Natural History of Poststroke Apathy During Acute Rehabilitation

From November 2013 to May 2014, we studied consecutively admitted patients undergoing acute rehabilitation for an ischemic or a hemorrhagic stroke that occurred within 30 days of study enrollment. All patients had some impairment from their stroke that prevented them from returning home after their hospitalization (typically a deficit in mobility with or without other deficits).

We excluded patients who could have had apathy from causes other than stroke, such as a neurodegenerative condition, dementia (defined as a score >3.4 on the Informant Questionnaire of Cognitive Decline in the Elderly¹¹), or a medication that acted on dopamine (e.g., treatment for psychosis, nausea, or attention). We also excluded patients who were not independent before their current stroke (e.g., required assistance for mobility due to previous stroke or musculoskeletal disorder), because this would affect interpretation of outcome measures. We excluded patients admitted for <7 days, because this would give inadequate time to conduct our assessments. In addition, some patients were initially hypoaroused (i.e., required stimulation to maintain eye opening) as a result of stroke or medical issues; thus, we only studied them once or if they became consistently fully alert.

All measures reported here were included as part of the clinical record. The Burke Rehabilitation Hospital Institutional Review Board approved this analysis of the data, and procedures were followed in accordance with institutional guidelines.

We used the AI-C to determine the prevalence and natural history of apathy.¹⁰ The AI-C asks the clinician to report on the following: 1) emotional blunting, 2) loss of initiative (i.e., goal-directed behavior), and 3) loss of interest in activities and other people. Each question is scored on a 5-point scale ranging from 0 (no problem) to 4 (major problem), with a total score ranging from 0 to 12. We chose this measure because it allows an assessment of apathy solely based on observed behavior, which enabled us to include patients with aphasia. The more commonly used Apathy Scale¹² and the Apathy Evaluation Scale¹³ assess patients’ internal states, which cannot be done in patients with aphasia. In addition, these more commonly used scales contain questions that are difficult to interpret for patients admitted to an inpatient rehabilitation unit.

The patients’ primary speech-language pathologist performed the AI-C starting 1 week after admission and weekly thereafter. The speech-language pathologists were asked to score based on behaviors observed during the entire previous week. For prevalence data, for patients without aphasia we report the AI-C performed closest in time to the measures of cognition and depression; for patients with aphasia we report the first AI-C.

We interviewed patients with intact language using the Montgomery-Åsberg Depression Rating Scale (0–60, with higher scores representing worse depression) to quantify depressive symptoms.¹⁴

Patients with intact language performed version 1 of the Montreal Cognitive Assessment (0–30, with lower scores indicating worse cognition) to measure overall cognition.¹⁵ We converted these scores to a z score based on a large reported sample, taking into account age and education.¹⁶

We used the FIM score (18–126, with lower scores representing more disability; UB Foundation Activities, Inc., Buffalo, NY) to determine the level of disability from admission (first 3 days) to discharge (final 3 days). We used the change in the total FIM as well as the FIM efficiency (change in total FIM score divided by length of stay) to measure improvement from admission to discharge. We used a line cancellation test (≤34 of 36 considered abnormal) to determine the presence of neglect.¹⁷ Finally, we used the Fugl-Meyer assessment to determine motor function.¹⁸

All statistical analyses were performed in MATLAB software (MathWorks, Natick, MA) using built-in and Statistics Toolbox codes. Gaussian-distributed data are reported as means and standard deviations; non-Gaussian–distributed data are reported as medians and interquartile ranges. The AI-C was treated as an ordinal variable because it is not a linear measure of apathy severity. We used the Mann-Whitney U test for correlation of the AI-C with binary variables, producing a z score and a p value. We used the Spearman’s rank-order correlation coefficient for correlation with continuous variables, producing a coefficient ranging from −1 to 1 and a p value. Box plots were created using MATLAB’s “boxplot.m” with default parameters. The thick lines within the gray boxes represent the median, whereas the edges of the gray boxes represent the 25th to 75th percentiles; whiskers extend to the most extreme data points not considered outliers; outliers (crosses) are those values outside the 25th to 75th percentiles by +1.5 times the interquartile range, corresponding to approximately 99.3% coverage if the data are normally distributed.

On the basis of the AI-C score from the treating speech-language pathologist, we found that 27 patients (28%) had apathy (AI-C score ≥4, with at least one of the three dimensions ≥2). Apathy severity was not normally distributed, because 42 patients (44%) had a score of zero (i.e., no signs of apathy) (Figure 1).

We explored the relationships among the three subscores of the AI-C (emotional blunting, loss of interest, and loss of initiative) to determine whether patients presented with separate syndromes. We found that the scores generally correlated highly, because only seven of the 96 subjects had a subscore >1 point away from another subscore.

We documented apathy severity weekly, although patients had varied lengths of hospital stay; this resulted in fewer data points at the longer time durations. Patients without apathy at week one generally had no change in their apathy score over their stay (Figure 2A), though some worsened slightly with five developing apathy at some point during their stay. Patients with apathy at week 1 (AI-C ≥4) typically demonstrated improvement in apathy severity, although this improvement was only to a small degree (Figure 2B). Specifically, from week 1 to week 2, patients with apathy had a mean change of −1.04 (SD=1.73) in their AI-C score, with five of the 24 patients showing resolution of apathy (AI-C <4). From weeks 1 to 3, patients with apathy had a mean change of −2.40 (SD=2.03) in their AI-C score, with seven of the 15 patients showing resolution of apathy. From weeks 1 to 4, patients with apathy had a mean change of −2.14 (SD=2.03) in their AI-C score, with one of the seven patients showing resolution of apathy.

Aphasia correlated significantly with apathy severity (Figure 3 and Table 1). Using an AI-C cutoff value of 4 to define apathy, we determined that 10 (53%) of the 19 patients with aphasia were apathetic, whereas only 17 (22%) of the 77 patients without aphasia were apathetic. Regarding a change in apathy severity, patients with and without aphasia both showed a small degree of improvement during the first 2 weeks, but only the patients without aphasia improved during the subsequent weeks (Figure 2, D and F). Patients with aphasia were also less likely to have resolution of apathy. In patients who stayed at least 2 weeks, seven of 14 patients without aphasia had resolution of apathy compared with only three of 10 patients with aphasia.

We measured depression severity using the Montgomery-Åsberg Depression Rating Scale in the 77 patients without aphasia. Based on a published cutoff value of 18,¹⁹ 15 (19.5%) of the 77 patients were depressed. We found no correlation between the Montgomery-Åsberg Depression Rating Scale and AI-C scores (Figure 4 and Table 1).

Regarding other clinical variables, apathy severity had a significant correlation with the following: overall cognition (Montreal Cognitive Assessment z score); disability (admission FIM score); change in FIM score from admission to discharge, whether measured directly or divided by length of stay (FIM efficiency); presence of neglect (line cancellation); and motor impairment (Fugl-Meyer score) at discharge (Table 1). Patients with apathy were also more likely to go to a nursing home after discharge. Gender, age, days since stroke onset, and years of education did not have statistically significant associations with apathy severity.