Cognitive Assessment Tools for Screening Older Adults With Low Levels of Education: A Critical Review

Introduction: Cognitive assessment of older adults who are either illiterate or with low levels of education is particularly challenging because several battery tasks require a certain educational background. Early detection of mild cognitive impairment (MCI) in the elderly using validated screening tools is of great importance since this population group could benefit from new drugs that are being investigated for the treatment of dementias. Cutoff scores for psychometric properties of cognitive tests are not well established among adults with low levels of education. The present study aimed to critically review the literature on cognitive assessment tools for screening cognitive syndromes including MCI and Alzheimer’s disease (AD) in older adults with low levels of education. Methods: We conducted a systematic search of MEDLINE, LILACS, Cochrane, and SCOPUS electronic databases of cross-sectional and prospective studies with adults over 55 years of age. Results: We found a significant number of assessment tools available (n = 44), but only a few of them showed diagnostic accuracy for the diagnosis of MCI and AD in older adults with low levels of education: the Mini-Mental State Exam; the Montreal Cognitive Assessment; the Persian Test of Elderly for Assessment of Cognition and Executive Function; the Six-Item Screener; and the Memory Alteration Test. Few studies evaluated individuals with low levels of education, with a wide range of cutoff scores and cognitive test batteries. Conclusion: We found that a small number of studies evaluated adults with 4 years of formal education or less. Our findings further support the importance of developing specific tools for the assessment of older adults with low levels of education.


INTRODUCTION
Dementia is characterized by cognitive impairment and loss of function (1). The growth of population aging over the past few decades has been associated with an increase in cognitive disorders. Data from Alzheimer's Disease International (ADI) shows there were 46.8 million people living with dementia worldwide in 2015, and it is estimated this number will be 74.5 million in 2030 and 131.5 million in 2050. Alzheimer's disease (AD) is the most common form of dementia and accounts for 50-70% of dementia cases. There were an estimated 26 million people living with AD in 2015 and it is believed there will be as many as 41 million by 2030 and 72 million by 2050 (1).
Mild cognitive impairment (MCI) is the intermediate stage between cognitive decline of healthy aging and dementia (2). The prevalence of MCI is 12-18% among adults over 65 years of age and the annual progression rates from MCI to AD are 10-15% (3,4). Early detection of MCI in the elderly using validated screening tools is of great importance since this population group could benefit from new drugs that are being investigated for the treatment of neurodegenerative diseases including AD. Furthermore, evidence shows that, since MCI is a transitional phase between normal aging and AD, there is less brain involvement and those affected are more likely to benefit from drug therapies (5,6).
Cognitive assessment tools are commonly used for screening impairment, differential diagnosis, determining disease severity, as well as monitoring disease progression in patients (7). A major challenge for the initial assessment of age-related cognitive changes is to find a screening tool that is both sensitive and specific for differential diagnosis of cognitive impairment. Both ceiling effects and floor effects limit the ability of a test or some of its items to accurately assess cognitive decline (8). These effects have been reported in several studies and they are primarily related to educational background (9). The ceiling effect occurs when score distribution is skewed and a measurement is determined by the proportion of people scoring at the high end, thereby preventing to detect health improvements. The opposite is the floor effect that occurs when a measurement is determined by the proportion of people scoring at the low end, thereby preventing to detect health declines (10).
Another important aspect is to have available free, easy-to-use assessment tools that do not require specialized training and have the ability to accurately discriminate cognitive decline in adults with normal aging, MCI, and dementia (4). Cognitive assessment of older adults who are either illiterate or with low levels of education is particularly challenging because several battery tasks require a certain educational background (11)(12)(13). There are an estimated 758 million illiterate adults in the world (11) and 13 million people are estimated to be illiterate in Brazil (11). Prospective cohort studies have shown an association between low education and higher risk of developing AD (14)(15)(16)(17). Yet, few studies have examined the performance of cognitive assessment tools in adults with low education.
Cutoff scores for psychometric properties of cognitive tests are not well established among adults with low levels of education. Furthermore, there is a scarcity of studies evaluating assessment tools for screening older adults with low levels of education. A better understanding of the accuracy of different cognitive batteries is crucial for early diagnosis and intervention, and epidemiological studies are needed to further explore how education background affects an individual's performance on different cognitive dimensions.
The present study aimed to critically review the literature on cognitive assessment tools for screening cognitive syndromes including MCI and AD in older adults with low levels of education.

METHODS
An integrative literature review was conducted to gather and summarize the body of evidence available from original articles. This integrative review study included six stages: Step 1-formulation of the central research question (theme identification); Step 2-definition of inclusion and exclusion criteria and literature search; Step 3-categorization of primary studies (definition of data to be extracted from the selected studies); Step 4-assessment of the studies included; Step 5interpretation of results; Step 6-knowledge synthesis of the results obtained from the studies assessed (18)(19)(20).
The central research question was formulated using the PVO method where P is the study population (adults over 55 years of age with low education, i.e., 4 years of formal education or less); V is the variable (cognitive assessment tools); and O is the outcome (MCI and AD).
The guiding question of our review was: "Which assessment tools are used for cognitive screening of MCI or AD in older adults with low levels of education?" The inclusion criteria were English language articles in the electronic databases Medical Literature Analysis and Retrieval System Online (MEDLINE), Latin American and Caribbean Health Sciences Literature (LILACS), Cochrane, and SCOPUS; cross-sectional or prospective design; outpatient or population-based samples of adults over 55 years of age with low education (4 years of education or less); and assessment of the use of cognitive tools for MCI or AD diagnosis. We did not search the following information sources for this review: guidelines; institutional protocols; self-administered or telephonebased cognitive assessment instruments; and studies that used cognitive assessment instruments for diagnosing other psychiatric or neurological conditions. The publications were individually searched and selected by two investigators during June and July 2019.
The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines (21) were used as a basis for the search and selection of studies (Figure 1). A questionnaire was developed to help data extraction (22). Two matrices were constructed to present the results: the first one included study characteristics and the second one included cognitive tools and main results reported.
A search strategy was created to conduct searches in the following databases: MEDLINE via PubMed from the US National Library of Medicine; LILACS; Cochrane; and SCOPUS via Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) with no time restriction. To expand our search, we chose to use natural controlled language. The following descriptors (bold), synonyms, natural language, and Boolean operators were used to cross-check the databases: MEDLINE (Medical Subject Headings [MeSH]: search strategy-(aged or elderly or old or elder) and (literacy or illiteracy or education or "low education") and ("mental status and dementia tests" or tool or instrument or status or test) and ("Alzheimer disease" or alzheimer´s) and ("mild cognitive impairment" or "cognitive dysfunction").
To minimize selection bias (misinterpretation of results and study design), the literature search and data extraction were conducted by two investigators independently and any discrepancies were resolved by consensus. Figure 1 shows the flowchart of the study selection process according to the PRISMA guidelines. A total of 2,086 articles were retrieved and read. Thirty-six studies were selected for our review. Table 1 describes the studies assessed. The sample sizes ranged from 50 to 10,432 participants. The studies were conducted in 17 countries, and most of them (13.88%) were from China and Spain.

RESULTS
A wide range of cognitive assessment tools (n = 44) were used for MCI and AD diagnosis ( Table 1)      The studies included in our review evaluated adults with different educational backgrounds. However, detailed information was not available in all studies. Adults with AD had 1.69 (51) to 7.6 years (29) of schooling and those with MCI had 2.53 (38) to 10.93 years (33) of schooling. The proportion of illiterate adults ranged from 1.8% (35) to 32.1% (23).
The Persian Test of Elderly for Assessment of Cognition and Executive Function (PEACE) was used in one study (28) to establish cutoff scores in individuals with AD. The sample consisted of 38 subjects with AD; some of them were illiterate (proportion not available). A cutoff score of 67.5 was set (sensitivity = 75.8%; specificity = 97.4%). The Six-Item Screener (SIS) was used in another study (25) that evaluated 440 individuals with MCI with a small proportion of individuals (< 25%) with low education (< 6 years of schooling). The SIS showed low sensitivity for screening MCI in this population (sensitivity = 34.3%; specificity = 90.1%). The Memory Alteration Test (MAT) was used in a single study (38) for discriminating MCI and AD from healthy individuals. The AUC of MAT to discriminate between early AD and amnestic mild cognitive impairment (aMCI) was 99.60% (sensitivity = 100.00%; specificity = 97.53%) and to discriminate between aMCI and controls was 99.56% (sensitivity = 99.17%; specificity = 91.11%). The mean score was 17.54 ± 4.67 for individuals with AD, 30.53 ± 2.54 for individuals with MCI and 41.97 ± 2.6 for healthy individuals. AD and MCI individuals and controls had on average 2.65 ± 1.28, 2.53 ± 1.46, and 2.57 ± 1.45 years of education, respectively.
In this review, six studies ( Table 2) assessed cutoff scores of the MMSE for adults with 4 years of education or less (25,36,38,40,45,48). MCI cutoff scores (SD) ranged from 17.8 (1.9) to 21.36 (0.98), but there was great variation in sensitivity and specificity. The Montreal Cognitive Assessment-Basic (MoCA-B) was evaluated in three studies (45,55,57). One of these studies established a cutoff score of 19 for detecting MCI, with 87.9% sensitivity and 81.0% specificity (55). Another one reported a cutoff score (SD) of 21.3 (3.8) for detecting MCI in adults with 4 years of education or less (45). Cutoff scores (SD) for AD ranged from 12.64 (3.78) to 18.32 (2.78) in these same studies. Another cognitive test battery reported was the Addenbrooke's Cognitive Examination Revised (ACE-R), which was used in only one study but the cutoff score was not adjusted for low educational level. Mean ACE-R scores were 78.12 (12.79) for controls and 53.20 (14.76) for AD. This tool showed good diagnostic accuracy for diagnosing AD (AUC = 0.897) (25).

DISCUSSION
We carried out a critical review of cognitive assessment tools for screening cognitive syndromes in older adults with low levels of education. A significant number of assessment tools (n = 44) were used in the studies reviewed, but only a few of them showed diagnostic accuracy for the diagnosis of MCI and AD in adults with low education including MMSE, MoCA, PEACE, SIS, and MAT. The latter three were each used in one study only.
It is crucial to validate cognitive assessment instruments in populations with low education and to establish cutoff scores for screening these individuals in daily clinical practice. It would enable to monitoring healthy aging in such a quite large population (11) and evaluate older adults with low levels of education who are at risk of developing dementia syndromes (61). Besides, it could offer new insights to better understand the influence of education on cognitive reserve since there is a relationship between literacy and the functional organization of the human brain. Literacy acquisition improves early visual processing and phonological information processing (62). Indeed, functional neuroimaging studies have evidenced that large neural networks in both cerebral hemispheres have less functional connections in less educated individuals (63). Since there has been a move toward the development of diseasemodifying drugs for AD, it will be paramount to have validated diagnostic tools for population-based assessments including older adults with low levels of education (64).
In agreement with literature reports, the MMSE was the most frequently used cognitive tool in the studies assessed (65). The MMSE is easy to administer and requires no specialized training and it has been validated in many countries (66). We assessed in our review a study that showed good agreement of the MMSE for cognitive screening (κ = 0.86) between primary care and specialist practitioners (44). However, studies have demonstrated the effect of education on MMSE scores. The MMSE has low sensitivity for MCI, does not perform well in assessing executive functions and has limiting floor and ceiling effects (9,23,40). A study conducted in Brazil has established MMSE cutoff scores of 20 for illiterate adults and 25 for those with 4 years of education or less (67).
The second most frequently used cognitive tool was the MoCA. The MoCA is a cognitive battery that includes tests sensitive to executive functions and has higher sensitivity for diagnosing MCI (24,33,68). However, MoCA scores are strongly influenced by educational background as MoCA tasks are designed for a certain level of education making it difficult to assess individuals who are either illiterate or with low levels of education (30). Therefore, a MoCA basic version (MoCA-B) was developed to include tasks designed to assess the same cognitive domain regardless of the level of education (45,60,68).
A systematic review of cognitive screening tools showed that the ACE-R is an outstanding test battery. It takes approximately 20 minutes to be administered and it includes tasks designed for different levels of schooling (52,58). In our review, ACE-R cutoff scores for low education were not available.
The studies assessed included recommendations of specific cutoff scores and scales for diagnosis of MCI and AD in adults with low levels of education. One study using the MoCA-B suggested a cutoff score of 19 (55) for MCI diagnosis. For AD, one study showed a cutoff score of 23.5 (30) for the MMSE and another study suggested a cutoff score of 17 (41) for the MoCA.
The scarcity of cognitive assessment tests for evaluating adults with low levels of education is in line with the challenge of assessing cognitive function in individuals with low education (13). Individuals with low levels of education were excluded from many studies because there are no cutoff scores established for several assessment tools. Literacy acquisition increases performance in certain cognitive domains such as executive functions (14), improves visual processing, changes phonological codes, and strengthens the link between phonemic and graphic representation (62) However, to measure literacy through the number of years of formal education is not the most effective approach since there are so many different ways of learning even without attending school (12,62). This review study has some limitations that deserve mention. First, no information was available on the diagnostic accuracy of cognitive tools for MCI and AD. Furthermore, little information was available on the diagnostic accuracy of tools for assessing different MCI subtypes and stages of AD. Another caveat is that our search was limited to cognitive assessment tools that require a trained examiner and excluded self-administered and webbased screening tools. Besides, there is no consensus about the definition of low levels of education, which may partly explain heterogeneous results of the cognitive batteries evaluated. Lastly, the studies included this review applied various diagnostic criteria for AD, which prevented comparisons of results across them.

CONCLUSIONS
The use of cognitive assessment tools that are easy to administer is still challenging given the high prevalence of low education in the global population. This review provides an overview of the most commonly used instruments for cognitive screening. We found that a small number of studies evaluated adults with 4 years of formal education or less and a wide range of cutoff scores for various cognitive test batteries. Our findings further support the need for the development of specific tools for assessing illiterate adults. Cognitive ability, formal logic, and abstract reasoning should be assessed as they could provide more accurate input for screening and interpretation of cognitive tests in older adults who are either illiterate or with low levels of education. Low-cost test batteries that are easy to administer should be validated because they can make a significant impact on screening of cognitive syndromes and enable early therapeutic interventions aimed at reducing morbidity and mortality of dementia. Further studies of test batteries adjusted to larger groups of adults with low levels of education and specific MCI subtypes and AD stages could help shed light on these points.