frontotemporal dementia: an overview
TRANSCRIPT
Frontotemporal Dementia Frontotemporal Dementia An OverviewAn Overview
Frontotemporal Dementia Frontotemporal Dementia An OverviewAn Overview
October 13, 2012October 13, 2012
Brian S. Appleby, M.D.Brian S. Appleby, M.D.
Staff, Lou Ruvo Center for Brain Staff, Lou Ruvo Center for Brain Health, Cleveland ClinicHealth, Cleveland Clinic
DisclosuresDisclosuresDisclosuresDisclosures
• Co-PI, memantine for frontotemporal Co-PI, memantine for frontotemporal dementia, Forest Pharmaceuticalsdementia, Forest Pharmaceuticals
ObjectivesObjectivesObjectivesObjectives
• Describe the illnesses within the Describe the illnesses within the frontotemporal lobar degeneration frontotemporal lobar degeneration (FTLD) spectrum (FTLD) spectrum
• Characterize the common types of Characterize the common types of FTLDFTLD
• Illustrate case examples of FTLDIllustrate case examples of FTLD
Frontotemporal Lobar DegenerationFrontotemporal Lobar DegenerationFrontotemporal Lobar DegenerationFrontotemporal Lobar Degeneration
Semantic dementia
FTD
PPA
FTD-MND CBD
PSPAGD
NIFID IBMPFDFUS HSD
Papageorgiou S, et al. Alzheimer Dis Assoc Disord, 2009
AD
FTLD
Survival TimeSurvival TimeSurvival TimeSurvival Time
Garcin B, Neurology 2009
Appleby BS, Dementi Geriatr Cog Disord 2008
ZBI=Zarit Burden Interview Johns Hopkins FTD/YOD Clinic
CJD FTD SD PPA AD CBD
Hemispheric Asymmetry (MRI and PET)
Frontotemporal dementia (55%)
Primary progressive aphasia(25%)
Semantic dementia(20%)
Frontotemporal DementiaFrontotemporal DementiaFrontotemporal DementiaFrontotemporal Dementia
• Mean age of onset: 55-65 years-of-ageMean age of onset: 55-65 years-of-age• Male>FemaleMale>Female• Prominent frontal lobe symptomsProminent frontal lobe symptoms
- DisinhibitionDisinhibition- Poor insight/judgmentPoor insight/judgment- Loss of social gracesLoss of social graces- Perseverative behaviorsPerseverative behaviors- ApathyApathy
Primary Progressive AphasiaPrimary Progressive AphasiaPrimary Progressive AphasiaPrimary Progressive Aphasia
• Progressive non-fluent aphasiaProgressive non-fluent aphasia
• Decreased speech outputDecreased speech output
• Speech apraxiaSpeech apraxia
• Changes in grammar useChanges in grammar use
• Neuropathology is often progressive Neuropathology is often progressive supranuclear palsy or corticobasal supranuclear palsy or corticobasal degenerationdegeneration
Josephs KA, Brain 2006
Semantic DementiaSemantic DementiaSemantic DementiaSemantic Dementia
Animal
Bird
TreatmentTreatmentTreatmentTreatment
Cholinesterase InhibitorsCholinesterase InhibitorsCholinesterase InhibitorsCholinesterase Inhibitors
Irwin D, Am J Alzheimers Dis Other Disord 2010
MemantineMemantineMemantineMemantine
• Increases brain FDG-PET metabolism in Increases brain FDG-PET metabolism in FTD and SD (Chow 2011, 2012)FTD and SD (Chow 2011, 2012)
• No improvement in behavior/cognition No improvement in behavior/cognition (Diehl-Schmid 2008, Vercelletto 2011)(Diehl-Schmid 2008, Vercelletto 2011)
• Transient improvement in neuropsych Transient improvement in neuropsych symptoms in FTD and PPA (Swanberg symptoms in FTD and PPA (Swanberg 2007, Boxer 2009)2007, Boxer 2009)
• Currently in multisite RCTCurrently in multisite RCT
AntipsychoticsAntipsychoticsAntipsychoticsAntipsychotics
• Often used because of behavioral Often used because of behavioral symptomssymptoms
• Mounting evidence of hypersensitivity Mounting evidence of hypersensitivity to EPS in FTD (Mendez 2001, to EPS in FTD (Mendez 2001, Pijnenburg 2003, Czarnecki 2008)Pijnenburg 2003, Czarnecki 2008)
• Think of overlap of FTLD with Think of overlap of FTLD with “Parkinson’s-Plus” disorders“Parkinson’s-Plus” disorders
BenzodiazepinesBenzodiazepinesBenzodiazepinesBenzodiazepines
““Do you Do you reallyreally want to give a disinhibiting want to give a disinhibiting medication to a medication to a dementeddemented person with person with no no frontal lobesfrontal lobes?”?”
AntidepressantsAntidepressantsAntidepressantsAntidepressants
• Loss of serotonergic neurons->replete Loss of serotonergic neurons->replete with serotonergic drugswith serotonergic drugs
• Trazodone (Lebert 2004)Trazodone (Lebert 2004)
• SSRIs (Swartz 1997, Moretti 2003, SSRIs (Swartz 1997, Moretti 2003, Herrmann 2011)Herrmann 2011)
• Paroxetine: no effect, worsened Paroxetine: no effect, worsened cognition (Deakin 2004)cognition (Deakin 2004)
Non-Pharmacological Non-Pharmacological InterventionsInterventions
Non-Pharmacological Non-Pharmacological InterventionsInterventions
• Environment (locked behavioral Environment (locked behavioral dementia unit)dementia unit)
• Caregiver support (FTD support Caregiver support (FTD support groups)groups)
• SSDI Compassionate AllowancesSSDI Compassionate Allowances
• Elder care lawyer involvement earlyElder care lawyer involvement early
• Driving (different concerns)Driving (different concerns)
• Travel lettersTravel letters
Case #1Case #1Case #1Case #1• 58 y.o. AAM attorney with h/o dyslexia 58 y.o. AAM attorney with h/o dyslexia
with a 2 yr h/o cognitive decline and with a 2 yr h/o cognitive decline and personality changepersonality change
• Distracted, poor concentration, low Distracted, poor concentration, low mood, fatiguedmood, fatigued
• Only reads comic books and watches Only reads comic books and watches cartoons, often the same ones cartoons, often the same ones repeatedly repeatedly
ExamExamExamExam
GeneralGeneral: Asked to leave room several : Asked to leave room several times to walk around. Buccal times to walk around. Buccal stereotypies (i.e., blowing)stereotypies (i.e., blowing)
SpeechSpeech: Sparse, poverty of content: Sparse, poverty of content
AffectAffect: Flat, no brightening: Flat, no brightening
MMSEMMSE: 19/30: 19/30
Brain MRIBrain MRI: Mild generalized atrophy: Mild generalized atrophy
Further Work-upFurther Work-upFurther Work-upFurther Work-up
Case #2Case #2Case #2Case #2
• 60 y.o. WM with no past neuropsych hx60 y.o. WM with no past neuropsych hx
• Initial complaint is Initial complaint is stuttering/stammeringstuttering/stammering
• Phonemic paraphrasic errors on examPhonemic paraphrasic errors on exam
• MoCA=28/30MoCA=28/30
• ““f”=2 words, “animals”=18f”=2 words, “animals”=18
• At next visit, has complaints of poor At next visit, has complaints of poor concentration and distractibility concentration and distractibility
Case #3Case #3Case #3Case #3
• 60 y.o. WF with h/o rheumatic fever, 60 y.o. WF with h/o rheumatic fever, GERD, vit D def, osteopenia, and GERD, vit D def, osteopenia, and liver/brain hemangiomasliver/brain hemangiomas
• 1 yr h/o progressive strabismus with 1 yr h/o progressive strabismus with diplopia (repaired with return 1 mo diplopia (repaired with return 1 mo later), parkinsonism, dysarthria, and later), parkinsonism, dysarthria, and short-term amnesia, fatigue, anxiety, short-term amnesia, fatigue, anxiety, panic attacks panic attacks
Exam Exam Exam Exam
SpeechSpeech: hypophonic, sparse, dysarthric: hypophonic, sparse, dysarthric
Thought ProcessThought Process: bradyphrenic: bradyphrenic
AffectAffect: stable, flat without brightening: stable, flat without brightening
MMSEMMSE: 7/30: 7/30
UPDRS IIUPDRS II: 43: 43
NeuroNeuro: vertical gaze impairment, choppy : vertical gaze impairment, choppy saccades, hypomimia, axial rigiditysaccades, hypomimia, axial rigidity
Case #4Case #4Case #4Case #4
• 50 y.o. female from Spain with 4 yr h/o 50 y.o. female from Spain with 4 yr h/o gradual executive dysfxn, short-term gradual executive dysfxn, short-term amnesia, progressive non-fluent amnesia, progressive non-fluent aphasia, parkinsonism, and myoclonusaphasia, parkinsonism, and myoclonus
• Paces frequently, apathetic, crying Paces frequently, apathetic, crying when frustrated, seen responding to when frustrated, seen responding to internal stimuli, and sometimes thinks internal stimuli, and sometimes thinks others are stealing from herothers are stealing from her
ExamExamExamExam
GaitGait: slow, shuffling, leans to left: slow, shuffling, leans to left
SpeechSpeech: Effortful, paraphrasic errors: Effortful, paraphrasic errors
MMSEMMSE: 5/30: 5/30
3MS3MS: 17/100: 17/100
ClockClock: 1/5: 1/5
UPDRS IIUPDRS II: 44: 44
•Myoclonus with speech and actionMyoclonus with speech and action
•Left-sided neglect, finger agnosiaLeft-sided neglect, finger agnosia
ExamExamExamExam
PentagonsPentagons ClockClock