Reduced brain amyloid burden in elderly patients with narcolepsy type 1 (original) (raw)

Objective: To determine whether brain amyloid burden in elderly patients with narcolepsy type 1 (NT1) is lower than in controls, and to assess in patients with NT1 the relationships between amyloid burden, cerebral spinal fluid (CSF) markers of Alzheimer's disease (AD), CSF orexin-A, and cognitive profile. Methods: Cognitive and 18 F-florbetapir-positron emission tomography (PET) data were compared in patients with NT1 aged ≥65 years (n=23) and in age-and sex-matched controls free of clinical dementia selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI, n=69) and the Multidomain Intervention Alzheimer's Prevention Trial (MAPT-AV45; n=23) cohorts. The standardized uptake values (SUV) of the cortical retention index for six regions of interest were computed and averaged to create a mean SUV ratio normalized to three subcortical reference regions (cerebellum, pons and a composite region). A cortical/cerebellum SUV ratio ≥1.17 defined positive PET amyloid. Results: Lower cortical amyloid burden was observed in the NT1 than in the ADNI and MAPT-AV45 groups (mean cortical/cerebellum SUV ratios: 0.95±0.15, 1.11±0.18 (p<0.0001), and 1.14 ±0.17 (p=0.0005), respectively). Similar results were obtained with all subcortical reference regions and for all cortical regions of interest, except cingulum. Only one patient with NT1 (4.4%) had positive PETamyloid compared with 27.5% in the ADNI and 30.4% in the MAPT group. In the NT1 group, cortical or regional amyloid load was not associated with CSF orexin-A, CSF AD biomarkers or neuropsychological profile. Interpretation: Lower brain amyloid burden, assessed by 18 F-florbetapir-PET, in patients with NT1 suggests delayed appearance of amyloid plaques.