Dementia

Gale, Seth A; Acar, Diler; Daffner, Kirk R.

doi:10.1016/j.amjmed.2018.01.022

Cited by 460 publications

(398 citation statements)

References 77 publications

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“…Indeed, the number of people with AD in the UK is expected to nearly double by 2040 to 1.6 million patients, with the total cost of treating dementia expected to reach £94.1 bn by 2040 [2]. AD is an irreversible neurodegenerative disorder in which there is a progressive and continual deterioration in cognitive function [3]. Initial symptoms typically include confusion, repetitive questioning and…”

Section: Introductionmentioning

confidence: 99%

Comparative Kinetics of Acetyl- and Butyryl-Cholinesterase Inhibition by Green Tea Catechins|Relevance to the Symptomatic Treatment of Alzheimer’s Disease

Okello¹,

Mather

2020

Nutrients

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Alzheimer's disease (AD) is characterised by the apoptosis of cholinergic neurons and the consequent attenuation of acetylcholine mediated neurotransmission, resulting in neurodegeneration. Acetyl-cholinesterase (AChE) and butyryl-cholinesterase (BuChE) are attractive therapeutic targets in the treatment of AD since inhibition of these enzymes can be used to restore synaptic concentrations of acetylcholine. Whilst inhibitors for these enzymes such as galantamine and rivastigmine have been approved for use, none are able to halt the progression of AD and are responsible for the production of troublesome side-effects. Efficacious cholinesterase inhibitors have been isolated from natural plant-based compounds with many demonstrating additional benefits beyond cholinesterase inhibition, such as antioxidation and anti-inflammation, which are key parts of AD pathology. In this study, five natural flavan-3-ol (catechin) compounds: ((-)-epicatechin (EC), catechin, (-)-epicatechin-3-gallate (ECG),) (-)-epigallocatechin (EGC), (-)-epigallocatechin-3-gallate (EGCG), isolated from green tea, were screened for their cholinesterase inhibitory activity using the Ellman assay. The kinetics of inhibition was determined using reciprocal Lineweaver-Burk plots. EGCG was the only compound found to produce statistically significant, competitive inhibition, of both AChE (p < 0.01) and BuChE (p < 0.01) with IC50 values of 0.0148 µmol/mL and 0.0251 µmol/mL respectively. These results, combined with previously identified antioxidative and anti-inflammatory properties, highlight the potential use of EGCG in the treatment of AD, provided it can be delivered to cholinergic neurons in therapeutic concentrations. Further testing of EGCG in vivo is recommended to fully characterise the pharmacokinetic properties, optimal method of administration and efficacy of this novel plant-based compound.

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Section: Introductionmentioning

confidence: 99%

Comparative Kinetics of Acetyl- and Butyryl-Cholinesterase Inhibition by Green Tea Catechins|Relevance to the Symptomatic Treatment of Alzheimer’s Disease

Okello¹,

Mather

2020

Nutrients

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“…2A) is known to be one of the regions of deterioration in early-stage AD. The deterioration was associated with dysfunctions in memory, navigation and cognition, often observed in AD [20]. To investigate the possible mechanism of how beta-amyloid plaques can affect the activity and function of this region, a biophysical computational model of the hippocampal septal neuronal circuit model was modeled and simulated ( Fig.…”

Section: Probabilistic / Statistical Analysis and Modellingmentioning

confidence: 99%

“…Various genes are currently thought to be associated with these different AD types. Mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1) and presenilin-2 (PSEN2) are associated with familial AD while Apolipoprotein E (ApoE) gene has been linked to the sporadic type [20]. Other types of dementia include vascular dementia, frontotemporal dementia, Lewy body dementia, Huntington's disease, and Creutzfeldt-Jakob disease [20].…”

Section: Introductionmentioning

confidence: 99%

“…Mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1) and presenilin-2 (PSEN2) are associated with familial AD while Apolipoprotein E (ApoE) gene has been linked to the sporadic type [20]. Other types of dementia include vascular dementia, frontotemporal dementia, Lewy body dementia, Huntington's disease, and Creutzfeldt-Jakob disease [20]. The intermediate stage between healthy and AD is labelled mild cognitive impairment (MCI) [20].…”

Section: Introductionmentioning

confidence: 99%

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Computational Neurology: Computational Modeling Approaches in Dementia

et al. 2021

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Dementia is a collection of symptoms associated with impaired cognition and impedes everyday normal functioning. Dementia, with Alzheimer's disease constituting its most common type, is highly complex in terms of etiology and pathophysiology. A more quantitative or computational attitude towards dementia research, or more generally in neurology, is becoming necessary -Computational Neurology. We provide a focused review of some computational approaches that have been developed and applied to the study of dementia, particularly Alzheimer's disease. Both mechanistic modeling and data-driven, including AI or machine learning, approaches are discussed. Linkage to clinical decision support systems for dementia diagnosis will also be discussed.

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“…Major events, biological and genetic factors through the lifespan obviously contribute to the heterogeneity observed in samples of older individuals [2,3,12], both regarding the rate of structural brain changes [5], the rate and extent of cognitive changes [6] and in brain-cognition relations [7,12]. In the severe end of the distribution, the most extensive parenchyma loss is associated with dementia, a syndrome defined by a severe decline in cognitive function [8]. On the other end of the scale we find so-called ”superagers” [9].…”

Section: Introductionmentioning

confidence: 99%

Lateral ventricle volume trajectories predict response inhibition in older age - a longitudinal brain imaging and machine learning approach

Lundervold

Vik

Lundervold

2018

Preprint

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Objective: In a three-wave ∼6 yrs longitudinal study we investigated if expansion of lateral ventricle (LV) volumes (regarded as a proxy for brain parenchyma loss) predicts performance on a test of response inhibition. Participants and Methods: Anatomical trajectories of left (LH) and right (RH) lateral ventricle volumes across the three study-waves were quantified using the Longitudinal Stream in Freesurfer 5.3 and modelled using a linear mixed-effects (LME) algorithm. All participants (N = 74, mean age 60.7 yrs at inclusion, 48 females) performed the Color-Word Interference Test (CWIT). Response time on the third condition was used as a measure of response inhibition (RI) and divided into three classes (fast, medium and slow). The Extreme Gradient Boosting (XGBoost) algorithm was used for calculating the relative importance of selected LV volume features from the LME model in predicting RI class. Finally, the two most important extracted features were fed into a 10-fold cross-validation framework, estimating the accuracy, precision and recall of the RI class prediction. Results: Four LME based features were selected to characterize LV volume trajectories: steepness of LV volume change and the LV volume at the time of inclusion, each from the right and left hemisphere. The XGBoost procedure selected the steepness measure from the right and the volume at inclusion from the left hemisphere as the two most important features to predict RI performance. The 10-fold cross validation procedure showed a recall, precision and accuracy score (.40 -.50) that were clearly above chance level. Conclusion: Measures of the LV volume trajectories gave a fairly good prediction of response inhibition performance, confirming the role of LV volume as a biomarker of cognitive function in older adults. Future studies should investigate the value of the lateral ventricle volume trajectories as predictors of cognitive preservation or decline into older age.[*]Corresponding authorNormal aging is associated with morphometric changes in several brain regions and a 1 corresponding decline in cognitive function, with trajectories of age-related changes that 2 are characterized by individual differences [1]. Major events, biological and genetic 3 factors through the lifespan obviously contribute to the heterogeneity observed in 4 samples of older individuals [2, 3, 12], both regarding the rate of structural brain 5 changes [5], the rate and extent of cognitive changes [6] and in brain-cognition 6 relations [7, 12]. In the severe end of the distribution, the most extensive parenchyma 7 loss is associated with dementia, a syndrome defined by a severe decline in cognitive 8 function [8]. On the other end of the scale we find so-called "superagers" [9]. They show 9 maintained cognitive function into old age [10], with a corresponding preservation of 10 brain structure over time [11, 12]. These findings support that age-related structural 11 brain changes can act as strong predictors of cognitive abilities in old age, and 12 emphasize the importan...

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Dementia

Cited by 460 publications

References 77 publications

Comparative Kinetics of Acetyl- and Butyryl-Cholinesterase Inhibition by Green Tea Catechins|Relevance to the Symptomatic Treatment of Alzheimer’s Disease

Comparative Kinetics of Acetyl- and Butyryl-Cholinesterase Inhibition by Green Tea Catechins|Relevance to the Symptomatic Treatment of Alzheimer’s Disease

Computational Neurology: Computational Modeling Approaches in Dementia

Lateral ventricle volume trajectories predict response inhibition in older age - a longitudinal brain imaging and machine learning approach

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