DWI-based MR thermometry: could it discriminate Alzheimer's disease from mild cognitive impairment and healthy subjects?

PURPOSE: The aim of this study is to compare lateral ventricular cerebrospinal fluid (CSF) temperature of the patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy subjects (HS) using diffusion-weighted imaging (DWI)-based magnetic resonance (MR) thermometry. METHODS: Seventy-two patients (37 AD, 19 MCI, 16 HS) who underwent 3-T MR examination from September 2018 to August 2019 were included in this study. Smoking habits, education level, disease duration, and comorbidity status were recorded. Patients were assessed using Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR) score. Brain temperatures were measured using DWI-based MR thermometry. Group comparisons of brain temperature were performed using the Pearson chi-square, Mann-Whitney, and Kruskal-Wallis tests. Further analysis was performed using the post hoc Bonferroni test. Receiver operating characteristic (ROC) analysis was also used. RESULTS: A CDR score of 0.5, 1, and 2 was 2 (5.4%), 14 (37.8%), and 21 (56.8%) in AD, respectively. The median MMSE score had significant differences among groups and also in pairwise comparisons. The median CSF temperature (°C) values showed statistically significant difference among groups (HS: 38.5 °C, MCI: 38.17 °C, AD: 38.0 °C). The post hoc Mann-Whitney U test indicated a significant difference between AD patients and HS (p = 0.009). There were no significant CSF temperature differences in other pairwise comparisons. CONCLUSION: Lower CSF temperatures were observed in AD patients than in HS, probably due to decreased brain metabolism in AD. DWI-based MR thermometry as a noninvasive imaging method enabling the measurement of CSF temperatures may contribute to the diagnosis of AD.

Volumetric Assessment of Hippocampus and Subcortical Gray Matter Regions in Alzheimer Disease and Amnestic Mild Cognitive Impairment.

BACKGROUND: Quantitative MRI assessment methods have limited utility due to a lack of standardized methods and measures for Alzheimer disease (AD) and amnestic mild cognitive impairment (aMCI). OBJECTIVE: To employ a relatively new and easy-to-use quantitative assessment method to reveal volumetric changes in subcortical gray matter (GM) regions, hippocampus, and global intracranial structures as well as the diagnostic performance and best thresholds of total hippocampal volumetry in individuals with AD and those with aMCI. METHOD: A total of 74 individuals-37 with mild to moderate AD, 19 with aMCI, and 18 with normal cognition (NC)-underwent a 3T MRI. Fully automated segmentation and volumetric measurements were performed. RESULTS: The AD and aMCI groups had smaller volumes of amygdala, nucleus accumbens, and hippocampus compared with the NC group. These same two groups had significantly smaller total white matter volume than the NC group. The AD group had smaller total GM volume compared with the aMCI and NC groups. The thalamus in the AD group showed a subtle atrophy. There were no significant volumetric differences in the caudate nucleus, putamen, or globus pallidus between the groups. CONCLUSION: The amygdala and nucleus accumbens showed atrophy comparable to the hippocampal atrophy in both the AD and aMCI groups, which may contribute to cognitive impairment. Hippocampal volumetry is a reliable tool for differentiating between AD and NC groups but has substantially less power in differentiating between AD and aMCI groups. The loss of total GM volume differentiates AD from aMCI and NC.

The evaluation of thiol-disulfite balance, ischemia albumin modification and seruloplazmine as a new oxidative stress in mild cognitive impairment and early stage alzheimer's disease patients.

BACKGROUND: Alzheimer's Disease (AD) is the most common form of dementia seen in advanced age. It is characterized by progressive deterioration in cognitive functions. The prevalence of Alzheimer's disease increasing day by day due to the increase in the share of the elderly population in the general population due to developing health and living conditions, is limited and early diagnosis and effective treatment possibilities are very limited. From this point of view, a specific biomarker for AD is very important. As a new oxidative stress biomarker, the levels of thiol-disulfide balance, ischemia-modified albumin and seroloplazminin were evaluated. The aim of this study was to determine the serum levels of oxidative stress biomarkers in the early stages of the disease and to compare these oxidative stress markers with patients with mild cognitive impairment as a precursor form of Alzheimer's disease and to determine whether these markers develop at an earlier stage. METHODS: 30 volunteers with early stage AD according to NINCDS-ARDRA criteria, 19 volunteers with Midl Cognitive Impairment according to PCA criteria and 30 volunteers with defined criteria were selected from the subjects aged between 55 and 88 who applied to Gazi University Health Research. Statistical analysis of the data showed that there was a significant difference between the endgroups and biomarkers for the early diagnosis of Alzheimer's disease, but this complicated matter has to be investigated in more comprehensive and detailed studie. RESULTS: In the present study, we investigated oxidative stress parameters, thiol-disulphide balance, ischemia modified abumin and seruloplasmin in parallel with the impairment in cognitive dysfunction from control group to Mild Cognitive Impairment (MCD) and AD group by using a newly-developed method. CONCLUSIONS: This is the first study in literature comparing Early Stages Alzheimer Disease (ESAD), MCD and healthy volunteer groups. Our study has revealed that these newly developed tests may be candidates as oxidative stress biomarkers in pathgenesis of AD. However it was concluded that more comprehensive and detailed studies are required to enlighten this issue.

Relations between homocysteine, folate and vitamin B12 in vascular dementia and in Alzheimer disease.

OBJECTIVES: The aim of this study was to evaluate the relationship between homocysteine (Hcy), folate and vitamin B12 levels in vascular dementia (VaD) and Alzheimer Disease (AD) to elucidate if they had similar pathogenesis due to cerebrovascular injury. DESIGN AND METHODS: Plasma Hcy and serum folate, vitamin B12 levels were studied 67 VaD, 51 AD and 40 healthy control subjects. Vascular risk factors in these groups were also considered. RESULTS: The changes in the levels of Hcy, folate and vitamin B12 were found to be not related with vascular risk factors. In VaD, Hcy level was higher (p<0.001), folate and vitamin B12 levels were lower (p<0.05 for folate, p<0.001 for vitamin B12) than those in AD. Hcy level was negatively correlated with folate and vitamin B12 (p<0.05) in VaD but in AD. Hcy/folate and Hcy/vitamin B12 ratios were the highest in VaD. CONCLUSION: The increase of Hcy in AD were seemed to be not related to cerebrovascular injury. It is possibly related to biochemical damages as result of oxidative stress.

A case of sarcoidosis of the central nervous system and orbita.

Sarcoidosis is a multisystemic disease characterized by granulomatous inflammation. Lung or lymph node involvement is common. We present a rare case of sarcoidosis that began with orbital involvement, and a month later, due to insufficient treatment, it involved the central nervous system. A 49-year-old female patient began suffering from swelling in her right eye, redness, ptosis, and limited eye movements two months ago. Gadolinium-enhanced orbital magnetic resonance imaging showed thickening of the lacrimal gland and the right medial rectus muscle. After three weeks of local antibiotic and steroid treatments, her symptoms were resolved. One month ago, the patient reported sudden weakness in her right arm and leg. After laboratory tests and imaging studies, the patient was diagnosed with probable neurosarcoidosis using the Zajicek criteria and treated with prednisone (1 mg/kg/day). Although sarcoidosis frequently presents with lung and lymph node involvement, it is rarely accompanied by orbital involvement. Patients with orbital symptoms may receive a late diagnosis and insufficient central nervous system treatment. Involvement of the central nervous system in sarcoidosis leads to high morbidity and mortality rates. Therefore, early diagnosis and treatment are very important.

Evaluation of the nucleolar organizer regions in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder in middle and late age. Ribosomal RNA (rRNA) genes are located in the nucleolus (nucleolar organizer regions = NORs). There are increased deposits of beta-amyloid protein in the brains of the patients with AD and aged individuals with Down's syndrome (DS). The beta-amyloid gene is located in the acrocentric chromosome 21 that is responsible for rRNA synthesis. Therefore, it is possible that there is a relationship between ribosomal genes and AD. OBJECTIVE: To investigate the activities of ribosomal genes of AD patients by comparing the activities of NORs in AD patients and healthy controls with the silver-staining method. METHODS: NOR surface/the total nucleus surface proportions in interphase nuclei, and silver stainability and satellite association (SA) of acrocentric chromosomes in the metaphases of cultivated lymphocytes of 20 AD patients and 20 healthy controls (10 elderly and 10 young) were evaluated. RESULTS: A decrease in NOR surface/total nucleus surface proportions has been observed in the interphase nucleus of AD patients when compared with elderly controls (p = 0.035). When compared with the sizes of Ag+ segments of acrocentric chromosomes of AD patients and control groups, the Ag-staining size 1 of the chromosome 22 of AD patients was found to be more increased than that of the young controls (p = 0.018). There was no statistically significant difference between AD patients and control groups regarding the number of Ag+ acrocentric chromosomes, Ag+ chromosome 21 and SA frequency (p > 0.05). It has been found that there is only a slight increase in the total number of chromosomes in SA in AD patients when compared with elderly controls (p = 0.05). CONCLUSION: The decrease in NOR surface/total nucleus surface proportions of AD patients may indicate a reduction in the activity of the ribosomal genes of these patients.

A 12-month study of the efficacy of rivastigmine in patients with advanced moderate Alzheimer's disease.

The efficacy of a centrally active cholinesterase inhibitor, rivastigmine tartrate (ENA 713), in patients with advanced moderate Alzheimer's disease (AD) was evaluated in a 12-month placebo-controlled study. We aimed to investigate whether there was any evidence for the benefits of rivastigmine in patients with severe disease. These patients were compared with matched controls. In this study, 24 patients with advanced moderate AD received rivastigmine for 12 months. Another 20 patients received placebo. Mean daily doses of rivastigmine in the higher-dose group at 3, 6, 9, and 12 months were 6.1 +/- 1.0, 8.3 +/- 1.2, 8.9 +/- 1.3, and 10.7 +/- 1.6 mg/day, respectively. Cognitive abilities were assessed using the 11-item cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog). Forty-five percent of placebo-treated patients declined by at least 4 points on the ADAS-cog. Conversely, only 18.3% of patients treated with rivastigmine declined by 4 or more points. Functional disabilities, as assessed using the Disability Assessment for Dementia Scale, remained significantly superior in rivastigmine-treated patients compared with placebo-treated patients. Patients benefited from high-dose rivastigmine treatment on all outcome measures, including the Mini-Mental State Examination, Progressive Deterioration Scale, as well as the Global Deterioration Scale. Patients receiving rivastigmine for 12 months significantly improved compared with placebo-treated patients (p < 0.001). By 52 weeks, patients originally treated with 6-12 mg/day rivastigmine had a significantly better cognitive function than patients originally treated with placebo. Long-term rivastigmine treatment appeared to be well tolerated in patients with advanced moderate AD and significantly benefits the cognitive and functional symptoms of AD.

Effects of pentylenetetrazole-induced status epilepticus on behavior, emotional memory and learning in immature rats.

Status epilepticus (SE) can be harmful to the developing brain. Our knowledge of the emotional and behavioral consequences of generalized SE in developing animals remains limited. Therefore, we investigated the short- and long-term effects of pentylenetetrazole (PTZ)-induced SE on emotional memory and learning and behavioral parameters in immature rats. SE was induced in 16- to 20-day-old rats (P16-P20) using intraperitoneal injections of PTZ (n=21); control rats received saline (n=10). All animals were tested using an elevated T-maze and open-field test 2, 14, 30, and 180 days after SE, to evaluate emotional memory and learning and behavior. Anxiety levels decreased 2 and 14 days after SE, and conditioned learning of PTZ-treated immature rats was better than that of the control rats. These results indicate that a decreased anxiety level facilitates conditioned learning. Behavioral changes are transient, and no emotional memory or learning deficits occur following PTZ-induced SE in immature rats.