Symptom Clusters of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Their Comparative Risks of Dementia: A Cohort Study of 8530 Older Persons.

OBJECTIVES: Neuropsychiatric symptoms (NPS) have been recognized to increase the risk of dementia among individuals with mild cognitive impairment (MCI). However, it is unclear whether the risk is shared across the various NPS or driven primarily by selected few symptoms. This study sought to provide confirmatory evidence on the comparative risk of dementia across the various NPS in MCI.
DESIGN: Cohort study (median follow-up 4.0 years; interquartile range 2.1-6.4 years).
SETTING: Alzheimer's Disease Centers across the United States. PARTICIPANTS: Participants ≥60 years of age and diagnosed with MCI at baseline (n = 8530). MEASURES: Participants completed the Neuropsychiatric Inventory-Questionnaire at baseline and were followed up almost annually for incident dementia. Symptom clusters of NPS, as identified from confirmatory factor analyses, were included in Cox regression to investigate their comparative risks of dementia.
RESULTS: Three symptom clusters of NPS were identified among participants with MCI, namely hyperactivity, affective, and psychotic symptoms. The risk of dementia was present among participants with affective symptoms [hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.4-1.9] and psychotic symptoms (HR 1.6, 95% CI 1.2-2.2), but not among those with hyperactivity symptoms (HR 1.1, 95% CI 0.9-1.3). The risk was higher when affective symptoms and psychotic symptoms co-occurred (HR 2.5, 95% CI 2.0-3.2), with one-half of the participants in this group developing dementia within 2.7 years of follow-up. CONCLUSIONS AND IMPLICATIONS: The findings illustrate the potential usefulness of NPS as a convenient prognostic tool in the clinical management of MCI. They also suggest the need for future research to focus on affective/psychotic symptoms in MCI when studying the neurobiological links between NPS and neurodegenerative processes.