The mini-mental state examination in screening of cognitive dysfunction and dementia

The mini-mental state examination (MMSE) is one of the most widely used screening instruments for the detection of cognitive impairments, used primarily in connection with screening for dementia. The intent of this review is to describe the original purpose of the MMSE and how it is currently used in clinical practice and in research. Advantages and limitations of the MMSE in providing a valid diagnosis of cognitive impairments (dementia) are discussed including sensitivity and specificity, the issues of the relationship of the MMSE scores to sociodemographic variables and examinations of factor structures of the MMSE. It is concluded that the MMSE provides a valid diagnosis of cognitive impairments among people with moderate and severe dementia in general populations. However, MMSE is not recommended as a screening instrument for the detection of early stages of dementia. Studies are needed to extend the present knowledge about how or whether the MMSE can be used in the clinical diagnostic evaluation of dementia and how demented patients treated with medications should be monitored.     

The validity of psychometric instruments for detection of dementia in the elderly general population

OBJECTIVE: To compare the validity of different instruments for screening and diagnosis of dementia and to provide threshold scores for these purposes, ie screening focusing on a high sensitivity and diagnosis focusing on a high specificity. SETTING: 287 subjects from a general population sample who had completed more than one of these psychometric tests. METHODS: The performances of the Structured Interview for the Diagnosis of Dementia of the Alzheimer Type, Multi-Infarct Dementia and Dementias of Other Aetiology according to ICD-10 and DSM-III-R, the Mini-Mental State Examination, the Blessed Dementia Rating Scale, the Global Deterioration Scale, the Verbal Fluency Test, the Word list Learning Task, the Trail Making Test and the Labyrinth Test were compared using receiver operating characteristics analysis. RESULTS: The validity of composite instruments for the discrimination of dementia and cognitive health was higher than the validity of individual tests. However, some cognitive tests, ie verbal fluency and immediate recall of words, reached a high validity, making them useful and short screening instruments for dementia. CONCLUSION: There is no perfect instrument for screening and diagnosis of dementia. Different threshold scores for different purposes were provided in the present study. Recommendations for improving the validity of the Delayed Word List Learning Task for discriminating dementia and cognitive health include the expansion of list length and shortening of delay.     

Alzheimer's disease in the NAS-NRC Registry of aging twin veterans, IV. Performance characteristics of a two-stage telephone screening procedure for Alzheimer's dementia

In the course of a large twin study of Alzheimer's disease we used a two-stage telephone screening procedure. The modified Telephone Interview for Cognitive Status (TICS-m) served as an initial screen for dementia in 12709 individuals. The telephone Dementia Questionnaire (DQ) was then asked of collateral informants for subjects with TICS-m scores below 28, as well as for samples of persons with higher TICS-m scores. Based upon DQ responses, individuals with cognitive impairment not attributable to focal causes underwent assessment for the clinical diagnosis of Alzheimer's disease ('Alzheimer's dementia'), as did their twins. Well-defined Alzheimer's dementia was apparent in 39 subjects. Employing a cut-off of 27 or lower as indicative of cognitive impairment, the sensitivity of the TICS-m in the detection of Alzheimer's dementia was estimated at > 99% and specificity at 86%. Inclusion of the DQ increased the specificity at the 27/28 cut-point to 99%. The TICS-m score was associated with an area under the receiver operating characteristic (ROC) curve of 0.88 (95% confidence interval 0.81 to 0.94). The maximum number of cases of Alzheimer's dementia remaining undetected in the sample was estimated to be 34.     

Validation of a French version of an informant-based questionnaire as a screening test for Alzheimer's disease

BACKGROUND: Development of informant-based screening tests for dementia is an emerging field. The reliability and validity of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), an instrument that screens for dementia in general, have been established. We conducted a study to validate a French version of the IQCODE as a screening test for Alzheimer's dementia in the elderly living in the community. METHOD: In the Canadian Study of Health and Aging, subjects were screened in their own homes using the modified Mini-Mental State Exam (3-MS). Those who screened positive, along with a sample of subjects who screened negative, were referred for a complete clinical examination. In Quebec, an informant was asked to complete the French version, IQCODE(F), at that time. Based on the final clinical diagnoses, performances of the IQCODE(F) and Mini-Mental State Examination (MMSE, converted from 3-MS) in screening for Alzheimer's disease were evaluated. RESULTS: Of the 237 subjects, the mean IQCODE (F) score was 3.4 (s.d. = 0.6), on a 5-point scale (1 = improvement in condition over the past 10 years, 5 = marked deterioration, 3 = no change). The mean MMSE score was 23.1 (s.d. = 4.5). The scores on the two scales were correlated (r = -0.44, P < 0.001). The IQCODE(F) scores were unrelated to education (r = -0.07, P > 0.3) in contrast to the MMSE scores (r = 0.28, P < 0.001). With respect to a diagnosis of probable Alzheimer's disease, the IQCODE(F) (cut-off point 3.6) had a sensitivity of 75% and a specificity of 95.6%. The sensitivity and specificity of the MMSE (cut-off point 23) were 70% and 82.3% respectively. CONCLUSION: The findings of the IQCODE(F) are consistent with those of the English version in correlation with the MMSE and apparent freedom from educational bias. The IQCODE is superior to the MMSE as a screening test for probable Alzheimer's disease in the elderly living in the community. It may be a useful addition to the screening tests already available, especially for the less well educated.     

Alzheimer's Rural Care Healthline: Linking Rural Caregivers to Cognitive-Behavioral Intervention for Depression.

Objective: To describe the challenges faced by rural caregivers in providing assistance to older family members with Alzheimer's disease and closely related conditions. Procedure: Preliminary focus group findings from a new grant initiative, Alzheimer's Rural Care Healthline, that assesses the efficacy of telephone-based cognitive- behavioral intervention for rural dementia caregivers. Groups identified specific caregiver educational and skills-training requirements and best methods for soliciting referrals from rural health providers, community elder care agencies, and churches. Results: Trust emerged as an overarching theme, along with family and community privacy issues and the stigma associated with dementia. Conclusions: Future studies should consider the educational priorities, technological requirements, and sociocultural context of rural caregivers in designing telehealth-based interventions, including issues of privacy, stigma, and trust. Recognition of these factors may lead to increased acceptability, frequency of use, and sustainability of rural telehealth programs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Standardization of the diagnosis of dementia in the Canadian Study of Health and Aging

Standardization of diagnostic procedures for cognitive impairment in large epidemiologic surveys remains difficult. This paper reports results of diagnostic standardization in a subsample of 2,914 elderly (age 65 years+) Canadians from the Canadian Study of Health and Aging (CSHA; n = 10,263). The objectives were to measure the consistency of the CSHA diagnosis as a test of validity; to assess inter-rater reliability, and to assess the impact of neuropsychological data on the diagnosis of dementia. The CSHA clinical assessment included a nurse's examination, Modified Mini-Mental Status (3MS) exam and Cambridge Mental Disorders Examination, neuropsychological tests, medical history and examination, and laboratory investigations. A final diagnosis was reached in a consensus conference which incorporated preliminary diagnoses from both physicians and neuropsychologists. Computer algorithms, which were developed to check consistency between the clinical observations and the final diagnosis, demonstrated 98% concordance with DSM-III-R criteria for dementia and 92% with NINCDS-ADRADA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) criteria for probable Alzheimer's disease. Inter-rater agreement was high: kappa = 0.81 for dementia/no dementia; kappa = 0.74 for normal/cognitive impairment, not dementia/ dementia. Comparisons of diagnoses between raters by clinical specialty revealed few systematic differences. The impact of neuropsychological input on the physician's diagnosis was most marked in the borderline cases between diagnostic categories.     

Quality of life and dementia

OBJECTIVE: To review the relationship between quality of life (QOL) and dementia. Development. QOL is a factor which takes into account all the different aspects of life which make a person feel that life is worth living, such as: 1. Physical health. 2. Functional status. 3. Psychological and cognitive sphere, and 4. Social health. There are two types of instruments for evaluating these aspects: firstly general ones which measure the QOL independently of illness, and secondly those which are specific to the illness concerned. In dementia, QOL covers the same traditional areas: cognitive competence, capacity to carry out everyday activities, social conduct and the balance between positive and negative emotions. However, evaluation of QOL in dementia has its own specific difficulties, since it is often impossible to determine such a fundamental factor as the subjective well-being of the patient, in which case the opinion of the person looking after the patient is essential. According to Lawton's approximation, as well as the subjective aspect of perceived psychic welfare and quality of life, the QOL in dementia is composed of external social and objective dimensions such as behaviorally competence and the quality of the patient's environment. In a review done in 1995 it was found that most of the instruments designed to measure the QOL have not been sufficiently validated for Alzheimer's disease. CONCLUSIONS: QOL in dementia has specific features including external aspects such as the opinion of the carer and the quality of the patient's environment in addition to the subjective aspects. It is necessary to develop and validate specific instruments for QOL in dementia.     

Clock-face drawing, reading and setting tests in the screening of dementia in Chinese elderly adults

Comprehensive neuropsychological batteries focus on the subtle cognitive deficits in dementia, but a brief screening instrument is also of immense practical value. As the clock-drawing test encompasses a number of cognitive domains frequently disturbed by the dementing process, it is considered to be a suitable screening instrument for the disorder. We documented the usefulness of a new scoring method of the clock-drawing test for screening of dementia in the elderly Chinese in Hong Kong. Fifty-three demented individuals and 53 healthy elderly controls were assessed. At a cutoff score of 3/4, the sensitivity and specificity of the clock-drawing test in screening of dementia was 83% and 79%. With a composite test of clock reading and clock setting, the positive predictive value of the clock face test was 98%. This new scoring method of clock-drawing proved to be a valid measure for screening of dementia. It is applicable in non-English speaking populations and should be a useful adjunct for quick screening assessment of dementia.     

Tumor necrosis factor inhibits the transcriptional rate of glucose-6-phosphatase in vivo and in vitro

OBJECTIVE: After Alzheimer's disease, vascular dementia (VaD) and frontotemporal dementia (FTD) are among the most common dementing illnesses. FTD may have a neuropsychological profile similar to that of VaD, and patients with these dementias may be difficult to distinguish on clinical examination. The purpose of this study was to elucidate distinct cognitive profiles of a large group of FTD and VaD patients on a brief, clinical mental status examination. DESIGN: A comparison of 39 FTD patients and 39 VaD patients on a brief, clinical mental status examination. SETTING: A Dementia Research Center and affiliated, university hospitals. METHODS: The FTD patients were diagnosed by noncognitive clinical and neuroimaging criteria, and the VaD patients met NINDS-AIREN criteria for vascular dementia. The two dementia groups were comparable on three dementia assessment scales. MEASUREMENTS: The mental status measures included the neuropsychological battery from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), plus supplementation from the Neurobehavioral Cognitive Status Examination (NCSE) for cognitive areas not assessed by the CERAD). RESULTS: The FTD and VaD groups differed significantly on the mental status examination measures. FTD patients performed significantly better than the VaD patients on digit span and constructions, despite comparable performance by both groups on calculations. Although not statistically significant, the FTD group performed worse than the VaD group on verbal fluency and abstractions. These differences were not explained by group differences in age and education. CONCLUSION: These results suggest that cognitive differences between FTD and VaD groups reflect greater frontal pathology in contrast to relative sparing of posterior cortex and subcortical white matter in FTD. These cognitive differences as measured by a mental status examination may help distinguish between these two dementia syndromes.     

The Mini-Mental State Examination in general medical practice: clinical utility and acceptance

OBJECTIVE: To examine the psychometric properties, acceptance, and screening efficacy of the Mini-Mental State Examination (MMSE) in an internal medicine practice. MATERIAL AND METHODS: The MMSE was administered more than 4,000 times by 27 internists to 3,513 elderly patients (2,299 women and 1,214 men, 60 to 102 years old) who underwent general medical examinations. The efficacy of the MMSE for screening was measured in a subsample of age- and sex-matched patients with dementia (N = 185) and control subjects (N = 227). MMSE scores were correlated with age and education in the community sample. The attitudes of physicians about the MMSE were assessed with a 12-question survey. Sensitivity, specificity, and predictive values were calculated. RESULTS: Performance on the MMSE among persons older than 59 years was influenced by age and education but not by sex. During an interval of 1 to 4 years, a change of 4 or more points in the total MMSE score is needed to indicate substantial cognitive deterioration. Participating physicians considered the MMSE of little value for routine screening in unselected populations but wanted it available for use as a clinical test. The traditional MMSE cutoff score of 23 or less had a sensitivity of 69% and a specificity of 99%. Use of age- and education-specific cutoff scores improved the sensitivity to 82% with no loss of specificity. With use of typical base rates for dementia in a general medical practice, the positive predictive value was less than 35%. CONCLUSION: The clinical utility of the MMSE and acceptance by physicians may be improved through awareness of the influences of age and education on the MMSE and by its application in settings with a high base rate of dementia. The MMSE is ineffective when used to screen unselected populations; it should be used for persons at risk of cognitive compromise.     

The Alzheimer's Disease Assessment Scale: patterns and predictors of baseline cognitive performance in multicenter Alzheimer's disease trials

The cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) is used as an efficacy measure in clinical drug trials of Alzheimer's disease (AD). We used data from 1,648 AD participants in two identical 26-week multicenter drug trials to examine the distribution of baseline ADAS-Cog scores in relation to selected demographic and clinical variables, Mini-Mental State Exam (MMSE), Global Deterioration Scale (GDS), and Geriatric Evaluation by Relative's Rating Instrument (GERRI) scores. At baseline, the mean (+/-SD) MMSE score was 18 +/- 4, the ADAS-Cog score was 28 +/- 11, and most subjects were in GDS stage 4 or 5. The ADAS-Cog score was statistically significantly correlated with MMSE (R = -0.76, p < 0.0001) and GERRI (R = 0.40, p < 0.0001) total scores. Correlations among the ADAS-Cog items ranged from 0.19 to 0.59 and all were statistically significant (p < 0.0001). In a multiple regression model, younger age, male gender, older age at onset of dementia, use of concurrent estrogen, and use of concurrent anti-inflammatory agents were statistically significantly associated with superior cognitive performance. We also present data on the distribution of ADAS-Cog scores in relation to subjects' age, level of education, MMSE score, and GDS stage. Because age, MMSE score, and GDS stage (and not the ADAS-Cog) are commonly used to select subjects for AD clinical trials, our data should improve the ability of sponsors to predict ADAS-Cog scores of the subjects in their trials on the basis of the inclusion criteria used. Our data also suggest that age, gender, age at onset of dementia, level of education, and use of estrogen (in women) or anti-inflammatory drugs are related to cognitive abilities in AD. Further studies are needed to assess how and when cognitive differences related to these variables arise.     

Downgaze palsy and bilateral ptosis due to a thalamomesencephalic lesion

A telephone screening assessment designed to identify persons likely to have dementia was conducted in a random community sample of 4,403 adults. Because of the cognitive impairment of the subjects, information was obtained from caregivers. Twenty-nine subjects were identified as likely to have dementia. Of these, 15 agreed to a complete dementia assessment conducted in their residence, and all were diagnosed with dementia. There was high reliability between the caregiver telephone interview and the clinical examination.     

Vascular dementia: a contemporary review of epidemiology, diagnosis, prevention, and treatment

The past decade has seen a renewed interest in vascular dementia. Key epidemiologic studies have examined the prevalence, incidence, course and risk factors of vascular dementia. New classification systems have been developed to improve the reliability of the diagnosis, and there have been advances in diagnostic methodology, such as neuroimaging and neuropsychological assessment. New treatments for vascular dementia are being developed to protect the brain from cerebral ischemia and to limit progression of cognitive impairment. Diagnostic criteria for vascular dementia remain to be validated by carefully designed, systematic, clinicopathologic study. Once such criteria are validated, meaningful study of subgroups of vascular dementia can be explored. Until the relationship between vascular dementia and Alzheimer's disease is better defined, the nosology for vascular dementia may be defined best as dementia associated with stroke.     

Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease

Brain imaging techniques have the potential to characterize neurobiological changes that precede the onset of cognitive impairment in persons at risk for Alzheimer's disease. As previously described, positron emission tomography (PET) was used to compare 11 cognitively normal persons 50 to 62 years of age who were homozygous for the epsilon4 allele of apolipoprotein E and 22 persons without the epsilon4 allele with a reported family history of Alzheimer's dementia who were matched for sex, age, and level of education. The epsilon4 homozygotes had significantly reduced glucose metabolism in the same brain regions as patients with Alzheimer's dementia; the largest reduction was in the posterior cingulate cortex. As described here, magnetic resonance imaging (MRI) was used to compare hippocampal volumes in the same subject groups. The epsilon4 homozygotes showed nonsignificant trends for smaller left and right hippocampal volumes; overall, smaller hippocampal volumes were associated with reduced performance on a long-term memory test. Whereas PET measurements of cerebral glucose metabolism begin to decrease before the onset of memory decline, MRI measurements of hippocampal volume begin to decrease in conjunction with memory decline in cognitively normal persons at risk for Alzheimer's disease.     

Psychiatric manifestations in dementia: phenomenologic perspectives

The study of psychiatric manifestations in dementia has long been overshadowed by the more classical manifestations of the disease, such as memory loss and other cognitive deficits. In recent years, however, psychiatric symptoms as part of the demential process have attracted interest and research has become more specific. Clinicians are faced with diagnostic, treatment and management difficulties related to affective or psychotic symptoms, which account for much distress and morbidity. Several studies indicate that the prevalence of psychiatric manifestations in clinical populations of patients suffering from dementia is high: 15% to 30% for hallucinations, 15% to 30% for delusions, ten percent to 20% for major depression and 40% to 50% for depressed mood. These figures tend to confirm the hypothesis that psychiatric features in dementia are neither infrequent nor atypical. Thus, researchers have sought to link psychotic or depressive symptomatology with several clinical characteristics of dementia, namely stage, severity, prognosis or cognitive dysfunction. Some recent studies involving extensive neuropsychological evaluations indicate that subgroups of patients can be defined according to psychiatric criteria, as well as cognitive or neurological criteria. Unfortunately, results are inconsistent. Some of the contradictions in the literature are related to poorly defined terms and symptoms, a lack of reliable operational criteria, absence of validation of instruments and scales and heterogeneity of the populations studied. Ambiguous syndromes, such as pseudodementia, while illustrative of certain clinical situations, have not been helpful in categorizing demented patients. The author suggests that research focused on specific and clearly defined psychiatric symptoms in dementia will better serve our comprehension of mixed syndromes.     

Cognitive changes in very old persons with dementia: the influence of demographic, psychometric, and biological variables

Longitudinal changes in global cognitive functioning, indexed by the Mini-Mental State Examination (MMSE), in subjects with dementia (Alzheimer's disease and vascular dementia) were examined. The roles of several demographic, psychometric, and biological indices in predicting cognitive deterioration were also examined. The sample consisted of 36 very old (M age at entry = 83.0 years, range = 75-95) adults with dementia from a community-based study. Subjects were tested on two occasions separated by approximately 2.5 years. Results indicated significant longitudinal decline in MMSE scores over the retest interval; the average decline was estimated as 2.43 (SD = 1.81) points per year. Several factors were associated with cognitive deterioration. Higher initial MMSE scores were associated with greater deterioration, whereas superior forward digit span and Block Design at entry were associated with attenuated decline, once differences in baseline severity were accounted for. By contrast, a variety of other putatively important variables exhibited no relationship to decline, including age, gender, education, onset age, dementia type, backward digit span, as well as a number of biological parameters (e.g., vitamin B12, folic acid). The results suggest that although the magnitude of cognitive deterioration in dementia is highly variable, several indicators may be useful predictors of future changes in cognitive functioning.     

Confrontation naming in Alzheimer's patients: Relation to disease severity.

Reports of Alzheimer's disease patients in whom naming performance is disproportionate to other cognitive performances raise questions about the stage model, or dementia-severity level, for predicting naming performance. Thus, dementia severity as defined by Global Deterioration Scale ratings, Mini-Mental State Examination scores, and combinations of them was evaluated as a predictor of naming performance in 102 Alzheimer's patients and was found to account for approximately ? of performance variability. Additional contributions from age at onset, duration, family history, and gender were negligible. Therefore, naming ability can be argued to have a subcomponent that is not subsumed by overall cognitive ability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)