Olfactory Dysfunction and Cognitive Impairment in Age-Related Neurodegeneration: Prevalence Related to Patient Selection, Diagnostic Criteria and Therapeutic Treatment of Aged Clients Receiving Clinical Neurology and Community-Based Care

Abstract

A decrease in olfactory function with age has been attributed to a variety of factors including normal anatomical and physiological changes in aging, surgery, trauma, environmental factors, medications and disease. Olfactory impairment has also been associated with neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease. Deficits in these chemical senses cannot only reduce the pleasure and comfort from food, but represent risk factors for nutritional and immune deficiencies as well as adherence to specific dietary regimens. Therapy is limited, but one should be aware of the existing medical and surgical treatment modalities.Reactive oxygen and nitrogen species, copper and zinc ions, glycating agents and reactive aldehydes, protein cross-linking and proteolytic dysfunction may all contribute to neurodegeneration, olfactory dysfunction, AD. Carnosine (beta-alanyl-L-histidine) is a naturally-occurring, pluripotent, homeostatic transglycating agent. The olfactory lobe is normally enriched in carnosine and zinc. Loss of olfactory function and oxidative damage to olfactory tissue are early symptoms of AD. Protein and lipid oxidation and glycation are integral components of the AD pathophysiology. Carnosine can suppress amyloidbeta peptide toxicity, inhibit production of oxygen free-radicals, scavenge hydroxyl radicals and reactive aldehydes, and suppresses protein glycation. The observations suggest that patented non-hydrolyzed carnosine lubricant drug delivery or perfume toilet water formulations combined with related moiety amino acid structures, such as beta-alanine, should be explored for therapeutic potential towards olfactory dysfunction, AD and other neurodegenerative disorders. "The olfactory system, anatomically, is right in the middle of the part of the brain that's very important for memory. There are strong neural connections between the two." ~ Donald Wilson

The Chemistry of Neurodegeneration: Kinetic Data and Their Implications

“…It is believed that the naturally occurring dipeptide L-carnosine (β-alanyl-L-histidine) acts as an ion-chelating agent (mainly for Cu 2+ and Zn 2+ ), free-radical and reactive aldehyde scavenger [126] and anti-oxidant [127,128], as well as both an amyloid beta toxicity and protein glycation suppressor [129]. Moreover, it has the potential to maintain the level of GPx and SOD activity [130].…”

“…For this reason, the enzymatic hydrolysis of Lcarnosine is the main limitation for their possible effective pharmacological applications. Still, some authors put forward interesting hypotheses that lubricant drug delivery and perfume toilet water formulations [129], or lubricant eye drops and oral formulation [145], all based on non-hydrolyzed Lcarnosine, should be explored for their therapeutic potential in olfactory dysfunction, Alzheimer's disease and other neurodegenerative disorders.…”

Olfaction deterioration in cognitive disorders in the elderly

“…In particular, with regard to PD patients, studies indicate that pharmacological treatments of PD, Aging Clin Exp Res used to control motor dysfunction (i.e., L-DOPA, dopamine agonists, anticholinergic compounds), fail to restore olfactory function [12,38]. Although some studies conducted on mouse models of AD demonstrated that lipid-based diets [79,80] and estradiol injection in the hippocampus [81] can alleviate cognitive deficits and carnosine could be a promising dipeptide with therapeutic potential toward olfactory dysfunction in AD [79], there are no pharmacological treatments of olfaction. Deep brain stimulation has been proposed as a possible therapy in PD, as it has been demonstrated to improve odor discrimination (no effect on odor thresholds has been found).…”

Carnosine markedly ameliorates H9N2 swine influenza virus-induced acute lung injury

“…These compounds ultimately lead to profound injuries to the alveolocapillary membrane and respiratory failure (Lee & Downey, 2001;Khadaroo & Marshall, 2002;Chow et al, 2003). Furthermore, some investigations also indicated that inflammatory cytokines or ROS increased dramatically in H1N1 and H5N1 patients or some animal models (Akaike et al, 1996;He et al, 2013;Babizhayev et al, 2014). Interestingly, we found that the total WBC count in BALF decreased dramatically in the carnosine-treated H9N2-infected group compared with no-treatment H9N2-infected mice.…”

“…Cai et al (2003) also reported that inclusion of GSH in drinking water decreased the viral titre of influenza strain A/X-31 in both lung and trachea homogenates of BALB/c mice. Babizhayev et al (2014) found that oral carnosine decreased H1N1 viral replication by modulating respiratory burst and ROS production in neutrophils. So far, growing evidence indicates that viral replication is regulated by the redox state of the host cell, although the mechanisms underlying this virusrelated oxidative stress are still a matter of great debate (Vlahos et al, 2011(Vlahos et al, , 2012.…”