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Frontotemporal dementia
John Hodges
FRONTIERPrince of Wales Medical Research
Institute
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Causes of Early Onset Dementia
ADVASCULARFTDDLBOTHER
Prevalence per100, 000Total: 81 - 98AD: 11 - 41FTD: 4 - 15
City of 4 million= 3 to 4,000 EOD500-1000 FTD
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Frontotemporal Dementia
Behavioural form
PNFA semantic demen
Language form(Primary progressive apha
FTD or FTLD
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FTD: overlap Disorders
• FTD with motor neurone
diseaseChanges in personality and social behaviour
and/or aphasia typically precede bulbar type MND
Selective deficit in verb processing (Bak et al 2001)
High rate of psychosis and rapid progression
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Frontotemporal Dementia
Behavioural form
PNFA semantic demen
Language form(Primary progressive apha
FTD or FTLDMND
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Frontotemporal Dementia: overlaps
• Extrapyramidal
features are common in FTD (parkinsonism etc). Some cases develop severe apraxia
--> corticobasal
degeneration (CBD)
syndrome. Also cases with CBD commonly become aphasic.
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Frontotemporal Dementia
Behavioural form
PNFA semantic demen
Language form(Primary progressive apha
FTD or FTLDCorticobasaldegeneration MND
Pathological heterogeneity
Molecular Genetic:MAPTProgranulinCHMP2B
So far < 20% cases
Clinical classification
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Forms of FTD with tau
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FTD with TDP43Several patternsLentiform (cat’s eye) charcteristic of PGRN mutations
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FTD: Diagnosis
• Presenting/early features NOT JUST FRONTAL FEATURES WHICH OCCUR IN MANY DEMENTIAS AT LATE STAGE
• Patient and carer assessment with neuropsychological testing and imaging
• Distinct clinical profiles with matching changes on imaging
• Must exclude other potential causes of dementia
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FTD: Clinical variants
• Frontal variant FTD: orbital and mesial
frontalChanges in personality and social behaviour
• Semantic dementia (progressive fluent aphasia): polar & inferior temporal lobeAnomia, impaired comprehension & loss of knowledge
• Progressive nonfluent aphasia: perisylvianDisrupted speech output, phonological deficits
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• 65 year-old man, skilled craftsman
• 24 months word finding difficulty and “loss of memory for words”
• Impaired comprehension of word meaning
• Intact everyday activities
• Good day-to-day memory
Typical Semantic Dementia
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As time goes by
1998 2001 2003dog √ √ √horse √ √ creaturezebra √ horse creaturekangaro o
koala australia n
creature
eagle pigeon bird d.k.
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Semantic DementiaA distinct clinico-anatomical- (pathological) syndrome
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Semantic Dementia: clues
• Very anomic• Poor word definitions• Good repetition: word alienation• Surface dyslexic: Pint; soot etc• Impaired person identification RIGHT CASES• Excellent visuospatial skills and attention• Good autobiographical but poor verbal memory!!!!
• ACE-R very sensitive with big MMSE-ACE discrepancy
• Early behavioural changes: obsessions, jigsaws. Eating, empathy loss
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ACE-R• Incorporates MMSE takes 15 minutes• Sensitive to early AD and FTD• Five domains:
Orientation/attentionEpisodic memoryFluency P words and animalsLanguage: naming 12 line drawings, repetition & comprehensionVisuospatial
skills
• SD; good orientation/attention, very poor fluency and naming, good visuospatial skills
• Used in >30 countries, Australian versions, cut- offs (88 and 82)
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Progressive Non-Fluent Aphasia
• Markedly reduced conversational speech with preserved word knowledge
• Far more varied than SD but are there clear subtypes?
• Speech apraxia
= motor speech disorderSpeech dysfluent, halting, distortedPhonetic errors in spontaneous speechVery poor repetition of single words
e-lec-trick-ery (electricity)
Unable to repeat strings of syllables “PA, TA, KA”
• Grammatical errors and impaired sentence comprehensionIf the lion ate the tiger, who survived?
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Gorno-Tempini, et al. Annals Neurol, 2004
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Behavioural variant FTD • Slowly progressive insidious onset• No insight• Alterations in personality and behaviour• Apathy• Disinhibition• Loss of empathy and warmth• Alterations in eating habits and preferences• Strange obsessions and rituals• Poor planning and organisation• Mental rigidity• Decline in self-care
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John• 53 M• Left school at age 16• Head boy• Diploma engineering• joined family firm• Married, 2 children• No FH of dementia
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• Age 38 Marital dysharmony, alcohol excess• Age 53 Psychiatric referral then to memory clinic
– Family firm bankrupt– Disastrous financial decisions for 5 yrs
progressive personality change• Lack of thought for family• No empathy• Emotionally cold• e.g., failed to attend daughter’s graduation• Apathetic
– High scores on Cambridge Behavioural Inventory
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Modelled on Neuropsychiatric InventoryPlus cognitive and ADL sections80 questions cover:
MoodAbnormal beliefsChallenging behavioursDisinhibitionAppetite and eatingStereotypic behavioursMotivation
Cambridge Behavioural Inventory
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Tests: Undecided• Memory good
• Language and semantics good
• Executive FunctionWisconsin card sorting normalFAS letter fluency 30BADS Normal
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John:
• Next 4 years progressive decline• Euphoric, giggling inappropriately• Poor self-care• Grandiose, no insight
– Disinhibited• begging, stealing
– Preoccupied counting, checking• doors, locks, car suspension
– Excessive food consumption• sweet foods, hoarding chocolates
• Died suddenly
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Orbitofrontal atrophy
Amygdala atrophy
(JH 104) Neuropathology
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Emotion Processing
Motivation
Behavioural Regulation
DLPFCExecutive functions, working memory
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Faux pas test
Jeanette bought her friend Ann a crystal bowl for a wedding gift. Ann had a big wedding and there were a lot of presents to keep track
of.
About a year later, Jeanette was over one night at Anne’s for dinner. Jeanette dropped a wine bottle by accident on the crystal bowl, and the bowl shattered. “I’m really sorry, I’ve broken the bowl”
said
Jeanette. “Don’t worry”
said Anne “I never liked it anyway. Someone gave it to me for my wedding”
Faux Pas
bv-FTD Controls0.00
0.25
0.50
0.75
1.00
Com
posi
te S
core
Gregory et al. Brain 2000
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TASIT Results
Judgement of social scenarios by FTD patients
Sincere Sarcastic-5
-4
-3
-2
-1
0
1Z
-Sco
re
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Onset –
slow to presentGradual change in behaviourDisinhibited, stereotypicEating habits; sweet foodsApatheticLack of insight
CBI-
69
ACE –
90, MMSE 29
2 yrs rapid downhill courseTo nursing homeACE fell proressively
Onset –
slow to presentGradual change in behaviourDisinhibited, rigidPoor financial judgementApathetic, lacked empathyLack of insight
CBI-
70 (high)
ACE –
89, MMSE 30
10 yrs follow-upNo changeVariable performance on frontal TasksACE normal after 10 yrs
Case 1 Case 2
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bv-FTD
8 years
2 years
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The FTD phenocopy syndrome: a mystery solved ?
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What is the bvFTD-phenocopy syndrome?
• Neurodegenerative: very slow progress?
• Undiagnosed autism spectrum
• Psychiatric• Depression• Mania• Schizophrenia
• Mid-life regression in vulnerable personality
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Olivier PiguetClement LoyPatricia LilloBeatrice GarcinEneida MioshiMichael HornbergerWendy KelsoSharpley HsiehSharon SavageEmma SchofieldSarah Homewood
Pathology: Glenda Halliday and Jill Kril
Imaging: Lindy Rae and Steven Rose
Website
www.ftdrg.org