A neuropsychological and behavioral study of PLS

Figures & data

Table 1 Demographic and clinical characteristics.

	PLS (n = 30)
Male (n (%))	18 (60%)
Age at NPE (m yrs., (range))	66.4 (49–82)
Disease duration at NPE (m yrs., (range))	16.3 (7–31)
Bulbar onset (n (%))	3 (10%)
ALSFRS-R at NPE (m ± SD)	31.9 ± 6.9
Regions affected at NPE
Bulbar and spinal regions (n (%))	20 (67%)
Upper and lower extremities only (n (%))	6 (20%)
Lower extremities only (n (%))	4 (13.3%)
Level of education
Grade school (n (%))	1 (3.3%)
Secondary education (n (%))	3 (10.0%)
Post-secondary non-tertiary education (n (%))	13 (43.3%)
First stage of tertiary education (n (%))	9 (30.0%)
University (n (%))	4 (13.3%)
Handedness
Right (n (%))	27 (90%)
Left (n (%))	2 (6.7%)
Ambidextrous (n (%))	1 (3.3%)
HADS
HADS - A score (m ± SD)	3.6 ± 2.3
HADS - D score (m ± SD)	3.7 ± 2.0

ALSFRS-R: Revised ALS Functional Rating Scale; NPE: Neuropsychological Evaluation; HADS: Hospital Anxiety and Depression Scale.

Table 2 Overview neuropsychological test battery.

Cognitive domain	Test	Main cognitive process(es)	Source normative data
Executive functions	Trail Making Test - Part A	Attention
	Trail Making Test - Part B	Cognitive flexibility, Attention
	Trail Making Test (A - B)	Cognitive flexibility, Attention	(22)
	Rule Shift Cards (BADS)	Cognitive flexibility	(23)
	Digit Span Total score	Working memory, Attention:	(24)
	Digit Span Forwards	Attention
	Digit Span Backwards	Working memory, Attention
	Digit Span Sorting	Working memory, Attention
	Brixton Visuospatial Anticipation Test	Cognitive flexibility	(25)
Social Cognition	Hinting task	Cognitive theory of mind^a	(16)
	Reading the mind in the eyes	Affective theory of mind^a	(26)
Fluency	Verbal fluency test (letters K,O,M)	Semantic memory, cognitive flexibility, working memory	(27)
Language	Boston naming test	Visual perception/recognition, Lexical-semantic retrieval	(28)
Memory	RAVLT (15-word test)	Verbal episodic memory:	(22)
	Immediate recall	Short-term memory, Attention
	Delayed recall	Long-term memory: recollection
	Delayed recognition	Long-term memory: familiarity
	Corsi Block Tapping Task	Visuospatial short-term memory, Working memory	(29)
	Visual Association Task	Associative memory	(20)
Visuospatial functions	JLO	Visuospatial perception	(30)

BADS: Behavioral Assessment of the Dysexecutive Syndrome; RAVLT: Rey Auditory Verbal Learning Test; JLO: Judgement of Line Orientation.

^aTheory of mind (ToM) is the ability to reason about the thoughts, beliefs, and feelings of one’s self and others to predict behavioral responses (31). ToM can be divided into a cognitive and affective component. The Hinting task looks at cognitive ToM, which is focused on the beliefs, thought and intentions of others, whereas the Reading the mind in the eyes test looks at affective ToM, which is focused on the interpretation of emotions.

Table 3 Neuropsychological test results.

Domain	Test	N	Test maximum	Test score (median (range))	Percentile test result (median (range))	Performance <5th percentile (n (%))
Executive functions	Trail Making Test - Part A	25	NA	45.6 (26.6–245.3)	NA	NA^a
	Trail Making Test - Part B	24	NA	107.5 (51.0–425.4)	NA	NA^a
	Trail Making Test (A - B)	24	NA		34 (1–90)	4 (17%)^a
	Rule Shift Cards (BADS)	30	NA		67 (1–87)	6 (20%)
	Digit Span Total score	29	19	8 (4 -15)	24 (2–96)	1 (3%)
	Digit Span Forwards		19	8 (6–15)	24 (9–96)	0
	Digit Span Backwards		19	9 (3–15)	38 (1–96)	3 (10%)
	Digit Span Sorting		19	9 (3–14)	38 (1–90)	1 (3%)
	Brixton Visuospatial Anticipation Test	25	NA	16 (8–32)	54 (6–97)	0
	ECAS; domain score	28	48	34.5 (22–46)	25 (2–95)	3 (11%)
	FAB ^b	29	18	15 (9–18)	NA	2 (7%)
Social Cognition	Hinting task	25	20	18 (12–20)	43 (1–86)	3 (12%)
	Reading the mind in the eyes	25	36	22 (16–28)	14 (1–76)	11 (44%)
	ECAS; social cognition tasks	28	12	12 (9-12)	NA	NA
Fluency	Verbal fluency test (letters K,O,M)	26	NA	29 (8–57)	19 (1–95)	7 (27%)
	ECAS; domain score (letters T,N)	28	24	20 (12–24)	48 (1–99)	2 (7%)
Language	Boston naming test	30	90	83 (64–90)	37 (1–90)	2 (7%)
	ECAS; domain score	28	28	26.5 (20–28)	47 (1–93)	3 (11%)
Memory	RAVLT (15-word test)	25
	Immediate recall		75	40 (16–52)	18 (1–84)	5 (20%)
	Delayed recall		15	7 (0–14)	27 (1–95)	3 (12%)
	Delayed recognition^b		30	29 (22–30)	NA	6 (24%)
	Corsi Block Tapping Task	28	144	35 (12–60)	18 (3–80)	1 (4%)
	Visual Association Task	27	24	21 (13–24)	34 (2–70)	1 (4%)
	ECAS; domain score	28	24	16 (5–22)	25 (1–97)	2 (7%)
Visuospatial functions	JLO	29	30	25 (14–30)	72 (4–86)	1 (3%)
	ECAS; domain score	28	12	12 (8–12)	60 (1–66)	2 (7%)
ECAS composite scores	ECAS total score	28	136	110.5 (83–128)	22 (1–98)	4 (14%)
	ECAS ALS-specific score	28	100	80 (59–96)	25 (1–99)	3 (11%)
	ECAS ALS-nonspecific score	28	36	28 (17–34)	36 (2–95)	2 (7%)

ECAS: Edinburgh Cognitive and Behavioral ALS Screen; BADS: Behavioral Assessment of the Dysexecutive Syndrome; RAVLT: Rey Auditory Verbal Learning Test; JLO: Judgement of Line Orientation; FAB: Frontal Assessment Battery

a The TMT-A and TMT-B were not assessed individually due to their dependency on manual dexterity. The TMT-A-B score is relatively independent of manual dexterity and therefore more appropriate to use in our study.

^bNo percentile rank of scores were available. A score of <12 for the FAB and <27 for the RAVLT: delayed recognition were considered abnormal.

Table 4 Neuropsychological profiles of individual PLS patients based on the NPE and the ECAS behavioral interview.

Patients	Cognitive domains						Behavior		Classification
	Executive functions	Fluency	Social cognition	Language	Memory	Visuospatial functions	ECAS behavioral interview	ALS-FTD-Q	Strong consensus criteria^c
1							NA	NA
2	X	X	X		X		0	10	CI
3			X			X	NA	7	Unclassified
4	X	X	X	X	X	NA	LS, ST	21	bvFTD
5			X				AP, DI, HA, LS	25^a	bvFTD
6			X	X			NA	3	Unclassified
7							NA	NA
8	X		X		X		NA	NA	CI
9			X		X		ST	3	D
10		NA			X		DI, ST	22^a	BI
11	X	X					AP, LS	18	bvFTD
12	X	X	X				0	20	CI
13			X				NA	12	Unclassified
14					X		0	20	aMCI^d
15	X	X					0	6	CI
16		NA					0	3
17			X		X		LS	30^b	D
18					X		0	3	aMCI^d
19	X				X		NA	NA	CI
20							LS	17
21							AP	29^b	BI
22							NA	NA
23					X		NA	3	aMCI^d
24	X						NA	14	CI
25							0	17
26			X				AP, HA	NA	BI
27		NA					NA	12
28		NA					0	29^b	bvFTD
29	X	X					0	23^a	CBI
30	X	X	X		X		DI, HA, LS	41^b	bvFTD

ECAS: Edinburgh Cognitive and Behavioral ALS Screen; ALS-FTD-Q: ALS and Frontotemporal Dementia Questionnaire; AP: apathy; DI: disinhibition; HA: hyperorality/dietary changes; LS: loss of sympathy; ST: perseverative or stereotyped behavior; X: abnormal performance on at least one subtest (score below the 5^th percentile); NA: not available/missing item; CI: cognitive impairment; BI: behavioral impairment; CBI: cognitive and behavioral impairment; D: ALS with dementia, not typical of FTD; bvFTD: behavioral variant frontotemporal dementia.

^amild behavioral disturbances.

^bsevere behavioral disturbances^.

^cRevised consensus criteria for the diagnosis of frontotemporal dysfunction in amyotrophic lateral sclerosis (ALS) by Strong et al.(34).

^dAmnestic mild cognitive impairment, not part of the Strong consensus criteria.

Figure 1 Classification of patients according to the revised Strong consensus criteria. *The proportion of the total of patients (n = 30) included in the study categorized according to the revised consensus criteria for the diagnosis of frontotemporal dysfunction in amyotrophic lateral sclerosis (ALS) by Strong, et al.[34]. bvFTD: behavioral variant frontotemporal dementia; BI: behavioral impairment; CBI: cognitive and behavioral impairment; CI: cognitive impairment; D: ALS with dementia, not typical of FTD; *aMCI: amnestic mild cognitive impairment, not part of the revised Strong consensus criteria.

Figure 2 Correlation between disease duration and the number of abnormal cognitive domains. The number of abnormal cognitive domains (performance ≤5th percentile) varied between 0–5, with a theoretical maximum of 6: executive functions, social cognition, fluency, language, memory and visuospatial functions.

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