Several authors have recently shown that anterograde amnesia is often associated with semantic memory impairment in amnesic MCI patients. Similarly, after the MCI condition, some patients who convert to Alzheimer's disease (AD) show the classic onset (cAD) characterized by the impairment of memory and executive functions, whereas other AD patients show isolated defects of episodic and semantic memory without deficits in other cognitive domains. The latter have been considered an AD variant characterized by ‘focal Temporal Lobe Dysfunction’ (TLD). The aim of the present study was to assess the differences in disease progression between cAD and TLD. For this purpose a continuous series of newly diagnosed probable AD patients presenting as cAD (n = 30) and TLD (n = 25), matched for severity, and 65 healthy controls underwent a comprehensive neuropsychological evaluation at baseline; TLD and cAD were re-evaluated at a 24-month follow-up. At follow-up, TLD patients showed no significant worsening of cognitive functions, whereas cAD subjects displayed a significant worsening in all explored cognitive domains. In conclusion, our results confirm that probable AD presenting as TLD represents a specific onset of AD characterized by a slower rate of progression. (JINS, 2012, 18, 144–150)