Empirical Classification of Neuropsychiatric Symptoms and Association of Classes With Diagnostic Progression and Cognitive Decline in Mild Cognitive Impairment and Alzheimer's Disease Populations

Abstract

Background: The current study aimed to identify classes of cognitively impaired older individuals based on their neuropsychiatric symptoms (NPSs) and to investigate the contribution of NPS class to cognitive decline and Alzheimer's disease (AD) risk in mild cognitive impairment (MCI).

Methods: Our study included 1472 participants (age range 55-91 years) from the ADNI (Alzheimer's Disease Neuroimaging Initiative) who were diagnosed with MCI or mild AD and completed the Neuropsychiatric Inventory at their baseline visit. We used latent class analysis to categorize groups by NPS patterns. Linear mixed models of repeated measures were used to compare changes in cognitive performance across 5 years as a function of NPS class. Subsequently, Cox proportional hazards models were used in individuals with MCI to assess whether the rate of conversion to AD differed across the NPS groups.

Results: We identified 3 latent classes of NPSs: no NPS (n = 799, 51.7%), apathy/affective NPS (n = 572, 39.8%), and complex NPS (n = 108, 8.5%). In longitudinal analyses, we observed interactions between class and time, indicating accelerated cognitive decline in memory and executive function in the apathy/affective class. In MCI, hazard ratios for conversion to AD were 1.39 (95% CI, 1.10-1.76) for the apathy/affective class and 2.03 (95% CI, 1.33-3.10) for the complex class compared with the no NPS group after adjusting for age, sex, education, global cognition, and APOE ε4 positivity.

Conclusions: Among cognitively impaired older adults, empirically derived clusters of NPS profiles were associated with cognitive decline and risk of conversion from MCI to AD. Such NPS classes may reflect specific neurobiological mechanisms within or related to AD-related neurodegeneration. Further studies with biological markers are needed to clarify these neurobiological mechanisms.

Keywords: Alzheimer’s disease; Cognitive decline; Diagnostic progression; Mild cognitive impairment; Neuropsychiatric symptom.