The construct of mild cognitive impairment (MCI) has evolved over the past 10 years since the publication of the new MCI definition at the Key Symposium in 2003, but the core criteria have remained ...unchanged. The construct has been extensively used worldwide, both in clinical and in research settings, to define the grey area between intact cognitive functioning and clinical dementia. A rich set of data regarding occurrence, risk factors and progression of MCI has been generated. Discrepancies between studies can be mostly explained by differences in the operationalization of the criteria, differences in the setting where the criteria have been applied, selection of subjects and length of follow‐up in longitudinal studies. Major controversial issues that remain to be further explored are algorithmic versus clinical classification, reliability of clinical judgment, temporal changes in cognitive performances and predictivity of putative biomarkers. Some suggestions to further develop the MCI construct include the tailoring of the clinical criteria to specific populations and to specific contexts. The addition of biomarkers to the clinical phenotypes is promising but requires deeper investigation. Translation of findings from the specialty clinic to the population setting, although challenging, will enhance uniformity of outcomes. More longitudinal population‐based studies on cognitive ageing and MCI need to be performed to clarify all these issues.
Terahertz radiation has become an important diagnostic tool in the development of new technologies. However, the diffraction limit prevents terahertz radiation (λ ≈ 0.01–3 mm) from being focused to ...the nanometre length scale of modern devices. In response to this challenge, terahertz scanning probe microscopy techniques based on coupling terahertz radiation to subwavelength probes such as sharp tips have been developed. These probes enhance and confine the light, improving the spatial resolution of terahertz experiments by up to six orders of magnitude. In this Review, we survey terahertz scanning probe microscopy techniques that achieve spatial resolution on the scale of micrometres to ångströms, with particular emphasis on their overarching approaches and underlying probing mechanisms. Finally, we forecast the next steps in the field.Recent progress in terahertz scanning probe microscopy is reviewed with an emphasis on techniques that access length scales below 100 nm relevant to material science. An outlook on the future of nanoscale terahertz scanning probe microscopy is also provided.
Atomically precise electronics operating at optical frequencies require tools that can characterize them on their intrinsic length and time scales to guide device design. Lightwave-driven scanning ...tunnelling microscopy is a promising technique towards this purpose. It achieves simultaneous sub-ångström and sub-picosecond spatio-temporal resolution through ultrafast coherent control by single-cycle field transients that are coupled to the scanning probe tip from free space. Here, we utilize lightwave-driven terahertz scanning tunnelling microscopy and spectroscopy to investigate atomically precise seven-atom-wide armchair graphene nanoribbons on a gold surface at ultralow tip heights, unveiling highly localized wavefunctions that are inaccessible by conventional scanning tunnelling microscopy. Tomographic imaging of their electron densities reveals vertical decays that depend sensitively on wavefunction and lateral position. Lightwave-driven scanning tunnelling spectroscopy on the ångström scale paves the way for ultrafast measurements of wavefunction dynamics in atomically precise nanostructures and future optoelectronic devices based on locally tailored electronic properties.
The double-well potential is arguably one of the most important potentials in quantum mechanics, because the solution contains the notion of a state as a linear superposition of "classical" states, a ...concept which has become very important in quantum information theory. It is therefore desirable to have solutions to simple double-well potentials that are accessible to the undergraduate student. We describe a method for obtaining the numerically exact eigenenergies and eigenstates for such a model, along with the energies obtained through the Wentzel-Kramers-Brillouin (WKB) approximation. The exact solution is accessible with elementary mathematics, though numerical solutions are required. We also find that the WKB approximation is remarkably accurate, not just for the ground state, but also for the excited states. (Contains 4 figures and 10 footnotes.)
The hypothesis of a functional disconnection of neuro-cognitive networks in patients with mild cognitive impairment (MCI) and Alzheimer Dementia was investigated using baseline resting EEG data. EEG ...databases from New York (264 subjects) and Stockholm (155 subjects), including healthy controls and patients with varying degrees of cognitive decline or Alzheimer Dementia were analyzed using Global Field Synchronization (GFS), a novel measure of global EEG synchronization. GFS reflects the global amount of phase-locked activity at a given frequency by a single number; it is independent of the recording reference and of implicit source models. Patients showed decreased GFS values in Alpha, Beta, and Gamma frequency bands, and increased GFS values in the Delta band, confirming the hypothesized disconnection syndrome. The results are discussed within the framework of current knowledge about the functional significance of the affected frequency bands.
to investigate auditory function in subjects with early Alzheimer's disease, mild cognitive impairment and with subjective memory complaints, in search of signs of central auditory processing ...dysfunction even in early stages of cognitive impairment.
a consecutive group of men and women, referred to the Memory Clinic at the Karolinska University Hospital, was approached for inclusion in this prospective study. One hundred and thirty-six subjects, mean age 64 years (range 50-78 years), diagnosed with Alzheimer's disease (n = 43), mild cognitive impairment (n = 59) or with subjective memory complaints (n = 34), were included.
auditory function was assessed with pure tone audiometry, speech perception in quiet and in background noise and dichotic digits tests with two or three digits.
pure tone audiometry and speech perception scores in quiet and in background noise were normal for age and without between-group differences. Dichotic digits tests showed strongly significant differences between the three groups, where the Alzheimer's disease group performed significantly poorer than the other two groups, with the mild cognitive impairment group in an intermediate position.
our results demonstrate that central auditory processing dysfunction is highly evident in subjects with Alzheimer's disease, and to a considerable extent even in subjects with mild cognitive impairment.
.
The First Key Symposium was held in Stockholm, Sweden, 2–5 September 2003. The aim of the symposium was to integrate clinical and epidemiological perspectives on the topic of Mild Cognitive ...Impairment (MCI). A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics. Agreement on new perspectives, as well as recommendations for management and future research were discussed by the international working group. The specific recommendations for the general MCI criteria include the following: (i) the person is neither normal nor demented; (ii) there is evidence of cognitive deterioration shown by either objectively measured decline over time and/or subjective report of decline by self and/or informant in conjunction with objective cognitive deficits; and (iii) activities of daily living are preserved and complex instrumental functions are either intact or minimally impaired.
Mild cognitive impairment (MCI) is an operational definition for a cognitive decline in individuals with a greater risk of developing dementia. The amnestic subtype of MCI is of particular interest ...because these individuals most likely progress to Alzheimer’s disease (AD). Currently hypothesised therapeutic approaches in MCI are mainly based on AD treatment strategies. Long term secondary prevention randomised clinical trials have been completed in amnestic MCI populations, encompassing agents with various mechanisms of action: acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine), antioxidants (vitamin E), anti-inflammatories (rofecoxib), and nootropics (piracetam). The design of clinical trials in MCI is influenced by study objectives and definition of primary end points: time to clinical diagnosis of dementia, and AD in particular, or symptom progression. As none of the drugs previously shown to have clinical efficacy in AD trials or benefit in everyday practice have met the primary objectives of the respective trials, design of future clinical trials in MCI should be further developed particularly as regards the selection of more homogeneous samples at entry, optimal treatment duration, and multidimensional and reliable outcomes.
ABSTRACT
A new upper limit on the 21 cm signal power spectrum at a redshift of z ≈ 9.1 is presented, based on 141 h of data obtained with the Low-Frequency Array (LOFAR). The analysis includes ...significant improvements in spectrally smooth gain-calibration, Gaussian Process Regression (GPR) foreground mitigation and optimally weighted power spectrum inference. Previously seen ‘excess power’ due to spectral structure in the gain solutions has markedly reduced but some excess power still remains with a spectral correlation distinct from thermal noise. This excess has a spectral coherence scale of 0.25–0.45 MHz and is partially correlated between nights, especially in the foreground wedge region. The correlation is stronger between nights covering similar local sidereal times. A best 2-σ upper limit of $\Delta ^2_{21} \lt (73)^2\, \mathrm{mK^2}$ at $k = 0.075\, \mathrm{h\, cMpc^{-1}}$ is found, an improvement by a factor ≈8 in power compared to the previously reported upper limit. The remaining excess power could be due to residual foreground emission from sources or diffuse emission far away from the phase centre, polarization leakage, chromatic calibration errors, ionosphere, or low-level radiofrequency interference. We discuss future improvements to the signal processing chain that can further reduce or even eliminate these causes of excess power.
Objectives: The spatial aspects of brain electrical activity can be assessed by equivalent EEG frequency band generators. We aimed to describe alterations of these EEG generators in Alzheimer's ...disease (AD) and healthy aging and whether they could serve as predictive markers of AD in subjects at risk.
Methods: The amplitude and 3-dimensional localization of equivalent EEG sources were evaluated using FFT dipole approximation in 38 mild AD patients, 31 subjects with mild cognitive impairment (MCI) and 24 healthy control subjects.
Results: AD patients showed an increase of delta and theta global field power (GFP), which corresponds to the generalized EEG amplitude, as well as a reduction of alpha GFP when compared to the controls. A decrease of alpha and beta GFP was found in AD patients, as compared to the MCI subjects. With respect to topography in the antero-posterior direction, sources of alpha and beta activity shifted more anteriorly in AD patients compared to both the controls and MCI subjects. No significant difference was found between MCI and controls. Combined alpha and theta GFP were the best discriminating variables between AD patients and controls (84% correct classification) and AD and MCI subjects (78% correctly classified). MCI subjects were followed longitudinally (25 months on average) in order to compare differences in baseline EEG variables between MCI subjects who progressed to AD (PMCI) and those who remained stable (SMCI). Compared to SMCI, PMCI had decreased alpha GFP and a more anterior localization of sources of theta, alpha and beta frequency. In a linear discriminant analysis applied on baseline values of the two MCI subgroups, the best predictor of future development of AD was found to be antero-posterior localization of alpha frequency.
Conclusions: FFT dipole approximation and frequency analysis performed by conventional FFT showed comparable classification accuracy between the studied groups. We conclude that localization and amplitude of equivalent EEG sources could be promising markers of early AD.
PDF
