Impact of homocysteine on cortical perfusion and cognitive decline in mild <scp>A</scp>lzheimer's dementia

Huang, Chao‐Cheng; Chang, Wen‐Cheng; Huang, Sheng-Yao; Lui, Chun‐Chung; Chen, N.-C.; Chang, Ya Ting; Lee, C.-C.; Chang, Chiung Chih; Chang, Alice Y.W.

doi:10.1111/ene.12159

Cited by 33 publications

(38 citation statements)

References 36 publications

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“…The Mini-Mental State Examination (MMSE) [43] and the Cognitive Abilities Screening Instrument (CASI) [44] total scores were used as a global assessment of cognitive function. Attention, verbal fluency, abstract thinking, and mental manipulation sub-domain scores of the CASI were used to assess executive function test (EFT) [22], while the non-executive domains included orientation, short- and long-term memory, language ability, and drawing.…”

Section: Methodsmentioning

confidence: 99%

“…The presence of WMHs in AD may reflect multiple physiological and pathological changes such as breakdown of the blood-brain barrier [20], impaired cerebral auto-regulation [21], vasculopathies, and inflammation [22, 23]. In healthy adults, homozygotes for the IL-1 beta -511 T allele have been associated with increased inflammatory responses and larger WMHs than the other two genotypic combinations [24].…”

Section: Introductionmentioning

confidence: 99%

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Genetic effect of interleukin-1 beta (C-511T) polymorphism on the structural covariance network and white matter integrity in Alzheimer’s disease

Huang

Hsu

Tsai

et al. 2017

J Neuroinflammation

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BackgroundInflammatory processes play a pivotal role in the degenerative process of Alzheimer’s disease. In humans, a biallelic (C/T) polymorphism in the promoter region (position-511) (rs16944) of the interleukin-1 beta gene has been significantly associated with differences in the secretory capacity of interleukin-1 beta. In this study, we investigated whether this functional polymorphism mediates the brain networks in patients with Alzheimer’s disease.MethodsWe enrolled a total of 135 patients with Alzheimer’s disease (65 males, 70 females), and investigated their gray matter structural covariance networks using 3D T1 magnetic resonance imaging and their white matter macro-structural integrities using fractional anisotropy. The patients were classified into two genotype groups: C-carriers (n = 108) and TT-carriers (n = 27), and the structural covariance networks were constructed using seed-based analysis focusing on the default mode network medial temporal or dorsal medial subsystem, salience network and executive control network. Neurobehavioral scores were used as the major outcome factors for clinical correlations.ResultsThere were no differences between the two genotype groups in the cognitive test scores, seed, or peak cluster volumes and white matter fractional anisotropy. The covariance strength showing C-carriers > TT-carriers was the entorhinal-cingulum axis. There were two peak clusters (Brodmann 6 and 10) in the salience network and four peak clusters (superior prefrontal, precentral, fusiform, and temporal) in the executive control network that showed C-carriers < TT-carriers in covariance strength. The salience network and executive control network peak clusters in the TT group and the default mode network peak clusters in the C-carriers strongly predicted the cognitive test scores.ConclusionsInterleukin-1 beta C-511 T polymorphism modulates the structural covariance strength on the anterior brain network and entorhinal-interconnected network which were independent of the white matter tract integrity. Depending on the specific C-511 T genotype, different network clusters could predict the cognitive tests.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0791-z) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genetic effect of interleukin-1 beta (C-511T) polymorphism on the structural covariance network and white matter integrity in Alzheimer’s disease

Huang

Hsu

Tsai

et al. 2017

J Neuroinflammation

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“…The 30-item MMSE [63] and cognitive ability-screening instrument (CASI) [64] total scores were used as a global assessment of cognitive function. Attention, verbal fluency, abstract thinking, and mental manipulation sub-domain scores of the CASI were used to assess executive function test (EFT) [65], while the non-executive domains included orientation, short- and long-term memory, language ability, and drawing. We used the neuropsychiatric inventory (NPI) to evaluate changes in behavior.…”

Section: Methodsmentioning

confidence: 99%

Dose-dependent genotype effects of BDNF Val66Met polymorphism on default mode network in early stage Alzheimer's disease

et al. 2016

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In humans, brain-derived neurotrophic factor (BDNF) has been shown to play a pivotal role in neurocognition, and its gene contains a functional polymorphism (Val66Met) that may explain individual differences in brain volume and memory-related activity.In this study, we enrolled 186 Alzheimer's disease (AD) patients who underwent 3D T1 magnetic resonance imaging, and explored the gray matter (GM) structural covariance networks (SCN). The patients were divided into three groups according to their genotype: Met/Met (n = 45), Val/Met (n = 86) and Val/Val (n = 55). Seed-based analysis was performed focusing on four SCN networks. Neurobehavioral scores served as the major outcome factor.Only peak cluster volumes of default mode medial temporal lobe network showed significant genotype interactions, of which the interconnected peak clusters showed dose-dependent genotype effects. There were also significant correlations between the cognitive test scores and interconnected-cluster volumes, especially in the orbitofrontal cortex.These findings support the hypothesis that BDNF rs6265 polymorphisms modulate entorhinal cortex-interconnected clusters and the valine allele was associated with stronger structural covariance patterns that determined the cognitive outcomes.

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“…The Mini-Mental State Examination (MMSE) 15 and Cognitive Ability Screening Instrument (CASI) 11 were used to assess the general intellectual function. Nine subscores from CASI were analyzed.…”

Section: Methodsmentioning

confidence: 99%

“…11 Fourteen patients with a CDR score of 0.5 were defined as group 1, representing mild DLB stage, and 11 patients with CDR score of 1 or 2 were defined as group 2, as the dementia stage.…”

Section: Patient Grouping According To the Cognitive Functional Severitymentioning

confidence: 99%

Cortical Metabolic and Nigrostriatal Abnormalities Associated With Clinical Stage-Specific Dementia With Lewy Bodies

Huang¹,

Chang²,

Lui³

et al. 2015

Clinical Nuclear Medicine

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Impact of homocysteine on cortical perfusion and cognitive decline in mild Alzheimer's dementia

Abstract: Cognitive performance in mild AD can be reflected by hypo-perfusion of the temporo-parietal region while frontal hypo-perfusion may be mediated by tHcy. tHcy level is an independent risk factor for rapid cognitive decline, especially in the executive function.

Cited by 33 publications

References 36 publications

Genetic effect of interleukin-1 beta (C-511T) polymorphism on the structural covariance network and white matter integrity in Alzheimer’s disease

Genetic effect of interleukin-1 beta (C-511T) polymorphism on the structural covariance network and white matter integrity in Alzheimer’s disease

Dose-dependent genotype effects of BDNF Val66Met polymorphism on default mode network in early stage Alzheimer's disease

Cortical Metabolic and Nigrostriatal Abnormalities Associated With Clinical Stage-Specific Dementia With Lewy Bodies

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