Mini-Mental State Exam (MMSE)

M. F. Folstein, S. E. Folstein, and P. R. McHugh

Modified From: Rush J, et al: Psychiatric Measures, APA, Washington DC, 2000.

GOALS The Mini-Mental State Exam (MMSE) (Folstein et al. 1975) was originally designed to provide a brief, standardized assessment of mental status that would serve to differentiate between organic and functional disorders in psychiatric patients. As experience with the test has increased over the years, its major function has now become to detect and track the progression of cognitive impairment associated with neurodegenerative disorders such as Alzheimers disease. DESCRIPTION The MMSE is a fully structured scale that consists of 30 points grouped into seven categories: orientation to place (state, county, town, hospital, and floor), orientation to time (year, season, month, day, and date), registration (immediately repeating three words), attention and concentration (serially subtracting 7, beginning with 100, or, alternatively, spelling the word world backward), recall (recalling the previously repeated three words), language (naming two items, repeating a phrase, reading aloud and understanding a sentence, writing a sentence, and following a three-step command), and visual construction (copying a design). Several shortened forms of the MMSE have been developed on the basis of linear regression analyses that used the individual test items to predict the total score. Although these versions vary somewhat, they are generally limited to the orientation, attention and concentration, and recall items. There are also at least two telephone versions: the Telephone-Assessed Mental State (TAMS) (Lanska et al. 1993) and the Telephone Interview for Cognitive Status (TICS) (Brandt et al. 1988). Several expanded versions of the MMSE have been developed to assess a greater range and depth of cognitive functioning or to increase the tests sensitivity to subtle cognitive deficits that may occur in specific neurological diseases such as multiple sclerosis (e.g., the Cognitive Abilities Screening Instrument [CASI] [Teng et al. 1994], the Modified Mini-Mental State [3MS] Examination [Teng and Chui 1987], and the expanded MMSE). The MMSE is scored in terms of the number of correctly completed items; lower scores indicate poorer performance and greater cognitive impairment. The total score ranges from 0 to 30 (perfect performance). Although scoring for most MMSE items is simple and straightforward, several different scoring methods have been used for the attention and concentration item. The most commonly used procedure is to present both the serial subtraction and backward spelling items and use the higher of the two scores in calculating the MMSE total score. Comprehensive normative data (N = 18,056) on the MMSE (Crum et al. 1993) collected through the Epidemiologic Catchment Area (ECA) study provide age- and education-related median, upper quartile, and lower quartile scores that can be used to identify abnormal performance. An initially recommended MMSE cutoff score of 23 or 24 provides good sensitivity and specificity for the detection of dementia; however, several recent studies suggested that this cutoff score may be too low, particularly with highly educated individuals. These studies showed that dementia can be clinically diagnosed with good accuracy in many individuals who score between 24 and 27 on the MMSE. However, these figures are focused on accuracy in community populations. For clinical purposes, even a score of 27 may be insufficiently sensitive

to detect dementia in individuals with extensive education, whereas a cutoff score of 24 may be insufficiently specific in individuals with little education. PRACTICAL ISSUES It takes approximately 510 minutes to administer the MMSE. The test is designed to be easily administered by any health care professional or trained technician who has received minimal instruction in its use. The MMSE is not commercially available, but the test items, instructions for administration, and extensive normative data have been published (Crum et al. 1993; Folstein et al. 1975). The copyright for the MMSE is wholly owned by Mini Mental LLC, a Massachusetts limited liability company. For information about how to obtain permission to use or reproduce the MMSE in any written materials, contact . John Gonsalves Jr. Administrator of the Mini Mental LLC 31 St. James Avenue, Suite 1 Boston, MA 02116 Phone: 617-587-4215 PSYCHOMETRIC PROPERTIES Reliability Two studies that examined the internal consistency of the MMSE obtained Cronbachs alphas of 0.82 and 0.84 in elderly patients admitted to a medical service (N = 372) and elderly nursing home residents (N = 34), respectively. The joint reliability of the MMSE was found to be 0.827 in a study of patients with Dementia (N = 19), 0.95 in a study of patients with various neurological disorders (N = 15), and 0.840.99 in two studies with elderly residents of nursing homes (N = 35 and 70). Intraclass correlation coefficients ranging from 0.69 to 0.78 were obtained in another study of elderly nursing home residents (N = 48). A mean kappa of 0.97 was obtained when five examiners separately scored the MMSE performance for 10 neurological patients. The test-retest reliability of the MMSE in patients with dementia (usually of the Alzheimers type) ranged from 0.75 to 0.94 (Pearson r) in 10 studies that employed testretest intervals of 1 day to 9 weeks (N = 1258). A Kendall t of 0.65 (N = 30 neurologically impaired patients) and an intra-class correlation coefficient of 0.69 (N = 48 elderly nursing home residents) were found in two studies that examined the test-retest reliability of the MMSE over a 1-day and 2-week interval, respectively. The test-retest reliability of the MMSE was found to be 0.56 over a 1-day interval in patients with delirium (N = 7) and 0.600.74 over a 4- to 6-week interval in patients with schizophrenia (N = 22). A test-retest reliability of 0.88 (intraclass correlation coefficient) was obtained with a 1- or 2-year interval in geriatric patients with schizophrenia (N = 224). In elderly individuals without dementia, the test-retest reliability of the MMSE over a 1-day to 8-week interval was found to range from 0.64 to 0.85 (N = 57481) and from 0.23 to 0.45 over a 1- to 2-year interval (N = 60122) using various statistics. Validity Performance on the MMSE has been shown to be significantly correlated with a variety of other tests that measure intelligence, memory, and other aspects of cognitive functioning in a wide variety of populations. For example, scores on the MMSE significantly correlated with the full, verbal, or performance intelligence quotients from the Wechsler Adult Intelligence Scale (WAIS) (Wechsler 1958) or its revision (WAIS-R)

(Wechsler 1981) in patients with dementia, stroke patients, patients with schizophrenia or depression, hospitalized and nonhospitalized developmentally delayed young adults, and psychiatrically healthy elderly individuals. MMSE performance has also been shown to be strongly correlated with the memory quotient from the Wechsler Memory Scale (Wechsler 1945) in patients with dementia and in neurologically impaired patients and with scores on the Information-Memory-Concentration (IMC) Test in patients with Alzheimers disease, cognitively impaired individuals, and psychiatrically healthy control subjects. MMSE scores were also significantly correlated with scores on the Clock Drawing Test in geriatric patients and patients with Alzheimers disease, with scores on the Alzheimer s Disease Assessment Scale Cognitive (ADAS-COG) in patients with Alzheimers disease or patients referred for psychiatric evaluations, and with scores on a composite neuropsychological test battery in patients referred for dementia evaluation. In addition, significant levels of agreement were obtained between MMSE-determined impairment and impairment determined by a composite neuropsychological test battery in a study of patients evaluated after cardiac surgery (N = 247). Numerous studies have shown that MMSE performance correlates with scores on scales that measure functional competence. One study found that activities of daily living (ADL) or instrumental ADL (IADL) scores were significantly worse in patients who scored 23 on the MMSE than in those who scored <23 on the test (N = 244). Two studies found that MMSE and ADL scores were significantly correlated (r = 0.480.76) in nursing home residents (N = 70) and in patients with Alzheimers disease (N = 86), and three studies found that MMSE scores accounted for significant amounts of variance in ADL scores in individuals with dementia (N = 59201; R 2 = 0.280.49) and in elderly individuals residing in the community (N = 1,637; R 2 = 0.23). Three studies showed that MMSE and Dementia Rating Scale (DRS) scores were correlated in patients with dementia (N = 115; r = 0.71 to 0.86), patients with Alzheimers disease (N = 41; r = 0.73), and elderly patients referred for dementia evaluation (N = 226; r = 0.86). MMSE scores were correlated with Brief Cognitive Rating Scale (BCRS) scores (r = 0.79) in a study of patients with dementia (N = 82), with Global Deterioration Scale (GDS) scores (r = 0.890.90) in two studies of psychiatrically healthy elderly patients (N = 154) or patients with Alzheimers disease (N = 30), with Clinical Dementia Rating (CDR) Scale scores (r = 0.78) in a study of elderly individuals with and without dementia (N = 668) and in a study of patients with dementia (N = 93; kappa = 0.33), and with Functional Assessment Staging (FAST) scores (r = 0.87) in a study of patients with Alzheimers disease and psychiatrically healthy control subjects (N = 40). MMSE scores were also found to decline significantly with FAST stages in a study of patients with Alzheimers disease (N = 70). Performance on the MMSE was shown to be significantly correlated with physicians ratings of function (r = 0.310.67; N = 115) and with childrens ratings of level of need (R 2 = 0.33; N = 201) in two studies of dementia patients, with nursing home staff ratings of cognition (r = 0.74), and with nursing home staff ratings of communication (r = 0.74). Three studies demonstrated a significant relationship between scores on the MMSE and quantitative measures of pathology in patients with Alzheimers disease. MMSE scores were correlated (r = 0.77) with synaptic density in biopsied tissue from the frontal cortex in patients with Alzheimers disease (N = 8) and with beta amyloid load (r = 0.90) in the cortex of patients with autopsy-proven Alzheimers disease (N = 20). MMSE scores were also

significantly correlated with midfrontal synaptic density (r = 0.728), inferior parietal synaptic density (r = 0.645), neurofibrillary tangles in the inferior parietal cortex (r = 0.564), and neurofibrillary tangles in the midfrontal cortex (r = 0.517) of patients with Alzheimers disease (N = 15). Furthermore, a multiple regression analysis in the latter study showed that these measures and the level of choline acetyltransferase in the midfrontal cortex accounted for 86% of the variance in the MMSE scores of the patients with Alzheimers disease. Another study demonstrated a significant relationship between a quantitative electroencephalogram frequency measure and the MMSE scores of patients with Alzheimers disease (r = 0.623; N = 21) and psychiatrically healthy elderly individuals (r = 0.451; N = 21). In 63 neurological patients referred for computed tomography (CT) imaging, those with a positive CT image showing atrophy or atrophy and focal abnormalities had lower MMSE scores than those with a negative CT image. The total lesion volume observed on the magnetic resonance images of the brains of patients with multiple sclerosis (N = 56) was correlated with their MMSE scores (r = 0.28), although this correlation failed to reach significance. In another study, 23% of patients with schizophrenia who scored 25 on the MMSE (N = 19) had very enlarged lateral ventricles on CT images, whereas only 5% of the patients with schizophrenia who scored >25 on the test (N = 36) had very enlarged ventricles. Five studies reported that the MMSE is sensitive to dementing disorders. In one of these studies, patients with dementia (N = 29) scored significantly lower on the MMSE than patients with depression and cognitive impairment (N = 10), depressed patients without cognitive impairment (N = 30), and psychiatrically healthy control subjects (N = 63). In another study, patients with dementia (N = 44) scored lower on the MMSE than patients without dementia who had another psychiatric diagnosis (N = 33) or a neurological diagnosis (N = 33) or psychiatrically healthy control subjects (N = 23). A study that focused on elderly individuals in a residential facility (N = 201) found that those with dementia scored significantly lower on the MMSE than those without dementia or those with only possible dementia. Patients with moderate Alzheimers disease (N = 50) in another study had lower MMSE scores than those with mild dementia (N = 24), who in turn had lower scores than psychiatrically healthy control subjects (N = 74). Finally, patients with organic mental disorder (N = 23) achieved significantly lower MMSE scores than patients with nonorganic mental disorders (N = 9) or no mental disorder at all (N = 68). In other studies, MMSE scores of patients with Alzheimers disease (N = 141) were significantly negatively related to estimated duration of illness (r = 0.50), and a significantly higher proportion of adult neurology patients with a cerebral abnormality (50%; N = 42) than those with only a peripheral abnormality (0%; N = 26) scored <24 on the MMSE; patients with schizophrenia with negative symptoms (N = 16) scored significantly lower on the MMSE than patients with schizophrenia with positive symptoms (N = 18) or mixed symptoms (N = 18). A score of 23 on the MMSE was originally proposed as a cutoff score indicative of cognitive dysfunction. This score was determined on the basis of the finding that no elderly psychiatrically healthy control subject scored <21 in the initial study that introduced the MMSE (N = 63) and that 95% of individuals in a population-based probability sample (N = 3,481) scored >23 on the test, whereas no subject with a diagnosis of Alzheimers disease scored >23. Another study found 80% agreement between MMSE scores <23 and clinically diagnosed dementia in elderly patients referred for evaluation by general practice

physicians (N = 226). In 13 subsequent studies that examined the effectiveness of an MMSE cutoff of 23 for detecting dementia, sensitivity ranged from 63% to 100% and specificity ranged from 52% to 99% when measured against an independent clinical diagnosis of dementia (N = 2374 individuals with dementia and 242,663 individuals without dementia). Three studies that proposed higher MMSE cutoff scores of between 25 and 27 found sensitivity to range from 78% to 90% and specificity to range from 70% to 87% for the detection of clinically diagnosed dementia or cognitive impairment (N = 5080 individuals with dementia and 5393 subjects without dementia). Five studies also proposed lower MMSE cutoff scores of between 17 and 22 and reported sensitivity for the detection of dementia that ranged from 52% to 98% and specificity that ranged from 68% to 100%. Two studies that used the MMSE to detect cognitive impairment in patients with multiple sclerosis (N = 56173) found that a cutoff score of 27 resulted in sensitivity of 63%84% and specificity of 79%94% compared with detection by a larger battery of cognitive tests. Five studies demonstrated that the various shortened versions of the MMSE are also sensitive to dementia. Two of these studies reported that the optimal cutoff scores on the tests provided sensitivity that ranged from 83% to 96% and specificity that ranged from 83% to 95% for the detection of dementia (N = 7274 patients with dementia of the Alzheimers type and 74144 subjects without dementia). Another study that supplemented the shortened MMSE with verbal fluency and visual retention tests found 100% sensitivity and 90% specificity for the detection of dementia in a large epidemiological study in France (N = 64 patients with dementia and 2,663 without dementia). A study reported that the internal consistency of a shortened MMSE was 0.77 (Cronbachs alpha) and that the test provided 96% sensitivity and 91% specificity for detecting impairment that was defined as a score of 22 on the full MMSE. A correlation of r = 0.940.97 was observed between the full MMSE and a shortened version in a study that included a random sample of elderly women (N = 783). The MMSE was negatively correlated with age in several community surveys of the elderly(e.g., in the ECA study, r = 0.38), but this relationship most likely reflects the age-related increase in the prevalence of Alzheimers disease and other dementias. A significant correlation remains, however, when age is compared with MMSE performance in patients with diagnoses of Alzheimers disease (r = 0.30 to 0.34; N = 5186). MMSE performance is also related to level of education. Of 12 studies with individuals residing in the community (N = 21418,056), 10 reported a significant positive relationship between level of education and MMSE scores (r = 0.300.51; multiple regression analysis R 2 = 0.100.21; or significantly lower mean MMSE scores in cohorts with low vs. high education). In contrast, four studies reported no significant correlation between education and MMSE scores in patients with dementia (r = 0.30.13; N = 51141 patients with Alzheimers disease). Five studies that examined the sensitivity of the MMSE to cognitive decline in patients with dementia (N = 44115, mostly Alzheimers disease) found annual rates of change in scores that ranged from 1.8 to 3.2 points per year. In one of these studies, the slope in the annual change in MMSE scores of participants in an adult day care (N = 82, of whom 57 had dementia) was significantly correlated with the slopes in the annual change in scores on the BCRS (r = 0.55) and a measure of ADL (r = 0.28) (the Maryland Appraisal of Patient Progress [Porte 1986]).

CLINICAL UTILITY The MMSE is a very brief, easily administered mental status examination that has proved to be a highly reliable and valid instrument for detecting and tracking the progression of the cognitive impairment associated with neurodegenerative diseases. Consequently, the MMSE is the most widely used mental status examination in the world. The test has been translated into many languages and has been used as the primary cognitive screening instrument in several large-scale epidemiological studies of dementia. The test is also used widely in clinical practice and is often reported in research studies as a benchmark of the severity of dementia that can be used to compare patient cohorts across studies. This prominence of the MMSE as a cognitive screening instrument is attested to by its inclusion along with the Diagnostic Interview Schedule (DIS), in the National Institute of Mental Health ECA study and by its listing as a recommended measure of cognitive functioning in the diagnostic criteria for Alzheimers disease developed by the onsortium of the National Institute of Neurological and Communication Disorders and Stroke and the Alzheimers Disease and Related Disorders Association (McKhann et al. 1984). Extensive psychometric data on the MMSE confirm that the test has very good test-retest and joint reliability and excellent validity as measured against independent clinical diagnosis of dementia and Alzheimers disease, measures of functional impairment, or performance on other (often more rigorous) neuropsychological tests and against neuropathological features of Alzheimers disease. Because performance on the MMSE can be adversely affected by low education in psychiatrically healthy elderly individuals, some investigators recommend the use of age- and education-adjusted cutoff scores for the detection of dementia. The MMSE has been shown to be sensitive to cognitive decline in patients with Alzheimers disease; scores decline an average of 1.83.2 points per year. This feature of the scale has led to its use as a primary or secondary outcome measure in some studies that have examined the efficacy of pharmacological agents that might slow the progression of cognitive deterioration in patients with Alzheimers disease. The MMSE is also somewhat effective in differentiating between dementing disorders that differ in their etiology and sites of predominant neuropathology. For example, in one study, it was reported that Alzheimers disease and Huntingtons disease patients differed in the profile of deficits they produced on the individual MMSE items. The most commonly cited limitations of the MMSE are its marginal or absent assessment of some cognitive abilities that are affected early in the course of Alzheimers disease or other dementing disorders (e.g., limited memory and verbal fluency items and no problem solving or judgment items), its relative insensitivity to very mild cognitive decline (particularly in highly educated individuals), and its susceptibility to floor effects in tracking the progression of dementia in patients with moderate to severe cognitive impairment. Although these limitations diminish the usefulness of the MMSE to some degree, the test remains a very valuable instrument for the assessment of cognitive decline. REFERENCES AND SUGGESTED READINGS Anthony JC, LeResche L, Niaz U, et al: Limits of the Mini-Mental State as a screening test for dementia and delirium among hospital patients. Psychol Med 12:397 408, 1982 Brandt J, Spencer M, Folstein M: The Telephone Interview for Cognitive Status. Neuropsychiatry Neuropsychol Behav Neurol 1:111117, 1988

Crum RM, Anthony JC, Bassett SS, et al: Population-based norms for the Mini-Mental State Examination by age and educational level. JAMA 269:23862391, 1993 Folstein MF, Folstein SE, McHugh PR: Mini-Mental State : a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189198, 1975 Lanska DJ, Schmitt FA, Stewart JM, et al: Telephone-Assessed Mental State. Dementia 4:117119, 1993 McKhann G, Drachman D, Folstein M, et al: Clinical diagnosis of Alzheimer s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer s Disease. Neurology 34:939944, 1984 Porte P: Severity of illness, long term care, and cost control: Maryland's approach. J Am Med Rec Assoc 57:3435, 1986 Regier DA, Myers JK, Kramer LN, et al: The NIMH Epidemiologic Catchment Area (ECA) program: historical context, major objectives, and study population characteristics. Arch Gen Psychiatry 41:934941, 1984 Teng EL, Chui HC: The Modified Mini-Mental State (3MS) Examination. J Clin Psychiatry 48:314318, 1987 Teng EL, Hasegawa K, Homma A, et al: The Cognitive Abilities Screening Instrument (CASI): a practical test for cross-cultural epidemiologic studies of dementia. Int Psychogeriatr 6:4556, 1994 Tombaugh TM, McIntyre NJ: The Mini-Mental State Examination: a comprehensive review. J Am Geriatr Soc 40:922935, 1992 Wechsler D: A standardised memory scale for clinical use. J Psychol 19:8795, 1945 Wechsler D: Wechsler Adult Intelligence Scale manual. New York, Psychological Corporation, 1955 Wechsler D: Wechsler Adult Intelligence Scale-revised manual. New York, Psychological Corporation, 1981