Spatial analysis of thickness changes in ten retinal layers of Alzheimer’s disease patients based on optical coherence tomography

Abstract The retina is an attractive source of biomarkers since it shares many features with the brain. Thickness differences in 10 retinal layers between 19 patients with mild Alzheimer’s disease (AD) and a control group of 24 volunteers were investigated. Retinal layers were automatically segmented and their thickness at each scanned point was measured, corrected for tilt and spatially normalized. When the mean thickness of entire layers was compared between patients and controls, only the outer segment layer of patients showed statistically significant thinning. However, when the layers were compared point-by point, patients showed statistically significant thinning in irregular regions of total retina and nerve fiber, ganglion cell, inner plexiform, inner nuclear and outer segment layers. Our method, based on random field theory, provides a precise delimitation of regions where total retina and each of its layers show a statistically significant thinning in AD patients. All layers, except inner nuclear and outer segments, showed thickened regions. New analytic methods have shown that thinned regions are interspersed with thickened ones in all layers, except inner nuclear and outer segments. Across different layers we found a statistically significant trend of the thinned regions to overlap and of the thickened ones to avoid overlapping.

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Assessment the Changes of Cortical Thickness in Alzheimer’s Disease in MR Images Using Freesurfer Software

Basic and Clinical Neuroscience Journal ◽

10.32598/bcn.2021.1779.1 ◽

2021 ◽

Author(s):

Nasim Sattari ◽

◽

Fariborz Faeghi ◽

Babak Shekarchi ◽

Mohammad Hossein Heidari ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Diagnosis ◽

Sensitivity And Specificity ◽

Cortical Thickness ◽

Analysis Of Covariance ◽

Control Group ◽

Significant Difference ◽

The Mean ◽

The Brain

Purpose: In this study, the main goal was to determine the correlation between the thickness of cerebral cortex and the severity of cognitive disorder in Alzheimer's disease Materials and method: Twenty patients diagnosed with Alzheimer’s disease with mean age of 72.95 year(14 women and 6 men) and Ten Cognitively normal (CN) subjects with mean age of 70.50 year( 7 women and 3 men) were included to the study. Of the AD patient and CN subjects, 70% were female and 30% were male. All individual underwent 1.5 T MRI. The MR scanning protocol included 3D MPRAGE (3D-T1W) sequence. All images were analyzed using Freesurfer v5.3 and then calculated the brain cortical thickness in 7 cortex( Inferior temporal, Middle temporal, Superior temporal, parahippocamp, parstriangularis, rostralmiddle frontal, Superior frontal). Result: The Analysis of covariance (ANCOVA) was conducted to compare the means of each region between the patient whilst control group. There was a significant difference in mean of cortical thickness in all regions. In all cases the mean of cortical thickness in CN subjects were greater than AD patients. However, the mean of Parstriangularis left hand in CN subjects was not significantly greater than the one in AD patients. The receiver operating characteristic system (ROC) was designed to evaluate the predictive power of the patient and the healthy person. We have selected a thousand cut-off points from 1.5 to 3.5mm for cortical thickness. When the cut-off points were interval (2.276878, 2.299680) millimeter in left hemisphere, the Youden’s index was maximized. The sensitivity and specificity in this case were 80%. Also when the cut-off points were within the range (2.263278, 2.282278) mm in right hemisphere, the sensitivity and specificity were 90% and 80%, respectively. Conclusion: This study demonstrates the importance of quantify the cortical thickness changes in early diagnosis of Alzheimer’s disease. In addition, examining the pattern of changes and the quantifying the reduction in the thickness of the cortex is an important tool for displaying the local and global atrophy of the brain. Also, this pattern can be used as an alternative marker for the diagnosis of dementia. Finally, to the best of our knowledge, our study is the first one to report finding on the range of cortical thickness that would help clinician to have better differential diagnose and also in this study have checked the possibility of early diagnosis of the disease.

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Young Coconut Juice Reduces Some Histopathological Changes Associated with Alzheimer’s Disease through the Modulation of Estrogen Receptors in Orchidectomized Rat Brains

Journal of Aging Research ◽

10.1155/2019/7416419 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14

Author(s):

Tatcha Balit ◽

Mosaad A. Abdel-Wahhab ◽

Nisaudah Radenahmad

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Estrogen Receptors ◽

Estradiol Benzoate ◽

Protective Role ◽

Control Group ◽

Amyloid A ◽

Estrogen Receptor Modulators ◽

End Of Treatment ◽

The Brain

Propose. This study aimed to evaluate the protective role of young coconut juice (YCJ) against the pathological changes in Alzheimer’s disease (AD) in orchidectomized (orx) rats. Methods and Results. Animals were divided into 7 groups including: baseline normal control group, sham control, orx rat group, orx rat group injected with 2.5 μg/kg b.w. estradiol benzoate (EB) 3 days a week for 10 weeks, and the orx rat groups treated orally with 10, 20, and 40 ml/kg b.w. of YCJ for 10 weeks. At the end of treatment period, animals were sacrificed and the brain of each rat was removed, fixed in 10% neutral formalin, and stained by specific antibodies against NF200, parvalbumin (PV), β-amyloid (Aβ), and estrogen receptors (ERα and ERβ). The results showed that the number of NF200- and PV-reactive neurons in the hippocampus and cerebral cortex was significantly reduced in orx rats. However, it restored to normal in orx rats injected with EB or those administrated with YCJ in a dose-related manner. Neurons containing β-amyloid (Aβ), a hallmark of Alzheimer’s disease (AD), were found to be increased in the orx rats; however; they were reduced by EB injection or YCJ administration. These results suggested the binding of the YCJ active ingredient(s) with estrogen receptors (ERs) in the brain as indicated by the detection of ERα and ERβ in neurons since a significant correlation was detected between NF200-/PV-reactive neurons vs ERα-/ERβ-reactive neurons.Conclusion. It could be concluded that YCJ is effective as EB in reducing AD pathology, probably by being selective estrogen receptor modulators.

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Electroacupuncture Improves Clearance of Amyloid-β through the Glymphatic System in the SAMP8 Mouse Model of Alzheimer’s Disease

Neural Plasticity ◽

10.1155/2021/9960304 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Pei-zhe Liang ◽

Li Li ◽

Ya-nan Zhang ◽

Yan Shen ◽

Li-li Zhang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Neurodegenerative Disorder ◽

Amyloid Β ◽

Control Group ◽

Nissl Staining ◽

Glymphatic System ◽

Model Of Alzheimer’S Disease ◽

The Brain

Background. Memory loss and cognitive impairment characterize the neurodegenerative disorder, Alzheimer’s disease (AD). Amyloid-β (Aβ) is the key factor that triggers the course of AD, and reducing the deposition of Aβ in the brain has been considered as a potential target for the treatment of AD. In clinical and animal studies, electroacupuncture (EA) has been shown to be an effective treatment for AD. In recent years, substantial evidence has accumulated suggesting the important role of the glymphatic system in Aβ clearance. Objective. The purpose of this study was to explore whether EA modifies the accumulation of Aβ through the glymphatic system and may thus be applied to alleviate cognitive impairments. Methods. Seven-month-old SAMP8 mice were randomized into a control group (Pc) and an electroacupuncture group (Pe). Age-matched SAMR1 mice were used as normal controls (Rc). Mice in the Pe group were stimulated on Baihui (GV20) and Yintang (GV29) for 10 min and then pricked at Shuigou (GV26) for ten times. EA treatment lasted for 8 weeks. In each week, EA would be applied once a day for the first five consecutive days and ceased at the remaining two days. After EA treatment, Morris water maze (MWM) test was used to evaluate the cognitive function; HE and Nissl staining was performed to observe the brain histomorphology; ELISA, contrast-enhanced MRI, and immunofluorescence were applied to explore the mechanisms underlying EA effects from Aβ accumulation, glymphatic system function, reactivity of astrocytes, and AQP4 polarization, respectively. Results. This EA regime could improve cognition and alleviate neuropathological damage to brain tissue. And EA treatment might reduce Aβ accumulation, enhance paravascular influx in the glymphatic system, inhibit the reactivity of astrocytes, and improve AQP4 polarity. Conclusion. EA treatment might reduce Aβ accumulation from the brain via improving clearance performance of the glymphatic system and thereby alleviating cognitive impairment.

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CT features of atrophy of the brain temporal lobes characteristic for Alzheimer’s disease with different stages of dementia

European Psychiatry ◽

10.1016/s0924-9338(11)72646-3 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 941-941

Author(s):

I.V. Maksimovich

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Control Group ◽

Study Group ◽

List Type ◽

Type Number ◽

Severe Dementia ◽

Temporal Lobes ◽

Clinical Stages ◽

The Brain

BackgroundWhile diagnosing Alzheimer’s disease, there appear certain difficulties in the correlation of cerebral atrophy and the patient's clinical status.Methods93 patients were examined.Study group - 42 patients aged 34-79 with preclinical and clinical stages of Alzheimer’s disease:(1)- patients with high risk of acquiring the disease (those suffering from impaired memory, without any manifestations of dementia, whose 2 or more immediate relatives suffered from Alzheimer’s disease) 6 patients(2)- patients with mild dementia 14(3)- patients with moderate dementia 15(4)- patients with severe dementia 7Control group - 51 patients aged 28–78 with various kinds of brain lesions accompanied by dementia but not suffering from Alzheimer’s disease:-chronic cerebrovascular insufficiency 21 patients-severe vascular dementia 6-atherosclerotic parkinsonism 14-Binswanger’s disease 6-Parkinson’s disease 4ResultsIn Study group 1, 4 (66.6%) patients showed decrease of 4–8% in the size of the brain temporal lobes.In Study group 2, 14 (100%) patients showed decrease of 9–18%.In Study group 3, 15 (100%) patients showed decrease of 19–32%.In Study group 4, 7 (100%) patients showed decrease of 33–62%.Control group patients had no similar changes in the temporal lobes.ConclusionsStructural and morphological changes of the brain characteristic for Alzheimer’s disease are atrophy of the temporal lobes and hippocampus which makes 4–8% in pre-clinical stages of the disease, 9–18% in mild, 19–32% in moderate and 33–62% in severe dementia.

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Easy Identification of Optimal Coronal Slice on Brain Magnetic Resonance Imaging to Measure Hippocampal Area in Alzheimer’s Disease Patients

BioMed Research International ◽

10.1155/2020/5894021 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

P. Zach ◽

A. Bartoš ◽

A. Lagutina ◽

Z. Wurst ◽

P. Gallina ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Magnetic Resonance ◽

Brain Magnetic Resonance Imaging ◽

Control Group ◽

Resonance Imaging ◽

Hippocampal Area ◽

Left And Right ◽

The Brain

Introduction. Measurement of an- hippocampal area or volume is useful in clinical practice as a supportive aid for diagnosis of Alzheimer’s disease. Since it is time-consuming and not simple, it is not being used very often. We present a simplified protocol for hippocampal atrophy evaluation based on a single optimal slice in Alzheimer’s disease. Methods. We defined a single optimal slice for hippocampal measurement on brain magnetic resonance imaging (MRI) at the plane where the amygdala disappears and only the hippocampus is present. We compared an absolute area and volume of the hippocampus on this optimal slice between 40 patients with Alzheimer disease and 40 age-, education- and gender-mateched elderly controls. Furthermore, we compared these results with those relative to the size of the brain or the skull: the area of the optimal slice normalized to the area of the brain at anterior commissure and the volume of the hippocampus normalized to the total intracranial volume. Results. Hippocampal areas on the single optimal slice and hippocampal volumes on the left and right in the control group were significantly higher than those in the AD group. Normalized hippocampal areas and volumes on the left and right in the control group were significantly higher compared to the AD group. Absolute hippocampal areas and volumes did not significantly differ from corresponding normalized hippocampal areas as well as normalized hippocampal volumes using comparisons of areas under the receiver operating characteristic curves. Conclusion. The hippocampal area on the well-defined optimal slice of brain MRI can reliably substitute a complicated measurement of the hippocampal volume. Surprisingly, brain or skull normalization of these variables does not add any incremental differentiation between Alzheimer disease patients and controls or give better results.

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Influence of PICALM and CLU risk variants on beta EEG activity in Alzheimer’s disease patients

Scientific Reports ◽

10.1038/s41598-021-99589-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Aarón Maturana-Candelas ◽

Carlos Gómez ◽

Jesús Poza ◽

Víctor Rodríguez-González ◽

Vìctor Gutiérrez-de Pablo ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Regional Distribution ◽

Control Group ◽

Protective Effects ◽

Beta Band ◽

Eeg Activity ◽

Spatial Entropy ◽

Beta Power ◽

The Brain

AbstractPICALM and CLU genes have been linked to alterations in brain biochemical processes that may have an impact on Alzheimer’s disease (AD) development and neurophysiological dynamics. The aim of this study is to analyze the relationship between the electroencephalographic (EEG) activity and the PICALM and CLU alleles described as conferring risk or protective effects on AD patients and healthy controls. For this purpose, EEG activity was acquired from: 18 AD patients and 12 controls carrying risk alleles of both PICALM and CLU genes, and 35 AD patients and 12 controls carrying both protective alleles. Relative power (RP) in the conventional EEG frequency bands (delta, theta, alpha, beta, and gamma) was computed to quantify the brain activity at source level. In addition, spatial entropy (SE) was calculated in each band to characterize the regional distribution of the RP values throughout the brain. Statistically significant differences in global RP and SE at beta band (p-values < 0.05, Mann–Whitney U-test) were found between genotypes in the AD group. Furthermore, RP showed statistically significant differences in 58 cortical regions out of the 68 analyzed in AD. No statistically significant differences were found in the control group at any frequency band. Our results suggest that PICALM and CLU AD-inducing genotypes are involved in physiological processes related to disruption in beta power, which may be associated with physiological disturbances such as alterations in beta-amyloid and neurotransmitter metabolism.

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A Comparative Study of the Detection of cAMP response element binding protein (CREB) in the Peripheral Blood of Alzheimer's Patients and the Healthy subjects as a Biomarker for the diagnosis of Alzheimer

Internal Medicine And Medical Investigation Journal ◽

10.24200/imminv.v4i2.211 ◽

2019 ◽

Vol 4 (2) ◽

Author(s):

Ahmad Chitsaz ◽

Masih Falahatian ◽

Moneer Hadadian

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Peripheral Blood ◽

Binding Protein ◽

Adenosine Monophosphate ◽

Camp Response Element Binding ◽

Control Group ◽

Case Group ◽

Healthy Elderly ◽

The Mean

Introduction: Alzheimer's disease is a neurodegenerative disease, which usually helps some biomarkers, such as amyloid proteins, to diagnose the disease. Therefore, the purpose of this study was to compare the expression of a protein binding protein to the adjuvant responder to circular adenosine monophosphate (CREB) in peripheral blood of patients to Alzheimer's and healthy elderly people as a biomarker for diagnosing Alzheimer. Materials and Methods: In this case-control study, 32 patients with Alzheimer's disease and 32 normal blood samples were taken. Using real time PCR, CREB expression was evaluated. Results: The mean CREB level in the case group was 0.89 ± 0.30 and in the control group was 1.01 ± 0.03. The mean of BDNF level in the case group was significantly higher than the control group (P <0.001). There was no significant relationship between the level of CREB with age, sex, MMSE score and Cornell scale for depression in dementia (P> 0.05). Conclusion: Reducing CREB levels in people with Alzheimer's disease can be a factor in diagnosis in comparison to healthy people.

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The Role of Galanin, Alarin, Irisin, PGC1-Α and BDNF in the Pathophysiology of Alzheimer's disease

International Journal Of Medical Science And Clinical Invention ◽

10.18535/ijmsci/v8i06.09 ◽

2021 ◽

Vol 8 (06) ◽

pp. 5498-5507

Author(s):

Huseyin Fatih Gul ◽

Caner Yildirim ◽

Can Emre Erdogan ◽

Ozlem Gul ◽

Nazlı Koc

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Control Group ◽

Peroxisome Proliferator ◽

The Novel ◽

Cross Sectional ◽

Peroxisome Proliferator Activated Receptor ◽

The Mean ◽

Positive Correlations

The roles of novel peptides such as peroxisome proliferator-activated receptor gamma coactivator 1- alpha (PGC1-α), irisin, brain-derived neurotrophic factor (BDNF), galanin and alarin in Alzheimer's disease (AD) are not fully known. It was aimed to plasma levels of the novel peptides that may affect the pathophysiology of AD were examined. This study was conducted as a cross-sectional. The study consisted of two groups, including 45 newly diagnosed individuals with AD and 45 healthy individuals. The peptide levels in plasma samples collected from the groups were measured by the ELISA method. The mean plasma peptide levels and age differences, between the groups, and the correlations between them were analyzed by the statistically. The means ages of both groups were over 65 years old. When plasma PGC1-α, irisin, BDNF, galanin, and alarin levels between the groups were examined, decreases were found in the group with AD (3.56±0.79ng/mL, 16.33±4.07ng/mL, 3.36±1.47ng/mL, 13.93±4.24ng/L, 31.99±11.89pg/mL, respectively) compared to the control group (4.23±1.31ng/mL, 22.19±9.61ng/mL, 4.58±2.10ng/mL, 14.4±9.01ng/L, 54.93±15.80pg/mL, respectively). In the negative correlations observed between age and plasma peptide levels. Significant positive correlations were observed between plasma PGC1-α levels and irisin, alarin, and BDNF, and the significant positive correlations were also observed between plasma BDNF levels and irisin and alarin. As far as we know, the study is the first report in which the peptides mentioned in AD were examined together. We consider that more detailed studies are needed to shed light on the roles and mechanisms of these peptides in AD.

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Longitudinal Changes in Individual BrainAGE in Healthy Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

GeroPsych ◽

10.1024/1662-9647/a000074 ◽

2012 ◽

Vol 25 (4) ◽

pp. 235-245 ◽

Cited By ~ 64

Author(s):

Katja Franke ◽

Christian Gaser

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Healthy Aging ◽

Brain Aging ◽

Elderly Subjects ◽

Additional Increase ◽

Longitudinal Changes ◽

Novel Method ◽

The Brain

We recently proposed a novel method that aggregates the multidimensional aging pattern across the brain to a single value. This method proved to provide stable and reliable estimates of brain aging – even across different scanners. While investigating longitudinal changes in BrainAGE in about 400 elderly subjects, we discovered that patients with Alzheimer’s disease and subjects who had converted to AD within 3 years showed accelerated brain atrophy by +6 years at baseline. An additional increase in BrainAGE accumulated to a score of about +9 years during follow-up. Accelerated brain aging was related to prospective cognitive decline and disease severity. In conclusion, the BrainAGE framework indicates discrepancies in brain aging and could thus serve as an indicator for cognitive functioning in the future.

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