BackgroundThe epidemiologic study of comorbidities of an index health problem represents a methodological challenge. This study cross-sectionally describes and analyzes the comorbidities associated with dementia in older patients and reviews the existing similarities and differences between identified comorbid diseases using the statistical methods most frequently applied in current research.MethodsCross-sectional study of 72,815 patients over 64 seen in 19 Spanish primary care centers during 2008. Chronic diseases were extracted from electronic health records and grouped into Expanded Diagnostic Clusters®. Three different statistical methods were applied (i.e., analysis of prevalence data, multiple regression and factor analysis), stratifying by sex.ResultsThe two most frequent comorbidities both for men and women with dementia were hypertension and diabetes. Yet, logistic regression and factor analysis demonstrated that the comorbidities significantly associated with dementia were Parkinson’s disease, congestive heart failure, cerebrovascular disease, anemia, cardiac arrhythmia, chronic skin ulcers, osteoporosis, thyroid disease, retinal disorders, prostatic hypertrophy, insomnia and anxiety and neurosis.ConclusionsThe analysis of the comorbidities associated with an index disease (e.g., dementia) must not be exclusively based on prevalence rates, but rather on methodologies that allow the discovery of non-random associations between diseases. A deep and reliable knowledge about how different diseases are grouped and associated around an index disease such as dementia may orient future longitudinal studies aimed at unraveling causal associations.