ORGANUM
Frontotemporal dementia (FTD) is a neurodegenerative disorder, with a preponderance of atrophy in the frontotemporal regions. These regions also have neuronal loss, gliosis, and neuronal Pick bodies, which are masses of cytoskeletal elements. The early stages of FTD is characterised by personality and behavioral changes, with relative preservation of other cognitive functions, and it typically begins before 75-years of age.
The cause is unknown, but the disease constitutes 5% of irreversible dementias. It is most common in men, especially those who have a first-degree relative with the condition.
FTD is classified into two distinct subtypes
Behavioural variant FTD (bvFTD)
Language type : nonfluent variant primary progressive aphasia (nfvPPA), and semantic variant primary progressive aphasia (svPPA). This depends on the area of neuronal loss in frontal and temporal lobes.
FTD is mainly sporadic; genetics also plays a key role where approx. 40% of cases are familial in origin. 13.4% of familial cases have an autosomal dominant inheritance. Mutations in over 20 genes have been identified - commonly involved are microtubules associated protein tau located on chromosome 17q21.32, granulin on chromosome 17q21.32 and hexanucleotide repeat expansion on chromosome 9 open-reading-frame 72 on chromosomal location 9p12.2 (responsible for cytoskeleton organisation). C9orf72 mutation is a continuum between FTD and Amyotrophic Lateral Sclerosis (MND): responsible for the occurence of both entities.
Head trauma and thyroid disease have been linked with the development of FTD with a 3.3-fold higher risk and 2.5-fold higher risk, respectively.
The incidence is 2.2/100,000 between age 40-49, 3.3/100,000 between 50-59 and peaks to 8.9/100,000 between age 60-69. Although the age at onset varies, the mean age at presentation is 58. Behaviour variant (bvFTD) and semantic variant (svPPA) are more prevalent in men, while nfvPPA predominantly occurs in women. The average survival time is 7.5 years
FTD has three distinct clinical syndromes based on the underlying pathologic mechanism characterised by intracellular deposition of abnormal proteins aggregates in the frontal and temporal lobes resulting in the degeneration of neurons, microvacuoles formation, and astrocytosis. Abnormal aggregates of transactive DNA-binding protein TDP-43 account for 50% of cases, microtubules-associated tau protein for 45% and in 5% to 10% cases, tumour-associated protein fused in sarcoma has been found.
The abnormal tau protein aggregates have been identified as the main culprit in patients with both sporadic and familial types of FTD except in the svPPA, in which TDP-43 aggregates predominate.
Initial presentation may be mistaken for psychiatric disorders or a stroke; a through history and physical examination, especially from caregivers, are pertinent. FTD has a wide range of presentation in relation to the areas involved. In all forms of FTD, functional ability and activities.
Behaviour variant type FTD (bvFTD)
It is the most common phenotype. Patients suffering from bvFTD may present with a cluster of altered behaviour and personality changes earlier in the disease process, which include disinhibition, loss of emotional reactivity and disease insight, apathy, impaired abstract thinking, and executive function that worsens over time. it may demonstrate a change in dietary behaviour and loss of fundamental emotions and empathy but with intact memory until late in the disease.
Semantic variant FTD
In this form of FTD, patients manifest language difficulties characterised by paraphasia (impaired word-finding ability or loss of vocabulary), difficulty in understanding the meaning of words, impaired comprehension and difficulty in recognising unfamiliar objects or faces. Their speech is fluent but does not make any sense. Memory is affected late in the disease.
Nonfluent variant Primary Progressive Aphasia (nfvPPA)
Patients with nfvPPA present clinically with effortful halted speech and paraphasia (jumbled words), difficulty in understanding complex sentences and naming objects.
Various bedside tests can be performed if clinical suspicion for FTD is high:
Go-no-go test: In this test, the patient is asked to perform an action in response to a different stimuli
Letter fluency test: In this test, the patient is asked to say as many words (except proper nouns), starting with a single letter in one minute
Attention test: It is used to evaluate the attention span. It is done either by serial seven subtractions from 100 or spells the world 'world' backwards.
Similarities and differences: Done to evaluate abstract thinking. The patient is instructed to compare items - table and chair, apple and orange.
Neural and axonal cytoskeletons are mainly composed of neurofilaments, which are further made up of small subunits called neurofilament light chains. Neurofilament light chains among other biomarkers can be increasingly seen in blood and CSF of patients with FTD.
Radiographic tests such as MRI, CT or PET can be used to demonstrate atrophy and hypoperfusion in the frontal and temporal lobes. The findings are not specific - imaging may aid in the diagnosis or to rule out other etiologies.
EEG: It is not very helpful for FTD as it is for Alzheimer's disease; however, in comparison to the health group, a typically EEG pattern was observed in several patients with FTD and was marked by the reduction of fast activities (alpha, beta1-beta3), but no difference in slow activities (delta and theta waves).
Neurocognitive exams: MMSE, Montreal cognitive assessment and functional cognitive assessment.