FRONTOTEMPORAL

DEMENTIA(FTD) 

& PRIMARY
PROGRESSIVE
APHASIA (PPA)
Wikawee Sirisuk ,MD.
● First description In 1892, Arnold Pick
● a patient with progressive aphasia associated with frontal and
temporal lobar atrophy.
● In 1911, Alois Alzheimer recognised the characteristic association
with Pick bodies and named the clinicopathological entity Pick’s
disease which led to the use of Pick’s disease as a synonym for
frontotemporal dementia.
● In 1982, Mesulam reported six patients with “slowly progressive
aphasia,” and later introduced the term primary progressive
aphasia (PPA).
● Brun and Gustafson in Sweden (Gustafson et al., 1990) and Neary
and Snowden in the UK (Neary et al., 1988) termed the group of
disorders “frontal lobe dementia of the non-Alzheimer type”, and
“dementia of the frontal type,” respectively.
 ● Definition “FTD”
▪ Group of clinical syndromes characterized by degeneration
Frontotemporal of the frontal and temporal lobes
dementia 

(FTD)
 FTLD (Frontotemporal lobar degeneration)

 ▪ The spectrum of pathology associated with FTD
“ WHO estimates that dementia
rates will double every 20 years,
reaching 115·4 million in 2050.”
▪ Frontotemporal dementia
was the second or third most
prevalent dementia subtype in
most studies
▪ A prevalence ranging
from 3% to 26%
Frontotemporal dementia (FTD)

▪ Behavioral-variant frontotemporal dementia

- Early behavioral and executive deficits

▪ Primary progressive aphasia

◦ Non-fluent variant PPA
- Progressive deficits in speech,
grammar , and word output
◦ Semantic-variant PPA
- Progressive disorder of semantic
knowledge and naming
 ● Change in personality and behavior
● Disinhibition
Behavioral-variant ● Apathy
frontotemporal ● Sociopathy
● Euphoria
dementia
● Executive dysfunction
● Poor planning
(BV-FTD) ● Loss of judgement
● Difficulty with organization
● Loss of insight
Behavioral-variant
frontotemporal
dementia

(BV-FTD)
 A group of disorders where neurodegeneration targets the language
network.
▪ Non-fluent variant PPA (Progressive agrammatic/nonfluent aphasia)
▪ Semantic-variant PPA (Semantic dementia)
Primary
progressive
aphasia 



(PPA)
 Progressive Agrammatic/Nonfluent Aphasia
(Non-Fluent Variant Primary Progressive Aphasia)

● Non-fluent , Hesitant speech

● Agrammatism
Telegraphic speech
Misuse of pronouns
Errors in sentence construction

● Word and object knowledge is relatively spared.

● Patients often develop a parkinsonian syndrome

 Semantic Variant Primary progressive dementia
(Semantic dementia)

● Fluent aphasia

● Prominent anomia with loss of single word meaning.

● Nouns are particularly difficult to comprehend.

● Patients will replace a specific word with a more general word

such as “it” for “telephone”

● Surface dyslexia ; irregularly pronounced words

such as “colonel,” “pint” are pronounced phonetically.

● Most repetition spared and grammar remains intact.

● May develop loss of visual object meaning and prosopagnosia (difficulty recognizing familiar faces) ; Effect
Right temporal > Left temporal

● Range of presentation between 66 and 70 years of age

● svPPA tend not to have parkinsonism, a family history of dementia, or associated motor neuron disease
Features of
FTD
Subtypes
 Neuropathology
▪ Frontotemporal lobar degeneration
- neuronal loss, gliosis, and microvacuolar changes of frontal lobes, anterior temporal lobes, anterior cingulate cortex,
and insular cortex.

▪ Subtypes are associated with characteristic patterns of abnormal protein deposition.

▪ Initial changes occur in the anterior cingulate cortex, fronto-insular cortex, orbitofrontal cortex, and cingulatefrontal
transitional zones.

▪ Either the microtubule-associated protein tau (MAPT), the TAR DNA-binding protein with molecular weight 43 kDa
(TDP-43), or the fused-in-sarcoma (FUS) protein account for nearly all cases of frontotemporal lobar degeneration.

▪ The corresponding pathological subtypes of frontotemporal lobar degeneration are frontotemporal lobar
degeneration-tau, frontotemporal lobar degeneration-TDP, and frontotemporal lobar degeneration-FUS.

A few cases of frontotemporal lobar degeneration have ubiquitin-only or p62-only positive inclusions, or no
inclusions at all.
 Genetics
A positive family history occurs in approximately 40% of FTD cases.

Several genes associated with FTD have been described.

The three major genes include

1.Microtubule associated protein tau (MAPT) 5%–10% of FTD cases
2.Progranulin which accounts for 10% of FTD cases
3.Chromosome 9 open reading frame 72 (C9ORF72) which accounts for approximately 15% (25% of
familial cases) of FTD cases.

These genes are dominantly inherited.

Several other genes have been implicated in FTD including :

- Charged multivesicular body protein 2B (CHMP2B) on chromosome 3
- Valosin containing protein (VCP) mutations on chromosome 9.
Mutations in VCP cause a syndrome of inclusion body myopathy, Paget disease of bone, and
frontotemporal dementia.
- TAR DNA-binding protein 43 mutations have been reported in patients with FTD with or without
MND
Structural MRI



◦ BV-FTD atrophy occurs in
the orbitofrontal cortex, insula,
anterior cingulate, medial and
dorsolateral frontal lobes

◦ SV-PPA left anterior temporal
pole

Other regions that can be involved include the orbitofrontal
region, insula, anterior cingulate right anterior temporal lobe,
and hippocampus 



◦ Agrammatic PPA left
inferior frontal atrophy 

Functional imaging



FDG-PET : improve accuracy of
diagnosis

- bvFTD –bilateral frontal-
temporal hypometabolism

- nfvPPA – left posterior inferior
frontal lobe hypometabolism.

- svPPA – left anterior temporal
hypometabolism



PiB-PET : useful in
discriminating FTD from AD. 

PiB-PET is more sensitive than
FDG-PET on both visual
interpretation and quantitative
measures while FDG-PET is
more specific only quantitatively

 Laboratory investigation

● FTD spectrum disorders : serum and CSF studies are normal.

Active investigation for the role of serum and CSF biomarkers in predicting pathology for FTD subtypes is
underway.

● Progranulin serum levels have shown promise in discriminating those with and without progranulin mutations
(Finch et al., 2009).

● Some studies have demonstrated plasma TDP-43 and CSF TDP-43 may predict TDP-43 pathology although more
research is needed to confirm these findings
 FTD Treatment
No medications FDA approved for the treatment of FTD.

SSRIs in FTD to improve behavioral symptoms

FDA has issued a warning that antipsychotic drugs increase risk of death in dementia patients(Cardiac
events, falls , and Infection), such agents must be used with caution.

Nonpharmacological interventions including home safety evaluation and removal of weapons from the
home are important.

Family education about the disease and caregiver support groups can be helpful.

Patients with PPA may benefit from evaluation and treatment by speech language pathologists to help
with communication strategies.
 References

Bradley’s Neurology in Clinical

Practice ,seventh Edition

Lancet 2015; 386: 1672–82