Association Between Homocysteine and Vitamin Levels in Demented Patients

Hoffmann, Jessica; Busse, Stefan; Hoff, F; Borucki, Katrin; Frodl, Thomas; Busse, Mandy

doi:10.3233/jad-201481

Cited by 9 publications

(14 citation statements)

References 79 publications

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“…Results of the previous studies (Luchsinger et al, 2004;Ma et al, 2017) were inconsistent, but the overall results showed that elevated tHcy levels were associated with an increased risk of cognitive impairment, vascular dementia, and AD (Clarke et al, 1991;Seshadri et al, 2002;Ravaglia et al, 2005). The folate and vitamin B12 deficiency might impair methylation reactions to be involved in the pathogenesis of AD (Selhub et al, 1993;Hoffmann et al, 2021). In addition, folate and vitamin B12 are important mediators of tHcy levels, indirectly correlated with AD (Selhub et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, folate and vitamin B12 are important mediators of tHcy levels, indirectly correlated with AD (Selhub et al, 1993). Accordingly, some (Clarke et al, 1998;Ravaglia et al, 2005;Hoffmann et al, 2021), but not all studies (Ma et al, 2017;Rabensteiner et al, 2020) have shown that low levels of folate and vitamin B12 were associated with AD. More recent studies have specifically addressed the association between a significant elevation of tHcy levels and neurodegenerative diseases including Parkinson's disease (PD) and multiple system atrophy (MSA; Zhang et al, 2015;Sleeman et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…B vitamins including vitamin B12 and folate are essential factors involved in nucleotide synthesis, one-carbon metabolism, and DNA-methylation; they are also 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 thus 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). Homocysteine, the cytotoxic product of the methionine cycle, is a sensitive marker of folate and vitamin B12 status and may have a direct toxic effect on both blood vessels and neurons (Welch and Loscalzo, 1998;Ho et al, 2002;Refsum et al, 2004;Pusceddu et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Liu²,

Chen³

et al. 2021

Front. Aging Neurosci.

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Zhang

Liu²,

Chen³

et al. 2021

Front. Aging Neurosci.

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“…In another study [ 116 ], the HCy levels were measured in nine FTD and nine LBD, and no significant different was found, in either group, with respect to healthy controls.…”

Section: Homocysteine and Degenerative Brain Diseasesmentioning

confidence: 96%

Homocysteine, Cognitive Functions, and Degenerative Dementias: State of the Art

et al. 2022

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There is strong evidence that homocysteine is a risk factor not only for cerebrovascular diseases but also for degenerative dementias. A recent consensus statement renewed the importance and the role of high levels of homocysteine in cognitive decline in several forms of degenerative dementia, such as Alzheimer’s disease. Although the molecular mechanisms by which homocysteine causes cell dysfunction are known, both the impact of homocysteine on specific cognitive functions and the relationship between homocysteine level and non-Alzheimer dementias have been poorly investigated. Most of the studies addressing the impact of hyperhomocysteinemia on dementias have not examined the profile of performance across different cognitive domains, and have only relied on screening tests, which provide a very general and coarse-grained picture of the cognitive status of the patients. Yet, trying to understand whether hyperhomocysteinemia is associated with the impairment of specific cognitive functions would be crucial, as it would be, in parallel, learning whether some brain circuits are particularly susceptible to the damage caused by hyperhomocysteinemia. These steps would allow one to (i) understand the actual role of homocysteine in the pathogenesis of cognitive decline and (ii) improve the diagnostic accuracy, differential diagnosis and prognostic implications. This review is aimed at exploring and revising the state of the art of these two strictly related domains. Suggestions for future research are provided.

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“…Alternatively which is essential for of S-adenosyl-methionine (SAM) synthesis, and required for methylation of DNA/RNA and proteins ( 15 ), its impairment caused hypermethylated redox-related genes (NUDT15 and TXNRD1). Independently, B vitamins deficiency also induced cerebrovascular dysfunction, activation of tau kinases and enhanced Aβ metabolism contributed to AD development ( 16 – 18 ). David Smith and colleagues' studies also indicated a possible pathogenetic role of B vitamins (B12, Folate) in mild cognitive impairment, as B vitamins therapy could abrogate effects of iron-associated brain atrophy rate ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

Association Between Blood Biochemical Factors Contributing to Cognitive Decline and B Vitamins in Patients With Alzheimer's Disease

et al. 2022

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BackgroundMalnutrition, metabolism stress, inflammation, peripheral organs dysfunction, and B vitamins deficiency significantly contribute to the progression and mortality of Alzheimer's disease (AD). However, it is unclear which blood biochemical indicators are most closely related to cognitive decline and B vitamins deficiency (thiamine, folate, vitamin B12) in patients with AD.MethodsThis was a cross-sectional study of 206 AD patients recruited from six hospitals in China. Thiamine diphosphate (TDP), the bioactive form of thiamine, was measured by high-performance liquid chromatography fluoroscopy (HPLC) at a single center. Levels of biochemical indicators (except TDP) were measured by regular and standard laboratory tests in each hospital. Pearson's rank correlation analysis was used to assess relationships between B vitamins and biochemical indicators. T-test was used to compare the difference between ApoE ε4 and non-ApoE ε4 groups. Differences were considered statistically significant as P < 0.05.ResultsAmong the biochemical results, in AD population, malnutrition indicators (erythrocyte, hemoglobin, serum albumin, and total protein) were most significantly associated with cognitive function, as was free triiodothyronine (FT3) levels which had been observed in previous study. Malnutrition and FT3 levels depend on age but not apolipoprotein E (ApoE) genotype. Meanwhile, Among the B vitamins, TDP was the most significantly associated with malnutrition indicators and FT3.ConclusionOur results indicated that TDP reduction could be a modifiable risk factor for malnutrition and FT3 that contributed to cognitive decline in AD patients. Correcting thiamine metabolism could serve as an optional therapy target for AD treatment.

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Association Between Homocysteine and Vitamin Levels in Demented Patients

Cited by 9 publications

References 79 publications

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

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

Homocysteine, Cognitive Functions, and Degenerative Dementias: State of the Art

Association Between Blood Biochemical Factors Contributing to Cognitive Decline and B Vitamins in Patients With Alzheimer's Disease

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