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Standardized Mini-Mental State Examination Scores and Verbal Memory Performance at a Memory Center: Implications for Cognitive Screening

American Journal of Alzheimer’s Disease & Other Dementias® 2015, Vol. 30(2) 145-152 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/1533317514539378 aja.sagepub.com

Maureen Lacy, PhD1, Tobias Kaemmerer, MA2, and Sheena Czipri, MA2

Abstract Memory decline is often among the first signs heralding the emergence of mild cognitive impairment or dementia regardless of etiology. Despite its limited inclusion of memory screening, the Mini-Mental State Exam (MMSE) continues to be the most ubiquitous, first-line screening tool for dementia and cognitive decline. In response to well documented problems with the sensitivity of this instrument and the growing importance of cognitive screening, we assessed the utility of the MMSE as a screening tool among older adults presenting for evaluation at a memory clinic. The Standardized MMSE and a standardized verbal memory test — the Hopkins Verbal Learning Test-Revised (HVLT-R) — were administered to 304 consecutive referrals at a universitybased outpatient memory clinic. Among patients scoring above 25 on the MMSE (n ¼ 169), over half exhibited at least moderate memory impairment (HVLT-R delayed recall z  2.0) and more than 25% showed severe impairment (delayed recall z  3.0). Perhaps even more striking was that among those who achieved perfect (30/30) or near perfect (29/30) scores on the MMSE (n ¼ 70), 43% displayed moderate to severe memory impairment. Although newer screening measures have shown improved sensitivity, more in-depth memory testing appears to be a vital component of successful screening and early detection.

Keywords MMSE, HVLT-R, dementia, mild cognitive impairment, cognitive screening

Background Memory loss is a growing concern among older adults seeking consultation with their general care physicians. According to the Alzheimer’s Association, an estimated 7.1 million Americans aged 65 years and older will have Alzheimer’s disease in 2025, representing a roughly 40% increase over the next decade.1 Mild cognitive impairment is a term coined by Petersen and colleagues2 to define individuals who display cognitive deficits without functional impairment. Although a mild cognitive impairment diagnosis does not require memory impairment, amnestic mild cognitive impairment is the most prevalent subtype3,4 and may convert to dementia more frequently and more quickly than nonamnestic subtypes.5-8 Given the central role of memory impairment in both dementia (regardless of etiology) and the most common type of mild cognitive impairment, successful screening and early detection of these disorders hinge largely on adequately sensitive detection of memory impairment. Over 2 decades ago, Welsh and colleagues9 demonstrated that tests of delayed recall had particular utility in the early detection of Alzheimer’s

disease, suggesting that such tests should be a point of focus in screening for dementia. The Mini-Mental State Examination (MMSE)10 has been the most widely utilized screening tool for dementia for more than 25 years. Although initially viewed as an inpatient screen for general cognitive impairment, it is often utilized as the standard screening tool for cognitive impairment and dementia in outpatient settings.11 Mitchell12 conducted a meta-analysis of 39 studies examining the utility of the MMSE for detecting cognitive impairment across a variety of clinical settings. In memory clinic settings, the MMSE was found to have a pooled sensitivity of 0.79, a positive predictive value of 0.86, and a

1 2

Department of Psychiatry, University of Chicago, Chicago, IL, USA Department of Psychology, Roosevelt University, Chicago, IL, USA

Corresponding Author: Maureen Lacy, PhD, University of Chicago, 5841 S Maryland Avenue, Chicago, IL 60637, USA. Email: [email protected]

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American Journal of Alzheimer’s Disease & Other Dementias® 30(2)

146 negative predictive value of 0.73 for detection of dementia. The case-finding ability of the MMSE was best in specialist settings when used to confirm a suspected diagnosis. Despite these relatively promising findings, the problem of high false-negative rates has surfaced repeatedly across 3 decades of literature on the MMSE.13-17 For instance, echoing longstanding concern over the measure’s inadequate sensitivity, Galasko and colleagues18 found that 5 (nearly 19%) of 27 patients with a diagnosis of mild Alzheimer’s disease scored 27 or above on the MMSE. Shiroky et al19 revealed that, although uncommon (eg, 8 of 632 patients in their study), patients with a diagnosis of probable Alzheimer’s disease can actually perform perfectly (30 of 30) on the MMSE. More recent investigations have revealed that the MMSE is particularly insensitive to subtle cognitive deficits and is not a valid screening tool for early stage Alzheimer’s disease20 or mild cognitive impairment.21 For instance, using the commonly employed a cutoff of 25, Nasreddine and colleagues21 revealed that the MMSE had a sensitivity of only 18% for the detection of mild cognitive impairment. Debate over the sensitivity and overall utility of the MMSE has been compounded by a considerable lack of uniformity or agreement around a single standard cutoff score. In fact, a rather wide range of cutoff scores has been suggested with no single cutoff emerging as a ‘‘gold standard’’ for classifying a patient as impaired. In addition, based on longstanding evidence that MMSE scores are mediated by age and educational attainment,22,23 attempts have been made to identify optimal cutoffs for different groups based on these demographic factors.24-26 In spite of such efforts, there remains a lack of uniform clinical guidelines for adjusting the cutoff score based on age and education, leaving clinicians to rely solely on their judgment on a case-by-case basis. In a recent review and update of cognitive screening procedures,11 a cutoff of 25 was indicated as reflective of normal, intact functioning. However, others27 have recently demonstrated that a higher cutoff of 28 may be most useful in screening for mild cognitive impairment. Thus, there remains a lack of clarity as to what score may indicate impairment and for whom. In response to concerns about individual raters using idiosyncratic procedures (ie, offering hints and giving half points) when administering and scoring the MMSE, attempts have been made to standardize administration and scoring procedures so as to improve the interrater and intrarater reliability of this measure. The Standardized MMSE (SMMSE),28 although identical to the original MMSE with respect to test content, follows strict guidelines and instructions for standardized administration and scoring. Specifically, the SMMSE provides verbatim instructions to be read aloud to the examinee for each item, detailed rules for standardized scoring, and time limits on all tasks (see Molloy and Standish for a review).28 Against a backdrop of a wide range of suggested cutoffs and serious concerns about the test’s sensitivity, a number of authors have explored the specific limitations of the content and structure of the MMSE. Leading criticisms include the fact that embedded memory testing is limited to a brief delayed

recall of 3 words with no long delayed recall or recognition component; the lack of direct tests of executive/frontal abilities; single-item assessment of most functions with no graded scoring; and the lack of more challenging, cognitively demanding items.29 The lack of sufficient memory assessment may be the most limiting characteristic of the test, as detection of memory impairment is fundamental to the diagnosis of amnestic mild cognitive impairment and dementia. Many formal neuropsychological measures have been developed to provide more robust, in-depth assessment of memory function. Given concerns over the sensitivity of the MMSE, authors have directly compared its utility to that of standard neuropsychology memory tests in the detection of dementia. Frank and Byrne30 compared the sensitivity of the MMSE to that of the original list-learning measure, the Hopkins Verbal Learning Test (HVLT),31 in the detection of mild dementia among older adult participants. The authors found the raw learning score on the HVLT to be more sensitive (0.96) but less specific (0.80) to mild dementia than the MMSE (sensitivity ¼ 0.88; specificity ¼ 0.93) using optimal cutoff scores of 18 and 25, respectively. Noting the higher susceptibility of MMSE to ceiling effects among those with mild impairments, the authors concluded that the HVLT may be more useful in the early detection of dementia. Building on these findings, Hogervorst and colleagues32 found that the inclusion of the HVLT recognition discrimination index improved the test’s sensitivity in the detection of dementia slightly from 0.87 (raw learning score alone) to 0.91 (raw learning score and recognition discrimination index combined). Others have called into question the overall utility of the original HVLT, which lacks a delayed recall trial, as a dementia screening tool. Kuslansky and colleagues33 noted relatively modest sensitivities and positive predictive values for both the MMSE (sensitivity ¼ 0.86) and the HVLT (sensitivity ¼ 0.83) in the detection of dementia, suggesting that a large number of individuals with significant cognitive impairment would be misclassified as ‘‘intact’’ by either test used alone. The most recent version of the HVLT, the Hopkins Verbal Learning Test-Revised (HVLT-R),34 was reworked to include a delayed (20 minutes) free recall trial. This newer version has been shown to have high sensitivity (0.95) and moderate specificity (0.83) in distinguishing patients with probable Alzheimer’s disease from normal controls.35 Given that tests of delayed recall have been shown to have good utility for cognitive screening,9 there is a need to compare the utility of the MMSE to that of the HVLT-R in screening for cognitive impairment among older adults presenting with cognitive complaints. This need is underscored by ongoing uncertainty and debate as to the viability of the MMSE as a screen for milder manifestations of cognitive impairment.

Objective Given the current public focus on early detection of memory decline and the central diagnostic role of memory decline in dementia diagnosis across etiologies, the focus of this

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investigation was to address the sensitivity of the MMSE as a screening measure for memory impairment. By International Classification of Diseases, Tenth Revision diagnostic definition,36 memory impairment is a core symptom of dementia, regardless of etiology. In addition, although several subtypes of mild cognitive impairment are recognized, the amnestic subtype is most prevalent and may convert to dementia more frequently and more rapidly than other subtypes.3-8 Thus, successful detection depends largely on the utilization of screening measures that are adequately sensitive to memory impairment, including more subtle, emergent memory deficits. Although a total SMMSE score above 25 has recently been indicated as reflective of normal, intact functioning,11 others27 have revealed that a cutoff of 28 may be most useful in detecting mild cognitive impairment. Using both of these cutoffs (25 and 28) successively, we examined the utility and sensitivity of the SMMSE as a screening tool by exploring the extent to which it captured those individuals with significant memory impairment as defined by performance on a more in-depth, standardized verbal memory measure.

Design This study was approved by the University of Chicago institutional review board. Retrospective data from a clinical database of older adult (65 years or older) memory center patients seen for neuropsychological evaluation by a University of Chicago neuropsychologist were collected and analyzed. Medical records and neuropsychological reports were examined for demographic data along with SMMSE raw scores; Wide Range Achievement Test-Fourth Edition (WRAT4)37 Reading subtest standard scores; and HVLT-R raw and z scores for total learning (ie, total correct responses across 3 immediate recall trials), delayed recall (ie, total correct responses spontaneously recalled after a 20-minute delay), and recognition discrimination (ie, number of true positives  number of false positives on the recognition paradigm). Hopkins Verbal Learning Test-Revised delayed recall and recognition discrimination z scores served as our primary indicators of memory performance. All measures were administered on the same day by a master-level neuropsychology-trained technician under direct supervision of a licensed clinical neuropsychologist. All data analyses were conducted using SPSS-19. In order to analyze the screening utility (in this case, the sensitivity to memory impairment as observed on the HVLT-R) of the SMMSE at 2 different cutoffs proposed in the recent literature,11,27 participants were initially grouped based on a SMMSE cutoff score of 25 and then again at a cutoff score of 28. Additionally, memory performance of those scorings perfectly on the SMMSE was analyzed.

Participants Patients (N ¼ 304) were older adults referred for neuropsychological examination by their geriatrician, neurologist, or primary care physician. Patients’ ages ranged from 65 to 95

years (mean ¼ 78.55; standard deviation [SD] ¼ 7.24). In all, 30% were caucasian and 67% were African American. Mean education was 13.47 years (SD ¼ 3.48). In all, 31% were male and 69% were female.

Measures The SMMSE is a 30-item clinician-administered cognitive screening measure allowing for brief and simple assessment of a limited set of cognitive abilities. It has been shown to have adequate test–retest and interrater reliability (r ¼ .89 and .82, respectively) and to discriminate between patients with probable Alzheimer’s disease and healthy controls with 87% sensitivity and 82% specificity.29 The HVLT-R is a clinician-administered auditory verbal list-learning task consisting of 3 learning trials of a 12-item word list, 1 delayed (20 minutes) recall trial, and a recognition discrimination paradigm. This measure has been shown to have adequate test–retest reliability (total recall r ¼ .74).34 For the purposes of our study, z scores for total learning, delayed recall, and recognition discrimination were analyzed. Consistent with common standards for interpreting neuropsychological performance on standardized measures, ‘‘mild’’ impairment was defined as a performance of at least 1.5 SDs below the mean (z  1.5), ‘‘moderate’’ impairment was defined as a performance of at least 2 SDs below the mean (z  2), and ‘‘severe’’ impairment was defined as a performance of at least 3 SDs below the mean (z  3). The WRAT4 Reading subtest has been shown to have strong internal consistency, moderate alternate-form reliability, and adequate concurrent validity as measures of verbal intellectual achievement.37 It is a widely utilized estimate of premorbid intellectual functioning.

Statistical Analyses The relative contribution of age, educational attainment, estimated premorbid intellect, gender, and race to SMMSE scores in the full sample was explored via multiple regression analysis. Based on results, partial correlations were performed to analyze the correlation between SMMSE scores and HVLT-R memory performance while controlling for age and education. After analyzing SMMSE and HVLT-R performance of the full sample, we split the sample into ‘‘intact’’ and ‘‘impaired’’ groups based on a SMMSE cutoff of 25 and conducted within-group and between-group analyses of HVLT-R memory performance. The group means for HVLT-R total learning z score, HVLT-R delayed recall z score, and HVLTR recognition discrimination z score were then calculated. Frequency distributions were analyzed to determine percentages of ‘‘intact’’ patients (SMMSE > 25) demonstrating mild, moderate, and severe levels of memory impairment on the HVLT-R. Finally, independent samples t tests were conducted to compare HVLT-R memory performance between ‘‘intact’’ (SMMSE > 25) and ‘‘impaired’’ (SMMSE 25)

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Table 1. Age, Education, and Estimated Premorbid Intellect Among ‘‘Intact’’ Versus ‘‘Impaired’’ Participants Using a SMMSE Cutoff of 25. Intact (SMMSE > 25; n ¼ 169)

Impaired (SMMSE  25; n ¼ 135)

t(df)

P

77.47 (7.82) 14.33 (3.04) 101.59 (21.41)

79.89 (6.22) 12.39 (3.69) 88.90 (24.82)

2.93 (302) 5.02 (302) 4.78 (302)

.004a 25 Intact n ¼ 169

t(df)

SMMSE Cutoff of 28 28 Impaired n ¼ 234

P

>28 Intact n ¼ 70

t(df)

P

a

Mean HVLT-R total learning z score (SD) 2.45 (.90) 1.42 (.95) 9.52 (302)

Standardized mini-mental state examination scores and verbal memory performance at a memory center: implications for cognitive screening.

Memory decline is often among the first signs heralding the emergence of mild cognitive impairment or dementia regardless of etiology. Despite its lim...
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