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)
CPT CODES: 85025 (CBC with differential), 80048 (BMP (Na, K, BUN, Cr, glucose)), 84443 (TSH), 82607 (Vitamin B12), 82746 (Folate), 80076 (Hepatic panel (AST, ALT, albumin, ammonia)), 82310 (Calcium), 81001 (Urinalysis), 86592 (RPR or VDRL), 87389 (HIV testing), 85651 (ESR), 86235 (ANA), 82550 (Creatine kinase), 95907-95913 (EMG/NCS referral), 83519 (Serum progranulin level), 81479 (C9orf72 hexanucleotide repeat expansion), 86255 (Anti-neuronal antibodies (NMDA-R, LGI1, CASPR2, GAD65)), 70551 (MRI Brain without contrast), 70450 (CT Head non-contrast), 78816 (FDG-PET Brain), 70553 (MRI Brain volumetrics), 95819 (EEG), 95810 (Sleep study (polysomnography)), 78607 (DaTscan (ioflupane I-123)) 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: Approved
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