Apathy After Hip Fracture: A Potential Target for Intervention to Improve Functional Outcomes

The study recruited consecutive hip fracture admissions to an acute care hospital from March 2002 to October 2004, as described previously. 16 Participants received surgical repair and were ages 60 or older, able to provide informed consent, free of metastatic cancer, and had a Mini-Mental State Examination (MMSE) 17 score greater than 15. This study was approved by the university’s institutional review board.

Participants were prospectively observed for 6 months. They were assessed at the end of their acute hospital stay (i.e., at baseline) and then 2 weeks later with the Apathy Evaluation Scale (AES) 15 to measure signs and symptoms of apathy. The AES is a comprehensive measure of the observable behavioral, cognitive, and emotional concomitants of goal-directed behavior; it has 18 items and scores range from 18 to 72, with higher scores indicating more apathy. It measures how a subject feels at a particular time (rather than functioning as a dispositional or trait-like measure) and therefore can be used to examine changes in apathy over time. Cronbach alpha for the measure in this study was 0.93. Participants were also assessed for depressive symptoms with the 17-item Hamilton Depression Rating Scale (HAM-D) 18 and the Cornell Scale for Depression in Dementia. 19 – 20 Cognitive functioning was measured with the MMSE, the initiation/perseveration subscale of the Dementia Rating Scale, 21 the Trail Making test parts A and B, 22 and the logical memory subtest of the Wechsler Memory Scale, 3rd ed. 23 Delirium was measured with the Delirium Rating Scale. 24 Additionally, medical comorbidity was measured using the Cumulative Illness Rating Scale for Geriatrics. 25 This scale has items (scored from 0 to 4) for different domains of medical illness; for example, those with neurological illness (e.g., prior stroke) would have a positive score on the neurological item (#12).

Functional status was measured at baseline and at 2, 12, and 26 weeks later, using the 13 motor items of the Functional Independence Measure (FIM-motor). 26 This instrument rates dependency on other persons or assistive devices for activities of daily living and mobility tasks and is scored on a range from 13 (complete dependency for all activities of daily living and mobility tasks) to 91 (complete independence). For those who received rehabilitation in a skilled nursing facility or inpatient rehabilitation hospital, we measured their participation in physical and occupational therapy using the Pittsburgh Rehabilitation Participation Scale (PRPS), 27 a validated scale of patient participation in inpatient rehabilitation which provides a clinician-measured summary score (1–6, with higher scores indicating better participation) for each therapy session.

The first hypothesis was that baseline apathy symptoms predicted functional recovery. Thus we examined (1) distribution of baseline AES scores and rate of clinically significant apathy symptoms, (2) demographic and clinical characteristics associated with apathy symptoms using Pearson correlation coefficients, and (3) baseline apathy symptoms as a predictor of trajectory of FIM-motor scores over 6 months, using a mixed effect repeated measures analysis.

Our second hypothesis was that improved apathy was associated with improved functional recovery. Thus we (1) examined distribution of changes from baseline to week 2 among initially high-apathy participants; (2) compared functional recovery between patients grouped by high versus low baseline and follow-up levels of apathy symptoms with persistently high AES scores (“high-high”) and persistently low-apathy patients using a mixed effect repeated measures model; and (3) examined correlates of improved apathy among cognition, depression, and other variables using Pearson correlation coefficients and t tests.

We approached 141 patients; 13 refused the study (or dropped out before providing baseline data) and two were excluded from further participation because of moderate to severe cognitive impairment. Thus, the study group comprised 126 patients. Baseline and week 2 characteristics of the participants are summarized in Table 1 .

The mean AES score was 33.7 (SD=9.4) at baseline and 33.4 (SD=9.6) at week 2. Examining the distributions found no natural cutoff; therefore, we chose the cutoff of ≥38 as a definition of clinically significant apathy symptoms, as previously reported. 15 By this cutoff, 46/126 patients (37%) had clinically significant apathy at baseline and 36/113 patients (32%) had clinically significant apathy at week 2.

Next we examined the correlation of baseline Apathy Evaluation Scale (AES) scores with age and baseline clinical characteristics. Of the two depression measures, AES scores were significantly correlated (p<0.001) with both the Cornell Scale for Depression in Dementia (r=0.42, n=90) and HAM-D scores (r=0.40, n=126). Among measures of cognitive function, AES scores were significantly correlated (p<0.001) with general cognitive ability as based on the MMSE (r=−0.42, n=126) as well as measures of executive function (Delirium Rating Scale initiation/perseveration subscale, r=−0.57, n=82 and Trails B, r=0.51, n=88) and attention/psychomotor speed (Trails A, r=0.49, n=92), but not delayed recall (Logical Memory Test, r=−0.12, n=108). Scores on the AES scores also correlated (p<0.001) with Delirium Rating Scale scores (r=0.37, n=126), postfracture FIM-motor scores (r=−0.38, n=126), and age (r=0.27, n=126). Scores on the AES were not significantly associated with overall medical burden (Cumulative Illness Rating Scale for Geriatrics score, r=0.14, n=121) or neurological illness (Cumulative Illness Rating Scale for Geriatrics item 12, r=0.14, n=125). At baseline, 41 patients (33%) were taking sedative medications, and 64 patients (52%) were taking opiate pain medications; apathy scores were not different in those taking these medications versus those without, nor were these medications associated with functional recovery (data not shown).

For depression and delirium measures we examined correlations with and without items in those scales that overlapped with the apathy construct, consistent with prior literature. 6 Thus, we removed three items from the HAM-D (item 7, “work and activities,” item 8, “psychomotor retardation,” and item 13, “somatic symptoms general”), four items (items 3, 6, 8, and 11) from the Cornell Scale for Depression in Dementia, and one item (item 9, “apathy”) from the Delirium Rating Scale. However, removing these items did not appreciably change either the magnitude or significance of the correlations of AES with these measures (data not shown).

Table 2 shows the results of a series of univariate mixed-effects models predicting functional recovery from the baseline (immediate postfracture) period to 26 weeks. AES scores predicted recovery, with a moderate effect size, while depression measures were not significant predictors. In a multivariate model including all covariates that were potential predictors of recovery ( Table 3 ), AES scores remained a significant predictor of functional recovery, albeit with reduced effect size. Comparing high baseline apathy (AES >38) with low apathy groups in a mixed effects model found similar results; apathy group was a significant predictor (F=20.7, df=1, 124, p<0.001), with FIM-motor improvement at 2 weeks of 8.9 versus 27.6 in the high versus low groups, respectively. By 26 weeks, the FIM-motor improvement was 17.7 versus 31.4 in the high versus low groups, respectively.

Because these findings supported our hypothesis that baseline apathy symptoms predicted functional recovery, we then examined whether rehabilitation participation may account for the association of AES scores with functional recovery, as prior research has found that apathy predicts participation in rehabilitation 14 and that rehabilitation participation predicts functional outcome. 28 First, we confirmed that AES scores correlated with Pittsburgh Rehabilitation Participation Scale (PRPS) scores: baseline AES was correlated with mean PRPS scores in occupational therapy (r=−0.39, p<0.001, n=97) and physical therapy (r=−0.29, p<0.01, n=103). Next, we added mean PRPS scores to the multivariate model presented in Table 3 . While PRPS scores predicted poorer functional outcome in this revised model (F=8.96, df=1, 96, p=0.0035, effect size=0.27), the effect size of the association of AES with functional outcome did not change. Finally, we examined a reduced model that included AES, PRPS, and an AES × PRPS interaction term; this term was trend-level significant (F=3.2, df=1, 104, p=0.08) while AES was not significant (F=0.6, df=1, 104, p=0.46). Ensuing correlations showed a significant relationship between PRPS and FIM-motor outcome in individuals with AES score ≥38, and no relationship among those with AES score <38.

To examine changes in apathy from baseline to week 2, we divided the sample into four groups: those with high AES scores (≥38) at both time points (“high-high” or persistently high apathy, n=25), those with high baseline AES scores but with lower scores (<38) at week 2 (“high-low” or improved apathy, n=13), those with low AES scores (<38) at both time points (“low-low” or persistently low apathy, n=64), and those with initially low AES scores but high scores at week 2 (“low-high,” n=11). We grouped participants in this way to provide clinically salient observations. The improved apathy group had a mean (SD) change of −8.2 (4.5) in AES scores, corresponding to a 19% decline, from baseline to week 2, while the persistent apathy group had a change of 1.6 (5.7), corresponding to a 4% increase in scores.

Figure 1 shows the trajectory of FIM-motor scores in these four groups. The main interest was to contrast those with improved (“high-low”) apathy with those with persistent (“high-high”) apathy. As the figure shows, individuals with improved apathy had a better functional recovery; however, the modeled data are suggestive of an effect early but not late in recovery. Therefore we ran post-hoc tests comparing the groups in terms of FIM-motor improvements at 2 weeks, 12 weeks, and 26 weeks. As this figure shows, those with initially high but improved apathy symptoms showed significantly better functional recovery at 2 weeks, but not at 12 or 26 weeks, compared to those with persistently high apathy symptoms.

Because these findings supported our hypothesis that improved apathy symptoms were associated with better functional recovery than persistent symptoms, we then examined clinical and demographic correlates of improved apathy. Delirium scores were lower and MMSE scores higher at both baseline and week 2 for those with improved apathy than for those with persistently high apathy; no other demographic or clinical features (including neurological illness, benzodiazepine use, or opiate use) differed significantly between these two groups. Baseline delirium scores and MMSE for the “high-low” and “high-high” apathy groups were 4.0 (SD=2.0) versus 8.6 (SD=5.6) and 24.9 (SD=2.8) versus 22.1 (SD=3.7), respectively. Adding these terms to the model did not change the strength of the difference between improved and persistent apathy symptoms in terms of functional outcomes (data not shown).

We also examined whether AES scores in the overall sample changed in concert with cognitive or depressive symptom scores between baseline and week 2. However, we found small and nonsignificant correlations of change in AES score with change in MMSE score (r=0.14, n=109), change in Delirium Rating Scale score (r=0.13, n=111), and change in HAM-D score (r=−0.08, n=112). Thus, changes in apathy symptoms between baseline and week 2 were independent of changes in cognition, delirium, or depressive symptoms.