J.Y. WANG 1, A.C. TSAI 1,2

05 TSAI_04 LORD_c 05/03/14 10:19 Page594 THE SHORT-FORM MINI-NUTRITIONAL ASSESSMENT IS AS EFFECTIVE AS THE FULL-MINI NUTRITIONAL ASSESSMENT IN PREDICTING FOLLOW-UP 4-YEAR MORTALITY IN ELDERLY TAIWANESE J.Y. WANG 1, A.C. TSAI 1,2 1. From the Department of Healthcare Administration, Asia University, 500 Liufeng Road, Wufeng, Taichung 41354, Taiwan; 2. Department of Health Services, School of Public Health, China Medical University, 91 Hsueh-Shih Road, Taichung 40402, Taiwan. Corresponding author: Alan C. Tsai, Ph.D., Professor, Department of Healthcare Administration, Asia University, -500 Liufeng Rd., Wufeng, Taichung, 41354, Taiwan. -Tel.: +886-4-23323456 ext.1943. Fax: 886-4-2332-1206, E-mail: atsai@umich.edu Abstract: Objective: To compare the mortality-predictive ability of the full- and short-form (SF) Mini Nutritional Assessment (MNA). Design: A prospective cohort study. Setting: Population-representative sample. Participants: 2872 65-year old men and women. Measurements: The study analyzed 1999 and 2003 datasets of the Taiwan Longitudinal Survey on Aging (TLSA). Subjects were graded for nutritional status with the full- MNA and MNA-SF of a Taiwanese-specific version (T2, containing calf circumference instead of BMI) at baseline (1999) and tracked their survival status for 4 years. Mortality-predictive abilities of the full-mna and MNA-SF were compared using Cox regression analysis and Net Reclassification Improvement (NRI). Results: The full-mna and MNA-SF have comparable abilities in predicting follow-up 4-year mortality risk according to the hazard ratios (all p<0.001) and Akaike information criterion (AIC). It also showed a slight improvement (not significant) if the full-mna in a predictive model was replaced by the MNA-SF (NRI=0.09%, p=0.956). Conclusion: The MNA-SF has at least comparable or even slightly better ability in predicting follow-up 4-year mortality risk of elderly Taiwanese. Results suggest that MNA-SF with calf circumference may possess some basic characteristics of a comprehensive and universal geriatric screening scale. Key words: Nutritional status, mortality, elderly, Mini Nutritional Assessment. Introduction Elderly have high risk of malnutrition and functional dependency. Because frailty and functional dependency are associated with poor nutritional status (1), nutritional assessment should be taken as a part of comprehensive geriatric assessment. The Mini-Nutritional Assessment (MNA) is one of the most widely used nutritional screening/assessment tools. The MNA is composed of four nutritional dimensions (dietary, anthropometric, global and self-rated indicators) and has a total of 18 items (2, 3). It could also be used as a two-part and twostage scale (4). Elderly suspected of malnutrition are first screened with the short-form (SF) MNA with 6 key questions. Those who are rated as at risk of malnutrition are further evaluated with the rest of the full-mna. The MNA-SF generally performs well in rating the nutritional status of the elderly and results usually agree well with that rated with the full-mna (5). As a result, the MNA-SF has been recommended to function as a stand-alone unit and like the full-mna, results are classified into three levels (normal, at risk of malnutrition and malnourished). An alternative version where calf-circumference (CC) replaces BMI was also recommended (6). In Taiwan, we had also developed a similar alternative version, MNA-T2 (equivalent to CC-MNA) for elderly Taiwanese (7). MNA-T2 was modified from MNA-T1, a version equivalent to BMI-MNA but with Taiwanese anthropometric cutoffs (8). Because of the simplicity, performance and time-saving features, the MNA-SF is often preferred over the full-mna in clinical and community settings. CC is more accessible and easier to measure than BMI. We have found that MNA-T2-SF performs better than or at least equal to MNA-T1-SF in elderly Taiwanese (9). In addition to rating the nutritional status, the full-mna has been shown to have prognostic values. It can predict frailty, physical and cognitive functional declines, falling and even follow-up mortality in elderly persons (10). Some recent studies have further shown that the SF also possesses similar prognostic properties as the full-mna and the predictive abilities in many cases are as good as or even slightly better than the full-mna (10-12). We found that the full-mna-t2 and MNA-T2-SF performed well in rating the nutritional status of elderly Taiwanese (8) and the two scales have comparable abilities in predicting physical functional and cognitive declines (unpublished observation) and follow-up mortality in elderly Taiwanese (8, 13, 14). However, the ability of the two scales in predicting follow-up mortality has not been carefully examined. Thus, the present study was aimed to compare the mortalitypredictive ability of the two forms of MNA-T2. The long-term goal of the present study is to gain an understanding of the potential for developing CC-MNA-SF for a comprehensive and universal geriatric screening tool. Methods Subjects Data of the present study were from a populationrepresentative longitudinal study "Taiwan Longitudinal Survey Received December 17, 2012 Accepted for publication January 30, 2013 594

05 TSAI_04 LORD_c 05/03/14 10:19 Page595 JNHA: NUTRITION on Aging" (TLSA). The study was initiated in 1989 and subjects in the survey were interviewed with a structured questionnaire every 3-4 years (1989, 1993, 1996, 1999, 2003 and 2007) (15). A research institute trained all interviewers to ensure good interview quality. All components of the questionnaire were pretested and field-tested to ensure the validity and reliability before data collection. The completion rate of the survey ranged from 79.1% to 91.8%. Further detail of the design and sampling process has been described elsewhere (14). The 1999 survey contained a special component for assessing subjects nutritional status and therefore was designated as baseline for the present study. A total of 2872 men and women who aged over 65 years completed the questionnaire. We tracked their survival status during the follow-up 4 years and took the 2003 survey as the end-point. Measurements In the present study, nutritional status of the participants was rated with the full and short-form of MNA-T2. MNA-T2 was modified from MNA-T1 by replacing calf circumference for BMI, and both versions adopted Taiwanese-specific anthropometric cutoffs (8). MNA-T1 is equivalent to the original MNA or BMI-MNA while MNA-T2 is equivalent to CC-MNA developed by Kaiser et al. (6). MNA-T2 has been shown to perform better than the original MNA or MNA-T1 (7). Subjects were classified as malnourished, at risk of malnutrition or normal according to the full- or SF version of MNA-T2. For the full-mna, the cutoffs were 16.5, 17-23.5 and 24 for malnourished, at risk of malnutrition and normal, respectively; for SF, the cut-offs were 7, 8-11; and 12, respectively. Dependency of the Activities of Daily Living (ADL) was rated according to Fitti and Kovar (16). ADL rates the ability of performing bathing, dressing, transferring, eating, walking or toileting independently. An item that one cannot do independently is considered dependent for that item. The total number of dependency denotes the level of dependency of a person. Mortality data were obtained from records maintained by the survey project and confirmed with records kept by the Universal Health Insurance Program and by the National Household Registration records. Statistical Analysis Descriptive statistics (n and % for qualitative data; mean and standard deviation for quantitative data) were used to show subjects baseline characteristics, nutritional status and the follow-up 4-year mortality. Cox regression analysis was performed to estimate the relative mortality risk among the rated nutritional classifications, controlled for demographic, lifestyle, living arrangement and health-related variables. The changes in Akaike Information Criterion (AIC) values in Cox regression were calculated for assessing the model fitting. The smaller of the AIC value implies the better of the model fitting (17). We also calculated the Net Reclassification Improvement (NRI) (18) to compare the predictive ability of the two forms of MNA. The NRI was proposed to evaluate the improvement of a predictive model with inclusion of a new marker (18). A positive (negative) value of NRI implies better (worse) improvement of the predictive model after inclusion of the new marker. In this study, the NRI was defined as [proportion of subjects in the death group reclassified at higher risk proportion reclassified at lower risk] minus [proportion of subjects in the survival group reclassified at higher risk proportion reclassified at lower risk] after the full-mna was replaced by MNA-SF in the predictive model. Calculations of the NRI were performed with Microsoft Excel 2007 (Microsoft Corporation) and all other statistical analyses were performed with the SAS software (version 9.1; SAS Institute Inc., Cary, NC). A weighing process was involved in the data analysis according to the sampling design of the survey. Statistical significance for all analyses was set at α = 0.05. Results Table 1 shows the characteristics of subjects at baseline (the 1999 survey). The cohort included slightly more males. Almost 2/3 of the subjects were 65-74 years old; only 21.4% had 7 years or more of formal education; 84.7% are family-living; 45.4% exercised 3 or more times per week; 25% were current smokers; 14% drank once or more per week; 5.5% had at least one kind of ADL dependency. According to the full-mna, 2.7% of elderly were malnourished, 12.7% at risk of malnutrition and 84.6% were normal. According to MNA-SF, 3.5% were malnourished, 19.0% were at risk and 77.5% were normal. The two-forms had high agreement in grading the nutritional status of subjects (weighted kappa=0.686, 95% CI=0.655-0.716, p<0.001). Table 2 shows the significance of the hazard ratio and model fitting of the full-mna and MNA-SF in Cox regression. MNA- SF had comparable or even slightly better ability (with higher chi-square and smaller AIC values) in predicting 4-year followup mortality, adjusted for possible confounding variables. Table 3 shows that the net reclassification improvement (NRI) was 0.09% (SE=0.015, p=0.956) if the full-mna was replaced by the MNA-SF in the predictive model. It suggests that the MNA-SF was as capable as the full-mna in predicting follow-up mortality. Discussion Predicting follow-up mortality with the full-mna and MNA-SF Using Cox regression and NRI, we have conclusively shown that the MNA-SF (with CC) is at least as capable as the full- MNA in predicting the follow-up 4-year mortality risk in elderly Taiwanese. The MNA-SF is an abbreviated version of the full-mna and it consists of the first 6 (supposedly the items 595

05 TSAI_04 LORD_c 05/03/14 10:19 Page596 MNA PREDICTS FOLLOW-UP MORTALITY with better predictive abilities) of the 18 items of the full- MNA. Because of its good ability in rating nutritional status and high agreement with the full scale, MNA-SF has recently been recommended to function as a stand-alone unit (6). By consisting only 6 relatively simple items and having good predictive ability, the MNA-SF quickly gained popularity in recent years. However, MNA-SF appeared to be more appropriate for the community-dwelling elderly and less efficient than the full-mna for nursing home residents (19, 20). Table 1 Characteristics and distribution of nutritional status of the study sample at baseline (N=2892) Variables N (before weighting) % (weighted) a Male 1570 54.5 Age (y) 65-74 1622 64.9 75 1270 35.1 Formal education (y) 0 1039 34.6 6 1230 44.0 7 449 21.4 Living arrangement With family members 2430 84.7 Alone 324 10.9 Institutions 118 4.1 Physical activity (times/week) 0 1138 39.0 1-2 445 15.6 3 1288 45.4 Smoking 726 25.0 Drinking 407 14.1 Number of ADL dependency 0 2699 94.5 1-2 66 2.1 3 107 3.3 Nutritional classification by the full-mna Malnourished 78 2.7 At risk of malnutrition 365 12.7 Normal 2429 84.6 Nutritional classification by the MNA-SF Malnourished 101 3.5 At risk of malnutrition 545 19.0 Normal 2226 77.5 ADL: Activities of Daily Living, MNA: Mini Nutritional Assessment, SF: short-form; a. Weighting-adjusted according to study design; Weighted kappa=0.686, (95% CI=0.655-0.716, p<0.001) between results rated with the two forms. CC-MNA-SF has other prognostic abilities Several studies including our own have shown that the MNA-SF also have good prognostic properties, in addition to predicting nutritional status. Donini et al. (21) have observed that low MNA score was predictive of greater incidence of adverse clinical events during hospitalization and of higher mortality. Salvi et al. (12) have observed that MNA-SF was associated with poor clinical outcomes and was able to predict functional decline in older patients admitted to an acute medical ward. Dent et al. (11) evaluated the efficacy of both the full-mna and MNA-SF in identifying frailty in hospitalized older people and found that the MNA-SF was better than the full-mna in predicting frailty. In a systematic review Dent et al. (10) found that both the MNA and MNA-SF were significantly associated with subsequent mortality. In our laboratory, we have seen that nutritional status of elderly living in community, care-center and nursing-home settings rated with the short-form of MNA-T1 or MNA-T2 agreed well with that rated with the full scales, and MNA-T2 (CC-MNA) performed better than MNA-T1 (BMI-MNA) in all cases (7). We have also found that MNA-T2 was at least as effective as MNA-T1 in reflecting concurrent physical functional status and MNA-T2-SF performed at least as well as the MNA-T1-SF in predicting functional decline four years later in the general elderly population (14). In a more recent study using Cox regression and NRI we have found that of MNA-T2-SF was comparable to the full-mna-t2 in improving the ability of ADL in predicting follow-up four-year mortality (22). Taken together, these results suggest that in addition to rating the nutritional risk, the MNA-SF (especially with CC) possesses prognostic properties. MNA-SF is nearly as effective as the full-mna in reflecting concurrent functional status and is highly effective in predicting subsequent frailty, functional (physical and cognitive) decline and follow-up mortality in the elderly. The implication The MNA-SF contains 6 simple and non-invasive items. The original version contains BMI, thus needing weight and height measurements which can be difficult in case subject is frail or bed-ridden; whereas T2 (CC-version) would need to measure only CC which is quite accessible under most circumstances. We have almost always seen that the MNA-T2 performs better than the MNA-T1 whether in rating nutritional status or in predicting prognostic indicators and whether it is the full-scale or the short-form in elderly Taiwanese living in most settings. Considering its simplicity, good nutrition-rating ability and the prognostic values, MNA-T2-SF is a preferred version for rating the nutritional status under most settings. With its ability to predict frailty, physical functional decline, cognitive decline and even falling, the MNA-T2-SF sees no peer in being a candidate for developing into a comprehensive and universal geriatric screening tool. The quest for a simple and easy comprehensive and universal tool never ends but it appears that we have moved one notch closer to this goal. Features and limitations of the study A feature of the present study is that it is a longitudinal study involving a national random sample. Study results can infer a causal relationship with the follow-up mortality. Study results should be applicable to Chinese populations who share similar anthropometric features as the Taiwanese. The study also has some limitations. (a) Most participants were community-living and there were insufficient number of participants living in 596

05 TSAI_04 LORD_c 05/03/14 10:19 Page597 JNHA: NUTRITION Table 2 Hazard ratio estimations and model fitting assessments in Cox regression models with inclusion of the full-mna or MNA-SF Full-MNA MNA-SF Item HR 95% CI chi-sq p-value HR 95% CI chi-sq p-value Age (y) 1.09 (1.08, 1.10) 198.9 *** 1.09 (1.08, 1.10) 202.4 *** Male gender 1.84 (1.53, 2.22) 41.1 *** 1.86 (1.54, 2.25) 41.9 *** Formal education (y) 0.99 (0.97, 1.01) 1.0 ns 0.99 (0.97, 1.01) 0.9 ns Living alone 1.38 (1.09, 1.75) 7.3 ** 1.37 (1.08, 1.73) 6.7 ** Physical activity 0.64 (0.53, 0.77) 21.2 *** 0.64 (0.53, 0.78) 20.9 *** Drinking 0.99 (0.78, 1.26) 0.0 ns 0.99 (0.78, 1.26) 0.0 ns Smoking 1.01 (0.83, 1.23) 0.0 ns 0.99 (0.81, 1.21) 0.0 ns ADL score 1.07 (1.04, 1.09) 35.5 *** 1.07 (1.05, 1.09) 47.0 *** Hypertension 1.22 (1.01, 1.48) 4.1 * 1.21 (1.00, 1.47) 3.8 * Diabetes 0.53 (0.43, 0.66) 35.2 *** 0.55 (0.45, 0.68) 32.1 *** Heart disease 1.07 (0.86, 1.34) 0.4 ns 1.07 (0.86, 1.34) 0.4 ns Stroke 0.80 (0.60, 1.06) 2.4 ns 0.82 (0.62, 1.09) 1.8 ns Cancer 0.51 (0.33, 0.80) 8.5 ** 0.51 (0.33, 0.79) 8.8 ** Nutritional status 1 At risk 1.63 (1.31, 2.02) 19.0 *** 1.67 (1.37, 2.03) 26.2 *** Malnourished 3.26 (2.31, 4.60) 44.9 *** 3.00 (2.20, 4.11) 47.3 *** Model fitting AIC 8434.4 8427.9 Changes in AIC 2 39.5 46.0 MNA = Mini Nutritional Assessment, SF = short-form, HR: hazard ratio, CI = confidence interval, chi-sq = chi-square, ns = not significant, AIC = Akaike Information Criterion. * p<0.05, ** p<0.01, *** p<0.001; 1. Normal as the reference; 2. Comparing the current model to the model without inclusion of MNA (AIC=8473.9). Table 3 Risk reclassification for models with the full-mna and MNA-SF in predicting the risk of 4-year mortality Model with Model with MNA-SF full-mna 1 0%-15% 15%-30% 30%-50% >50% Total, n 0%-15% b Died, n 107 11 0 0 118 Survived, n 1458 58 0 0 1516 15%-30% Died, n 13 131 18 0 162 Survived, n 48 452 22 0 522 30%-50% Died, n 1 12 89 10 112 Survived, n 2 26 133 16 177 >50% Died, n 0 0 11 175 186 Survived, n 0 1 13 65 79 Total Died, n 121 154 118 185 578 Survived, n 1508 537 168 81 2294 MNA = Mini Nutritional Assessment, SF = short-form, CI: confidence interval. 1. Predicted risk of mortality was classified into 4 levels (<15, 15-30, 30-50, >50% mortality risk) in order to calculate the net reclassification improvement (NRI). Both models were controlled for demographic (age, gender, years of formal education and living arrangement), lifestyle (smoking status, alcohol-drinking and routine physical activity) and health-related (ADL score, hypertension, diabetes, heart disease, stroke and cancer) variables. Replacing MNA-SF for the full- MNA, reclassification improved by 0.35% in the death group (39 to 37 of 578) and worsened in the survival group by 0.26% (90 to 96 of 2294), leading to a net reclassification improvement of 0.09% (standard error=0.015, p=0.956) long-term care settings such as care center, rehabilitation centers or nursing homes to allow independent analysis. (b) Data were collected through face-to-face interviews. Interview data generally have acceptable accuracy but incorrect recall or reporting could happen, especially to elderly who were cognitively impaired or reported by proxies. We also performed the sensitivity analyses without including the institutionalized subjects and the results (HRs of nutritional status and the value of NRI) were similar to that presented. (c) No biochemical data were available in the datasets, so confirmation of the rated nutritional status with biochemical nutritional indicators was not possible. 597

05 TSAI_04 LORD_c 05/03/14 10:19 Page598 MNA PREDICTS FOLLOW-UP MORTALITY Conclusion By applying Cox regression (with AIC analysis) and NRI, we have conclusively shown that the MNA-T2-SF is at least as effective as the full scale in predicting follow-up 4-year mortality in elderly Taiwanese. MNA-T2-SF also has prognostic properties for predicting future frailty, physical functional decline and cognitive decline. MNA-T2-SF appears to possess the basic characteristics for developing into a comprehensive and universal geriatric screening tool. Acknowledgments: This study is based on data from "the Taiwan Longitudinal Survey on Aging (TLSA)" provided by the Bureau of Health Promotion, Department of Health, R.O.C (Taiwan). Descriptions or conclusions herein do not represent the viewpoint of the Bureau. The authors declare that they have no competing interests. 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