Association of Neuropsychiatric Symptom Profiles With Cognitive Decline in Patients With Parkinson Disease and Mild Cognitive Impairment

Background and ObjectivesNeuropsychiatric symptoms (NPS) are closely associated with cognitive decline in patients with Parkinson disease (PD). We investigated which profiles of NPS are associated with the risk of dementia in PD with mild cognitive impairment (PD-MCI).MethodsWe retrospectively assessed 338 patients with PD-MCI from a single tertiary hospital, who underwent neuropsychological tests and a neuropsychiatric inventory (NPI) questionnaire. We conducted a factor analysis of the dichotomized presence of 12 NPI symptoms, yielding 3 NPI factors: factor 1, mood symptoms; factor 2, hyperactivity-related symptoms; and factor 3, psychotic symptoms. Factor analysis of the severity of NPI symptoms also identified similar NPI factors. The neuropsychiatric correlates of NPI factors were evaluated using general linear models for cognitive tests. Subsequently, we evaluated the hazard ratio (HR) of NPI factors on conversion to dementia.ResultsA higher prevalence factor 1 score was associated with lower scores in the verbal memory (β = -0.15; 95% CI -0.24 to -0.06; p = 0.001) and executive domains (β = -0.16; 95% CI -0.28 to -0.04; p = 0.007), whereas higher severity factor 2 scores were associated with lower scores in the naming (β = -0.16; 95% CI -0.28 to -0.03; p = 0.012), visuospatial (β = -0.24; 95% CI -0.41 to -0.07; p = 0.005), and verbal memory domains (β = -0.15; 95% CI -0.24 to -0.05; p = 0.005). A higher severity factor 3 score was associated with lower scores in the visuospatial domain (β = -0.25; 95% CI -0.46 to -0.07; p = 0.007). Cox regression models demonstrated that the risk of dementia was increased in those with higher prevalence factor 1 (HR = 1.48, 95% CI 1.17-1.88, p = 0.001) and factor 2 scores (HR = 1.27, 95% CI 1.07-1.51, p = 0.007) and severity factor 3 score (HR = 1.52, 95% CI 1.29-1.80, p < 0.001) after adjusting for age, sex, education, disease duration, scores for cognition and parkinsonism, and levodopa equivalent dose.DiscussionThis study demonstrated that a higher burden of NPS is associated with dementia conversion in patients with PD-MCI.