An Overview of Frontotemporal Dementia
and Non-Alzheimer’s Dementias
Kimiko Domoto-Reilly, MD1,2,5
Daisy Sapolsky, MS, CCC-SLP1,3,4
Aly Negreira, BA1,3
1Frontotemporal
Disorders Unit, Departments of 2Neurology, 3Psychiatry,
4Speech and Language Pathology, Massachusetts General Hospital,
5Brigham Behavioral Neurology Group, Boston, MA
Outline
 dementia overview
 FTD and related dementias
 brain anatomy / pathology
 clinical signs / symptoms and progression
 treatment
 research
 multidisciplinary care team
 communication
 support resources
Dementia: Definition
 acquired loss of multiple cognitive abilities significant
enough to interfere with typical daily activities
 multiple potential causes
 stroke
 amyloid angiopathy
 traumatic brain injury
 normal pressure hydrocephalus
 other medical conditions (e.g., thyroid disorder, low vit B12)
 toxin exposure
 infection
 neurodegeneration
Progression of Neurodegenerative Diseases
Presymptomatic
Prodromal
Dementia
Cognitive /
Behavioral /
Motor
Function
~5-20? years
~1-10? years
~2-20 years
Years
Progression of Neurodegenerative Diseases
Presymptomatic
Prodromal
Dementia
Cognitive /
Behavioral /
Motor
Function
gradual
accumulation of
neuropathology
Years
Neurodegenerative Diseases
 Alzheimer’s disease
 frontotemporal dementia (FTD)
 behavioral variant (“Pick’s disease”)
 primary progressive aphasias
predominantly
cognitive
symptoms
 posterior cortical atrophy (PCA)
 progressive supranuclear palsy (PSP)
 corticobasal degeneration (CBD)
 dementia with Lewy bodies (DLB)
cognitive &
motor
symptoms
 Huntington’s disease
 Parkinson’s disease
 ALS (Lou Gehrig’s disease)
predominantly
motor
symptoms
Case 1: Alzheimer’s Disease
 71 ♂: 2 year history of cognitive/behavioral
changes
 difficulty coming up with people’s names
 left the keys in the front door several times
 while vacationing, got lost coming back from the store
 continues to play tennis, but loses track of the score
 gets confused about checking versus savings account
 no longer cooking the elaborate meals he was known for
 less patient with the grandchildren
Case 2: Non-Alzheimer’s dementia
 60♀: 2 year history of cognitive/behavioral
changes
 no longer called children “just to check in”
 family: “She has no filter! Don’t ask her a question you




don’t want answered”
continues to perform chores around the house, but
insists on a specific routine
started smoking, including around the grandchildren
(had quit in her 20s)
drives through stop signs and red lights
needs to be reminded to change her clothes
Case 3: Non-Alzheimer’s dementia
 53♀: 2 year history of cognitive/behavioral
changes
 several “dings” while parking the car
 trouble keeping eyes on page while reading
 difficulty pouring liquids into measuring cups
 significant difficulty adjusting to house renovations
 occasionally wear shirts inside out
Case 4: Non-Alzheimer’s dementia
 68♂: 2 year history of cognitive/behavioral
changes
 left hand tremor
 quieter at family gatherings, speech softer and slower
 drifts off to sleep during the day
 wife often woken up at night when he seems to be
acting out his dreams
 asked family, “Whose dog is that?”
Brain Anatomy
PARIETAL
FRONTAL
TEMPORAL
Brain Anatomy
Lobe
Function
frontal
restraint, planning, initiative
empathy
language production (left)
temporal
memory
face and object identification
language comprehension (left)
parietal
spatial processing
occipital
visual processing
FTD: Brief History
 1892: case descriptions by Arnold Pick
 71♀ with gradual behavioral decline followed by speech
and language deterioration
 brain with frontal and temporal lobar atrophy
 1911: pathologic description by Alois Alzheimer
 1982: “PPA” coined by Marsel Mesulam
 1998: first “consensus” diagnostic criteria for FTD
 2000s: more new discoveries than in past 100 years
 2011: new international consensus diagnostic criteria
FTD: Demographics
 3rd most common neurodegenerative dementia
 15% of all dementias
 most common early onset dementia (50s-60s)
 estimated to affect 250,000 Americans
 typically more rapid decline than AD
 10% inherited, ~60% sporadic
FTD: Brain Anatomy
FTD: Brain Anatomy
FTD: Brain Pathology
 normal proteins in brain cells → twisted & tangled
 clump within cells → clog machinery → damage cell
 disease focality: specific cells types in certain brain regions
 FTD proteins: tau, TDP-43, FUS, amyloid
FTD: Clinical Findings
 behavioral variant (bvFTD)
 disinhibition
 socially inappropriate behavior
 impulsivity
 apathy
 loss of interest, drive, motivation
 loss of sympathy / empathy
 repetitive / compulsive / ritualistic behavior
 language variants (3 subtypes)
 progressive nonfluent aphasia (PNFA)
 logopenic progressive aphasia (LPA)
 semantic dementia (SD)
FTD: Diagnosis
 history from patient and family
 review possible alternative diagnoses
 medication side effects
 primary psychiatric / seizure / sleep disorder
 brain tumor
 additional tests
 neuropsychology testing
 brain scans: structural (MRI), functional (PET)
 lumbar puncture
* continued follow up *
bvFTD: Structural Imaging Findings
MRI: atrophy of frontal and temporal lobes
normal
bvFTD
bvFTD: Functional Imaging Findings
PET: hypometabolism of frontal and temporal lobes
FTD: Clinical Course
 starts out distinctly as one variant, indicating
brain region initially involved
 often progresses to involve other domains
 language variants may include behavioral changes
 behavioral variants may include language changes
 changes in movement may also occur
 coordination problems, slowing, stiffness, falls
 changes in eye movements
 impaired swallowing
 survival is 2 – 20+ years after onset of symptoms
FTD: Treatment
 disease modifying medication (slow / stop / reverse)
 none currently
 symptomatic medications
 nothing is yet proven
 Alzheimer’s medications: Aricept (donepezil),
Namenda (memantine)
 antidepressants / mood stabilizers: SSRIs, valproate
 stimulants?
FTD: Research
Presymptomatic
Prodromal
Dementia
Cognitive /
Behavioral /
Motor
Function
Presymptomatic /
Prodromal
gradual
decrease
accumulation of
neuropathology neuropathology
Years
 understand natural history of FTD
 “calibrate” tools for monitoring
 risk factors
 genetics
 treatment
 disease modifying
Non-Alzheimer’s Dementias
 posterior cortical atrophy (PCA)
 brain anatomy: parietal lobes
 protein: often amyloid
 symptoms: difficulties with spatial relationships
 clinical course: functionally blind
 treatment: Alzheimer’s medication; antidepressants
normal
PCA
McMonagle & Kertesz
Neurology 2006
Non-Alzheimer’s Dementias
 progressive supranuclear palsy (PSP)
 brain anatomy: deep structures of brain
 protein: tau
 symptoms: vertical eye movement
abnormalities, slowed thinking /
movements, axial rigidity, postural
instability with falls backwards,
abnormal displays of emotional
 clinical course: wheelchair bound
 treatment (supportive): prism glasses,
support stockings for blood pressure drops,
change diet for swallowing difficulties
normal
“hummingbird
sign”
Kato et al J Neurol Sci 2003
Non-Alzheimer’s Dementias
 corticobasal degeneration (CBD)
 brain anatomy: asymmetric, frontoparietal
 protein: mixed
 symptoms: asymmetric limb stiffness, alien limb,
myoclonic jerks, apraxia
 clinical course: may overlap with PNFA
 treatment: limited
Non-Alzheimer’s Dementias
 dementia with Lewy bodies (DLB)
 brain anatomy: occipital lobe
 protein: amyloid, α-synuclein (Lewy bodies)
 symptoms: visual hallucinations, fluctuating alertness,
sleep disorder, Parkinsonian features
 clinical course: may develop delusions
 treatment: Parkinson’s medications, Alzheimer’s
medications; sensitivity to antipsychotics
bvFTD
DLB
Non-Alzheimer’s Dementias
 Huntington’s disease
 brain anatomy: deep structures (basal ganglia)
 protein: huntingtin
 symptoms: fidgity → chorea
 clinical course: impulsivity, poor judgment, suicidality
 treatment: tetrabenazine if movements become
problematic; feeding tube
 genetics: autosomal dominant
Non-Alzheimer’s Dementias
 FTD-ALS
 brain anatomy: motor system
 protein: TDP-43
 symptoms: muscle weakness, muscle twitching,
muscle wasting, nasal voice, behavioral changes
 clinical course: weakness ↔ disinhibition; rapid decline
 treatment: riluzole; motorized wheelchair, feeding tube
Case Review
 Case 1: 71♂
 prominent memory problems, but also difficulty with
navigation, multistep tasks
>> AD
 Case 2: 60♀
 lack of empathy, poor decisions and insight, rigid routine
>> bvFTD
 Case 3: 53♀
 problems with spatial relationships
>> PCA
 Case 4: 68♂
 visual hallucinations, sleep abnormalities
>> DLB
Why Bother?
“This is dementia. There is no cure.”
 importance of diagnosis
 ensure diagnosis is correct
 which symptoms are part of the disease, which aren’t
 plan appropriately for future
 potential genetic implications
 multidisciplinary team
 appropriate monitoring
 provide support and education for patient and caregivers
 receive treatment as soon as it becomes available