Screening for Cognitive Impairment in Multiple Sclerosis An Evaluation of the Mini-Mental State Examination William W.
Beatty, PhD, Donald
E.
Goodkin,
\s=b\ The usefulness of the Mini-Mental State Examination (MMSE) as a screening test for identifying cognitive impairment in patients with multiple sclerosis (MS) has been questioned because many patients who score above the suggested cutoff score of 24 exhibit severe focal or global cognitive deficits. We reevaluated the usefulness of the MMSE by studying 85 patients with clinically definite MS who also received an extensive battery of neuropsychological tests. Although scores on the MMSE were negatively correlated with the number of neuropsychological tests on which patients with MS displayed impairment, the MMSE was not sufficiently sensitive to identify precisely defined dementia in these patients. The MMSE was nonetheless a useful predictor of focal cognitive impairment, particularly in re-
lapsing-remitting patients with relatively minor physical disabilities. Additional analyses suggested strategies for minor modifications of the MMSE that may improve its sensitivity and specificity for identifying dementia while preserving its major advantages as a screening examination: brevity and ease of administration and scoring. (Arch Neurol. 1990;47:297-301)
Xp ormai neuropsychological testing has
repeatedly demonstrated that all, patients with multi-
many, but not
Accepted for publication August 2,
1989. From the Clinical Neuroscience Research Program, Neuropsychiatric Research Institute, Fargo, ND (Dr Beatty); the Department of Psychology, North Dakota State University, Fargo (Dr Beatty); and the Mellen Center, The Cleveland (Ohio) Clinic Foundation (Dr Goodkin). Reprint requests to The Cleveland Clinic Foundation, The Mellen Center, Area U1, 9500 Euclid Ave, Cleveland, OH 44106 (Dr Goodkin).
MD
pie sclerosis (MS) exhibit significant cognitive impairment, especially on tasks that require rapid information processing, recall of newly acquired knowledge, or problem-solving abil¬ ity.1 As confidence in the reproducibil¬ ity of these observations has grown, neurologists' need for a brief but reli¬ able way of screening for cognitive impairment in patients with MS has increased. In addition to brevity and ease of scoring, an ideal screening ex¬ amination would predict performance on a broad range of cognitive func¬ tions, including some that are not as¬ sessed directly by the test. Many neu¬ rologists have employed the MiniMental State Examination (MMSE)2
for this purpose, but found the test to be insensitive to cognitive impairment in MS when the recommended cutoff scores (usually below 24)34 were used. For example, Franklin and colleagues5 recently compared the ability of the MMSE and a neuropsychological screening battery (NSB) that they de¬ veloped to detect cognitive impairment in a sample of 60 patients with clini¬ cally definite chronic-progressive (CP) MS who were diagnosed using the cri¬ teria of Schumacher et al.6 Although none of their patients scored below 24 on the MMSE, 83% were impaired on a composite summary score derived by considering performance on all of the tests included in their NSB, and 60% of the patients were impaired on a com¬ posite cognitive summary score ob¬ tained by considering only those subtests judged to require minimal upper-extremity motor skills. By con¬ trast, Franklin et al5 also reported that "only 20% of patients were impaired on the Folstein MMSE with cutoffs
developed using data from the NSB standardization sample." While the results demonstrate the greater sensi¬
tivity of the NSB compared with the MMSE for routine cognitive screening of patients with MS, the NSB takes at least 45 minutes to administer, while
the MMSE can be administered and scored in a neurologist's office in 5 to 10 minutes. In addition, correlations be¬ tween NSB scores and other cognitive testing (ie, problem solving and re¬ mote memory) are as yet undeter¬ mined. In this article, we show that while the MMSE does predict the existence of focal cognitive deficits in patients with MS reasonably well, in its present form, the test is too insensitive to reli¬
ably identify global cognitive impair¬ ment. We also suggest specific strate¬ gies for modifications of the MMSE that may improve its sensitivity for detecting dementia without exces¬ sively increasing the administration and scoring times required for a screening test. PATIENTS AND METHODS
Data are reported for 43 patients with CP MS and 42 patients with relapsing-remitting (RR) MS who served as subjects in on¬ going research studies of cognitive function in MS." All patients met criteria for clini¬ cally definite MS10; precise definitions used to classify the patients by disease type have been reported elsewhere." For our pur¬ poses, dementia was defined as impairment (ie, scores at or below the fifth percentile for controls) in three of four cognitive func¬ tions: (1) naming, ie, the total number cor¬ rect without cues on the 60-item version of the Boston Naming Test (BNT)"; (2) prob¬ lem solving, ie, the number of categories achieved (out of six) on the Wisconsin Card Sorting Test (WCST),12 a test that requires
Downloaded From: http://archneur.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/26/2015
subjects to form and shift concepts based on feedback from the examiner; (3) speed of information processing (impairment on ei¬ ther the FAS test, which requires generat¬ ing words that begin with the letters F, A, or S as quickly as possible, or the Symbol Digit Modalities Test [SDMT],13 which re¬ quires substituting numbers for geometric symbols as rapidly as possible); and (4) memory (impairment on three of the five measures of anterograde and remote mem¬ ory considered in this article). The memory measures were (1) the total number of words recalled after a 15-second delay on a 10-trial short-term memory test in which four words were given per trial, (2) the to¬ tal number of words recalled immediately after presentation of a 14-word list that was presented for four trials, (3) the percent correct on a recognition test for the same word list given 30 minutes later, (4) the to¬ tal number of items recalled on a test of re¬ mote memory that required identifying fa¬ mous people from photographs or answer¬ ing questions about past public events, and (5) the total number of items correctly rec¬ ognized on the same remote memory test. Patients with RR MS averaged 38.1 ± 7.7 (SD) years of age, 14.3 ± 2.0 years of edu¬ cation, and 4.3 ± 3.2 years of disease since diagnosis, and attained mean scores of 2.1 ± 1.9 on the Expanded Disability Status Scale (EDSS)14 and 1.8 ± 1.7 on the Annu¬ lation Index.15 Patients with CP MS aver¬ aged 48.9 ± 10.9 years of age, 13.7 ± 2.7 years of education, and 18.7 ± 9.8 years since diagnosis of disease, and attained mean scores of 6.6 ± 1.5 on the EDSS and 6.2 ± 2.0 on the Ambulation Index. Thus, the CP patients were older (P < .001), had MS longer (P < .001), and were more se¬ verely disabled physically (P < .001 for both EDSS and Ambulation Index) than the RR patients, but the CP and RR groups did not differ significantly in length of ed¬ ucation. More detailed descriptions of the test materials and procedures can be found in previous reports" or in published test manuals."13 Our patients and controls re¬ sponded orally to the SDMT to minimize the potential confounding of impaired up¬ per-extremity motor activity.13 Only 22 CP patients were assessed on the WCST; oth¬ erwise, all patients completed all tests. The important features of the version of the MMSE used in our study are as follows: (1) the concrete nouns ring, apple, and ele¬ phant were used for the registration and recall phases; (2) only serial 7s was used in the calculation phase; (3) patients for whom writing was very difficult because of obvious upper-extremity deficits were allowed to produce a complete sentence orally; (4) the three-stage command used required the patient to pick up a small object in the nondominant hand, shake it, and place it on a book located on the table where the patient was seated. This modified three-stage com¬ mand was employed to preclude the possi¬ bility that patients with impairments in balance might fall and injure themselves while attempting to place the folded paper on the floor (the three-stage command from the Folstein version of the MMSE requires subjects to pick up a piece of paper, fold it
in
averaged 28.5 (SD, 2.4; range, 14 to 30); the 3 patients scoring below 24 at¬
half, and place it on the floor); and (5) patients and controls who lived more
most
than 50 miles from our clinic were tested in their own homes. Those who were not were asked to name the county in which they re¬ sided. Previous results7 have indicated that there are no statistically significant differ¬ ences in neuropsychological test perfor¬ mance of patients or controls between those tested at home and those tested in the clinic.
tained scores of 23, 20, and 14. It is evident from the data in Table 1 that as scores on the MMSE dropped from the maximum value of 30, the proportion of patients exhibiting im¬ pairment increased. Essentially, the same pattern was observed for each of the nine neuropsychological tests. The tests were, however, differentially sen¬ sitive to impairment. The most sensi¬ tive tests were the SDMT, the WCST,
RESULTS
Table 1 shows the proportion of all patients with MS displaying impair¬ ment on various cognitive tests as a
and immediate recall of the word list, which more than 25% of the pa¬ tients with MMSE scores in the normal on
function of their score on the modified version of the MMSE described above. For each measure, impairment was defined as a score at or below the fifth percentile of age- and educationmatched controls. Controls averaged 29.4 (SD, 0.8; range, 28 to 30) on the MMSE, while the 85 patients with MS
range
Table 1.—Percentages of Patients Exhibiting Score
on
impaired.
Impairment
Cognitive Tests*
on
Mini-Mental State Examination
29(21)
30(35) Anterograde
were
Previous studies9·16 have demon¬ strated that the cognitive impair¬ ments of CP patients are more severe than those of RR patients. It was there¬ fore of interest to determine whether or not the MMSE is equally useful in
28(11)
27(9)
(No. of Patients)
24-26(6)
Beatty, PhD, Donald
E.
Goodkin,
\s=b\ The usefulness of the Mini-Mental State Examination (MMSE) as a screening test for identifying cognitive impairment in patients with multiple sclerosis (MS) has been questioned because many patients who score above the suggested cutoff score of 24 exhibit severe focal or global cognitive deficits. We reevaluated the usefulness of the MMSE by studying 85 patients with clinically definite MS who also received an extensive battery of neuropsychological tests. Although scores on the MMSE were negatively correlated with the number of neuropsychological tests on which patients with MS displayed impairment, the MMSE was not sufficiently sensitive to identify precisely defined dementia in these patients. The MMSE was nonetheless a useful predictor of focal cognitive impairment, particularly in re-
lapsing-remitting patients with relatively minor physical disabilities. Additional analyses suggested strategies for minor modifications of the MMSE that may improve its sensitivity and specificity for identifying dementia while preserving its major advantages as a screening examination: brevity and ease of administration and scoring. (Arch Neurol. 1990;47:297-301)
Xp ormai neuropsychological testing has
repeatedly demonstrated that all, patients with multi-
many, but not
Accepted for publication August 2,
1989. From the Clinical Neuroscience Research Program, Neuropsychiatric Research Institute, Fargo, ND (Dr Beatty); the Department of Psychology, North Dakota State University, Fargo (Dr Beatty); and the Mellen Center, The Cleveland (Ohio) Clinic Foundation (Dr Goodkin). Reprint requests to The Cleveland Clinic Foundation, The Mellen Center, Area U1, 9500 Euclid Ave, Cleveland, OH 44106 (Dr Goodkin).
MD
pie sclerosis (MS) exhibit significant cognitive impairment, especially on tasks that require rapid information processing, recall of newly acquired knowledge, or problem-solving abil¬ ity.1 As confidence in the reproducibil¬ ity of these observations has grown, neurologists' need for a brief but reli¬ able way of screening for cognitive impairment in patients with MS has increased. In addition to brevity and ease of scoring, an ideal screening ex¬ amination would predict performance on a broad range of cognitive func¬ tions, including some that are not as¬ sessed directly by the test. Many neu¬ rologists have employed the MiniMental State Examination (MMSE)2
for this purpose, but found the test to be insensitive to cognitive impairment in MS when the recommended cutoff scores (usually below 24)34 were used. For example, Franklin and colleagues5 recently compared the ability of the MMSE and a neuropsychological screening battery (NSB) that they de¬ veloped to detect cognitive impairment in a sample of 60 patients with clini¬ cally definite chronic-progressive (CP) MS who were diagnosed using the cri¬ teria of Schumacher et al.6 Although none of their patients scored below 24 on the MMSE, 83% were impaired on a composite summary score derived by considering performance on all of the tests included in their NSB, and 60% of the patients were impaired on a com¬ posite cognitive summary score ob¬ tained by considering only those subtests judged to require minimal upper-extremity motor skills. By con¬ trast, Franklin et al5 also reported that "only 20% of patients were impaired on the Folstein MMSE with cutoffs
developed using data from the NSB standardization sample." While the results demonstrate the greater sensi¬
tivity of the NSB compared with the MMSE for routine cognitive screening of patients with MS, the NSB takes at least 45 minutes to administer, while
the MMSE can be administered and scored in a neurologist's office in 5 to 10 minutes. In addition, correlations be¬ tween NSB scores and other cognitive testing (ie, problem solving and re¬ mote memory) are as yet undeter¬ mined. In this article, we show that while the MMSE does predict the existence of focal cognitive deficits in patients with MS reasonably well, in its present form, the test is too insensitive to reli¬
ably identify global cognitive impair¬ ment. We also suggest specific strate¬ gies for modifications of the MMSE that may improve its sensitivity for detecting dementia without exces¬ sively increasing the administration and scoring times required for a screening test. PATIENTS AND METHODS
Data are reported for 43 patients with CP MS and 42 patients with relapsing-remitting (RR) MS who served as subjects in on¬ going research studies of cognitive function in MS." All patients met criteria for clini¬ cally definite MS10; precise definitions used to classify the patients by disease type have been reported elsewhere." For our pur¬ poses, dementia was defined as impairment (ie, scores at or below the fifth percentile for controls) in three of four cognitive func¬ tions: (1) naming, ie, the total number cor¬ rect without cues on the 60-item version of the Boston Naming Test (BNT)"; (2) prob¬ lem solving, ie, the number of categories achieved (out of six) on the Wisconsin Card Sorting Test (WCST),12 a test that requires
Downloaded From: http://archneur.jamanetwork.com/ by a Karolinska Institutet University Library User on 05/26/2015
subjects to form and shift concepts based on feedback from the examiner; (3) speed of information processing (impairment on ei¬ ther the FAS test, which requires generat¬ ing words that begin with the letters F, A, or S as quickly as possible, or the Symbol Digit Modalities Test [SDMT],13 which re¬ quires substituting numbers for geometric symbols as rapidly as possible); and (4) memory (impairment on three of the five measures of anterograde and remote mem¬ ory considered in this article). The memory measures were (1) the total number of words recalled after a 15-second delay on a 10-trial short-term memory test in which four words were given per trial, (2) the to¬ tal number of words recalled immediately after presentation of a 14-word list that was presented for four trials, (3) the percent correct on a recognition test for the same word list given 30 minutes later, (4) the to¬ tal number of items recalled on a test of re¬ mote memory that required identifying fa¬ mous people from photographs or answer¬ ing questions about past public events, and (5) the total number of items correctly rec¬ ognized on the same remote memory test. Patients with RR MS averaged 38.1 ± 7.7 (SD) years of age, 14.3 ± 2.0 years of edu¬ cation, and 4.3 ± 3.2 years of disease since diagnosis, and attained mean scores of 2.1 ± 1.9 on the Expanded Disability Status Scale (EDSS)14 and 1.8 ± 1.7 on the Annu¬ lation Index.15 Patients with CP MS aver¬ aged 48.9 ± 10.9 years of age, 13.7 ± 2.7 years of education, and 18.7 ± 9.8 years since diagnosis of disease, and attained mean scores of 6.6 ± 1.5 on the EDSS and 6.2 ± 2.0 on the Ambulation Index. Thus, the CP patients were older (P < .001), had MS longer (P < .001), and were more se¬ verely disabled physically (P < .001 for both EDSS and Ambulation Index) than the RR patients, but the CP and RR groups did not differ significantly in length of ed¬ ucation. More detailed descriptions of the test materials and procedures can be found in previous reports" or in published test manuals."13 Our patients and controls re¬ sponded orally to the SDMT to minimize the potential confounding of impaired up¬ per-extremity motor activity.13 Only 22 CP patients were assessed on the WCST; oth¬ erwise, all patients completed all tests. The important features of the version of the MMSE used in our study are as follows: (1) the concrete nouns ring, apple, and ele¬ phant were used for the registration and recall phases; (2) only serial 7s was used in the calculation phase; (3) patients for whom writing was very difficult because of obvious upper-extremity deficits were allowed to produce a complete sentence orally; (4) the three-stage command used required the patient to pick up a small object in the nondominant hand, shake it, and place it on a book located on the table where the patient was seated. This modified three-stage com¬ mand was employed to preclude the possi¬ bility that patients with impairments in balance might fall and injure themselves while attempting to place the folded paper on the floor (the three-stage command from the Folstein version of the MMSE requires subjects to pick up a piece of paper, fold it
in
averaged 28.5 (SD, 2.4; range, 14 to 30); the 3 patients scoring below 24 at¬
half, and place it on the floor); and (5) patients and controls who lived more
most
than 50 miles from our clinic were tested in their own homes. Those who were not were asked to name the county in which they re¬ sided. Previous results7 have indicated that there are no statistically significant differ¬ ences in neuropsychological test perfor¬ mance of patients or controls between those tested at home and those tested in the clinic.
tained scores of 23, 20, and 14. It is evident from the data in Table 1 that as scores on the MMSE dropped from the maximum value of 30, the proportion of patients exhibiting im¬ pairment increased. Essentially, the same pattern was observed for each of the nine neuropsychological tests. The tests were, however, differentially sen¬ sitive to impairment. The most sensi¬ tive tests were the SDMT, the WCST,
RESULTS
Table 1 shows the proportion of all patients with MS displaying impair¬ ment on various cognitive tests as a
and immediate recall of the word list, which more than 25% of the pa¬ tients with MMSE scores in the normal on
function of their score on the modified version of the MMSE described above. For each measure, impairment was defined as a score at or below the fifth percentile of age- and educationmatched controls. Controls averaged 29.4 (SD, 0.8; range, 28 to 30) on the MMSE, while the 85 patients with MS
range
Table 1.—Percentages of Patients Exhibiting Score
on
impaired.
Impairment
Cognitive Tests*
on
Mini-Mental State Examination
29(21)
30(35) Anterograde
were
Previous studies9·16 have demon¬ strated that the cognitive impair¬ ments of CP patients are more severe than those of RR patients. It was there¬ fore of interest to determine whether or not the MMSE is equally useful in
28(11)
27(9)
(No. of Patients)
24-26(6)
