Kimiko Domoto-Reilly, MD 1,2,5 Daisy Sapolsky, MS, CCC-SLP 1,3,4 Aly Negreira, BA 1,3 1...

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.”