The main finding from the present study was that patients with DLB and patients with PDD differed in certain aspects of the verbal learning and memory deficits they exhibited. In particular, DLB patients were more impaired than the PDD patients on all but one of the recall measures, a finding that was highlighted by the fact that DLB patients displayed a more rapid rate of forgetting than that of PDD patients. PDD patients, on the other hand, committed a greater percentage of perseveration errors when recalling the word list than did either the DLB patients or NC subjects. These differences were rather robust when one considers the effect sizes (see and 3). Importantly, these observed differences cannot be attributed to overall level of cognitive impairment in that the DLB and PDD patients did not differ in their total scores on the MDRS, nor can they be due to differences in demographic factors such as age, gender, or level of education, as the two patient groups were matched on these variables.
Despite the differences in recall level and recall errors between the DLB and PDD groups, the two groups showed similar patterns in their learning characteristics. The semantic cluster and serial cluster ratios for the DLB and PDD patients did not differ significantly, although DLB patients had higher serial clustering ratios than the NC group, which was not the case for the PDD patients. This may be due a greater frontal lobe pathology (Double et al., 1996
; Harrington et al., 1994
) and executive dysfunction (Aarsland et al., 2004
; Aarsland et al., 2003
; Downes et al., 1998
) in DLB compared to PDD, as higher serial clustering ratios have been reported in demented individuals with greater frontal lobe pathology (Glosser, Gallo, Clark, & Grossman, 2002
). There were no significant differences in terms of recalling words from the primacy, middle, or recency regions of the word list. When considered with the observed differences between DLB and PDD patients in recall and percent savings, these results suggest that the two groups differ less in terms of their approach to acquiring verbal information than in their ability to actually learn and retain such information.
Although mathematically the DLB patients had lower recognition discriminability scores than PDD patients, the two groups did not differ significantly on any of the recognition measures. Thus, DLB and PDD patients show fairly comparable levels of recognition memory despite the fact that DLB patients have worse learning and retention of verbal information. These findings suggest that patients with DLB might benefit more from recognition testing than do patients with PDD. Because recognition memory is less dependent upon effortful retrieval processes than free recall, the enhanced recognition benefit of the DLB patients compared to PDD patients may indicate that they have a greater retrieval deficit than the PDD patients. These results are consistent with recent reports indicating that patients with PD do not always display improved performance on recognition testing compared to other patients with primarily subcortical pathology (Zizak et al., 2005
The finding that DLB and PDD patients demonstrate differences in learning and memory is important given that neuropathological and structural imaging studies have not been able to consistently distinguish between these two disorders (Burton et al., 2004
; Guo, Itaya, Takanashi, Mizuno, & Mori, 2005
; Harding & Halliday, 2001
; Tam et al., 2005
; Tsuboi & Dickson, 2005
), even when examining the medial temporal lobe brain regions believed to be critical for the type of declarative memory tested by the CVLT (although see Tam et al., 2005
, for some evidence of greater medial temporal lobe atrophy in DLB than PDD). The failure to observe consistent structural medial temporal lobe differences stands in contrast to our results showing poorer learning, delayed recall and more rapid forgetting in DLB than in PDD patients. Impaired delayed recall and rapid forgetting are characteristic features of patients with medial temporal lobe damage, such as patients with AD or focal medial temporal lobe damage (Kohler et al., 1998
; Squire, Stark, & Clark, 2004
). It is possible that the memory differences we observed are due to greater concomitant AD pathology in the DLB patients as compared to the PDD patients. Indeed, the majority of DLB patients in the current study had significant AD pathology in medial temporal lobe regions as indicated by a Braak stage of IV or greater. However, neither the CVLT savings score (r
=.87) nor cued intrusions (r
=.93) of the DLB patients correlated with Braak stage, so it does not appear that differences in medial temporal lobe involvement can entirely account for the differences in forgetting rates in the two groups.
The finding that PDD patients committed a greater percentage of perseveration errors than DLB patients was somewhat surprising given previous reports of worse executive dysfunction in DLB patients than in PDD patients (Aarsland et al., 2004
; Aarsland et al., 2003
; Downes et al., 1998
), and greater frontal lobe pathology in DLB than PDD (Double et al., 1996
;Harrington et al., 1994
). However, a recent study found that PDD patients have a greater decrease in cholinergic activity in the mediodorsal nucleus of the thalamus as compared to patients with DLB (Ziabreva et al., 2006
). This brain region has extensive connections to the anterior cingulate cortex, so it is possible that the greater magnitude of perseverations in the PDD patients is related to dysfunction in this region. In addition, it has become increasingly clear that various executive functions can be dissociated (Faw, 2003
; Possin et al., 2005
) and that different frontal regions might contribute to various executive processes (Faw, 2003
; Fuster, 1999
). As such, it is possible that the greater executive functioning deficits previously observed in DLB patients and the greater tendency towards perseverative responding in the PDD patients in the present study are due to the involvement of different regions of the frontal cortex.
The results of the discriminant function analysis using short delay cued recall, percent perseverations, and list b recall differentiated the DLB and PDD patients with 81.3% accuracy. Sensitivity for the diagnosis of PDD relative to DLB was fairly adequate (75%) as was the specificity (87.5.0%). The application of the discriminant function algorithm to the PDD patients not included in the original analyes resulted in a 78.6.% correct classification rate. These results are somewhat promising in that a fairly high accuracy was obtained with just a single memory test. It is very possible that the inclusion of other tests, such as measures of executive functions, would provide an even greater degree of diagnostic accuracy. To test this possibility, future studies will have to include additional measures as well as conduct a cross-validation of the discriminant function from this study in a new sample of DLB patients.
A majority of previous studies have failed to identify clear differences between DLB and PDD patients on various cognitive measures (Ballard et al., 2002
; Cormack, Aarsland et al., 2004
; Horimoto et al., 2003
; Noe et al., 2004
), leading some investigators to conclude that DLB and PDD result in only subtle, if any, differences in cognition that will have little clinical utility in distinguishing between these diseases (Aarsland et al., 2004
; Ballard et al., 2002
). The conclusions that can be drawn from these studies are limited, however, because they usually employed relatively broad and insensitive cognitive measures. The results of the current study show that a more in-depth analysis of cognition, such as that provided by the multiple measures of verbal learning and memory of the CVLT, can identify potentially important differences between patients with DLB and PDD. This was also recently shown in the domain of visual cognition. Although a study examining basic visual perceptual and visual spatial processes in DLB and PDD failed to identify any differences between these groups (Mosimann et al., 2004
), another study showed that DLB patients, but not those with PDD, were impaired on a visual search task that provided an intricate assessment of visual pre-attentive processes (Cormack, Gray et al., 2004
There are several limitations of our study that should be noted. First, only verbal learning and memory were examined so it is impossible to determine the extent to which deficits in other cognitive abilities may have contributed to the observed differences in CVLT performance. As noted above, prior studies have shown that DLB patients perform worse than PDD patients on certain measures of executive functioning (Aarsland et al., 2003
; Downes et al., 1998
; Gnanalingham, Byrne, Thornton, Sambrook, & Bannister, 1997
), and it is possible that these differences play an important role in the divergent CVLT performances. Second, the PDD patients were drawn from different geographic locations and tested during different years than the DLB patients, so there may be cohort differences that could account for our findings. It should be noted, however, that standardized criteria for the diagnosis of PDD were applied at each of the sites to minimize cohort differences, and that the DLB patients were all autopsy-confirmed to further reduce this potential source of bias. Third, we had autopsy-confirmation on only two of the PDD patients, so it impossible to determine if other pathological features, such as concomitant AD, could account for the pattern of memory deficits they exhibited. However, Braak and colleagues (Braak, Rub, Jansen Steur, Del Tredici, & de Vos, 2005
) recently reported that cognitive status in PD could be adequately accounted for by the stage of Parkinson's pathology, and that although AD-type pathology can occur in PD patients with cognitive impairment, the degree of such pathology may not be sufficient to account for the significant cognitive deficits observed in PDD (see also) (Aarsland et al., 2005
). Finally, we identified differences between mildly demented patients with DLB or PDD, but it is not known if such differences remain in patients with a more severe level of cognitive impairment. Future studies should address this issue.
In conclusion, the results of the current study indicate that patients with DLB and patients with PDD exhibit different patterns of verbal learning and memory deficits. These differences suggest that there are distinct pathological features in the two diseases, although these features cannot be identified at this point. Overall, these results provide some support for the validity and usefulness of separate clinical diagnoses of DLB and PDD, and offer a potential clinical feature that may help in making a differential diagnosis.