Homocysteine and Cognitive Impairment

Sala, Isabel; Sánchez-Saudinós, María Belén; Molina‐Porcel, Laura; Lázaro, Estela; Gich, Ignasi; Clarimón, Jordi; Blanco‐Vaca, Francisco; Blesa, Rafael; Gómez-Isla, Teresa; Lleó, Alberto

doi:10.1159/000173710

Cited by 40 publications

(14 citation statements)

References 108 publications

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“…In the present study, we have examined the relation between plasma tHcy, its determinants and MMSE score in consecutively enrolled elderly patients with dementia or other psychogeriatric diseases. Similar types of patients have been studied by Lehmann et al [3] , Quadri et al [4] and Sala et al [48] . These studies, however, have not investigated the influence of plasma tHcy determinants on the relation between plasma tHcy and cognition.…”

Section: Discussionmentioning

confidence: 57%

“…Age was an even more important predictor for MMSE score than the plasma tHcy concentration itself. Several other studies [28,48,49] in elderly community-dwelling subjects or in patients with dementia have reported that age is an important predictor for cognitive functions. Thus, in the present study, plasma tHcy concentration in elderly patients with dementia or other psychogeriatric diseases only showed a modest relationship with MMSE scores (predictive value about 5%).…”

Section: Discussionmentioning

confidence: 97%

“…These studies, however, have not investigated the influence of plasma tHcy determinants on the relation between plasma tHcy and cognition. Lehmann et al [3] and Quadri et al [4] reported that plasma tHcy concentration was related to MMSE score and Sala et al [48] that plasma tHcy concentration was related to visuoconstructional performance. In the present study, plasma tHcy was related to cognitive function as measured by MMSE score in all patients as well as in different subgroups of patients.…”

Section: Discussionmentioning

confidence: 99%

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Plasma Homocysteine and Cognition in Elderly Patients with Dementia or Other Psychogeriatric Diseases

Nilsson¹,

Gustafson²,

Hultberg

2010

Dement Geriatr Cogn Disord

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Background: Total plasma homocysteine (tHcy) concentration is elevated in elderly patients with mental illness, and patients with vascular disease have higher plasma tHcy concentrations than patients without vascular disease. Increasing evidence indicates that vascular risk factors play a role in the development of cognitive impairment. Method: We have investigated the relation between plasma tHcy, its determinants and cognition, measured as MMSE, in 448 consecutively enrolled patients with dementia or other psychogeriatric diseases. Results: Multiple regression analyses showed that plasma tHcy was related to cognitive function in all patients as well as in demented and non-demented patients. The apparent close relationship between plasma tHcy and cognition was mainly dependent on its determinant age, whereas the other determinants of plasma tHcy exhibited a limited influence on the relation between plasma tHcy and cognition. Plasma tHcy has its own, albeit modest, relationship to cognitive function (predictive value about 5%). Conclusion: Plasma tHcy itself seems to play a minor role in cognitive impairment in patients with dementia or other psychogeriatric diseases. When investigating the relation between plasma tHcy and cognition, it is important to consider the distribution of the main determinants of plasma tHcy and to correct plasma tHcy for these variables.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Plasma Homocysteine and Cognition in Elderly Patients with Dementia or Other Psychogeriatric Diseases

Nilsson¹,

Gustafson²,

Hultberg

2010

Dement Geriatr Cogn Disord

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“…Experimental procedures were approved by the corresponding Ethics Committees. Patients underwent an extensive neuropsychological evaluation 20 including Mini-Mental State Examination scores of 16–26. All participants gave written consent for the study.…”

Section: Methodsmentioning

confidence: 99%

Loss of serum IGF-I input to the brain as an early biomarker of disease onset in Alzheimer mice

et al. 2013

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Circulating insulin-like growth factor I (IGF-I) enters the brain and promotes clearance of amyloid peptides known to accumulate in Alzheimer's disease (AD) brains. Both patients and mouse models of AD show decreased level of circulating IGF-I enter the brain as evidenced by a lower ratio of cerebrospinal fluid/plasma IGF-I. Importantly, in presymptomatic AD mice this reduction is already manifested as a decreased brain input of serum IGF-I in response to environmental enrichment. To explore a potential diagnostic use of this early loss of IGF-I input, we monitored electrocorticogram (ECG) responses to systemic IGF-I in mice. Whereas control mice showed enhanced ECG activity after IGF-I, presymptomatic AD mice showed blunted ECG responses. Because nonhuman primates showed identically enhanced electroencephalogram (EEG) activity in response to systemic IGF-I, loss of the EEG signature of serum IGF-I may be exploited as a disease biomarker in AD patients.

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“…The elevated levels of homocysteine (Hcy) known as hyperhomocysteinemia (HHcy) cause vascular dementia, cerebral vascular complication and retardation (Nilsson et al ., 2008; Sala et al ., 2008; Davis et al ., 2009; Kivipelto et al ., 2009; Regalado Dona et al, 2009). Hyperhomocysteinemia causes constrictive vascular remodelling by increased collagen deposition in the vessel wall (Guo et al ., 2008).…”

Section: Introductionmentioning

confidence: 99%

X-ray imaging of differential vascular density in MMP-9−/−, PAR-1−/+, hyperhomocysteinemic (CBS−/+) and diabetic (Ins2−/+) mice

Givvimani

Sen

Tyagi

et al. 2010

Archives of Physiology and Biochemistry

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Although protease activated receptor-1 (PAR-1) and matrix metalloproteinase-9 (MMP-9) play significant role in vascular remodelling in hyperhomocysteinemia (HHcy due to cystathionine beta synthase deficiency, CBS−/+) and diabetes, mechanism remains nebulous. We hypothesized that differential vascular density and remodelling in different vascular beds in HHcy and diabetes were responsible for an adaptive metabolic homeostasis during the pathogenesis. To test this hypothesis, vascular density in mice lacking PAR-1, MMP-9, CBS and Insulin-2 gene mutant (Ins2−/+, Akita) was measured and compared with wild type (WT, C57BL/6J) mice. The vascular density was detected by x-ray angiography using KODAK 4000 MM image station, using barium sulphate as contrasting agent. The % vascular density in the hearts of WT, CBS−/+ (HHcy), MMP-9−/−, PAR-1−/+ and Ins2−/+ (type-1 diabetes) was 100 ± 2.8, 85 ± 3.3, 90 ± 3.3, 95 ± 3.8 and 73 ± 1.7, respectively. The vascular density in CBS−/+ and Akita hearts decreased while it was increased in lungs of CBS−/+ and MMP-9−/−. There was decreased vascular density in liver and kidney of Akita mice. Vascular density in brain, kidney and mesentery was decreased in CBS−/+ mice. These findings support the notation that metabolic derangement in diabetes and HHcy causes the chronic decline and/or rarefaction in vascular density.

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Homocysteine and Cognitive Impairment

Cited by 40 publications

References 108 publications

Plasma Homocysteine and Cognition in Elderly Patients with Dementia or Other Psychogeriatric Diseases

Plasma Homocysteine and Cognition in Elderly Patients with Dementia or Other Psychogeriatric Diseases

Loss of serum IGF-I input to the brain as an early biomarker of disease onset in Alzheimer mice

X-ray imaging of differential vascular density in MMP-9−/−, PAR-1−/+, hyperhomocysteinemic (CBS−/+) and diabetic (Ins2−/+) mice

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