The results showed that the MES may be a suitable screening method for MCI and mild dementia. First, time was saved as the most involved cognitive domains were evaluated selectively; second, the score range for memory and executive function was large enough to identify MCI; third, it was independent of pencil and paper, and reading and writing skills were not required of subjects. Hence, education was not a factor with the MES score.
In order to reach our aim, much preliminary work was carried out. With regard to the memory materials in the neuropsychological tests, the sentence, rather than word list, is more suitable for the illiterate and low-educated people. Lengths of sentences and numbers of trials and recalls were determined by careful consideration and repeatable pilot studies. Second, as implicit memory is relatively preserved for mild AD patients [38
], memory materials chosen were unfamiliar. Person (Li Xiao-ming) and place names (He-xi town and Yong-an county) were imaginary. Third, auditory memory material appeared to be more sensitive than visual material for the Chinese elderly [26
]. Delayed recall of episodic memory may be the most sensitive predictor for AD, but only long delay recall, easily producing floor effects, was not applied to evaluate severity of memory damage and cognitive change at follow-up. Accordingly, in our study, the summation of immediate and delayed recall performances was the indicator for the memory factor.
For patients with AD, executive function was another cognitive domain involved in addition to memory function, and the initial damaged domain for FTLD and VaD patients. In the beginning of the process of compiling the MES, we searched for various executive memory tests independent of pencil and paper in the literature [35
]. The initial tests included the Category Fluency Test,the Object Figure Naming and Sorting Test, the Conflicting Instructions Task, the Go/No Go Task, the Sequential Movement Tasks, the Oral Symbol Digit Modality Test, Stroop Color Words Test, the Similarities Test, the Proverbs Test, the Wisconsin Card Sorting Test, the California Cards Sorting Test, the Tower of London or Tower of Hanoi, and the Paced Auditory Serial Addition Test. Preliminary application and verification were undertaken. Considering the rate, reliability and validity of accomplishment, we selected the Conflicting Instructions Task, the Go/No Go Task, the Sequential Movement Tasks and the Verbal Fluency Test as the subtests of the MES-EX. The tests could be used for the two usual components of executive function including the set shift and dominant inhibition. The MES ratio (MES-5R/MES-EX) may apply for distinguishing between AD and FTLD or VaD. There is one point that we should emphasize, namely, that the four subtests of the MES-EX are similar to the four tests of the frontal assessment battery( FAB) [41
] in the meaning of the tests, but the concrete operations, procedure and scoring standard are different.
The MES was related to aging. Many studies have shown that executive function may decrease with increasing age [42
]. Level of education was not related to MES performance. In western countries, the education level for the elderly is generally high, and the focus of researchers may be the effects of age and gender on neuropsychological tests. However, in a developing country like China, illiterate persons remain a significant proportion of the population. According to the sixth population censuses in 2010, of the total population, the proportion of persons with education exceeding university level accounted for 8.7%, senior high school for 13.7%, junior high school for 37.9%, and primary school for 26.2%, while the illiteracy rate was 13.5%. The numbers of elderly with low levels of education was therefore expected to be large. As the result, it was necessary to compile tests suitable for people with low education levels. In our sample, there were quite a lot of persons with low education levels, or even illiterate, and also individuals with high education levels and university careers. The statistical results showed that the MES was independent of education and knowledge. As the subtests were the items independent of reading and writing, the MES may be used for cross-cultural comparison of different countries.
At present, there have been few studies about the MCI subtypes of single-domain and. multiple-domain mild cognitive impairment [44
]. Newer prospective studies show that multiple-domain MCI (particularly amnestic) confers greater risk of progression to dementia than single-domain MCI, even when examining multiple domains of MCI [45
]. Those with single-domain MCI and naMCI (non-amnestic MCI) have a relatively high rate of reversion to normal cognition [48
]. Mitchell et al. [50
]discovered that of the multi-domain MCI group, 59% progressed to dementia and only 5% improved. By contrast, in pure aMCI, only 18% progressed and 41% improved by two-year follow-up. These findings may simply reflect a threshold/definitional effect, in that multiple-domain impairment represents more advanced disease than single-domain impairment and is closer to the dementia threshold, that is, the outcome of interest is very similar to the predictor. As a result, differentiation of MCI subtypes has been necessary. The MES test, as a tool to identify single-domain and multiple-domain subtypes at a given point, may be helpful for the prognosis of MCI.
Total time for MES administration and scoring averages approximately seven minutes, similar to the time for the MMSE or DemTect and notably less than that of the MoCA and the seven minute neurocognitive screening battery (which actually needs 12 minutes).
As a screening test, the content of items of the MES is different from other common neuropsychological tests such as the MMSE, the Mini-Cog, and the ADAS-cog [51
], and could be administered together with those tests. As a part of the annual health check for the elderly, the MES could also be performed alongside other routine measurements (height, weight, and blood pressure) as a measurement of objective cognitive function. The MES would increase the probability of earlier diagnosis and improve ability to monitor change over time and treatment response in clinic outpatients. The feasibility of the MES as a follow-up tool has been validated in the process.