Frontotemporal Dementia (FTD) (Ist. Auxologico)
Frontotemporal Dementia is characterized by two main clinical phenotypes: the first characterized by behavioral disorders and executive dysfunction (behavioral variant), and the second by language disorders (primary progressive aphasias) with three distinct clinical forms. It represents the second or third most common form of dementia in the Western world and typically manifests around age 65, earlier than Alzheimer’s disease, with a devastating impact on the family due to behavioral aspects. In approximately 40% of cases, there is a responsible gene, thus raising the issue of a family-impact pathology.
The etiology of Frontotemporal Dementia is multifactorial and involves a combination of genetic and environmental factors. The primary pathological markers are aggregates of tau, TDP-43, and FUS proteins in their various forms. Several causative genes—such as C9orf72, MAPT, GRN, FUS, and TDP-43—initially allowed for the definition of pathogenic mechanisms; however, for the majority of cases, the etiology remains unknown, involving an overlap of common neurodegenerative mechanisms (excitotoxicity, oxidative stress, neuroinflammation, and mitochondrial dysfunction)
The patient presents to the doctor often urged by the partner for various even severe behavioral manifestations also associated with nutritional variations with increased appetite that often lead erroneously to a psychiatric consultation. The personality alterations, the reduced empathy, the inappropriate language with inadequate social conduct evolve over time into a clinical picture difficult to manage. The forms instead of primary progressive aphasia express themselves with language difficulties not classifiable with other pathologies.
- Clinical assessment: anamnesis, neuropsychological tests and cognitive rating scale.
- Neuroimaging: Magnetic Resonance Imaging (MRI) to identify specific brain atrophy
- PET for the study of brain metabolism (FDG-PET)
- Genetics: research of the genes most involved in the pathology (MAPT, GRN, C9orf72, FUS, TARDBP)
- Biomarkers: cerebrospinal fluid analysis to detect the negativity of specific biomarkers of Alzheimer’s disease
Available therapies
- Symptomatic Drugs: cholinesterase inhibitors, serotonergic antidepressants (SSRIs), atypical antipsychotics, memantine.
- Experimental Therapies: anti-GRN antibodies.
- Non-pharmacological interventions: cognitive stimulation, TMS (Transcranial Magnetic Stimulation), physical activity and dietary approaches (Mediterranean diet).
Research in progress
- Identification of new biomarkers for early diagnosis.
- Genetic studies to better understand the role of hereditary factors in the disease.
- Personalized therapies based on the genetic and molecular profiles of patients.
- Definition of markers useful for the diagnosis of LATE (Limbic-predominant Age-related TDP-43 Encephalopathy).
Reference laboratory
Contacts and informations
Key Contacts: Vincenzo Silani, Federico Verde, Nicola Ticozzi, Barbara Poletti, Stefano Cappa, Alberto Doretti, Antonia Ratti
E-mail / Ph: vincenzo@silani.com / 02 61911 2937