Defining cognitive impairment in amyotrophic lateral sclerosis: an evaluation of empirical approaches

Figures & data

Table 1 Study populations from which normative data were collected, statistical methods, and threshold strategies used to define cognitive impairment on the ECAS.

	2SD-UK	2SD-NAC	QR-NAC
Study population	N = 40	N = 269	N = 269
	UK Controls	North American Controls	North American Controls
		(CALSNIC, CRiALS, PENN)	(CALSNIC, CRiALS, PENN)
Statistical method	Mean ± 2SD	Mean ± 2SD	Quantile regression
Threshold strategy	2SDs below the mean^a	2SDs below the mean	5th percentile, adjusting for age and education

SD: standard deviation; NAC: North American Controls. ^aCutoff values previously published⁵.

Table 2 Summary demographics and ECAS performance from three cohort studies of healthy adults, constituting our North American Controls (N = 269).

Demographics	Overall		CALSNIC		CRiALS		PENN
Total N (% female)	269 (56%)		147 (54%)		40 (70%)		82 (52%)
Age, mean (SD)	55.5 (11.5)		56.7 (9.9)		50.2 (12.8)		56.0 (13.0)
≥College education, %	60%		50%		80%		70%
ECAS Performance	Mean	Median	Mean	Median	Mean	Median	Mean	Median
	(SD)	[25–75 %tile]	(SD)	[25–75 %tile]	(SD)	[25–75 %tile]	(SD)	[25–75 %tile]
Language	26.5	27	26.4	27	26.6	27	26.7	27
(Max score = 28)	(1.8)	[26, 28]	(2.0)	[26, 28]	(1.7)	[26, 28]	(1.5)	[26, 28]
Fluency	18.6	20	18.0	20	18.9	20	19.5	20
(Max score = 24)	(4.0)	[16, 20]	(4.3)	[16, 20]	(3.0)	[18, 20]	(3.8)	[18, 22]
Executive	39.8	41	39.3	41	39.9	41	40.7	42
(Max score = 48)	(4.5)	[38, 43]	(4.9)	[38, 43]	(4.4)	[38, 43]	(3.6)	[38, 43]
Memory	17.1	17	16.8	17	18.2	19	17.1	17
(Max score = 24)	(2.9)	[15, 19]	(3.0)	[15, 19]	(2.4)	[16.75, 20]	(2.7)	[15, 18.75]
Visuospatial	11.8	12	11.8	12	11.8	12	11.8	12
(Max score = 12)	(0.5)	[12, 12]	(0.4)	[12, 12]	(0.5)	[12, 12]	(0.6)	[12, 12]
ALS Specific	84.9	87	83.7	86	85.4	87	86.9	89
(Max score = 100)	(8.1)	[81, 90]	(8.9)	[80, 89]	(6.6)	[81, 9]	(6.7)	[84, 91]
ALS Nonspecific	29.0	29	28.7	29	30.0	31	29.0	29
(Max score = 36)	(3.0)	[27, 31]	(3.1)	[27, 31]	(2.4)	[28, 32]	(2.8)	[27, 30.75]
Total	113.9	115	112.4	114	115.4	117	115.9	116
(Max score = 136)	(9.3)	[110, 120]	(10.5)	[108, 120]	(7.6)	[110, 121]	(7.3)	[112, 122]

Figure 1 Quantile regression model for ECAS Total, ALS Specific, and ALS Nonspecific scores across age, including 5^th percentile cutoff (red) as well as for the comparison of two standard deviation approach for North America (2SD-NAC; orange) and United Kingdom (2SD-UK; blue).

Table 3 Comparison of ECAS cutoffs determined using two standard deviation approach with published United Kingdom values (2SD-UK) (5) and, in the North American Controls, using a two standard deviation (2SD-NAC) and quantile regression (QR-NAC) statistical approaches.

ECAS Score	2SD-UK	2SD-NAC	Education	QR-NAC (age)^a
				35	40	45	50	55	60	65	70	75
Language	26	23	<College	24	24	24	24	24	23	23	22	22
(Max value = 28)			≥College	24	24	24	24	24	23	23	22	22
Fluency	14	11	<College	12	12	12	11	11	9	8	6	5
(Max value = 24)			≥College	14	14	14	13	13	11	10	8	7
Executive	33	31	<College	33	32	32	31	31	30	30	29	29
(Max value = 48)			≥College	32	31	31	30	30	29	29	29	28
Memory	13	11	<College	14	13	13	12	11	11	10	9	9
(Max value = 24)			≥College	15	15	14	13	13	12	11	11	10
Visuospatial	10	11	<College	11	11	11	11	11	11	11	11	11
(Max value = 12)			≥College	11	11	11	11	11	11	11	11	11
ALS Specific	77	69	<College	74	73	72	71	70	68	67	66	65
(Max value = 100)			≥College	77	76	75	73	72	71	70	69	67
ALS Nonspecific	24	23	<College	26	25	25	24	23	23	22	22	21
(Max value = 36)			≥College	27	26	25	25	24	24	23	23	22
Total	105	95	<College	102	101	99	98	96	94	92	90	87
Max value = 136)			≥College	106	105	103	101	100	98	96	93	91

^aQuantile regression technique used to estimate the 5th percentile values adjusted for age and education.

Figure 2 Prevalence of impairment on the ECAS in 182 ALS patients using three different sets of normative cutoffs. QR-NAC: Quantile regression North American Controls; 2SD-NAC: 2 standard deviation cutoff North American; 2SD-UK: 2 standard deviation cutoff United Kingdom.

Abrahams S, Newton J, Niven E, Foley J, Bak TH. Screening for cognition and behaviour changes in ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2014;15:9–14.

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