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Dementia
9 notes available
1 Last Minute Review 2 Alzheimer Disease 3 Frontotemporal Dementia 4 Lewy Body & Parkinson Dementia 5 Vascular Cognitive Impairment 6 Rapidly Progressive Dementias 7 Reversible & Secondary Dementias 8 Mild Cognitive Impairment & Dementia Workup 9 Behavioral & Psychiatric Features
Clinical › Dementia

Frontotemporal Dementia

Frontotemporal Dementia

What You'll Learn

  • Second most common early-onset dementia (after AD) — typical onset age 45–65; equal sex distribution
  • Three clinical syndromes: behavioral variant FTD (bvFTD), nonfluent/agrammatic PPA (nfvPPA), and semantic variant PPA (svPPA); logopenic PPA (lvPPA) is usually AD pathology
  • Behavioral variant hallmarks: early disinhibition, apathy, loss of empathy, compulsive behaviors, hyperorality, executive dysfunction with relative sparing of episodic memory and visuospatial function
  • Genetics: ~30–50% have autosomal dominant family history; C9orf72 hexanucleotide repeat is the most common genetic cause and links FTD to ALS
  • Neuropathology classified by protein inclusion — FTLD-tau (Pick bodies, PSP, CBD), FTLD-TDP (types A–E), FTLD-FUS — NOT by clinical syndrome
  • No disease-modifying therapy: SSRIs and trazodone for behavioral symptoms; avoid cholinesterase inhibitors (may worsen bvFTD behavior)
  • Key differentiator from AD: personality/behavioral change precedes memory loss; frontal > temporal atrophy; younger age at onset
HighYield Pearls
  • bvFTD core criteria: early disinhibition + apathy + loss of empathy + perseverative/compulsive behavior + hyperorality/dietary changes + executive dysfunction with relative sparing of memory and visuospatial function; need ≥3 of 6 for possible bvFTD (Rascovsky 2011)
  • svPPA: loss of single-word comprehension + anomia + surface dyslexia + loss of object knowledge; LEFT anterior temporal “knife-edge” atrophy; usually FTLD-TDP type C
  • nfvPPA: effortful speech + agrammatism + apraxia of speech; LEFT inferior frontal/insular atrophy; usually 4R tauopathy (CBD/PSP spectrum) — may evolve into CBS or PSP
  • lvPPA pitfall: word-finding pauses + impaired sentence repetition + phonologic errors + LEFT temporoparietal atrophy → USUALLY AD PATHOLOGY, NOT FTLD (amyloid PET positive) — classic board trap
  • FTD-ALS / FTD-MND: motor neuron disease + bvFTD — C9ORF72 GGGGCC hexanucleotide expansion is the most common cause; TDP-43 type B pathology; survival shortens to 2–3 years
  • Genetics quick map: C9ORF72 → TDP-43 type B (FTD-ALS); GRN/PGRN haploinsufficiency → TDP-43 type A with neuronal intranuclear inclusions (low plasma progranulin screen); MAPT → tauopathy (3R, 4R, or mixed; Pick bodies if 3R)
  • Pathology spectrum: FTLD-tau (Pick 3R, PSP 4R, CBD 4R, MAPT mutations); FTLD-TDP (most common, types A–E); FTLD-FUS (rare, young-onset, severe basal ganglia atrophy)
  • bvFTD mimics: primary psychiatric disease, AD with behavioral presentation, vascular dementia, alcoholism — distinguish with structural MRI (frontotemporal atrophy) + FDG-PET frontotemporal hypometabolism + amyloid PET (negative)
  • Treatment: NO disease-modifying therapy; SSRIs (citalopram, sertraline) for behavioral symptoms; trazodone for sleep/agitation; avoid anticholinergics; atypical antipsychotics only as last resort
  • DO NOT use cholinesterase inhibitors in bvFTD — no benefit and may worsen disinhibition/agitation; key distinction from AD/DLB management
🔍 Quick ReferenceClinical · Imaging · Pathology / genetics
Clinical phenotype
  • Early disinhibition + hyperorality + utilization behavior → bvFTD
  • Loss of word meaning + surface dyslexia (“pint” rhymed with “mint”) → svPPA
  • Apraxia of speech + agrammatism (effortful, telegraphic) → nfvPPA
  • Impaired sentence repetition + phonologic errors → lvPPA (usually AD)
  • ALS + frontal behavioral change → FTD-ALS (C9ORF72)
  • Environmental dependency syndrome / applause sign → bvFTD (frontal release)
  • “Sweet tooth,” carbohydrate craving, Kluver-Bucy features → late bvFTD
  • Behavioral disinhibition in middle-aged adult with preserved memory → bvFTD > AD
  • Emergent visual-artistic ability as language declines → svPPA / right-temporal FTD
Imaging signs
  • Symmetric/asymmetric frontotemporal atrophy on MRI & FDG-PET hypometabolism → bvFTD
  • LEFT anterior temporal “knife-edge” atrophy → svPPA
  • LEFT inferior frontal / insular atrophy (perisylvian) → nfvPPA
  • LEFT temporoparietal junction atrophy → lvPPA (AD-pattern)
  • Cortical ribbon thinning in mesial frontal / orbitofrontal / anterior cingulate → bvFTD
  • Preserved hippocampi early → FTD (vs AD encoding deficit)
  • Spared posterior cortex → FTD (vs posterior cortical atrophy)
  • Negative amyloid PET → true FTLD; positive amyloid PET → lvPPA / AD
Pathology / genetics
  • Pick bodies (rounded 3R τ intracytoplasmic inclusions) → Pick disease
  • Tufted astrocytes (4R τ) → PSP
  • Astrocytic plaques (4R τ) → CBD
  • TDP-43 type A + neuronal intranuclear inclusions → GRN (progranulin)
  • TDP-43 type B → C9ORF72 / FTD-ALS
  • TDP-43 type C (long dystrophic neurites, sparse NCI) → svPPA
  • FUS-positive inclusions → atypical young-onset FTD (aFTLD-U, NIFID, BIBD)
  • GGGGCC hexanucleotide repeat expansion → C9ORF72 (most common familial FTD & ALS)
  • MAPT mutation (3R / 4R / mixed tauopathy) → familial FTD with parkinsonism (FTDP-17)
  • Low plasma progranulin level → GRN haploinsufficiency screen
FTD Spectrum Overview

Key Epidemiologic and Clinical Features

  • Prevalence: 15–22 per 100,000 in those aged 45–65; second only to AD in early-onset dementia
  • Mean age of onset: ~58 years (range 21–85, but most 45–65)
  • Equal sex distribution (unlike AD, which is more common in women)
  • Mean survival: 6–8 years from symptom onset (shorter with concomitant ALS: 2–3 years)
  • Most patients initially misdiagnosed as psychiatric illness (depression, bipolar, personality disorder) due to prominent behavioral changes

Clinical Spectrum

Syndrome Core Feature Atrophy Pattern Common Pathology
bvFTD Behavioral/personality change Frontal > temporal (bilateral, often asymmetric) ~45% tau, ~45% TDP-43, ~10% FUS (especially young-onset)
nfvPPA Effortful, agrammatic speech Left posterior frontal / insular Usually FTLD-tau (mostly 4R: CBD/PSP; sometimes 3R: Pick); minority FTLD-TDP type A (often GRN)
svPPA Loss of word/object meaning Left anterior temporal Usually TDP-43 (type C)
lvPPA Word-finding difficulty, impaired repetition Left posterior temporal / inferior parietal Usually AD pathology (amyloid+)
💎 Board Pearl
  • lvPPA is the outlier — despite being classified as a PPA variant, the underlying pathology is usually Alzheimer disease (amyloid-positive), NOT FTLD. This is a favorite board question
  • bvFTD is the most common FTD variant — accounts for ~60% of all FTD cases
Behavioral Variant FTD (bvFTD)

Rascovsky Diagnostic Criteria (2011)

  • Requires ≥3 of 6 core features for possible bvFTD
  • Probable bvFTD: possible criteria + functional decline + characteristic neuroimaging (frontal/anterior temporal atrophy or hypoperfusion/hypometabolism)
  • Definite bvFTD: probable criteria + histopathologic confirmation or known pathogenic mutation
Core Feature Examples / Details
1. Early behavioral disinhibition Socially inappropriate behavior, loss of manners/decorum, impulsive/reckless actions
2. Early apathy/inertia Loss of motivation, initiative, and interest; often misdiagnosed as depression
3. Early loss of sympathy/empathy Diminished response to others’ needs/feelings; social coldness
4. Perseverative/compulsive behaviors Simple repetitive movements, hoarding, ritualistic behavior, stereotypies
5. Hyperorality/dietary changes Binge eating, carbohydrate craving, oral exploration of inedible objects, increased alcohol/tobacco use
6. Executive dysfunction with relative sparing of memory and visuospatial function Impaired planning, abstraction, mental flexibility; episodic memory and visuospatial skills relatively preserved early

Clinical Features by Frontal Subregion

Predominant Atrophy Clinical Presentation
Orbitofrontal / ventromedial Disinhibition, impulsivity, sociopathic behavior, poor judgment
Dorsolateral prefrontal Executive dysfunction, poor planning, perseveration
Anterior cingulate / medial frontal Apathy, abulia, loss of motivation
Right temporal predominant Behavioral changes + prosopagnosia, loss of person-specific knowledge
💎 Board Pearl
  • Apathy is the most common symptom of bvFTD — more common than disinhibition, but disinhibition is more distinctive and recognizable
  • “Sweet tooth” and carbohydrate craving are classic bvFTD features — ask about dietary changes in every suspected case
  • Memory can be impaired in bvFTD but it is a retrieval deficit (improves with cueing), unlike the encoding deficit in AD (does not improve with cueing)
  • Nascent or emergent artistic abilities — new visual-artistic productivity (paintings, sculptures, musical composition) emerging as language declines is a classic feature of svPPA / right-temporal FTD; thought to reflect disinhibition of right-hemisphere visual systems when left-temporal language is degraded. Frequently cited board pearl (Miller et al., Neurology 1998).
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