Diagnostic Utility of Montreal Cognitive Assessment in the Fifth Edition of Diagnostic and Statistical Manual of Mental Disorders: Major and Mild Neurocognitive Disorders

Diagnostic Utility of Montreal Cognitive Assessment in the Fifth Edition of Diagnostic and Statistical Manual of Mental Disorders: Major and Mild Neurocognitive Disorders

JAMDA 16 (2015) 144e148 JAMDA journal homepage: www.jamda.com Original Study Diagnostic Utility of Montreal Cognitive Assessment in the Fifth Editi...

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JAMDA 16 (2015) 144e148

JAMDA journal homepage: www.jamda.com

Original Study

Diagnostic Utility of Montreal Cognitive Assessment in the Fifth Edition of Diagnostic and Statistical Manual of Mental Disorders: Major and Mild Neurocognitive Disorders Tau Ming Liew MRCPsych a, *, Lei Feng PhD b, Qi Gao PhD b, Tze Pin Ng MD b, Philip Yap MRCP c a b c

Department of Geriatric Psychiatry, Institute of Mental Health, Singapore Gerontology Research Program, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Department of Geriatric Medicine, Khoo Teck Puat Hospital, Singapore

a b s t r a c t Keywords: DSM-5 neurocognitive disorder Montreal Cognitive Assessment quantified clinical assessment diagnostic performance

Objectives: The Montreal Cognitive Assessment (MOCA) is a screening tool for mild cognitive impairment (MCI) and dementia. The new criteria for Diagnostic and Statistical Manual of Mental DisorderseFifth Edition (DSM-5) mild neurocognitive disorder (NCD) define participants with cognitive decline but no dementia, and major NCD (dementia). We explored the usefulness of MOCA to detect major and mild NCD. Design: Cross-sectional test research. Setting: Tertiary hospital memory clinic and community-based Singapore Longitudinal Aging Study (SLAS). Participants: Participants with questionable dementia (clinical dementia rating, CDR ¼ 0.5) and early dementia (CDR 1) over a period of 1 year were identified from the memory clinic registry. The patient records were reviewed and the diagnostic labels of major and mild NCD were applied accordingly. Healthy controls (HC) (CDR ¼ 0, Mini-Mental State Examination >26) were recruited from the on-going SLAS. Measurements: Major and mild NCD were diagnosed based on medical history, clinical examination, basic and instrumental activities of daily living, locally validated bedside cognitive tests (Mini-Mental State Examination, Frontal Assessment Battery, and Clock Drawing Test), relevant laboratory investigations and standardized neuropsychological assessment. Results: Two hundred fifty-one participants were included (41 mild NCD, 64 major NCD, 146 HC). On receiver operating characteristic curve analysis, the diagnostic performance by area under the curve (AUC) for MOCA was 0.99 [95% confidence interval (CI) 0.98e1.0] for major NCD and 0.77 (95% CI 0.67 e0.86) for mild NCD. For diagnosis of mild NCD, MOCA performed better in those with lower education (primary and below) (AUC 0.90) compared with those with secondary education and beyond (AUC 0.66). Conclusion: MOCA has high diagnostic utility for major NCD but its usefulness in detecting mild NCD is more modest. Possible reasons include greater heterogeneity in participants with mild NCD and how “quantified clinical assessment” in the DSM-5 mild NCD criteria is interpreted and operationalized. Ó 2015 AMDA e The Society for Post-Acute and Long-Term Care Medicine.

The authors declare no conflicts of interest. The Singapore Longitudinal Aging Study (SLAS) is supported by a research grant (No. 03/1/21/17/214) from the Biomedical Research Council, Agency for Science, Technology and Research (A*STAR). * Address correspondence to Tau Ming Liew, MRCPsych, Department of Geriatric Psychiatry, Institute of Mental Health, 10 Buangkok View, Singapore 539747. E-mail address: [email protected] (T.M. Liew). http://dx.doi.org/10.1016/j.jamda.2014.07.021 1525-8610/Ó 2015 AMDA e The Society for Post-Acute and Long-Term Care Medicine.

With the recent release of Diagnostic and Statistical Manual of Mental DisorderseFifth Edition (DSM-5), the diagnostic criteria of cognitive impairment were revised to keep pace with research findings in recent years and to better reflect current understanding on the participant. The new criteria for DSM-5 encompass major neurocognitive disorder (NCD) and mild NCD.1 The former replaces but is synonymous with dementia, whereas the latter defines participants with modest cognitive impairment but no dementia, akin to the widely used mild cognitive impairment (MCI) concept.

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Compared with the Diagnostic and Statistical Manual of Mental Disorders-Fourth edition, the major NCD criteria in DSM-5 places less emphasis on memory impairment, includes complex attention, learning, perceptual-motor, and social cognition in the criteria for cognitive impairment and involves a change in the clause “sociooccupational dysfunction” to “interference with independence.” On the other hand, mild NCD, which defines participants with no dementia, entails the following: (1) mild decline in cognitive function, (2) modest impairment in cognitive performance, and (3) no interference with capacity for independence. It is noteworthy that DSM-5 criteria for both major and mild NCD included the necessity for standardized neuropsychological testing, or in its absence, another quantified clinical assessment. Montreal Cognitive Assessment (MOCA), a convenient bedside cognitive test, has been shown in several populations to have good diagnostic utility for dementia, especially Alzheimer’s disease, and MCI.2e8 Given MOCA’s broader coverage of the main cognitive domains assessed, it can potentially overcome the inherent issues with the widely utilized Mini-Mental State Examination (MMSE), in particular, inadequate assessment of executive function and ceiling effects. These features make MOCA an ideal and convenient bedside test to identify persons with early cognitive deficits, such as those with mild NCD. To our knowledge, there has yet been any published literature on the diagnostic utility of MOCA for DSM-5 major and mild NCD. Hence, this study aims to explore the usefulness of MOCA to detect DSM-5 major and mild NCD in patients presenting to a tertiary hospital memory clinic. Methods Participants and Procedures Participants with questionable dementia and early dementia, as defined by clinical dementia rating scores of 0.5 and 1.0, over a period of 1 year were identified from the memory clinic registry of a tertiary hospital in Singapore. Participants with delirium, reversible causes of cognitive impairment, and major psychiatric illnesses, such as major depressive disorder or schizophrenia, were excluded. Ethics approval was obtained from the National University of Singapore Institutional Review Board. The database records of the participants were carefully reviewed and the diagnostic labels of major and mild NCD were applied accordingly on the basis of medical history, clinical examination, basic, and instrumental activities of daily living, locally validated bedside cognitive tests (Mini-Mental State Examination, Frontal Assessment Battery, and a bedside clock drawing task, CLOX),911 relevant blood investigations and brain imaging. Results of standardized neuropsychological assessment covering the major cognitive domains of attention, memory, language, visuospatial and constructional abilities, and executive function were also reviewed. However, this information was available in only 25% participants because many patients in the memory clinic did not undergo the assessment. This was because patients had to pay for neuropsychological assessment and many opted out of it. The healthy control (HC) participants were recruited from the on-going community based Singapore Longitudinal Aging Study (SLAS). The detailed methodology of SLAS has been described in prior publications12 and is described briefly herein. The SLAS is a community-based prospective cohort study of aging and health whereby residents aged 55 years and above in the south-east region, south-central, and south-west region of Singapore are identified in a door-to-door census and invited to participate in a comprehensive set of assessments covering demographic, health, behavior, functional,

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and cognitive domains. A total of 6000 participants were recruited and regular follow-up assessments were conducted at 2- to 4-year intervals. For this study, all HC scored 27 in the MMSE, had a clinical dementia rating score ¼ 0, had no history of significant head injury, stroke or evidence of cerebrovascular disease, other neurologic disease, systemic illness, or medical conditions that may affect cognitive functioning and activities of daily living, clinical depression, or other psychiatric and substance-related disorders, which affect cognitive functioning, and use of long-acting benzodiazepines or barbiturates within the past 2 years. MOCA was administered to all participants, and the results were not taken into consideration in applying the DSM-5 criteria to avoid circularity in the diagnostic process. Cognitive Assessment Instruments The MOCA was modified for Singaporeans by a senior psychologist and a specialist/neurologist providing dementia care. The adaptations of the test items were made in consultation with the original MOCA test developer and have been reported previously.13 The translation and back-translation of the Chinese and Malay versions of the MOCA were undertaken by bilingual psychologists and 3 equivalent versions (in English, Chinese, and Malay) of the MOCA were established. The MMSE is a widely used cognitive assessment tool. It has a maximum score of 30, with individual items covering orientation, memory, concentration, language and constructional praxis. The area under the curve (AUC) of MMSE was 95% on the receiver operating characteristic (ROC) curve in an earlier study in Singapore.9 Frontal Assessment Battery (FAB) was developed as a brief bedside test to assess frontal lobe function.14 It comprises 6 subtests: (1) conceptualization [conceptualization links between 2 objects from the same category, (eg an orange and a banana)], (2) mental flexibility (animal naming in a 1-minute trial), (3) motor programming (Luria’s ‘fist-edge-palm’ motor series), (4) sensitivity to interference [conflicting instructions in which participants must provide an opposite response to the examiner’s alternating signal (eg tapping once when the examiner taps twice)], (5) inhibitory control [go/no-go paradigm where the participant must inhibit a response that was previously given to the same stimulus, (eg not tapping when the examiner taps twice)], and (6) environmental autonomy (placing your hands out and instructing the participant not to touch them, looking out for abnormal behavior such as imitation, utilization, and prehension behavior). Each subtest is scored from 0 to 3, yielding a total score of 18. FAB achieved AUC of 84% to 94% on the ROC curve in a previous Singapore study.10 CLOX is a clock drawing task developed by Royall et al.15 The test is divided into 2 parts, CLOX1, where participant is required to draw on a blank surface a clock face showing “1:45”, and CLOX2, where participant is asked to copy a clock face. CLOX is scored with respect to (1) its resemblance of visual attributes to a standard analogue clock and (2) the constructional sequence (making the 4 quadrants by placing the numbers 12, 6, 3 and 9 first in order to facilitate the positioning of the entire number set). Each CLOX subtest is scored on a 15-point scale. Lower CLOX scores denote greater cognitive impairment. CLOX1 and CLOX2 was previously validated in Singapore with AUC of 84% and 85%, respectively, on the ROC curve.11 DSM-5 Diagnostic Criteria1 Major NCD was diagnosed using the DSM-5 criteria as follows: (A1) concern of the individual, a knowledgeable informant or the clinician that there has been a significant decline in cognitive function, (A2) a substantial impairment in cognitive performance preferably documented by standardized neuropsychological testing or,

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Table 1 Characteristics of the Study ParticipantseWith (a) Unmatched Health Control (n ¼ 146); and (b) Health Control Matched by Age to Mild NCD (n ¼ 69) Variable

Major NCD (n ¼ 64)

Mild NCD (n ¼ 41)

Healthy Control (n ¼ 146)

P*

Matched Healthy Control (n ¼ 69)

Py

Age, year, mean (SD) Female, n (%) Education level Nil, n (%) Primary school, n (%) Secondary school or equivalent, n (%) Pre-university or polytechnic, n (%) University and above, n (%) MMSE total score, mean (SD) MOCA total score, mean (SD) FAB total score, mean (SD) CLOX1 total score, mean (SD) CLOX2 total score, mean (SD) Dementia subtype Alzheimer’s disease, n Alzheimer’s disease with CVD, n Vascular dementia, n

75.8 (7.29) 42 (65.6)

71.8 (6.71)z 21 (51.2)

64.9 (7.0) 72 (49.3)

<.001 .087

69.9 (5.9)z 25 (36.2)

<.001 .003

16 15 29 2 2 22.5 16.5 12.1 9.4 11.6

15 7 11 2 6 25.7 21.6 13.4 11.3 13.5

27 66 42 9 2 28.7 25.2 NA NA NA

<.001

13 37 14 4 1 28.8 25.1

<.001

(25.0) (23.4) (45.3) (3.1) (3.1) (1.94) (3.31) (2.85) (3.69) (3.19)

36 24 4

(36.6) (17.1) (26.8) (4.9) (14.6) (2.30) (4.00) (2.87) (2.56) (1.4)

NA NA NA

(18.5) (45.2) (28.8) (6.2) (1.4) (1.19) (2.13)

<.001 <.001 .04 .005 <.001

NA NA NA

NA

(18.8) (53.6) (20.3) (5.8) (1.4) (1.24) (1.86)

<.001 <.001

NA NA NA

NA

SD, standard deviation. *P values to evaluate for differences between the groups of major NCD, mild NCD, and unmatched HC. y P values to evaluate for differences between the groups of major NCD, mild NCD, and HC matched by age to mild NCD. z P ¼ .126 when comparing the age between matched healthy control and mild NCD.

in its absence, another quantified clinical assessment, and (B) the cognitive deficits interfere with independence in everyday activities. Mild NCD was defined based on the new criteria from DSM-5 as follows: (A1) concern of the individual, a knowledgeable informant, or the clinician that there has been a mild decline in cognitive function, (A2) a modest impairment in cognitive performance preferably documented by standardized neuropsychological testing or, in its absence, another quantified clinical assessment, and (B) the cognitive deficits do not interfere with capacity for independence in everyday activities (complex instrumental activities of daily living such as paying bills or managing medications are preserved, but greater effort, compensatory strategies, or accommodation may be required). Criteria (C) and (D), which entail exclusion of delirium and other psychiatric disorders, are not elaborated herein. Statistical Analysis To evaluate for differences in participant variables between the groups of major NCD, mild NCD, and HC, t test was employed for continuous variables and c2 test for categorical variables. The ROC analysis was conducted to assess the performance of MOCA in differentiating major and mild NCD from HC. The analysis was conducted for the whole sample and stratified for the education subgroups: primary school and below; secondary school and above. Diagnostic performance by sensitivity, specificity, and AUC was

established. IBM SPSS Statistics 20 for Windows (IBM SPSS Inc, Chicago, IL) was used for all the data analyses. HC was matched by age to the mild NCD and sensitivity analysis was conducted. With the new HC group, the ROC curve analysis was repeated to re-assess for any changes in the performance of MOCA in differentiating major and mild NCD from HC. Results The total sample size was 251, comprising 64 participants with major NCD (25.5%), 41 with mild NCD (16.3%), and 146 HC (58.2%). The demographic and clinical characteristics of the participants are shown in Table 1(a). The diagnostic performance of MOCA in differentiating major and mild NCD from normal cognition is shown in Table 2 and Table 3, respectively, stratified according to different cut-off scores and education levels. The AUC of MOCA was 0.99 (95% CI 0.98e1.0, P < .001) for major NCD and 0.77 (95% CI 0.67e0.86, P < .001) for mild NCD. For mild NCD, MOCA performed better in those with lower education (primary and below) (AUC 0.90, 95% CI 0.83e0.96, P < .001) compared with those with secondary education and above (AUC 0.66, 95% CI 0.51e0.81, P ¼ .038). The optimal MOCA cut-off score was 21/22 for major NCD (sensitivity 92%, specificity 96% and accuracy 95%) and 24/25 for mild NCD (sensitivity 78%, specificity 62% and accuracy 65%).

Table 2 The Performance of MOCA Test in Differentiating Major Neurocognitive Disorder From Healthy Control Cut Score

Total Sample

17/18 18/19 19/20 20/21 21/22 22/23 AUC (95% CI)

0.66 1 0.75 1 0.80 1 0.84 0.89 0.92 0.96 0.95 0.88 0.99 (0.98‒1.00)*

Se

Ac, accuracy; Se, sensitivity; Sp, specificity. *P < .001.

Primary and Below Education Sp

Ac

Se

0.90 0.92 0.94 0.87 0.95 0.90

0.81 1 0.84 1 0.90 1 0.94 1 0.97 0.95 0.97 0.85 0.99 (0.98‒1.00)*

Sp

Secondary and Above Education Ac

Se

0.95 0.96 0.98 0.99 0.95 0.88

0.52 1 0.67 1 0.70 1 0.76 1 0.88 1 0.94 0.98 0.99 (0.69‒1.00)*

Sp

Ac 0.82 0.87 0.88 0.91 0.95 0.96

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Table 3 The Performance of MOCA Test in Differentiating Mild Neurocognitive Disorder From Healthy Control Cut Score

Total Sample Se

22/23 23/24 24/25 25/26 26/27 27/28 AUC (95% CI)

Primary and Below Education Sp

0.54 0.88 0.63 0.76 0.78 0.62 0.78 0.46 0.90 0.29 0.93 0.15 0.77 (0.67‒0.86)*

Ac

Se

Sp

0.80 0.73 0.65 0.53 0.42 0.32

0.68 0.85 0.82 0.76 1 0.55 1 0.42 1 0.22 1 0.09 0.90 (0.83‒0.96)*

Secondary and Above Education Ac

Se

0.82 0.77 0.64 0.53 0.37 0.26

0.37 0.93 0.42 0.76 0.53 0.76 0.53 0.53 0.79 0.42 0.84 0.26 y 0.66 (0.51‒0.81)

Sp

Ac 0.78 0.67 0.70 0.53 0.52 0.41

Ac, accuracy; Se, sensitivity; Sp, specificity. *P < .001. y P ¼ .038.

In the sensitivity analysis with HC matched by age to mild NCD [Table 1(b)], the results remained very similar for the diagnostic performance of MOCA in major NCD (optimal cut-off score 21/22, sensitivity 92%, specificity 97%, and accuracy 95%) and mild NCD (optimal cut-off score 24/25, sensitivity 78%, specificity 62%, and accuracy 68%). Discussion The results demonstrate MOCA’s high diagnostic utility for major NCD (dementia). However, its usefulness in detecting mild NCD was more modest, especially in those with higher educational attainment (secondary and above education). The same findings are reproduced in sensitivity analysis, reinforcing the internal validity. The influence of education on MOCA has been reported in several studies. MOCA scores in a sample of Chinese American were much influenced by educational level, requiring different cut-offs of 20, 22, and 24 in low (1e6 years), middle (7e11 years), and high (12e20 years) education groups respectively.16 A recent study in Singapore17 found education to be a highly significant independent factor impacting MOCA score and also influenced its diagnostic accuracy. At the cut-off limit of 10 years of education, sensitivity of MOCA for the differentiation of amnestic MCI from mild AD dropped from 72.09% to 48.84% and in the same vein, for the differential diagnosis of normal controls from amnestic MCI, sensitivity of MOCA dropped from 88.35% to 50.49%. Similarly, another recent study from Beijing on patients with vascular cognitive impairment showed that the sensitivity of MOCA between the primary, secondary and tertiary educated groups to vary considerably at 97.06%, 56.10%, and 40%, respectively.18 MOCA’s poorer performance in mild NCD may be related to greater heterogeneity in participants with mild NCD. Among those with secondary education and beyond, the range in educational levels is very broad, ranging from secondary to college, diploma and university education. As the baseline cognitive competencies of these participants can expectedly be varied, it is not surprising that their performance in the MOCA can be wide-ranging, hence, compromising on the ability of MOCA to uniformly detect early cognitive deficits if present. In addition, there may also be heterogeneity within the subtypes of mild NCD, comprising amnestic, nonamnestic, singledomain and multi-domain type of early cognitive impairment, with MOCA possibly performing better in some subtypes than others. The DSM-5 criteria for mild NCD may in part contribute to its poorer performance compared with major NCD. DSM-5 mandates standardized neuropsychological testing as part of the assessment, and in its absence, another quantified clinical assessment.1 This option of “another quantified clinical assessment” addresses the practical difficulty of obtaining neuropsychological test for all patients. Although the DSM-5 manual provides examples of cognitive assessments for the various cognitive domains, there is little elaboration

on the minimum composition of “another quantified clinical assessment,” rendering interpretation and implementation subjective and variable. In MCI diagnoses, which necessitate satisfying established normative neuropsychological tests cut-offs, extant literature has generally shown good diagnostic performance of MOCA.2e8 In this study, MOCA performed less well in mild NCD with MMSE, FAB, and CLOX constituting the quantified clinical assessment. Assuming MOCA to be a viable tool for detecting early cognitive impairment as evidenced by published literature, it begs the question of whether the problem may lie with how “another quantified clinical assessment” is operationalized. To standardize the diagnosis of mild NCD, clarification on what cognitive tests within “a quantified clinical assessment” are adequate alternatives to traditional neuropsychological tests may be necessary. Some limitations of this study should be noted. First, the assessment of MOCA was done cross-sectionally at a single time point, and no longitudinal follow-up testing was done to confirm the validity of the assessment. Second, as mentioned above, heterogeneity in the education level and subtypes of mild cognitive impairment would have negatively affected the performance of MOCA, and this problem could have been alleviated had a more uniform sample regarding education and cognitive deficits had been recruited. Homogeneity in the study sample was difficult to achieve as the participants were recruited from a naturalistic memory clinic setting. Finally, the study sample size was modest especially for the mild NCD group. A larger sample size could have possibly reduced heterogeneity and improved the diagnostic performance of MOCA. Conclusions In conclusion, MOCA shows good utility for detecting DSM-5 major NCD but is modest for the diagnosis of mild NCD. It appears that the diagnosis of DSM-5 mild NCD, like for MCI, is still much dependent on fulfilling objective neuropsychological tests criteria in addition to clinical criteria. In this respect, the clause “another quantified clinical assessment” in place of neuropsychological testing may need more clarification. Acknowledgments The SLAS is supported by a research grant (No. 03/1/21/17/214) from the Biomedical Research Council, Agency for Science, Technology and Research (A*STAR). The authors thank the following voluntary welfare organizations for their support of the SLAS studies: Geylang East Home for the Aged, Presbyterian Community Services, Thy Hua Kwan Moral Society (Moral Neighbourhood Links), Yuhua Neighbourhood Link, Henderson Senior Citizens’ Home, NTUC Eldercare Co-op Ltd, Thong Kheng Seniors Activity Center (Queenstown Center), Redhill Moral Seniors Activity Center, SARAH Seniors Activity Center, and Training, Research Academy at Jurong Point (TaRA@JP).

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