In a prospectively followed sample of patients with clinical consensus panel and dopamine transporter SPECT confirmed diagnosis of AD or DLB, cross-sectional assessments identified expected between-group similarities and differences in cognitive scores and clinical scales in addition to a higher level of carer distress relating to the symptoms of DLB patients. We identified no differences in rate of progression of cognitive or neuropsychiatric variables over a 12-month follow-up period. Our inclusion of only patients whose consensus clinical diagnosis was in keeping with neuroimaging results make it likely that diagnostic accuracy was very high.
The AD and DLB groups were well matched in terms of age and degree of cognitive impairment at baseline. The finding that patients with DLB had higher scores on the NPI, clinician assessment of fluctuation and Cornell Scale for Depression in dementia were expected given the recognised diagnostic criteria.2
NPI score was higher at both time points in DLB, despite similar cognitive and baseline CDR scores; this was associated with higher levels of care giver distress and is in keeping with other published data.4
Severity of neuropsychiatric symptoms in AD31
has been shown to be a predictor of both care giver distress and nursing home placement. Care giver distress has also been shown to be an independent risk factor for nursing home placement in dementia.33
It is possible that the shorter time to nursing home placement that has been reported in DLB compared with AD34
is related to neuropsychiatric symptoms and associated care giver distress. Not all studies are consistent, however, and marginal6
or no differences8
in time to placement have also been reported. Furthermore, costs of care in DLB and AD have been shown to correlate with impairments in activities of daily living (ADLs) and not NPI scores.4
Severity of neuropsychiatric symptomatology, and hallucinations in particular, has also been associated with steeper decline in cognitive scores and increased risk of mortality and institutionalisation in AD, independent of antipsychotic drug use.35
These studies have lacked autopsy confirmation of diagnosis, and it is possible that the AD groups included individuals with undiagnosed DLB, who are more likely to experience hallucinations. We are not aware of any published data related to the impact of neuropsychiatric symptom severity on illness progression and survival in DLB.
We did not identify any between-group differences in change over time of any of the variables examined, that is, NPI, fluctuations and cognitive performance. It is possible that the lack of detectable difference in decline of NPI and fluctuation scores over time is related to the already high scores at baseline in DLB. The majority of studies of the rate of cognitive decline in DLB versus AD have also reported no differences, for example,7
although the earliest reports were of more rapid decline in cognition in DLB,37
as were more recent studies.5
Several studies have reported relatively preserved cognitive scores, particularly in recall, before death in DLB compared with AD.5
As mentioned in ‘Results’, patients diagnosed as having DLB at baseline who were lost to follow-up were significantly more cognitively impaired than patients diagnosed as having AD at baseline who were lost to follow-up. These patients were not included in the final analysis, as the cohort analysed was derived from the final consensus diagnosis made at follow-up. Thus, although patients lost to follow-up appeared to differ cognitively depending on diagnosis and this could have affected the study's results, their diagnoses were not made at the same time point as for the patients included in the final cohort. Reviewing the characteristics of patients lost to follow-up must therefore be done tentatively, as their diagnoses were subject to change.
It has been suggested that DLB may be associated with a more rapid decline in global measures of dementia severity or measures of ADLs while cognitive performance is relatively preserved. However, no significant differences in change in CDR score over time between the DLB and AD groups have yet been identified.7
We did not examine performance on ADLs. Cross-sectional assessments of activities of living have reported higher levels of impairment in DLB than in AD,9
which may be related to extrapyramidal motor symptoms.38
Longitudinal data, however, suggest no difference or a marginal difference in rate of decline of ADLs between AD and DLB.9
While ours and the majority of studies do not support the idea of a more rapid decline in cognition in DLB, the available literature is split more evenly between findings of either similar or shorter survival in DLB compared with AD. One possibility is that reports of worse outcomes in DLB are related to increased frequency of antipsychotic use as a result of greater severity of neuropsychiatric symptoms. While more DLB than AD participants were prescribed neuroleptics in the present study, no differences in rate of progression were identified. Previous studies of cognitive decline in AD and DLB that have presented data on neuroleptic prescribing did not report any differences between the groups in use of these medications.8
In terms of survival, both early40
and more recent6
studies have reported shorter survival in DLB versus AD, despite likely changes in neuroleptic prescribing over this time as a result of better understanding of the potentially harmful effects in both DLB 2
and dementia as a whole. It therefore seems unlikely that reported differences in survival between DLB and AD could be entirely accounted for by antipsychotic use.
The literature surrounding the differences in longitudinal outcomes in DLB and AD is therefore not easy to interpret. Overall, studies report outcomes in DLB that are either no different from or worse than in AD. Some of the difficulties involved in interpreting and comparing these findings are the differences in study design, use of clinical rather than pathological diagnosis, differing pathological definitions and retrospective analysis of clinical data. In addition, studies often rely on relative's reports on the onset of dementia, or use as baseline the time of referral, diagnosis or entry into the study. None of these methods necessarily identify equivalent disease stages and these difficulties highlight the complexity of the task of comparing the rate of decline between two disorders with different clinical phenotypes. In DLB, episodic memory is relatively spared in the early stages, but the presence of attentional and visuospatial impairments, visual hallucinations or movement disorder might be more disabling. Comparisons between AD and DLB are therefore not straightforward, and it is hard to define what is an ‘equivalent’ disease stage. The picture is further complicated by the frequent overlap of AD and DLB neuropathology and the insidious onset of both of these conditions.
Our study would have been improved by a longer duration of follow-up and a more detailed breakdown of cognitive, behavioural and clinical measures. Furthermore, patients' ability to carry out ADLs was not measured, and this can be a useful marker of disease severity and progression. Exclusion of individuals with severe dementia and higher attrition (not returning for follow-up visit) of DLB cases with more severe cognitive impairment precluded detection of differences in progression that are present only in later disease stages. Larger cohorts of patients who could be stratified by stages of severity of dementia are needed to examine this possibility. The DLB group had a higher mean depression score at baseline and more patients took a neuroleptic. Both neuroleptics and antidepressants have been shown to have detrimental effect on patients with dementia and could lead to faster progression but this did not seem to be the case over the duration of 1 year. Without autopsy diagnosis, we were not able to differentiate patients with pure and combined pathology.
In conclusion, on global cognitive measures, we did not find any difference in rate of progression between the mild–moderate AD and DLB groups over a 1-year period of observation. Cognitive decline is only one aspect of dementia and other impairments may in fact be more important and disabling.