What is the extent of reliability and validity evidence for screening tools for cognitive and behavioral change in people with ALS? A systematic review

Figures & data

Figure 1. Prisma flow diagram.

Table 1. Search terms for systematic review evaluating the reliability and validity of cognitive and behavioral screening tools.

Category

Search terms

Screening tools for cognitive/behavioral change

ECAS OR Edinburgh Cognitive and Behavio*ral ALS Screen OR Edinburgh Cognitive Behavio*ral ALS Screen OR Edinburgh Cognitive and Behavio*ral Amyotrophic Lateral Sclerosis Screen OR Edinburgh Cognitive Behavio*ral Amyotrophic Lateral Sclerosis Screen OR  ALS-CBS OR ALS CBS OR Amyotrophic Lateral Sclerosis CBS OR ALS Cognitive Behavio*ral Screen OR Amyotrophic Lateral Sclerosis Cognitive Behavio*ral Screen OR Amyotrophic Lateral Sclerosis-CBS OR ALS-Cognitive Behavio*ral Screen OR Amyotrophic Lateral Sclerosis-Cognitive Behavio*ral Screen OR Mini-ACE OR Mini ACE OR Mini Addenbrooke’s Cognitive examination OR Mini-Addenbrooke’s Cognitive examination OR M-ACE OR MACE OR  ALS-FTD-Q OR Amyotrophic Lateral Sclerosis-FTD-Q OR Amyotrophic Lateral Sclerosis FTD-Q OR Amyotrophic Lateral Sclerosis Frontotemporal Dementia Questionnaire OR Amyotrophic Lateral Sclerosis-Frontotemporal Dementia Questionnaire OR ALS Frontotemporal Dementia questionnaire OR ALS-Frontotemporal Dementia Questionnaire  OR BBI OR Beaumont Behavio* Inventory, OR  MiND-B OR Motor Neuron* Disease Behavio*r scale OR Motor Neuron* Disease-Behavio*r scale

Table 2. Demographic characteristics.

Measure	Author	Sample size (n)	Age Mean (sd)	Female (%)	Years of education Mean (sd)	Language
ECASc	Abrahams et al., 2014	C:40; ALS:48	ALS:60.0 (11.4); C:59.2 (12.6)	C:55.0; ALS:31.3	ALS:11.5 (2.2); C:12.3 (2.5)	English
ECASc	Lulé et al., 2015	ALS:136; C:60; IRR-C:10	ALS:60.0 (10.1); C:60.0 (12.6)	ALS:33.1; C:50.0	ALS:13.7 (2.9); C:13.9 (3.1)	Swiss-German
ECASc	Niven et al., 2015	ALS:40; C:40	ALS:64.5 (10.2); C:62.7 (10.5)	C:35.0; ALS:35.0	ALS:11.2 (2.0); C:12.3 (3.4)	English
ECAS	Poletti et al., 2016	ALS:107; C:248; IRR-C:30	ALS:63.0 (12.5); C:57.8 (10.6)	ALS:34.6; C:58.1	ALS:10.8 (4.2); C:14.1 (4.6)	Italian
ECASc	Ye et al., 2016	ALS:84; C:84	ALS:55.1 (10.7); C:54.8 (11.0)	ALS:31.0; C:32.1	ALS:11.5 (3.4); C:11.5 (3.4)	Chinese
ECASc	de Icaza Valenzuela et al., 2018	C:57	56.0 (13.3)	40.4	NR	English
ECASc	Bakker et al., 2019	ALS:428; C:428	ALS:63.7 (10.8); C:63.7 (10.8)	ALS:38.3; C:38.3	NR	Dutch
ECASc	Díaz et al., 2019	ALS:18	64.5 (11.6)*	45.0*	NR	Spanish
ECASc	Saxon et al., 2020	bvFTD:23; ALS-FTD:20; C:30	ALS-FTD:65.0 (8.0); bvFTD:60.0 (7.0); C:59.0 (8.0)	ALS-FTD:40.0; bvFTD:39.1; C:30.0	ALS-FTD:13.0 (3.0); bvFTD:12.0 (3.0); C:14.0 (3.0)	English
ECASc	Mojtabavi et al., 2021	ALS:30; C:31	ALS:53.9 (13.7); C:50.2 (11.5)	ALS:46.7; C:74.9	ALS:11.7 (3.6); C:14.0 (2.7)	Persian
ECASc	Fazio et al., 2021	C:102	54.9 (14.6)	52.9	14.5 (2.4)	Czech
ECASc	Beeldman et al., 2021	ALS:29	62.0 (8.7)	31.0	14.2 (2.6)	Dutch
ECASc	Watanabe et al., 2021	ALS:35; C:28	ALS:68.2 (7.4); C:63.8 (12.7)	ALS:42.9; C:42.9	ALS:11.9 (2.7); C:13.0 (2.4)	Japanese
ECASc	Aiello et al., 2022	ALS:89	63.1 (10.4)	43.8	11.7 (4.2)	Italian
ECASc	Albertyn et al., 2022	ALS:21; C:21; IRR-C:45	ALS:53.2 (13.4); C:53.9 (12.5)	ALS: 61.9; C:57.1	ALS:9.7 (2.8); C:10.2 (2.9)	Afrikaans; English
ECASc	Kacem et al., 2022	C:97; ALS:85	C:59.5 (11.7); ALS:59.5 (11.7)	C:40.2; ALS:31.4	NR	Tunisian Arabic
ECASc	Lee et al., 2023	ALS:38	61.3 (9.2)	50.0	12 (9-16)**	Korean
ECAS ALS-CBS	Mora et al., 2018	ALS:102; C:40; ALS-FTD:8	ALS:56.4 (NR); C:55.4 (NR); ALS-FTD:61.5 (NR)	ALS:36.3; C: 60.0; ALS-FTD:37.5	C:19.1 (NR); ALS:18.5 (NR); ALS-FTD:17.0 (NR)	Spanish
ECASc ALS-CBSc	Greco et al., 2021	ALS:154	66.3 (10.2)	46.1	NR	Italian
ECASc ALS-CBSc	Aiello, Solca, Greco, Torre, et al., 2023	ALS:293	64.6 (11.1)	48.1	11.6 (4.4)	Italian
ECAS ALS-CBS Mini-ACE	Kourtesis et al., 2019	C:52; ALS 28; AD:26	ALS:68.5 (7.1); AD:67.2 (4.1); C:NR	ALS:41.7; AD:46.2	ALS:11.1 (3.2); AD:11.1 (3.2)	Greek
ALS-CBS	Woolley et al., 2010	ALS:31; C:15	ALS:56.0 (NR); C:54.0 (NR)	ALS:45.0; C:67.0	ALS:14.5 (NR); C:14.0 (NR)	English
ALS-CBS	Turon-Sans et al., 2016	ALS:50	62.3 (NR)	36.0	NR	Spanish
ALS-CBS	Murphy et al., 2016	ALS:274	60.5 (10.1)	41.6	NR	English
ALS-CBSc	Branco et al., 2017	ALS:49; C:10	ALSci:60.3 (12.7); ALSni:55.1 (8.2); C:56.5 (7.7)	ALSci:40.0; ALSni:41.0; C:20.0	ALSci:7.5 (3.4); ALSni:9.9 (5.2); C:11.8 (3.8)	Portuguese
ALS-CBSc	Tremolizzo et al., 2020	C:458; ALS:100	C:56.4 (16.8); ALS:64.3 (10.2)	ALS:33.0	C:11.4 (4.7); ALS:10.1 (4.2)	Italian
ALS-CBSb ECASb	Aiello, Solca, Greco, La Tona, et al., 2023	ALS:265	65.0 (10.9)	47.9	11.4 (4.2)	Italian
ALS-CBSb	Murphy et al., 2015	ALS:24	59.6 (1.8)	38.0	14.6 (1.7)	English
ALS-FTD-Q	Raaphorst et al., 2012	ALS:103; ALS-bvFTD:10; bvFTD:25; MC:39; C:31	ALS:61.4 (11.9); ALS-bvFTD:60.2 (10.4); bvFTD:63.4 (6.2); MC:58.7 (13.3); C:58.3 (11.7)	ALS:29.1; ALS-bvFTD:30.0; bvFTD:32.0; MC:43.6; C:51.6	NR	Dutch
ALS-FTD-Q	Watanabe et al., 2016	ALS:92; ALS-bvFTD:6; bvFTD:16; C:32	ALS:67.7 (10.2); ALS-bvFTD:67.2 (6.9); bvFTD:67.1 (8.4); C:62.1 (8.6)	ALS:40.2; ALS-bvFTD: 50.0; bvFTD:37.5; C:56.3	NR	Japanese
ALS-FTD-Q BBI	Pinto-Grau et al., 2017	ALS:60	65.4 (9.7)	30.0	13.2 (3.4)	English
BBI	Elamin et al., 2017	ALS:85; C:78	ALS:63.1 (12.3); C:63.2 (9.6)	ALS:32.9; C:47.4	ALS:13.3 (3.4); C:14.1 (3.9)	English
BBI	Burke et al., 2017	ALS:317; C:66	ALS:63.0 (11.1); C:61.4 (13.7)	ALS:49.0; C:55.0	ALS:12.9 (3.8); C:13.5 (3.8)	English
BBI	Iazzolino et al., 2022	ALS:90; C:100	ALS:63.3 (10.6); C:62.3 (11.7)	ALS:56.7; C:51.0	ALS:11.7 (4.2); C:12.2 (3.9)	Italian
MiND-B	Mioshi et al., 2014	ALS:79	limb onset: 60.4 (11.6); bulbar onset: 58.7 (10.4)	limb onset:40.0; bulbar onset:54.0	limb onset:13.7 (3.2); bulbar onset:14.1 (2.9)	English
MiND-B ECASc	Rahimzadeh Goradel et al., 2023	ALS:46	54.9 (10.3)	32.6	NR	Persian
MiND-B Mini-ACE	Hsieh, Caga, et al., 2016	ALS:70; ALSPlus:19; ALS-FTD:24; C:45	ALS:56.3 (11.8); ALSPlus:57.6 (10.3); ALS-FTD:63.1 (8.9); C:67.6 (5.9)	ALS:40.7; ALSPlus:36.8; ALS-FTD:33.3; C:48.9	ALS:13.5 (3.1); ALSPlus:12.5 (2.9); ALS-FTD:12.3 (3.1); C:13.1 (2.9)	English

Note: C = control. MC = muscle disease control. ALSci = ALS with cognitive impairment. ALSni = ALS with no impairment. bvFTD = behavioral variant frontotemporal dementia. ECASc = ECAS cognitive section. ALS-CBSc = ALS-CBS cognitive section. NR = Not reported. * = these statistics are representative of the wider sample of 40 ALS participants. IRR-C = healthy controls studied to determine inter-rater reliability. * Language refers to the language in which the screening tool was delivered. ** = Median (IQR) is reported in place of mean (sd).

Table 3. ALS sample characteristics.

Measure	Author	Disease duration (months) Mean (sd)	ALSFRS-R Mean (sd)	Onset site (%)
ECASc	Abrahams et al., 2014	25.0 (NR)**	25.2 (11.4)	Bulbar: 29.2
ECASc	Lulé et al., 2015	39.0 (41.4)	34.9 (7.8)	Spinal: 80.2; Bulbar: 19.9
ECASc	Niven et al., 2015	25.5 (NR)**	35.7 (NR)	NR
ECAS	Poletti et al., 2016	21.1 (19.4)	37.2 (6.8)	Bulbar: 21.5; Limb: 76.6
ECASc	Ye et al., 2016	15.8 (14.5)	41.3 (4.6)	Bulbar: 19.1; Thoracic: 3.6; Cervical: 58.3; Lumbar: 19.1
ECASc	Bakker et al., 2019	NR	37.6 (7.1)	Spinal: 72.2; Bulbar: 26.6
ECASc	Díaz et al., 2019	65.6 (54.8)*	25.2 (11.4)*	Spinal: 67.5; Bulbar: 32.5*
ECASc	Saxon et al., 2020	36.0 (3.0)	NR	NR
ECASc	Mojtabavi et al., 2021	NR	35.9 (7.2)	NR
ECASc	Beeldman et al., 2021	9.0 (NR)**	40.0 (NR)**	Limb: 72.4; Bulbar: 20.7; Mixed: 7.0
ECASc	Watanabe et al., 2021	55.3 (NR)**	33.3 (10.1)	Bulbar: 25.7; Cervical: 37.1; Lumbar: 37.1
ECASc	Aiello et al., 2022	NR	39.9 (4.7)	NR
ECASc	Albertyn et al., 2022	NR	35.8 (7.4)	Spinal: 76.2; Bulbar: 23.8
ECASc	Kacem et al., 2022	NR	38.3 (8.7)	Spinal: 72.1; Bulbar 19.8
ECASc	Lee et al., 2023	17.5 (10-31)**	37.5 (5.9)	Limb:71.1; Bulbar:28.9
ECAS ALS-CBS	Mora et al., 2018	ALS:40.5 (NR)**; ALS-FTD: 20.7 (NR)**	NR	ALS – Limb: 81.9; Bulbar: 13.8; Respiratory and other: 1.1; Unknown: 3.2 ALS-FTD – Limb: 75.0; Bulbar: 25.0
ECASc ALS-CBSc	Greco et al., 2021	56.1 (75.7)	28.0 (9.6)	Bulbar: 26.6; Spinal: 66.2; Generalized: 4.1
ALS-CBSc ECASc	Aiello, Solca, Greco, Torre, et al., 2023	21.9 (36.6)	33.1 (10.1)	NR
ECAS ALS-CBS Mini-ACE	Kourtesis et al., 2019	NR	NR	NR
ALS-CBS	Woolley et al., 2010	22.0 (NR)	34.0 (NR)	Limb: 66.0; Bulbar: 34.0
ALS-CBS	Turon-Sans et al., 2016	18.0 (NR)	29.2 (NR)	Spinal: 76.0; Bulbar: 22.0
ALS-CBS	Murphy et al., 2016	11.8 (4.5)	36.1 (6.6)	Bulbar: 32.1; Cervical: 32.5; Thoracic: 1.1; Lumbosacral: 32.1; Respiratory: 1.8; Other: 0.4
ALS-CBSc	Branco et al., 2017	ALSci:25.8 (29.7); ALSni:39.8 (52.7)	ALSci:35.3 (5.3); ALSni:35.0 (7.5)	NR
ALS-CBSc	Tremolizzo et al., 2020	42.0 (37.0)	31.2 (9.2)	Spinal: 81.0; Bulbar: 19.0
ALS-CBSb ECASb	Aiello, Solca, Greco, La Tona, et al., 2023	38.7 (52.7)	32.4 (10.1)	NR
ALS-CBSb	Murphy et al., 2015	56.0 (49.0)	28.0 (1.9)	NR
ALS-FTD-Q	Raaphorst et al., 2012	ALS:33.5 (NR)**; ALS-bvFTD:35.5 (NR)**	ALS:31.5 (9.2); ALS-bvFTD:32.9 (6.1)	ALS & ALS-bvFTD – Limb: 82.3
ALS-FTD-Q	Watanabe et al., 2016	ALS:21.0 (NR)**; ALS-bvFTD:30.0 (NR)**	ALS:33.7 (9.7); ALS-bvFTD:26.8 (8.2)	ALS – Limb: 75.0; Bulbar: 25.0 ALS-bvFTD - Limb: 50.0; Bulbar: 50.0
ALS-FTD-Q	Pinto-Grau et al., 2017	NR	33.4 (6.2)	Spinal: 64.0; Bulbar: 28.0; Respiratory: 8.0
BBI	Elamin et al., 2017	NR	37.7 (6.4)	NR
BBI	Burke et al., 2017	22.1 (16.1)	35.2 (7.9)	Spinal: 56.7; Bulbar: 23.2; Respiratory: 2.9
BBI	Iazzolino et al., 2022	NR	39.9 (4.7)	NR
MiND-B	Mioshi et al., 2014	limb onset: 27.6 (28.0); bulbar onset: 15.2 (18.0)	limb onset: 30.5 (13.8); bulbar onset: 31.7 (13.5)	Limb: 69.6; Bulbar: 30.4
MiND-B ECASc	Rahimzadeh Goradel et al., 2023	NR	32.0 (10.4)	NR
MiND-B Mini-ACE	Hsieh, Caga, et al., 2016	ALS:18.0 (14.2); ALSPlus:28.9 (21.2); ALS-FTD:40.1 (26.3)	ALS:40.3 (6.9); ALSPlus:38.4 (6.4); ALS-FTD:37.9 (5.7)	ALS - Bulbar: 88.9; Limb: 11.1 ALSPlus – Bulbar: 36.8; Limb: 63.2 ALS-FTD – Bulbar: 66.7; Limb: 33.3

Note: ALSci = ALS with cognitive impairment. ALSni = ALS with no impairment. FTD = frontotemporal dementia. bvFTD = behavioral variant FTD. NR = not reported. ALSPlus = ALS with cognitive and/or behavioral impairment. ECASc = ECAS cognitive section. ALS-CBSc = ALS-CBS cognitive section. NA = not applicable. * = these statistics are representative of the wider sample of 40 ALS participants, rather than the sub-set of 18 participants for which validation statistics were generated. ** = Median (IQR) is reported in place of mean (sd).

Table 4. Risk of bias and study quality assessment.

Measure	Author	N ≥ 30 (0–1)*	ALS cohort (0-1)**	Validated against gold standard (0–2)***	Bias/quality score (% of available total)
ECASc	Abrahams et al., 2014	1	1	0	50
ECASc	Lulé et al., 2015	1	1	NA	100
ECASc	Niven et al., 2015	1	1	2	100
ECAS	Poletti et al., 2016	1	1	NA	100
ECASc	Ye et al., 2016	1	1	0	50
ECASc	de Icaza Valenzuela et al., 2018	1	0	NA	50
ECASc	Bakker et al., 2019	1	1	NA	100
ECASc	Díaz et al., 2019	0	1	NA	50
ECASc	Saxon et al., 2020	1	1	NA	100
ECASc	Mojtabavi et al., 2021	1	1	1	75
ECASc	Fazio et al., 2021	1	0	0	25
ECASc	Beeldman et al., 2021	0	1	2	75
ECASc	Watanabe et al., 2021	1	1	0	50
ECASc	Aiello et al., 2022	1	1	2	100
ECASc	Albertyn et al., 2022	0	1	NA	50
ECASc	Kacem et al., 2022	1	1	NA	100
ECASc	Lee et al., 2023	1	1	NA	100
ECAS ALS-CBS	Mora et al., 2018	1	1	0	50
ECASc ALS-CBSc	Greco et al., 2021	1	1	NA	100
ALS-CBSc ECASc	Aiello, Solca, Greco, Torre, et al., 2023	1	1	NA	100
ECAS ALS-CBS Mini-ACE	Kourtesis et al., 2019	1	1	2	100
ALS-CBS	Woolley et al., 2010	1	1	2	100
ALS-CBS	Turon-Sans et al., 2016	1	1	2	100
ALS-CBS	Murphy et al., 2016	1	1	NA	100
ALS-CBSc	Branco et al., 2017	1	1	2	100
ALS-CBSc	Tremolizzo et al., 2020	1	1	NA	100
ALS-CBSb ECASb	Aiello et al., 2023	1	1	NA	100
ALS-CBSb	Murphy et al., 2015	0	1	NA	50
ALS-FTD-Q	Raaphorst et al., 2012	1	1	NA	100
ALS-FTD-Q	Watanabe et al., 2016	1	1	NA	100
ALS-FTD-Q BBI	Pinto-Grau et al., 2017	1	1	NA	100
BBI	Elamin et al., 2017	1	1	1	75
BBI	Burke et al., 2017	1	1	NA	100
BBI	Iazzolino et al., 2022	1	1	2	100
MiND-B	Mioshi et al., 2014	1	1	2	100
MiND-B ECASc	Rahimzadeh Goradel et al., 2023	1	1	NA	100
MiND-B Mini-ACE	Hsieh, Caga, et al., 2016	1	1	2	100

Note: NA = not applicable as ROC curves were not generated and so gold standard classifications of impairment were not needed. ECASc = ECAS cognitive section. ALS-CBSc = ALS-CBS cognitive section. * N ≥ 30 was awarded one point. **Those using an ALS cohort were awarded one point. *** If validated against a gold standard of clinical diagnosis or outcome of a full neuropsychological test battery, two points were awarded; if validated against a widely accepted cognitive/behavioral measure, one point was awarded.

Table 5. Risk of bias and study quality assessment for inter-rater reliability assessments.

Measure	Author	N ≥ 30 (0–1)*	ALS cohort (0–1)**	Blinding (0–1)***	Randomly selected (0–1)****	Bias/quality score (% of available total)
ECASc	Lulé et al., 2015	0	0	1	0	25
ECASc	Poletti et al., 2016	1	0	1	1	75
ECASc	Albertyn et al., 2022	1	0	0	NAµ	33
ECASc	Kourtesis et al., 2019	1	1	1	NA	100

Note: µ = not relevant because whole sample was used or a separate additional sample was used. NA = not applicable. ECASc = ECAS cognitive section. *N ≥ 30 was awarded one point. **Those using an ALS cohort were awarded one point. ***If raters were blinded to scores given by other raters, studies were awarded one point. ****Where a sub-sample was selected from the larger main study sample, one point was awarded if the sub-sample was randomly selected.

Table 6. Internal consistency.

Measure	Author	Cronbach’s alpha
ECASc	Abrahams et al., 2014	ALS & C: 0.75; ALS: 0.77
ECASc	Poletti et al., 2016	0.86
ECASc	Ye et al., 2016	0.74
ECAS	Mora et al., 2018	ECASc: 0.78; ECASb: 0.56
ECASc	Kourtesis et al., 2019	0.84
ECASc	Mojtabavi et al., 2021	ALS & C: 0.79; ALS: 0.78
ECASc	Fazio et al., 2021	0.69
ECASc	Watanabe et al., 2021	0.77
ECASc	Kacem et al., 2022	0.85/0.87**
ECASc	Lee et al., 2023	0.87
ALS-CBSb	Aiello, Solca, Greco, La Tona, et al., 2023	0.90*
ALS-FTD-Q	Raaphorst et al., 2012	0.92
ALS-FTD-Q	Watanabe et al., 2016	0.92
BBI	Elamin et al., 2017	0.89
BBI	Burke et al., 2017	0.91
BBI	Iazzolino et al., 2022	0.93
MiND-B	Mioshi et al., 2014	0.97
MiND-B	Rahimzadeh Goradel et al., 2023	0.70

Note: Papers omitted from this table did not report internal consistency of the relevant screening tools. ECASc = ECAS cognitive section. *Internal reliability based on McDonald’s ω, rather than Cronbach’s α. C = control group. **Both statistics were reported in different places in the paper but the corresponding author did not respond to a request for clarification.

Table 7. Test cutoff scores, sensitivity, specificity, area under the curve and convergent validity.

Measure	Author	Cutoff (sensitivity; specificity)	AUC	Convergent validity
ECASc	Abrahams et al., 2014	105
ECASc	Lulé et al., 2015			ECASc/FAB: r = 0.53; ECASc/MoCA: r = 0.60
ECASc	Niven et al., 2015	^‡105 (69; 89); 110 (92; 81)	0.91
ECAS	Poletti et al., 2016			ECASc/MoCA: r = 0.70; ECASc/FAB: r = 0.63; ECASb/FBI: r = 0.63
ECASc	Ye et al., 2016	81.9
ECASc	de Icaza Valenzuela et al., 2018			ECASc/ACE-III: r = 0.54
ECASc	Díaz et al., 2019			Memory component of neuropsychological battery / ECASc: Cohen’s kappa = 0.75
ECASc	Saxon et al., 2020			ECASc naming/ Graded Naming Test: rs = 0.65; ECASc spelling/ PALPA spelling: rs = 0.86; ECASc sentence completion/ Hayling test: rs = 0.68; ECASc social cognition/ Judgment of Preference: rs = 0.64
ECASc	Mojtabavi et al., 2021	88.6 (100; 50)	0.87	ECASc/MoCA: rs = 0.74
ECASc	Fazio et al., 2021	86
ECASc	Beeldman et al., 2021	105* (83; 83)	0.90
ECASc	Watanabe et al., 2021	86.8		ECASc/MoCA: rs = 0.53; ECASc/FAB: rs = 0.59
ECASc	Aiello et al., 2022	** (74; 89)	** 0.87
ECASc	Albertyn et al., 2022			ECASc/MoCA: r = 0.59
ECASc	Kacem et al., 2022			ECASc/FAB: rs = 0.69; ECASc/MMSE: rs = 0.72
ECASc	Lee et al., 2023			ECASc/MoCA: r = 0.69 ECASc/FAB: r = 0.55
ECAS ALS-CBS	Mora et al., 2018	ECASc: 73	ECASc: 0.75	ECASc/ALS-CBSc: rs = 0.76; ECASb/ALS-CBSb: rs = −0.58
ECASc ALS-CBSc	Greco et al., 2021			ECASc/ALS-CBSc: rs = 0.64, Cohen’s kappa = 0.20
ECASc ALS-CBSc	Aiello, Solca, Greco, Torre, et al., 2023			ECASc/ALS-CBSc: R^2: 0.71
ECAS ALS-CBS Mini-ACE	Kourtesis et al., 2019	ECASc AD from ALS: 93 (92; 55); Mini-ACE AD from ALS: 23 (97; 71)	ECASc AD from ALS: 0.85; Mini-ACE AD from ALS: 0.87	ALS-CBSc/ECASc: r = 0.82; ALS-CBSc/Mini-ACE: r = 0.73; ALS-CBSb/ECASb: r = −0.75
ALS-CBS	Woolley et al., 2010	ALS-CBSc ALSci: 17 (85; 71); ALS-FTD: 10 (100; 100); ALS-CBSb ALSbi: 36 (90; 86); ALS-FTD: 32 (88; 80)
ALS-CBS	Turon-Sans et al., 2016	ALS-CBSc ALSci: 15 (86; 62); ALS-FTD: 8 (83; 75) ALS-CBSb ALSbi: 36 (93; 75); ALS-FTD: 35 (83; 69)	ALS-CBSc ALSci: 0.85; ALS-FTD: 0.87 ALS-CBSb ALSbi: 0.83; ALS-FTD: 0.81
ALS-CBS	Murphy et al., 2016			ALS CBSb/FBI-ALSb: rs = 0.72; ALS CBSc/FBI-ALSc: rs = 0.49
ALS-CBSc	Branco et al., 2017	ALSci: 10 (90; 87)	0.91
ALS-CBSc	Tremolizzo et al., 2020			ALS-CBSc/FAB: Cohen’s kappa = 0.55, rs = 0.60; ALS-CBSc/WST: Cohen’s kappa= 0.60, rs = 0.59
ALS-CBSb ECASb	Aiello, Solca, Greco, La Tona, et al., 2023			ALS-CBSb/FBI: rs = −0.80; ALS-CBSb/ECASb: rs = −0.59
ALS-CBSb	Murphy et al., 2015			ALS-CBSb/FBI-ALS negative subscale r = − 0.90; ALS-CBSb/FBI-ALS disinhibition subscale: r = − 0.82
ALS-FTD-Q	Raaphorst et al., 2012			ALS-FTD-Q/FrSBe: rs = 0.80; ALS-FTD-Q/FBI: rs = 0.79
ALS-FTD-Q	Watanabe et al., 2016			ALS-FTD-Q/FBI: rs = 0.79
ALS-FTD-Q BBI	Pinto-Grau et al., 2017			BBI/ALS-FTD-Q: rs = 0.81
BBI	Elamin et al., 2017	Mild: 7 (88; 79); Moderate: 22.5 (90; 96)	0.96	BBI/FrSBe: r = 0.76; BBI/FAB: r = 0.44
BBI	Iazzolino et al., 2022	11.5 (92; 78)	0.90
MiND-B	Mioshi et al., 2014	35 (90; 50); 33 (81; 75)
MiND-B ECASc	Rahimzadeh Goradel et al., 2023			MiND-B/ECASc: r = −.435^†
MiND-B Mini-ACE	Hsieh, Caga, et al., 2016	MiND-B: 33* (90; 79) Mini-ACE: 25* (65; 90)

Note: Papers omitted from this table did not report validity statistics of relevant screening tools. AUC = Area under the curve. * = used published cutoff score. ** = cutoff scores varied for age and education groups. ^† = Authors demonstrated divergent validity, that the MiND-B measures behavior, a concept that is separate to cognition (measured by the ECASc). ^‡ = Niven et al. (2015) proposed an ECASc cognitive impairment cutoff score of between 105 and 110. r = Pearson’s correlation coefficient. r_s = Spearman’s rho. AD: Alzheimer’s disease. ALSci – ALS with cognitive impairment. ALSbi – ALS with behavioral impairment. ALS FTD – ALS with frontotemporal dementia. ECASc = ECAS cognitive section. ALS-CBSc = ALS-CBS cognitive section. ACE-III = Addenbrooke’s Cognitive Examination (58). FrSBe = Frontal Systems Behavior Scale (53). FBI = Frontal Behavioral Inventory (54). FBI-ALS = Frontal Behavioral Inventory ALS version (59). FBI-ALSc - cognitive component of FBI-ALS. FBI-ALSb = behavioral component of FBI-ALS. MoCA = Montreal Cognitive Assessment (15). FAB = Frontal Assessment Battery (14). WST = Weigl sorting test (60). PALPA = Psycholinguistic Assessments of Language Processing in Aphasia (61). Sensitivity and specificity scores of 1.0 are described as perfect; 0.90-0.99 are excellent; 0.80-0.89 are very good; 0.70-0.79 are good; 0.60-0.69 are fair; and 0.50-0.59 are medium; this descriptive system was generated for this systematic review.

Mathuranath PS, Nestor PJ, Berrios GE, Rakowicz W, Hodges JR. A brief cognitive test battery to differentiate Alzheimer’s disease and frontotemporal dementia. Neurology 2000;55:1613–20.

 PubMed Web of Science ®Google Scholar

Grace J, Malloy P. Frontal systems behavior scale: professional manual. Lutz, Florida: Psychological Assessment Resources Inc; 2001.

 Google Scholar

Kertesz A, Davidson W, Fox H. Frontal behavioral inventory: diagnostic criteria for frontal lobe dementia. Can J Neurol Sci. 1997;24:29–36.

 PubMed Web of Science ®Google Scholar

Kertesz A, Nadkarni N, Davidson W, Thomas A. The Frontal Behavioral Inventory in the differential diagnosis of frontotemporal dementia. J Int Neuropsychol Soc. 2000;6:460–8.

 PubMed Web of Science ®Google Scholar

Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53:695–9.

 PubMed Web of Science ®Google Scholar

Dubois B, Slachevsky A, Litvan I, Pillon B. The FAB: A frontal assessment battery at bedside. Neurology 2000;55:1621–6.

 PubMed Web of Science ®Google Scholar

Weigl E. On the psychology of so-called processes of abstraction. J Abnorm Soc Psychol. 1941;36:3–33.

 Google Scholar

Kay J, Lesser R, Coltheart M. Psycholinguistic assessments of language processing in aphasia (PALPA). East Sussex: Lawrence Erlbaum Associates; 1992.

 Google Scholar