The Relationship between Associative Learning, Transfer Generalization, and Homocysteine Levels in Mild Cognitive Impairment

Abstract

Previous studies have shown that high total homocysteine levels are associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI). In this study, we test the relationship between cognitive function and total homocysteine levels in healthy subjects (Global Dementia Rating, CDR = 0) and individuals with MCI (CDR = 0.5). We have used a cognitive task that tests learning and generalization of rules, processes that have been previously shown to rely on the integrity of the striatal and hippocampal regions, respectively. We found that total homocysteine levels are higher in MCI individuals than in healthy controls. Unlike what we expected, we found no difference between MCI subjects and healthy controls in learning and generalization. We conducted further analysis after diving MCI subjects in two groups, depending on their Global Deterioration Scale (GDS) scores: individuals with very mild cognitive decline (vMCD, GDS = 2) and mild cognitive decline (MCD, GDS = 3). There was no difference among the two MCI and healthy control groups in learning performance. However, we found that individuals with MCD make more generalization errors than healthy controls and individuals with vMCD. We found no difference in the number of generalization errors between healthy controls and MCI individuals with vMCD. In addition, interestingly, we found that total homocysteine levels correlate positively with generalization errors, but not with learning errors. Our results are in agreement with prior results showing a link between hippocampal function, generalization performance, and total homocysteine levels. Importantly, our study is perhaps among the first to test the relationship between learning (and generalization) of rules and homocysteine levels in healthy controls and individuals with MCI.

Hyperhomocysteinemia and Neurologic Disorders: a Review

“…Clinical studies have shown that eHcy is associated with the transition from being cognitively healthy to developing dementia, 27 , 28 , 29 and that eHcy is an independent risk factor for the decline of cognitive performance in normal elderly subjects and patients with Alzheimer's disease (AD). Furthermore, eHcy was found in both healthy elderly with and without MCI.…”

Nutritional supplementation for Alzheimerʼs disease?

“…Statistical improvement in cognitive performance was observed for individuals with no known or suspected dementia within weeks and was maintained for 1 year (the length of the study). The general beneficial effects of Nutraceutical Formulation in preclinical studies may have alleviated Alzheimer's disease-related neuropathology: for example, oxidative stress is an early event in Alzheimer's disease neuropathology, homocysteine augments Abeta-induced oxidative damage and is correlated with impaired executive function, reduced levels of glutathione potentiates neuronal oxidative damage, and reduced acetylcholine levels correlate with impaired cognitive performance [54][55][56][57]. Cognitive performance and BPSD were stabilized for individuals with severe Alzheimer's disease for 9 months beyond those receiving placebo.…”

Plasma Homocysteine Concentrations in Dogs

“…Plasma Hcy concentrations also increase with age (Mijatovic et al, 1998). It has been reported that HHcy is related to diseases such as coronary heart disease (Cacciapuoti 2011;Frosst et al, 1995;Humphrey et al, 2008), kidney disease (Friedman et al, 2001), Alzheimer's disease (Moustafa et al, 2012), and rheumatoid arthritis (Roubenoff et al, 1997). Hcy also induces reactive oxygen species via HADPH activation, resulting in the production of several pro-inflammatory cytokines (Fujiki et al, 2012;Lawrence et al, 2002).…”

“…Recent studies suggest that plasma Hcy concentration may be a useful biomarker of cardiovascular or neurodegenerative disease (Humphrey et al, 2008;Moustafa et al, 2012). There have been only a few investigations of plasma Hcy concentrations in dogs (Lee and Hyun, 2012;Rossi Set al, 2008;Trisolini et al, 2008).…”