A comparison of resting state EEG and structural MRI for classifying Alzheimer's disease and mild cognitive impairment.

Alzheimer's disease (AD) is the leading cause of dementia, accounting for 70% of cases worldwide. By 2050, dementia prevalence will have tripled, with most new cases occurring in low- and middle-income countries. Mild cognitive impairment (MCI) is a stage between healthy aging and dementia, marked by cognitive deficits that do not impair daily living. People with MCI are at increased risk of dementia, with an average progression rate of 39% within 5 years. There is urgent need for low-cost, accessible and objective methods to facilitate early dementia detection. Electroencephalography (EEG) has potential to address this need due to its low cost and portability. Here, we collected resting state EEG, structural MRI (sMRI) and rich neuropsychological data from older adults (55+ years) with AD, amnestic MCI (aMCI) and healthy controls (~60 per group). We evaluated a range of candidate EEG markers (i.e., frequency band power and functional connectivity) for AD and aMCI classification and compared their performance with sMRI. We also tested a combined EEG and cognitive classification model (using Mini-Mental State Examination; MMSE). sMRI outperformed resting state EEG at classifying AD (AUCs â€‹= â€‹1.00 vs 0.76, respectively). However, both EEG and sMRI were only moderately good at distinguishing aMCI from healthy aging (AUCs â€‹= â€‹0.67-0.73), and neither method achieved sensitivity above 70%. The addition of EEG to MMSE scores had no added benefit relative to MMSE scores alone. This is the first direct comparison of EEG and sMRI for classification of AD and aMCI.

What does the broken brain say to the neuroscientist? Oscillations and connectivity in schizophrenia, Alzheimer's disease, and bipolar disorder.

The application of the concept and methods of brain oscillations has been an important research area in neurosciences. In the last decades, besides the application in cognitive processes, the study of changes in brain oscillations in diseases has also become an important focal point of research. In the present paper, some remarkable examples in three different diseases are taken into consideration: 1) schizophrenia (SZ), 2) Alzheimer's disease (AD), 3) bipolar disorders (BD). In the current literature, decreased oscillations in cortical recordings are observed in most of the pathologies. For example, decrease of gamma activity in SZ, decrease of delta activity in almost all diseases, as well as frequency shifts in alpha and the lower frequencies were recorded. However, there are also paradoxical cases in which an increase of oscillatory activities is observed. In BD, whereas alpha activity is greatly decreased, a huge increase of beta activity is observed. Or, in SZ, a paradoxical increase of gamma activity can be observed during cognitive loading. We also observed paradoxical changes in the analysis of connectivity. In AD, we find that alpha, delta, and theta coherences between distant parts of the cortex are greatly decreased, whereas in the gamma band, event-related coherences attain very high values. The comparison of the results and paradoxical changes in diseases may lead to important conclusions related to the web of oscillations and neurotransmitters. In turn, we could gain new insights to approach "brain function", in general.

Auditory delta event-related oscillatory responses are decreased in Alzheimer's disease.

BACKGROUND: Visual delta event-related (ERO) and evoked oscillations (EO) of Alzheimer patients (AD) are different than healthy. In the present study, the analysis is extented to include auditory ERO and EO in AD. The rationale is to reveal whether the auditory ERO delta responses are also reduced, and whether this is a general phenomenon in Alzheimer patients upon applying stimuli with cognitive load. METHODS: Thirty-four mild AD subjects [17 de-novo and 17 medicated (cholinergic)] and seventeen healthy controls were included. Auditory oddball paradigm and sensory auditory stimuli were applied to the subjects. Oscillatory responses were analyzed by measuring maximum amplitudes in delta frequency range (0.5-3.5 Hz). RESULTS: Auditory delta ERO (0.5-3.5 Hz) responses of healthy controls were higher than either de-novo AD or medicated AD group, without a difference between two AD subgroups. Furthermore, the auditory EO after presentation of tone bursts yielded no group difference. CONCLUSION: Our findings imply that delta ERO is highly unstable in AD patients in comparison to age-matched healthy controls only during the cognitive paradigm. Our results favor the hypothesis that neural delta networks are activated during cognitive tasks and that the reduced delta response is a general phenomenon in AD, due to cognitive impairment.

Distributions of 210Pb around a uraniferous coal-fired power plant in Western Turkey.

In the present study the spatial and the vertical distributions of 210Pb were investigated in the soils around a uranifereous coal fired power plant (CPP) in Yatagan Basin, in Western Turkey. The variation of 226Ra activity along the soil profiles was studied to assess the unsupported 210Pb distribution in the same samples. 226Ra was measured by gamma spectroscopy and 210Pb activities were determined from 210Po activities using radiochemical deposition and alpha spectroscopy. The total 210Pb activity concentrations in bulk core samples varied in the range of 38-250 Bq kg(-1) in the study sites and of 22-78 Bq kg(-1) in reference site. In the sectioned cores sampled from the study areas the ranges for activity concentrations of 226Ra, total 210Pb and unsupported 210Pb are 24-77; 39-344 and 4-313 Bq kg(-1), respectively. Corresponding ranges for reference site are 37-39; 39-122 and 1-83 Bq kg(-1).

Event-related delta oscillatory responses of Alzheimer patients.

BACKGROUND AND PURPOSE: Alzheimer type of dementia (AD) is the most common neuropsychiatric morbidity in elderly individuals. Event-related oscillations (ERO) provide an useful tool for detecting subtle abnormalities of cognitive processes with high temporal resolution. METHODS: In the present report, event-related oscillations of patients with AD were analyzed by using a visual oddball paradigm. A total of 22 mild probable AD subjects according to NINCDS-ADRDA criteria and 20 age-, gender-, and education-matched healthy control subjects were compared. AD group consisted from 11 untreated patients and 11 patients treated with cholinesterase inhibitor. Oscillatory responses were recorded from 13 scalp electrodes. RESULTS: Significant differences in delta frequency range were seen between the groups by using repeated measures of anova analysis [F(9.120) = 2.228; P = 0.022]. Post-hoc analyses using Wilcoxon test showed that at mid- and left central regions, (Cz, C3) peak amplitudes of delta responses of healthy subjects were significantly higher than either group. Also cholinesterase inhibitors did not have effect on delta oscillatory responses. CONCLUSIONS: Our findings imply that the delta oscillatory responses at central locations are highly instable in mild probable AD patients regardless of treatment when compared to the healthy aged controls. This study supports the importance of oscillatory event-related potentials for investigating AD brain dynamics.

Estimates of soil erosion using cesium-137 tracer models.

The soil erosion was studied by 137Cs technique in Yatagan basin in Western Turkey, where there exist intensive agricultural activities. This region is subject to serious soil loss problems and yet there is not any erosion data towards soil management and control guidelines. During the soil survey studies, the soil profiles were examined carefully to select the reference points. The soil samples were collected from the slope facets in three different study areas (Kirtas, Peynirli and Kayisalan Hills). Three different models were applied for erosion rate calculations in undisturbed and cultivated sites. The profile distribution model (PDM) was used for undisturbed soils, while proportional model (PM) and simplified mass balance model (SMBM) were used for cultivated soils. The mean annual erosion rates found using PDM in undisturbed soils were 15 t ha(-1) year(-1) at the Peynirli Hill and 27 t ha(-1) year(-1) at the Kirtas Hill. With the PM and SMBM in cultivated soils at Kayisalan, the mean annual erosion rates were obtained to be 65 and 116 t ha(-1) year(-1), respectively. The results of 137Cs technique were compared with the results of the Universal Soil Loss Equation (USLE).

Eye movement disorders in vitamin B12 deficiency: two new cases and a review of the literature.

Eye movement disorders are rarely reported in vitamin B12 deficiency. We describe two cases with eye movement disorder and vitamin B12 deficiency; one with bilateral internuclear ophthalmoplegia and the other with downbeat nystagmus. Both of the patients received replacement therapy but their eye movement disorders did not respond to treatment. We also review the nine previously reported cases.

Increased frontal phase-locking of event-related theta oscillations in Alzheimer patients treated with cholinesterase inhibitors.

This is a pilot study describing event-related oscillations in patients with Alzheimer-type dementia (AD). Theta responses of 22 mild probable AD subjects according to NINCDS-ADRDA criteria (11 non-treated, 11 treated by cholinesterase inhibitors), and 20 healthy elderly controls were analyzed by using the conventional visual oddball paradigm. We aimed to compare theta responses of the three groups in a range between 4-7 Hz at the frontal electrodes. At F(3) location, theta responses of healthy subjects were phase locked to stimulation and theta oscillatory responses of non-treated Alzheimer patients showed weaker phase-locking, i.e. average of Z-transformed means of correlation coefficients between single trials was closer to zero. In treated AD patients, phase-locking following target stimulation was two times higher in comparison to the responses of non-treated patients. The results indicate that the phase-locking of theta oscillations at F(3) in the treated patients is as strong as the control subjects. The F(4) theta responses were not statistically significant between the groups. Our findings imply that the theta responses at F(3) location are highly unstable in comparison to F(4) in non-treated mild AD patients and cholinergic agents may modulate event-related theta oscillatory activities in the frontal regions.

Comparing the moisturizing effects of ascorbic acid and calcium ascorbate against that of tocopherol in emulsions.

Calcium ascorbate (CAAS), which is a hydrophilic and stable derivative of ascorbic acid (vitamin C) (AA), is commonly used in foods as an antioxidative agent. There are very limited reports on its dermatological use in the literature. In this paper, it is reported that CAAS could be used in place of ascorbic acid, which has chemical stability problems in topicals due to degradation by oxidation. The aim of this study was to investigate the skin-hydrating effect of CAAS compared to those of ascorbic acid and tocopherol (vitamin E) (T), which is a potential skin moisturizer and commonly used in dermocosmetics. Vitamins are incorporated into two kinds of base creams (o/w and w/o emulsion creams), alone and in combinations. Formulations were applied to the inner forearms of volunteers, and skin conductance was measured by using a corneometer. Data obtained were statistically evaluated. It was found that the skin-hydrating effect of CAAS was higher than that of AA and lower than that of T. However, its effect was very close to that of T.

Skin moisturizing effect and skin penetration of ascorbyl palmitate entrapped in solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) incorporated into hydrogel.

This study was performed as a complimentary to our previous study regarding the chemical stability of ascorbyl palmitate (AP) in solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and for comparison, in nanoemulsion (NE) incorporated into a hydrogel produced by high pressure homogenization. AP is known as an effective antioxidant that protects tissue integrity similar to vitamin C. Recently, its moisturizing activity in conventional topical formulations was found to be high. The aim of the present study was to investigate the moisturizing potential of AP in SLN and NLC incorporated into hydrogel as colloidal carrier systems. It has been known that SLN and NLC have occlusive effects, but AP incorporation moisturized skin significantly better than placebo in short-term (p < 0.001) and long-term trials (p < 0.01) for both SLN and NLC. In the second part of the study, SLN and NLC were found to sustain the penetration of AP through excised human skin about 1/2 and 2/3 times compared to NE (p < 0.001 and p < 0.01), respectively, due to the solid state of Witepsol E85 in the lipid phase.

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for application of ascorbyl palmitate.

The aim of this study was to improve the chemical stability of ascorbyl palmitate (AP) in a colloidal lipid carrier for its topical use. For this purpose, AP-loaded solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and for comparison, a nanoemulsion (NE) were prepared employing the high pressure homogenization technique and stored at room temperature (RT), 4 degrees C and 40 degrees C. During 3 months, physical stability of these formulations compared to placebo formulations which were prepared by the same production method, was studied including recrystallization behaviour of the lipid with differential scanning calorimetry (DSC), particle size distribution and storage stability with photon correlation spectroscopy (PCS) and laser diffractometry (LD). After evaluating data indicating excellent physical stability, AP-loaded SLN, NLC and NE were incorporated into a hydrogel by the same production method as the next step. Degradation of AP by HPLC and physical stability in the same manner were investigated at the same storage temperatures during 3 months. As a result, AP was found most stable in both the NLC and SLN stored at 4 degrees C (p > 0.05) indicating the importance of storage temperature. Nondegraded AP content in NLC, SLN and NE was found to be 71.1% +/- 1.4, 67.6% +/- 2.9 and 55.2% +/- 0.3 after 3 months, respectively. Highest degradation was observed with NE at all the storage temperatures indicating even importance of the carrier structure.

Influence of surfactants on the physical stability of solid lipid nanoparticle (SLN) formulations.

The choice of surfactant or surfactant mixtures at suitable concentrations contributes to the stability of solid lipid nanoparticles (SLN). In this study, it was found that 1.5% TegoCare 450 was the most effective stabilizer for the Witepsol E85 SLN dispersion compared to Tween 80, Tyloxapol and Pluronic F68 according to the data obtained from differential scanning calorimetry (DSC), zeta potential (ZP) measurements and particle size analysis.

Moisturizing potentials of ascorbyl palmitate and calcium ascorbate in various topical formulations.

The aim of this study was to use two of Vitamin C derivatives, lipophilic ascorbyl palmitate and hydrophilic calcium ascorbate to determine their skin-hydrating effects for the first time. For this purpose, anhydrous cream, gel and w/o emulsion were prepared and applied to the volunteers' inner forearms. A commercial topical preparation containing a known moisturizer, Vitamin E, was also chosen and used for comparison. Moisture contents of the skin were measured by using corneometer.

Effect of vehicles and penetration enhancers on the in vitro percutaneous absorption of celecoxib through human skin.

The aim of this study was the comparison of three different formulations (gel, o/w emulsion, oleagenous cream) and two penetration enhancers (oleic acid and menthol) as vehicle systems for celecoxib in respect of release and penetration through excised human skin in vitro. The influence of the vehicle on the release rate was studied in vitro using a cellulose acetate membrane. The release rate could be increased by up to 6.5 and 2.5 times with gel and o/w emulsion compared to oleagenous cream respectively. Further in vitro penetration measurements using human skin on Franz diffusion cells were performed with and without oleic acid and menthol as enhancers. It was shown that the penetration rate is strongly dependent upon the enhancer type and concentration but not on the vehicle itself and could be increased by 48% when 5% oleic acid was used in oleagenous cream. In all formulations tested, celecoxib was released and penetrated into human skin more quickly and to a greater extent from the gel formulations. There is no topical formulation available of celecoxib and its penetration properties through human skin have not been investigated. Since celecoxib creates some gastrointestinal disturbances, topical formulations of celecoxib preferably in gel form including 5% oleic acid could be suggested as an alternative.

Accumulation rates and sediment deposition in the Gökova Bay in Aegean Sea Turkish Coast.

Sediment accumulation rates were estimated from the vertical distribution of excess 210Pb in sediment cores collected at six stations in the Gökova Bay near the heavily industrialized Turkish Coastal zone of the Aegean Sea. Total 210Pb was determined by measuring 210Po activities. The sediment accumulation rates were calculated to vary from 0.32+/-0.01 cm yr(-1) (0.17 +/- 0.01 g cm(-2) yr(-1)) to 1.92 +/- 0.20 cm yr(-1) (1.13 +/- 0.10 g cm(-2) yr(-1)). The unsupported 210Pb flux was calculated from the accumulated dry matter of the examined slices and their unsupported 210Pb concentrations. The flux of unsupported 210Pb varies between 62 +/- 5 and 105 +/- 8 Bq m(-2) yr(-1). The average depositional flux was found to be considerably higher for cores from the Mediterranean.

Phe 84 deletion of the PMP22 gene associated with hereditary motor and sensory neuropathy HMSN III with multiple cranial neuropathy: clinical, neurophysiological and magnetic resonance imaging findings.

Hereditary motor and sensory neuropathy (HMSN) is a heterogeneous group of peripheral neuropathies which are diagnosed on the basis of clinical, electrophysiological and neuropathological findings. Among the hypertrophic demyelinating neuropathies, HMSN III is the most severe. It is often associated with de novo mutations in the genes encoding for peripheral myelin proteins. While peripheral nerve hypertrophy is an expected finding in HMSN III, cranial nerve hypertrophy is exceptional. Here we describe a mutation in the PMP22 gene in a 19-year-old man with infantile onset of sensory motor polyneuropathy without family history and multiple cranial nerve hypertrophy shown by cranial magnetic resonance imaging.

A case with cerebral thrombosis receiving tamoxifen treatment.

Cerebral sinus thrombosis (CST) is known to be related to a number of underlying aetiologies including otitis media, trauma, pregnancy, birth control pills, tumours, malnutrition, dehydration, haematologic disorders and malignancy (Fishman, 2000; Raizer and Abbott, 2000). We present the case of a patient with breast cancer receiving the antioestrogen drug tamoxifen who developed CST. A 40-year-old female presented as an emergency with a 10-day history of headache and left sided weakness. On questioning her past medical history included a diagnosis of breast cancer 3 years ago treated by radical mastectomy and tamoxifen 20 mg daily. At the time of admission, neurologic examination revealed a mild left sided hemiparesis and a present Babinksi sign. Non-contrast enhanced tomography was normal. Magnetic resonance imaging (MRI) showed thrombosis in the superior sagittal sinus, right lateral sinus and jugular vein in addition venous infarction in the right temporal lobe was present (Figs 1a and b). Routine haematology and biochemistry was normal. Anticoagulation tests, antithrombin III, protein S and C levels were also found to be normal. She was treated with anticoagulation therapy and her hemiparesis improved within 3 days. Control MRI showed the resorption of the venous infarction and resolution of the thrombosis (Fig. 1c).

Basal and activational 99Tcm-HMPAO brain SPECT in Alzheimer's disease.

Early diagnosis in Alzheimer's disease (AD) is important for the administration of new treatments. The purpose of this study was to differentiate mildly/moderately demented AD patients from normal controls by means of activational brain SPECT, and to investigate the correlation between regional cerebral blood flow and dementia severity. Activational brain SPECT was performed 1 week after basal brain SPECT in 12 mild/moderate AD patients according to NINCDS-ADRDA criteria (mean age 69+/-7 years) and in seven healthy, age-matched, volunteer controls (mean age 65+/-9 years). In order to activate the parietal cortex, patients were asked to subtract serial 5's from 100, 2 min before and after the intravenous administration of 925 MBq technetium-99m labelled D,L-hexamethyl-propylene amine oxime (99Tcm-HMPAO). Using a three-headed gamma camera equipped with high resolution collimators, 128 images of 35 s duration in a 64 x 64 matrix were obtained over 360 degrees. Region to whole brain ratios (R/WB) were calculated in three consecutive transaxial slices 2 pixels thick above the orbitomeatal line, and the activation percentage was calculated. No statistical difference was detected between AD patients and normal controls for parietal cortex activation. The correlation coefficient between the Mini-Mental State Examination (MMSE) scoring and the activation percentage was 0.475 in normal controls and 0.175 in AD patients for the left anterior parietal cortex, and 0.353 in normal controls and 0.146 in AD patients for the right anterior parietal cortex. In a visual evaluation of parietal cortex activation, 50% of AD patients were able to activate the parietal cortex, whereas 86% of the normal controls could do so. In our current study, the subtraction of serial 5's was not regarded as a promising task. Further studies are needed to clarify the importance of such tasks in the differential diagnosis of mild/moderate AD patients from normal elderly.

Inclusion of ketoprofen with skimmed milk by freeze-drying.

Ketoprofen is a non-steroidal anti-inflammatory drug which is not soluble in water and creates gastrointestinal problems. In order to improve the solubility of the drug in water and enhance its dissolution rate, physical mixture (PM) and inclusion (IC) of ketoprofen with skimmed milk (SM) were prepared and investigated. Enhancement of solubility of ketoprofen was obtained by preparing its IC with SM which can be used because of its amino acid and surface active agents content and can also be used for treatment of gastric disturbance. Lyophilization technique was used to prepare the IC. Results obtained showed that the solubility of IC of ketoprofen with SM was almost four times greater than the solubility of the plain drug. Data from the dissolution rate determination have also indicated that IC of ketoprofen with SM significantly improved the dissolution rate of the drug compared with PM and the plain form. Differential scanning calorimetry (DSC), X-ray powder diffraction and scanning electron microscopic (SEM) analysis revealed the formation of IC of ketoprofen with SM.

Dermatomal and mixed nerve somatosensory evoked potentials in the diagnosis of neurogenic thoracic outlet syndrome.

To evaluate the diagnostic utility of dermatomal and mixed nerve somatosensory evoked potentials (SEPs) in patients with thoracic outlet syndrome (TOS) and to compare their value with routine electrodiagnostic methods, we studied a group of 44 patients with neurogenic TOS and 30 healthy controls. In addition to bilateral median and ulnar SEPs, evoked potentials were recorded after stimulation of C6 and C8 dermatomes from the first and fifth digits, respectively. The patients were classified into 3 groups according to the nature of their clinical condition. The abnormality rate for both ulnar and C8 dermatomal SEPs was 100% in a small group of patients with severe neurological signs like atrophy. In groups of patients with lesser degrees of neurogenic damage, abnormality rates for ulnar and C8 dermatomal SEPs on affected limb(s) were 67 and 50%, respectively. Same abnormality rates were 25 and 18% in patients with only subjective symptoms. In patients with objective neurological signs, the major increase in sensitivity was with electromyography (EMG). Abnormalities of routine nerve conduction studies and F-wave latency were observed in patients with severe neurogenic damage. We concluded that the most useful tests in the diagnosis of neurogenic TOS are needle EMG and ulnar SEPs.