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1.  Diagnostic Validity of Age- And Education-Corrections for the Mini-Mental State Examination (MMSE) in African American Elders 
Objectives
To investigate whether demographic (age and education) adjustments for the Mini-Mental State Examination (MMSE) attenuate mean score discrepancies between African American and Caucasian adults, and to determine whether demographically-adjusted MMSE scores improve the diagnostic classification accuracy of dementia in African American adults when compared to unadjusted MMSE scores.
Design
Cross-sectional study.
Setting
Community-dwelling adults participating in the Mayo Clinic Alzheimer’s Disease Patient Registry (ADPR) and Alzheimer’s Disease Research Center (ADRC).
Participants
Three thousand two hundred fifty-four adults (2819 Caucasian, 435 African American) aged 60 and older.
Measurements
MMSE at study entry.
Results
African American adults obtained significantly lower unadjusted MMSE scores (23.0 ± 7.4) compared to Caucasian adults (25.3 ± 5.4). This discrepancy persisted despite adjustment of MMSE scores for age and years of education using established regression weights or newly-derived weights. However, controlling for dementia severity at baseline and adjusting MMSE scores for age and quality of education attenuated this discrepancy. Among African American adults, an age- and education-adjusted MMSE cut score of 23/24 provided optimal dementia classification accuracy, but this represented only a modest improvement over an unadjusted MMSE cut score of 22/23. The posterior probability of dementia in African American adults is presented for various unadjusted MMSE cut scores and prevalence rates of dementia.
Conclusion
Age, dementia severity at study entry, and quality of educational experience are important explanatory factors to understand the existing discrepancies in MMSE performance between Caucasian and African American adults. Our findings support the use of unadjusted MMSE scores when screening African American elders for dementia, with an unadjusted MMSE cut score of 22/23 yielding optimal classification accuracy.
doi:10.1111/j.1532-5415.2011.03766.x
PMCID: PMC3288600  PMID: 22150301
MMSE; African American; ethnicity; dementia; cognition
2.  Diagnostic Accuracy of the MMSE in Detecting Probable and Possible Alzheimer's Disease in Ethnically Diverse Highly Educated Individuals: An Analysis of the NACC Database 
Background.
To validate and extend the findings of a raised cut score of O’Bryant and colleagues (O’Bryant SE, Humphreys JD, Smith GE, et al. Detecting dementia with the mini-mental state examination in highly educated individuals. Arch Neurol. 2008;65(7):963–967.) for the Mini-Mental State Examination in detecting cognitive dysfunction in a bilingual sample of highly educated ethnically diverse individuals.
Methods.
Archival data were reviewed from participants enrolled in the National Alzheimer's Coordinating Center minimum data set. Data on 7,093 individuals with 16 or more years of education were analyzed, including 2,337 cases with probable and possible Alzheimer's disease, 1,418 mild cognitive impairment patients, and 3,088 nondemented controls. Ethnic composition was characterized as follows: 6,296 Caucasians, 581 African Americans, 4 American Indians or Alaska natives, 2 native Hawaiians or Pacific Islanders, 149 Asians, 43 “Other,” and 18 of unknown origin.
Results.
Diagnostic accuracy estimates (sensitivity, specificity, and likelihood ratio) of Mini-Mental State Examination cut scores in detecting probable and possible Alzheimer's disease were examined. A standard Mini-Mental State Examination cut score of 24 (≤23) yielded a sensitivity of 0.58 and a specificity of 0.98 in detecting probable and possible Alzheimer's disease across ethnicities. A cut score of 27 (≤26) resulted in an improved balance of sensitivity and specificity (0.79 and 0.90, respectively). In the cognitively impaired group (mild cognitive impairment and probable and possible Alzheimer's disease), the standard cut score yielded a sensitivity of 0.38 and a specificity of 1.00 while raising the cut score to 27 resulted in an improved balance of 0.59 and 0.96 of sensitivity and specificity, respectively.
Conclusions.
These findings cross-validate our previous work and extend them to an ethnically diverse cohort. A higher cut score is needed to maximize diagnostic accuracy of the Mini-Mental State Examination in individuals with college degrees.
doi:10.1093/gerona/gls006
PMCID: PMC3403860  PMID: 22396476
Alzheimer's disease; Dementia diagnosis; Ethnicity; Language; Mini-Mental State Examination
3.  The usefulness of the Korean version of modified Mini-Mental State Examination (K-mMMSE) for dementia screening in community dwelling elderly people 
BMC Public Health  2004;4:31.
Background
We assessed whether the Korean version of modified Mini-Mental State Examination (K-mMMSE) has improved performance as a screening test for cognitive impairment or dementia in a general population compared with the Korean Mini-Mental State Examination (K-MMSE).
Methods
Screening interviews were conducted with people aged 65 and over in Noam-dong, Namwon-city, Jeonbuk province. There were 522 community participants, of whom 235 underwent clinical and neuropsychological examination for diagnosis of dementia and Cognitive Impairment No Dementia (CIND). Sensitivity, specificity and areas under the receiver operating characteristic (ROC) curves for the K-mMMSE and the K-MMSE were the main outcome measures.
Results
Cronbach's alpha for the K-mMMSE was 0.91, compared with 0.84 for the K-MMSE. The areas under the ROC curves in identifying all levels of CIND or dementia were 0.91 for the K-mMMSE and 0.89 for the K-MMSE (P < 0.05). For the K-mMMSE, the optimal cut-off score for a diagnosis of CIND was 69/70, which had a sensitivity of 0.86 and a specificity of 0.79, while, for a diagnosis of dementia, the optimal cut-off score of 59/60 had a sensitivity of 0.91 and a specificity of 0.78. The K-mMMSE also had a high test-retest reliability (r = 0.89).
Conclusion
Our findings indicate that the K-mMMSE is more reliable and valid than the K-MMSE as a cognitive screen in a population based study of dementia. Considering the test characteristics, the K-MMSE and modified version are expected to be optimally used in clinical and epidemiologic fields.
doi:10.1186/1471-2458-4-31
PMCID: PMC509251  PMID: 15283869
4.  Mini-Mental State Examination in patients with hepatic encephalopathy and liver cirrhosis: a prospective, quantified electroencephalography study 
BMC Gastroenterology  2013;13:107.
Background
Mini-Mental State Examination (MMSE) is one of the most commonly used methods in the assessment of cognitive mental status. MMSE has been used in hepatology but its usefulness in the evaluation of hepatic encephalopathy (HE) has never been properly assessed. The aim of the study was to investigate the value of MMSE in detection of HE in patients with cirrhosis.
Methods
One hundred and one consecutive patients with liver cirrhosis underwent neurological examination, MMSE and electroencephalography (EEG). Spectral analysis of EEG was done with calculation of mean dominant frequency (MDF) and relative power of delta, theta, alpha and beta rhythms. Minimal HE was diagnosed in patients with normal neurological status and alterations in spectral EEG. Statistical analysis included Fisher’s exact and Anova analysis. Categorical data were compared using Levene’s test for equality of variances. Correlation-coefficient analysis was performed by the Pearson’s r or Z-test, as needed. Tests performance was assessed by the calculating the area under the ROC curve (AUC) and evaluating its difference from reference area (AUC=0.5). A p value <0.05 was considered statistically significant.
Results
Overt HE was identified in 49 (48.5%) and minimal HE in 22 (21.8%) patients. Although there were significant correlations between both severity of liver disease (Child-Pugh classification), overt HE (West-Haven criteria) and various MMSE items, MDF showed no correlation with any of MMSE items as well as MMSE summary score. MMSE (score and items) did not discriminate patients without HE and minimal HE. The only significant differences between patients without HE and with overt HE were seen in respect of MMSE score (p<0.02), orientation to place (p<0.003), repetition (p<0.01) and complex commands-understanding (p<0.02). Test performance analysis has shown that MMSE has no value as a prediction method in determining minimal HE and in respect of overt HE has a sensitivity of 63% and specificity of 52% by a cut-off level at 27.5 points to diagnose overt HE.
Conclusions
In conclusion, although MMSE score and single items are altered in patients with overt HE, MMSE has no value in the assessment of minimal HE. Because MMSE could be impaired in several cognitive dysfunctions, more specific test should be used for measuring HE.
doi:10.1186/1471-230X-13-107
PMCID: PMC3716589  PMID: 23815160
Liver cirrhosis; Hepatic encephalopathy; Mini-mental state examination; Electroencephalography; Frequency analysis
5.  Validity of the MoCA and MMSE in the detection of MCI and dementia in Parkinson disease 
Neurology  2009;73(21):1738-1745.
Background:
Due to the high prevalence of mild cognitive impairment (MCI) and dementia in Parkinson disease (PD), routine cognitive screening is important for the optimal management of patients with PD. The Montreal Cognitive Assessment (MoCA) is more sensitive than the commonly used Mini-Mental State Examination (MMSE) in detecting MCI and dementia in patients without PD, but its validity in PD has not been established.
Methods:
A representative sample of 132 patients with PD at 2 movement disorders centers was administered the MoCA, MMSE, and a neuropsychological battery with operationalized criteria for deficits. MCI and PD dementia (PDD) criteria were applied by an investigator blinded to the MoCA and MMSE results. The discriminant validity of the MoCA and MMSE as screening and diagnostic instruments was ascertained.
Results:
Approximately one third of the sample met diagnostic criteria for a cognitive disorder (12.9% PDD and 17.4% MCI). Mean (SD) MoCA and MMSE scores were 25.0 (3.8) and 28.1 (2.0). The overall discriminant validity for detection of any cognitive disorder was similar for the MoCA and the MMSE (receiver operating characteristic area under the curve [95% confidence interval]): MoCA (0.79 [0.72, 0.87]) and MMSE (0.76 [0.67, 0.85]), but as a screening instrument the MoCA (optimal cutoff point = 26/27, 64% correctly diagnosed, lack of ceiling effect) was superior to the MMSE (optimal cutoff point = 29/30, 54% correctly diagnosed, presence of ceiling effect).
Conclusions:
The Montreal Cognitive Assessment, but not the Mini-Mental State Examination, has adequate psychometric properties as a screening instrument for the detection of mild cognitive impairment or dementia in Parkinson disease. However, a positive screen using either instrument requires additional assessment due to suboptimal specificity at the recommended screening cutoff point.
GLOSSARY
= Alzheimer disease;
= area under the curve;
= deep brain stimulation;
= Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
= Geriatric Depression Scale;
= Hopkins Verbal Learning Test;
= instrumental activities of daily living;
= mild cognitive impairment;
= Mini-Mental State Examination;
= Montreal Cognitive Assessment;
= negative predictive value;
= Parkinson disease;
= Parkinson disease dementia;
= positive predictive value;
= quality of life;
= receiver operating characteristic;
= Tower of London-Drexel;
= Unified Parkinson’s Disease Rating Scale.
doi:10.1212/WNL.0b013e3181c34b47
PMCID: PMC2788810  PMID: 19933974
6.  Predictors of Cognitive Decline in the Early Stages of Parkinson's Disease: A Brief Cognitive Assessment Longitudinal Study 
Parkinson's Disease  2013;2013:912037.
Our objectives were to perform a longitudinal assessment of mental status in early stage Parkinson's disease (PD) patients, with brief neuropsychological tests, in order to find predictive factors for cognitive decline. Sixty-one, early stage, and nondemented patients were assessed twice, over a 2-year interval, with a global cognitive test (mini-mental state examination (MMSE)) and a frontal function test (frontal assessment battery (FAB)) and motor function scales. Dementia and hallucinations were diagnosed according to the DSM-IV criteria. Cognitive function scores did not decrease significantly, except for FAB lexical fluency score. Four patients presented with dementia at followup. The MMSE score below cut-off, worse gait dysfunction, the nontremor motor subtype, and hallucinations were significantly related to dementia. Rigidity and speech dysfunction were related to dementia and a decrease in FAB scores. We can conclude that decline in the MMSE and FAB scores is small and heterogeneous in the early stages of PD. Scores below cut-off in the MMSE could be helpful to predict dementia. Nontremor motor deficits could be predictive factors for frontal cognitive decline and dementia.
doi:10.1155/2013/912037
PMCID: PMC3835472  PMID: 24303226
7.  Predictors of cognitive impairment in an early stage Parkinson’s disease cohort 
Movement Disorders  2014;29(3):351-359.
The impact of Parkinson’s disease (PD) dementia is substantial and has major functional and socioeconomic consequences. Early prediction of future cognitive impairment would help target future interventions. The Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), and fluency tests were administered to 486 patients with PD within 3.5 years of diagnosis, and the results were compared with those from 141 controls correcting for age, sex, and educational years. Eighteen-month longitudinal assessments were performed in 155 patients with PD. The proportion of patients classified with normal cognition, mild cognitive impairment (MCI), and dementia varied considerably, depending on the MoCA and MMSE thresholds used. With the MoCA total score at screening threshold, 47.7%, 40.5%, and 11.7% of patients with PD were classified with normal cognition, MCI, and dementia, respectively; by comparison, 78.7% and 21.3% of controls had normal cognition and MCI, respectively. Cognitive impairment was predicted by lower education, increased age, male sex, and quantitative motor and non-motor (smell, depression, and anxiety) measures. Longitudinal data from 155 patients with PD over 18 months showed significant reductions in MoCA scores, but not in MMSE scores, with 21.3% of patients moving from normal cognition to MCI and 4.5% moving from MCI to dementia, although 13.5% moved from MCI to normal; however, none of the patients with dementia changed their classification. The MoCA may be more sensitive than the MMSE in detecting early baseline and longitudinal cognitive impairment in PD, because it identified 25.8% of those who experienced significant cognitive decline over 18 months. Cognitive decline was associated with worse motor and non-motor features, suggesting that this reflects a faster progressive phenotype.
doi:10.1002/mds.25748
PMCID: PMC4235340  PMID: 24395708
Parkinson’s disease; mild cognitive impairment; dementia; Mini-Mental State Examination; Montreal Cognitive Assessment
8.  Novel image–novel location object recognition task sensitive to age-related cognitive decline in nondemented elderly 
Age  2011;34(1):1-10.
Traditional tests used in the clinic to identify dementia, such as the mini-mental state examination (MMSE), are useful to identify severe cognitive impairments but might be less sensitive to detect more subtle age-related cognitive changes. Previously, the novel image–novel location (NINL) object recognition test was shown to be sensitive to detect effects of apolipoprotein E4, a risk factor for developing age-related cognitive decline and Alzheimer’s disease, in nondemented elderly. In the present longitudinal study, performance on the MMSE and the NINL tests were compared over a 4-year period. Individual NINL scores over this period were highly correlated. In addition, while MMSE scores did not change over the 4-year period, NINL scores did. In a final testing session of a subset of the participants, NINL scores correlated with logical memory and word recall lists, cognitive tasks used to detect dementia in the clinic, as well as clinical dementia rating scales. These results support that the NINL might be a valuable tool to assess age-related cognitive decline.
doi:10.1007/s11357-010-9204-2
PMCID: PMC3260359  PMID: 21234692
Cognitive aging; Object recognition; Dementia
9.  Cognitive Assessment of Older Primary Care Patients with and Without Memory Complaints 
BACKGROUND
Dementia screening is currently recommended only for symptomatic patients.
OBJECTIVE
To evaluate memory complaints, a mental status test, and several cognitive tests as dementia screens in primary care.
DESIGN
Cross-sectional clinical epidemiologic study.
PARTICIPANTS
Three hundred thirty-nine comprehensively assessed, primary care patients aged ≥65 years.
MEASUREMENTS
Memory complaints were abstracted from chart review. Scores on Mini-Mental State Examination (MMSE) and domain-specific cognitive testing were compared to a dementia diagnosis based on Clinical Dementia Rating score ≥ 1, and areas under the receiver operating characteristic curves (AUC) were calculated. Classification and regression tree analyses were performed on memory complaints and tests with the highest AUCs.
RESULTS
Of 33 patients with dementia, only 5 had documented memory complaints. In 25 patients with documented memory complaints, no cognitive tests further improved identification of the 5 with dementia. In 28 patients with dementia but without memory complaints, an MMSE score < 20 identified 8 cases; among those with MMSE scores 20–21, a visual memory test identified a further 11 cases. Further cognitive testing could not detect 9 dementia cases without memory complaints and with MMSE scores ≥ 22.
CONCLUSIONS
In older primary care patients with memory complaints, cognitive screening does not help identify those who require further examination for dementia. Most patients with dementia do not report memory complaints. In these asymptomatic individuals, general mental status testing, supplemented by a memory test when the mental status score is equivocal, will identify lower-scoring patients who need dementia assessment. However, high-scoring asymptomatic dementia cases will remain undetected.
doi:10.1007/s11606-007-0198-0
PMCID: PMC2219718  PMID: 17453265
geriatrics; older adults; mental status; cognitive screening
10.  Korean Version of Mini Mental Status Examination for Dementia Screening and Its' Short Form 
Psychiatry Investigation  2010;7(2):102-108.
Objective
We developed a Korean version of Mini-Mental Status Examination (MMSE) optimized for screening dementia (MMSE-DS) and its' short form (SMMSE-DS).
Methods
We constructed the MMSE-DS using the items of the two current Korean versions of MMSE and then construct the SMMSE-DS consisted of 13 items from the MMSE-DS based on the diagnostic accuracy of individual items for dementia. We investigated reliability and validity of MMSE-DS and SMMSE-DS on 1,555 subjects (1,222 nondemented controls, 333 dementia patients). We compared the diagnostic accuracy of the SMMSE-DS with that of the three full Korean versions of MMSE, and examined its' age- and education-specific optimal cutoff scores for dementia.
Results
The internal consistency obtained by Cronbach's coefficient alpha was 0.826. The inter-rater reliability and test-retest reliability were 0.968 (p<0.001) and 0.825 (p<0.001), respectively. It showed significant correlation with the Clinical Dementia Rating (CDR) (r=-0.698, p<0.05) and the three full Korean versions of MMSE (r=0.839-0.938, p<0.001). The area under the receiver operator curve for dementia of the SMMSE-DS was larger than those of the three full Korean versions of MMSE (p<0.001). Age, education and gender explained 19.4% of the total variance of SMMSE-DS scores. The optimal cutoff scores for dementia of the SMMSE-DS were estimated differently by age and educational attainment of the subjects.
Conclusion
The SMMSE-DS was found to be accurate, brief and portable instrument for screening dementia in Korean elders, and may be particularly useful for screening dementia in elderly populations with wide variation in educational levels.
doi:10.4306/pi.2010.7.2.102
PMCID: PMC2890863  PMID: 20577618
Mini-Mental Status Examination; Short form; Dementia; Validity; Reliability; Korean
11.  Relative preservation of MMSE scores in autopsy-proven dementia with Lewy bodies 
Neurology  2009;73(14):1127-1133.
Background:
Recent studies raised questions about the severity of cognitive impairment associated with dementia with Lewy bodies (DLB). However, there have been few analyses of large, multicenter data registries for clinical–pathologic correlation.
Methods:
We evaluated data from the National Alzheimer's Coordinating Center registry (n = 5,813 cases meeting initial inclusion criteria) and the University of Kentucky Alzheimer's Disease Center autopsy series (n = 527) to compare quantitatively the severity of cognitive impairment associated with DLB pathology vs Alzheimer disease (AD) and AD+DLB pathologies.
Results:
Mini-Mental State Examination (MMSE) scores showed that persons with pure DLB had cognitive impairment of relatively moderate severity (final MMSE score 15.6 ± 8.7) compared to patients with pure AD and AD+DLB (final MMSE score 10.7 ± 8.6 and 10.6 ± 8.6). Persons with pure DLB pathology from both data sets had more years of formal education and were more likely to be male. Differences in final MMSE scores were significant (p < 0.01) between pure DLB and both AD+DLB and pure AD even after correction for education level, gender, and MMSE–death interval. Even in cases with extensive neocortical LBs, the degree of cognitive impairment was most strongly related to the amount of concomitant AD-type neurofibrillary pathology.
Conclusions:
Dementia with Lewy bodies can constitute a debilitating disease with associated psychiatric, motoric, and autonomic dysfunction. However, neocortical Lewy bodies are not a substrate for severe global cognitive impairment as assessed by the Mini-Mental State Examination. Instead, neocortical Lewy bodies appear to constitute or reflect an additive disease process, requiring Alzheimer disease or other concomitant brain diseases to induce severe global cognitive deterioration.
GLOSSARY
= Alzheimer disease;
= AD Center;
= Consortium to Establish a Registry for Alzheimer's Disease;
= dementia with Lewy bodies;
= Lewy bodies;
= Mini-Mental State Examination;
= National Alzheimer's Coordinating Center;
= neurofibrillary;
= National Institute of Aging-Reagan Institute;
= University of Kentucky Alzheimer's Disease Center.
doi:10.1212/WNL.0b013e3181bacf9e
PMCID: PMC2764396  PMID: 19805729
12.  Computer Assessment of Mild Cognitive Impairment 
Postgraduate medicine  2009;121(2):177-185.
Many older individuals experience cognitive decline with aging. The causes of cognitive dysfunction range from the devastating effects of Alzheimer’s disease (AD) to treatable causes of dysfunction and the normal mild forgetfulness described by many older individuals. Even mild cognitive dysfunction can impact medication adherence, impair decision making, and affect the ability to drive or work. However, primary care physicians do not routinely screen for cognitive difficulties and many older patients do not report cognitive problems. Identifying cognitive impairment at an office visit would permit earlier referral for diagnostic work-up and treatment. The Computer Assessment of Mild Cognitive Impairment (CAMCI) is a self-administered, user-friendly computer test that scores automatically and can be completed independently in a quiet space, such as a doctor’s examination room. The goal of this study was to compare the sensitivity and specificity of the CAMCI and the Mini Mental State Examination (MMSE) to identify mild cognitive impairment (MCI) in 524 nondemented individuals > 60 years old who completed a comprehensive neuropsychological and clinical assessment together with the CAMCI and MMSE. We hypothesized that the CAMCI would exhibit good sensitivity and specificity and would be superior compared with the MMSE in these measures. The results indicated that the MMSE was relatively insensitive to MCI. In contrast, the CAMCI was highly sensitive (86%) and specific (94%) for the identification of MCI in a population of community-dwelling nondemented elderly individuals.
doi:10.3810/pgm.2009.03.1990
PMCID: PMC2699993  PMID: 19332976
mild cognitive impairment; cognition; neuropsychological assessment; computer tests; elderly; Alzheimer’s disease; dementia; diagnostic screening
13.  The value of clock drawing in identifying executive cognitive dysfunction in people with a normal Mini-Mental State Examination score 
Background
Executive cognitive dysfunction can precede the memory disturbances of dementia. People with executive cognitive dysfunction can have a normal Mini-Mental State Examination (MMSE) score but still have severe functional limitations. We evaluated the usefulness of clock drawing in identifying people with executive dysfunction who have a normal MMSE score.
Methods
We reviewed the charts of consecutive patients referred between July 1999 and June 2000 to a multidisciplinary geriatric assessment clinic because of concerns about functional inabilities. The patients had all undergone the Executive Interview for the diagnosis of executive cognitive dysfunction as well as an MMSE and clock-drawing test (scored by 2 methods: one described by Watson and colleagues [the Watson method] and one described by Sunderland and colleagues [the Sunderland method]).
Results
We reviewed the charts of 68 patients (40 women, 28 men); their mean age was 79 years (range 55–94). Thirty-six patients had an MMSE score of less than 24, and 32 had a “normal” MMSE score (24–30). Among those with a normal MMSE score, 22 had an abnormal Executive Interview score. Using the Executive Interview as the gold standard, the sensitivity and specificity of the Watson method of scoring clock drawings to predict an abnormal Executive Interview score were 59% and 70% respectively; the corresponding values were 18% and 100% for the Sunderland method.
Interpretation
The presence of an abnormal MMSE score alerts clinicians to the possibility of cognitive impairment. For patients referred for geriatric assessment who have a normal MMSE score, a clock-drawing test, scored by either the Watson or the Sunderland method, is a moderately sensitive and specific adjunct for detecting executive cognitive dysfunction.
PMCID: PMC128397  PMID: 12406943
14.  Relationship of dementia screening tests with biomarkers of Alzheimer’s disease 
Brain  2010;133(11):3290-3300.
Screening tests for Alzheimer’s disease lack sensitivity and specificity. We developed the AD8, a brief dementia screening interview validated against clinical and cognitive evaluations, as an improvement over current screening methods. Because insufficient follow-up has occurred to validate the AD8 against the neuropathologic findings of Alzheimer’s disease, we investigated whether AD8 scores correspond to impairment in episodic memory testing and changes in biomarkers of Alzheimer’s disease (cerebrospinal fluid and amyloid imaging with Pittsburgh compound B) characteristic of symptomatic Alzheimer’s disease. We also compared informant-based assessments with brief performance-based dementia screening measurements such as the Mini Mental State Exam. The sample (n = 257) had a mean age of 75.4 years with 15.1 years of education; 88.7% were Caucasian and 45.5% were male. The sample was divided into two groups based on their AD8 scores: those with a negative dementia screening test (AD8 score 0 or 1, n = 137) and those with a positive dementia screening test (AD8 score ≥2, n = 120). Individuals with positive AD8 scores had abnormal Pittsburgh compound B binding (P < 0.001) and cerebrospinal fluid biomarkers (P < 0.001) compared with individuals with negative AD8 scores. Individuals with positive AD8 tests and positive biomarkers scored in the impaired range on the Wechsler Logical Memory Story A (mean score 7.0 ± 4.5 for Pittsburgh compound B; mean score 7.6 ± 5.3 for cerebrospinal fluid amyloid beta protein 1–42). The AD8 area under the curve for Pittsburgh compound B was 0.737 (95% confidence interval: 0.64–0.83) and for cerebrospinal fluid amyloid beta protein 1–42 was 0.685 (95% confidence interval: 0.60–0.77) suggesting good discrimination. The AD8 had superior sensitivity in detecting early stages of dementia compared with the Mini Mental State Examination. The AD8 had a likelihood ratio of a positive test of 5.8 (95% confidence interval: 5.4–6.3) and likelihood ratio of a negative test of 0.04 (95% confidence interval: 0.03–0.06), increasing the pre-test probability of an individual having symptomatic Alzheimer’s disease. Individuals with AD8 scores of ≥2 had a biomarker phenotype consistent with Alzheimer’s disease and lower performance on episodic memory tests, supporting a diagnosis of Alzheimer’s disease. Informant-based assessments may be superior to performance-based screening measures such as the Mini Mental State Examination in corresponding to underlying Alzheimer’s disease pathology, particularly at the earliest stages of decline. The use of a brief test such as the AD8 may improve strategies for detecting dementia in community settings where biomarkers may not be readily available, and may enrich clinical trial recruitment by increasing the likelihood that participants have underlying biomarker abnormalities.
doi:10.1093/brain/awq204
PMCID: PMC2965421  PMID: 20823087
AD8; Alzheimer’s disease; screening; biomarkers; preclinical; cognition
15.  Four Sensitive Screening Tools to Detect Cognitive Dysfunction in Geriatric Emergency Department Patients: Brief Alzheimer’s Screen, Short Blessed Test, Ottawa 3DY, and the Caregiver-completed AD8 
Background
Cognitive dysfunction, including dementia and delirium, is prevalent in geriatric emergency department (ED) patients, but often remains undetected. One barrier to reliable identification of acutely or chronically impaired cognitive function is the lack of an acceptable screening tool. While multiple brief screening instruments have been derived, ED validation trials have not previously demonstrated tools that are appropriately sensitive for clinical use.
Objectives
The primary objective was to evaluate and compare the Ottawa 3DY (O3DY), Brief Alzheimer’s Screen (BAS), Short Blessed Test (SBT), and caregiver-completed AD8 (cAD8) diagnostic test performance for cognitive dysfunction in geriatric ED patients using the Mini Mental Status Exam (MMSE) as the criterion standard. A secondary objective was to assess the diagnostic accuracy for the cAD8 (which is an informant-based instrument) when used in combination with the other performance-based screening tools.
Methods
In an observational cross-sectional cohort study at one urban academic university-affiliated medical center, trained research assistants collected patients’ responses on the Confusion Assessment Method for the Intensive Care Unit, BAS, and SBT. When available, reliable caregivers completed the cAD8. The MMSE was then obtained. The O3DY was reconstructed from elements of the MMSE and the BAS. Consenting subjects were non-critically ill, English-speaking adults over age 65 years, who had not received potentially sedating medications prior to or during cognitive testing. Using an MMSE score ≤ 23 as the criterion standard for cognitive dysfunction, the sensitivity, specificity, likelihood ratios, and receiver operating characteristic area under the curve were computed. Venn diagrams were constructed to quantitatively compare the degree of overlap among positive test results between the performance-based instruments.
Results
The prevalence of cognitive dysfunction for the 163 patients enrolled with complete data collection was 37%, including 5.5% with delirium. Dementia was self-reported in 3%. Caregivers were available to complete the cAD8 for 56% of patients. The SBT, BAS, and O3DY each demonstrated 95% sensitivity, compared with 83% sensitivity for the cAD8. The SBT had a superior specificity of 65%. No combination of instruments with the cAD8 significantly improved diagnostic accuracy. The SBT provided the optimal overlap with the MMSE.
Conclusions
The SBT, BAS, and O3DY are three brief performance-based screening instruments to identify geriatric patients with cognitive dysfunction more rapidly than the MMSE. Among these three instruments, the SBT provides the best diagnostic test characteristics and overlap with MMSE results. The addition of the cAD8 to the other instruments does not enhance diagnostic accuracy.
doi:10.1111/j.1553-2712.2011.01040.x
PMCID: PMC3080244  PMID: 21496140
16.  Prevalence and pattern of cognitive impairment in rural and urban populations from Northern Portugal 
BMC Neurology  2010;10:42.
Background
Despite worldwide recognition of the burden of dementia, no epidemiological data is yet available in Portugal. The objective of this study is to estimate the prevalence and describe the pattern of cognitive impairment with dementia or no dementia (CIND) in rural and urban populations from Northern Portugal.
Methods
Two random samples of residents aged 55 to 79 years in rural and urban communities were drawn from the health centres registries to be screened for cognitive impairment. The screening criteria for dementia were an abnormal Mini-Mental State Examination (MMSE) score or a Blessed Dementia Scale score. After excluding those who tested positive for dementia, cut-off points for CIND were set at 1 standard deviation below the mean of the MMSE according to educational level. All those who screened positive either for dementia or CIND were examined by a neurologist for establishing a definitive diagnosis.
Results
The prevalence of cognitive impairment was higher in rural than in urban populations, 16.8% (95% CI: 14.3-19.8%) vs. 12.0% (95%CI: 9.3-15.4%), with a rural/urban prevalence ratio (PR) of 2.16 (95% CI: 1.04-4.50) in the eldest and 2.19 (95% CI: 1.01-4.76) in persons with vascular risk factors. The prevalence of dementia was 2.7% (95% CI: 1.9-3.8%) with a rural/urban PR = 2.1 and the prevalence of CIND was 12.3% (95% CI: 10.4-14.4%) and PR = 1.3. The prevalence of dementia increases exponentially with age and in those with cerebrovascular disease or other comorbid conditions while the prevalence of CIND, besides these factors, is also higher in persons with low levels of education or vascular risk factors. Alzheimer's and vascular disease were equally likely aetiologies of dementia (38.7%), the later more common in men PR(F:M = 0.3) as opposed to the former PR(F:M = 2.0). Vascular CIND, associated either with cerebrovascular disease or vascular risk factors was more frequent (39.7%) then depression (18.4%) or any other aetiology.
Conclusions
The prevalence of cognitive impairment is higher in rural compared with urban populations. This is shown in the synergy between age and rurality, with the rural/urban prevalence ratio increasing with age. In this relatively young population from Northern Portugal, cerebrovascular disease as well as vascular risk factors account for 48% of overall cognitive impairment.
doi:10.1186/1471-2377-10-42
PMCID: PMC2905352  PMID: 20540726
17.  The accuracy of the MMSE in detecting cognitive impairment when administered by general practitioners: A prospective observational study 
BMC Family Practice  2008;9:29.
Background
The Mini-Mental State Examination (MMSE) has contributed to detecting cognitive impairment, yet few studies have evaluated its accuracy when used by general practitioners (GP) in an actual public-health setting.
Objectives
We evaluated the accuracy of MMSE scores obtained by GPs by comparing them to scores obtained by Alzheimer's Evaluation Units (UVA).
Methods
The study was observational in design and involved 59 voluntary GPs who, after having undergone training, administered the MMSE to patients with symptoms of cognitive disturbances. Individuals who scored ≤ 24 (adjusted by age and educational level) were referred to Alzheimer's Evaluation Units (UVA) for diagnosis (including the MMSE). UVAs were unblinded to the MMSE score of the GP. To measure interrater agreement, the weighted Kappa statistic was calculated. To evaluate factors associated with the magnitude of the difference between paired scores, a linear regression model was applied. To quantify the accuracy in discriminating no cognitive impairment from any cognitive impairment and from Alzheimer's disease (AD), the ROC curves (AUC) were calculated.
Results
For the 317 patients, the mean score obtained by GPs was significantly lower (15.8 vs. 17.4 for the UVAs; p < 0.01). However, overall concordance was good (Kappa = 0.86). Only the diagnosis made by the UVA was associated with the difference between paired scores: the adjusted mean difference was 3.1 for no cognitive impairment and 3.8 for mild cognitive impairment. The AUC of the scores for GPs was 0.80 (95%CI: 0.75–0.86) for discriminating between no impairment and any impairment and 0.89 (95%CI: 0.84–0.94) for distinguishing patients with AD, though the UVA scores discriminated better.
Conclusion
In a public-health setting involving patients with symptoms of cognitive disturbances, the MMSE used by the GPs was sufficiently accurate to detect patients with cognitive impairment, particularly those with dementia.
doi:10.1186/1471-2296-9-29
PMCID: PMC2426687  PMID: 18477390
18.  The Beijing version of the montreal cognitive assessment as a brief screening tool for mild cognitive impairment: a community-based study 
BMC Psychiatry  2012;12:156.
Background
A cross-sectional validation study was conducted in several urban and rural communities in Beijing, China, to evaluate the effectiveness of the Beijing version of the Montreal Cognitive Assessment (MoCA-BJ) as a screening tool to detect mild cognitive impairment (MCI) among Chinese older adults.
Methods
The MoCA-BJ and the Mini-Mental State Examination (MMSE) were administered to 1001 Chinese elderly community dwellers recruited from three different regions (i.e., newly developed, old down-town, and rural areas) in Beijing. Twenty-one of these participants were diagnosed by experienced psychiatrists as having dementia, 115 participants were diagnosed as MCI, and 865 participants were considered to be cognitively normal. To analyze the effectiveness of the MoCA-BJ, we examined its psychometric properties, conducted item analyses, evaluated the sensitivity and specificity of the scale, and compared the scale with the MMSE. Demographic and regional differences among our subjects were also taken into consideration.
Results
Under the recommended cut-off score of 26, the MoCA-BJ demonstrated an excellent sensitivity of 90.4%, and a fair specificity (31.3%). The MoCA-BJ showed optimal sensitivity (68.7%) and specificity (63.9%) when the cut-off score was lowered to 22. Among all the seven cognitive sub-domains, delayed recall was shown to be the best index to differentiate MCI from the normal controls. Regional differences disappeared when the confounding demographic variables (i.e., age and education) were controlled. Item analysis showed that the internal consistency was relatively low in both naming and sentence repetition tasks, and the diagnostic accuracy was similar between the MoCA-BJ and the MMSE.
Conclusions
In general, the MoCA-BJ is an acceptable tool for MCI screening in both urban and rural regions of Beijing. However, presumably due to the linguistic and cultural differences between the original English version and the Chinese version of the scale, and the lower education level of Chinese older adults, the MoCA-BJ is not much better than the MMSE in detecting MCI, at least for this study sample. Further modifications to several test items of the MoCA-BJ are recommended in order to improve the applicability and effectiveness of the MoCA-BJ in MCI screening among the Chinese population.
doi:10.1186/1471-244X-12-156
PMCID: PMC3499377  PMID: 23009126
MoCA-BJ; MMSE; Mild cognitive impairment; Dementia; Cognitive assessment
19.  Usefulness of medial temporal lobe atrophy visual rating scale in detecting Alzheimer's disease: Preliminary study 
Background:
The Korean version of Mini-Mental Status Examination (K-MMSE) and the Korean version of Addenbrooke Cognitive Examination (K-ACE) have been validated as quick neuropsychological tests for screening dementia in various clinical settings. Medial temporal atrophy (MTA) is an early pathological characteristic of Alzheimer's disease (AD). We aimed to assess the diagnostic validity of the fusion of the neuropsychological test and visual rating scale (VRS) of MTA in AD.
Materials and Methods:
A total of fifty subjects (25 AD, 25 controls) were included. The neuropsychological tests used were the K-MMSE and the K-ACE. T1 axial imaging visual rating scale (VRS) was applied for assessing the grade of MTA. We calculated the fusion score with the difference of neuropsychological test and VRS of MTA. The receiver operating characteristics (ROC) curve was used to determine optimal cut-off score, sensitivity and specificity of the fusion scores in screening AD.
Results:
No significant differences in age, gender and education were found between AD and control group. The values of K-MMSE, K-ACE, CDR, VRS and cognitive function test minus VRS were significantly lower in the AD group than control group. The AUC (Area under the curve), sensitivity and specificity for K-MMSE minus VRS were 0.857, 84% and 80% and for K-ACE minus VRS were 0.884, 80% and 88%, respectively. Those for K-MMSE only were 0.842, 76% and 72% and for K-ACE only were 0.868, 80% and 88%, respectively.
Conclusions:
The fusion of the neuropsychological test and VRS suggested clinical usefulness in their easy and superiority over neuropsychological test only. However, this study failed to find any difference. This may be because of small numbers in the study or because there is no true difference.
doi:10.4103/0972-2327.116951
PMCID: PMC3788286  PMID: 24101822
Alzheimer's disease; neuropsychological test; visual rating scale
20.  Improvement of Dementia Screening Accuracy of Mini-Mental State Examination by Education-Adjustment and Supplementation of Frontal Assessment Battery Performance 
Journal of Korean Medical Science  2013;28(10):1522-1528.
This study aimed to investigate whether the demographic variable-adjustment and supplementation of Frontal Assessment Battery (FAB) score can improve the screening ability of Mini-Mental State Examination (MMSE) for dementia and its subtypes. Five hundred forty-one non-demented comparison (NC) and 474 dementia (320 Alzheimer's disease [AD]; 139 non-Alzheimer's disease dementia [NAD]; and 15 mixed AD-NAD dementia) individuals living in the community were included. Education-adjusted MMSE (MMSE-edu) score showed significantly better screening accuracy for overall dementia, AD, and NAD than MMSE raw score. FAB-supplemented MMSE (MMSE-FAB) score had significantly better screening ability for NAD, but not for overall dementia and AD, than MMSE raw score alone. Additional supplementation of FAB to MMSE-edu further increased the ability for overall dementia or NAD screening, but not for AD screening. Further education adjustment of MMSE-FAB also improved its ability for overall dementia, AD, and NAD screening. These results strongly support the usefulness of education-adjustment and supplementation of frontal function assessment to improve screening performance of MMSE for dementia and its subtypes, NAD in particular.
doi:10.3346/jkms.2013.28.10.1522
PMCID: PMC3792609  PMID: 24133360
Mini-Mental State Examination; Frontal Assessment Battery; Education; Dementia; Screening Accuracy
21.  The Sensitivity and Specificity of Cognitive Screening Instruments to Detect Cognitive Impairment in Older Adults With Severe Psychiatric Illness 
Background
Older adults with severe psychiatric illness are often treated at community mental health centers (CMHCs) and these individuals commonly have numerous risk factors for cognitive impairment (CI). Brief cognitive screening instruments are frequently used to evaluate cognitive functioning in CMHCs, but the validity of these measures for detecting CI has not been adequately evaluated in this patient population.
Objectives
To determine the sensitivity and specificity of 2 cognitive screening measures (the Mini-Mental Status Examination [MMSE] and the Stroop Color and Word Test [SCWT]) for detecting CI in a sample of older adults with severe psychiatric illness.
Methods
Data were collected from 52 older adults receiving services at a CMHC. Diagnosis of CI was made by a neuropsychologist. Sensitivity and specificity coefficients for 2 cutoff scores for the MMSE and the SCWT were calculated.
Results
A cutoff score of 25 on the MMSE yielded a sensitivity of 43.3% and a specificity of 90.4% for detecting CI, whereas a cutoff score of 21 yielded sensitivity of 13.1% and 100% specificity. Using an age- and education-corrected scaled score (SS) on the SCWT falling at or below 7 as the criterion the SCWT had 88.8% sensitivity and 36.8% specificity, whereas a cutoff score of 5 or below yielded sensitivity of 59.2% and specificity of 57.8%.
Conclusions
Overall, the MMSE was found to be the more clinically useful cognitive screening tool for use in CMHC. Yet, because of the poor sensitivity of the MMSE for detecting CI in this patient population, alternative screening methods should be explored.
doi:10.1177/0891988709358589
PMCID: PMC3239217  PMID: 20101070
cognitive impairment; geriatric; Community Mental Health Center; Mini-Mental State Examination; Stroop Color and Word Test; sensitivity; specificity; severe psychiatric illness; depression; schizophrenia
22.  A comparison of cognitive functions in non-hypoxemic chronic obstructive pulmonary disease (COPD) patients and age-matched healthy volunteers using mini-mental state examination questionnaire and event-related potential, P300 analysis 
Objective:
To assess sub-clinical cognitive dysfunctions in stable chronic obstructive pulmonary disease (COPD) patients having no hypoxemia vs. age-matched healthy volunteers using (i) an electrophysiological test: Auditory event related potential, P300 test and (ii) a questionnaire tool: Mini-mental state examination (MMSE) questionnaire.
Materials and Methods:
Eighty male subjects were included: 40 stable COPD patients (smoking history >20 pack years) and 40 healthy volunteers (HVs). Age, duration of illness, smoking pack years, and spirometric indices were assessed. MMSE scores were evaluated in these groups. Latency of P300 wave and amplitude of P300 wave were studied in both groups to detect P300 abnormalities in COPD group. Correlations of P300 abnormalities with patient characteristic parameters and MMSE scores were assessed. In addition, individual COPD patients having significant cognitive dysfunctions beyond cut-off value of 99th percentile of HVs were analyzed.
Results:
We observed significantly prolonged P300 latency (P < 0.001) and decreased P300 amplitude (P < 0.001) in COPD group. MMSE scores were significantly reduced in COPD group (P < 0.001). 10/40 COPD patients had prolongation of P300 latency, and 27/40 COPD patients had reduced MMSE scores beyond 99th percentile of HV. However, we did not observe any statistically significant correlation between P300 abnormalities and patients’ characteristics or MMSE scores (P > 0.05 for all).
Conclusions:
Our study explores cognitive dysfunctions in stable COPD patients with no hypoxemia. This study highlights the relative importance of using MMSE and P300. Cognitive dysfunctions were detected both by MMSE and P300; however, MMSE abnormalities were more frequent compared to P300 abnormalities (27/40 vs. 10/40) in COPD patients.
doi:10.4103/0970-2113.106119
PMCID: PMC3644834  PMID: 23661909
Chronic obstructive pulmonary disease; cognitive functions; event-related potential; mini-mental state examination; P300
23.  Self administered cognitive screening test (TYM) for detection of Alzheimer’s disease: cross sectional study 
Objective To evaluate a cognitive test, the TYM (“test your memory”), in the detection of Alzheimer’s disease.
Design Cross sectional study.
Setting Outpatient departments in three hospitals, including a memory clinic.
Participants 540 control participants aged 18-95 and 139 patients attending a memory clinic with dementia/amnestic mild cognitive impairment.
Intervention Cognitive test designed to use minimal operator time and to be suitable for non-specialist use.
Main outcome measures Performance of normal controls on the TYM. Performance of patients with Alzheimer’s disease on the TYM compared with age matched controls. Validation of the TYM with two standard tests (the mini-mental state examination (MMSE) and the Addenbrooke’s cognitive examination-revised (ACE-R)). Sensitivity and specificity of the TYM in the detection of Alzheimer’s disease.
Results Control participants completed the TYM with an average score of 47/50. Patients with Alzheimer’s disease scored an average of 33/50. The TYM score shows excellent correlation with the two standard tests. A score of ≤42/50 had a sensitivity of 93% and specificity of 86% in the diagnosis of Alzheimer’s disease. The TYM was more sensitive in detection of Alzheimer’s disease than the mini-mental examination, detecting 93% of patients compared with 52% for the mini-mental state exxamination. The negative and positive predictive values of the TYM with the cut off of ≤42 were 99% and 42% with a prevalence of Alzheimer’s disease of 10%. Thirty one patients with non-Alzheimer dementias scored an average of 39/50.
Conclusions The TYM can be completed quickly and accurately by normal controls. It is a powerful and valid screening test for the detection of Alzheimer’s disease.
doi:10.1136/bmj.b2030
PMCID: PMC2694259  PMID: 19509424
24.  Development of a short form of Mini-Mental State Examination for the screening of dementia in older adults with a memory complaint: a case control study 
BMC Geriatrics  2011;11:59.
Background
Primary care physicians need a brief and accurate screening test of dementia. The objective of this study was to determine whether a short form of Mini-Mental State Examination (SMMSE) was as accurate as the Mini-Mental State Examination (MMSE) in screening dementia.
Methods
Based on case control design study, SMMSE and MMSE were assessed in 184 community-dwelling older adults (mean age 81.3 ± 6.5 years, 71.7% women) with memory complaint sent by their primary care physician to a memory clinic. Included participants were separated into two groups: cognitively healthy individuals and demented individuals.
Results
The trade-off between sensitivity and specificity of the SMMSE for clinically diagnosed dementia was 4. Based on the cut-off value ≤ 4 for SMMSE and a cut-off value ≤ 24 for MMSE, the sensitivity of both tests was similar (89.5% for SMMSE versus 90.0% for MMSE), whereas the specificity, the positive predictive values (PPV) and the negative predictive values (NPV) were higher for SMMSE compared to MMSE (85.4 versus 75.5% for specificity; 95.5% versus 92.8% for PPV; 70.0 versus 68.9 for NPV). The positive and negative Likehood Ratio (LR) of SMMSE were higher than those of MMSE (respectively, 6.1 versus 3.7; 8.1 versus 7.7). In addition, odds ratio (OR) for dementia was higher for the SMMSE compared to the MMSE (OR = 49.8 with 95% confident interval (CI) [18.0; 137.8] versus OR = 28.6 with 95% CI [11.6; 70.3]).
Conclusions
SMMSE seems to be an efficient short screening test for dementia among community-dwelling older adults with a memory complaint. Further research is needed to confirm its predictive values among unselected primary care older patients.
doi:10.1186/1471-2318-11-59
PMCID: PMC3203031  PMID: 21970520
25.  The factorial structure of the mini mental state examination (MMSE) in Japanese dementia patients 
BMC Geriatrics  2010;10:36.
Background
The Mini-Mental State Examination (MMSE) is one of the most commonly used instruments in the evaluation of global cognitive status. Few studies have investigated the relationship among its components in terms of factorial structure in Japanese individuals suffering from dementia. The aims of this study were: 1) to analyze the factorial structure of MMSE in Japanese dementia patients, 2) to clarify the MMSE static structure in identifying different cognitive profiles and understanding how these profiles are related to levels of dysfunction in subsets of dementia patients.
Methods
30,895 consecutive outpatients with dementia were evaluated. The 11 subtests composing the MMSE and the global MMSE score were analyzed. Factor analysis based on principal component analysis with Promax rotation was applied to the data representing the frequency of failures in each subtest as identified by the MMSE.
Results
Factor analysis identified three factors that explained approximately 44.57% of the total variance. The first factor, immediate memory, essentially constituted a simple index of the reading and writing subtests. The second factor, orientation and delayed recall, expressed the ability to handle new information. The third factor, working memory, was most closely related to the severity of dementia at the time of test administration.
Conclusions
Japanese dementia patients appear to develop difficulty handling new information in the early stages of their disease. This finding, and our finding that there is a factor associated with disease severity, suggest that understanding the specific factors related to subtest items, which underlie the total MMSE score may be useful to clinicians in planning interventions for Japanese patients in the early stages of dementia.
doi:10.1186/1471-2318-10-36
PMCID: PMC2903593  PMID: 20534132

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