Nervous System & Special Senses

Frontotemporal dementia: clinical features

Clinical Overview and When to Suspect Frontotemporal Dementia

— Behavioral variant FTD (bvFTD) — most common (~60%); progressive personality, behavior, and executive dysfunction

— Semantic variant primary progressive aphasia (svPPA) — loss of word/object meaning, fluent but empty speech

— Nonfluent/agrammatic variant PPA (nfvPPA) — effortful, halting speech with agrammatism

— Younger patient (<65) brought in by family (not self) for personality change, disinhibition, apathy, or social misconduct

— Early language breakdown without prominent memory loss

— Coexisting motor signs suggesting overlap syndromes — ALS (FTD-MND), corticobasal syndrome (CBS), or progressive supranuclear palsy (PSP)

— Strong family history of early dementia, ALS, or parkinsonism (~40% familial; C9orf72, MAPT, GRN mutations)

— FTLD-tau (Pick bodies, MAPT mutations, PSP, CBD)

— FTLD-TDP (TDP-43; GRN and C9orf72-associated)

— A minority are FTLD-FUS

Board pearl: A 58-year-old executive who starts shoplifting, makes inappropriate sexual comments, gorges on sweets, and shows preserved spatial navigation but blunted empathy is bvFTD until proven otherwise — not Alzheimer disease. Memory and visuospatial skills are characteristically spared early, which is the single most useful clinical wedge separating FTD from AD on Step 3 vignettes. Early loss of insight and empathy in a relatively young patient should anchor your differential before you even order imaging.

Frontotemporal dementia (FTD) is a neurodegenerative syndrome from focal atrophy of frontal and/or anterior temporal lobes, encompassing three core clinical phenotypes:

Epidemiology: second or third most common young-onset dementia (peak onset 45–65 years); roughly equal prevalence to Alzheimer disease (AD) before age 65

Suspect FTD when:

Pathology falls into two main molecular classes:

Presentation Patterns and Key History

— Early behavioral disinhibition — socially inappropriate acts, impulsivity, loss of manners

— Early apathy or inertia — withdrawal, decreased motivation (often mistaken for depression)

— Loss of sympathy/empathy — "cold," indifferent to loved ones' distress

— Perseverative, stereotyped, or compulsive behavior — hoarding, ritualized routines, repeated phrases

— Hyperorality and dietary changes — binge eating, sweet/carbohydrate craving, pica

— Dysexecutive neuropsychological profile with relative sparing of memory and visuospatial function

— Informant history is essential — patients lack insight

— Ask about financial mistakes, traffic violations, job loss, new criminal behavior

— Screen for ALS symptoms: dysphagia, fasciculations, weakness, dysarthria

— Family history: dementia, ALS, parkinsonism, psychiatric disease in first-degree relatives across 2+ generations

— Mid-life psychiatric "first break" (mania, OCD, psychosis) at age 55+ is a red flag for prodromal bvFTD or C9orf72

Key distinction: In AD, the wife reports memory loss; in bvFTD, the wife reports she barely recognizes her husband's personality. AD patients are typically embarrassed by errors; FTD patients are indifferent or amused by them. Loss of embarrassment itself is diagnostically suggestive.

Step 3 management: When the chief complaint is "personality change" in a 50–65-year-old, your first orders are collateral history, MoCA with frontal/executive items, depression screening (PHQ-9) to exclude pseudodementia, and MRI brain — not a memory-only workup.

bvFTD core features (need ≥3 of 6 within first 3 years for "possible" diagnosis per Rascovsky/IC-FTD criteria):

svPPA: fluent speech but anomia, impaired single-word comprehension, surface dyslexia, loss of object knowledge ("What is a zebra?" → "an animal?"). Often right-temporal variant presents instead with prosopagnosia and behavioral change

nfvPPA: apraxia of speech, agrammatism ("Yesterday… store… milk"), effortful production, preserved word meaning early

History pearls:

Physical Exam Findings (and Motor/Neurologic Assessment)

— Grasp reflex, palmomental, snout, glabellar (Myerson), rooting reflexes

— Utilization behavior — patient compulsively uses objects placed in front of them

— Imitation behavior — copies examiner's gestures unprompted

— Frontal Assessment Battery (FAB) — similarities, lexical fluency, motor programming (Luria fist-edge-palm), conflicting instructions, go/no-go, prehension

— Trails B, clock drawing (executive errors, not spatial), proverb interpretation (concrete answers)

— MoCA more sensitive than MMSE; MMSE often normal early in FTD — pitfall

— Confrontation naming (Boston Naming Test surrogate)

— Single-word comprehension ("Point to the anvil")

— Repetition of grammatically complex sentences

— Reading irregular words (surface dyslexia in svPPA: "yacht" → "yatched")

— ALS overlap: fasciculations (tongue, deltoid), atrophy, hyperreflexia with weakness, bulbar dysarthria — check fasciculations of the tongue at rest

— PSP: vertical gaze palsy (especially downgaze), axial rigidity, early falls

— CBS: asymmetric rigidity, apraxia, alien limb, cortical sensory loss, myoclonus

Board pearl: A patient with personality change who cannot look down voluntarily but can follow a finger downward (oculocephalic preserved) has supranuclear gaze palsy → PSP, an FTD-spectrum tauopathy. Vertical gaze testing is a 10-second exam maneuver that reframes the entire differential.

Step 3 management: Always perform a focused motor screen in any suspected dementia under age 70 — finding fasciculations changes prognosis from years to ~2–3 years (FTD-ALS) and prompts urgent neurology/ALS clinic referral and goals-of-care discussion.

General neurologic exam is often normal early in bvFTD — a critical and frequently tested point

Frontal release signs (late but high-yield):

Cognitive bedside exam:

Language exam:

Motor exam — screen for overlap syndromes:

Vitals/general: weight gain from hyperphagia, poor hygiene reflecting apathy

Diagnostic Workup — Initial Labs, Imaging, and Reversible Cause Screen

— CBC, CMP, TSH, B12, folate

— HIV, RPR (if risk factors or atypical features)

— Depression screening (PHQ-9) — pseudodementia mimics apathetic bvFTD

— Toxicology if behavioral change is abrupt

— Ceruloplasmin in patients <50 with movement signs → Wilson disease

— Focal frontal and/or anterior temporal atrophy, often asymmetric

— bvFTD: medial frontal, orbitofrontal, anterior cingulate atrophy ("knife-edge" gyri)

— svPPA: left anterior temporal atrophy (right-sided in right-temporal variant)

— nfvPPA: left inferior frontal/insular atrophy (Broca area territory)

— Compare with AD pattern: medial temporal/hippocampal and parietal atrophy

Key distinction: MRI atrophy pattern is the single highest-yield discriminator on imaging questions:

— Frontal/anterior temporal → FTD

— Hippocampal/parietal → AD

— Occipital → posterior cortical atrophy (atypical AD) or DLB

— Caudate atrophy → Huntington disease

— Midbrain "hummingbird"/"penguin" → PSP

Step 3 management: A 60-year-old with 2 years of disinhibition, normal TSH/B12/RPR, and MRI showing bifrontal atrophy with sparing of hippocampi — diagnosis is clinically probable bvFTD; do not anchor on AD just because the patient is older. Avoid empirically starting cholinesterase inhibitors at this stage — they can worsen behavior in FTD.

Reversible-dementia screen (do this in every new dementia evaluation, not just FTD):

Structural neuroimaging — MRI brain (preferred):

CT acceptable if MRI contraindicated but less sensitive for subtle frontotemporal volume loss

EEG: usually normal in FTD (vs. slowing in AD or CJD periodic complexes) — useful negative

ECG/orthostatics if syncope or falls — rule out DLB-associated dysautonomia

Standard age-appropriate labs and CXR if hospitalized for behavioral crisis

Diagnostic Workup — Advanced and Confirmatory Studies

— FDG-PET: frontal and anterior temporal hypometabolism — high sensitivity when MRI is equivocal early in disease

— Amyloid PET (florbetapir/florbetaben/flutemetamol): typically negative in FTD, positive in AD — useful when distinction is clinically critical (e.g., consideration of anti-amyloid therapy or research enrollment)

— Tau PET: emerging; positive patterns differ between AD and FTLD-tau

— AD profile: low Aβ42, high total tau and phospho-tau, low Aβ42/Aβ40 ratio

— FTD: typically normal Aβ42 with variable tau; normal CSF AD profile in a young dementia patient supports FTD

— Plasma biomarkers (p-tau217) increasingly used to rule out AD pathology

— Onset <65

— Positive family history of dementia, ALS, or parkinsonism

— FTD-ALS phenotype

— Panel: C9orf72 hexanucleotide repeat (most common; also causes ALS), GRN (progranulin; often asymmetric, may have parietal involvement), MAPT (tauopathy)

Board pearl: A negative amyloid PET in a 55-year-old with progressive behavioral change and frontal atrophy essentially rules out Alzheimer disease and locks in the FTD diagnosis. Conversely, a positive AD CSF profile in a patient with apparent bvFTD should make you reconsider — frontal-variant AD can mimic bvFTD.

Step 3 management: Refer for pre-test genetic counseling before ordering C9orf72/GRN/MAPT testing — results have major implications for asymptomatic first-degree relatives and insurance/employment (GINA protections are partial).

Functional/molecular imaging:

CSF biomarkers (mainly to exclude AD):

Neuropsychological testing: confirms dysexecutive + social cognition deficits with preserved episodic memory and visuospatial skills

Genetic testing — offer when:

EMG/NCS if any motor signs — confirms lower motor neuron involvement in FTD-ALS

Risk Stratification and Management Framework

— Safety assessment: driving, firearms, finances, cooking, wandering

— Capacity evaluation for medical, financial, and legal decisions — do this early while patient can still participate

— Caregiver support — FTD caregiver burden is among the highest of any dementia

— Advance directives, durable power of attorney, MOLST/POLST

— Disability paperwork — FTD qualifies for Social Security Compassionate Allowance (fast-tracked SSDI)

— Identify target symptom (disinhibition, compulsions, hyperphagia, agitation, apathy)

— Try environmental/behavioral interventions first (structure, routine, redirection, removing triggers)

— Reserve pharmacotherapy for symptoms causing harm or severe caregiver distress

— Median survival from symptom onset: 6–11 years for bvFTD/PPA

— FTD-ALS: 2–3 years

— PSP/CBS: 5–7 years

— Behavioral neurology or memory clinic

— Speech-language pathology (PPA variants)

— Genetic counseling

— Palliative care (early integration recommended)

— Social work for caregiver resources, FTD-specific support groups (AFTD)

CCS pearl: On an outpatient CCS case of newly diagnosed FTD, order in sequence: safety counseling (driving/firearms), capacity assessment, advance directive discussion, caregiver support referral, SLP referral (for PPA), and follow-up in 3 months — clock advances; do not delay disposition planning while waiting for genetic results.

Step 3 management: Driving must be addressed at diagnosis. State laws vary on mandatory reporting; document the recommendation and family discussion.

No disease-modifying therapy exists for FTD — management is symptomatic, multidisciplinary, and anticipatory

Initial management priorities after diagnosis:

Behavioral symptom triage:

Prognosis counseling:

Referrals:

Pharmacotherapy — Symptom-Targeted Regimens

— Sertraline 25–200 mg/day, citalopram ≤20 mg/day (QT caution, especially >60), escitalopram 10–20 mg, fluvoxamine, paroxetine (anticholinergic — avoid in elderly)

— Trazodone 50–300 mg/day — evidence for reducing agitation, irritability, depression in FTD; sedating, useful at bedtime

— Atypical antipsychotics with caution — quetiapine (lowest EPS risk), low-dose aripiprazole, or olanzapine

— FTD patients are exquisitely sensitive to EPS — start low, monitor for parkinsonism

— Black-box warning: increased mortality in elderly with dementia-related psychosis — document risk/benefit, time-limit therapy, attempt taper

— Avoid haloperidol and other high-potency typicals

— Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) — no benefit, may worsen agitation/disinhibition

— Memantine — RCTs negative in FTD; not recommended

— Benzodiazepines — paradoxical disinhibition, falls

— Anticholinergics broadly (worsen cognition)

Key distinction: Donepezil is reflexively right for AD and reflexively wrong for FTD — a classic Step 3 trap. If a vignette describes frontal atrophy and behavioral symptoms, do not pick a cholinesterase inhibitor.

Board pearl: Trazodone is the most evidence-supported single agent for behavioral symptoms in bvFTD aside from SSRIs and is preferable to antipsychotics when sedation/sleep is also a concern.

Disinhibition, compulsivity, hyperphagia, irritability → SSRIs are first-line:

Severe agitation, aggression, psychosis (when SSRIs fail and safety is at stake):

Avoid in FTD:

Apathy — no proven pharmacotherapy; stimulants (methylphenidate) tried off-label with mixed evidence

Motor symptoms (PSP/CBS overlap): levodopa trial often poorly responsive but worth attempting; botulinum toxin for focal dystonia

Non-Pharmacologic and Multidisciplinary Management

— Structured daily routine with predictable meals, activities, sleep schedule

— Trigger identification and avoidance — caregivers keep symptom diaries

— Redirection rather than confrontation (patients lack insight, arguing escalates)

— Simplify environment — remove credit cards, car keys, firearms, dangerous tools

— Lock pantries/refrigerators for hyperphagia; portion-control meals

— Childproof locks on doors if wandering; GPS trackers, MedicAlert

— svPPA: compensatory communication strategies, scripts, communication books

— nfvPPA: articulation therapy, augmentative/alternative communication (AAC) devices as speech deteriorates

— Counseling on transition to nonverbal communication

— AFTD (Association for Frontotemporal Degeneration) support groups, helpline

— Respite care — adult day programs, in-home aides

— Caregiver mental health screening — high rates of depression and burnout

— Education on disease trajectory and what behaviors are neurologic, not willful

CCS pearl: Order home safety evaluation and caregiver support referral at the index visit — these are high-impact and frequently rewarded in CCS scoring for dementia cases.

Behavioral/environmental interventions are first-line and often more effective than drugs:

Speech-language therapy (essential in PPA variants):

Occupational therapy: home safety evaluation, adaptive equipment, structured activity programming

Physical therapy: balance/gait training, particularly in PSP/CBS overlap (falls are leading injury)

Nutrition: dietitian for hyperphagia/weight gain or, late-stage, dysphagia and weight loss

Dental hygiene often neglected due to apathy — proactive care

Caregiver interventions:

Long-term placement planning — memory care units familiar with young-onset dementia (FTD patients are often physically strong, ambulatory, and behaviorally complex — many facilities decline them)

Special Populations — Elderly, Renal, and Hepatic Impairment

— Reconsider late-onset AD with frontal variant, vascular dementia (frontal strokes), DLB, normal-pressure hydrocephalus, and chronic subdural hematoma

— Lower threshold for amyloid PET or CSF AD biomarkers — frontal-variant AD is more common with age than late-onset bvFTD

— Polypharmacy review — anticholinergic burden, benzodiazepines, opioids, and steroids can mimic frontal syndromes

— Delirium screen (CAM) — acute behavioral change is delirium until proven otherwise

— Citalopram/escitalopram dose reduction if CrCl <20 (citalopram ≤20 mg total)

— Sertraline preferred — minimal renal adjustment, hepatic metabolism

— Memantine would require renal adjustment, but it's not indicated in FTD anyway

— Antipsychotics: quetiapine generally safe in CKD; monitor sedation

— Sertraline, paroxetine: hepatic metabolism; reduce dose in cirrhosis

— Trazodone: hepatic metabolism; avoid in severe hepatic dysfunction

— Avoid valproate (sometimes used off-label for agitation) in liver disease

— Check baseline LFTs before initiating psychotropics; recheck in 4–8 weeks

— Baseline ECG before citalopram/escitalopram, antipsychotics, and methadone or ondansetron co-prescription

— Citalopram >20 mg in >60 → prolonged QTc, FDA warning

Key distinction: NPH triad (gait apraxia, urinary incontinence, cognitive slowing) in an elderly patient with frontal symptoms is often missed — order MRI looking for ventriculomegaly out of proportion to atrophy and consider high-volume LP as a diagnostic trial. NPH is potentially reversible with shunting; FTD is not.

Step 3 management: In an elderly patient with new "FTD-like" behavior over days to weeks, the answer is delirium workup (UA, CBC, BMP, med review, imaging if focal), not dementia subtyping.

Elderly (>70) with new FTD-like presentation:

Renal impairment:

Hepatic impairment:

QTc considerations:

Frailty and falls: minimize sedating agents; deprescribe at each visit

Special Populations — Young-Onset, Genetic Carriers, and FTD-ALS

— Huntington disease — caudate atrophy, chorea, autosomal dominant, CAG repeats

— Wilson disease — Kayser-Fleischer rings, low ceruloplasmin, hepatic dysfunction

— Niemann-Pick type C — vertical supranuclear gaze palsy in a young adult, splenomegaly

— Autoimmune/limbic encephalitis — subacute, antibody panel (NMDA-R, LGI1)

— HIV-associated neurocognitive disorder, neurosyphilis, CJD

— Primary psychiatric disease — bipolar, schizophrenia (especially in C9orf72 carriers)

— Pre-symptomatic genetic testing only after formal counseling

— Discuss psychological impact, insurance (GINA covers health but NOT life/disability/long-term care), family planning

— Many enroll in research cohorts (ALLFTD, GENFI) for biomarker tracking

— Rapidly progressive; combines behavioral/cognitive decline with bulbar or limb-onset weakness

— Multidisciplinary ALS clinic referral

— Early discussion of PEG tube, NIV/BiPAP, tracheostomy preferences, advance directives

— Riluzole and edaravone for ALS component (no benefit for cognitive symptoms)

— Survival typically 2–3 years

Board pearl: A 50-year-old with new psychosis, behavioral change, and a brother who died of "Lou Gehrig disease" — test for C9orf72 hexanucleotide repeat expansion. C9orf72 is the most common genetic cause of both familial FTD and familial ALS and frequently presents with late-onset psychiatric symptoms.

Step 3 management: Offer genetic counseling before testing; document discussion of GINA limitations regarding life and long-term care insurance.

Young-onset FTD (<45) is rare; consider:

Pregnancy: FTD itself is rare in childbearing years; if a genetic carrier is pregnant, refer for preimplantation genetic diagnosis counseling for future pregnancies

Asymptomatic at-risk family members (autosomal dominant mutations):

FTD-ALS (often C9orf72):

Pediatric considerations: children of mutation carriers — age-appropriate education, school support, mental health monitoring

Complications and Adverse Outcomes

— Financial exploitation and ruin — impulsive spending, scams, gambling; up to 50% of FTD patients

— Legal entanglements — shoplifting, traffic violations, sexual misconduct, assault

— Motor vehicle crashes — impaired judgment, distractibility; FTD has higher crash risk than AD

— Firearm injuries — disinhibition + access

— Wandering and elopement

— Weight gain and metabolic syndrome from hyperphagia and carbohydrate craving early

— Weight loss, sarcopenia, dehydration late-stage

— Choking and aspiration from dysphagia (especially PPA, FTD-ALS, PSP)

— Aspiration pneumonia — leading cause of death

— Depression, anxiety, burnout

— Divorce rates elevated

— Financial strain — young-onset means loss of breadwinner; children still at home

— Misdiagnosis as primary psychiatric disease (bipolar, depression, schizophrenia) → years of inappropriate treatment, lost preparation time

— Suicidality in patients with preserved insight (more in PPA than bvFTD)

— Antipsychotic-induced parkinsonism, sedation, falls, increased mortality

— Benzodiazepine paradoxical disinhibition

— Inappropriate cholinesterase inhibitor trials worsening behavior

Board pearl: Aspiration pneumonia is the leading immediate cause of death in advanced FTD; dysphagia screening and SLP involvement reduce risk and should be standard at each follow-up once swallowing changes emerge.

Step 3 management: At every visit, ask three screening questions: driving, firearms, finances. Documenting these is a board-favored quality metric for dementia care.

Behavioral and safety complications:

Nutritional/metabolic:

Falls and fractures — especially PSP/CBS variants

Pressure injuries in late-stage immobility

Infections — UTI, pneumonia

Caregiver complications:

Psychiatric:

Iatrogenic:

When to Escalate Care — Hospitalization, Consults, and Crisis

— Suicidal/homicidal ideation with plan

— Aggression with imminent risk to self or others

— Severe psychosis unresponsive to outpatient management

— Caregiver inability to ensure safety in the community

— Aspiration pneumonia, sepsis, severe dehydration

— Status epilepticus (FTD has elevated seizure risk, especially GRN)

— Acute delirium superimposed on dementia with unclear cause

— Severe failure to thrive

— Hip fracture or other significant trauma

— Behavioral neurology / memory clinic — diagnosis and longitudinal care

— Neuropsychology — diagnostic clarification

— Psychiatry — refractory behavioral symptoms, comorbid mood

— Speech-language pathology — PPA management, dysphagia evaluation

— Genetics — family history or early onset

— Palliative care — early integration (consider at diagnosis, not end-of-life only)

— Social work — disability, placement, caregiver resources

— Elder/adult protective services — if exploitation or self-neglect

— FTD patients decompensate rapidly in unfamiliar environments

— Avoid restraints, multiple Foleys, tethering; minimize lines

— Avoid benzodiazepines and anticholinergics for "agitation" — they worsen it

— Use family at bedside, sitter, structured routine

— Update home medications carefully; avoid initiating donepezil reflexively

CCS pearl: When admitting an FTD patient for aspiration pneumonia, simultaneously order SLP swallow evaluation, aspiration precautions, head-of-bed elevation, sitter for safety, and goals-of-care conversation with the documented surrogate. Antibiotic choice depends on severity and aspiration setting (e.g., ampicillin-sulbactam for community-acquired aspiration with risk factors).

Step 3 management: Discharge planning must include 24-hour supervision verification — releasing an FTD patient to an empty home is a sentinel safety event.

Indications for inpatient psychiatric admission:

Indications for medical admission:

Consultations (outpatient and inpatient):

Hospital management pitfalls:

Key Differentials — Other Dementias

— Episodic memory loss first; visuospatial decline later

— MRI: hippocampal/medial temporal atrophy

— CSF/PET: positive amyloid; high tau

— Cholinesterase inhibitors + memantine helpful

— Frontal-variant AD can mimic bvFTD — disambiguate with amyloid PET/CSF

— Fluctuating cognition, visual hallucinations, REM sleep behavior disorder (RBD), parkinsonism

— Severe neuroleptic sensitivity — antipsychotics can be life-threatening

— DAT-SPECT shows reduced striatal dopamine uptake

— Stepwise decline, vascular risk factors, focal deficits, white matter disease on MRI

— Strategic frontal infarcts can mimic bvFTD — imaging distinguishes

— svPPA and nfvPPA are FTD spectrum

— Logopenic variant PPA (lvPPA) is usually AD pathology — word-finding pauses, impaired repetition, phonologic errors; amyloid-positive

Key distinction (the 4 dementia MRI patterns to memorize):

— Frontotemporal → FTD

— Hippocampal/parietal → AD

— Diffuse + occipital, normal-appearing → DLB

— Vascular lesions/white matter → VaD

Board pearl: Logopenic PPA = Alzheimer pathology in ~80%; despite being a "PPA," it is not in the FTD molecular family for treatment purposes — these patients may benefit from cholinesterase inhibitors.

Alzheimer disease (AD):

Dementia with Lewy bodies (DLB):

Parkinson disease dementia: parkinsonism precedes dementia by >1 year (vs. DLB <1 year — the "1-year rule")

Vascular dementia:

Primary progressive aphasia variants:

Progressive supranuclear palsy (PSP): early falls, vertical gaze palsy, axial rigidity — FTLD-tau

Corticobasal syndrome (CBS): asymmetric apraxia, alien limb, rigidity — heterogeneous pathology (CBD, AD, FTLD-TDP)

Huntington disease: chorea, psychiatric symptoms, caudate atrophy, autosomal dominant CAG repeats

Key Differentials — Non-Degenerative Mimics

— Late-onset bipolar mania — episodic, mood-congruent, often responds to mood stabilizers; FTD is progressive and unrelenting

— Major depressive disorder with apathy ("pseudodementia") — responds to antidepressants; cognitive deficits improve

— Obsessive-compulsive disorder — preserved insight, ego-dystonic; bvFTD compulsions are ego-syntonic with no insight

— Schizophrenia — onset typically earlier; FTD-onset psychosis after 50 is suspicious for C9orf72

— Chronic alcohol use → Wernicke-Korsakoff, frontal lobe damage

— Stimulant or sedative misuse

— Cannabis-induced apathy in older adults

— Benzodiazepines, opioids, anticholinergics, steroids ("steroid psychosis"), antiepileptics

— Hypothyroidism, B12/folate deficiency, hyponatremia, hypercalcemia, hepatic encephalopathy

— Cushing syndrome — mood, cognition, behavior

— Neurosyphilis, HIV, chronic Lyme (rare), PML, Whipple disease

— Autoimmune limbic encephalitis (anti-NMDAR, LGI1, CASPR2) — subacute, may have seizures, dysautonomia

— Hashimoto encephalopathy — steroid-responsive

— Chronic subdural hematoma — elderly with falls/anticoagulation

— Frontal meningioma, glioma

— Normal-pressure hydrocephalus

Key distinction: Course tempo matters:

— Days–weeks → delirium, encephalitis, stroke, drug effect

— Weeks–months → CJD, autoimmune encephalitis, paraneoplastic, NPH

— Years → FTD, AD, DLB, VaD

Step 3 management: Rapidly progressive dementia (<1–2 years) requires urgent workup including MRI with DWI, EEG, LP with autoimmune/paraneoplastic panel and prion markers, not routine outpatient referral.

Primary psychiatric disorders:

Substance use:

Medication-induced:

Endocrine/metabolic:

Infectious/inflammatory:

Structural:

Prion disease: Creutzfeldt-Jakob — rapid progression (months), myoclonus, ataxia, MRI cortical/basal ganglia DWI hyperintensity, 14-3-3 and RT-QuIC in CSF

Long-Term Plan and Discharge Considerations

— SSRI (sertraline most common) for behavioral symptoms — continue if effective

— Trazodone at bedtime if sleep/agitation

— Quetiapine at lowest effective dose only if necessary; time-limited with planned reassessment

— Deprescribe: cholinesterase inhibitors, memantine, benzodiazepines, anticholinergics

— Statins, antihypertensives, diabetes meds continued per usual indications

— Surrogate decision-maker (durable POA for healthcare)

— MOLST/POLST: CPR, intubation, hospitalization, artificial nutrition (PEG)

— Hospice referral when FAST stage 7 or weight loss + recurrent infections

— SSDI Compassionate Allowance for FTD

— Power of attorney for finances

— Will/estate planning while capacity preserved

— Long-term care insurance (often disqualified after diagnosis)

Key distinction: Hospice eligibility in FTD differs from AD — FTD patients often remain physically robust until very late, so triggers are typically dysphagia, recurrent aspiration, severe weight loss, or bedbound status rather than MMSE thresholds.

Step 3 management: A documented goals-of-care conversation within 90 days of diagnosis is the quality marker — bundle it with the first follow-up visit.

No FDA-approved disease-modifying therapy — emerging trials for progranulin replacement (GRN carriers) and antisense oligonucleotides for C9orf72; refer interested families to clinicaltrials.gov and ALLFTD consortium

Maintenance medication regimen at discharge or outpatient stabilization:

Vaccinations: influenza, pneumococcal (PCV20 or PCV15+PPSV23), COVID-19, RSV (≥60), shingles, Tdap — particularly important given aspiration pneumonia risk

Advance care planning — revisit at each major decline:

Financial/legal:

Driving cessation — formal driving evaluation through OT or DMV; document

Firearm removal from home — explicit, documented

Genetic testing follow-through for at-risk relatives if appropriate

Follow-Up, Monitoring, and Rehabilitation

— Every 3 months during initial titration of psychotropics or behavioral crises

— Every 6 months once stable

— Sooner for new symptoms, falls, aspiration events, caregiver crisis

— Symptom checklist: behavior, language, motor signs, mood, sleep, appetite, weight, continence

— Safety: driving, firearms, finances, wandering, falls

— Medications: efficacy, side effects, deprescribing opportunities

— Caregiver wellbeing: Zarit Burden Interview or simple screening; PHQ-2/9

— Functional status: ADLs, IADLs, FAST staging

— Weight and nutrition — trend critical; sudden weight loss suggests dysphagia

— Vital signs, orthostatics (especially on psychotropics/antipsychotics)

— Metabolic panel, lipids, HbA1c if on atypical antipsychotics (weight gain, dyslipidemia, diabetes)

— LFTs if on hepatically metabolized agents

— ECG for QTc with citalopram, escitalopram, antipsychotics

— SLP for ongoing dysphagia and communication strategies

— PT/OT for falls, gait, contracture prevention

— Dietitian for thickened liquids, dysphagia diet, caloric goals

— Behavior is neurologic, not willful — recurring teaching point

— Disease trajectory — what to expect in next 6–12 months

— Respite use before crisis, not after

— Support groups (AFTD, online)

— Self-care, sleep, mental health

— Memory care or skilled nursing

— Hospice when criteria met

— Bereavement support after death; offer brain donation for FTLD research (families often welcome this conversation)

CCS pearl: A 3-month follow-up that documents caregiver burden screening, deprescribing review, dysphagia screen, and advance directive status scores higher than one that only adjusts SSRI dose.

Routine follow-up cadence:

At each visit, monitor:

Labs:

Rehabilitation referrals as disease progresses:

Caregiver counseling priorities:

Late-stage transitions:

Ethical, Legal, and Patient Safety Considerations

— Capacity is decision-specific (consent for surgery ≠ managing finances)

— Assess understanding, appreciation, reasoning, ability to express a choice

— FTD patients may retain rote intellectual function but lack insight and judgment — formal capacity assessment is essential and is a frequent Step 3 topic

— Document capacity at each major decision point; reassess as disease progresses

— FTD patients may verbalize understanding of a procedure yet lack appreciation of how it applies to them — this fails capacity even if MMSE is preserved

— Surrogate decision-maker (per state hierarchy or designated DPOA-HC) consents

— Advance directives completed early are honored

— Many states require physician reporting of cognitively impaired drivers (e.g., California, Pennsylvania, Oregon)

— Others encourage but don't mandate

— Document the discussion, recommendation, and patient/family understanding

— Ask explicitly; recommend removal or secure storage outside the home

— Document; many states have extreme risk protection orders (red flag laws) if family cooperation fails

— FTD patients are at exceptionally high risk

— Recommend early DPOA-finances, joint accounts with trusted relative, credit freezes

— Mandatory reporting to Adult Protective Services if exploitation or self-neglect is suspected (varies by state, generally required for "vulnerable adults")

— Shoplifting, sexual misconduct — disease, not character; documentation can support legal defense

— Forensic neurology consultation if charges arise

— Pre-test counseling mandatory; consider implications for relatives, employment, GINA does not cover life/disability/long-term care insurance

— Predictive testing of asymptomatic minors is generally deferred until adulthood

— FTD patients are at high risk during handoffs (ED → admission, hospital → SNF) because behavior may be misinterpreted as delirium or "difficult patient"

— Communicate FTD diagnosis prominently in transfer notes; specify medication avoid-list (benzos, anticholinergics, haloperidol high-dose) and behavioral management plan

Board pearl: Reporting an FTD patient who continues to drive despite recommendations is ethically and often legally required — protecting third parties supersedes confidentiality.

Decision-making capacity:

Informed consent edge case:

Driving and mandatory reporting:

Firearm safety:

Financial exploitation:

Criminal behavior:

Genetic testing ethics:

Research participation: consider capacity to consent; use legally authorized representative when impaired

Transition-of-care safety:

High-Yield Associations and Rapid-Fire Facts

Board pearl: Three "F"s of bvFTD: frontal atrophy, family doesn't recognize them, feeding (hyperphagia and sweets). Three "no"s of treatment: no donepezil, no memantine, no benzos.

Three core syndromes: bvFTD, svPPA, nfvPPA

Average onset: 45–65 years — younger than AD

Memory and visuospatial function: relatively preserved early — key AD discriminator

MRI signature: frontal and/or anterior temporal atrophy ("knife-edge" gyri)

Most common genetic causes: C9orf72 > GRN > MAPT

C9orf72: FTD-ALS overlap, late-onset psychosis, hexanucleotide repeat

GRN (progranulin): asymmetric atrophy, may have parietal involvement, TDP-43 pathology

MAPT: tauopathy, often with parkinsonism

Pathology classes: FTLD-tau (Pick bodies, PSP, CBD) and FTLD-TDP (most common; C9orf72, GRN); minority FTLD-FUS

Pick disease: historical term for tau-positive Pick bodies in FTLD-tau

Hyperorality with sweet/carb preference: classic bvFTD feature

Klüver-Bucy syndrome features (hyperorality, hypersexuality, placidity) — bilateral anterior temporal lobe involvement

Right-temporal variant FTD: prosopagnosia + behavioral change

PSP: vertical supranuclear gaze palsy, early falls, axial rigidity, "hummingbird sign" midbrain atrophy on sagittal MRI

CBS: asymmetric apraxia, alien limb, cortical sensory loss, myoclonus

Logopenic PPA: usually AD pathology — disambiguate with amyloid PET

FTD-ALS survival: 2–3 years; bvFTD/PPA survival 6–11 years

First-line drug: SSRI (sertraline, citalopram, escitalopram, trazodone)

Avoid: cholinesterase inhibitors, memantine, benzodiazepines, anticholinergics, high-potency typical antipsychotics

SSDI Compassionate Allowance: FTD qualifies — fast-tracked

Leading cause of death: aspiration pneumonia

MMSE: insensitive early; use MoCA + FAB

Driving and firearms: ask and document at every visit

Caregiver burden: highest among dementias

Brain donation: offer late in disease for diagnostic and research confirmation

Board Question Stem Patterns

— 55-year-old executive, 2 years of progressive personality change: shoplifting, telling crude jokes, eating sweets compulsively, indifferent to grandchild's death. MMSE 27/30 with preserved memory. MRI: bifrontal atrophy. Diagnosis? → bvFTD. Next step? → SSRI + safety counseling. Avoid? → donepezil.

— 62-year-old, "I can't remember what words mean." Fluent, empty speech; cannot define "anchor" or "zebra." Recognizes letters. MRI: left anterior temporal atrophy. → svPPA.

— 65-year-old with effortful, halting speech, agrammatism, preserved comprehension. MRI: left inferior frontal/insular atrophy. → nfvPPA.

— 52-year-old with apathy and disinhibition + new dysphagia, tongue fasciculations, hyperreflexia, brother died of ALS. → Test C9orf72; refer to multidisciplinary ALS clinic; survival ~2–3 years.

— 70-year-old with recurrent backward falls, axial rigidity, inability to look down. → PSP; MRI shows midbrain atrophy ("hummingbird").

— Asymmetric arm rigidity + apraxia + alien limb + cortical sensory loss. → CBS.

— Donepezil offered for any dementia — wrong for FTD

— Lorazepam for agitation — wrong (paradoxical disinhibition, falls, mortality)

— Memantine — wrong (negative trials)

— Haloperidol high-dose — wrong (EPS sensitivity)

— MMSE 28 "rules out dementia" — wrong (insensitive for FTD)

— "Memory loss" assumed → AD — wrong if memory is preserved with personality change

— Patient still driving despite diagnosis → counsel, document, report per state law

— Family asks about predictive genetic testing for adult son → refer to genetic counseling, discuss GINA limitations

— Patient signs over savings to a stranger → APS report, assess capacity, engage DPOA

— Bifrontal atrophy → FTD

— Hippocampal atrophy → AD

— Midbrain atrophy ("hummingbird") → PSP

— Caudate atrophy → Huntington

Step 3 management: When the stem ends "what is the next best step," favor safety, capacity, advance directive, caregiver support answers over additional diagnostic testing once diagnosis is clinically established.

Classic bvFTD stem:

svPPA stem:

nfvPPA stem:

FTD-ALS stem:

PSP stem:

CBS stem:

Distractor traps:

Ethics/safety stems:

Imaging stems:

One-Line Recap

Frontotemporal dementia is a young-onset (45–65) neurodegenerative syndrome defined by early personality, behavior, or language change with preserved memory and visuospatial function, focal frontal/anterior temporal atrophy on MRI, no disease-modifying therapy, and management built on SSRIs/trazodone for behavior, multidisciplinary support, early advance-care planning, and strict avoidance of cholinesterase inhibitors, memantine, and benzodiazepines.

Rapid recap bullets:

Board pearl: If the vignette gives you a middle-aged patient whose family (not the patient) is worried, whose personality has changed, whose memory is intact, and whose MRI shows frontal atrophy — the answer is FTD, the drug to start is an SSRI, and the drug to avoid is donepezil.

Suspect FTD in any patient <65 with personality change or progressive language breakdown before memory loss; MMSE can be normal — use MoCA + FAB, get MRI showing frontal/anterior temporal atrophy, and rule out reversible causes (TSH, B12, RPR, HIV, depression).

Treat behavior with SSRIs (sertraline, citalopram, escitalopram) or trazodone first; reserve low-dose atypical antipsychotics (quetiapine) for severe agitation with documented risk/benefit; never use donepezil, memantine, benzodiazepines, or high-potency typicals as first-line — they worsen outcomes and are favorite Step 3 distractors.

Front-load safety and planning: at diagnosis, address driving, firearms, finances, capacity assessment, advance directives, DPOA, SSDI Compassionate Allowance, caregiver support (AFTD), and genetic counseling when family history or onset <65 suggests C9orf72, GRN, or MAPT mutation.

Monitor for aspiration pneumonia (leading cause of death), caregiver burnout (highest among dementias), and FTD-ALS overlap (survival 2–3 years vs. 6–11 years for pure bvFTD/PPA); transition to palliative care and hospice when dysphagia, recurrent infections, or bedbound status emerge.