Association of Elevated Plasma Total Homocysteine With Dementia With Lewy Bodies: A Case-Control Study.

Guili Zhang,Lingyun Ma,Shuai Liu,Xudong Li,Yong Ji,Zhihong Shi,Zhichao Chen,Xiaodan Wang,Wenzheng Hu

doi:10.3389/fnagi.2021.724990

Abstract

Background: Elevated plasma total homocysteine (tHcy) level, a known risk factor for vascular disease, is reported to be an independent risk factor for cognitive impairment and Alzheimer’s disease (AD) in most studies. tHcy may also be associated with dementia with Lewy bodies (DLB).Objective: To investigate the association between plasma tHcy levels and DLB or AD.Methods: This is a case-control study including 132 DLB patients, 264 AD patients, and 295 age-matched healthy controls. We used multivariate logistic regression model to analyze the data with adjustments for confounding variables.Results: The highest tHcy tertile (>13.9 μmol/L) was significantly independently associated with DLB [adjusted odds ratio (OR): 4.65, 95% confidence interval (CI): 1.95–11.10, P = 0.001] and AD (adjusted OR: 1.82, 95% CI: 1.02–3.23, P = 0.041) compared to the lowest tertile (<10.7 μmol/L). The cumulative frequency plots showed a shift in the distribution of the tHcy concentrations to higher values in patients with DLB compared to AD. The mean tHcy levels were stable and not altered by the duration of cognitive impairment prior to the collection of blood samples from DLB patients.Conclusion: Elevated plasma tHcy levels were independently associated with DLB, and the association was stronger for DLB than for AD. The lack of a relationship between tHcy levels and symptom duration may refute these observed associations being a consequence of DLB, and future longitudinal studies will be required to confirm whether tHcy plays a causative role in DLB.

Highlights

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia in older people following Alzheimer’s disease (AD; Walker et al, 2015)
B vitamins including vitamin B12 and folate are essential factors involved in nucleotide synthesis, one-carbon metabolism, and DNA-methylation; they are necessary for the well-being and normal function of the brain and have been linked to cognitive impairment, AD, and dementia, though results have been inconclusive far (Clarke et al, 1998; Ravaglia et al, 2005; Gillette Guyonnet et al, 2007; Pusceddu et al, 2017; Rabensteiner et al, 2020; Hoffmann et al, 2021)
212 individuals were excluded for the following reasons: their plasma total homocysteine (tHcy), serum folate, and vitamin B12 concentrations were unavailable (n = 102); they were suffering from malnutrition and vitamin B12 deficiency; they were treated with folate or vitamin B12 in the last 3 months (n = 89); or their clinical details were absent (n = 21)

Summary

Introduction

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia in older people following Alzheimer’s disease (AD; Walker et al, 2015). It is important to identify the treatable risk factors for cognitive dysfunction and the core symptoms of DLB to reduce the prevalence and the caregiver burdens of this disease. Elevated total homocysteine (tHcy) levels are a risk factor for vascular diseases and for cognitive impairment and AD (Clarke et al, 1991; Seshadri et al, 2002; Ravaglia et al, 2005). On the basis of these studies, it has been hypothesized that elevated plasma tHcy levels, a risk for vascular disease and AD, may play a role in DLB. Elevated plasma total homocysteine (tHcy) level, a known risk factor for vascular disease, is reported to be an independent risk factor for cognitive impairment and Alzheimer’s disease (AD) in most studies. Elevated plasma total homocysteine (tHcy) level, a known risk factor for vascular disease, is reported to be an independent risk factor for cognitive impairment and Alzheimer’s disease (AD) in most studies. tHcy may be associated with dementia with Lewy bodies (DLB)

Methods

Results

Conclusion