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Hyperphosphorylated tau and tangle development are more closely associated with synaptic dysfunction and cognitive decline (including conversion to mild cognitive impairment and AD dementia) compared to A alone [110,111,112]

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persistent, severe abdominal pain) Hypersensitivity to DPP-4 inhibitors in the past Pregnancy/breastfeeding Some DPP-4 inhibitors are contraindicated at certain thresholds of renal impairment (see Table 2 ) Some DPP-4 inhibitors are contraindicated in hepatic impairment (see Table 3 ) Type 1 diabetes Diabetic ketoacidosis Cautions History of pancreatitis Moderate heart failure (saxagliptin only, due to limited experience) Severe heart failure (saxagliptin and vildagliptin, due to limited experience) Some DPP-4 inhibitors are cautioned at certain thresholds of renal impairment, and dose reductions may be required (see Table 2 ) Drug interactions No significant interactions have been reported between DPP-4 inhibitors and any other drugs