Disruptive Behaviors in Alzheimer's Disease
Abstract & Commentary
By Michael Lin, MD Assistant Professor of Neurology and Neuroscience, Weill Medical College of Cornell University Dr. Lin reports no financial relationships relevant to this field of study.
Synopsis: Disruptive behaviors are a poor prognostic sign in patients with Alzheimer's disease.
Source: Scarmeas N, et al. Disruptive behavior as a predictor in Alzheimer disease. Arch Neurol 2007;64:1755-1761.
Disruptive behavioral symptoms (DBSs) such as wandering, outbursts, threats/violence, agitation/ restlessness, and sundowning are well known to occur in Alzheimer's disease (AD), particularly as the disease advances. Somewhat surprising, however, is that the relationship between DBSs and disease outcomes has not been consistent in the literature, possibly due to variability in symptom ascertainment, disease stage, and consideration of neuroleptics.
To address the relationship between DBSs and disease outcomes in AD, Scarmeas and colleagues analyzed 497 patients with moderate AD (average MMSE [Mini Mental State Examination] 20.4, range 5-30), recruited from 5 university-based memory disorders clinics in North America and Europe. Subjects were examined every 6 months for an average of 4.4 years, and the presence of DBSs was assessed using the Columbia University Scale for Psychopathology in AD. Use of cholinesterase inhibitors and neuroleptics was also recorded.
The primary endpoints of the study were: 1) cognitive outcome (Folstein MMSE < 10/30); 2) functional outcome (Blessed Dementia Rating Scale Parts I and II score > 10/17); 3) institutionalization (as determined by actual institutionalization or an equivalent institutional care dependency scale); and 4) mortality.
DBSs were extremely common. Although only 48% of subjects exhibited a DBS at baseline, this rose to 83% at some point during follow-up. Throughout followup, subjects had on average 2.3 +/- 1.5 DBSs, which increased over time. Agitation/restlessness was present in ~3 of every 4 patients, outbursts and sundowning in ~1 of every 2 patients, and wandering and threats/violence in ~1 of every 3 patients.
DBSs also were predictive of disease outcomes, increasing the risks of cognitive decline, functional decline, and institutionalization each by a factor of approximately 1.5. There was no effect on mortality. Specific DBSs appeared to be more strongly predictive of certain outcomes than others. Neuroleptic use was associated with a higher risk of functional decline (hazard ratio [HR] 1.57) and institutionalization (HR 1.57), but not with cognitive outcome or mortality. Cholinesterase inhibitors were associated with a lower risk of institutionalization (HR 0.47) and mortality (HR 0.36), but not with cognitive or functional outcomes.
Finally, autopsy data were available for 96 patients. Ninety-three percent of cases had AD-type pathology, 21% of which also had Lewy body pathology. Exclusion of subjects with Lewy body pathology did not change the prevalence of DBSs or their association with the disease outcomes.
Commentary
This is a strong study, one of the largest to examine DBSs in AD. It was conducted at university centers by experts in memory disorders, had extensive and nearly complete follow-up (94%), and assessed all the variables of interest over multiple visits in a time-dependent fashion. On the other hand, the population was limited to highly specialized referral centers and was predominantly Caucasian with few comorbidities; this potentially limited the ability to generalize the results. Assessment of predictors and outcomes was conducted by the same examiners, a potential source of bias. The neuropathology underlying DBSs and their association with disease outcomes remain to be explored.
The take home points of this article include the very high prevalence of DBSs in AD, and their predictive value for disease outcomes. Additionally, the study provides further evidence for use of cholinesterase inhibitors in improving disease outcome, and for minimizing the use of neuroleptics.
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