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Dehydration is a reliable predictor of impaired cognitive status. Objective data, using tests of cortical function, support the deterioration of mental performance in mildly dehydrated younger adults. Dehydration frequently results in delirium as a manifestation of cognitive dysfunction. Although, the occurrence of delirium suggests transient acute global cerebral dysfunction, cognitive impairment may not be completely reversible. Animal studies have identified neuronal mitochondrial damage and glutamate hypertransmission in dehydrated rats. Additional studies have identified an increase in cerebral nicotinamide adenine dinucleotide phosphate-diaphorase activity (nitric oxide synthase, NOS) with dehydration. Available evidence also implicates NOS as a neurotransmitter in long-term potentiation, rendering this a critical enzyme in facilitating learning and memory. With ageing, a reduction of NOS activity has been identified in the cortex and striatum of rats. The reduction of NOs synthase activity that occurs with ageing may blunt the rise that occurs with dehydration, and possibly interfere with memory processing and cognitive function. Dehydration has been shown to be a reliable predictor of increasing frailty, deteriorating mental performance and poor quality of life. Intervention models directed toward improving outcomes in dehydration must incorporate strategies to enhance prompt recognition of cognitive dysfunction.