To verify whether the C825T polymorphism of the GNB3 influences the response to neuropsychological tests, mini-mental state examination, digit span (DS), immediate and delayed prose memory, memory with interference at 10 and 30 seconds (MI 10 and 30), trail making tests (TMTs) A and B, abstraction task, verbal fluency (VF) test, figure drawing and copying, overlapping figures test and clock test were performed in 220 elderly men and women free from clinical dementia and from neurological and psychiatric diseases randomly taken from the Italian general population and analysed across the C825T polymorphism. The performance of DS, immediate and delayed prose memory, VF, and TMTs was worse in subjects who were TT for the polymorphism in comparison to the C-carriers. The performance of all tests declined with age. In the case of DS, immediate and delayed prose memory, MI 10 and VF, this trend was maintained in the C-carriers but not in TT. In the case of prose memory, of memory with interference, and of VF, schooling reduced the detrimental interaction between age and genotype. The C825T polymorphism of GNB3 gene therefore influences memory and verbal fluency, being additive to the effects of age and partially mitigated by schooling. 1. Introduction The heteromeric guanine nucleotide-binding proteins (G-proteins) are composed of α, β, and γ subunits. The β subunit is a regulator of signal transduction receptors and effectors. The C825T single-nucleotide polymorphism in the guanine nucleotide-binding protein beta polypeptide 3 (GNB3) gene encoding for β3 subunit located on chromosome 12p13 has been found to be associated with essential hypertension [1] and obesity [2]. In recent literature, this polymorphism has also been associated with neurological and psychic conditions such as depression [3–6], dementia [7], dependence [8], dyskinesia [9], and neurologically determined functional diseases [10, 11] and with response to antidepressant [5] or antipsychotic [12] drugs. Nevertheless, all these studies have been performed on psychiatric patients or in subsets of selected subjects. To our knowledge, no one of the studies dealing with this association was population based. Neuropsychological tests allow standard evaluation of cognitive functions. Memory, language, and executive functions can be assessed and quantified by numeric scores. General cognitive assessment can be performed by means of mini-mental state examination [13]. A comprehensive neuropsychological battery of validated paper and pencil tests is also relevant for exploring focally the areas of
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