Folate vascular dementia

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Its clinical manifestations include a progressive loss of memory and other cognitive domains, as well as brain atrophy. An elevated homocysteine level (>15 µmol/L), known as hyperhomocysteinemia, is also an attributing risk factor for AD, vascular pathologies, and brain atrophy. Neuroimaging studies including T2-weighted magnetic resonance imaging (MRI) scans revealed white matter hyperintensities (WMHs) in the periventricular and deep white matter, enlarged ventricles, widened sulci, and decreased white matter mass, which are features of aging, as well as cerebrovascular changes...

Previous researchers have tried to explore the association between folate/folic acid intake and dementia incidence, but the results remain controversial. We evaluated the associations of folate/folic acid supplementation alone and in combination with other B vitamins on dementia risk and brain structure. A total of 466,224 UK Biobank participants were investigated. Cox proportional hazards models were used to assess the associations between folate/folic acid supplementation status and the risk of Alzheimer's disease (AD) and vascular dementia (VD)...

BACKGROUND: Cobalamin (Cbl) and folate are common supplements clinicians prescribe as an adjuvant therapy for dementia patients, on the presumption of their neurotrophic and/or homocysteine (Hcy) lowering effect. However, the treatment efficacy has been found mixed and the effects of Cbl/folate/Hcy on the human brain remain to be elucidated. OBJECTIVE: To explore the neurovascular correlates of Cbl/folate/Hcy in Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SIVD)...

The biologically important amino acid homocysteine links sulfur, methionine, and one-carbon metabolism. This review describes its initial discovery, the identification of the clinical condition of "homocystinuria" and the recognition of its close relationship to folate and vitamin B12 metabolism. It discusses the history behind its current association with diverse diseases including neural tube defects, cardio- and cerebrovascular disease and, more recently, dementia and Alzheimer's Disease. It also explores current controversies and considers potential future research directions...

BACKGROUND: Although elevated levels of homocysteine (Hcy) are associated with cognitive impairment and dementia, the relevance of Hcy, vitamin B12, and folate levels to subtypes of dementia are still unknown. OBJECTIVE: To investigate the changes of Hcy, vitamin B12, and folate levels in mild cognitive impairment (MCI) and subtypes of dementia including Alzheimer's disease (AD), vascular dementia (VaD), frontotemporal dementia (FTD), and Lewy body dementia (LBD), and their relationships with cognitive function and magnetic resonance imaging (MRI) markers...

Vascular contributions to cognitive impairment and dementia (VCID) particularly Alzheimer's disease and related dementias (ADRDs) are increasing; however, mechanisms driving cerebrovascular decline are poorly understood. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in the folate and methionine cycles. Variants in MTHFR, notably 677 C   > T, are associated with dementias, but no mouse model existed to identify mechanisms by which MTHFR677C > T increases risk. Therefore, MODEL-AD created a novel knock-in (KI) strain carrying the Mthfr677C > T allele on the C57BL/6J background ( Mthfr677C > T ) to characterize morphology and function perturbed by the variant...

NAFLD is the most common cause of abnormality in liver function tests. NAFLD is considered a potential cardiovascular risk factor and is linked to cardiovascular risk factors such as obesity, hypertension, type 2 diabetes, and dyslipidemia. Few previous studies have investigated whether NAFLD could be independently associated with cognitive impairment. The current study aims to find a possible role of NAFLD in the development of subcortical vascular dementia (sVaD). We considered NAFLD as a possible independent vascular risk factor or, considering its metabolic role, associated with other commonly accepted sVaD risk factors, i...

Frailty is a geriatric syndrome that combines physiological decline, disruptions of homeostatic mechanisms across multiple physiologic systems and thus, strong vulnerability to further pathological stress. Previously, we provided the first evidence that increased risk of poor health outcomes, as quantified by a frailty index, is associated with an alteration of the central nervous system (CNS) biomechanical response to blood pulsatility. In this study, we explored correlation between fourteen biological parameters, the CNS elastance coefficient and frailty index...

BACKGROUND: Vascular contributions to cognitive impairment and dementia (VCID) are a major cause of dementia worldwide. Studies have shown Apolipoprotein E (ApoE) genotype is a risk factor for VCID in humans. Our lab has previously demonstrated recapitulation of aspects of human VCID using a hyperhomocysteinemia (HHcy)-inducing dietary model in mice. The goal of this study was to assess the impact of ApoE genotype on the vascular pathology and neuroinflammatory changes generated by the induction of HHcy...

BACKGROUND: Vascular contributions to cognitive impairment and dementia (VCID) are one of the leading causes of dementia. High levels of plasma homocysteine or hyperhomocysteinemia has been characterized as a risk factor for VCID however, the mechanism underlying this connection remains elusive. I hypothesize that hyperhomocysteinemia initiates a pro-inflammatory cascade that increases the activity of matrix metalloproteinase 9 (MMP9) causing perivascular astrocytes to dissociate from their vessels, leading to blood brain barrier dysfunction and the progression toward VCID pathology...

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...

Background: Recent studies have reported that homocysteine (Hcy) may play a vital role in the pathogenesis of vascular dementia (VaD) and Alzheimer's disease (AD). Our study explored the relationship between the plasma Hcy and folate levels and the risk of dementia. Methods: We searched Embase, PubMed, and Web of Science for published literature, including case-control studies and prospective cohort studies, and performed a systematic analysis. Results: The results of our meta-analysis, consisting of case-control studies, showed higher levels of Hcy and lower levels of folate in dementia, AD, and VaD patients than those in non-demented controls (for dementia: SMD = 0...

BACKGROUND: Alzheimer's disease (AD) may be a vascular disorder with neurodegenerative consequences opening possibility of preventing AD by targeting vascular risk factors including homocysteine. OBJECTIVE: The study aims were to assess homocysteine distribution in different forms and severity of cognitive impairment (CogI) [mild cognitive impairment (MCI), probable AD (Prob-AD), possible AD (Poss-AD), and vascular dementia (VaD)] and in NoCogI, and to estimate possible association between hyperhomocysteinemia levels with functional deficit severity and psychobehavioral complications...

BACKGROUND: Although it is known that the nutritional status among elderly persons and, in particular, patients with dementia, is compromised, malnutrition that results in insufficient uptake of several vitamins is often not diagnosed. OBJECTIVE: An elevated homocysteine level is a known strong risk factor for vascular dementia (VaD) and Alzheimer's disease (AD). Several B vitamins are involved in the metabolism of homocysteine. Therefore, we investigated the serum levels of vitamin B1, vitamin B6, folate, and vitamin B12 in 97 patients with mild cognitive impairment (MCI) or different forms of dementia and 54 elderly control persons without dementia...

We report a case of a 77 years old patient who was admitted to our memory clinic because of progressive gait impairment and amnestic cognitive decline associated with extrapyramidal symptoms and behavioral changes. The clinical picture was consistent with a possible diagnosis of Alzheimer's Disease associated with parkinsonian symptoms or with a Parkinson Plus syndrome. After a complete investigation, she was found to have a high plasma level of homocysteine due to homozygous methylene-tetrahydrofolate reductase (MTHFR) gene C665 T polymorphism, cognitive and motor impairment were associated with a severe cortical atrophy and mild subcortical vascular disease...

OBJECTIVES: There are a few studies showing how nutritional parameters are affected according to dementia subtypes. The aim of this study was to compare the parameters characterizing nutritional status and micronutrient levels according to different dementia subtypes. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Four hundred forty outpatients aged 65 years or older. MEASURES: Newly diagnosed patients with dementia, who underwent comprehensive geriatric assessment (CGA), were retrospectively evaluated...

OBJECTIVES: Nutritional insufficiencies have been associated with cognitive impairment. Understanding whether nutritional biomarker levels are associated with clinical progression could help to design dietary intervention trials. This longitudinal study examined a panel of nutritional biomarkers in relation to clinical progression in patients with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). DESIGN, SETTING AND PARTICIPANTS: We included 299 patients without dementia (n = 149 SCD; age 61 ± 10 years, female 44%, n = 150 MCI; age 66 ± 8 years, female 38%)...

BACKGROUND: Vascular contributions to cognitive impairment and dementia (VCID) are the second leading cause of dementia behind only Alzheimer's disease (AD); however, VCID is commonly found as a co-morbidity with sporadic AD. We have previously established a mouse model of VCID by inducing hyperhomocysteinemia in both wild-type and amyloid depositing mice. While we have shown the time course of neuropathological events in the wild-type mice with hyperhomocysteinemia, the effect of amyloid deposition on this time course remains unknown; therefore, in this study, we determined the time course of neuropathological changes in our mouse model of hyperhomocysteinemia-induced VCID in amyloid depositing mice...

The gaseous physiological modulator hydrogen sulfide (H2 S) has recently been shown to exert a variety of neuroprotective effects. In particular, the treatment of transgenic mouse models of Alzheimer's disease (AD) with agents that release H2 S aids preservation of cognitive function, suppresses brain production of amyloid beta, and decreases tau phosphorylation. The possible physiological relevance of these findings is suggested by the finding that brain and plasma levels of H2 S are markedly lower in AD patients than matched controls...

The pathomechanisms that associate a deficit in folate and/or vitamin B12 and the subsequent hyperhomocysteinemia with pathological brain ageing are unclear. We investigated the homocysteinylation of microtubule-associated proteins (MAPs) in brains of patients with Alzheimer's disease or vascular dementia, and in rats depleted in folate and vitamin B12, Cd320 KO mice with selective B12 brain deficiency and H19-7 neuroprogenitors lacking folate. Compared with controls, N-homocysteinylated tau and MAP1 were increased and accumulated in protein aggregates and tangles in the cortex, hippocampus and cerebellum of patients and animals...