Cognitive functioning and survival in the elderly: the SSADH C538T polymorphism

The variability of the Succinic Semialdehyde Dehydrogenase (SSADH, or ALDH5A1) gene affects both pathological and normal phenotypes correlated to cognitive function. We tested the association between the C538T polymorphism of the SSADH gene and preservation of cognitive function in the elderly, and its possible effects on survival. A sample from southern Italy (514 subjects; 18-107 years) was screened for C538T variability. We found that, within the 65-85 years age range, the T/T genotype is overrepresented in subjects with impaired cognitive function (MMSE < or = 23) compared to those with conserved cognitive function (MMSE > 23). Furthermore, we found that the T/T genotype affects survival after 65 years of age. In fact, after this age, the survival function of T/T homozygous subjects is lower than that of the others. Given that the enzymatic activity of the protein encoded by allele T is 82.5% of the activity of the protein encoded by allele C, our results suggest that the efficiency of the SSADH enzyme is important for the preservation of cognitive function and survival in the elderly.