Summary of thesis on doctor of medicine: Research into morphological features and some special pulse sequence on brain magnetic resonance in alzheimer patients

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Practical questions put forward by clinicians in the past have been researched and settled in the thesis. The AD diagnosis is completely based on clinics and the implementation of clinical tests for the diagnosis work depends on assessors’ subjectivity. Therefore, the development of MRI techniques shall help clinicians make diagnosis more quickly and objectively.

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Nội dung Text: Summary of thesis on doctor of medicine: Research into morphological features and some special pulse sequence on brain magnetic resonance in alzheimer patients

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH HANOI MEDICAL UNIVERSITY NGOC TRAN VAN RESEARCH INTO MORPHOLOGICAL FEATURES AND SOME SPECIAL PULSE SEQUENCE ON BRAIN MAGNETIC RESONANCE IN ALZHEIMER PATIENTS Specialism : Radiology Diagnosis Code : 62720166 SUMMARY OF THESIS ON DOCTOR OF MEDICINE HANOI – 2021
Research completed at: HANOI MEDICAL UNIVERSITY Scientific instructors: ASSOC. PROF & PHD THANG PHAM ASSOC. PROF & PHD LUU VU DANG Defender 1: Defender 2: Defender 3: The Thesis shall be defended at the PhD Council of Medicine at Hanoi Medical University At on 2021 The Thesis can be found at: - National Library; - Library of Hanoi Medical University
1 INTRODUCTION Alzheimer disease is the degeneration pathology of the central nerve system with features of gradually increasing but unrecoverable progression. It causes the memory loss, cognitive disorder, and changes in behaviors, which affects patients’ occupation and social lives. Current criteria for Alzheimer disease is mainly diagnosed based on such three globally accepted current clinical criteria as DSM V1, ICD X2, NINCDS-ADRDA3. Magnetic resonance images (MRI) can be considered as paraclinical tests relevant to Alzheimer disease diagnosis as they allow to precisely measure the brain weight in 3 directions (3D), especially the size of the hippocampus and related areas5 as well as image changes in AD patients based on their diffusion, spectro, and perfusion. Therefore, the development of image diagnosis methods by MRI for Alzheimer disease in the pre-clinical stage is very vital and pressing, especially for the 3 pulse sequences: diffusion, spectro, and perfusion. This has brought about a positive imaging method in AD diagnosis. Some researchers in Vietnam have initially studied the MRI morphology. However, none of them has utilized such pulse sequences as: diffusion, spectro, and perfusion to quantify changes in brain images in AD patients. We have conducted the theme: “Research into morphological features and some special pulse sequences on brain magnetic resonance in Alzheimer disease patients” in order to: 1. Description of brain’s morphological features in Alzheimer disease patients; 2. Analysis of magentic resonance features like diffusion, perfusion, and spectro in Alzheimer disease patients’ brains. 3. Assessment on changes in pulse sequences of brain magnetic resonance in Alzheimer disease patients based on other age, gender, and disease level variables. 1. The thesis’s topicality Practical questions put forward by clinicians in the past have been researched and settled in the thesis. The AD diagnosis is completely based on clinics and the implementation of clinical tests for the diagnosis work depends on assessors’ subjectivity. Therefore, the development of
2 MRI techniques shall help clinicians make diagnosis more quickly and objectively. Besides, parameters of pulse sequences of Diffusion-weighted imaging show the number of AD infected people patients quickly increases in countries worldwide in general and in Vietnam in particular. This causes pressure for diagnosis, cares, and treatment. The search for an early and precise diagnosis method is necessary. The thesis orients toward changes in AD patients’ brains compared to those people with normal brains based on MRI filming, especially the application of pulse sequences of diffusion, spectro, and perfusion. Although the benefits of using MRI to diagnose AD have been studied and pointed out by many researchers, there have been remained several inconsistent viewpoints and assessment by researchers in the world. The benefits need further researching in machines of new generations and higher magnetics whereas there haven't been any researches into these three pulse sequences in Vietnam yet. 2. The thesis’s new contributions The use of clinical diagnostic tests causes many difficulties in diagnosis, especially at those places where there are not specialists. Results from brain MRI of our AD patients may help clinicians gain more foundations for AD diagnosis in line with the Vietnamese’s parameters. The T13D pulse sequence shows differentiation in AD patients’ brain morphology compared to that in the control group in terms of changes in MTA, IUD, B, E Indicators, and especially the volume of the hippocampus. The clinicians may base on these to make diagnosis. This is the first research in Vietnam with diffusion, spectro, and perfusion that utilizes MRI to quantify changes in AD patients’ brains and point out clear differentiation compared to those in the control group. By measuring the changes in these pulse sequences, it is easy to identify brain injuries caused by AD. These Indicators may suggest identifying the parameters to diagnose AD as well as those in Vietnamese people with normal brains. The conclusions of this research do not only help radiologists gain foundations for identification of brain injuries in AD patients on MRI image films, especially on diffusion, spectro, and perfusion but help
3 clinicians and researchers in diagnosing, treating, following up and making other researches into AD patients as well. 3. The thesis’s lay-out The thesis is 150 page thick. In addition to the questioning (3 pages), the conclusion part (2 pages), the part that tells about restrictions (1 page), and the part with proposals (1 page); there are 4 chapters, including: Chapter 1: The overview part which is 42 page long, Chapter 2: The part of research subjects and methods with 23 pages, Chapter 3: The part of research results with 41 pages; Chapter 4: Discussion part with 37 pages. The thesis consists of 63 charts, 01 column chart, 30 visuals, and 148 references. CHAPTER 1: OVERVIEW 1.1. Brain anatomy and functions Anatomy, brain’s functions and components; The brain lobes: frontal lobe, temporal lobes – hippocampal lobes, occipital lobe, and parietal lobe. 1.2. Pathogenesis, risk factors, epidemiology of Alzheimer disease  Pathogenesis;  Risk factors of Alzheimer disease: Risk factors of vascular pathology, social psychology, lifestyle factors, and other ones.  Alzheimer disease’s epidemiology 1.3. Injuries in Alzheimer disease patients’ brains Massive changes arising in the whole brain; Injuries caused by pathological Molecular imaging lesions. 1.4. Alzheimer disease diagnosis Since the 1970s of the 20th Century, many SSTT and Alzheimer disease diagnostic criteria have been used: those diagnostic criteria upon DSM - IV - TR1, diagnostic criteria upon the 10th International Classification of Diseases (ICD X)2, and those on NINCDS-ADRDA3 which are the 3 criteria sets used to diagnose Alzheimer disease. 1.5. Magnetic resonance pulse sequences in Alzheimer disease diagnosis 1.5.1. T1W - 3D pulse  Brain injury images on magnetic resonance in Alzheimer disease patients: White matter abnormalities, cerebrovascular
4 disease, ventricular dilatation phenomenon, and brain atrophy phenomenon;  Assessment on brain atrophy in Alzheimer disease patients;  Volume of the hippocampus;  IUD interuncal distance and Bicaudate proportion:  Evan Indicator. 1.5.2. Diffusion-weighted imaging (DWI) Pathological lesion images are detected thanks to the Diffusion- weighted imaging in diagnosis of white matter disease, fibrous plaques, changes in diffusion in brain regions. Diffusion-weighted imaging is the valuable imaging technique, especially in further provision of crucial information on many pathological processes in the cranium which it is impossible or very difficult to assess in tumor disease, inflammation, and white matter disorder, etc., in Alzheimer disease if applying the routine magnetic resonance. 1.5.3. Magnetic resonance cisternography (MRC) Such peak concentration of substances as N-acetylaspartate (NAA), Myoinositol (Myo), Choline (Cho), Creatine (Cr), Glutamate và Glutamine (Glx), Lactate, Alanine (Ala), and Lipids in the magnetic resonance cisternography is measured to assess changes in the brain when clinical injuries have not been caused. Upon observation researches, N-acetyl aspartate in Alzheimer disease patients remarkably decreases in brain regions and bilateral hippocampus. The NAA/Cr proportion greatly decreases in the posterior brain region. Simultaneously, the Myo/Cr proportion remarkably decreases, not only in the posterior brain region but in the gray matter area as well. The data point out that NAA, Myo, and NAA/Cr proportion may be potential biomarkers of brain dysfunctions in AD patients. Choline (Cho)/Cr and Myo/NAA may make contributions to the diagnosis process. The magnetic resonance cisternography imaging is cheaper, contamination-free, and may be applied in the big community. 1.5.4. Magnetic resonance perfusion weighted imaging/MRP Researches into magnetic resonance perfusion weighted imaging: Alzheimer disease may reduce target neuron’s activities in the cortical area and cerebral blood flows (CBF) in such areas. The correlation
5 between CBF in the injured areas shows the reduction in magnetic resonance perfusion weighted imaging and changes in the white matter in AD while micro-weakness may make greater impacts in the progression stages. Measurement of cebreral blood flow (CBF) is similar to a biomarker that may arise the most early and reliably for Alzheimer disease diagnosis. Magnetic resonance imaging (MRA/Magnetic Resonance Angiography) by arterial pulse (MR) measures CBF by marking arteries and utilizing it as an endogenous probe. 1.6. Local and foreign research situation 1.6.1. Local research situation MRI had been applied to diagnose cardiovascular pathology and later, to diagnose such brain pathologies as tumor, injuries, and strokes in Vietnam from the 1990s of the 20th century. The researchers have recently started to study AD pathology, which will help clinicians to manage to early make diagnosis and differientiate other brain pathologies. Despite some initial researches into images of AD patients’ brain injuries on MRI films, they have only focused on the use of basic pulse sequences to assess the morphology and volume of some brain areas. None of the researchers has ever deeply analyzed brain injuries in AD patients based on pulse sequences, especially in MRI to early diagnose AD patients. 1.6.2. Foreign research situation Many recent researches into Alzheimer disease have focused on different approaches to search for images of brain injuries through MRI pulse sequences. Dahlbeck and partners48 introduce one variable named Interuncal Distance (IUD) which is the tool to measure the atrophy level of the hippocampus. This tool is presented as a simple diagnosis method for Alzheimer disease patients and a distance of 30mm upward may mean the existence of the disease. Scheltens and partners49 report the sensitivity of 81% by visual assessment on the hippocampal and temporal lobes (MTA: Medical Technology Assessment). This result is reported to be significantly correlated with volume atrophy.
6 The remarkable decrease of the average diffusion when making diffusion MRI in the affected areas: the hippocampus, the one near the hippocampus, and cingulate gyrus is the foundation for Alzheimer disease early diagnosis. On magnetic resonance cisternography, NAA decreases while MyoInositol increases in such areas as occipital, temporal, parietal, and frontal lobes in Alzheimer disease patients. Lately, MRS has shown the ability to diagnose mild cognitive impairment (MCI) which is a pathology recorded as the start of dementia. MRS is also able to anticipate that MCI in patients will evolve into Alzheimer disease. Cerebral blood flow (CBF)’s decrease on brain lobes is a reliable biomarker that may arise early when diagnosing Alzheimer disease in the perfusion magnetic resonance. MRI identifes changes in the brain, which helps diagnose Alzheimer disease from the early stage: Magnetic resonance pulse sequences show the images of brain atrophy, especially those of medial temporal and hippocampal lobes in AD patients, the average diffusion level in different brain areas with increases & decreases of substance concentration in the spectro and decreases in brain regions on perfusion pulse sequence, then, Alzheimer disease can be early diagnosed and detected. CHAPTER 2 RESEARCH SUBJETS AND METHODS 2.1. Research subjects, areas, and timing 2.1.1. Research subjects 2.1.1.1. Selection criteria * The group of Alzheimer disease infected patients (The disease group): The group consists of patients who go for medical checks-up and treatments at the Central Geriatric Hospital during the research period. They are 55 years old plus regardless of their genders. Patients will be diagnosed as suffering from dementia caused by Alzheimer disease upon the criteria of the 5th adjusted Diagnostic & Statistical Manual of Mental Disorders (DSM V) of American Psychiatric Association at the Central Geriatric Hospital. They are given with sufficient diagnosis tests. * The control group of patients (The control group):
7 The group consists of patients who go for medical checks-up and treatments at Bach Mai Hospital. They are assigned to have cranium MRI at Electro Optical Center at Bach Mai Hospital and injected with magnetic contradictory drug to complete diagnostic billan. They are 55 years old plus and do not catch any brain-related diseases. 2.1.1.2. Exclusion Criteria - They are patients who suffer from the dementia due to some other reasons like blood vessels, Lewy, frontal – temporal lobes, and in Pick disease. - Patients who suffer from diseases that may cause impacts in such awareness and cognitive activities as cerebrovascular strokes, encephalitis, brain abscess, meningitis, metabolic disorder, and traumatic brain injury. 2.1.2. Research area The rersearch was made at Central Geriatric Hospital and the Electro Optical Center of Bach Mai Hospital. 2.1.3. Research timing The research had been made from September 2016 until September 2020. 2.2. Research method 2.2.1. Research design The theme is conducted upon the cross-sectional descriptive research method with the comparison between the two groups. 2.2.2. Sample size: + The sample size applied to the cross-sectional descriptive research with the comparison between the two mean values: In which: n: Sample size; µ1: NAA/Cr proportion in AD patients, μ1 = 1,27 53 µ2: NAA/Cr proportion in people with normal brains μ2 = 1,5 53 δ: Criterion deviation, δ = 0,19 α: Statistical significance level. α = 0.05 1 - β: Sample force selected by researchers. Take 1 - β = 0,8
8 Research co-efficient: 3 The sample size for each disease group and control group to analyze the differentiation between AD infected people and AD non-infected one is 40. The total number of research participants is 80. The sample size for the research into assessment on changes in AD patients’ brain images on pulse sequences of T13D, diffusion, spectro, and perfusion with age, gender, and level variables is 40. 2.2.3. Sampling method We randomly select samples of patients who go to Central Geriatric Hospital for medical checks-up, treatments, are diagnosed as catching Alzheimer disease and fully meet criteria to be accepted as patients in the research group until reaching the number of 40 patients. Similarly, we randomly select 40 qualified patients to be included in the control group. The numbers of the research and the control groups meet the sample sizes (at least 33 patients in each group) to assure for the research’s statistical significance. During the day with screening tests by specialty, we randomly select one patient diagnosed as catching AD with all criteria for selection, approach, explanation, and encouragement for his/her participation in the research process. If the patient agrees, we shall select him/her for the research group and conduct an MRI in line with the research process. If the patient refuses, we will move to the next patient who will also be selected in a similar way on the next specialty check-up day. The patients selected for the control group are those who go for the first-time check-up and are clinically diagnoses as they do not catch AD. We approach them, give explanations, and encourage them to participate in the research process. If they agree, we shall select them for the control group. Afterward, MRI will be provided to them in line with the research process. Finally, we shall compare the results with exclusion criteria. If any patients do not meet the criteria, we shall exclude them and continue replacing them with other next patients until reaching the sufficient sample size for the research. 2.2.4. Research variables 2.2.4.1. Variables of patient features + Ages: AD often arises in people of 65 years old plus. However, there remain cases in which the disease arises in younger people. In
9 order to cover the age data and simultaneously to further learn about the proportion of AD infected people less than 65 years old, we choose samples of people over 55 years old for the research as it is the retirement age of female employees in Vietnam. + Gender is considered as one of the causes of AD. Many researchers have pointed out that the disease is more common in women. However, there have been researches recently that suppose the proportions in women and men are equal. It seems the proportion in women is higher because of such factors as longevity, living conditions, occupation, habits, and customs, ect., these are the data collected from patients’ medical records for treatments. + MMSE point is assessed based on MMSE test kit (appendix) by groups of neurologists at Central Geriatric Hospital with PhD degree upward. - The assessment MMSE scale is presented as the followings: + Level 1: The cognitive impairment has not arisen: ≥ 24 + Level 2: Mild cognitive impairment: 20 - 23 + Level 3: Medium cognitive impairment: 14 - 19 + Level 4: Severe cognitive impairment: 0 – 13 - Patients who do not catch Alzheimer disease (Level 0) in the control group all gain the maximum MMSE points of 30. 2.2.4.2. Morphological survey pulse variables on cranium magnetic resonance imaging * Temporal lobe atrophy: To assess the temporal lobe atrophy based on the MTA scale which is the easily conducted visual assessment method. This is a crucial tool to diagnose AD. The criteria scale (Scheltens) is utilized to assess MTA based on image copies of T1W 3D pulse sequence. * Interuncal distance: Interuncal distance measurement technique (interuncal distance, IUD) is identified as the shortest distance between the two hippocampal heads on the axial cutting layer at the level where the front edge appears for the first time. * Bicaudate proportion: In reality, it is very difficult to assess the interuncal distance because of brain sizes and volumes among different groups and races of people to lessen this restriction and eliminate impacts of the head size and brain volume. The researchers standardize
10 values and divide the interuncal distance to the bitemporal distance to gain Bicaudate proportion Interuncal distance Bicaudate proportion = Intertemporal lobe distance * Evan Indicator: Evan Indicator is identified as the proportions of the distances between the two frontal horns of the ventricles and the intracranial width. Normally, this Indicator is less than 0.3. If it is over 0.3, this proves the dilation of the ventricles and diffusion cerebral atrophy. The distance between the identified two frontal horns of the ventricles is the longest distance between the two frontal horns of the lateral ventricles. We also utilize the distance formula between two points on Descartes coordinate system as the one to measure the interuncal distance. Evan Indicator = * Volume of hippocampus: in order to measure the volume of hippocampus, we have identified the hippocampus in the cranium magnetic resonance imaging from the first cutting layer where the hippocampus appears and a boundary line shall be drawn. This means the hippocampus area reaching the cutting layer. The volumetric result of the hippocampus is recorded. 2.2.4.3. Variables for diffusion pulse sequence: Technical parameters: TR: 1524ms, TE: 40ms; Slice: 5mm, Phase (cutting direction) R>L, Matrix: 92X90; FOV: 224x224, Gap (Distance among slices):0 Average (Average number of received times): 1 Parameters that need collecting: Average apparent diffusion coefficient Location to take measurements: at the hippocampus and 4 brain lobes: temporal, parietal, frontal, and occipital lobes on both 2 brain left & right lobes. 2.2.4.4. Variables for magnetic resonance cisternography (MRS): Technical parameters: TR: 900ms, TE: 144ms; Slice: 3mm, Phase (cutting direction) A>P, Matrix:180X160; FOV: 180x180, Gap
11 (Distance among slices): 0; Average (Average number of received times): 1 Parameters that need collecting: * NAA concentration Myo – inositol concentration, Cr, Cho, Lip, Lac, Glx, and Ala on magnetic resonance cisternography & the NAA/ Cr proportion. Location to take measurements: Temporal lobes and the hippocampus on both right & left brains. 2.2.4.5. Variables for Magnetic resonance perfusion weighted imaging: * Technical parameters: TR: 1524ms, TE: 40ms; Slice: 5mm, Phase (cutting direction) R>L, Matrix:92X90; FOV: 224x224, Gap (Distance among slices): 0 Average (Average number of received times): 1 * Parameters - Cerebral Blood Flow CBF (ml of blood /100gr of organization/min): CBF of the average brain’s white matter is at 22 +/- 5 ml/100g/min. - Cerebral Blood Volume CBV (ml of blood/100gr): CBV of the average brain’s white matter is at 1.7 +/- 0.4 ml/100g. - Time for drug concentration through tissues to reach to the peak (time to peak) TTP (sec) - Mean Transit Time/MTT (sec) CBF = CBV/MTT: 4.8 sec on the white matter region on average. * Measurement locations: The hippocampus and 4 brain lobes: temporal, parietal, frontal, and occipital lobes on both 2 brain left & right lobes. 2.2.5. Means and methods of data collection Cranial MRI imaging research equipment: MRI imaging machines Philips Ingenia 1.5 Tesla are placed Electro Optical Center of Bach Mai Hospital. Cranial MRI imaging scan process: After choosing qualified patients in terms of sample and research subject selection for the research, the following processes like: prepartion of patients, common drugs & medical supplies, and steps of implementation will be conducted.
12 2.2.6. Data processing method Quantitative data: Collected data will be cleaned, punched, and analyzed by using SPSS 22.0 software. 2.2.7. Moral aspect in the research This research proposal has been approved by Judging Committee for Phd thesis proposal of Hanoi Medical University whereas the theme’s research process has been approved by Science Council of the Central Geriatric Hospital. CHAPTER 3: RESEARCH RESULTS 3.1. General features of research subjects 3.1.1. Age feature AD group’s average age is at 73.07 ± 9.24 while the control group’s average age is at: 71.67 ± 9.13. There are not any age gaps between the AD patient group and the control one with p > 0.05. 3.1.2. Gender feature The men proportion in the AD patient group is at 52.5% (21) while the women one is at 47.5% (19). The former proportion in the control group is at 62.5% (25) whereas the women one is at 37.5% (15). There are not any gender gaps between the AD patient group and the control one with p > 0.05. 3.1.3. Features of the AD infected patient group (the research group) Upon the four levels of MMSE scale: the 3rd level accounts for 35% while the 2nd one accounts for 27.5%; the 1st level is at 20%; and the 4th one is at 17.5%. There is the differentiation between the mean MMSE score among the levels in the AD group with p < 0.05. There are not any gender or age gaps in the AD patient group with p > 0.05. All patients in the control group gain an MMSE of 30 scores. 3.2. Morphological features (T1W - 3D pulse sequence) 3.2.1. Visual ssessments on medial temporal lobe atrophy on MRI (MTA) The mean MTA in the AD group on the right brain is at 2.20 while that in the control group is at 0.65. There is the differentiation between the mean MTA in the AD group’s left brains of 2.20 and that in the control group with p < 0.05.
13 3.2.2. Ressearch subjects’ hippocampal volume The mean right hippocampal volume in the AD group is at 2.48 ± 0.86 while the one in the control group is at 3.15 ± 0.55; the left hippocampal volume in the AD group is at 2.50 ± 0.78 whereas the one in the control group is at 3.10 ± 0.61. The statistical differentiation is with p < 0.05. 3.2.3. Interuncal distance (IUD) The mean IUD is 2.86 ± 0.42; the mean BTD is 12.80 ± 0.56; and the mean B proportion is at 0.19 ± 0.80 in the AD group. Those in the control group are at 2.52 ± 0.32; 12.83 ± 0.79; and 0.15 ± 0.80 successively. There is the differentiation with p < 0.05 in the mean IUDs and B proportions in the AD group and the control one but There is not any differentiation with p > 0.05 in terms of BTD. 3.2.4. Evan Indicator The mean BTH distance is at 3.97 ± 0.54; the mean ICW distance is at 12.62 ± 0.85; and the mean E proportion is at 0.29 ± 0.15 in the AD group. Those in the control group are at 3.57 ± 0.46; 12.38 ± 0.84; and 0.23 ± 0.14 successively. There is the differentiation with p < 0.05 in the mean BTH distances and the E proportions in the AD group and the control one but There is not any differentiation with p > 0.05 in terms of ICW distances. 3.3. Research subjects’ brain images on special pulse sequences 3.3.1. Research subjects’ brain images on diffusion-weighted imaging The mean apparent diffusion coefficients at the right hippocampus and the left one in the AD group are 162.86 & 146.48 lower than those in the control group whereas those at the right & left temporal lobes are at 84.31 and 93.92 successively; those at the right & left parietal lobes are at 104.36 and 108.72; those at the right & left forehead lobes are at 78.33 and 94..88; and those at the right & right occipital lobes are at 138.1 and 130.25 all successively. There is the differentiation with p < 0.05 in the mean apparent diffusion coefficients in the AD group and the control one at measuring positions. 3.3.2. Research subjects’ brain images on magnetic resonance cisternography The parietal magnetic resonance cisternography at the temporal lobes and hippocampus in the AD group is with decreasing NAA peak and
14 NAA.Cr indicator but increasing Myo, Cr, and Cho compared to those in the control group. There is the differentiation with p < 0.05 between the AD group and the control one. The remaining mean peaks of intermediate metabolites are Lip, Lac, Glx, and Ala at the temporal lobes and hippocampus in the AD group and the control one change. However, there is not any differentiation with p > 0.05. The NAA/Cr proportions at the right and left temporal lobes experience a mean reduction of 0.2167 (1.2881 and 1.5048) & 0.2166 (1.2876 and 1.5042); The NAA/Cr proportions at the right and left hippocampuses experience a mean reduction of 0.2622 (1.2701 and 1.5323) & 0.2743 (1.2611 and 1.5354). 3.3.3. Research subjects’ brain images on magnetic resonance perfusion weighted imaging CBF indicators measured at temporal, parietal, occipital, frontal, and hippocampal lobes in the AD group all decrease compared to those in the control group. The differentiation is statistically significant with p < 0.05. CBV indicators measured at parietal and hippocampal lobes in the AD group increase compared to those in the control group. The differentiation is statistically significant with p < 0.05. On the contrary, CBV indicators measured at temporal, occipital, and frontal lobes in the AD group show no differentiation compared to those in the control group with p > 0.05. MTT and TTP indicators measured at temporal, parietal, occipital, frontal, and hippocampal lobes in the AD group all increase compared to those in the control group. The differentiation is statistically significant with p < 0.05. 3.4. Morphological changes by age, gender, and disease severity 3.4.1. Changes in MTAs by age, gender, and disease severity There is the differentiation with p < 0.05 in the mean MTA score in the right brain by age group while there is not any differentiation in the left brain. Neither is there in the mean MTA scores by gender and disease severity with p > 0.05.
15 3.4.2. Changes in hippocampal volumes by age, gender, and disease severity There is the differentiation with p < 0.05 in the hippocampal volume in the right brain by age group while there is not any differentiation in the left brain. Neither is there in the hippocampal volume by gender and disease severity with p > 0.05. 3.4.3. Changes in IUDs and B proportions by age, gender, and disease severity There is not any differentiation with p > 0.05 in the mean IUDs and BTDs by the age and gender groups. There is the differentiation with p < 0.05 in the mean B proportion. There is not any differentiation with p > 0.05 in the mean IUDs, BTDs, and B proportion by disease severity. 3.4.4. Changes in BTH distances by age, gender, and disease severity There is not any differentiation with p > 0.05 in the mean BTH distance, ICW distance, and E proportion by the age, gender, and disease severity. 3.5. Changes in special pulse sequences by age, gender, and disease severity 3.5.1. Changes in diffusion indicators by age, gender, and disease severity The mean apparent diffusion coefficients by the age and gender groups at temporal, frontal, occipital, and hippocampal lobes change. There is not any differentiation with p > 0.05. The differentiation at the parietal lobe is statistically significant with p < 0.05. There is not any differentiation with p > 0.05 in the mean apparent diffusion coefficients by disease severity in the AD group at the measuring positions. 3.5.2. Changes in magnetic resonance cisternography by age, gender, and disease severity (ppm) There is the differentiation with p < 0.05 in spectral concentrations of metabolites at the temporal and hippocampal lobes by age group and decreasing NAA. There is not any differentiation with p > 0.05 in the NAA/Cr proportion and peak concentrations of the remaining metabolites. Spectral concentrations of metabolites and NAA/Cr proportion by gender at the temporal lobes change which is not statistically significant
16 with p > 0.05. Peak concentrations of intermediate metabolites - Cr at the hippocampus by gender increase more in men than in women. There is the differentiation with p < 0.05. Peak concentrations of intermediate metabolite named as Glx at the right hippocampus decrease more in men than in women p < 0.05. The NAA/Cr proportion at the hippocampus in the AD group decreases more in men than in women with p < 0.05. Peaks of the remaining metabolites change. There is not any differentiation with p > 0.05. There is not any differentiation with p > 0.05 in peak concentrations of intermediate metabolites and the NAA/Cr proportion at the temporal and hippocampal lobes in the AD group. 3.5.3. Changes in magnetic resonance perfusion weighted imaging in AD patients by age, gender, and disease severity There is the differentiation with p < 0.05 in decreasing CBF indicators by age in the AD group at the temporal, occipital, and hippocampal lobes; however, there is not any differentiation with p > 0.05 at the parietal and frontal lobes. CBV indicator increases by age group. There is the differentiation with p < 0.05 at the parietal and frontal lobes but there is not any differentiation with p > 0.05 at the temporal, occipital, and hippocampal lobes. MTT and TTP indicators by age group increase at all 5 lobes. The differentiation is statistically significant with p < 0.05. The mean CBF, CBV, MTT, and TTP indicators at the temporal, parietal, occipital, frontal, and hippocampal lobes in the AD group by gender and disease severity change. There is not any differentiation with p > 0.05. CHAPTER 4: DISCUSSION 4.1. AD patients’ features 4.1.1. Age features AD patients’ average age is at 73.07; those ranging from 70 to 80 years old account for 47.5%. This result is similar to that of Jacquier researcher who states the average age of the AD group is at 73.3 which is lower than that of 74.7 ages stated by the researchers named Nguyen Thi Thanh Binh and Saka; while Jack and partners state it at
17 79.6 ages & the one by the researcher named Schuff N. is at 75.8, because our Alzheimer disease patients’ ages are evenly spread. Nevertheless, the average age in other researches is lower than that in our research. Laakso shows the AD patients’ average age is at 70 but at 72.3 ages by Convit & 70.7 ages by Scarmeas. The average age taken from the samples from the community may be lower than that concluded from researches at hospitals. 4.1.2. Gender features The proportion of AD male patients is 52.5% while that of female ones is at 47.5%, which is similar to those of 52% and 48% successively stated by Schuff N., however, the proportion of AD male patients at 54% stated by the researcher named Scarmeas is rather high compared to the one in other researches. Most of local and global researchers suppose that the proportion of female patients is higher than that of male patients. This differentiation is explained that women’s longevity is higher than men’s. In terms of genetics and endocrine, women are more vulnerable to catch Alzheimer disease to men. Women’s academic levels are usually lower than those in men. More women work manually than men. 4.1.3. Disease severity features MMSE score is currently still considered as the main criterion to diagnose and assess the disease’s severity levels. The maximum MMSE score of 30 is the normal one (not suffering from the disease) while there is the differentiation with p < 0.05 among the levels. There is not any differentiation with p > 0.05 in the distribution of the disease severity levels by gender and age groups. 4.2. Patients’ brain morphological featurs 4.2.1. Patients’ MTA scores The AD group’s the mean MTA score between the right and left brains, in our research, is at 2.20 – 1.5 score different from that in the control group. The researcher named Duara points out that when MTA score is over 1.33, the risk to suffer from AD shall be up to 85%. The researchers Claus and Jules J. propose the specific MTA cutoff score at 1.5 for clinical application, which means if MTA > 1.5, it can be
18 concluded that patients suffer from the temporal lobe atrophy and may catch AD. 4.2.2. Patients’ hippocampal volume The AD group’s right and left hippocampal volumes reduce by 0.67 and 0.6 successively compared to those in the control group with p < 0.05. According to Qian Shen, the AD group’s right and left hippocampal volumes both reduce similarly to those in our research. They reduce by 0.68 and 0.73 successively; Mikko Laakso shows the reduction in the hippocampus is higher than that in our research at 1.05 and 1.34 successively in the right & left hippocampal volumes. The reduction in the hippocampal volumes in MR means patients may catch AD. Thus, the quantification of hippocampal volumes may be a clinical diagnosis technique for AD. 4.2.3. IUD and Bicaudate proportion The AD group’s IUD is 0.34 higher while the B proportion is 0.04 higher compared to those in the control group with p < 0.05. Mikko Laakso researches the AD group and finds out its IUD is at 3.10 while that by the researcher Nguyen Duy Bac is at 3.4 which is higher than the IUD in our research, perhaps because of the sampling selection or the differentiation in the brain volume in each different race and age. Many other researchers also point out that when the IUD indicator is higher than 30mm, this means the high specificity for the AD. However, there are also conflicting data in screening capacity of IUD size due to the overlapping between AD and the control group. 4.2.4. Evan Indicator BTD and E proportion in the AD group, in our research, are higher than those in the control group with p < 0.05. The researcher Mengqui Liu measures the indicator E in AD patients with mild cognitive impairment at 0.29. This makes suggestions on screening those people with an indicator E > 0.3 so AD can be diagnosed. 4.3. Patients’ brain images on the special pulse sequence 4.3.1. Alzheimer disease patients’ brain images on the diffusion magnetic resonance In our research, the AD group’s mean apparent diffusion coefficient is lower than that in the control group at such measuring