Alzheimers

Disease vs
Frontotemporal
Dementia

Alzheimers Disease vs
Frontotemporal Dementia
1. Clinical presentation that would
substantiate a differential diagnosis.
2. Risk factors associated with each of these
disorders.
3. Management or intervention strategies
currently available for each disorder.
4. Post mortem neuropathology that may
help confirm each diagnosis.

Clinical presentation that

would substantiate a
differential diagnosis
o differences in behavior and performance in basic clinical
presentation
o differences in the time course of disease manifestation
o differences in imaging

Alzheimers disease (AD)

Alzheimers disease (AD) is a chronic
neurodegenerative disease with an insidious
onset and progressive but slow decline. AD is
the most common type of dementia worldwide.
The hallmark symptoms in AD are memory loss,
impairment of daily activities, and
neurobehavioral abnormalities.

Frontotemporal dementia
(FTD)
Frontotemporal dementia (FTD) is an umbrella clinical term that
comprises a heterogeneous group of conditions and is the most
frequent primary neurodegenerative brain disease after
Alzheimers disease. FTD can mimic different psychiatric
disorders because of the prominent behaviour change.

The main early symptoms for FTD depends on the

region affected (depending on the FTD variant); they
may have progressive personality change, language,
change in social behavior, self regulation of drives,
emotions and behavior

Behaviour
In FTD there is a marked change in behavior and
personality early in the course of disease when the frontal
lobe is affected. It is unusual for AD to have behavioral and
personality change in the early course of the disease and
this tends to occur later in disease progression.

These early behavior and personality

changes may include socially
inappropriate behaviors in FTD due to an
inability to read emotion on other people.
AD patients commonly have preserved
ability to read emotions and do not
display socially inappropriate behavior in

Motor signs
Motor signs are more common on FTD (in
particular FTD with motor neuron disease)
and are less common in AD

Memory impairment
Memory impairment is
more common for AD than
FTD in particular in the
early stages and may help
differentiate FTD from AD.
However this is not a
diagnostic criteria anymore as
some patient with FTD,
especially advanced, can
have significant memory

Visuospacial defects
Visuospatial defects
are common for
patients suffering
from AD (eg. which
can cause the
patient to become
lost and not find their
way home) and
relatively rare in FTD.

Language problems
There are two types of FTD where language is
impaired progressive nonfluent aphasia (The ability
to speak fluently is gradually lost) and semantic
dementia (the ability to assign meaning to words is
gradually lost. Reading, spelling, comprehension and
expression are usually affected).
In AD , the language decline is mostly related to
their memory impairment (difficulty with recalling
names and words) and have less difficulty to be
understood or understand other people around
them.

Mood:
FTD: Marked irritability,
anhedonia, withdrawal,
alexithymia (difficulties in
understanding, processing, or
describing emotions), euphoria,
lack of guilt, apathy (eg reduced
conversation / activities), or
suicidal ideation
AD: sadness, tears, anhedonia,
apathy and guilt

Psychotic feature:
Delusions and hallucination are
relatively common in AD which
usually have delusion of
misidentification or
persecutory type which usually
occur in middle or late stage
AD.
Hallucinations and delusions
are relatively uncommon in
FTD.

Appetite , dietary change

In FTD, increased appetite and
changes in food preference are
relatively common with a
preference for carbohydrate
which can lead to weight gain.

Dietary changes are less common for AD

patient who tend more to lose weight and
display anorexia.

Time course of disease

manifestation
FTD has a peak onset between 50 years old and 70 years
old. It is not impossible to have FTD onset after 75 years
old but it is much rarer.
AD is age related with increasing prevalence with age.
Early onset AD is autosomally dominantly inherited and
accounts for <1% of cases.
AD affects around 5% of the population below 70 years
of age. The prevalence increases to 40% in those >80
years old (US data)

Imaging in AD
Imaging can help to differentiate these 2 diseases and rule
out other structural causes of dementia.
In AD Brain CT or MRI shows global atrophy. There may also
be hippocampal atrophy which is highly suggestive of AD.
PET scan and SPECT scanning can be helpful for
complicated cases. PET scan using amyloid-binding ligands
are often used in research rather than clinical settings but
can differentiate AD from FTD because amyloid deposition is
not a neuropathological feature of FTD.

Imaging in FTD
In FTD a CT or brain MRI can shows a focal atrophy
in the frontal and /or the temporal lobes. The
atrophy is frequently characterized by left-right
asymmetry.
A PET or SPECT scanning shows reduced brain
activities in the frontal and temporal lobes and it
not only useful to distinguish from AD but has the
potential to differentiate among frontotemporal
lobar degeneration syndromes.

Risk factors associated with

each of these disorders.
o environmental factors or events in a patients history that
might be supplied by informants such as family
o other non-environmental risk factors that may be relevant

environmental factors
Evidence of Environment etiologies of AD is weak and inconsistent.
Head injuries have been identified to be a risk for the development of AD by several
studies.
Increased homocysteine levels and blood cholesterol level may increase risk of
developing AD.
The link between vitamins (i.e. vitamin C and E) and the risk of developing AD is still
controversial.
Finally obesity, smoking, high saturated fat in diet increase also the risk for the
development of AD.
No clear non-genetic aetiological factors are known for FTD. A study published in 2010
showed that traumatic head injury may increase the risk of developing FTD by causing a
reduction in Progranulin level.

GENETICS risk factor for AD

Several genes have been associated with AD.

Less than 5% of all AD cases are familial.
ApoE-4 (chromosome 19) contributes to sporadic cases of late-onset AD. The
ApoE-2 gene is protective factor.
Presenilin 1 (chromosome 14) and presenilin 2 (chromosome 1) and abnormal
amyloid precursor protein (APP) (chromosome 21) are associated with early
onset of AD.
The mutations in chromosome 21 found in Downsyndrome are associated
with the development of Pre-senile AD

Genetics risk factor for FTD

Genetics is an important risk factor for FTD.
A family history of dementia is reported in 40% of
cases with FTD, however autosomal dominant
inheritance accounts for only 10% of cases.
Genes implicated include the microtubuleassociated protein tau (MAPT) gene on
chromosome 17, progranulin (PGRN) gene on
chromosome 17, CHMP2B gene on chromosome 3
and Valosin-containing protein, VCP.

Management or intervention
strategies currently
available
In both diseases for
careereach
supportdisorder.
and psychosocial

interventions are key to managing the disease

course and should be tailored to individuals
based on their symptoms and social situation.
In both diseases the management requires a
multidisciplinary team approach (Occupational
therapist, doctors, psychologist, social workers)
to provide psychoeducation, support and
resources to family and patient.
Pharmacotherapy is different for both diseases.

Management or intervention
strategies currently
for each
disorder.
In AD:available
cholinesterase inhibitors
(ie donepezil
and gelantamine)

are commenced when the diagnosis of mild AD is made.

Antidepressant medications
(SSRIs) are often used as
depression is very common in
AD with a significant impact on
cognitive function. Mirtazapine is
an appropriate treatment when
poor appetite and insomnia are
present, as suggested in a

Management or intervention
strategies currently
each
disorder.
There available
are no drugs availablefor
which can
modify the
course of FTD and the

pharmacological management of FTD is tailored at specific symptoms.

The cholinesterase inhibitors do not have any place in the treatment of FTD
and can potentially worsen symptoms.
Benzodiazepines or neuroleptics can be use for acute irritability and
agitation.
Antidepressant medications can be use for compulsions which impede daily
function.
Sodium valproate can be used for euphoria, mania and impulsivity and
topiramate for gluttony.

Post mortem
neuropathology in AD.

Post mortem
neuropathology in AD.
The post mortem histopathology of AD is characterized by
senile plaques, neurofibrillary tangles, and neuronal loss.
There is an aggregation of abnormal tau-protein inside
neurons which build up to neurofibrillary tangles, neuropil
threads and dystrophic neurites in neuritic plaques.
There is also a deposition of amyloid beta-protein
extracellularly, these changes are well established and
follow a hierarchical order.

Post mortem
neuropathology in FTD.
In FTD, brain histology may reveal diagnostic findings (such as Pick
bodies composed of tau protein, TDP-43 proteinopathy, or FUS
proteinopathy).
The FTDs are charactisederized by atrophy of the frontal and temporal
lobes which is different from the general atrophy found in AD.
Microscopically we can found neuronal loss and gliosis, ballooned
neurons and vacuolization of the superficial cortex.
All FTDs show abnormal protein inclusions in glial cells and neurons, the
different types of proteins differentiate the different subtypes of FTD .

Alzheimers Disease vs
Frontotemporal Dementia
1. Clinical presentation that would
substantiate a differential diagnosis.
2. Risk factors associated with each of these
disorders.
3. Management or intervention strategies
currently available for each disorder.
4. Post mortem neuropathology that may
help confirm each diagnosis.