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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
An Overview of Frontotemporal Dementia and Non-Alzheimer’s
Dementias
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
Years
Cognitive / Behavioral
/ Motor Function
Presymptomatic
Prodromal
Dementia
~5-20? years~1-10? years
~2-20 years
Progression of Neurodegenerative Diseases
Progression of Neurodegenerative Diseases
Years
Cognitive / Behavioral
/ Motor Function
Presymptomatic
Prodromal
Dementia
gradual accumulation of neuropathology
Neurodegenerative Diseases Alzheimer’s disease frontotemporal dementia (FTD)
behavioral variant (“Pick’s disease”) primary progressive aphasias
posterior cortical atrophy (PCA)
progressive supranuclear palsy (PSP) corticobasal degeneration (CBD) dementia with Lewy bodies (DLB) Huntington’s disease
Parkinson’s disease ALS (Lou Gehrig’s disease)
predominantly cognitive symptoms
predominantly motor
symptoms
cognitive & 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
FRONTAL
PARIETAL
TEMPORAL
Lobe Functionfrontal restraint, planning, initiative
empathylanguage production (left)
temporal memoryface and object
identificationlanguage comprehension
(left)
parietal spatial processing
occipital visual processing
Brain Anatomy
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 FindingsMRI: 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
understand natural history of FTD “calibrate” tools for monitoring
risk factors genetics
treatment disease
modifying
Years
Cognitive /
Behavioral / Motor Function
Presymptomatic
ProdromalDementi
a
gradual accumulation
of neuropatholo
gy
Presymptomatic / Prodromal
decrease neuropatholo
gy
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
McMonagle & Kertesz Neurology 2006
normal PCA
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
Kato et al J Neurol Sci 2003
“hummingbird sign”
normal
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?
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
“This is dementia. There is no cure.”