Organophosphate pesticides, cholinergic function and cognitive performance in advanced age

The present communication will address the question of whether older individuals/animals are at greater risk to the cognitive impairment induced by exposure to organophosphates (OPs). There is considerable evidence for a decline in cholinergic indices (choline acetyltransferase, acetylcholinesterase, and muscarinic acetylcholine receptors) with aging. Whether these decreases lead to a greater or smaller response to OPs will depend on the relative rate of change in the specific indices. Some studies have shown that aged animals are more sensitive to cholinergic (muscarinic) agonists, even though the receptors are reduced. These findings suggest that aged individuals may be more sensitive to OPs. There is also much evidence documenting the decline in cognitive function in aged animals, a process which is accentuated in Alzheimer's disease and which has been attributed, in part, to the decline in cholinergic indices. Several studies have reported an improvement in cognitive functioning in aged animals/humans following treatment with acetylcholinesterase inhibitors. Thus, it is possible that the cognitive impairment, which occurs during aging, may be partially counteracted during treatment with certain cholinesterase inhibitors (both OPs and nonOPs). Whether the cognitive impairment reported by younger individuals some time after exposure to OPs would be greater in the elderly cannot be predicted on the basis of the available evidence. However, the findings in an animal model of dietary-induced cholinergic hypofunction developed by Roger Russell and colleagues may shed light on this question.