The neurodegeneration of the cholinergic pathways in subtypes of subjective cognitive decline

Abstract Background Neurodegeneration of cholinergic pathways may be present in individuals with subjective cognitive decline (SCD). However, variability between SCD individuals in the integrity of cholinergic pathways needs to be elucidated. Our objective was to determine characteristics of neurodegeneration of cholinergic pathways in different SCD subtypes (i.e. amnestic vs. non‐amnestic). Method Individuals with amnestic SCD (n = 47), non‐amnestic SCD (n = 38), and healthy controls without cognitive complaints (HC; n = 20) from the GENIC database were included (all: >60 years old; 58% females). White matter integrity was estimated by mean diffusivity (MD) on diffusion tensor imaging (DTI) for cingulum and external cholinergic pathways. Both pathways were previously modelled using tractography on DTI. Memory performance was measured based on Visual reproduction WMS‐III and TAVEC (the Spanish version of the California Verbal Learning Test, CVLT). ANOVA and bivariate Pearson correlation were used for the statistical analysis. Result Amnestic and non‐amnestic SCD groups were comparable to HC in the integrity of cholinergic WM pathways. Bivariate Pearson correlation analyses showed different patterns of association between the cholinergic pathways and cognition within each group. In amnestic‐SCD, worse WM integrity in both cholinergic pathways was associated with poorer immediate recall of visual information (external capsule: r xy = ‐0.42; p<0.05; cingulum: r xy = ‐0.34; p<0.05). In non‐amnestic‐SCD, worse WM integrity in both cholinergic pathways was associated with poorer delayed recall of verbal information (external capsule: r xy = ‐0.54; p<0.05; cingulum: r xy = ‐0.42; p<0.05); and worse WM integrity in the external capsule pathway was associated with poorer performance in immediate and delayed recall of visual information (r xy = ‐0.37; p<0.05 and r xy = ‐0.46; p<0.05). In HC, none of the cognitive outcomes was associated with the integrity of the cholinergic pathways. Conclusion The cholinergic pathways were mainly associated with immediate recall in the amnestic SCD (i.e. acquisition of new information); whereas in non‐amnestic SCD the integrity of cholinergic pathways was associated with several subcomponents of memory performance (i.e. acquisition and recall of new information). Thus, SCD subtypes show unique patterns of associations between poorer integrity of the cholinergic system and memory performance.