurocognitive disorder if risk factors | Negative |
| ESR (CPT 85651), CRP (CPT 86140) | - | ROUTINE | ROUTINE | - | Inflammatory or autoimmune causes; baseline before immunotherapy | Normal |
| ANA (CPT 86235), RF (CPT 86431) | - | ROUTINE | ROUTINE | - | Screen for systemic autoimmune disease | Negative |
| Creatine kinase (CPT 82550) | - | ROUTINE | ROUTINE | - | Elevated in FTD-ALS; baseline for motor neuron involvement | Normal (elevated suggests MND) |
| EMG/NCS referral (CPT 95907-95913) | - | ROUTINE | ROUTINE | - | If motor symptoms present; evaluate for ALS overlap | Normal or denervation pattern |
| Serum progranulin level (CPT 83519) | - | - | ROUTINE | - | Low levels suggest GRN mutation (screening test) | Normal (low <100 ng/mL suggests GRN mutation) |
1C. Rare/Specialized (Genetic and Atypical Evaluation)¶
| Test | ED | HOSP | OPD | ICU | Rationale | Target Finding |
|---|---|---|---|---|---|---|
| C9orf72 hexanucleotide repeat expansion (CPT 81479) | - | - | ROUTINE | - | Most common genetic cause of FTD; also causes ALS | <30 repeats (pathogenic >30) |
| MAPT (tau) gene sequencing (CPT 81479) | - | - | ROUTINE | - | Familial FTD with parkinsonism; tau-positive pathology | No pathogenic mutation |
| GRN (progranulin) gene sequencing (CPT 81479) | - | - | ROUTINE | - | Familial FTD; asymmetric atrophy; TDP-43 pathology | No pathogenic mutation |
| FTD genetic panel (TARDBP, VCP, CHMP2B, FUS) (CPT 81479) | - | - | EXT | - | Extended genetic evaluation if first-line negative | No pathogenic mutation |
| Paraneoplastic antibody panel (CPT 86235) | - | EXT | EXT | - | Rapid behavioral change; history of cancer; atypical features | Negative |
| Anti-neuronal antibodies (NMDA-R, LGI1, CASPR2, GAD65) (CPT 86255) | - | EXT | EXT | - | Autoimmune encephalitis mimicking FTD | Negative |
| Heavy metal panel (lead, mercury, arsenic) (CPT 83015/83825/82175) | - | - | EXT | - | Occupational exposure history; atypical presentation | Normal |
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 | Frontal and/or anterior temporal atrophy; asymmetric patterns; rule out structural causes | MRI-incompatible devices, severe claustrophobia |
| CT Head non-contrast (CPT 70450) | STAT | STAT | ROUTINE | - | If MRI unavailable or contraindicated | Rule out mass, hemorrhage, hydrocephalus; frontal atrophy visible | None |
2B. Extended¶
| Study | ED | HOSP | OPD | ICU | Timing | Target Finding | Contraindications |
|---|---|---|---|---|---|---|---|
| FDG-PET Brain (CPT 78816) | - | - | ROUTINE | - | Diagnostic confirmation; differentiate from AD | Frontal and/or anterior temporal hypometabolism; sparing of posterior parietal (unlike AD) | None |
| MRI Brain volumetrics (CPT 70553) | - | - | ROUTINE | - | Quantify regional atrophy; track progression | Frontal/temporal volume loss; hemispheric asymmetry | MRI contraindications |
| Amyloid PET (CPT 78816) | - | - | ROUTINE | - | Exclude AD pathology if clinical uncertainty | Negative amyloid supports FTD diagnosis | None |
| EEG (CPT 95819) | URGENT | ROUTINE | ROUTINE | - | Seizures; behavioral episodes; differentiate from CJD | Usually normal or mild slowing; no periodic discharges (CJD has) | None |
| Sleep study (polysomnography) (CPT 95810) | - | - | ROUTINE | - | RBD suggests DLB rather than FTD; sleep disturbance common | REM without atonia absent (if RBD, reconsider DLB) | None |
2C. Rare/Specialized¶
| Study | ED | HOSP | OPD | ICU | Timing | Target Finding | Contraindications |
|---|---|---|---|---|---|---|---|
| DaTscan (ioflupane I-123) (CPT 78607) | - | - | EXT | - | Parkinsonism present; differentiate PSP/CBD from PD/DLB | Reduced uptake in PSP/CBD; may be normal early in bvFTD | Iodine hypersensitivity |
| Tau PET (flortaucipir) (CPT 78816) | - | - | EXT | - | Research; distinguish tau-positive from TDP-43 FTD | Tau-positive FTD shows frontal/temporal uptake | None |
| Whole body PET-CT (CPT 78816) | - | EXT | EXT | - | Paraneoplastic workup if suspected | Rule out occult malignancy | None |
LUMBAR PUNCTURE¶
Indication: Exclude other causes (infection, inflammation, CJD); biomarker support for diagnosis; CSF NfL for prognosis Timing: ROUTINE for diagnostic evaluation; 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 89050/89051) | URGENT | ROUTINE | ROUTINE | - | Rule out infection, inflammation | WBC <5, protein <45 mg/dL, glucose >60% serum |
| CSF Aβ42/Aβ40 ratio (CPT 83519) | - | ROUTINE | ROUTINE | - | Distinguish from AD (normal in FTD) | Normal ratio >0.08 supports non-AD etiology |
| CSF total tau (t-tau) (CPT 83519) | - | ROUTINE | ROUTINE | - | Non-specific neurodegeneration marker | May be elevated but less than AD |
| CSF phosphorylated tau (p-tau181) (CPT 83519) | - | ROUTINE | ROUTINE | - | AD-specific; should be normal in FTD | Normal p-tau supports FTD over AD |
| CSF NfL (neurofilament light) (CPT 83519) | - | ROUTINE | ROUTINE | - | Neurodegeneration marker; prognostic; very high in ALS-FTD | Elevated (higher = faster progression) |
| 14-3-3 protein (CPT 83519) | - | ROUTINE | ROUTINE | - | Rapid progression; rule out CJD | Negative (positive suggests CJD) |
| RT-QuIC (CPT 83519) | - | ROUTINE | EXT | - | Prion disease confirmation if suspected | Negative |
| Autoimmune encephalitis panel (CSF) (CPT 86255) | - | EXT | EXT | - | Subacute behavioral change; seizures | 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¶
CRITICAL NOTE: No FDA-approved disease-modifying treatments exist for FTD. Treatment is symptomatic and supportive. Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are NOT recommended and may worsen behavioral symptoms.
3A. Acute/Emergent (Behavioral Crisis Management)¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Lorazepam | PO/IM/IV | Acute severe agitation when de-escalation fails | 0.5 mg :: PO/IM/IV :: PRN :: 0.5-1 mg PO or IM; may repeat q30min PRN; max 4 mg; short-term use only | Respiratory depression; severe hepatic impairment; paradoxical agitation risk in elderly | Respiratory status; sedation; paradoxical reactions | STAT | STAT | - | - |
| Haloperidol | IM/IV | Severe aggression/psychosis when benzodiazepines insufficient | 0.5 mg :: IM/IV :: PRN :: 0.5-2 mg IM q4-6h PRN; lowest effective dose; short-term crisis only | QT prolongation; Parkinson's disease; FTD-parkinsonism overlap (avoid if possible) | QTc; EPS; akathisia; sedation | STAT | EXT | - | - |
| Environmental de-escalation | N/A | First-line for all behavioral disturbance | N/A :: N/A :: N/A :: Reduce stimulation; dim lights; calm voice; remove triggers; one-to-one observation; familiar caregiver presence | None | Response to intervention | STAT | STAT | ROUTINE | - |
3B. Symptomatic Treatments (Behavioral and Neuropsychiatric)¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Trazodone | PO | Agitation; irritability; disinhibition; insomnia; compulsive behaviors | 25 mg :: PO :: BID :: Start 25-50 mg BID; titrate by 25-50 mg q3-5d; typical 150-300 mg/day divided; max 400 mg/day | Concurrent MAOIs; significant QT prolongation | Orthostatic hypotension (fall risk); priapism (rare); QTc; sedation | - | ROUTINE | ROUTINE | - |
| Sertraline (Zoloft) | PO | Depression; apathy; anxiety; compulsive behaviors; disinhibition | 25 mg :: PO :: daily :: Start 25 mg daily; increase by 25-50 mg every 1-2 weeks; typical 100-200 mg daily; max 200 mg | MAOIs; uncontrolled seizures (lowers threshold slightly) | GI symptoms; bleeding risk; apathy (rarely worsens) | - | ROUTINE | ROUTINE | - |
| Citalopram | PO | Depression; anxiety; compulsive behaviors | 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 | - | ROUTINE | ROUTINE | - |
| Escitalopram (Lexapro) | PO | Depression; anxiety; better tolerated than citalopram | 5 mg :: PO :: daily :: Start 5 mg daily; increase to 10 mg after 1 week; max 10 mg in elderly | QT prolongation; concurrent MAOIs | QTc if cardiac risk factors | - | ROUTINE | ROUTINE | - |
| Fluvoxamine | PO | Compulsive behaviors; repetitive behaviors; may have specific benefit in FTD | 25 mg :: PO :: qHS :: Start 25 mg qHS; titrate by 25-50 mg weekly; typical 100-200 mg/day; max 300 mg/day | MAOIs; alosetron, tizanidine (drug interactions) | Multiple drug interactions (CYP1A2, 2C19, 3A4 inhibitor); GI symptoms | - | ROUTINE | ROUTINE | - |
| Mirtazapine (Remeron) | PO | Depression with poor appetite, weight loss, and insomnia | 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 in FTD); sedation; hyperlipidemia | - | ROUTINE | ROUTINE | - |
| Bupropion (Wellbutrin) | PO | Apathy-predominant FTD; depression; may help with motivation | 100 mg :: PO :: BID :: Start 100 mg BID or 150 mg SR daily; titrate to 150 mg SR BID or 300 mg XL daily | Seizure disorder; bulimia/anorexia; concurrent MAOIs; abrupt alcohol withdrawal | Seizure risk (dose-related); insomnia; agitation (may worsen some patients) | - | - | ROUTINE | - |
| Melatonin | PO | Sleep disturbance; circadian rhythm dysfunction; sundowning | 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 | - |
3C. Second-line/Refractory (Behavioral Management)¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Quetiapine (Seroquel) | PO | Severe agitation/psychosis when non-pharmacologic and first-line fail | 12.5 mg :: PO :: qHS :: Start 12.5-25 mg qHS; titrate slowly (25 mg increments); keep dose as low as possible; max 200 mg/day | Black box: increased mortality in dementia; avoid in FTD-parkinsonism | Metabolic effects; sedation; falls; QTc; EPS | - | EXT | ROUTINE | - |
| Olanzapine | PO/IM | Severe agitation when other options fail; IM for acute crisis | 2.5 mg :: PO/IM :: daily :: PO: Start 2.5 mg daily; increase slowly; max 10 mg; IM: 2.5-5 mg for acute crisis | Black box: increased mortality in dementia; diabetes; QT prolongation | Weight gain; metabolic syndrome; sedation; EPS | EXT | EXT | EXT | - |
| Dextromethorphan/quinidine (Nuedexta) | PO | Pseudobulbar affect; emotional lability; pathological laughing/crying | 20/10 mg :: PO :: daily :: Start 20/10 mg daily x 7 days; then 20/10 mg BID | QT prolongation; concurrent MAOIs; quinidine hypersensitivity; complete AV block | QTc; avoid in hepatic/renal impairment | - | ROUTINE | ROUTINE | - |
| Valproic acid | PO | Impulsivity; aggression; mood instability (off-label) | 125 mg :: PO :: BID :: Start 125-250 mg BID; titrate to 500-1000 mg/day; monitor levels | Hepatic disease; urea cycle disorders; mitochondrial disorders | Valproate level, LFTs, CBC, ammonia; weight gain; tremor; thrombocytopenia | - | ROUTINE | ROUTINE | - |
| Memantine (Namenda) | PO | May help some behavioral symptoms; limited evidence | 5 mg :: PO :: daily :: Start 5 mg daily; increase by 5 mg/week to 10 mg BID; evidence weak in FTD | Severe renal impairment (reduce dose) | Confusion, dizziness; generally well tolerated | - | - | ROUTINE | - |
| Methylphenidate | PO | Severe apathy unresponsive to other treatments | 2.5 mg :: PO :: BID :: Start 2.5-5 mg BID (morning and noon); titrate slowly; max 20 mg/day | Severe anxiety; cardiac arrhythmias; glaucoma; concurrent MAOIs | BP, HR; appetite; insomnia; agitation; abuse potential | - | - | EXT | - |
3D. Treatments to AVOID in FTD¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Donepezil (Aricept) | PO | AVOID - May worsen behavioral symptoms in FTD | AVOID :: PO :: N/A :: Do NOT use; cholinesterase inhibitors can worsen disinhibition, agitation, and behavioral symptoms in FTD | FTD diagnosis | Worsening behavior if inadvertently started | - | - | - | - |
| Rivastigmine (Exelon) | PO/TD | AVOID - May worsen behavioral symptoms in FTD | AVOID :: PO/TD :: N/A :: Do NOT use; cholinesterase inhibitors not recommended in FTD; may cause paradoxical worsening | FTD diagnosis | Worsening behavior if inadvertently started | - | - | - | - |
| Galantamine (Razadyne) | PO | AVOID - May worsen behavioral symptoms in FTD | AVOID :: PO :: N/A :: Do NOT use; cholinesterase inhibitors contraindicated in FTD | FTD diagnosis | Worsening behavior if inadvertently started | - | - | - | - |
Note on Antipsychotics: Use with extreme caution. Increased mortality risk in dementia; increased risk of EPS in FTD-parkinsonism; reserve for severe, refractory cases where safety is at risk.
3E. FTD-ALS/Motor Neuron Disease Overlap¶
| Treatment | Route | Indication | Dosing | Contraindications | Monitoring | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|---|---|
| Riluzole | PO | FTD with ALS overlap; may modestly slow MND progression | 50 mg :: PO :: BID :: 50 mg PO BID; take 1 hour before or 2 hours after meals | Hepatic impairment; pregnancy | LFTs monthly x 3 months, then q3mo; neutropenia | - | ROUTINE | ROUTINE | - |
| Edaravone (Radicava) | IV/PO | FTD-ALS if early in disease course | 60 mg :: IV/PO :: daily :: Initial: 60 mg IV daily x 14 days; maintenance: 60 mg IV daily x 10 days of 14-day cycles; oral formulation available | Hypersensitivity; sulfite allergy | Infusion reactions; hypersensitivity | - | ROUTINE | ROUTINE | - |
| ~~Sodium phenylbutyrate/taurursodiol (Relyvrio)~~ | ~~PO~~ | ~~FTD-ALS overlap; neuroprotective~~ | WITHDRAWN :: N/A :: N/A :: WITHDRAWN FROM MARKET (April 2024) - Amylyx withdrew Relyvrio after the Phase III PHOENIX trial failed to demonstrate efficacy. No longer available for prescribing. | N/A | N/A | - | - | - | - |
4. OTHER RECOMMENDATIONS¶
4A. Referrals & Consults¶
| Recommendation | ED | HOSP | OPD | ICU |
|---|---|---|---|---|
| Behavioral/cognitive neurology for diagnosis confirmation, FTD subtype classification, and treatment guidance | - | ROUTINE | ROUTINE | - |
| Neuropsychology for comprehensive cognitive testing to establish baseline, characterize deficits, and track progression | - | - | ROUTINE | - |
| Genetic counseling for all patients with suspected FTD given high heritability (30-50% familial); discuss testing implications | - | - | ROUTINE | - |
| Speech-language pathology for language variant PPA evaluation, communication strategies, and swallowing assessment | - | ROUTINE | ROUTINE | - |
| Geriatric psychiatry for complex behavioral management and psychotropic medication optimization | - | ROUTINE | ROUTINE | - |
| Social work for caregiver support resources, community services, respite care, and long-term care planning | - | ROUTINE | ROUTINE | - |
| Occupational therapy for ADL assessment, cognitive strategies, home safety evaluation, and activity structuring | - | ROUTINE | ROUTINE | - |
| Physical therapy for fall prevention, mobility assessment, and exercise program particularly if motor features present | - | ROUTINE | ROUTINE | - |
| Palliative care for symptom management and goals of care discussions, especially with advanced disease or ALS overlap | - | ROUTINE | ROUTINE | - |
| Neuromuscular specialist if motor neuron disease features (weakness, fasciculations, bulbar symptoms) present | - | ROUTINE | ROUTINE | - |
| Elder law attorney for advance directives, healthcare proxy, conservatorship, and financial planning while capacity exists | - | - | ROUTINE | - |
4B. Patient Instructions¶
| Recommendation | ED | HOSP | OPD |
|---|---|---|---|
| Return immediately if sudden worsening of behavior, new weakness, difficulty breathing, or inability to swallow safely | STAT | STAT | ROUTINE |
| Complete advance directives (living will, healthcare proxy, POLST) while patient retains capacity; FTD can progress rapidly | - | ROUTINE | ROUTINE |
| Designate durable power of attorney for healthcare AND finances early as judgment may be impaired before memory | - | ROUTINE | ROUTINE |
| Do not drive; FTD impairs judgment, impulse control, and decision-making even if memory appears intact | - | ROUTINE | ROUTINE |
| Remove access to weapons, power tools, and dangerous equipment due to impaired judgment and safety awareness | - | ROUTINE | ROUTINE |
| Supervise financial decisions; patients with FTD are vulnerable to fraud, impulsive spending, and poor judgment | - | ROUTINE | ROUTINE |
| Secure medications to prevent accidental or intentional overdose; use locked medication storage | - | ROUTINE | ROUTINE |
| Monitor for wandering; consider GPS tracking devices and door alarms as disease progresses | - | ROUTINE | ROUTINE |
| Report diagnosis to DMV per state requirements; most states require physician reporting for unsafe drivers | - | - | ROUTINE |
| Genetic testing results have implications for family members; discuss with genetic counselor before testing | - | - | ROUTINE |
4C. Lifestyle & Prevention¶
| Recommendation | ED | HOSP | OPD |
|---|---|---|---|
| Structured daily routine with consistent schedule reduces anxiety and behavioral symptoms | - | ROUTINE | ROUTINE |
| Regular physical activity (walking, supervised exercise) improves mood and maintains function | - | ROUTINE | ROUTINE |
| Simplified communication using short sentences, yes/no questions, and visual cues for PPA variants | - | ROUTINE | ROUTINE |
| Avoid overstimulation; reduce noise, crowds, and complex environments that trigger agitation | - | ROUTINE | ROUTINE |
| Caregiver education through AFTD (Association for Frontotemporal Degeneration) resources and support groups | - | ROUTINE | ROUTINE |
| Respite care for caregivers to prevent burnout; FTD caregiving is particularly demanding due to behavioral symptoms | - | ROUTINE | ROUTINE |
| Address hyperorality and dietary changes with portion control, healthy snack availability, and locked food storage if needed | - | ROUTINE | ROUTINE |
| Safe environment modifications: remove fall hazards, lock cabinets with dangerous items, install stove knob covers | - | ROUTINE | ROUTINE |
| One-to-one supervision may be needed for safety; consider adult day programs or in-home care | - | ROUTINE | ROUTINE |
| Smoking cessation and alcohol avoidance to prevent additional brain injury and drug interactions | - | ROUTINE | ROUTINE |
SECTION B: REFERENCE¶
5. DIFFERENTIAL DIAGNOSIS¶
| Alternative Diagnosis | Key Distinguishing Features | Tests to Differentiate |
|---|---|---|
| Alzheimer's disease | Memory impairment prominent early; episodic memory loss; posterior cortical atrophy pattern | CSF Aβ42 low, p-tau elevated; amyloid PET positive; temporal-parietal atrophy on MRI |
| Dementia with Lewy bodies | Visual hallucinations; parkinsonism; REM sleep behavior disorder; fluctuating cognition | DaTscan reduced; RBD on sleep study; better response to cholinesterase inhibitors |
| Primary psychiatric disorder | Onset often younger; personal/family psychiatric history; may have insight; responds to treatment | Normal MRI; normal FDG-PET; improvement with psychiatric treatment |
| Huntington's disease | Chorea; family history (autosomal dominant); psychiatric symptoms precede motor | CAG repeat expansion; caudate atrophy on MRI |
| Progressive supranuclear palsy (PSP) | Vertical gaze palsy; axial rigidity; early falls; frontal features | "Hummingbird sign" on MRI; poor levodopa response |
| Corticobasal syndrome (CBS) | Asymmetric apraxia; alien limb; cortical sensory loss; dystonia | Asymmetric atrophy; may have FTD overlap |
| Creutzfeldt-Jakob disease | Rapid progression (weeks-months); myoclonus; ataxia; startle | MRI DWI ribboning; EEG periodic discharges; CSF RT-QuIC positive |
| Autoimmune encephalitis | Subacute onset; seizures; psychiatric features; often younger | Autoantibody panel positive; MRI limbic changes; CSF inflammation |
| Normal pressure hydrocephalus | Gait disturbance predominant; urinary incontinence; magnetic gait | MRI ventriculomegaly out of proportion to atrophy; large-volume LP improvement |
| Vascular dementia | Stepwise decline; vascular risk factors; focal deficits | Extensive white matter disease and strategic infarcts on MRI |
| Medication/substance-induced | Temporal relationship to drug exposure; anticholinergics, sedatives common culprits | Medication reconciliation; improvement with discontinuation |
| Late-onset bipolar disorder | Episodic mood symptoms; family history; intact cognition between episodes | Normal neuroimaging; psychiatric evaluation; treatment response |
6. MONITORING PARAMETERS¶
| Parameter | Frequency | Target/Threshold | Action if Abnormal | ED | HOSP | OPD | ICU |
|---|---|---|---|---|---|---|---|
| Cognitive testing (MoCA, MMSE, or FTLD-specific battery) | Every 6-12 months | Document trajectory; identify rapid decline | Adjust care level; medication review; genetics if rapid | - | ROUTINE | ROUTINE | - |
| Frontal assessment battery (FAB) | Every 6-12 months | Track executive function specific to FTD | Increase supervision; safety planning | - | - | ROUTINE | - |
| Functional status (ADL/IADL, FBI, CBI) | Every 6 months | Monitor independence and safety | Increase caregiver support; consider placement | - | ROUTINE | ROUTINE | - |
| Behavioral assessment (NPI-Q, FBI) | Each visit | Quantify behavioral symptoms and treatment response | Adjust medications; non-pharmacologic strategies | - | ROUTINE | ROUTINE | - |
| Motor function (if FTD-ALS) | Every 3-6 months | FVC, ALSFRS-R for motor progression | Respiratory support; PT/OT; feeding tube discussion | - | ROUTINE | ROUTINE | - |
| Weight | Each visit | Stable; monitor for hyperorality weight gain OR wasting | Nutritional consult; address hyperphagia or dysphagia | - | ROUTINE | ROUTINE | - |
| Swallowing function | Every 6-12 months or if symptoms | Safe oral intake | Speech therapy; diet modification; feeding tube if needed | - | ROUTINE | ROUTINE | - |
| Caregiver burden (Zarit Burden Interview) | Every 6-12 months | Early identification of burnout | Respite care; support groups; social work | - | - | ROUTINE | - |
| Safety assessment | Each visit | No harm to self or others; safe environment | Increase supervision; remove hazards; consider placement | - | ROUTINE | ROUTINE | - |
| ECG (if on QT-prolonging medications) | Baseline; with dose changes | QTc <470 ms (men), <480 ms (women) | Reduce dose or switch medication | - | ROUTINE | ROUTINE | - |
| LFTs (if on valproic acid or riluzole) | Monthly x 3, then q3mo | Normal transaminases | Reduce or discontinue if >3x ULN | - | ROUTINE | ROUTINE | - |
7. DISPOSITION CRITERIA¶
| Disposition | Criteria |
|---|---|
| Discharge home | Behavioral crisis resolved; safe environment; adequate caregiver supervision; outpatient follow-up arranged; medications optimized |
| Admit to floor | Severe behavioral disturbance unsafe for home; medical workup needed; medication adjustment requiring monitoring; caregiver unable to manage |
| Admit to psychiatry | Danger to self or others; severe aggression; psychotic features; requires locked unit for safety |
| Memory care/Long-term care | Progressive decline; wandering risk; 24-hour supervision needed; caregiver unable to provide safe care |
| Hospice | End-stage FTD; minimal responsiveness; recurrent aspiration; weight loss; goals focused on comfort; FVC <50% in FTD-ALS |
| Outpatient follow-up | Neurology/cognitive neurology every 3-6 months; more frequent if on psychotropics or rapid progression; genetics follow-up after testing |
8. EVIDENCE & REFERENCES¶
| Recommendation | Evidence Level | Source |
|---|---|---|
| Diagnostic criteria for bvFTD (International Consensus) | Class I, Level A | Rascovsky et al. Brain 2011 |
| Diagnostic criteria for PPA variants | Class I, Level A | Gorno-Tempini et al. Neurology 2011 |
| SSRIs for behavioral symptoms in FTD | Class II, Level B | Herrmann et al. J Clin Psychiatry 2012 |
| Trazodone for FTD behavioral symptoms | Class II, Level B | Lebert et al. Dement Geriatr Cogn Disord 2004 |
| Cholinesterase inhibitors not recommended in FTD | Class II, Level B | Mendez et al. Am J Alzheimers Dis Other Demen 2007 |
| Antipsychotic mortality risk in dementia | Class I, Level A | Schneider et al. JAMA 2005 |
| C9orf72 as most common genetic cause of FTD/ALS | Class I, Level A | DeJesus-Hernandez et al. Neuron 2011; Renton et al. Neuron 2011 |
| MAPT and GRN mutations in familial FTD | Class I, Level A | Rohrer et al. Lancet Neurol 2009 |
| FDG-PET in FTD diagnosis | Class II, Level B | Foster et al. Ann Neurol 2007 |
| CSF NfL as prognostic biomarker in FTD | Class II, Level B | Rohrer et al. Neurology 2016 |
| Memantine limited efficacy in FTD | Class II, Level C | Boxer et al. Lancet Neurol 2013 |
| FTD-ALS continuum | Class I, Level A | Burrell et al. Lancet Neurol 2016 |
| Serum progranulin as GRN mutation screen | Class II, Level B | Finch et al. J Mol Diagn 2009 |
| Practice guidelines for FTD management | Class III, Level C | Tsai et al. Neurology 2021 |
| Riluzole in ALS | Class I, Level A | Miller et al. Cochrane 2012 |
| Relyvrio (AMX0035) withdrawn after PHOENIX trial failure | N/A | Amylyx Pharmaceuticals press release, April 2024; PHOENIX trial (NCT05021536) |
CHANGE LOG¶
v1.1 (January 30, 2026) - Reformatted lab tables (1A/1B/1C) to standard column order: Test | ED | HOSP | OPD | ICU | Rationale | Target Finding - Reformatted imaging tables (2A/2B/2C) and LP table to standard column order with venues in positions 2-5 - Added inline CPT codes to all lab tests, imaging studies, and LP studies - Fixed structured dosing format: starting dose only in first field across all treatment sections - SAFETY: Annotated Relyvrio (sodium phenylbutyrate/taurursodiol) as WITHDRAWN from market (April 2024) after PHOENIX trial failure - Added clinical synonyms for searchability - Added VERSION/CREATED/REVISED header block - Added Relyvrio withdrawal to Evidence & References section
v1.0 (January 27, 2026) - Initial template creation - International consensus diagnostic criteria for bvFTD and PPA variants - Comprehensive genetic evaluation (C9orf72, MAPT, GRN) - SSRIs and trazodone as first-line behavioral treatments - Explicit guidance to AVOID cholinesterase inhibitors - FTD-ALS overlap section with riluzole and edaravone - Caregiver support and safety planning emphasis - Structured dosing format for order sentence generation - PubMed-linked citations
APPENDIX A: FTD Clinical Variants¶
Behavioral Variant FTD (bvFTD)¶
Core Features (International Consensus Criteria - Rascovsky 2011):
Early behavioral disinhibition (at least one of): - Socially inappropriate behavior - Loss of manners or decorum - Impulsive, rash, or careless actions
Early apathy or inertia (at least one of): - Loss of motivation or drive - Emotional blunting - Withdrawal from activities
Early loss of sympathy or empathy (at least one of): - Diminished response to others' needs - Diminished social interest, warmth - Personal coldness
Early perseverative, stereotyped, or compulsive/ritualistic behavior (at least one of): - Simple repetitive movements - Complex compulsive behaviors - Stereotypy of speech
Hyperorality and dietary changes (at least one of): - Altered food preferences (especially sweets) - Binge eating or increased consumption - Oral exploration of inedible objects
Neuropsychological profile: - Executive deficits - Relative sparing of episodic memory - Relative sparing of visuospatial skills
Possible bvFTD: 3 of 6 features Probable bvFTD: Possible + functional decline + characteristic imaging Definite bvFTD: Histopathological or pathogenic mutation confirmation
Semantic Variant PPA (svPPA)¶
Core Features: - Impaired confrontation naming - Impaired single-word comprehension
Supportive Features (3 of 4 required): - Impaired object knowledge - Surface dyslexia or dysgraphia - Spared repetition - Spared speech production (grammar and motor speech)
Imaging: Anterior temporal atrophy (typically left > right)
Nonfluent/Agrammatic Variant PPA (nfvPPA)¶
Core Features (at least one): - Agrammatism in language production - Effortful, halting speech with inconsistent speech sound errors (apraxia of speech)
Supportive Features (2 of 3 required): - Impaired comprehension of syntactically complex sentences - Spared single-word comprehension - Spared object knowledge
Imaging: Left posterior fronto-insular atrophy
APPENDIX B: Genetic Evaluation Guide¶
When to Consider Genetic Testing¶
Strongly Consider Testing: - Family history of FTD, ALS, or unspecified dementia in first-degree relative - Age of onset <60 years - FTD-ALS phenotype - Known family mutation
Consider Testing: - Any FTD diagnosis (30-50% have genetic component) - Research participation interest - Family planning implications for children
Major FTD Genes¶
| Gene | Protein | Frequency | Phenotype | Pathology |
|---|---|---|---|---|
| C9orf72 | None (repeat expansion) | 25-40% of familial | bvFTD, ALS, FTD-ALS, psychosis | TDP-43, p62 inclusions |
| GRN | Progranulin | 15-25% of familial | bvFTD (asymmetric), PPA, CBS | TDP-43 type A |
| MAPT | Tau | 10-20% of familial | bvFTD, parkinsonism, PSP-like | Tau pathology |
| TARDBP | TDP-43 | <5% | ALS, FTD-ALS | TDP-43 |
| VCP | Valosin-containing protein | <5% | IBM, Paget's, FTD | TDP-43 |
| FUS | FUS | <1% | ALS, FTD | FUS inclusions |
Progranulin Screening¶
Serum progranulin level can screen for GRN mutations: - Normal: >100 ng/mL (varies by assay) - Low: <100 ng/mL suggests GRN mutation; confirm with gene sequencing
C9orf72 Interpretation¶
- Normal: <30 hexanucleotide repeats
- Pathogenic: >30 repeats (typically hundreds to thousands)
- Intermediate: 20-30 repeats (clinical significance unclear)
APPENDIX C: Safety and Supervision Planning Checklist¶
Immediate Safety (All FTD Patients)¶
- Driving cessation discussed and documented
- Weapons removed from home
- Medications secured (locked storage)
- Financial oversight arranged
- Stove/appliance safety (knob covers, auto-shutoff)
- Door alarms/locks for wandering risk
Advance Planning¶
- Healthcare power of attorney designated
- Durable financial power of attorney designated
- Living will/advance directive completed
- POLST form if appropriate
- Long-term care financing discussed
- Genetic counseling offered to family
Caregiver Support¶
- AFTD (theaftd.org) resources provided
- Local support group identified
- Respite care options discussed
- Adult day program referral if appropriate
- Home health aide evaluation
- Social work consultation
Monitoring Red Flags¶
Contact Provider If: - New or worsening aggression - Suicidal statements or self-harm behavior - Inability to recognize caregivers - Falls with injury - Significant weight loss or gain - Swallowing difficulties - New weakness (FTD-ALS concern) - Caregiver exhaustion/burnout