Neuropsychiatric Profile as a Predictor of Cognitive Decline in Mild Cognitive Impairment

Abstract

Introduction: Mild cognitive impairment is often associated with affective and other neuropsychiatric symptoms (NPS). This co-occurrence might have a relevant impact on disease progression, from MCI to dementia. Objective: The aim of this study was to explore the trajectories of cognitive decline in an MCI sample from a memory clinic, taking into consideration a perspective of isolated cognitive functions and based on NPS clusters, accounting for the different comorbid symptoms collected at their baseline visit. Methods: A total of 2,137 MCI patients were monitored over a 2.4-year period. Four clusters of NPS (i.e., Irritability, Apathy, Anxiety/Depression and Asymptomatic) were used to run linear mixed models to explore the interaction of cluster with time on cognitive trajectories using a comprehensive neuropsychological battery (NBACE) administered at baseline and at the three subsequent follow-ups. Results: A significant interaction between cluster and time in cognitive decline was found when verbal learning and cued-recall were explored (p = 0.002 for both memory functions). For verbal learning, the Irritability cluster had the largest effect size (0.69), whereas the Asymptomatic cluster showed the smallest effect size (0.22). For cued-recall, the Irritability cluster had the largest effect size among groups (0.64), and Anxiety/Depression had the smallest effect size (0.21). Conclusions: In MCI patients, the Irritability and Apathy NPS clusters shared similar patterns of worsening in memory functioning, which could point to these NPS as risk factors of a faster cognitive decline, acting as early prognostic markers and helping in the diagnostic process.

Keywords: anxiety; apathy; cognitive decline; depression; irritability; mild cognitive impairment; neuropsychiatric symptoms.

FIGURE 1

Cognitive decline across clusters for verbal learning. Measures for each group were obtained using LMM means by calculating differences between baseline and follow-ups for each time point. Slopes for each cluster were calculated using the 2-known points approach. Negative values correspond to decrements: the larger the absolute values the steeper the line. Numbers at the end of the lines indicate the cognitive slopes for each class.

FIGURE 2

Cognitive decline across clusters for cued-recall. Measures for each group were obtained using LMM means by calculating differences between baseline and follow-ups for each time point. Slopes for each cluster were calculated using the 2-known points approach. Negative values correspond to decrements: the larger the absolute values the steeper the line. Numbers at the end of the lines indicate the cognitive slopes for each class.