A total of 108 patients were included (Table 1, Figure 2). Among the 108 patients, 67 had a memory complaint, 19 a language complaint, 6 had both memory and language complaint and 16 had another complaint (behavioral disorder, hallucination...). Mean age of the population was 66.9 ± 8.5 years old and 51% were women. Mean education level was 8.9 ± 5.16 years, illiterate patients represented 27% of the population, French was the native language for 47% of patients and mean MMSE score was 17 ± 5.48 (Table1). All patients had a brain imaging. 91 patients had a cerebral MRI, 89 patients had a PET scan.
Patients were classified into two groups according to the ATN criteria: there were 80 patients in the A+ group, corresponding to patients with amyloid abnormalities and 28 in the A- group, corresponding to patients without amyloid abnormalities. Patients in A+ group were clinically defined as having AD (n=53 patients), Lewy body dementia (LBD) (n=12 patients), both diseases (LBD and AD n=2), vascular dementia (n=4), mixed dementia (vascular and AD disease, n=3), fronto-temporal dementia (n=2), semantic dementia (n=2), Parkinson's disease dementia (n=1) or corticobasal dementia (n=1). In A- group, patients were clinically defined as having psychiatric disorders (n=6 patients), fronto-temporal dementia (n=7), normal pressure hydrocephalus (n=2), vascular dementia (n=4), semantic dementia (n= 3), LBD (n= 2), sequelae of inflammatory pathology of the central nervous system (n=1), vitamin deficiency (n=1) and progressive supranuclear palsy (n= 2).
1. Comparison of A+ and A- patients
1.1 Whole group of patients (Table 1)
Age, gender and education did not significantly differ between A+ and A- groups. MMSE score was significantly more altered in A+ than in A- group (A+: 16.2±5.0; A-: 19.2±6.2; p=0.01).
Regarding TNI-93 scores, patients from the A+ group (N= 80) were significantly more impaired than patients from the A- group (N=28) on immediate recall (A+: 5.9±2.8; A-: 7.4±2.6; p=0.001), free recall (A+: 3.5±2.7; A-: 5.9±2.8; p< 0.001) and total recall (A+: 5.7±3.5; A-: 7.8±2.8; p< 0.001) (Table2) and on number of intrusions during the recall phase (A+: 1±1.8; A-: 0.1±0.3; p=0.002). We found no differences between both groups in naming, number of encoding attempts and intrusions during encoding.
Table 1. Comparison between A+ and A- patients
|
all N=108
|
A+ N=80 (74.07%)
|
|
A- N=28 (25.93%)
|
Pvalue ‡
|
Age
|
66.93 ± 8.49
|
67.86 ± 7.53
|
|
64.28 ± 10.50
|
0.054
|
Gender (F)
|
55 (50.93%)
|
42 (52.50%)
|
|
13 (46.43%)
|
0.663
|
Education (years)
|
8.89 ± 5.16
|
8.81 ± 5.03
|
|
9.11 ± 5.61
|
0.796
|
Native language (French)
|
51 (47%)
|
40(50%)
|
|
11 (39%)
|
|
Illiterate
|
29 (26.85%)
|
20 (25.00%)
|
|
9 (32.14%)
|
0.467
|
Disease duration (years)(Y)
|
2.38 ± 2.86
|
2.27 ± 2.11
|
|
2.71 ± 4.39
|
0.489
|
MMSE (/30)
|
17.00 ± 5.48
|
16.20 ± 5.02
|
|
19.29 ± 6.17
|
0.010*
|
Motif
|
|
|
|
|
|
memory
|
67 (62.04%)
|
52 (65.00%)
|
|
15 (53.57%)
|
|
language
|
19 (17.59%)
|
14 (17.50%)
|
|
5 (17.86%)
|
|
memory+language
|
6 (5.56%)
|
6 (7.50%)
|
|
0 (0.00%)
|
|
others
|
16 (14.81%)
|
8 (10.00%)
|
|
8 (28.57%)
|
0.069
|
Tau
|
52 (48.15%)
|
50 (62.50%)
|
|
2 (7.14%)
|
<0.001*
|
Denomination
|
7.81 ± 1.91
|
7.78 ± 1.94
|
|
7.93 ± 1.88
|
0.883
|
Immediate recall
|
6.25 ± 2.80
|
5.85 ± 2.77
|
|
7.39 ± 2.59
|
0.001*
|
Number of encoding §
|
2.04 ± 0.89
|
2.22 ± 0.90
|
|
1.54 ±0.65
|
0.287
|
Encoding intrusion §
|
0.96 ± 1.48
|
1.10 ± 1.46
|
|
0.58 ± 1.50
|
0.309
|
Free recall
|
4.14 ± 2.59
|
3.54 ± 2.67
|
|
5.86 ± 2.84
|
<0.001*
|
Total recall
|
6.24 ± 3.43
|
5.68 ± 3 .47
|
|
7.82 ± 2.82
|
< 0.001*
|
Recall intrusion §
|
0.75 ± 0 .61
|
1 ± 1.84
|
|
0.12 ± 0.33
|
0.002*
|
Notes. Data are given as mean ± standard deviation for continuous variables and as count (percentages) for categorical variables.
‡ Welch’s t-test was used to compare groups for continuous variables and Fisher’s exact test for qualitative variables. For TNI subscores, p values were extracted from GLMs and thus, were adjusted for age, gender, education, MMS and Tau status. They were corrected from multiple testing using Benjamini-Hochberg correction.
§ GLMs with Poisson family and logarithm link and GLMs with binomial family and logit link otherwise.F: female, Y: years, m: mean, SD: standard deviation, Tau: presence of phosphorylate Tau, *: statistically significant.
1.2 TNI-93 scores in subgroups according to clinical presentation (Figure 3)
In the subgroup of patients with memory complaint (N=67), A+ patients (N=52) were significantly more altered than A- patients (N=15) on immediate recall (p<0.001), free recall (p< 0.001) and total recall (p< 0.001). A+ patients had also significantly more intrusions during recall than A- patients Naming, number of encoding attempts and intrusions during encoding did not differ between both groups. To sum up, similar results were observed in the memory subgroup than in the whole group of patients, and a similar tendency was observed in the language subgroup.
In the subgroup of patients with presentation other than memory complaint (ie language impairment or others presentation such as behavioural and hallucination), we observed no difference between A+ and A- patients on the TNI-93 scores.
2. Comparison of TNI-93 scores in A+T+ patients and A-T- patients (Table 2)
A+T+ patients (N=50) were significantly more impaired than A-T- patients (N=26) on immediate recall (p<0.001), free recall (p<0.001) and total recall (p<0.001). A+T+ patients also had significantly more intrusions during recall than A-T- patients (p<0.001), more encoding attempts (p=0.049), and more intrusions during encoding (p=0.038). There was no difference between A+T+ and A-T- patients in naming.
Table 2: Comparison of TNI-93 score between patients from A+T+ group and A-T- group
|
A-T- N=26 (34.21%)
|
A+T+ N=50 (65.79%)
|
Pvalue corrected
|
Denomination
|
7.85 ± 1.93
|
7.54 ± 2.05
|
0.941
|
Immediate recall
|
7.69 ± 2.22
|
5.42 ± 2.82
|
<0.001*
|
Number of encodage §
|
1.52 ± 0.65
|
2.38 ± 0.86
|
0.049*
|
Encodage intrusion §
|
0.52 ± 1.50
|
1.25 ± 1.12
|
0.038*
|
Free recall
|
6.12 ± 2.69
|
3.44 ± 2.65
|
<0.001*
|
Total recall
|
8.15 ± 2.44
|
5.51 ± 3 .19
|
<0.001*
|
Recall intrusion §
|
0.12 ± 0.34
|
1.24 ± 2.19
|
<0.001*
|
Notes. Data are given as mean ± standard deviation. P values were extracted from GLMs and thus, were adjusted for age, gender, education and MMS. They were corrected from multiple testing using Benjamini-Hochberg correction.
§ GLMs with Poisson family and logarithm link and GLMs with binomial family and logit link otherwise
*: statistically significant
3. ROC curves
Analyses of the ROC curves revealed that the best scores of the TNI 93 test to discriminate A+ patients from A- were immediate recall (Area under curve (AUC): 0.70), free recall (AUC: 0.74) and total recall (AUC: 0.74) (Figure 4). An immediate recall under 6 offered a sensitivity of 54% and specificity of 83%. A free recall under 4 and a total recall under 8 offered respectively a sensitivity of 63% and 72% and a specificity of 77% and 73% (Table 3).
Table 3. Results of the ROC curve analyses to discriminate A+ and A-
|
optimal cutpoint
|
accuracy
|
sensitivity
|
specificity
|
AUC
|
|
Denomination
|
8
|
0.55
|
0.54
|
0.57
|
0.55
|
|
Immediate recall
|
6
|
0.62
|
0.54
|
0.83
|
0.7
|
|
Number of encoding*
|
3
|
0.57
|
0.44
|
0.93
|
0.73
|
|
Encoding intrusion
|
1
|
0.61
|
0.54
|
0.79
|
0.66
|
|
Free recall
|
4
|
0.66
|
0.63
|
0.77
|
0.74
|
|
Total recall
|
8
|
0.72
|
0.72
|
0.73
|
0.74
|
|
Recall intrusion
|
1
|
0.52
|
0.37
|
0.89
|
0.64
|
|
* numbers of trials at encoding.