the 2nd most common cause of dementia in those under 65yrs age, and the 4th most common cause in those over 65 yrs of age (when vascular and Lewy Body dementia become more common)
characterized by atrophy in the frontal lobe and temporal lobe of the brain, with sparing of the parietal and occipital lobes
Epidemiology
prevalence 9-22 per 100,000 persons
1.6 to 2.3 new cases per 100,000 person-years
peak age of onset between the ages of 50 and 65
Aetiology / risk factors
most are sporadic with no known genetic cause
~40% are genetic
mutations in the Tau gene (MAPT gene)
over 40 mutations known and can cause FTLD-tau
frontotemporal dementia and parkinsonism linked to q arm of chromosome 17 (FTDP-17)
MAPT mutations account for up to 50% of FTDP-17 cases
very rare (100 families worldwide) an autosomal dominant with incomplete penetrance
behavioral and personality changes
may include disinhibition, apathy, poor judgment, compulsive behavior, hyperreligiosity, alcoholism, illicit drug addiction, verbal and physical aggression, and abusive behaviors
cognitive impairment
progressive speech difficulties with non-fluent aphasia and executive function disorders
later echolalia, palilalia, verbal and vocal perseverations develop and eventually, mutism and progressive dementia set in
FTDP-17 Parkinsonism motor symptoms but with lack of resting tremor and poor or no response to levodopa therapy
mutations in the progranulin gene (PGRN)
can cause FTLD-TDP43
mutations in the CHMP2B gene
associated with a rare behavioural syndrome with ubiquitin positive pathology
hypermorphic mutations in the VCP gene
cause a TDP-43-positive FTLD which is associated with multisystem proteinopathy (MSP) which includes Paget's disease and inclusion body myopathy
hypomorphic mutation in the VCP gene
cause a unique type of FTLD-tau called vacuolar tauopathy with neurofibrillary tangles and neuronal vacuoles
mutations in the TDP-43 gene (known as TARBP or TAR DNA-binding protein)
very rare cause of FTLD, more commonly cause ALS
may be linked to C9ORF72 gene
Pathophysiology
most have tau or ubiquitin inclusions on histology
histologic subtypes
FTLD-tau
Pick bodies - tau positive inclusion bodies
45% of cases
subtypes:
Pick's disease
corticobasal degeneration
progressive supranuclear palsy
FTLD-TDP (or FTLD-U )
ubiquitin and TDP-43 positive, tau negative, FUS negative inclusion bodies
~50% of cases
5 subtypes:
Type A
Type B
often associated with ALS and C9ORF72 mutations
Type C
often associated with semantic dementia
Type D
associated with VCP mutations
Type E
has been associated with behavioral variant of frontotemporal dementia with a rapid clinical course
FTLD-FUS
rare genetic/pathological subtype
single-digit percentage of cases
Clinical features
3 main clinical subtypes characterized by impairments in specific neural networks:
behavioural-variant frontotemporal dementia (bvFTD) accounts for 36-50% of cases