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