Examining differences in neuropsychiatric symptom factor trajectories in empirically derived mild cognitive impairment subtypes

Abstract

Objective The aim of this study was to examine neuropsychiatric symptom (NPS) factor severity progression over time in empirically derived (ED) mild cognitive impairment (MCI) subtypes. Methods Participants in the Alzheimer's Disease Neuroimaging Initiative study diagnosed with MCI by Alzheimer's Disease Neuroimaging Initiative protocol using conventional clinical (CC) criteria (n = 788) were reclassified using cluster analysis as amnestic, dysnomic, dysexecutive MCI, or cluster‐derived normal (CC‐Normal) using empirical criteria. Cognitively normal (CN) participants (n = 207) were also identified. The Neuropsychiatric Inventory‐Questionnaire (NPI‐Q) was administered from baseline through 48‐month follow‐up. Exploratory factor analysis was completed to determine the NPI‐Q factor structure at 6‐month follow‐up. Multilevel modeling was used to determine NPI‐Q symptom severity factor and apathy symptom progression over time by cognitive subtype. Results The exploratory factor analysis revealed that the NPI‐Q consisted of 2 factors: hyperactivity/agitation and mood symptoms. Using clinical and empirical criteria, all MCI groups were identified as having more severe hyperactivity/agitation symptoms than CN participants. However, only the amnestic MCI group identified using empirical criteria showed an increase in symptom severity over time relative to CN participants. Mood factor and apathy symptoms were found to be more severe in dysexecutive and amnestic groups in both models. Similarly, both models identified a significant worsening of mood and apathy symptoms over time for dysexecutive and amnestic groups relative to CN participants. Conclusions This study provides further support that empirical criteria aid in examining the progression of clinical characteristics associated with MCI. Further, it helps to identify which MCI subtypes may be at higher risk for NPS progression.

Interaction of neuropsychiatric symptoms with APOE ε4 and conversion to dementia in MCI patients in a Memory Clinic

“…Scientific literature has considered that different patterns of NPS are associated with distinct MCI subtypes, and differences in conversion rates between NPS could be partially consequence of these clinical subtypes. For example, more severe agitation/hyperactivity symptoms over time are observed in MCI patients with anamnestic profile subtype 30 . Other explanations have been formulated connecting the occurrence of particular NPS with specific brain networks or circuits in the brain 32 or proposing that brain changes, presented in preclinical stages, could be explaining the differential clinical progression of patients, including NPS manifestations 33 .…”

Comparing behavioral and psychological symptom structures on the Neuropsychiatric Inventory Questionnaire.

“…In addition to statistical heterogeneity, many studies used variants in NPI-Q scoring procedures, with the most common being a dichotomized presence/absence (de Vito et al, 2018; Sayegh & Knight, 2014; Siafarikas et al, 2018; Thakur et al, 2021) and 4-point ordinal severity (Feghali et al, 2021; Seidl & Massman, 2016; Siafarikas et al, 2021; Trzepacz et al, 2013). Many studies also eliminated items because they had low rates of endorsement in their samples, high cross-loadings, and/or failed to load adequately on a single factor (de Vito et al, 2018; Sayegh & Knight, 2014; Seidl & Massman, 2016; Thakur et al, 2021; Trzepacz et al, 2013). These modifications to the test item structure further obscure cross-study comparison.…”

“…There may also be true differences in the structure of the NPI-Q depending on the population sampled. Specifically, many studies limited their inclusion to select participants (e.g., those diagnosed with probable Alzheimer’s disease [AD]) or cognitive impairment severity or only included those who had BPS concerns (de Vito et al, 2018; Feghali et al, 2021; Sayegh & Knight, 2014; Seidl & Massman, 2016; Trzepacz et al, 2013). For instance, two studies using NPI-Q and NPI found variations in item loadings and number of factors when EFA was performed separately in AD severity subgroups (Aalten et al, 2003; Siafarikas et al, 2018).…”

“…In addition to statistical heterogeneity, many studies used variants in NPI-Q scoring procedures, with the most common being a dichotomized presence/absence (de Vito et al, 2018;Sayegh & Knight, 2014;Siafarikas et al, 2018;Thakur et al, 2021) and 4point ordinal severity (Feghali et al, 2021;Seidl & Massman, 2016;Siafarikas et al, 2021;Trzepacz et al, 2013). Many studies also This document is copyrighted by the American Psychological Association or one of its allied publishers.…”

“…Despite its wide dissemination, there is disarray in the literature regarding what subscales or symptom domains the NPI-Q captures, which impedes consistent and accurate use of the scale by clinicians and researchers. Most concerning, extant studies examining principal component and factor analyses of the NPI-Q have revealed a strikingly wide range of single-level models, ranging from 2 to 10 factors (de Vito et al, 2018;Feghali et al, 2021;Sayegh & Knight, 2014;Seidl & Massman, 2016;Siafarikas et al, 2018Siafarikas et al, , 2021Thakur et al, 2021;Trzepacz et al, 2013). The wide variability in factor structure may be related to differences in statistical methodology, measure modifications, and the sampled populations.…”