Amyloid and tau deposition influences cognitive decline in Down syndrome

Abstract

AbstractBackgroundAmyloid‐β accumulation in the brain has been associated with decline in cognitive functioning in adults with Down Syndrome (DS). Despite the significant relationship between in vivo Amyloid‐β and tau pathology, no studies have assessed whether tau potentiates the relationship between amyloid‐β and cognitive decline in DS. Here we investigate whether (i) tau has an independent effect on changes in cognition; (ii) tau has a synergistic relationship with amyloid in the exacerbation of cognitive decline.MethodA baseline cohort of 105 participants with DS underwent PET AV‐1451 and PiB scans to quantify tau and Amyloid‐β deposition. Neuropsychological assessment of participants included a test for episodic memory (Cued Recall), visuospatial ability (WISC‐IV Block Design and Haxby Extension) and global cognition (DSMSE). Cognition was re‐assessed at 16 (n = 105) and 32 months (n=26) after baseline. Amyloid‐β burden was quantified categorically as PiB+/‐ where PiB+ status was defined as PiB standard uptake value ratio (SUVR) above a defined threshold. Braak regions (2‐6) and the Striatum were used for generating the SUVR for AV‐1451. Linear Mixed Effects models were implemented to assess the independent effects of tau and PiB status on change in cognition. Additional models tested the 3‐way interactions between tau, PiB status and time for each ROI. P‐values were adjusted via the FDR method.ResultFor the memory outcome, the interactions between time and tau (with PiB status – time interactions also included in the model) were significant for all ROIs, except the Striatum, while Braak regions 3 to 5 were significantly associated with change in DSMSE scores. All ROIs’ tau showed a significant interaction with time for the Block Design task. The three‐way interaction between time, PiB status and striatal tau was significant in the models of memory change. Braak 5 and tau showed a significant interaction with time and PiB status for the visuospatial ability outcome (Fig 1‐4).ConclusionThere was evidence for a significant independent effect of baseline tau on cognitive change, over and above the effect of amyloid status. We also found evidence for a synergistic relationship between PiB status and tau as predictors of change in memory and visuospatial ability.