Disruptive Behavior as a Predictor in Alzheimer Disease

Abstract

Background: Disruptive behavior is common in Alzheimer disease (AD). There are conflicting reports regarding its ability to predict cognitive decline, functional decline, institutionalization, and mortality.Objective: To examine whether the presence of disruptive behavior has predictive value for important outcomes in AD.Design: Using the Columbia University Scale for Psychopathology in Alzheimer Disease (administered every 6 months, for a total of 3438 visit-assessments and an average of 6.9 per patient), the presence of disruptive behavior (wandering, verbal outbursts, physical threats/violence, agitation/restlessness, and sundowning) was extracted and examined as a timedependent predictor in Cox models. The models controlled for the recruitment cohort, recruitment center, informant status, sex, age, education, a comorbidity index, baseline cognitive and functional performance, and neuroleptic use. Setting: Five university-based AD centers in the United States and Europe (Predictors Study). Participants: Four hundred ninety-seven patients with early-stage AD (mean Folstein Mini-Mental State Examination score, 20 of 30 at entry) who were recruited and who underwent semiannual follow-up for as long as 14 (mean, 4.4) years. Main Outcome Measures: Cognitive (Columbia Mini-Mental State Examination score, Յ 20 of 57 [approximate Folstein Mini-Mental State Examination score, Յ10 of 30]) and functional (Blessed Dementia Rating Scale score, parts I and II, Ն 10) ratings, institutionalization equivalent index, and death.Results: At least 1 disruptive behavioral symptom was noted in 48% of patients at baseline and in 83% at any evaluation. Their presence was associated with increased risks of cognitive decline (hazard ratio 1.45 [95% confidence interval (CI), 1.03-2.03]), functional decline (1.66 [95% CI, 1.17-2.36]), and institutionalization (1.47 [95% CI, 1.10-1.97]). Sundowning was associated with faster cognitive decline, wandering with faster functional decline and institutionalization, and agitation/restlessness with faster cognitive and functional decline. There was no association between disruptive behavior and mortality (hazard ratio, 0.94 [95% CI, 0.71-1.25]). Conclusion:Disruptive behavior is very common in AD and predicts cognitive decline, functional decline, and institutionalization but not mortality.

Utilization of Antihypertensives, Antidepressants, Antipsychotics, and Hormones in Alzheimer Disease

“…The finding of worse cognition and functioning being associated with higher likelihood of antipsychotic use is in accordance with previous findings from the Predictors Study that both delusions and hallucinations17 and disruptive behavioral symptoms18 were associated with increased risk for cognitive and functional decline. Further analyses may help elucidate if use of antipsychotics in this cohort is related to other disruptive behavioral symptoms that are common in AD, including agitation, aggression, disinhibition, irritability, and wandering 19.…”

Utilization of Antihypertensives, Antidepressants, Antipsychotics, and Hormones in Alzheimer Disease

“…The finding of worse cognition and functioning being associated with higher likelihood of antipsychotic use is in accordance with previous findings from the Predictors Study that both delusions and hallucinations17 and disruptive behavioral symptoms18 were associated with increased risk for cognitive and functional decline. Further analyses may help elucidate if use of antipsychotics in this cohort is related to other disruptive behavioral symptoms that are common in AD, including agitation, aggression, disinhibition, irritability, and wandering 19.…”

Sleep quality in healthy older people: Relationship with ¹H magnetic resonance spectroscopy markers of glial and neuronal integrity.

“…ease, elevated levels of mI have indeed been reported in the cerebral cortex and hippocampus of patients with mild to moderate Alzheimer's disease (Miller et al, 1993). Sleep-wake cycles are also significantly altered in Alzheimer's and other neurodegenerative diseases (Zhong, Naismith, Rogers, & Lewis, 2011), and when sleep disturbance is present, cognitive decline appears to be more pronounced (Scarmeas et al, 2007). Although it was not our primary focus to examine depressive symptoms, we did find an association between hippocampal Cr ϩ PCr and GDS scores.…”

Deep Brain Stimulation of Nucleus Basalis of Meynert improves learning in rat model of dementia

“…In the Kuhn trial of NBM DBS in 6 AD patients, the group mean worsened by 3 points in the AD assessment score (ADAS-Cog) over the course of the year (Kuhn et al, 2015a) with tonic stimulation. This represents a preliminary improvement over the decrease of 4.5 seen in a large long-term study of progression of AD in patients treated with anti-dementia drugs (Scarmeas et al, 2007), the 4.2 point worsening seen in the Phase 1 fornix DBS trial, and the complete lack of benefit reported in the Phase 2b Fornix trial. It is similar to the 10 point worsening at 76 weeks in the Donanemab trial compared with 13 point worsening in the placebo group(Sims et al, 2023).…”

Utilization of Antihypertensives, Antidepressants, Antipsychotics, and Hormones in Alzheimer Disease

“…The finding of worse cognition and functioning being associated with higher likelihood of antipsychotic use is in accordance with previous findings from the Predictors Study that both delusions and hallucinations17 and disruptive behavioral symptoms18 were associated with increased risk for cognitive and functional decline. Further analyses may help elucidate if use of antipsychotics in this cohort is related to other disruptive behavioral symptoms that are common in AD, including agitation, aggression, disinhibition, irritability, and wandering 19.…”

Sleep quality in healthy older people: Relationship with ¹H magnetic resonance spectroscopy markers of glial and neuronal integrity.

“…ease, elevated levels of mI have indeed been reported in the cerebral cortex and hippocampus of patients with mild to moderate Alzheimer's disease (Miller et al, 1993). Sleep-wake cycles are also significantly altered in Alzheimer's and other neurodegenerative diseases (Zhong, Naismith, Rogers, & Lewis, 2011), and when sleep disturbance is present, cognitive decline appears to be more pronounced (Scarmeas et al, 2007). Although it was not our primary focus to examine depressive symptoms, we did find an association between hippocampal Cr ϩ PCr and GDS scores.…”

Deep Brain Stimulation of Nucleus Basalis of Meynert improves learning in rat model of dementia

“…In the Kuhn trial of NBM DBS in 6 AD patients, the group mean worsened by 3 points in the AD assessment score (ADAS-Cog) over the course of the year (Kuhn et al, 2015a) with tonic stimulation. This represents a preliminary improvement over the decrease of 4.5 seen in a large long-term study of progression of AD in patients treated with anti-dementia drugs (Scarmeas et al, 2007), the 4.2 point worsening seen in the Phase 1 fornix DBS trial, and the complete lack of benefit reported in the Phase 2b Fornix trial. It is similar to the 10 point worsening at 76 weeks in the Donanemab trial compared with 13 point worsening in the placebo group(Sims et al, 2023).…”

Utilization of Antihypertensives, Antidepressants, Antipsychotics, and Hormones in Alzheimer Disease

“…The finding of worse cognition and functioning being associated with higher likelihood of antipsychotic use is in accordance with previous findings from the Predictors Study that both delusions and hallucinations17 and disruptive behavioral symptoms18 were associated with increased risk for cognitive and functional decline. Further analyses may help elucidate if use of antipsychotics in this cohort is related to other disruptive behavioral symptoms that are common in AD, including agitation, aggression, disinhibition, irritability, and wandering 19.…”

Sleep quality in healthy older people: Relationship with ¹H magnetic resonance spectroscopy markers of glial and neuronal integrity.

“…ease, elevated levels of mI have indeed been reported in the cerebral cortex and hippocampus of patients with mild to moderate Alzheimer's disease (Miller et al, 1993). Sleep-wake cycles are also significantly altered in Alzheimer's and other neurodegenerative diseases (Zhong, Naismith, Rogers, & Lewis, 2011), and when sleep disturbance is present, cognitive decline appears to be more pronounced (Scarmeas et al, 2007). Although it was not our primary focus to examine depressive symptoms, we did find an association between hippocampal Cr ϩ PCr and GDS scores.…”

Deep Brain Stimulation of Nucleus Basalis of Meynert improves learning in rat model of dementia

“…In the Kuhn trial of NBM DBS in 6 AD patients, the group mean worsened by 3 points in the AD assessment score (ADAS-Cog) over the course of the year (Kuhn et al, 2015a) with tonic stimulation. This represents a preliminary improvement over the decrease of 4.5 seen in a large long-term study of progression of AD in patients treated with anti-dementia drugs (Scarmeas et al, 2007), the 4.2 point worsening seen in the Phase 1 fornix DBS trial, and the complete lack of benefit reported in the Phase 2b Fornix trial. It is similar to the 10 point worsening at 76 weeks in the Donanemab trial compared with 13 point worsening in the placebo group(Sims et al, 2023).…”