中度至晚期路易体痴呆的认知波动、神经精神负担与生活质量：自主神经功能障碍的作用

原文

BACKGROUND AND OBJECTIVES: Cognitive fluctuations are reported in 90% of individuals with dementia with Lewy bodies (DLB) and along with dysautonomia, are a key source of disability. Through this effort, we sought to investigate the relationship between autonomic burden and cognitive fluctuations, neuropsychiatric burden and quality of life in moderate-advanced DLB. METHODS: This multicenter, prospective, observational, longitudinal cohort study, Predicting ACcurately End-of-Life in Dementia With Lewy Bodies and Promoting Quality End-of-Life Experiences (PACE-DLB), was conducted in the United States to study individuals with moderate-advanced DLB. The primary exposure for the current analysis was time-varying total autonomic burden, as measured by the autonomic symptom checklist (ASC) at baseline and follow-up visits. The primary outcomes were cognitive fluctuations measured by Clinician Assessment of Fluctuations (CAF) scores and neuropsychiatric burden as measured by Neuropsychiatric Inventory Questionnaire (NPI-Q) scores. Secondary outcomes included quality of life (QoL) captured through the Quality of Life-Alzheimer's Disease scale. Mixed-effects regression analyses were conducted to assess the effect of autonomic burden on each primary outcome, with age, sex, education, Charlson Comorbidity Index, anticholinergic burden, levodopa equivalent daily dosage, and EPWORTH sleepiness scale scores adjusted as potential confounders. We additionally conducted modified graphical network model analyses. RESULTS: A total of 189 patients with 745 longitudinal observations were included in the analysis. Mean age of the cohort was 74.92 years (SD 7.77 years) with 22% female participants. At baseline, ASC was directly associated with CAF (RC = 0.16; 95% CI 0.01-0.31; p = 0.032) and NPI-Q (RC = 3.27; 95% CI 2.37-4.18; p < 0.001). In longitudinal analysis, ASC remained directly associated with CAF (RC = 0.18; 95% CI 0.11-0.24; p < 0.001) and NPI-Q (RC = 2.10; 95% CI 1.49-2.71; p < 0.001). ASC scores were inversely associated with QoL of the caregiver (RC = -0.04; 95% CI -0.06 to -0.02) in longitudinal adjusted analysis. Graphical network modeling incorporating possible relationships across characteristics showed that autonomic burden was directly and stably associated with cognitive fluctuations (weight = 0.15) and neuropsychiatric burden (weight = 0.47). DISCUSSION: Autonomic burden correlates with severity of cognitive fluctuations and neuropsychiatric burden in moderate-advanced DLB. It also correlates with the QoL of the caregiver over time. These results encourage investigation into novel potential therapeutic avenues in moderate-advanced DLB.