Delusions and hallucinations are associated with worse outcomes in Alzheimer Disease.
Scarmeas N, Brandt J, Albert M, Hadjigeorgiou G, Papadimitriou A, et al. ;
Commented by , 22 Nov 2005
Aim of the study
Examine whether the presence of delusions or hallucinations early in the course of AD has a predictive value for important outcomes.
Method
456 patients with early AD (mean Folstein MMSE scores of 21) were assessed semiannually for up to 14 years in five university-based AD Centers in the USA and Europe.
Using the Columbia University Scale for Psychopathology in AD, the presence of delusions and hallucinations were extracted as time-dependent predictors in Cox models controlled for cohort effect, recruitment center, informant status, gender, education, co-morbidity, baseline cognitive and functional performance, behavioral symptoms, use of neuroleptics and of cholinesterase inhibitors.
The main outcomes were cognitive (low score on Columbia MMSE score), functional (high score on Blessed Dementia Rating Scale), institutionalization and death.
Results
During the full course of follow-up, 38% of patients reached the cognitive, 41% the functional, 54% the institutionalization and 49% the mortality end-points. Delusions were present for 34% of patients at baseline and 70% at any evaluation, increasing risk of cognitive (risk ratio [RR] 1.50) and functional (RR 1.41) decline.
Hallucinations were present in 7% of patients at initial visit and 33% at any visit, with increased risk for cognitive decline (RR 1.62), functional decline (RR 2.25), institutionalization (RR 1.60) and death (RR 1.49).
Professor Gauthier's comments
There is more and more interest in finding biological and clinical markers predicting a faster progression in the course of AD. This would have relevance to clinical practice, e.g. preparing patients and families for the stages of disease to come, and relevance to clinical research, e.g. designing the best possible trial designs to prove the efficacy of potential disease-modifying treatments.
For instance apoE4 genotype predicts faster conversion from amnestic MCI to dementia, so much so that this marker is used for stratification (or balanced allocation) in clinical trials for that population. This genotype does not seem as important once dementia has been diagnosed.
Clinical markers such as early hallucinations could indicate alternative diagnosis, such as Lewy Body Dementia, or a predicted faster progression in AD. Early and prominent hallucinations and delusions may require earlier use of typical or atypical neuroleptics, which may themselves increase mortality (a hotly debated subject).
The authors of this article must be congratulated for their anticipation of the need for long-term natural follow-up studies which will help in designed better intervention studies, both pharmacological and non-pharmacological.
Future studies looking at behavioral symptoms may find that long term use of the standard drug treatments (cholinesterase inhibitors and the NMDA antagonist memantine) delay clinical milestones such as cognitive and functional decline, institutionalization and death.