Neuropsychiatric Symptoms Present Differently in Individuals with Different High-Risk States of Dementia

Introduction: Neuropsychiatric symptoms (NPS) are common in neurocognitive disorders. However, the differences in presentation of NPS in high-risk states for dementia such as mild neurocognitive disorder (Mild NCD) and remitted major depressive disorder (rMDD) remain unclear. The purpose of this study was to compare the frequency and factor structure of NPS in Mild NCD, rMDD, and Mild NCD with rMDD (Mild NCD-rMDD).

We analyzed baseline data from the multicenter Prevention of Alzheimer's Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression trial (NCT0238667). NPS were assessed using the Neuropsychiatric Inventory Questionnaire in those with Mild NCD, rMDD, and Mild NCD-rMDD. We compared the NPS frequency and factor structure across the three groups.

Among 374 participants with a mean (SD) age = 72.0 (6.3) years, the overall frequency of any NPS was highest in Mild NCD-rMDD (75.9%), as compared to Mild NCD (63.5%) or rMDD (55.7%) groups (p = 0.014). Depression/dysphoria was the most common NPS in all three groups. In factor analyses, NPS grouped into four factor structures in all three groups, but the composition of factors of individual symptoms (delusions, motor disturbances, nighttime behaviors, anxiety, and apathy) were different.

NPS are common in high-risk states of dementia, and the frequency of NPS is higher in Mild NCD-rMDD as compared to only Mild NCD or rMDD. Further, there are key differences in presentation of NPS in Mild NCD, rMDD, and Mild NCD-rMDD. Future studies should investigate the relevance of these differences for cognition, function, and disease biomarkers.