Assessing the stability of clusters of neuropsychiatric symptoms in Alzheimer’s disease and mild cognitive impairment

Aim: The aim of the study was to investigate the factors that underpin neuropsychiatric symptoms and how they might evolve over time, in people with Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD) dementia.

Background: Neuropsychiatric symptoms are psychiatric and behavioural manifestations that occur in people with AD. These are highly prevalent along the continuum of the disease, including at the stage of MCI, as well as before cognitive decline. Various small- and large-scale projects have investigated the underlying factors that underpin these symptoms, however, the identification of clear clusters is still a matter of debate; furthermore, no study has investigated how the clusters might change across the development of AD pathology, by comparing different time points.

Objective: Our objective was to investigate the factors that underpin neuropsychiatric symptoms in Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI), and to assess how the loadings might differ based on considerations such as disease stage of the samples.
Methods: Data was obtained from the Alzheimer’s Disease Neuroimaging Initiative database (adni.loni.usc.edu), using scores from the Neuropsychiatric Inventory, followed up yearly from baseline until month 72. Participant groups included those with MCI or AD dementia, or a mixture of both, with all participants presenting with at least one neuropsychiatric symptom. A series of exploratory Principal Component and Factor (Principal Axis) Analyses were performed using Direct Oblimin rotation.

Results: The best-fitting structure was interpreted for each time point. A consistent unique structure could not be identified, as the factors were unstable over time, both within the MCI and AD groups. However, some symptoms showed a tendency to load on the same factors across most measurements (i.e., agitation with irritability, depression with anxiety, elation with disinhibition, delusions with hallucinations).

Conclusion: Although the analyses revealed some degree of co-occurrence of neuropsychiatric symptoms across time points/samples, there was also considerable variation. In the AD group, more discrete syndromes were evident at the early time points, whereas a more complex picture of co-occurring symptoms, with differences likely reflecting disease staging, was seen at later time points. As a clear and distinctive factor structure was not consistently identified across time points/samples, this highlights the potential importance of sample selection (e.g., disease stage and/or heterogeneity) when studying, for example, the neurobiological underpinnings of neuropsychiatric symptoms.