Spatial inhibition of return is impaired in mild cognitive impairment and mild Alzheimer's disease.
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ABSTRACT:
SUBMITTER: Jiang X
PROVIDER: S-EPMC8202934 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Effective and accurate diagnosis of Alzheimer's disease (AD), as well as its prodromal stage (i.e., mild cognitive impairment (MCI)), has attracted more and more attention recently. So far, multiple biomarkers have been shown to be sensitive to the diagnosis of AD and MCI, i.e., structural MR imaging (MRI) for brain atrophy measurement, functional imaging (e.g., FDG-PET) for hypometabolism quantification, and cerebrospinal fluid (CSF) for quantification of specific proteins. However, most existing research focuses on only a single modality of biomarkers for diagnosis of AD and MCI, although recent studies have shown that different biomarkers may provide complementary information for the diagnosis of AD and MCI. In this paper, we propose to combine three modalities of biomarkers, i.e., MRI, FDG-PET, and CSF biomarkers, to discriminate between AD (or MCI) and healthy controls, using a kernel combination method. Specifically, ADNI baseline MRI, FDG-PET, and CSF data from 51AD patients, 99 MCI patients (including 43 MCI converters who had converted to AD within 18 months and 56 MCI non-converters who had not converted to AD within 18 months), and 52 healthy controls are used for development and validation of our proposed multimodal classification method. In particular, for each MR or FDG-PET image, 93 volumetric features are extracted from the 93 regions of interest (ROIs), automatically labeled by an atlas warping algorithm. For CSF biomarkers, their original values are directly used as features. Then, a linear support vector machine (SVM) is adopted to evaluate the classification accuracy, using a 10-fold cross-validation. As a result, for classifying AD from healthy controls, we achieve a classification accuracy of 93.2% (with a sensitivity of 93% and a specificity of 93.3%) when combining all three modalities of biomarkers, and only 86.5% when using even the best individual modality of biomarkers. Similarly, for classifying MCI from healthy controls, we achieve a classification accuracy of 76.4% (with a sensitivity of 81.8% and a specificity of 66%) for our combined method, and only 72% even using the best individual modality of biomarkers. Further analysis on MCI sensitivity of our combined method indicates that 91.5% of MCI converters and 73.4% of MCI non-converters are correctly classified. Moreover, we also evaluate the classification performance when employing a feature selection method to select the most discriminative MR and FDG-PET features. Again, our combined method shows considerably better performance, compared to the case of using an individual modality of biomarkers.
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Project description:Recent evidence has implicated areas within the posterior parietal cortex (PPC) as among the first to show pathophysiological changes in Alzheimer's disease (AD). Focal brain damage to the PPC can cause optic ataxia, a specific deficit in reaching to peripheral targets. The present study describes a novel investigation of peripheral reaching ability in AD and mild cognitive impairment (MCI), to assess whether this deficit is common among these patient groups. Individuals with a diagnosis of mild-to-moderate AD, or MCI, and healthy older adult controls were required to reach to targets presented in central vision or in peripheral vision using two reaching tasks; one in the lateral plane and another presented in radial depth. Pre-registered case-control comparisons identified 1/10 MCI and 3/17 AD patients with significant peripheral reaching deficits at the individual level, but group-level comparisons did not find significantly higher peripheral reaching error in either AD or MCI by comparison to controls. Exploratory analyses showed significantly increased reach duration in both AD and MCI groups relative to controls, accounted for by an extended Deceleration Time of the reach movement. These findings suggest that peripheral reaching deficits like those observed in optic ataxia are not a common feature of AD. However, we show that cognitive decline is associated with a generalised slowing of movement which may indicate a visuomotor deficit in reach planning or online guidance.
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Project description:IntroductionIt has been reported that environmental factors such as hypoxia could contribute to the pathogenesis of Alzheimer's disease (AD). Therapeutics like hyperbaric oxygen treatment, which improves tissue oxygen supply and ameliorates hypoxic conditions in the brain, may be an alternative therapy for AD and amnestic mild cognitive impairment (aMCI). The present work aims to investigate the potential therapeutic effect of hyperbaric oxygen treatment for AD and aMCI.MethodsWe recruited 42 AD, 11 aMCI, and 30 control AD patients in this study. AD and aMCI patients were treated with 40 minutes of hyperbaric oxygen once a day for 20 days and assessed by neuropsychiatric assessments including Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Activities of Daily Living (ADL) scale before and at 1-, 3-, and 6-month follow-up after treatment. Control AD patients who were not given hyperbaric oxygen treatment had similar clinical profile as hyperbaric oxygen treated AD. We examined 10 of the AD/aMCI patients with fluorodeoxyglucose positron emission tomography.ResultsIn self-comparison study, one course of hyperbaric oxygen treatment significantly improved the cognitive function assessed by MMSE and MoCA in AD patients after 1-month follow-up; such treatment also significantly improved MMSE score at 3-month follow-up and MoCA score at 1- and 3-month follow-up in aMCI patients. The ADL scale was significantly improved in AD patients after 1- and 3-month follow-up. Compared to the control AD patients, the MMSE and MoCA in hyperbaric oxygen treated AD patients were significantly improved after 1-month follow-up. Hyperbaric oxygen treatment also ameliorated the reduced brain glucose metabolism in some of the AD and aMCI patients.ConclusionBased on previous studies and our recent findings, we propose that hyperbaric oxygen treatment may be a promising alternative therapy for AD and aMCI.
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Project description:We investigated why the cerebrospinal fluid (CSF) concentrations of A?42 are lower in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. Because A?38/42 and A?40/43 are distinct product/precursor pairs, these four species in the CSF together should faithfully reflect the status of brain ?-secretase activity, and were quantified by specific enzyme-linked immunosorbent assays in the CSF from controls and MCI/AD patients. Decreases in the levels of the precursors, A?42 and 43, in MCI/AD CSF tended to accompany increases in the levels of the products, A?38 and 40, respectively. The ratios A?40/43 versus A?38/42 in CSF (each representing cleavage efficiency of A?43 or A?42) were largely proportional to each other but generally higher in MCI/AD patients compared to control subjects. These data suggest that ?-secretase activity in MCI/AD patients is enhanced at the conversion of A?43 and 42 to A?40 and 38, respectively. Consequently, we measured the in vitro activity of raft-associated ?-secretase isolated from control as well as MCI/AD brains and found the same, significant alterations in the ?-secretase activity in MCI/AD brains.
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Project description:BackgroundHistopathological studies and animal models suggest that hippocampal subfields may be differently affected by aging, Alzheimer's disease (AD), and other diseases. High-resolution images at 4 Tesla depict details of the internal structure of the hippocampus allowing for in vivo volumetry of different subfields. The aims of this study were as follows: (1) to determine patterns of volume loss in hippocampal subfields in normal aging, AD, and amnestic mild cognitive impairment (MCI). (2) To determine if measurements of hippocampal subfields provide advantages over total hippocampal volume for differentiation between groups.MethodsNinety-one subjects (53 controls (mean age: 69.3 ± 7.3), 20 MCI (mean age: 73.6 ± 7.1), and 18 AD (mean age: 69.1 ± 9.5) were studied with a high-resolution T2 weighted imaging sequence aimed at the hippocampus. Entorhinal cortex (ERC), subiculum, CA1, CA1-CA2 transition zone (CA1-2), CA3 & dentate gyrus (CA3&DG) were manually marked in the anterior third of the hippocampal body. Hippocampal volume was obtained from the Freesurfer and manually edited.ResultsCompared to controls, AD had smaller volumes of ERC, subiculum, CA1, CA1-2, and total hippocampal volumes. MCI had smaller CA1-2 volumes. Discriminant analysis and power analysis showed that CA1-2 was superior to total hippocampal volume for distinction between controls and MCI.ConclusionThe patterns of subfield atrophy in AD and MCI were consistent with patterns of neuronal cell loss/reduced synaptic density described by histopathology. These preliminary findings suggest that hippocampal subfield volumetry might be a better measure for diagnosis of early AD and for detection of other disease effects than measurement of total hippocampus.
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