PURPOSE The aim of this paper was to explore the applicability of dementia clinical guidelines (CGs) to older patients, to patients with one or several comorbidities, and to both targets in order to evaluate if an association between the applicability and quality of the CGs exists. MATERIALS AND METHODS A systematic search strategy conducted on electronic databases identified CGs on diagnosis and treatment of dementia published from 2000 to 2013. In addition, websites of organizations devoted to the treatment and awareness of dementia were searched. The quality of evidence was assessed using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. Two investigators independently scored the relevance of the CGs by means of a specific tool. Descriptive and inferential analyses were performed (Mann-Whitney test, 0.05 α-level). RESULTS Twenty-two CGs met our inclusion criteria. On average, the quality of the CGs was higher than 70% in three of six domains measured by the AGREE tool. The domains with lower mean scores (less than 50%) were "Applicability" and "Editorial independence". Considering applicability to older patients, 20 CGs (91%) addressed issues of treatment for older patients, five of them (23%) classified older patients by age, and 13 CGs (60%) addressed issues of comorbidity. Only seven (32%) discussed the quality of evidence for patients with multiple comorbid conditions. Thirteen CGs (60%) reported recommendations for patients with at least one comorbid condition, while seven of them (32%) reported on several comorbid conditions. No statistically significant association between CG quality and relevance to care of older people with or without comorbidity was found (P>0.05). CONCLUSION This study showed that dementia CGs poorly address treatment for older patients with comorbidities, regardless of their quality. Therefore, they scarcely satisfy the need of modern clinical practice.