383.4 📋 章末速蚘 Summary

383.4.1 🔑 䞀句話瞜結

Frontotemporal dementia (FTD) = 2nd most common dementia in age < 65 (after AD); spectrum with frontal/temporal lobe degeneration; three clinical syndromes — (1) behavioral variant FTD (bvFTD, most common) — personality + behavior + executive change: apathy + disinhibition (impulsive, social transgressions) + loss of empathy/insight + perseveration (stereotyped repetitive behavior) + hyperorality (sweet tooth, overeating, pica) + executive dysfunction + relatively preserved memory + visuospatial early; (2) primary progressive aphasia (PPA) — language-dominant: semantic variant (svPPA, semantic dementia) — loss of semantic knowledge + surface dyslexia (irregular words “yacht” → “yatched”) + word meaning loss + object recognition impaired + asymmetric anterior temporal atrophy + FTD-TDP-C pathology; nonfluent/agrammatic variant (nfvPPA) — agrammatism + apraxia of speech (effortful, distorted) + complex syntax comprehension impaired + word meaning preserved + left frontal/insular atrophy + FTD-tau or FTD-TDP pathology; logopenic variant (lvPPA) — anomia + sentence repetition impaired + phonological errors + posterior parietal/temporoparietal atrophy + OFTEN AD PATHOLOGY (not FTD!); (3) FTD-motor overlap — FTD-ALS (~ 15% of FTD; ~ 50% of ALS develop FTD features; C9orf72 common) + FTD-PSP + FTD-CBS; pathology heterogeneous — FTD-TDP (most common ~ 50%, types A-D) — type A GRN/sporadic, type B C9orf72/FTD-ALS, type C svPPA, type D VCP + FTD-tau (~ 40% — Pick disease 3R, PSP/CBD 4R, MAPT mutations mixed 3R/4R) + FTD-FUS (5-10%, young onset); genetic ~ 30-50% familial — C9orf72 hexanucleotide repeat expansion (most common, AD, also ALS, repeat > 30 pathogenic, psychosis common, RAN translation toxic dipeptide repeats) + MAPT + GRN (progranulin haploinsufficiency, TDP-43 pathology) + TBK1, VCP, CHMP2B, FUS (rarer); clinical diagnosis Rascovsky bvFTD criteria 2011 — possible (3 of 6 behavioral/cognitive features) + probable (+ functional decline + characteristic imaging) + definite (pathology or mutation); imaging — MRI frontotemporal atrophy (symmetric in bvFTD, asymmetric L in PPA) + FDG-PET frontotemporal hypometabolism + amyloid PET usually negative (helps distinguish from lvPPA = AD); biomarkers — plasma neurofilament light (NfL) often elevated + CSF helpful to exclude AD; NO DISEASE-MODIFYING therapy — multiple trials failed (latrepirdine, etc.); emerging — GRN-directed (latozinemab, PR006) in trials + C9orf72 antisense oligonucleotides (BIIB078) phase 1 + MAPT-targeted (BIIB080); symptomatic + supportive — SSRIs (sertraline, citalopram) for disinhibition + compulsive behaviors + trazodone for agitation + judicious atypical antipsychotics (sensitivity to EPS) + AVOID cholinesterase inhibitors (may worsen behavior in FTD — distinguishes from AD); speech-language therapy for PPA; caregiver education essential (behavioral focus, different from AD, avoid confrontation, structured environment); FTD vs AD distinguishing — FTD age < 65 often + behavior/language first + memory relatively preserved early + insight impaired + frontotemporal atrophy + 30-50% genetic + no DMT; AD age > 65 often + memory first + insight variable + hippocampal/temporal atrophy + < 5% familial + symptomatic ChEI/memantine + anti-amyloid mAbs available; specific entities — bvFTD phenocopy syndrome (doesn’t progress, may be psychiatric, normal imaging, 6-12 mo observation) + right temporal variant svPPA (prosopagnosia + person-specific knowledge loss + behavioral) + Pick disease (historical, 3R tau, Pick bodies, subset of FTD-tau) + KlÃŒver-Bucy syndrome features (hyperorality + hypersexuality + placidity + hyperphagia + visual agnosia, originally bilateral temporal lobectomy) + psychiatric misdiagnosis (depression-apathy, mania-disinhibition, schizophrenia-especially C9orf72, bipolar, OCD-perseveration)。

383.4.2 💊 治療粟芁

  • bvFTD behavioralSSRIs first-line — sertraline 25-200 mg/d + citalopram 10-40 mg/d (QT concern) + escitalopram 5-20 mg/d + fluoxetine 10-60 mg/d for disinhibition + compulsive behaviors; trazodone 25-150 mg HS for agitation/sleep; AVOID benzodiazepines (worsen behavior)
  • bvFTD severe behavioralcautious atypical antipsychotics (quetiapine 12.5-100 mg, aripiprazole 2-15 mg) off-label — AVOID typical antipsychotics + risperidone (worsen EPS sensitivity); AVOID cholinesterase inhibitors (worsen behavior in FTD, unlike AD)
  • PPA languagespeech-language therapy + communication strategies + communication aids (AAC devices) + caregiver education
  • FTD-ALSsee ALS treatment Ch388 (riluzole + edaravone + tofersen if SOD1; supportive)
  • FTD-PSP / FTD-CBSsee Ch380 (limited levodopa response + supportive)
  • emerging disease-modifyingGRN-directed latozinemab (FTLD-GRN, phase 2) + C9orf72 antisense oligonucleotides BIIB078 (FTLD-ALS C9orf72, phase 1) + MAPT-targeted BIIB080 (FTLD-tau) — in trials
  • caregiver supporteducation on behavioral focus (different from AD memory) + avoid confrontation + structured environment + distraction + caregiver respite + support groups (Association for Frontotemporal Degeneration AFTD) + ethical/legal planning early (often younger patients with significant family/work implications)
  • genetic counselingrefer if family history of FTD/ALS (especially 1st-degree); pre-symptomatic testing options for known mutations

383.4.3 🎯 盧醫垫的考前提醒

  1. FTD = 2nd most common dementia in age < 65 (after AD); 3 clinical syndromes — (1) bvFTD behavioral variant (most common) + (2) primary progressive aphasia PPA (svPPA, nfvPPA, lvPPA) + (3) FTD-motor (FTD-ALS, FTD-PSP, FTD-CBS)
  2. bvFTD features (memorize): apathy + disinhibition (impulsive, social transgressions) + loss of empathy/insight + perseveration + hyperorality (sweet tooth, overeating, pica) + executive dysfunction + relatively preserved memory/visuospatial early — often misdiagnosed as psychiatric (depression, mania, schizophrenia especially C9orf72)
  3. PPA subtypes distinction: svPPA (semantic dementia — loss of word meaning + surface dyslexia + object recognition impaired) + nfvPPA (agrammatism + apraxia of speech) + lvPPA (anomia + sentence repetition impaired + OFTEN AD PATHOLOGY — consider amyloid PET, may be eligible for anti-amyloid mAbs)
  4. Pathology heterogeneous: FTD-TDP (most ~ 50%, including C9orf72) + FTD-tau (~ 40% — Pick 3R, PSP/CBD 4R, MAPT mixed) + FTD-FUS (~ 5-10%, young onset)
  5. Genetic ~ 30-50% familial (memorize): C9orf72 hexanucleotide expansion (most common AD, also ALS, repeat > 30, psychosis common) + MAPT (tau) + GRN (progranulin haploinsufficiency, TDP-43) + TBK1 + VCP + CHMP2B
  6. FTD-ALS overlap: ~ 15% of FTD develop ALS + ~ 50% of ALS develop FTD features; C9orf72 most common cause of both
  7. Imaging: MRI frontotemporal atrophy (symmetric in bvFTD, asymmetric L in PPA) + FDG-PET frontotemporal hypometabolism + amyloid PET usually NEGATIVE (positive helps distinguish lvPPA = AD)
  8. No disease-modifying therapy yet — multiple trials failed; emerging GRN-directed latozinemab + C9orf72 antisense BIIB078 + MAPT-targeted BIIB080 in trials
  9. Symptomatic management: SSRIs first-line for disinhibition + compulsive (sertraline, citalopram, escitalopram, fluoxetine) + trazodone agitation/sleep + cautious atypical antipsychotics + AVOID cholinesterase inhibitors (worsen FTD behavior, unlike AD — important distinction!) + AVOID benzodiazepines + speech therapy for PPA
  10. FTD vs AD distinguishing: FTD younger onset + behavior/language first + memory relatively preserved early + insight impaired + frontotemporal atrophy + 30-50% genetic vs AD older + memory first + hippocampal atrophy + < 5% familial + ChEI/memantine/anti-amyloid mAbs available; right temporal variant svPPA → prosopagnosia + person-specific knowledge loss; psychiatric misdiagnosis common (depression-apathy, mania-disinhibition, schizophrenia-psychosis especially C9orf72)