Frontotemporal dementia

Generality

Frontotemporal dementia is a neurodegenerative disorder of the brain, which occurs due to the progressive deterioration of neurons located in the frontal and temporal lobes of the brain.

These brain areas control language, behavior, part of the movement and thinking skills, so their gradual degeneration involves alterations in the aforementioned areas. These are typical problems: the difficulties in articulating a speech, sudden personality changes, balance disorders and amnesia.

Despite the discoveries of recent decades, the mechanism that leads to the deterioration of neurons still has some question marks.

Diagnosing frontotemporal dementia is not easy at all, and several tests and assessment tests are needed.

Unfortunately, as with many other forms of dementia, one is not yet in possession of a cure that will cure or regress the disease.

What is frontotemporal dementia?

Frontotemporal dementia is a form of dementia that arises following a degeneration of nerve cells (or neurons), located in the frontal and temporal lobes of the brain .

DEFINITION OF DEMENTIA

In medicine, the term dementia indicates a neurodegenerative disease of the brain, typical of the elderly (but not exclusive to old age), which involves the progressive and almost always irreversible reduction of a person's intellectual (or cognitive) faculties.

This reduction has numerous consequences: it interferes with the performance of the simplest daily activities, with interpersonal relationships (that is, between people), with the ability to think and memory, with the use of a clear and appropriate language, with the balance, with motor muscles, behavior, personality and emotionality.

Epidemiology

Frontotemporal dementia is the fourth most common form of dementia, after known Alzheimer's disease, vascular dementia and dementia with Lewy bodies .

Compared to these diseases just mentioned (which mainly affect the elderly), it tends to arise in younger individuals, generally between 40 and 65 years old.

It affects both sexes equally.

Causes

The exact mechanism that induces the onset of frontotemporal dementia has been only partially clarified.

The most recent research, based on post-mortem analysis of patients, revealed that:

The progressive deterioration of the neurons of the frontal and temporal lobes is subsequent to the formation, within the same cells, of anomalous protein aggregates . Protein aggregates are small clusters of proteins.
Among the proteins that make up the aggregates, the most representative and "famous" is tau . Tau is a microtubule protein, that is, small intracellular structures that regulate the transport of fundamental elements within the cell. When tau forms the aggregates, the microtubules no longer function properly and the cell involved dies .
Frontotemporal dementia can also be a genetic disease transmitted from parents to children . At first, it was only hypothesized by the observation that about a third of the sick had the father or mother with the same pathology.
Subsequently it was also demonstrated with the identification of equal genetic mutations in members of the same family, carriers of frontotemporal dementia.
The genes, which, if mutated, predispose to frontotemporal dementia, have at least three: MAPT, GRN and C9ORF72 . MAPT resides on chromosome 17 and is involved in the synthesis of the "usual" protein tau; GRN and C9ORF72 reside respectively on chromosome 17 and on chromosome 9 and, together, cooperate in the synthesis and proper functioning of a protein called TDP-43.
Mutations affecting MAPT, GRN and C9ORF72 induce the accumulation, within neurons, of the proteins with which they are associated, therefore tau and TDP-43.
For all those cases in which there seems to be no familiarity, the appearance of protein aggregates occurs for reasons that are still unknown.

SUBTIPES OF FRONTAL DEMENTIA

Thanks also to the scientific discoveries reported in the previous points, the neurodegenerative disease experts have identified 3 subtypes of frontotemporal dementia:

Pick's disease . Characterized by intracellular clusters of tau protein ("called Pick bodies"), it appears to be unrelated to any genetic-hereditary mutation.
In most cases it occurs after the age of 50.
Pick refers to the researcher who first described it, a certain Arnold Pick.
Frontotemporal dementia with parkinsonism, linked to chromosome 17 . It is in fact an inherited disease, characterized by an alteration of the MAPT gene and the presence of clusters of tau protein.
Primary progressive aphasia . With a typical onset around the age of 40 and with slow and gradual symptom progression, it is only in rare cases associated with inherited mutations of the MAPT, GRN and C9ORF72 genes. In fact, it usually appears as a disease with unknown causes.

Symptoms and Complications

Among the various functions performed, the frontal lobes and temporal lobes of the brain also control behavior, language, thinking skills, part of the body's movements and some muscles .

Therefore, the deterioration of their nerve cells involves a series of symptoms and signs, which refer mainly to these areas.

Frontotemporal dementia has a progressive trend. This means that its effects tend to get worse with time (generally within a few years).

NB: for some patients, the deterioration of neurons can only affect the frontal lobes or only the temporal lobes. This results in an incomplete symptomatic picture, which depends on the brain area involved.

BEHAVIOR PROBLEMS

Along with those of language, behavioral problems are the first symptoms to appear in those suffering from frontotemporal dementia.

They can consist of:

Inappropriate behavior in public.
Impulsiveness.
Decrease or total loss of inhibitory brakes.
Neglect towards personal hygiene.
Extreme gluttony, sudden change in tastes and food preferences and inappropriate behavior at the table (lack of good manners, etc.).
Irritability and aggression.
Coldness, indifference and inability to empathize with others.
Selfish behaviors.
Assumption of indiscreet or very rough attitudes.
Repetitive or obsessive behaviors, such as constantly rubbing hands or walking the same path repeatedly and several times a day.
Loss of enthusiasm and signs of lethargy.

As the disease progresses, the aforementioned disorders worsen and the patient usually tends to isolate himself from the social context and interrupt any relationship with other people.

LANGUAGE PROBLEMS

Speech problems are very common in those suffering from frontotemporal dementia. They generally consist of:

Incorrect use of words. For example, a patient could use the word "sheep" instead of the word "dog".
Reduced vocabulary and difficulty when reading a text.
Use of a limited number of sentences and tendency to repeat them often.
Fatigue in articulating a normal and complete speech.
Tendency to automatically repeat sentences or words spoken by other people.
Conversations and speeches that are always shorter and with less content.

As the disease worsens, patients tend to progressively lose their ability to speak.

Indeed, in the final stages of the illness, they usually become mute.

PROBLEMS WITH THE THOUGHTS ABILITY

When frontotemporal dementia impairs thinking skills, patients manifest:

Ease of distraction.
Poor planning, judgment and organization skills.
Lack of self-sufficiency. They need to be told, step by step, what to do.
Rigidity and inflexibility of thought.
Inability to abstract and to understand abstract concepts.
Memory difficulties.

It must be specified that memory disorders usually arise at an advanced stage of the disease.

PHYSICAL AND MOVEMENT PROBLEMS

Generally, when it has reached a very advanced stage, frontotemporal dementia impairs the ability to move and control some muscles.

Going into the details of the symptomatology, patients can manifest:

Stiffness similar to that induced by Parkinson's disease .
Lack of control of bladder muscles (urinary incontinence) and intestinal (fecal incontinence).
Progressive weakness, associated with muscle atrophy (ie reduction in muscle mass). In these cases, it is said that the patient suffers from one of the so-called motor neuron diseases .
Difficulty in controlling the limbs of the body, loss of balance and coordination, slowness of movement and reduced mobility. Doctors identify these disorders as cortico-basal degeneration .
The typical signs of the so-called progressive supranuclear palsy, or disorders of: balance, eye movement and swallowing.

Summary of symptoms and typical signs of various subtypes of frontotemporal dementia
Subtype	Characteristic symptomatology
Pick's disease	Speech problems, difficulty concentrating, impaired thinking, sudden changes in personality, abnormal behavior, passivity and lack of tact.
Frontotemporal dementia with parkinsonism, linked to chromosome 17	Rigidity (typical of Parkinson's disease), depression, hallucinations, obsessive behavior, lack of judgment, problems relating to other people and difficulties in planning and concentration.
Primary progressive aphasia	Personality changes, bizarre behavior, amnesia, poor attention span, serious language problems and difficulty reading a text.

Diagnosis

Especially when it is in its early stages, frontotemporal dementia is somewhat difficult to diagnose, as its manifestations can be confused with those of similar diseases or conditions.

In general, the diagnostic process involves the performance of various assessments, including:

A thorough physical examination . It consists in the analysis of symptoms and signs reported or manifested by the patient.
A neurological exam . It is the evaluation of tendon reflexes, behavior, motor skills, mental faculties and memory skills.
An analysis of any drugs taken by the patient under investigation . It is performed because certain medicines produce side effects similar to those caused by frontotemporal dementia.
Blood tests . They are carried out to exclude that the symptoms are due to vitamin deficiencies (vitamin B12) or to other similar causes.
Diagnostic imaging tests, such as brain CT or nuclear magnetic resonance (NMR) of the brain. CT and MRI of the brain show the appearance and above all the state of health of the various brain areas. In the case of frontotemporal dementia, the frontal and temporal lobes show quite evident alterations.

GENETIC TESTS

Family members who experience frontotemporal dementia can undergo a particular genetic test, which will tell them whether or not they carry mutations in the MAPT, GRN or C9ORF72 genes.

Treatment

Unfortunately, frontotemporal dementia is a disease that cannot be cured.

However, with some appropriate treatments, it is possible to slow down its progression and alleviate its symptoms.

PHARMACOLOGICAL THERAPY

The pharmacological choice is really small.

The few medicines that are sometimes used are:

Selective serotonin reuptake inhibitors ( SSRIs ). Belonging to the antidepressant category, they are prescribed against loss of inhibitory brakes and obsessive behavior.
Trazodone . It is an antidepressant that can alleviate, in some cases, behavioral disorders.
Haloperidol . Among the most important antipsychotic, it is rarely prescribed and only in the presence of serious behavior problems, as it can cause serious side effects.

TREATMENTS FOR DAMAGED DISEASES

Any person with dementia - therefore also the individual with frontotemporal dementia - is subjected to this series of symptomatic treatments (ie aimed at alleviating symptoms):

Occupational therapy . It has mainly two objectives: to make the patient as independent as possible from others and re-insert him in a social context.
Language therapy . It aims to at least partially re-establish the spoken language and improve communication problems.
Physiotherapy . It aims to improve motor and balance problems.
Cognitive stimulation . It consists in having patients perform exercises aimed at improving memory, language and the so-called problem solving skills .
Behavioral therapy . It aims to improve the problem behaviors induced by the disease (extreme gluttony, impulsiveness, etc.).