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)
Il paziente si presenta al medico spesso spinto dal compagno per manifestazioni comportamentali svariate anche gravi associate anche a variazioni nutrizionali con incrementato appetito che portano spesso erroneamente ad una consulenza psichiatrica. Le alterazioni di personalità, la ridotta empatia, il linguaggio inappropriato con condotte sociali inadeguate evolvono nel tempo in un quadro clinico difficilmemte gestibile. Le forme invece di afasia primaria progressiva si esprimono con difficoltà del linguaggio non inquadrabili con altre patologie.
- Valutazione clinica: anamnesi, test neuropsicologici e scala di valutazione cognitiva.
- Neuroimaging: Risonanza Magnetica (RM) per identificare atrofia cerebrale specifica
- PET per studio del metabolismo cerebrale (FDG-PET)
- Genetica: ricerca dei geni maggiormente implicati nella patologia (MAPT, GRN, C9orf72, FUS, TARDBP)
- Biomarcatori: analisi del liquido cerebrospinale per rilevare la negatività dei biomarcatori specifici della malattia di Alzheimer
Terapie disponibili
- 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).
Ricerca in corso
- 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).
Laboratorio di riferimento
Contatti e approfondimenti
Nome del referente: Vincenzo Silani, Federico Verde, Nicola Ticozzi, Barbara Poletti, Stefano Cappa, Alberto Doretti, Antonia Ratti
E-mail / Telefono: vincenzo@silani.com / 02 61911 2937
Link a risorse utili: Auxologico.it (Demenza Frontotemporale)