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[IEEE 2019 Joint Conference of the IEEE International Frequency Control Symposium anEuropean Frequency and Time Forum (EFTF/IFC) - Orlando, FL, USA (2019.4.14-2019.4.18)] 2019 Joint Conference of the IEEE International Frequency Control Symposium and European Frequency and Time Forum (EFTF/IFC) - Phase Noise Directely Measurement of Optical Second Harmonic Generation in MgO:PPLN Waveguide based on the 120-degree Phase Difference Interferometer
摘要： We examine whether modeling of the causal dynamic relationships between frontal and occipital electroencephalogram (EEG) time-series recordings reveal reliable differentiating characteristics of Alzheimer’s patients versus control subjects in a manner that may assist clinical diagnosis of Alzheimer’s disease (AD). The proposed modeling approach utilizes the concept of principal dynamic modes (PDMs) and their associated nonlinear functions (ANF) and hypothesizes that the ANFs of some PDMs for the AD patients will be distinct from their counterparts in control subjects. To this purpose, global PDMs are extracted from 1-min EEG signals of 17 AD patients and 24 control subjects at rest using Volterra models estimated via Laguerre expansions, whereby the O1 or O2 recording is viewed as the input signal and the F3 or F4 recording as the output signal. Subsequent singular value decomposition of the estimated Volterra kernels yields the global PDMs that represent an ef?cient basis of functions for the representation of the EEG dynamics in all subjects. The respective ANFs are computed for each subject and characterize the speci?c dynamics of each subject. For comparison, signal features traditionally used in the analysis of EEG signals in AD are computed as benchmark. The results indicate that the ANFs of two speci?c PDMs, corresponding to the delta–theta and alpha bands, can delineate the two groups well.
关键词： assistive diagnosis,Alzheimer’s disease,nonlinear modeling,EEG signal processing
更新于2025-09-19 17:13:59
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Assessing Neural Compensation with Visuospatial Working Memory Load using Near-Infrared Imaging
摘要： Alzheimer’s disease is characterized by the progressive deterioration of cognitive abilities particularly working memory while mild cognitive impairment (MCI) represents its prodrome. It is generally believed that neural compensation is intact in MCI but absent in Alzheimer’s disease. This study investigated the effects of increasing task load as a means to induce neural compensation through a novel visual working memory (VSWM) task using functional near-infrared spectroscopy (fNIRS). The bilateral prefrontal cortex (PFC) was explored due to its relevance in VSWM and neural compensation. A total of 31 healthy controls (HC), 12 patients with MCI and 18 patients with mild Alzheimers disease (mAD) were recruited. Although all groups showed sensitivity in terms of behavioral performance (i.e. score) towards increasing task load (level 1 to 3), only in MCI load effect on cortical response (as measured by fNIRS) was significant. At lower task load, bilateral PFC activation did not differ between MCI and HC. Neural compensation in the form of hyperactivation was only noticeable in MCI with a moderate task load. Lack of hyperactivation in mAD, coupled with significantly poorer task performance across task loads, suggested the inability to compensate due to a greater degree of neurodegeneration. Our findings provided an insight into the interaction of cognitive load theory and neural compensatory mechanisms. The experiment results demonstrated the feasibility of inducing neural compensation with the proposed VSWM task at the right amount of cognitive load. This may provide a promising avenue to develop an effective cognitive training and rehabilitation for dementia population.
关键词： mild cognitive impairment,visuospatial working memory,normal aging,functional near-infrared spectroscopy,neural compensation,mild Alzheimer’s disease
更新于2025-09-12 10:27:22
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CAN MILD COGNITIVE IMPAIRMENT BE STABILIZED BY SHOWERING BRAIN MITOCHONDRIA WITH LASER PHOTONS?
摘要： There is now substantial evidence that cerebral blood flow (CBF) declines with age. From age 20 to 60, CBF is estimated to dip about 16% and continues to drop at a rate of 0.4%/year. This CBF dip will slowly reduce oxygen/glucose delivery to brain thus lowering ATP energy production needed by brain cells to perform normal activities. Reduced ATP production from mitochondrial loss or damage in the wear-and-tear of aging worsens when vascular risk factors (VRF) to Alzheimer’s disease develop that can accelerate both age-decline CBF and mitochondrial deficiency to a level where mild cognitive impairment (MCI) develops. To date, no pharmacological or any other treatment has been successful in reversing, stabilizing or delaying MCI. For the first time in medical interventions, a non-pharmacological, non-invasive, well-tolerated, easy to perform, free of significant side effects and cost-effective treatment may achieve what virtually all AD treatments in the past have been unable to accomplish. This intervention uses transcranial infrared brain stimulation (TIBS), a form of photobiomodulation (PBM). PBM is a bioenergetic non-ionizing, therapeutic approach using low level light emission from laser or light emitting diodes. PBM has been used in a number of neurological conditions including Parkinson’s disease, depression, traumatic brain injury, and stroke with diverse reported benefits. This brief review examines the impact of reduced energy supply stemming from chronic brain hypoperfusion in the aging brain. In this context, the use of TIBS is planned in a randomized, placebo-controlled study of MCI patients to be done at our University Clinic.
关键词： chronic brain hypoperfusion,laser,ATP,cerebral blood flow,Alzheimer’s disease,mild cognitive impairment,photobiomodulation,axonal transport,neuronal energy,transcranial infrared brain stimulation
更新于2025-09-12 10:27:22
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Visible-Light-Controlled Reaction-Separation for Asymmetric Sulfoxidation in Water with Photoresponsive Metallomicelles
摘要： Alzheimer’s disease (AD) is one of the major global health challenges of the 21st century. More than 200 distinct mutations in presenilin 1 (PSEN1) cause severe early-onset familial AD (FAD) and are thus of central interest to the etiology of AD. PSEN1 is the catalytic subunit of γ-secretase that produces β-amyloid peptide (Aβ), and the mutations tend to increase the produced Aβ42/Aβ40 ratio. The molecular reasons for the pathogenesis of these mutations are unknown. We studied a close-to-complete data set of PSEN1 mutations using 21 different computational methods hypothesized to reproduce pathogenesis, using both sequence- and structure-based methods with the full γ-secretase complex as input. First, we tested whether pathogenicity can be estimated accurately using all possible mutations in PSEN1 as a direct control. Several methods predict the pathogenicity of the mutations (pathogenic vs all other possible mutations) well, with accuracies approaching 90%. We then designed a stricter test for predicting the severity of the mutations estimated by the average clinical age of symptom onset for mutation carriers. Surprisingly, we can predict the clinical age of symptom onset at 95% confidence or higher with several methods. Accordingly, our results show that simple biochemical properties of the amino acid changes rationalize an important part of the pathogenicity of FAD-causing PSEN1 mutations. Although pathogenic mutations generally destabilize γ-secretase, all of the tested protein stability methods failed to predict pathogenicity. Thus, either the static cryogenic-electron-microscopy-derived molecular-dynamics-equilibrated structures used as input fail to capture the stability effect of mutated side chains or protein stability is simply not a key factor in the pathogenicity. Our findings suggest that the chemical causes of FAD may be modeled and lend promise to the development of a semiquantitative model predicting the age of onset of mutation carriers that could eventually become of care-strategic value.
关键词： computational methods,β-amyloid peptide,presenilin 1,Alzheimer’s disease,γ-secretase,mutations,pathogenicity
更新于2025-09-11 14:15:04
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Characterization of Inner Retinal Hyperreflective Alterations in Early Cognitive Impairment on Adaptive Optics Scanning Laser Ophthalmoscopy
摘要： PURPOSE. To examine inner retinal hyperre?ective features on adaptive optics scanning laser ophthalmoscopy (AOSLO) in individuals with early cognitive impairment. METHODS. In this prospective, cross-sectional study, we enrolled 12 participants with either amnestic mild cognitive impairment (aMCI, n ? 10) or early dementia due to Alzheimer’s disease (eAD, n ? 2) and 12 age-, sex-, and race-matched cognitively normal controls. All participants completed AOSLO imaging of the peripapillary area were graded for hyperre?ective features including granular membranes, mottled membranes, and nummular features. Regions of interest on AOSLO were compared qualitatively to corresponding optical coherence tomography (OCT) cross sections. OCT was also used to analyze peripapillary retinal nerve ?ber layer (RNFL) thickness. RESULTS. Cognitively impaired individuals had a signi?cantly higher number of granular membranes with a larger overall area compared to controls. The proportion of cognitively impaired individuals with two or more granular membranes was 41.7% compared to none in the control group. Granular membrane area was also inversely correlated with cognitive performance on the Montreal Cognitive Assessment. There was no difference between the two groups in terms of other membrane types or RNFL thickness. CONCLUSIONS. Individuals with early cognitive impairment related to Alzheimer’s show hyperre?ective granular membranes on high-resolution imaging, which we hypothesize to be manifestations of inner retinal gliosis. The presence of these subtle hyperre?ective membranes may obscure underlying RNFL thinning in these eyes on OCT imaging. The distinctive phenotype of granular membranes surrounding the optic nerve on AOSLO may represent a new potential biomarker of early Alzheimer’s.
关键词： cognitive impairment,adaptive optics scanning laser ophthalmoscopy,aoslo,alzheimer’s disease,gliosis
更新于2025-09-11 14:15:04
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Label-free imaging of amyloid plaques in Alzheimer’s disease with stimulated Raman scattering microscopy
摘要： One of the key pathological features of Alzheimer’s disease (AD) is the existence of extracellular deposition of amyloid plaques formed with misfolded amyloid-β (Aβ). The conformational change of proteins leads to enriched contents of β sheets, resulting in remarkable changes of vibrational spectra, especially the spectral shifts of the amide I mode. Here, we applied stimulated Raman scattering (SRS) microscopy to image amyloid plaques in the brain tissue of an AD mouse model. We have demonstrated the capability of SRS microscopy as a rapid, label-free imaging modality to differentiate misfolded from normal proteins based on the blue shift (~10 cm?1) of amide I SRS spectra. Furthermore, SRS imaging of Aβ plaques was verified by antibody staining of frozen thin sections and fluorescence imaging of fresh tissues. Our method may provide a new approach for studies of AD pathology, as well as other neurodegenerative diseases associated with protein misfolding.
关键词： amyloid plaques,protein misfolding,Alzheimer’s disease,stimulated Raman scattering microscopy,label-free imaging
更新于2025-09-09 09:28:46
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Study of memory deficit in Alzheimer’s disease by means of complexity analysis of fNIRS signal
摘要： Working memory deficit is a signature of Alzheimer’s disease (AD). The free and cued selective reminding test (FCSRT) is a clinical test that quantifies memory deficit for AD diagnosis. However, the diagnostic accuracy of FCSRT may be increased by accompanying it with neuroimaging. Since the test requires doctor–patient interaction, brain monitoring is challenging. Functional near-infrared spectroscopy (fNIRS) could be suited for such a purpose because of the fNIRS flexibility. We investigated whether the complexity, based on sample entropy and multiscale entropy metrics, of the fNIRS signal during FCSRT was correlated with memory deficit in early AD. fNIRS signals were recorded over the prefrontal cortex of healthy and early AD participants. Group differences were tested through Wilcoxon–Mann–Whitney test (p < 0.05). At group level, we found significant differences for Brodmann areas 9 and 46. The results, although preliminary, demonstrate the feasibility of performing ecological studies on early AD with fNIRS. This approach may provide a potential neuroimaging-based method for diagnosis of early AD, viable at the doctor’s office level, improving test-based diagnosis. The increased entropy of the fNIRS signal in early AD suggests the opportunity for further research on the neurophysiological status in AD and its relevance for clinical symptoms.
关键词： entropy,functional near-infrared spectroscopy,Alzheimer’s disease,free and cued selective reminding test
更新于2025-09-09 09:28:46
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Automated Behavioral Analysis of Large <em>C. elegans</em> Populations Using a Wide Field-of-view Tracking Platform
摘要： Caenorhabditis elegans is a well-established animal model in biomedical research, widely employed in functional genomics and ageing studies. To assess the health and fitness of the animals under study, one typically relies on motility readouts, such as the measurement of the number of body bends or the speed of movement. These measurements usually involve manual counting, making it challenging to obtain good statistical significance, as time and labor constraints often limit the number of animals in each experiment to 25 or less. Since high statistical power is necessary to obtain reproducible results and limit false positive and negative results when weak phenotypic effects are investigated, efforts have recently been made to develop automated protocols focused on increasing the sensitivity of motility detection and multi-parametric behavioral profiling. In order to extend the limit of detection to the level needed to capture the small phenotypic changes that are often crucial in genetic studies and drug discovery, we describe here a technological development that enables the study of up to 5,000 individual animals simultaneously, increasing the statistical power of the measurements by about 1,000-fold compared to manual assays and about 100-fold compared to other available automated methods.
关键词： nematode library,neurodegeneration,amyloid formation,Alzheimer's disease,Drug discovery,Issue 141,phenotype-based screening,high-throughput screening,Immunology and Infection,C. elegans,large population analysis
更新于2025-09-09 09:28:46
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Early Detection of Alzheimer’s Disease Using Non-invasive Near-Infrared Spectroscopy
摘要： Mild cognitive impairment (MCI) is a cognitive disorder characterized by memory impairment, wherein patients have an increased likelihood of developing Alzheimer’s disease (AD). The classification of MCI and different AD stages is therefore fundamental for understanding and treating the disease. This study aimed to comprehensively investigate the hemodynamic response patterns among various subject groups. Functional near-infrared spectroscopy (fNIRS) was employed to measure signals from the frontal and bilateral parietal cortices of healthy controls (n = 8), patients with MCI (n = 9), mild (n = 6), and moderate/severe AD (n = 7) during a digit verbal span task (DVST). The concentration changes of oxygenated hemoglobin (HbO) in various subject groups were thoroughly explored and tested. Result revealed that abnormal patterns of hemodynamic response were observed across all subject groups. Greater and steeper reductions in HbO concentration were consistently observed across all regions of interest (ROIs) as disease severity developed from MCI to moderate/severe AD. Furthermore, all the fNIRS-derived indexes were found to be significantly and positively correlated to the clinical scores in all ROIs (R ≥ 0.4, P < 0.05). These findings demonstrate the feasibility of utilizing fNIRS for the early detection of AD, suggesting that fNIRS-based approaches hold great promise for exploring the mechanisms underlying the progression of AD.
关键词： oxygenated hemoglobin,functional near-infrared spectroscopy,Alzheimer’s disease,hemodynamic response,mild cognitive impairment
更新于2025-09-09 09:28:46
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A curcumin-based NIR fluorescence probe for detection of amyloid-beta (Aβ) plaques in Alzheimer's disease
摘要： Amyloid-beta (Aβ) peptide as one of the main components of senile plaques is closely related to the onset and progression of incurable Alzheimer's disease (AD). In recent years, it is reported that curcumin derivatives have been used as the near-infrared (NIR) fluorescence imaging probes of Aβ plaques for the early diagnosis of AD. To further develop a curcumin-based NIR fluorescent probe for Aβ plaques, in this work, we have synthesized three novel curcumin-based NIR Dyes. Among them, the curcumin derivative Dye 2 showed a significant enhancement in its fluorescence intensity (λem, 635 nm; 19.5-fold increase in quantum yield, Φ = 0.36; Kd, 1.13 μM) after binding to Aβ plaques. Additionally, in vitro and in vivo fluorescence imaging of Aβ plaques strained with Dye 2 confirmed that the compound was a potential probe to detect Aβ plaques in AD. This work opens a perspective to rationally design novel curcumin-based NIR compound for Aβ detection.
关键词： Alzheimer’s Disease,Fluorescence imaging,Amyloid-beta deposits,NIR fluorescence probe,Curcumin,Amyloid-beta plaques
更新于2025-09-09 09:28:46