Background
Methods
Participants, diagnosis and assessments
Assessment of memory
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The French version of the Free and Cued Selective Reminding Test (RL/RI-16 [38]): This verbal memory test is based on semantic cuing, which allows controlling for encoding and facilitates retrieval. Sixteen words are presented that are associated with a category cue. Participants are asked to recall the words in three successive trials, then to recognise the 16 items between 32 distractors before recalling them in a 30-minute delayed trial. Each trial includes free recall (FR) and cued recall (CR) tasks whereby the category cue is provided for the items not spontaneously recalled. The total recall (TR) score is the sum of the FR and the CR.
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The Delayed Matching to Sample-48 items (DMS-48 [39]): The DMS-48 consists of a visual forced-choice recognition test. After an implicit encoding phase where 48 coloured items are presented, an immediate recognition trial (set 1) and a 1-h delayed recognition trial (set 2) are proposed in which participants are asked to choose between the target and a distractor. Two different sets of distractors are used.
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Forward and backward digit spans [40]: These tests allow evaluation of short-term and working memory. The short-term memory span is the longest list of numbers the participant can recall in correct order immediately after presentation. Backward memory span is the longest list of numbers the participant can recall in reverse order immediately after presentation.
Assessment of executive function
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Frontal Assessment Battery (FAB [41]): The FAB briefly assesses six cognitive function domains sustained by the frontal lobes: conceptualisation, mental flexibility, motor programming, sensitivity to interference, inhibitory control and environmental autonomy. Three points are awarded for every perfect response (maximum score 18).
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Trail Making Test (TMT) A and B [42]: Both parts consist of 25 circles distributed over a sheet of paper. In TMT A, the circles are numbered 1–25, and the participant is asked to draw lines to connect the numbers in ascending order as quickly as possible. In the TMT B, the circles include both numbers (1–13) and letters (A–L). The participant has to draw lines to connect the circles in an ascending pattern as quickly as possible while alternating between the numbers and letters. The completion time and the number of errors are recorded.
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Formal lexical evocation [43]: The participant is asked to generate as many words as possible that start with the letter P within 2 minutes.
Assessment of processing speed
Assessment of instrumental function
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Rey-Osterrieth Complex Figure test (ROCF [45]): Participants were presented with the ROCF stimulus card and asked to draw the same figure. The figure is subcategorised into 18 elements, and these are scored on the basis of their presence, completeness and correct placement (0.5, 1 or 2 points per element; maximum score 36).
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The following subtests using the Visual Object and Space Perception battery (VOSP [46]) allow the evaluation of visuoperceptual and visuospatial abilities:
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Screening: The participant has to identify whether there is a degraded ‘X’ on 20 patterned sheets of paper. One point is given for each correct answer (maximum score 20).
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Incomplete letters: Twenty incomplete letters are shown, and the subject is asked to name or identify them. A point is awarded for each correct answer (maximum score 20).
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Dot count: The participant is asked to count how many black dots there are on a white card. There are ten cards. A point is awarded for every correct count (maximum score 10).
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Position discrimination: Ten boards are presented. Each board has two squares with a black dot in the centre each. In one of the squares, the point is exactly in the centre, whereas the other point is slightly off-centre. The participant is asked to identify the square in which the black spot is located exactly in the centre. The number of correct answers is recorded (maximum score 10).
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‘Number location’: Ten boards are presented in this test. Each board has two squares arranged one above the other. The top square contains numbers arranged randomly. The bottom square contains only a black dot. The participant is asked to identify which number corresponds to the black dot. Each correct identification earns 1 point (maximum score 10).
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Cube analysis: Ten boards are presented. Each board features a design of solid structures. The participant is asked to identify how many solids (cubes) there are on each board. The boards are presented in increasing degree of difficulty (maximum score 10).
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Praxis is tested by the means of a brief battery [47] evaluating five symbolic gestures (scored 0 or 1 point), five pantomimes (scored 0, 1 or 2 points) and imitation of eight meaningless gestures (scored 0 or 1 point).
Evaluation of social cognition
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Mini-Social Cognition & Emotional Assessment (mini-SEA [48]) test battery: The mini-SEA comprises a facial emotion recognition test and a shortened version of the Faux Pas Recognition Test (FPRT [49]). Emotion recognition is assessed by means of 35 photographs from a series of pictures of facial affect [50]. The faces display one of the six basic emotions (i.e., happiness, sadness, disgust, fear, surprise and anger) or a neutral facial expression. After looking at each photograph, participants choose the emotion that best corresponds to their opinion of that facial expression. The maximum score, indicating best performance, is 35. The FPRT consists of ten short stories, five with and five without a faux pas. Each story has two types of questions, namely six theory of mind (ToM) questions and two control questions. The ToM questions assess the detection and understanding of faux pas and the understanding of the speaker’s and the listener’s mental states. One point is given for each correct answer on the faux pas questions, and two points are given for each correct rejection of control stories (maximum score 40). Raw scores are converted to weighted scores. Both scores are weighted out of 15, resulting in a total weighted score out of 30.
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French version of the Reading the Mind in the Eyes (RME) test [51]: This test evaluates the ability of an individual to determine the mental state of another individual by looking at a picture of the latter’s eyes. The task consists of 36 items showing the eye region of 36 different faces in black-and-white photographs. Each picture has four mental state terms printed below it, and the participant has to choose the word that best describes what the person in the photograph is feeling or thinking. The number of correct answers is recorded (maximum score 36).
Data analyses
Results
Participants’ characteristics
Characteristic | Patients with DLB | HCs |
p Value |
---|---|---|---|
n
| 37 | 29 | |
Age, yearsa
| 67.19 (8.64) | 68.79 (7.94) | NS |
Education, yearsa
| 11.97 (4.14) | 13.18 (3.08) | NS |
Sex, M/F | 18/19 | 15/14 | NS |
Handedness, R/L | 35/2 | 27/2 | NS |
IADL scorea,b
| 3.75 (0.50) | 4 (0) | 0.02 |
ADL scorea,c
| 5.89 (0.39) | 6 (0) | NS |
MCI single/multiple domains | |||
Amnestic | 0/18 | – | – |
Non-amnestic | 10/9 | – | – |
Parkinsonism, n (%)d
| |||
Rigidity | 28/37 (76) | 0/23 | <0.001 |
Akinesia | 22/37 (59) | 1/24 | <0.001 |
Tremor at rest | 10/37 (27) | 1/24 | 0.02 |
Hallucinations, n (%)d
| 24/37 (65) | 1/24 | <0.001 |
Fluctuations, n (%)d,e
| 28/37 (76) | 0/24 | <0.001 |
CSFf,g
| |||
Aβ42
| 902.6 (265.1, 2) | – | – |
p-Tau | 43.4 (12.2, 2) | – | – |
Tau | 306.1 (264.1, 1) | – | – |
Hippocampal atrophy, 0/1/2/3/4h
| |||
Left hippocampus | 17/8/9/2/0 | 14/8/2/0/0 | NS |
Right hippocampus | 15/10/11/0/0 | 11/11/2/0/0 | NS |
Cognition
Patients with DLB (n = 37) | HCs (n = 29) |
p Value | ||||
---|---|---|---|---|---|---|
Raw scorea
| z-Scorea
| Raw scorea
| z-Scorea
| |||
Global functioning | MMSE (score/30) | 27.36 (1.97) | 29.00 (0.90) | 0.008 | ||
Memory | ||||||
FCSRT | IR | 15.11 (1.72) | −0.17 (2.34) | 15.90 (0.31) | 0.81 (0.49) | NS |
FR1 | 7.31 (2.36) | −0.66 (1.00) | 8.79 (2.09) | 0.02 (0.78) | 0.006 | |
FR2 | 8.28 (2.91) | −0.55 (1.18) | 10.62 (2.43) | 0.40 (0.91) | 0.001 | |
FR3 | 9.89 (2.67) | −0.51 (1.01) | 11.38 (2.50) | 0.08 (0.91) | 0.035 | |
TR1 | 14.22 (1.85) | −0.27 (1.12) | 15.07 (1.22) | 0.29 (0.62) | NS | |
TR2 | 14.81 (2.03) | −0.35 (1.76) | 15.72 (0.65) | 0.49 (0.40) | NS | |
TR3 | 15.43 (0.95) | −0.11 (1.04) | 15.83 (0.38) | 0.31 (0.46) | NS | |
Recognition | 15.79 (0.59) | 0.16 (0.93) | 15.89 (0.31) | 0.35 (0.53) | NS | |
DFR | 9.97 (3.82) | −0.50 (1.69) | 12.45 (1.66) | 0.53 (0.68) | 0.003 | |
DTR | 15.15 (1.67) | −0.46 (2.05) | 15.90 (0.31) | 0.47 (0.66) | NS | |
DMS-48 | Set 1 |
44.05 (5.35)
|
−2.72 (5.71, 32.4)
| 46.93 (1.28) | 0.21 (0.97) | 0.021 |
Set 2 |
44.23 (4.73)
|
−2.14 (4.05, 48.6)
| 47.10 (0.94) | 0.14 (0.72) | 0.008 | |
Digit span (number of digits) | 5.25 (1.13) | 5.92 (1.02) | 0.042 | |||
Executive function | ||||||
FAB |
15.49 (2.67)
|
−2.81 (4.61, 32.4)
| 17.29 (1.15) | −0.02 (1.44) | 0.014 | |
TMT A |
64.89 (34.11)
|
3.00 (4.32, 51.4)
| 40.62 (11.00) | 0.09 (0.90) | 0.011 | |
TMT B |
139.13 (79.20)
|
3.06 (6.45, 45.9)
| 90.34 (31.56) | 0.12 (1.00) | 0.049 | |
Digit span backward (number of digits) | 3.61 (0.90) | 4.42 (0.83) | 0.002 | |||
Formal lexical evocation | 17.28 (7.42) | −0.45 (1.09) | 23.55 (7.11) | 0.38 (1.09) | 0.007 | |
Digit symbol (standard score/19) | 8.18 (3.23) | 11.69 (2.65) | NS | |||
Instrumental function | ||||||
Praxis | Symbolic gesture (score/5) | 4.81 (0.46) | 4.90 (0.41) | NS | ||
Pantomime of tool use (score/10) | 9.22 (1.03) | 9.83 (0.38) | 0.002 | |||
Imitation of meaningless gesture (score/8) | 6.92 (1.44) | 7.76 (0.69) | 0.005 | |||
Language | DO80 | 77.61 (2.78) | 0.39 (1.04) | 79.62 (0.62) | 0.95 (0.27) | 0.022 |
Formal semantic evocation | 25.00 (7.72) | −0.88 (1.36) | 37.38 (7.05) | 0.69 (0.94) | <0.001 | |
Visuoconstruction | ROCF |
31.44 (5.25)
|
−1.95 (3.41, 32.4)
| 34.37 (1.82) | 0.13 (0.68) | NS |
Visuoperception (VOSP) | Screening (score/20) | 19.55 (1.09) | 19.96 (0.20) | NS | ||
Incomplete letters (score/20) | 18.85 (1.66) | 19.41 (0.80) | NS | |||
Dot counting (score/10) | 9.78 (0.55) | 10.00 (0.00) | NS | |||
Position discrimination (score/20) | 19.05 (1.43) | 18.73 (2.39) | NS | |||
Number location (score/10) | 8.47 (1.78) | 9.46 (0.81) | 0.047 | |||
Cube analysis (score/10) | 9.47 (1.11) | 9.71 (0.55) | NS | |||
Social cognition | ||||||
Mini-SEA | FPRT | 11.40 (2.39) | −1.20 (1.59) | 12.73 (2.39) | −0.32 (1.11) | 0.026 |
Facial emotion recognition | 12.12 (1.44) | −0.44 (1.31) | 12.44 (1.43) | −0.15 (1.30) | NS | |
RME test | 21.19 (4.95) | −0.19 (1.23) | 23.19 (3.61) | 0.35 (0.88) | 0.046 |