Patterns of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Risk of Dementia

Abstract

Objectives To identify clusters of patients with incident mild cognitive impairment based on their neuropsychiatric symptoms (NPS) and to examine the risk of progression to dementia, based on these clusters. Design Cohort study with 2 years median length follow-up. Setting: Alzheimer’s disease Centers from the National Alzheimer’s Coordinating Center (NACC). Participants Patients with MCI who were at least 60 years old with complete data and follow-up (n = 540). Measurements Latent class analysis was used to identify clusters of patients based on their NPS, and Cox proportional hazards models were used to examine risk of progression to dementia based on clusters. Incident MCI was defined as a participant having MCI at a current visit, but having been cognitively normal at his or her previous (yearly) visit. NPI-Q assessed presence of twelve neuropsychiatric behavioral domains. Results Three clusters were identified: a severe cluster (agitation, anxiety, apathy, nighttime behaviors, inhibition), an affective cluster (depression, anxiety, irritability, nighttime behaviors), and an asymptomatic cluster. The prevalence of each class was 56% for the asymptomatic class followed by the affective class (37%) and finally the severe class (7%). Compared to the asymptomatic class, the severe class had more than twice the hazard of progression to dementia (2.69, CI: 1.12–2.70) and the affective class had over one and a half times the hazard of progression to dementia (1.79, CI: 1.12–2.70). Conclusions Among persons with incident MCI, patterns of NPS may increase the likelihood of progression to dementia. Implications for early detection and treatment are discussed.

Neuropsychiatric Symptoms and Cognitive Impairment: Understanding the Importance of Co-Morbid Symptoms

“…This relationship was not apparent for MCI or CN-AR. The results are consistent with previous reports that dementia diagnosis is associated with a greater number of NPS [4,8,19]. Studies of longitudinal trajectories of NPS from MCI to dementia [24,38] report that although most of those with MCI (90%) demonstrate a low NPS burden that is stable over time [38], those who demonstrate increasing NPS burden (7%) or a high NPS burden at baseline have a 1.74 [38] to 2.55 [24] fold increase in risk of progression to dementia at follow-up.…”

“…This NPS-class is similar to the symptom pattern commonly reported in studies of MCI samples [5,8,19,24,39,40], and also the 'affective' cluster reported in studies of dementia samples [18]. In our study, 28% of all those with dementia (n = 11) and 19% of those with MCI (n = 25) were classified as having an affective/low comorbidity NPS pattern.…”

“…Accordingly, 'high comorbidity/high prevalence' was a rare but distinct cluster in our study, accounting for 1-4% of those without dementia, and 10% of those with dementia. A similar 'severe' cluster was observed by Forrester et al [19] which accounted for 7% of their clinically referred MCI sample (n = 540) and had a high risk of progression to dementia at two-years follow-up.…”

“…However, while a systematic review of NPS found low concordance of evidence for NPS clusters derived from the Neuropsychiatric Inventory (NPI) in dementia samples [18], some NPS may define potential sub-syndromes of AD. Interestingly, Forrester et al [19] recently linked patterns of NPS in incident MCI to an increased likelihood of progression to dementia, demonstrating the severe symptom class (consisting of agitation, anxiety, apathy, night-time behaviors, inhibition) to have a 2-fold higher risk of progressing to dementia (hazard ratio (HR) = 2.69, 95% confidence interval (CI): 1.12-2.70), while the affective class (consisting of depression, anxiety, irritability, night-time behaviors) had a one-point-five-times higher risk of progressing to dementia (HR = 1.70, 95% CI: 1.12-2.70) when compared to the asymptomatic class.…”

“…Most of the studies on NPS to date have focused on highly selective clinical samples recruited from tertiary care centers [12,[23][24][25] or as subsamples of population-based cohorts [4,7,8,14,19,26]. This means that there is a gap in our knowledge about the spectrum of NPS occurring in the population across different cognitive phenotypes, disorders, outcomes, and status.…”