Neuropsychiatric Symptoms as Predictors of Progression to Severe Alzheimer’s Dementia and Death: The Cache County Dementia Progression Study

Abstract

Objective Little is known about factors influencing the rate of progression of Alzheimer’s dementia. Using data from the Cache County Dementia Progression Study, we examined the link between clinically significant neuropsychiatric symptoms in mild Alzheimer’s dementia and progression to severe dementia or death. Method The Cache County Dementia Progression Study is a longitudinal study of dementia progression in incident cases of the condition. Survival analyses included unadjusted Kaplan-Meier plots and multivariate Cox proportional hazard models. Hazard ratio estimates controlled for age of dementia onset, dementia duration at baseline, gender, education level, General Medical Health Rating, and apolipoprotein E epsilon 4 (APOE-ε4) genotype. Results Three hundred thirty-five patients with incident Alzheimer’s dementia were studied. Sixty-eight (20%) developed severe dementia over the follow-up. Psychosis (hazard ratio=2.007, p=0.028), agitation/aggression (hazard ratio=2.946, p=0.004), and any one clinically significant neuropsychiatric symptom (domain score of ≥4, hazard ratio=2.682, p=0.001) were associated with more rapid progression to severe dementia. Psychosis (hazard ratio=1.537, p=0.011), affective symptoms (hazard ratio=1.510, p=0.003), agitation/aggression (hazard ratio=1.942, p=0.004), mildly symptomatic neuropsychiatric symptoms (domain score of 1–3, hazard ratio=1.448, p=0.024), and clinically significant neuropsychiatric symptoms (hazard ratio=1.951, p=<0.001) were associated with earlier death. Conclusions Specific neuropsychiatric symptoms are associated with shorter survival time from mild Alzheimer’s dementia to severe dementia and/or death. The treatment of specific neuropsychiatric symptoms in mild Alzheimer’s dementia should be examined for its potential to delay time to severe dementia or death.

Beyond Memory: A Focus on the Other Neuropsychiatric Symptoms of Dementia

“…Rates of increase in agitation/aggression separately correlated with rates of decline in both outcomes. This is consistent with recent work from our group in the Cache County Dementia Progression Study (9), where psychosis, agitation/aggression, and any one clinically significant NPS were associated with more rapid progression from dementia onset to severe dementia. Psychosis, affective symptoms, agitation/aggression, and mildly symptomatic / clinically significant NPS were associated with earlier death.…”

Incident Psychosis in Subjects With Mild Cognitive Impairment or Alzheimer’s Disease

“…In comparison to AD subjects without psychosis (AD-P), subjects who have AD with psychosis (AD+P) have more rapid cognitive decline 234 ; more rapid functional decline 5 ; higher rates of aggression 6 ; worse overall health 7 , and shorter time to placement in a nursing home 5;8 . As a result, psychotic symptoms in individuals with AD are associated with more distress for the caregiver 9 .…”

A preclinical screen to evaluate pharmacotherapies for the treatment of agitation in dementia

“…There is a growing recognition that neuropsychiatric symptoms, such as agitation, might increase the rate of progression of dementia. And this is particularly relevant to AD, where it has been found that neuropsychiatric symptoms, such as psychosis, agitation and aggression were associated with a more rapid progression to severe dementia and reduced survival times (Peters et al, 2015).…”