Frontotemporal dementia, a rare neurodegenerative disease

Frontotemporal dementia, a rare neurodegenerative disease

Frontotemporal dementia (FTD), now called frontotemporal lobar degeneration, is a disease related to Alzheimer’s disease. However, it is distinguished by different characteristics. Explanations from Dr Isabelle Le Ber, neurologist specializing in FTD at the reference center for rare dementias at Pitié-Salpêtrière and researcher at the Institut du Cerveau – ICM (Paris).

What is frontotemporal dementia?

Formerly called frontotemporal dementia, frontotemporal lobar degeneration (FTLD) is a group of rare neurodegenerative diseases caused by progressive damage to certain parts of the brain. Like Alzheimer’s disease, to which they are related, fronto-temporal degenerations are cognitive and behavioral diseases; but the similarities end there. “The brain lesions are not the same, nor are the brain structures affected, and the symptoms differ somewhat.”underlines Dr Isabelle Le Ber, neurologist in the reference center for rare or early dementia at the Pitié-Salpêtrière hospital (Assistance Publique-Hôpitaux de Paris – APHP).

And the DFT specialist clarified: “In fronto-temporal lobar degeneration, the affected brain structures are the frontal (located at the front of the brain) and temporal (laterally) lobes. Seats of reasoning, abstract thoughts and planning, the frontal lobes are also involved in the control of our social behavior and our emotions. It is the more or less rapid destruction of the neurons of these brain structures that causes fronto-temporal dementia.

In Europe, between 15,000 and 20,000 people are affected by this neurodegenerative disease, which affects both men and women. Frontotemporal dementia recently made headlines after Bruce Willis revealed he had it.

What are the causes of frontotemporal dementia?

Frontotemporal degenerations are due to the abnormal accumulation of proteins in neurons. There are 3 subtypes of FTD, depending on the type of proteins accumulated. For the moment, only the autopsy makes it possible to determine the nature of these proteins and therefore the brain lesions, indicates Dr Le Ber. “The most common form of FTD (60% of cases) is due to the accumulation of the TDP43 protein; Approximately 30% of cases result from the accumulation of the Tau protein; and a minority of cases can be explained by that of the Fus protein”.

Genetic mutations in 1/3 of cases

A genetic cause is found in approximately 1/3 of people with FTD, indicates Dr. Le Ber. “The genes involved in these familial forms are transmitted in an autosomal dominant manner, which means that the offspring has a one in two risk of inheriting them and developing the disease. To date, around twenty genes responsible – when mutated – for hereditary forms of fronto-temporal dementia have been identified; the most frequent mutations are those of the C9Orf72 gene which cause the development of FTD and/or amyotrophic lateral sclerosis (ALS or Charcot disease), those of the progranulin gene (or GRN gene) and mutations of the MAPT gene “.

No cause in 2/3 of cases

Two thirds of people with FTD have no family history. In these cases, the cause of the disease is most often not known.

However, no environmental risk factors have been identified.

What are the symptoms of frontotemporal dementia?

At what age does frontotemporal dementia begin?

The first symptoms generally appear between the ages of 55 and 65, but there is great variability from one patient to another. “There are earlier forms and others later, with great variability within families in genetic forms. underlines the specialist. “The most common genetic form, linked to the C9Orf72 gene, can thus begin from the age of 40 and up to the age of 80”.

How does a DFT start?

Most of the time, the disease first manifests itself by behavioral disorders, such as progressive apathy, loss of interest, social withdrawal. An initial phase characterized by a lack of initiative, a loss of desire and general disinterest, very often wrongly attributed to depression. “Especially since it appears at an age when, very often, retirement is approaching, children are leaving the family home, etc. So many elements which can actually be responsible for an authentic depressive syndrome”acquiesces Dr Le Ber.

During the course of the disease, other symptoms appear, which relate to social behaviors: disinhibition, loss of social conventions. Patients may, for example, make familiar remarks or exhibit abnormal social behavior. Indeed, affected people have difficulty respecting practices of “good social behavior”: they may make inappropriate jokes or inappropriate comments, incur excessive and inappropriate expenses, rush to eat food to the point of bulimia..”, we can read on the Orphanet website. Having become impatient and easily irritable, it is possible that some patients may appear antisocial, aggressive or even possibly violent. Some may also develop stereotypical or ritualized behaviors.

As the disease progresses, apathy often becomes the predominant symptom.

Language disorders

Frontotemporal dementia can also begin with language disorders such as difficulty finding words, constructing sentences, an impoverishment of vocabulary which gradually evolves into a loss of language (aphasia). For other patients, the disorders will manifest themselves more in the form of problems understanding words, linked to a loss of their meaning. Ultimately, these difficulties lead to communication problems which can isolate the patient.

Eating disorders (TCA)

We also observe problems controlling emotions and eating disorders. These generally manifest themselves in the form of a change in eating habits, excessive consumption of certain foods, particularly sweet foods, or even bulimia which can be accompanied by significant weight gain.

What is the progression of frontotemporal dementia?

The condition of people with frontotemporal lobar degeneration deteriorates progressively. “The disease progresses over around ten years towards a worsening of symptoms and apathy. This development leads to a loss of autonomy, punctuated by complications (infections, serious falls, etc.) which can lead to the death of patients.indicates Dr Le Ber.

How is frontotemporal dementia diagnosed?

“FTD is first suspected thanks to the testimony of relatives who report the recent appearance of behavioral disorders, a change in personality or language difficulties”, indicates the neurologist. Additional examinations are nevertheless necessary to confirm the diagnosis and rule out other neurodegenerative pathologies likely to present common symptoms.

Cognitive or neuropsychological tests are therefore offered to assess patients’ reasoning, judgment, attention and even memory abilities. They can be supplemented by a language assessment carried out by speech therapists. Brain imaging tests, such as magnetic resonance imaging or MRI (structural imaging test), and positron emission tomography or PET (functional imaging test), are used to detect damage or dysfunction of the frontal and temporal regions of the brain. Finally, carrying out a lumbar puncture makes it possible to exclude other causes such as Alzheimer’s disease for example. “The latter can be identified through the abnormality of specific biomarkers in the cerebrospinal fluid – which is not the case for frontotemporal degeneration. The normality of these biomarkers therefore makes it possible to rule out the diagnosis of Alzheimer’s disease and direct it towards that of FTD.”.

Finally, a genetic consultation and analysis can be offered in family forms. On the ICM website, we also learn that a test assessing empathy was developed in collaboration with an international team in this institute and at IM2A. “This test makes it possible to better differentiate between FTD and Alzheimer’s disease, which are still too often confused. Ultimately, it could become one of the reference diagnostic tests for this pathology.we can read.

How to treat frontotemporal dementia?

Frontotemporal dementia, an incurable disease

Currently, there is no treatment that can cure frontotemporal dementia. The treatment of people suffering from this disease is essentially symptomatic and aims to improve behavioral problems. It is based on both drug treatments and paramedical care.

What medications?

These are mainly antidepressants (serotonin reuptake inhibitors) which are prescribed to improve certain behavioral disorders. Other treatments, such as neuroleptics, should be avoided, indicates Dr. Le Ber. Likewise, medications indicated for people with Alzheimer’s disease (acetylcholinesterase inhibitors) have no effect in FTD and are even prohibited in this condition.

Paramedical care

They essentially consist of offering cognitive stimulation and/or language re-education through…