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Both hyper- and hypo-activation to cognitive challenge are associated with increased beta-amyloid deposition in healthy aging: A nonlinear effect.

ABSTRACT: Beta-amyloid (A?) positive individuals hyper-activate brain regions compared to those not at-risk; however, hyperactivation is then thought to diminish as Alzheimer's disease symptomatology begins, evidencing eventual hypoactivation. It remains unclear when in the disease staging this transition occurs. We hypothesized that differential levels of amyloid burden would be associated with both increased and decreased activation (i.e., a quadratic trajectory) in cognitively-normal adults. Participants (N = 62; aged 51-94) underwent an fMRI spatial distance-judgment task and Amyvid-PET scanning. Voxelwise regression modeled age, linear-A?, and quadratic-A? as predictors of BOLD activation to difficult spatial distance-judgments. A significant quadratic-A? effect on BOLD response explained differential activation in bilateral angular/temporal and medial prefrontal cortices, such that individuals with slightly elevated A? burden exhibited hyperactivation whereas even higher A? burden was then associated with hypoactivation. Importantly, in high-A? individuals, A? load moderated the effect of BOLD activation on behavioral task performance, where in lower-elevation, greater deactivation was associated with better accuracy, but in higher-elevation, greater deactivation was associated with poorer accuracy during the task. This study reveals a dose-response, quadratic relationship between increasing A? burden and alterations in BOLD activation to cognitive challenge in cognitively-normal individuals that suggests 1) the shift from hyper-to hypo-activation may begin early in disease staging, 2) depends, in part, on degree of A? burden, and 3) tracks cognitive performance.

SUBMITTER: Foster CM

PROVIDER: S-EPMC5747976 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Both hyper- and hypo-activation to cognitive challenge are associated with increased beta-amyloid deposition in healthy aging: A nonlinear effect.

Foster Chris M CM Kennedy Kristen M KM Horn Marci M MM Hoagey David A DA Rodrigue Karen M KM

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Beta-amyloid (Aβ) positive individuals hyper-activate brain regions compared to those not at-risk; however, hyperactivation is then thought to diminish as Alzheimer's disease symptomatology begins, evidencing eventual hypoactivation. It remains unclear when in the disease staging this transition occurs. We hypothesized that differential levels of amyloid burden would be associated with both increased and decreased activation (i.e., a quadratic trajectory) in cognitively-normal adults. Participan ...[more]

PMID: 29108941

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Project description:Background and aimsRecent evidence suggests that acute kidney injury (AKI) is the main predictor of postparacentesis bleeding in patients with cirrhosis. To assess the factors responsible for bleeding tendency in AKI, we performed a prospective study comparing all three aspects of hemostasis (platelets, coagulation, and fibrinolysis) in patients with decompensated cirrhosis with and without AKI.Approach and resultsPrimary hemostasis assessment included platelet aggregation and secretion (platelet function markers) and von Willebrand factor. Secondary hemostasis assessment included pro-coagulant (factor VIII and factor XIII) and anti-coagulant (protein C, protein S, and antithrombin) factors and thrombin generation. Tertiary hemostasis assessment included fibrinolytic factors and plasmin-antiplasmin complex. Eighty patients with decompensated cirrhosis were recruited (40 each with and without AKI). Severity of cirrhosis and platelet count were comparable between groups. Median serum creatinine was 1.8 mg/dL and 0.8 mg/dL in patients with and without AKI, respectively. At baseline, patients with cirrhosis and AKI had lower platelet aggregation and secretion, indicative of impaired platelet function (increased bleeding tendency), without differences in von Willebrand factor. Regarding coagulation factors, factor VIII was higher, whereas protein C, protein S, and antithrombin were all lower, which, together with increased thrombin generation, indicate hypercoagulability. In contrast, factor XIII was lower in AKI (increased bleeding tendency). Finally, while both hypofibrinolytic and hyperfibrinolytic changes were present in AKI, a higher plasmin-antiplasmin complex indicated a hyperfibrinolytic state. After AKI resolution (n = 23 of 40), platelet function and coagulation improved to levels observed in patients with cirrhosis patients without AKI; however, fibrinolysis remained hyperactivated.ConclusionsIn patients with decompensated cirrhosis, AKI is associated with both hypocoagulable and hypercoagulable features that can potentially increase the risk of both bleeding and thrombosis.

Dataset Information

Both hyper- and hypo-activation to cognitive challenge are associated with increased beta-amyloid deposition in healthy aging: A nonlinear effect.

Publications

Both hyper- and hypo-activation to cognitive challenge are associated with increased beta-amyloid deposition in healthy aging: A nonlinear effect.

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