Similar to previous findings from this laboratory [15
], we found a significant difference in the WRT scores of the AD compared to the MCI and NC groups. Even though the WRT classified correctly NC and AD 81% of the time, it showed lower diagnostic sensitivity (72%) and specificity (76%) than previously found (77% and 92% respectively). On average, the AD subjects included in our study have shorter WRT and the MCI have somewhat longer WRT than those in Massoud’s study (Massoud: MCI 60.3 ± 15.9 ms and AD 122.6 ± 70.8 ms; Present study: MCI 73.4 ± 25.7 ms and AD 92.6 ± 31.7 ms).
It is worth noting that we found slightly bigger standard deviations in the NC and MCI groups, and smaller ones in the AD group than what was previously reported, indicating that our groups might have been less homogenous. Examining the individuals scores from Massoud’s study [15
] and our own replication study illustrates this difference clearly (Figure ). In the pilot study, only 1 out of 12 NC had a WRT score greater than the 85 ms, compared to 8 out of 33 in our follow-up study. Similarly, in Massoud’s study, only 3 out of 13 AD patients scored below the cut-off, compared with 8 out of 25 in the current study. We simply failed to maintain this striking separation between NC and AD patients in a larger cohort. Even though the age and dementia severity, measured by MMSE, of the groups were similar in the two studies, we must conclude that the pilot study, being smaller, simply showed less heterogeneity than was found in our replication study.
The ROC analyses showed that WRT does not perform better than chance level in classifying MCI individuals who will progress to AD or not (AUC = 0.45, p > 0.1). Indeed, in the current study, WRT only correctly classified 32% of the MCI individuals who progressed to dementia, which is less impressive than what Massoud and his colleagues had found, where all of the MCI subjects who had scored ≥ 85 ms on WRT had progressed to AD after 2 years of follow-up. It is important to note that the follow-up period in our study was of 8 years. Massoud’s study included 4 individuals with MCI who progressed to AD, which is within the expected published rates of progression to AD (15% a year). The current study, in contrast, yielded a larger sample of converters. However, the average rate of progression from MCI to AD in our study (about 4% a year) is lower than in most studies [17
]. In addition, examination of the AUC for other neuropsychological tests reveals that the delayed recall of Logical Memory and Ray Auditory Verbal Learning Tests were better at discriminating MCIp from MCInp (Table ).
Massoud and colleagues found that WRT scores correlated with scores on a global cognitive assessment test, the MMSE. In our study, we replicated this finding, but we wanted to evaluate whether WRT scores were related to those of other cognitive tests. We found evidence for an association between WRT scores and measures of memory and language. These associations might be spurious, however, as they were found only when the three groups were collapsed, with the exception of the lexical subtest of the Controlled Word Association test in the NC group. WRT scores were also correlated with measures of attention, more precisely Trail Making Test A and Stroop dots subtest. This suggests that performance on WRT is related to overall mental speed and attention processing. However, we found that the association with Trail Making Test A was maintained in the NC, MCInp, and AD groups, but not in the MCIp group. Similarly, the association with Stroop dots remained significant only in the NC and MCInp groups. Although explaining the absence of correlation in the MCIp or AD groups is beyond the scope of this study, it might suggest that at the MCI stage of AD pathology different cognitive domains are affected to different degrees. As for the absence of correlation between MMSE and WRT scores in the NC and MCI groups, it can easily be explained by ceiling effect. In the NC and MCI groups, MMSE scores do not vary enough, whereas in the AD group, MMSE scores range from 11 to 29.
Despite the fact that we selected the participants of our study in the same way as Massoud and colleagues did, MCI individuals whose WRT was greater than 85 ms were not more likely to progress to AD after 8 years follow-up. This can be explained again by the larger sample size. The original study was a small pilot study and it is common for larger samples to lack the robust separation found in smaller, more homogeneous samples. Without doubt, our larger sample introduced heterogeneity, as expressed in the increased standard deviations in WRT scores of NC and MCI individuals. The follow up period in our replication study was significantly longer than in Massoud’s study, which brings more support to the present findings. The participants included in our replication study compared fairly well to those of Massoud’s. They had similar education and MMSE score, as well as similar duration of illness (this study: 3.9 (0–15), Massoud’s study: 4.5 (2–10) for the MCI and AD groups. The participants also compared well in term of age and BNT scores.