The apolipoprotein E (APOE) ε4 allele is the major genetic risk factor for the development of late-onset Alzheimer's disease (AD), whereas the presence of the APOE ε2 allele seems to confer protection. Here, we report that healthy young APOE ε4 carri

Background/Objectives: Cognitive dysfunction is a common aspect of the spectrum of symptoms of geriatric depression. High homocysteine levels have been linked to cognitive decline in neuropsychiatric disorders. The present study investigated possible associations between cognitive impairment observed in geriatric depression and homocysteine levels. Methods: The performance of 25 mentally healthy individuals and 40 patients with geriatric depression in terms of language processing, processing speed, concentration and attention was assessed with the Stroop Test and the d2 Test of Attention. Serum homocysteine was determined with an enzyme immunoassay. Results: The performance of depressed patients was significantly worse in language processing (p = 0.001) and processing speed (p < 0.0001). Depressed patients with high levels of homocysteine performed better than patients with homocysteine concentrations ≤11.7 µmol/l in both cognitive domains (p = 0.006 and 0.009, respectively). Moreover, homocysteine level was positively associated with language processing (p = 0.002) and processing speed (p = 0.002). Conclusions: These findings indicate that under the special circumstances of geriatric depression (perturbation of glutamatergic transmission and glutamate metabolism), homocysteine is positively associated with the performance in language processing and processing speed.

Acute homocysteine elevation has been shown to have a significant impact on cognitive function in animal models. Investigation of the short-term impact of elevation of plasma homocysteine levels through a dietary intervention on cognitive abilities of young healthy adults. 100 healthy medical students of both genders were enrolled in the study. Homocysteine levels and cognitive abilities were measured at 08:30 (before breakfast) and at 15:00 (two hours after lunch and six hours after breakfast). Food intake was restricted to specified comestibles. The cognitive assessment comprised a version of the Short Test for General Intelligence, three subtests of the Syndrome Short Test and the Stroop test. At 15:00 plasma homocysteine was significantly elevated in 56 participants (P<0.00001), whilst in 44 it was decreased (P0.05) and the direction of the changes did not differ between them. Accordingly, the multiple linear regression analysis did not reveal an important influence of homocysteine elevation on cognitive performance variations. Significant increase of plasma homocysteine is not associated with a straightforward inhibitory or facilitatory short-term effect on physiological cognitive parameters in young healthy adults.