3. Objectives
1. Provide an overview of the cause underlying
frontotemporal dementia (FTD)
2. Provide an overview of the clinical symptoms
and diagnosis of FTD
3. Explore caregiver burdens of caring for
individuals with FTD and subsequent
management options
5. Neurodegenerative Dementias
Protein Misfolding Disorders (PMD)
Disease
Protein
Alzheimer’s disease
A-beta (plaques)
Phosphorylated tau (tangles)
Parkinson’s disease
Alpha-synuclein (Lewy bodies)
Prion disease
Prion protein
Frontotemporal dementias
Various
- Phosphorylated tau
- Ubiquinated inclusions
(TDP-43)
6. PMD Origins
Root Causes
Example
Overproduction of proteins
Trisomy 21, AD
Inefficient protein metabolism
Presenilin mutations in AD
Impaired protein clearance
Tauopathies-impaired transport
Neurotoxicity
Protein oligomers in most PMD
Exictotoxicity
“Working overtime”-glutamate toxicity
Unfolded protein response
Stop making the normal proteins
AD=Alzheimer’s disease; PMD=protein misfolding disorders
10. Causes
• Sporadic
• Familial (~25%)
• Environmental Risk Factors (?)
– Traumatic brain injury
– Pathology of chronic traumatic encephalopathy is
similar to FTD with some important differences
15. 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
16. FTD Case Study
• 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
17. 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
20. 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
21. PPA Case Study
•
•
•
•
•
•
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
23. Semantic Dementia Case Study
• 77 y.o. WF with a 2 year history of “losing
words”
• Initial symptom was forgetting the essence of
and word for “furnace filter”
• Calls everyone “honey-child”
• More frontal behaviors/personality changes
• Obsessed with puzzles
24. Exam
Speech: fluent, but lacks content and is vague
with generalization of word usage
Verbal fluency: “f”=12 words, “animals”=1
Behaviors: Some perseverative picking
Memory and visuospatial skills were completely
intact
25. Progressive Supranuclear Palsy
Case Study
• 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 shortterm amnesia, fatigue, anxiety, panic
attacks
27. Cortical Basal Degeneration
Case Study
• 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 (1/2)
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
33. Memantine
• Increases brain FDG-PET metabolism in FTD
and SD (Chow 2011, 2012)
• No improvement in behavior/cognition (DiehlSchmid 2008, Vercelletto 2011)
• Transient improvement in neuropsych
symptoms in FTD and PPA (Swanberg 2007, Boxer 2009)
• Large double-blind, RCT, no effects (Boxer A, Lancet
Neurol 2013)
34. 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’sPlus” disorders
44. Recommendations
• FTD-specific support group
• “What if it isn’t Alzheimer’s?” by Lisa Radin
• At least ½ day per week of personal time for
caregivers
• Speak to children early and often
• Social Security Disability Insurance (SSDI)
Compassionate Allowances (“fast track”)
45. Resources
• Alzheimer’s Association (www.alz.org)
• Association for Frontotemporal Dementia
(AFTD) (www.theaftd.org)
• FTD specific support groups (Alz Assoc/AFTD)
(Columbus, Akron, Cleveland)
