Frontotemporal dementia

Frontotemporal dementia (FTD) is a clinical syndrome caused by degeneration of the frontal lobe of the brain and may extend back to the temporal lobe. It is one of three syndromes caused by frontotemporal lobar degeneration, and the second most common early-onset dementia after Alzheimer's disease.

Signs and symptoms
Symptoms can be classified (roughly) into two groups which underlie the functions of the frontal lobe: behavioural symptoms (and/or personality change) and symptoms related to problems with executive function.


 * Behavioural symptoms include lethargy and aspontaneity or oppositely disinhibition. Apathetic patients may become socially withdrawn and stay in bed all day or no longer take care of themselves. Disinhibited patients can make inappropriate (sometimes sexual) comments or perform inappropriate acts. Patients with FTD can sometimes get into trouble with the police because of inappropriate behaviour such as stealing. Recent findings indicate that psychotic symptoms are rare in FTD, possibly due to limited temporal-limbic involvement in this disorder. Among FTD patients, only approximately 2% have delusions, sometimes with paranoid ideation; hallucinations are rare. This is significantly less than AD patients, where approximately 20% have delusions and paranoia. See ref. "Psychotic symptoms."


 * Executive function is the cognitive skill of planning and organizing. Patients become unable to perform skills that require complex planning or sequencing.

Language skills can be affected in a number of ways with two broad patterns. Some patients remain fluent with normal phonology and syntax but increasing difficulty with naming and word comprehension, known as semantic dementia in which there is atrophy of the anterior temporal lobes, typically with an asymmetric pattern. Other patients, by contrast, present with a breakdown in speech fluency due to articulation difficulty, phonological and/or syntactic errors but preservation of word comprehension, referred to as progressive nonfluent aphasia.

In addition to the characteristic cognitive dysfunction, a number of primitive reflexes known as frontal release signs are often able to be elicited. Usually the first of these frontal release signs to appear is the palmomental reflex which appears relatively early in the disease course whereas the palmar grasp reflex and rooting reflex appear late in the disease course.

FTD can occur in patients with motor neuron disease (also known as amyotrophic lateral sclerosis) in a small number of cases. The prognosis for people with MND is worse when combined with FTD, shortening survival by about a year.

Pathology
A number of case series have now been published looking at the pathological basis of frontotemporal dementia. As with other syndromes associated with FTLD, a number of different pathologies are associated with FTD:
 * Pick's disease (3-repeat Tau inclusions)
 * Other tau-positive pathology including FTDP-17, corticobasal degeneration, progressive supranuclear palsy
 * Frontotemporal lobar degeneration with ubiquitin positive, tau- and alpha-synuclein negative inclusions with and without motor neuron degeneration (recently characterized by nuclear and cytoplasmic staining of TDP-43 protein)
 * Dementia lacking distinctive histology
 * In rare cases, patients with clinical FTD were found to have changes consistent with Alzheimer's disease on autopsy
 * Evidence suggests that FTD selectively impairs spindle neurons, a type of neuron which has only been found in the brains of humans, great apes, and whales.

Diagnosis
According to DSM-IV diagnosis is mainly clinical including changed behaviors, changes in language and others, using also image exams and neuropsychological tests.

Structural MRI scans often reveal frontal lobe and/or anterior temporal lobe atrophy but in early cases the scan may seem normal. Atrophy is often asymmetric. Registration of images at different time points (e.g. one year apart) can show evidence of atrophy in two cross-sectional images that may be reported as normal. This is a useful diagnostic technique. However, many research groups are currently looking at ways of making an early diagnosis of FTD using other techniques (magnetic resonance spectroscopy, functional imaging, cortical thickness measurements etc.). FDG-PET scans classically show frontal and/or anterior temporal hypometabolism, which helps differentiate from Alzheimer's disease. The PET scan in Alzheimer's disease classically shows biparietal hypometabolism. Meta-analyses based on imaging methods have shown that frontotemporal dementia mainly affects a frontomedian network discussed in the context of social cognition or 'theory of mind'. This is entirely in keeping with the notion that, on the basis of cognitive neuropsychological evidence, the ventromedial prefrontal cortex is a major locus of dysfunction early on in the course of the behavioural variant of frontotemporal degeneration. The language subtypes of frontotemporal lobar degeneration (semantic dementia and progressive nonfluent aphasia) can be regionally dissociated by imaging approaches in vivo.

Genetics
A higher proportion of FTD cases seem to have a familial component (perhaps more so than Alzheimer's disease). Two known mutations are associated with familial FTD:


 * tau-positive frontotemporal dementia with parkinsonism (FTDP-17) with mutations in the MAPT gene on chromosome 17
 * tau-negative frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U; positive for TDP-43) with progranulin mutations (also on chromosome 17)

However, it is estimated that each of these two genes only accounts for about 5–10% of all cases of FTD, thus other genes or heritable components are likely responsible for the high degree of heritability in FTD.

Management
There is no known curative treatment for FTD. Supportive care is essential. Management of behavioural symptoms may be necessary (e.g. SSRIs for depression; atypical neuroleptics etc.).

Because FTD often occurs in younger people (i.e. in their 40's or 50's), it can severely affect families. Patients often still have children living in the home. Financially, it can be devastating as the disease strikes at the time of life that is often the top wage-earning years.

Prognosis
Median survival time is 7 years.