Frontotemporal Dementia (FTD)

Frontotemporal dementia (FTD) is a neurodegenerative syndrome that affects the frontal and/or temporal lobes of the brain. Unlike Alzheimer's disease, which primarily affects memory, FTD manifests with symptoms related to behavior, personality, and language. It is the most common form of dementia among people under the age of 65.

The main clinical manifestations are:

Behavioral Variant (bvFTD). This causes an alteration in personality and behavior, with symptoms such as apathy, disinhibition, and loss of empathy.

Primary Progressive Aphasia (PPA). This is characterized by a progressive deterioration of language. Willis's case falls into this variant, where difficulty speaking or understanding words are the first evident symptoms.

The causes of FTD are complex and not yet fully understood, but research has identified three main factors that interact in a multifactorial way:

Genetic causes (1/3 of cases). FTD can be inherited due to mutations in specific genes such as C9ORF72, MAPT (which produces the tau protein), and GRN [1]. These mutations lead to the production or alteration of proteins that become toxic to neurons.

Protein alterations. Even in non-hereditary cases, the main cause is the accumulation of abnormal proteins inside neurons [2]. The proteins involved are mainly the tau protein and TDP-43. These proteins are naturally produced by our cells and have vital roles. The problem is not their presence, but their misfolding and subsequent aggregation. Due to processes that are still unknown, these proteins fold into an abnormal shape and accumulate in toxic clumps. These clumps damage neurons and impair their function, leading to their death.

Environmental factors. Although their influence is not yet definitive, it is hypothesized that external factors may also play a role. Research is evaluating the effect of repeated head injuries, which can accelerate the development of tau protein-related diseases, and exposure to environmental toxins, such as certain pesticides.

Neurotoxicity of pesticides and multifactoriality

The scientific debate is particularly heated on the role of certain pesticides [6]. Many are designed to act on the nervous system of insect pests, blocking crucial enzymes like acetylcholinesterase. The question is whether these substances, if they enter our diet, can have a similar effect on humans. Chronic and prolonged exposure to low doses can cause oxidative stress and chronic inflammation, both of which are known to contribute to neuronal damage and the alteration of key protein folding like tau and TDP-43 [7, 8].

This leads to the concept of multifactoriality, where the disease arises from the interaction between a predisposed genetic background and environmental agents. An individual with genetic mutations in MAPT or GRN could be more vulnerable to the toxic effects of certain substances, with the environmental factor acting as an "accelerator" that triggers the disease.

If research were to confirm the causal or co-causal role of these substances, it would open a clear path for prevention. The solution would not be to eliminate pesticides, but to support them with alternative substances that do not act on the nervous system. Innovation in agricultural chemistry could focus on active ingredients that act on other biological mechanisms of the pest, thereby reducing the risk of human exposure to neurotoxins in the food chain.

Current prevention and treatments

Currently, there is no cure or treatment that can stop the progression of FTD. The therapeutic approach focuses on symptom management to improve the patient's quality of life. This includes:

Non-pharmacological therapies. Speech therapy, occupational therapy, and psychological support.

Symptomatic treatments. Medications that can help manage behavioral symptoms.

Bruce Willis's story has not only increased awareness of FTD but has also underscored the crucial importance of family support. His battle has transformed a private tragedy into a powerful message of hope and awareness, prompting the scientific community to intensify efforts to find a cure.

*Board Member, SRSN (Roman Society of Natural Science)
Past Editor-in-Chief Italian Journal of Dermosurgery