Subthreshold amyloid pathology and changes in functional brain networks in patients with delayed cognitive decline after stroke

Abstract

AbstractBackgroundIn clinical practice, some of the stroke survivors who have normal cognitive function until three to six months after index stroke, develop cognitive decline gradually after then. Although amyloid deposits and advanced small vessel disease are reported to be the possible predictors, pathogenesis for delayed cognitive decline has not been identified yet. Thus, we aimed to explore the brain network characteristics in those with delayed cognitive decline after stroke compared to those without.MethodUsing a prospective stroke registry, we identified patients with ischemic stroke who had undergone the cognitive evaluations including mini‐mental state examination (MMSE) twice or more after index stroke. We included patients whose baseline cognitive evaluation (between 1 and 12 months after stroke) was normal and who had one or more follow‐up evaluations after more than 6 months from the baseline evaluation. Among 222 eligible patients, decliners were defined as having a decline in 3 or more per year or an absolute decline of 5 or more between baseline and follow‐up MMSE, while non‐decliners as having a decline of 1 point per year or less and an absolute decline of less than 3 points. Brain network attributes were analyzed using resting‐state functional MRI, and superimposed amyloid positivity was assessed using 18F‐florbetaben PET.ResultEleven patients (5%, 11/222) met the criteria for decliners, and ten matched non‐decliners were enrolled. For about 5.7 years of follow‐up, the mean change of MMSE scores was ‐9.1 points in the decliners, while ‐0.2 point in the non‐decliners. Ten (10/11) decliners were amyloid‐negative on the amyloid PET, and the APOE e4 allele was identified in one decliner. However, the global SUVR value showed a negative correlation with the final MMSE scores as well as the amount of MMSE change. Normalized transitivity was lower in decliners compared to non‐decliners. Mean connectivity strengths were averaged based on the seven canonical functional networks, and the intra‐network connections within the frontoparietal network showed the considerable differences between groups. (Figure)ConclusionThis study suggests that alteration of brain networks may explain the pathogenesis of the delayed post‐stroke cognitive decline independent of amyloid PET positivity and APOE genotype.