Progression and effect of cognitive-behavioral changes in patients with amyotrophic lateral sclerosis

Abstract

Background: To prospectively evaluate the progression of cognitive-behavioral function in amyotrophic lateral sclerosis (ALS) and examine the association of cognitive-behavioral deficits with disease progression, patient quality of life (QOL), and caregiver burden.

Methods: We evaluated cognitive-behavioral function using the Amyotrophic Lateral Sclerosis Cognitive Behavioral Screen at enrollment and after 7 months in a cohort of patients with ALS. Paired t tests were used to evaluate the change in the 2 assessments. Linear regression and Kruskal-Wallis tests were applied to investigate how initial cognitive or behavioral status related to outcomes.

Results: The mean test-retest interval was 6.8 months (SD 1.6). Cognitive status of the study population (n = 49) overall did not change over the study period (p = 0.06) despite progression of motor weakness (p < 0.001), though small subsets of the sample demonstrate cognitive change. Patients initially classified as behaviorally normal showed increased behavioral problems over time (t = -2.8, p = 0.009). Decline in cognitive (β = -1.3, p = 0.03) and behavioral (β = -0.76, p = 0.002) status predicted increasing caregiver burden. Behavioral abnormalities predicted decline in forced vital capacity and ALS Functional Rating Scale-Revised score (p = 0.008, 0.012) in the study population and patient QOL in the most severely affected group (t = 4.3, p = 0.003).

Conclusions: Cognitive-behavioral change is a key aspect of disease heterogeneity in ALS. Executive function in ALS overall remains stable over 7 months as detected by an administered screening tool. However, patients may develop caregiver-reported behavioral symptoms in that time period. Screening for caregiver-reported symptoms has a particular utility in predicting future clinical decline, increased caregiver burden, and worsening patient QOL.

Figure 1. Change in Amyotrophic Lateral Sclerosis Cognitive Behavioral Screen (ALS CBS) cognitive subscore over time

(A) Normal. (B) Cognitive impairment. (C) Frontotemporal dementia (FTD). Change in ALS CBS cognitive subscore from initial to follow-up assessment stratified by cognitive category at baseline. Changes for individual participants are shown with gray lines and the average change for the group is shown as a red line. Dotted lines indicate normative cutoffs between cognitive categories (ALS CBS cognitive score ≥17 is normal, 11–16 is cognitive impairment, and ≤10 is FTD range). *Change is significant (p < 0.05).

Figure 2. Change in Amyotrophic Lateral Sclerosis Cognitive Behavioral Screen (ALS CBS) behavioral subscore over time

(A) Normal. (B) Behavioral impairment. (C) Frontotemporal dementia (FTD). Change in ALS CBS behavioral subscore from initial to follow-up assessment stratified by behavioral category at baseline. Changes for individual participants are shown with gray lines and the average change for the group is shown as a red line. Dotted lines indicate normative cutoffs between cognitive categories (CBS behavioral score ≥37 is normal, 33–36 is behavioral impairment, and ≤32 is FTD range). *Change is significant (p < 0.05).

Figure 3. Change in patient quality of life (QOL) over time

(A) Change in QOL by cognitive category. (B) Change in QOL by behavior category. Change in patient QOL as measured by the McGill Quality of Life Single-Item Score over time stratified by initial cognitive and behavioral category among 46 patients with amyotrophic lateral sclerosis. FTD = frontotemporal dementia.