This study of CI and DEM screening test assessment in an urban population with a low educational level shows that MMSE is not very useful for DEM screening, despite its widespread utilization. Its results were improved by adopting the correction criteria proposed by Escribano-Aparicio et al for populations with low educational level, but they remained significantly inferior to those obtained with Phototest and MIS.
Phototest, a short instrument that is rapid and easy to use, showed a substantial diagnostic concordance for DEM, correctly classifying 86% of the study sample, similar to the percentage obtained using MIS with a cutoff score of 3/4. However, unlike Phototest, MIS requires reading ability and could not be applied to an appreciable proportion of our study population (16.4%).
Although all instruments were significantly less useful for CI than for DEM, Phototest correctly classified 78% of patients as CI or non-CI, a similar percentage to that obtained with MIS. MMSE was the least useful instrument to screen for CI.
To our knowledge, this is the first study of CI and DEM screening tests to evaluate the costs associated with utilization of the test instruments. MMSE was associated with significantly higher costs for both DEM and CI, with no significant difference in the costs of Phototest and MIS. Considering the whole study sample, there was a difference between Phototest and the optimal MMSE approach of 13,807.3 € for CI screening and 9,468 € for DEM. Extrapolation of this difference to the whole population served by the unit (i.e., around 500,000 versus 66,713 subjects) indicates that the use of Phototest instead of MMSE would yield savings of around 70,000-135,000 € per year at present prices. Although the present study is not strictly a cost-effectiveness analysis , it can be concluded from our data on effectiveness and costs that Phototest is the best option for CI and DEM screening, offering higher effectiveness at lower cost in comparison to MMSE and allowing the assessments of all subjects, unlike MIS. This is valuable information for the efficient allocation of resources when these are limited .
The fact that MIS cannot be used with illiterates may appear irrelevant given the tendency to an improvement in educational level and the aim of universal literacy . However, illiteracy remains a worldwide problem, with over 750 million illiterates in 2010 , and it is not limited to underdeveloped countries, affecting 3% of adults in the USA. i.e., around 7 million people . Account must also be taken of the increasing frequency of "relative illiteracy" derived from emigration and tourism , resulting in large numbers of people who are literate in their mother tongue and can express themselves verbally in the language of their country of residence but have inadequate reading skills in the new language for assessment with instruments that require this ability. This situation is considered to affect 2% of adults in the USA, i.e., around four million people . In short, instruments that do not require reading skills remain necessary to assess the whole population.
The main strengths of this study are the prospective, consecutive, and systematic nature of the recruitment, the long study period, the virtual absence of exclusion criteria, and the low loss index. As a result, the study sample is a faithful reflection of the diagnostic challenges faced under routine clinical conditions in this field of care, making the study naturalistic and pragmatic and allowing robust results that can be considered effectiveness rather than efficacy estimators. Furthermore, the main biases in diagnostic test assessment studies  were avoided by the fact that all subjects underwent all screening tests, all received a gold standard diagnosis, regardless of their screening test results, and the screening test results and gold standard diagnoses were all evaluated in a blinded and independent manner.
One study limitation is that it may not be possible to extrapolate the results, especially those for the MMSE, to more educated populations. The low specificity of MMSE was undoubtedly due to the low educational level of our sample. This shortcoming is avoided by the Phototest, whose results are not affected by educational level . The present results for the overall usefulness of the Phototest are virtually identical to those obtained in a previous multicenter study (FOTOTRANS study) conducted under routine clinical conditions, which used the same cutoff points and found a sensitivity of 0.88 and specificity of 0.87 for DEM, and sensitivity of 0.68 and specificity of 0.89 for CI [25, 26]. In the FOTOTRANS study, the diagnostic accuracy of the Phototest was similar to that of the Eurotest , another valid and reliable cognitive test applicable to illiterates and developed by our group [48, 49]. However, the Eurotest requires 7 minutes to complete and is therefore less useful in PC, in which time constraints are crucial .
The present results found for MIS with a cutoff point of 3/4 are also very similar to the findings by Perez-Martinez et al in a prospective clinical sample with low educational level (Sn = 0.93, Sp = 0.73)  but differ from those reported in two other studies (Sn = 0.74, Sp = 0.96, and Sn = 0.84, Sp = 0.94, respectively) [19, 20]. In these two studies, the specificity was higher than the sensitivity, possibly because of the different cutoff point used (4/5), the cross-sectional design of the studies, and the higher overall educational level of the samples, which did not include subjects with CI, facilitating the discrimination between DEM and non-DEM and therefore overestimating the diagnostic usefulness.
Although our sample size may appear to be a limitation, it allowed the precise estimation of proportions (6-8%). Furthermore, the use of a one-year recruitment period allowed seasonal biases to be avoided and ensured greater sample representativeness.
Finally, our economic analysis was simplistic and basic and cannot strictly be considered a cost-effectiveness study . Nevertheless, our approach to minimum costing was real and pragmatic and allowed differential costs to be established among the different screening test options. Our data should facilitate decision-making to improve the assignment of resources. In this regard, our results suggest that MMSE is not suitable for use in our setting and that MIS and Phototest are preferable due to their lower cost and higher effectiveness. The Phototest can be especially recommended because, unlike the MIS, it can be completed by all subjects, including the illiterate.