2molecule is a risk factor for vascular disease, elevated levels of plasma homocysteine canlead to changes in vasculature and impair blood coagulation pathways, which then mayresult in the decreased supply of blood to neurons, causing neuronal death. Thishypothesis may explain the deficit of cholinergic neurons that is often observed in patients with AD (Mizrahi, 2002). Second, homocysteine has been shown to haveneurotoxic effects
It binds to NMDA receptors in the brain, causing calciuminflux and triggering generation of reactive oxygen species (ROS), ultimately fosteringapoptosis (Mizrahi, 2002; Morris, 2003). Third, homocysteine may induce DNA breakage in neurons by impaired methylation reactions (Shea, 2002). Lastly, perhapsmost trivially, homocysteine simply might not be a causative factor and instead aconsequence of the poor dieting habits of those with AD.Most of the aforementioned studies that investigated the role of homocysteine inAD and vascular disease were cross-sectional in design, making difficult thedetermination of whether hyperhomocysteinemia is a causative factor of AD or simply aramification of the disorder. The longitudinal study of cognitive trajectories in older persons conducted by Mungas et al. (2010) showed that such trajectories appear heterogeneous after follow-ups. More recent studies, however, suggested thatcharacteristics such as levels of C-reactive protein and MRI-based brain measurementswere closely related to rate of cognitive decline in older patients (Bettcher et al., 2012;Carmichael et al., 2012). Thus, the possibility that plasma homocysteine levels can predict cognitive decline and onset of Alzheimer’s disease remains open.The purpose of this study was to determine whether plasma levels of homocysteine could serve as a predictive biomarker for cognitive decline in older individuals. It was hypothesized that higher levels of plasma homocysteine would predictincreased risk of cognitive decline and AD onset.
Subject information and recruitment
A total of 103 subjects were recruited for this study. Informed consent for thisstudy was obtained from all subjects prior to experimentation. Based on clinicalobservations, subjects were placed into one of three groups: No Impairment (n=63), MildCognitive Impairment (MCI, n=29), and Alzheimer’s (AD, n=11). Subjects wererelatively age-matched across diagnostic groups, with the mean ages ranging from 73.1 – 77.5 (Table 1).
Diagnosis Males Females Mean Age S.D
No Imp. 22 41 73.1 6.4MCI 13 16 76.2 5.8AD 1 10 77.5 6.5
Assessing plasma homocysteine
Blood samples were collected from patients by standard venipuncture. Plasmacysteine and homocysteine concentrations were measured by high performance liquidchromatography with postcolumn fluorescence detection, which has been shown to be areliable and rapid way to quantify homocysteine concentrations (Vester & Rasmussen,