Association of anorexia/appetite loss with malnutrition and mortality in older populations: A systematic literature review

Abstract

Anorexia/appetite loss in older subjects is frequently underrecognized in clinical practice, which may reflect deficient understanding of clinical sequelae. Therefore, we performed a systematic literature review to assess the morbidity and mortality burden of anorexia/appetite loss in older populations. Following PRISMA guidelines, searches were run (1 January 2011 to 31 July 2021) in PubMed, Embase® and Cochrane databases to identify English language studies of adults aged ≥ 65 years with anorexia/appetite loss. Two independent reviewers screened titles, abstracts and full text of identified records against pre-defined inclusion/exclusion criteria. Population demographics were extracted alongside risk of malnutrition, mortality and other outcomes of interest. Of 146 studies that underwent full-text review, 58 met eligibility criteria. Most studies were from Europe (n = 34; 58.6%) or Asia (n = 16; 27.6%), with few (n = 3; 5.2%) from the United States. Most were conducted in a community setting (n = 35; 60.3%), 12 (20.7%) were inpatient based (hospital/rehabilitation ward), 5 (8.6%) were in institutional care (nursing/care homes) and 7 (12.1%) were in other (mixed or outpatient) settings. One study reported results separately for community and institutional settings and is counted in both settings. Simplified Nutritional Appetite Questionnaire (SNAQ Simplified, n = 14) and subject-reported appetite questions (n = 11) were the most common methods used to assess anorexia/appetite loss, but substantial variability in assessment tools was observed across studies. The most commonly reported outcomes were malnutrition and mortality. Malnutrition was assessed in 15 studies, with all reporting a significantly higher risk of malnutrition in older individuals with anorexia/appetite loss (vs. without) regardless of country or healthcare setting (community n = 9, inpatient n = 2, institutional n = 3, other n = 2). Of 18 longitudinal studies that assessed mortality risk, 17 (94%) reported a significant association between anorexia/appetite loss and mortality regardless of either healthcare setting (community n = 9, inpatient n = 6, institutional n = 2) or method used to assess anorexia/appetite loss. This association between anorexia/appetite loss and mortality was observed in cohorts with cancer (as expected) but was also observed in older populations with a range of comorbid conditions other than cancer. Overall, our findings demonstrate that, among individuals aged ≥ 65 years, anorexia/appetite loss is associated with increased risk of malnutrition, mortality and other negative outcomes across community, care home and hospital settings. Such associations warrant efforts to improve and standardize screening, detection, assessment and management of anorexia/appetite loss in older adults.

Keywords: anorexia; appetite loss; malnutrition; mortality; prevalence; systematic literature review.

Figure 1

PRISMA flow diagram. Publications were identified from searches of Embase, PubMed and Cochrane databases. Duplicate entries or irrelevant types of publications (e.g., editorials, letters, reviews, congress abstracts, case reports, animal studies and paediatric studies) were removed initially before screening.

Figure 2

Summary of association between anorexia/appetite loss and outcomes in studies identified (n = 58 articles), shown by healthcare setting. White squares indicate the number of studies assessing the outcome; red circles indicate the number of studies where anorexia/appetite loss was associated with poor outcomes; and yellow circles indicate the number of studies where anorexia/appetite loss was not associated with the outcome. HRQoL, health‐related quality of life. ^a‘Other’ includes studies with mixed settings (no separate results by setting) and studies where care was provided in an outpatient setting. ^bBased on findings from a univariate analysis, a significant association was found between anorexia/appetite loss and mortality in reference but not in reference. An association between anorexia/appetite loss and treatment interruption was found in univariate, but not multivariate, analysis. ^cIn Kiesswetter et al. (2020), an association of appetite loss with malnutrition was reported separately for both community‐dwelling and institutional care cohorts; therefore, this study has been counted in both the categories. ^dSarcopenia was reported in seven studies. ^ePoor appetite alone was not significantly associated with sarcopenia development in participants with poor appetite and without low masticatory function; however, a significantly higher risk of sarcopenia was observed in those who had both poor appetite and low masticatory function. ^fIn Nakatsu et al. (2015), the authors measured walking speed, chair stand time, hand‐grip strength and timed ‘Up and Go’ test and characterized these outcomes as measures of physical performance and not sarcopenia; however, other studies also used these measures to assess sarcopenia. A significant correlation between walking speed, chair stand time and timed ‘Up and Go’ test and better appetite was noted, whereas the correlation between hand‐grip strength and appetite was not statistically significant. ^gLack of appetite was found to be associated with HRQoL as assessed by the Short Form‐12 mental component summary score only, but not with the Short Form‐12 physical component summary score. ^hAnorexia was found to be associated with a significantly higher risk of disability in both studies in unadjusted or non‐fully adjusted models, but this association was no longer significant in fully adjusted models., ⁱ‘Other outcomes’ includes frailty, general health, infection, major adverse cardiovascular or cerebrovascular events, sleep quality, stroke, treatment (chemotherapy) interruption and weight loss, which are reported in one study each. The two inpatient studies both had some “other outcomes” that were associated with anorexia/appetite loss and some that were not. Thus, they are shown in both categories in the figure.

Figure 3

Relationship between anorexia/appetite loss and malnutrition in studies reporting odds ratios. Community‐dwelling represents independent living or free living in the community. Institutional care represents living in a nursing care facility or care home. Inpatient represents being hospitalized or staying in a hospital ward. Other represents living in healthcare setting not covered (e.g., outpatient or conducted in mixed healthcare setting). Studies above the dashed line used better appetite as the reference group (positive odds ratio = more risk of malnutrition), whereas studies below the dashed line used worse appetite as the reference group (negative odds ratio = less risk of malnutrition). BMI, body mass index; CI, confidence interval; ESAS, Edmonton Symptom Assessment System; FAACT, Functional Assessment of Anorexia/Cachexia Treatment; Q, question. ^aFifteen of the 58 studies identified investigated and reported a significant relationship between anorexia/poor appetite and malnutrition, with 10 studies presenting data as an odds ratio. ^bOdds ratio [95% CI] = 0.82 [0.70, 0.95]. ^cUnadjusted odds for better appetite associated with a lower risk of malnutrition, other studies were adjusted for baseline variables. ^dUnivariate odds ratio for relationship between BMI and malnutrition (i.e., higher BMI is associated with a lower risk of malnutrition).

Figure 4

Relationship between anorexia/appetite loss and mortality^a. (A) Data as hazard ratio. (B) Data as relative risk. (C) Data as odds ratio. (D) Other mortality data. CI, confidence interval; CNAQ, Council on Nutrition Appetite Questionnaire; COVID‐19, coronavirus disease 2019; F, female; M, male; SNAQ, Simplified Nutritional Appetite Questionnaire. ^aOf the 58 studies identified, 18 longitudinal studies investigated the relationship between anorexia/poor appetite and mortality. Of these, 17 studies showed a significant association (P < 0.05) and are presented. ^bFive‐year survival based on decline in appetite from baseline to 3 months. ^cFive‐year survival based on decline in appetite from baseline to 6 months. ^dAnalysis in female was non‐significant. ^eUnadjusted hazard ratio, other studies adjusted for baseline variables as detailed in Table S5 . ^fData show that better appetite (i.e., higher CNAQ/SNAQ scores) is associated with lower risk of mortality. Findings agree with other studies showing that loss of appetite is associated with higher risk of mortality. ^gOdds ratio [95% CI] = 1.02 [1.00, 1.03], P = 0.01, with higher scores indicating better appetite (score inversely related to mortality). ^hOne‐year mortality was not significant for good appetite (3.8%) versus less appetite (5.9%), P = 0.46.