At older age, a lower tau burden might be sufficient to produce a dementia syndrome due to the co-occurrence of other age-related pathologies (e.g., TDP-43, α-synuclein, or vascular pathology, [36, 37]) that contribute to cognitive decline (i.e., the “double-hit hypothesis” [38]) or to reduced efficiency of functional repair mechanisms associated with chronological aging that may magnify the cognitive consequences of tau pathology [16, 39]. This evidence concerns the gene TARDBP and Mental deterioration.