Leszek Noga

Evaluation of CSF-Chlamydia pneumoniae, CSF-tau, and CSF-Abeta42 in Alzheimer’s disease and vascular dementia

The potential role of microbiological factors such as Chlamydia pneumoniae (ChP) in the pathogenesis of neurodegenerative disorders, including Alzheimer’s disease (AD) and vascular dementia (VD), has been suggested, but the correctness of this hypothesis still needs to be tested. In this study the appearance of ChP in the cerebrospinal fluid (CSF) of 57 AD and 21 VD patients and in 47 controls (CG) as well as the influence of ChP on the levels of tau protein and Aβ42 were investigated. The frequency of ChP occurrence in the AD patient group (43.9%) was significantly higher (p < 0.001) than in the control group (10.6%). In the case of VD patients, 9.5% of this group was positive for ChP. The presence of ChP DNA in the CSF of patients with AD significantly increases the occurrence of this disease (odds ratio = 7.21). Cerebrospinal fluid Aβ42 levels were significantly lower in patients with AD than in the CG (p < 0.001). Cerebrospinal tau protein was significantly higher in AD vs. CG (p = 0.007). However, no relationships between the presence of the bacterium in CSF and the level of either tau or Aβ42 protein were observed. In conclusion, we may suspect that testing for the presence of ChP in CSF, along with the tau and Aβ42 markers, may be used in the clinic diagnosis of AD.

Multimodal imaging in diagnosis of Alzheimer's disease and amnestic mild cognitive impairment: value of magnetic resonance spectroscopy, perfusion, and diffusion tensor imaging of the posterior cingulate region.

The purpose of this study was to assess metabolic, perfusion, and microstructural changes within the posterior cingulate area in patients with Alzheimers disease (AD) and amnestic mild cognitive impairment (aMCI) using advanced MR techniques such as: spectroscopy (MRS), perfusion weighted imaging (PWI), and diffusion tensor imaging (DTI). Thirty patients with AD (mean age 71.5 y, MMSE 18), 23 with aMCI (mean age 66 y, MMSE 27.4), and 15 age-matched normal controls (mean age 69 y, MMSE 29.5) underwent conventional MRI followed by MRS, PWI, and DTI on 1.5 Tesla MR unit. Several metabolite ratios (N-acetylaspartate [NAA]/creatine [Cr], choline [Ch]/Cr, myoinositol [mI]/Cr, mI/NAA, mI/Cho) as well as parameters of cerebral blood volume relative to cerebellum and fractional anisotropy were obtained in the posterior cingulate region. The above parameters were correlated with the results of neuropsychological tests. AD patients showed significant abnormalities in all evaluated parameters while subjects with aMCI showed only perfusion and diffusion changes in the posterior cingulate area. Only PWI and DTI measurements revealed significant differences among the three evaluated subject groups. DTI, PWI, and MRS results showed significant correlations with neuropsychological tests. DTI changes correlated with both PWI and MRS abnormalities. Of neuroimaging methods, DTI revealed the highest accuracy in diagnosis of AD and aMCI (0.95, 0.79) followed by PWI (0.87, 0.67) and MRS (0.82, 0.47), respectively. In conclusion, AD is a complex pathology regarding both grey and white matter. DTI seems to be the most useful imaging modality to distinguish between AD, aMCI, and control group, followed by PWI and MRS.

Evaluation of the Posterior Cingulate Region with FDG-PET and Advanced MR Techniques in Patients with Amnestic Mild Cognitive Impairment: Comparison of the Methods

BACKGROUND The posterior cingulate region is an area of the earliest pathological changes in amnestic mild cognitive impairment (aMCI). The utility of FDG-PET imaging in dementia is already well established. OBJECTIVES The aim of the study was to compare FDG-PET with advanced MR measurements: MR spectroscopy (MRS), perfusion weighted imaging (PWI), and diffusion tensor imaging (DTI) within the posterior cingulate region in patients with aMCI. METHODS Fifty-five patients diagnosed with aMCI (66.5 y) and 20 age-matched controls (69 y) underwent MR examination including MRS, PWI, and DTI followed by FDG-PET scanning. Values of MRS metabolite ratios (NAA/Cr, Cho/Cr, mI/Cr), PWI cerebral blood volume (rCBV), and DTI fractional anisotropy (FA) were compared to the FDG-PET rates of glucose metabolism. RESULTS Compared to controls, aMCI patients showed significant (p < 0.05) glucose hypometabolism, and lower rCBV and FA values. FDG-PET results correlated significantly with rCBV values. Compared to FDG-PET, PWI showed similar and DTI greater accuracy in distinguishing aMCI from controls. According to FDG-PET findings, two groups of aMCI patients were established: those with lower (PET-positive) and normal (PET-negative) glucose uptake. PET-positive aMCI subjects showed normal MRS findings, lower rCBV and FA values, while PET-negative patients revealed normal MRS and PWI results but significantly lower FA values. CONCLUSIONS Advanced MR techniques such as PWI and particularly DTI may be regarded as competitive techniques to FDG-PET. DTI was the only method to show alterations in aMCI patients with normal FDG-PET, PWI, and MRS findings. DTI seems to be a very sensitive biomarker of early degeneration in aMCI.

The Usefulness of the TOAST Classification and Prognostic Significance of Pyramidal Symptoms During the Acute Phase of Cerebellar Ischemic Stroke.

Cerebellar stroke is a rare condition with very nonspecific clinical features. The symptoms in the acute phase could imitate acute peripheral vestibular disorders or a brainstem lesion. The aim of this study was to assess the usefulness of the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification in cerebellar stroke and the impact of clinical features on the prognosis. We retrospectively analyzed 107 patients with diagnosed ischemic cerebellar infarction. We studied the clinical features and compared them based on the location of the ischemic lesion and its distribution in the posterior interior cerebellar artery (PICA), superior cerebellar artery (SCA), and anterior inferior cerebellar artery (AICA) territories. According to the TOAST classification, stroke was more prevalent in atrial fibrillation (26/107) and when the lesion was in the PICA territory (39/107). Pyramidal signs occurred in 29/107 of patients and were more prevalent when the lesion was distributed in more than two vascular regions (p = 0.00640). Mortality was higher among patients with ischemic lesion caused by cardiac sources (p = 0.00094) and with pyramidal signs (p = 0.00640). The TOAST classification is less useful in assessing supratentorial ischemic infarcts. Cardioembolic etiology, location of the ischemic lesion, and pyramidal signs support a negative prognosis.

Assessment of metabolic changes within normal appearing gray and white matter in children with growth hormone deficiency: magnetic resonance spectroscopy and hormonal correlation.

OBJECTIVE The pathogenesis of idiopathic growth hormone deficiency (GHD) in children, including possible cerebral metabolic alterations, remains unclear. The aim of the study was to evaluate metabolic changes within the normal appearing brain in children with GHD using MR spectroscopy (MRS) and to correlate MRS measurements with hormonal concentrations and with pituitary gland size. METHODS Seventy children with GHD (mean age 7.8 yrs) and 11 healthy controls (mean age 8.4 yrs) were enrolled in the study. The MRS examinations were performed on a 1.5T scanner. Voxels were located in the posterior cingulate gyrus (PCG) and the left parietal white matter (PWM). The NAA/Cr, Cho/Cr and mI/Cr ratios were analyzed. The metabolite ratios, pituitary gland size and hormonal concentrations: growth hormone (GH) in two stimulation tests and GH during the night, as well as IGF-1 (insulin-like growth factor) and IGFBP3 (insulin-like growth factor-binding protein) levels were also correlated. RESULTS There was a significant (p < 0.05) decrease of the NAA/Cr ratios in PCG and PWM in children with GHD compared to the normal subjects. Other metabolite ratios showed no significant differences. We also found significant positive correlations between NAA/Cr ratio in PWM and IGFBP3 level, as well as with GH concentration in a stimulation test with glucagon. CONCLUSIONS The reduction of NAA/Cr ratios may suggest loss of neuronal activity within normal appearing gray and white matters in children with GHD. MRS could be a sensitive marker of cerebral metabolic disturbances associated with GHD and maybe used as an additional indicator for therapy with recombinant GH.

Cognitive Impairment in Parkinson s Disease

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder with characteristic clinical motor features combined with non-motor symptoms. Cognitive impairment has a very significant impact on the patient’s quality of life. The risk of developing dementia is six times higher in PD patients than in general population and increases with longer duration of the disease. Objectives: The aim of this study is to assess cognitive impairment in PD patients and its characteristics and to explore the correlation between duration of the disease, its stage, and neuroimaging of the brain. Material and methods: The study involved 64 patients with clinical diagnosis of PD established on the basis of the UKPDS BB criteria. Patients with PD were subdivided into two groups: patients with disease duration under five years and over five years. Participation in the study included taking medical history, collecting information on the course of the disease and its treatment, identification of comorbidities, and neurological examination. A neuropsychological assessment was carried out for all the patients and included: MMSE, CDT, verbal fluency test (both semantic and phonemic tasks) and, in part, the ADAS-cog test. The examination also included the BDI (Beck Depression Inventory) test. CT and MRI scans were performed of PD patients in order to assess atrophy of the brain and hippocampus. Results: Most of the PD patients suffer from visuospatial and semantic fluency dysfunctions. The level of cognitive impairment in PD is dependent on the patient’s age and the motor symptom severity assessed using the H-Y scale. We observed a clear relationship in PD between cognitive impairment and atrophy of the hippocampus, temporal and parietal lobes, and vascular lesion. Conclusion: Cognitive function impairment appears in Parkinson’s patients without diagnosed dementia. The executive functions are especially affected with the level of impairment dependent on the patient’s age and the degree of movement impairment.