Background and Objectives:The ATN framework has been developed to categorize biological processes within the Alzheimer’s disease (AD) continuum. Since AD pathology often coincides with dementia with Lewy Bodies (DLB), we aimed to investigate the distribution of ATN profiles in DLB and associate ATN-profiles in DLB to prognosis.Methods:We included 202 DLB patients from the Amsterdam Dementia Cohort (68±7yrs, 19%F, MMSE: 24±3, DAT-SPECT abnormal: 105/119). Patients were classified into eight profiles according to the ATN framework, using CSF Aβ42 (A), CSF p-tau (T) and medial temporal atrophy scores (N). We compared presence of clinical symptoms in ATN profiles and used linear mixed models to analyze decline on cognitive tests (follow-up 3±2yrs for n=139). Mortality risk was assessed using Cox proportional hazards analysis. Analyses were performed on both the eight profiles, as well as three clustered categories (normal AD biomarkers, non-AD pathologic change, AD continuum).Results:Fifty (25%) DLB patients had normal AD biomarkers (A-T-N-), 37 (18%) had non-AD pathologic change (A-T+N-: 10%/A-T-N+: 6%/A-T+N+: 3%) and 115 (57%) were classified within the AD continuum (A+T-N-: 20%/A+T+N-: 16%/A+T-N+: 10%/A+T+N+: 9%). A+T+N+ patients were older and least often had RBD symptoms. Parkinsonism was more often present in A+T-, compared to A-T+ (independent of N). Compared to patients with normal AD biomarkers, patients in A+ categories showed steeper decline on memory tests and higher mortality risk. Cognitive decline and mortality did not differ between non-AD pathologic change and normal AD biomarkers.Discussion:In our DLB cohort, we found clinically relevant associations between ATN categories and disease manifestation. Patients within the AD continuum had steeper cognitive decline and shorter survival. Implementing the ATN framework within DLB patients aids in subtyping patients based on underlying biological processes and could provide targets for future treatment strategies, e.g. AD modifying treatment. Expanding the framework by incorporating markers for alpha-synucleinopathy would improve the use of the framework to characterize dementia patients with mixed pathology, which could enhance proper stratification of patients for therapeutic trials.
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.
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