1. Frontotemporal Dementia
An Overview
October 13, 2012
Brian S. Appleby, M.D.
Staff, Lou Ruvo Center for Brain
Health, Cleveland Clinic

2. Disclosures
• Co-PI, memantine for frontotemporal
dementia, Forest Pharmaceuticals

3. Objectives
• Describe the illnesses within the
frontotemporal lobar degeneration
(FTLD) spectrum
• Characterize the common types of
FTLD
• Illustrate case examples of FTLD

4. Frontotemporal Lobar Degeneration
Semantic
PPA
dementia PSP
AGD
FTD
FTD-MND CBD
FUS NIFID HSD IBMPFD

5. Papageorgiou S, et al. Alzheimer Dis Assoc Disord, 2009
AD
FTLD

6. Survival Time
Garcin B, Neurology 2009

7. Appleby BS, Dementi Geriatr Cog Disord 2008

8. CJD FTD SD PPA AD CBD
ZBI=Zarit Burden Interview Johns Hopkins FTD/YOD Clinic

9. Hemispheric Asymmetry (MRI and PET)

10. Frontotemporal dementia (55%)
Primary progressive aphasia Semantic dementia
(25%) (20%)

11. Frontotemporal Dementia
• Mean age of onset: 55-65 years-of-age
• Male>Female
• Prominent frontal lobe symptoms
- Disinhibition
- Poor insight/judgment
- Loss of social graces
- Perseverative behaviors
- Apathy

12. Primary Progressive Aphasia
• Progressive non-fluent aphasia
• Decreased speech output
• Speech apraxia
• Changes in grammar use
• Neuropathology is often progressive
supranuclear palsy or corticobasal
degeneration
Josephs KA, Brain 2006

13. Semantic Dementia
Animal
Bird

14. Treatment

15. Cholinesterase Inhibitors
Irwin D, Am J Alzheimers Dis Other Disord 2010

16. Memantine
• Increases brain FDG-PET metabolism in
FTD and SD (Chow 2011, 2012)
• No improvement in behavior/cognition
(Diehl-Schmid 2008, Vercelletto 2011)
• Transient improvement in neuropsych
symptoms in FTD and PPA (Swanberg
2007, Boxer 2009)
• Currently in multisite RCT

17. Antipsychotics
• Often used because of behavioral
symptoms
• Mounting evidence of hypersensitivity
to EPS in FTD (Mendez 2001,
Pijnenburg 2003, Czarnecki 2008)
• Think of overlap of FTLD with
“Parkinson’s-Plus” disorders

18. Benzodiazepines
“Do you really want to give a disinhibiting
medication to a demented person with no
frontal lobes?”

19. Antidepressants
• Loss of serotonergic neurons->replete
with serotonergic drugs
• Trazodone (Lebert 2004)
• SSRIs (Swartz 1997, Moretti 2003,
Herrmann 2011)
• Paroxetine: no effect, worsened
cognition (Deakin 2004)

20. Non-Pharmacological
Interventions
• Environment (locked behavioral
dementia unit)
• Caregiver support (FTD support
groups)
• SSDI Compassionate Allowances
• Elder care lawyer involvement early
• Driving (different concerns)
• Travel letters

21. Case #1
• 58 y.o. AAM attorney with h/o dyslexia
with a 2 yr h/o cognitive decline and
personality change
• Distracted, poor concentration, low
mood, fatigued
• Only reads comic books and watches
cartoons, often the same ones
repeatedly

22. Exam
General: Asked to leave room several
times to walk around. Buccal
stereotypies (i.e., blowing)
Speech: Sparse, poverty of content
Affect: Flat, no brightening
MMSE: 19/30
Brain MRI: Mild generalized atrophy

23. Further Work-up

24. Case #2
• 60 y.o. WM with no past neuropsych hx
• Initial complaint is
stuttering/stammering
• Phonemic paraphrasic errors on exam
• MoCA=28/30
• “f”=2 words, “animals”=18
• At next visit, has complaints of poor
concentration and distractibility

25. Case #3
• 60 y.o. WF with h/o rheumatic fever,
GERD, vit D def, osteopenia, and
liver/brain hemangiomas
• 1 yr h/o progressive strabismus with
diplopia (repaired with return 1 mo
later), parkinsonism, dysarthria, and
short-term amnesia, fatigue, anxiety,
panic attacks

26. Exam
Speech: hypophonic, sparse, dysarthric
Thought Process: bradyphrenic
Affect: stable, flat without brightening
MMSE: 7/30
UPDRS II: 43
Neuro: vertical gaze impairment, choppy
saccades, hypomimia, axial rigidity

27. Case #4
• 50 y.o. female from Spain with 4 yr h/o
gradual executive dysfxn, short-term
amnesia, progressive non-fluent
aphasia, parkinsonism, and myoclonus
• Paces frequently, apathetic, crying
when frustrated, seen responding to
internal stimuli, and sometimes thinks
others are stealing from her

28. Exam
Gait: slow, shuffling, leans to left
Speech: Effortful, paraphrasic errors
MMSE: 5/30
3MS: 17/100
Clock: 1/5
UPDRS II: 44
•Myoclonus with speech and action
•Left-sided neglect, finger agnosia

29. Exam
Pentagons Clock