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

Abstract

Objective To estimate the incidence of psychotic symptoms in Alzheimer disease. Methods The study consists of 776 elderly subjects presenting to the Alzheimer Disease Research Center at the University of Pittsburgh between May 9, 2000 and August 19, 2014. All participants were diagnosed with mild cognitive impairment (National Institute on Aging-Alzheimer’s Association workgroup criteria), possible, or probable Alzheimer disease (National Institute of Neurologic and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association criteria) and were without psychosis at entry. Psychotic symptoms were evaluated using the Consortium to Establish a Registry for Alzheimer Disease Behavioral Rating Scale (BRS) every 6 months. 1-, 3- and 5-year cumulative incidences of psychosis were calculated. Results The 1-year psychosis incidence was 10% (95% CI, 8% – 12%) and this annual rate remained remarkably consistent at 3 and 5 years. Psychosis incidence was related to cognitive status at all time points. However, the incidence rate reached a plateau during the disease course. Cumulative psychosis incidence at 5 years was 61% (95% CI, 52% – 69%) in individuals with moderate to severe AD, not statistically significantly different from the cumulative incidence at 3 years in this group which was 48% (95% CI, 40% – 55%), or from the 5-year incidence in individuals who entered the study with mild AD which was 48% (95% CI, 41% – 56%). Conclusion Psychosis in AD has been associated with a number of adverse clinical outcomes. We provide estimates of the risk of psychosis onset within clinically defined subgroups of individuals, a tool clinicians can use in treatment planning. Anticipating which subjects are at high risk for psychosis and its associated poor outcomes can help with family education and support decisions to implement non-pharmacologic strategies that may reduce or prevent symptoms.

Kalirin reduction rescues psychosis-associated behavioral deficits in APPswe/PSEN1dE9 transgenic mice

“…Consistent with these observations, we recently estimated the annual incidence of psychosis in AD subjects at ~10% (Weamer et al, 2016). The most rapid increase in rates of psychosis in AD is in the transition from mild cognitive impairment to early and middle stages of disease, with a plateau in later stages (Lopez et al, 2003; Ropacki and Jeste, 2005; Weamer et al, 2016). When present, psychotic behaviors in AD have an adverse impact on the patient and family.…”

Genetic risk for schizophrenia and psychosis in Alzheimer disease

“…We recently estimated the annual incidence of psychosis in AD at 10%. 40 Thus there is an opportunity to intervene prior to psychosis onset if individual predictors can be identified. Although currently no treatments are established for prevention of AD+P, selective serotonin reuptake inhibitors have some efficacy for treating it, 22 ; 23 and they have acceptable tolerability.…”

“…Importantly, subjects with a primary diagnosis of Dementia with Lewy bodies 38 were excluded. The above diagnoses resulted from diagnostic evaluations, cognitive testing, and in some cases neuropathologic assessment, conducted during subjects’ participation in the following programs as previously described: the University of Pittsburgh Alzheimer Disease Research Center (ADRC), 39 ; 40 the Genetic and Environmental Risk in AD Consortium 1 (UK), 29 ; 41 ; 42 the National Institute on Aging’s Late Onset Alzheimer’s Disease Family Study (NIA-LOAD), 4 ; 28 the National Institute of Mental Health Genetics Initiative AD Cohort (NIMH), 25 the Fundació ACE Barcelona Alzheimer Treatment and Research Center (ACE), 41 ; 43 , the Cardiovascular Health Study (CHS), 3 ; 41 and a consortium of National Institute on Aging Alzheimer Disease Centers (ADC). 44 Collection of clinical data and genetic samples were approved by each sites local Institutional Review Board or Medical Ethics Committee, as appropriate.…”

Determining the impact of psychosis on rates of false‐positive and false‐negative diagnosis in Alzheimer's disease

“…As well, psychosis is a common feature in AD, estimated to occur in as many as 50% of patients [23] . Recent studies have suggested in fact an incidence rate of 10% per year [24] . Thus, it is possible that the high prevalence of psychosis in AD may partially explain the observed findings.…”