Risk of Dementia Associated with Elevated Plasma Homocysteine in a Latin American Population

Abstract

The relationship between total homocysteine (tHcy) and dementia risk remains controversial, as the association varies among populations and dementia subtypes. We studied a Venezuelan population that has high prevalence of both elevated tHcy and dementia. We tested the hypotheses that (1) elevated tHcy is associated with increased dementia risk, (2) the risk is greater for vascular dementia (VaD) than for Alzheimer's disease (AD), and (3) a history of stroke may partly explain this association. 2100 participants (≥55 years old) of the Maracaibo Aging Study underwent standardized neurological, neuropsychiatric, and cardiovascular assessments. Elevated tHcy was significantly associated with dementia, primarily VaD. When history of stroke and other confounding factors were taken into account, elevated tHcy remained a significant risk factor in older (>66 years), but not in younger (55–66 years) subjects. Ongoing studies of this population may provide insight into the mechanism by which tHcy increases risk for dementia.

Biomarkers in vascular dementia: A recent update

“…Hyperhomocysteinemia is a wellestablished vascular risk factor and increased level of serum homocysteine proves a causal relationship with vascular lesions and thereby VaD. 37,38 Elevated levels of serum homocysteine were also seen in AD patients and are considered to contribute to vascular pathogenesis of AD. Recently, many studies have shown that elevated serum homocysteine is associated with hippocampal and cortical atrophy in patients with VaD.…”

Oxidative and Nitrosative Stress and Immune-inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

“…Regland and others [ 70 ] reported elevated levels of homocysteine in the CSF of people diagnosed with ME/CFS which correlated significantly with disease severity. Elevated levels of homocysteine are known to be a cause of blood brain barrier disruption [ 71 , 72 ] and neurotoxicity [ 73 , 74 ]. In addition to disruption of the blood brain barrier, homocysteine is likely to also contribute to neurotoxicity by activating N-Methyl-D-aspartate (NDMA) receptors in the brain [ 75 ].…”

Identification of biomarkers for vascular dementia: a literature review

“…Ray et al (2013) suggested that the elevated level of serum homocysteine in the Alzheimer's disease group compared with age-matched controls seen in their own and other studies probably contributes to the genesis of vascular pathology in Alzheimer's disease. This view of hyperhomocysteinaemia accounting for the vascular component of Alzheimer's disease pathology has also been proposed by Chacón et al (2009). Although this study suggests significantly higher homocysteine levels in vascular dementia than in Alzheimer's disease, it does not provide clear evidence of homocysteine levels specifically related to vascular dementia.…”

“…This is in keeping with previous studies suggesting a strong association of hyperhomocysteinaemia with both diseases (Leblhuber 2000; Seshadri 2002; Ravaglia 2005). Hyperhomocysteinaemia is a well-known vascular risk factor and a higher level of serum homocysteine in people with vascular dementia is probably causal, owing to the vascular lesions underlying this disorder (Chacón 2009). Ray et al (2013) suggested that the elevated level of serum homocysteine in the Alzheimer's disease group compared with age-matched controls seen in their own and other studies probably contributes to the genesis of vascular pathology in Alzheimer's disease.…”