Goal: To measure Health Related Quality of Life (HRQoL) in people with different primary degenerative dementias and compare them with 50+ years old older individuals with mild cognitive impairment (MCI) and healthy controls (HCs). Materials and Methods: In all, 45 participants suffered from Alzheimer’s disease (AD) dementia, 27 from Lewy body dementia (LBD), 17 from frontotemporal dementia (FTD), 43 from MCI, and 31 HCs (n = 163). The 12-Item Short Form Health Survey, version 2 (SF-12-v2) and Mini Mental State Examination were administered. Reisberg’s Global Deterioration Scale (GDS) was completed by a neurologist. HRQoL indices obtained via the SF-12-v2 were compared between different subgroups. Results: Physical Function, Physical Role, Emotional Role, and Physical Summary Composite scores showed the best scores for patients with AD, followed by HC and MCI, and finally FTD and LBD. Discussion: A differentiated profile in HRQoL is shown in dementia subgroups, and may be useful to support differential diagnosis