Dehydration and Cognition in Geriatrics: A Hydromolecular Hypothesis

Abstract

Dehydration is one of the ten most frequent diagnoses responsible for the hospital admission of elderly in the United States. It is associated with increased mortality, morbidity and an estimated cost of 1.14 billion per year (Xiao et al., 2004; Schlanger et al., 2010; Pretorius et al., 2013; Frangeskou et al., 2015). Older individuals are predisposed to dehydration encephalopathy as a result of decreased total body water (TBW) and diminished sensation of thirst. We hypothesize that thirst blunting in older individuals is the result of a defective microRNA-6842-3p failing to silence the expression of the vesicular GABA transporters (VGAT) and alpha 7 cholinergic nicotinic receptors in the subfornical organ (SFO) of the hypothalamus. We hypothesize further that resultant dehydration facilitates protein misfolding and aggregation, predisposing to neurocognitive disorders. We completed a search of predicted microRNA targets, utilizing the public domain tool miRDB and found that microRNA-6842-3p modulates the SLC6A1 and CHRNA7 genes both of which were previously hypothesized to inhibit the thirst sensation by their action on SFO. The primary aim of this article is to answer two questions: Can prevention and correction of dehydration in elderly lower age-related cognitive deterioration? Can exosomal miR-6842 in the peripheral blood predict dehydration encephalopathy in elderly?

Neurocognitive Disorders and Dehydration in Older Patients: Clinical Experience Supports the Hydromolecular Hypothesis of Dementia

“…Several consequences of these changes can appear, such as homeostatic inelasticity [ 6 ], that is, a limited ability to adjust water balance, leading to dehydration and hyperosmolality [ 4 , 7 , 8 ]. This defect could be a consequence to the loss of normal neural pathways that transmit sensory input to higher cortical centers where stimuli are perceived, and from which the response emanates [ 4 , 9 ]. We consider, in accordance with the recent hydromolecular hypothesis [ 10 ], the abnormalities of water homeostasis to be early expressions of neuronal dysfunction, brain atrophy, chronic cerebrovasculopathy and Alzheimer’s disease.…”

Awareness of dehydration state and fluid intake practice among adults population in the Jazan Region of Saudi Arabia, 2019

“…Limited knowledge of dehydration consequences were reported by Zuo et al, in China, and Shaheen et al, in Saudi Arabia (11,13) . The impact of severe dehydration on brain functioning has been well established in the literature, particularly in elderly adults and young children (24)(25)(26)(27) . Even mild dehydration has been linked to significant effects on everyday functioning (28) .…”

Chronic Dehydration in Nursing Home Residents

“…A previous study proposed the hypomolecular hypothesis, which postulates that cognitive impairment is caused by protein misfolding and subsequent aggregation in the brain under conditions of decreased interstitial fluid volume resulting from dehydration. Defective proteins may lead to cognitive impairment by hindering information processing in the biomolecular networks of the brain or through synaptic damage [ 46 ]. Patients with cognitive decline such as those with Alzheimer’s disease have a higher risk of dehydration, and dehydration is associated with the risk of dementia [ 47 ].…”