ATN classification in dementia with Lewy bodies: Association with clinical profile, cognitive decline and survival

Abstract

Background The ATN framework has been developed to characterize biological processes within the Alzheimer’s disease (AD) continuum. Since AD pathology often coincides with dementia with Lewy Bodies (DLB), we aimed to examine the distribution of ATN profiles in DLB and associate ATN‐profiles in DLB to prognosis. Method We included 192 DLB patients from the Amsterdam Dementia Cohort (68±7yrs, 19%F, MMSE: 24±3, DAT‐SPECT abnormal: 104/114). Patients were classified according to the ATN framework, using CSF Aβ1‐42 (A), CSF p‐tau (T) and medial temporal atrophy scores (N). Categories were compared on presence of clinical symptoms and demographics. To yield sufficient power for longitudinal analyses, the eight profiles were combined into four categories: normal AD biomarkers (A‐T‐N‐, reference), non‐AD pathologic change (A–T–N+/A–T+N–/A–T+N+), amyloid‐only (A+T‐N‐) and amyloid‐plus (A+T–N+/A+T+N–/A+T+N+). We used linear mixed models to analyze decline in MMSE (follow‐up 3±2yrs for n=137). We assessed differences in mortality using Cox proportional‐hazards models. Result Fifty (26%) DLB patients had normal AD biomarkers (A‐T‐N‐), 36 (19%) had non‐AD pathologic change (A‐T+N‐: 10%/A‐T‐N+: 6%/A‐T+N+: 3%) and 106 (55%) were classified within the AD‐continuum (A+T‐N‐: 20%/A+T+N‐: 16%/A+T‐N+: 10%/A+T+N+: 9%)(figure 1). A+T+N+ patients were older and less often had RBD symptoms. Compared to patients with normal AD biomarkers, those with amyloid‐only had steeper decline in MMSE (β±SE=‐0.82±0.28, p=0.005), while amyloid‐plus was associated to higher mortality rate (HR: 1.85[1.09‐3.13]). Cognitive decline and mortality did not differ between non‐AD pathologic change and normal AD biomarkers (figure 2‐3). Conclusion In our DLB cohort, we found clinically relevant associations between ATN categories and disease manifestation. Patients within the AD‐continuum had steeper cognitive decline (especially amyloid‐only) and shorter survival (amyloid‐plus). Individuals with non‐AD pathologic change did not differ from those with normal AD biomarkers in clinical presentation, decline or survival. Implementing the ATN framework within DLB patients could aid in subtyping patients based on underlying biological processes and provide targets for future treatment strategies, e.g. AD modifying treatment.