Serum HDL Associated Antioxidant Activity in Alzheimer's Disease: Paraoxonase1 and Dysfunctional HDL.

BACKGROUND: Human serum paraoxonase1 (PON1) is a high-density lipoprotein (HDL) associated antioxidant enzymes. We aimed to research the PON1 activity in Alzheimer's disease (AD) not accompanied with any disorders and other conditions influencing the PON1 activity. METHODS: We studied the PON1 activity and PON1 related lipid parameters in two groups, probable sporadic late onset AD (n:30) and those with healthy subjects (n:32). These groups were homogeneous, in which the subjects did not have any cardiovascular risk factors or other conditions affecting PON1 activity. RESULTS: We found increased high-density lipoprotein cholesterol (HDL-C) and significantly decreased PON1 activity in the AD patients. A patient with a PON1 activity value of ≤ 151 U/L had a 5.48-fold higher risk for AD, compared to those with a PON1 activity value of > 151 U/L. CONCLUSIONS: Decreased PON1 activity may play a role in the oxidative stress (OS) related pathogenesis of AD. An increased HDL-C with the decreased PON1 activity may bring the concept of dysfunctional HDL into question in the pathogenesis of AD. It may be emphasized in the pathogenesis of AD for further studies.

Clinical and radiological features in CADASIL and NOTCH3-negative patients: a multicenter study from Turkey.

BACKGROUND: The diversity of clinical presentation and neuroimaging findings of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) from different regions of the world has not yet been studied in depth. Here we investigated the variability of clinical, radiological and genetic data of 48 patients analyzed for NOTCH3 mutation in Turkey. METHODS: Clinical evaluation was made according to a preformed questionnaire. Cranial neuroimaging findings were determined on the basis of T1, T2, FLAIR and proton-density magnetic resonance scans. For genetic analysis, polymerase chain reaction was performed with primers flanking exons 2-6 and 11 of NOTCH3 gene. RESULTS: Twenty-five patients (52.1%) were diagnosed as CADASIL with NOTCH3 mutation, while 23 patients (47.9%) had no mutation (NOTCH3-negative patients). The mean age and age at stroke onset were lower in male CADASIL patients (p < 0.03). A family history of migraine (p = 0.012), stroke (p < 0.001), recurrent strokes (p = 0.020) and dementia (p = 0.012) was more common in CADASIL patients. Temporal pole involvement was more common in CADASIL patients (p = 0.004). CONCLUSION: It is of clinical importance to identify the heterogeneity of CADASIL from different countries due to a low correlation of clinical and radiological data with respect to NOTCH3 mutation.

Altered diastolic function and aortic stiffness in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is closely linked to cardiovascular risk factors. METHODS: Echocardiographic studies were performed, including left ventricular diastolic functions, left and right atrial conduction times, and arterial stiffness parameters, namely stiffness index, pressure-strain elastic modulus, and distensibility, on 29 patients with AD and 24 age-matched individuals with normal cognitive function. RESULTS: The peak mitral flow velocity of the early rapid filling wave (E) was lower, and the peak velocity of the late filling wave caused by atrial contraction (A), deceleration time of peak E velocity, and isovolumetric relaxation time were higher in the AD group. The early myocardial peak (Ea) velocity was significantly lower in AD patients, whereas the late diastolic (Aa) velocity and E/Ea ratio were similar between the two groups. In Alzheimer patients, stiffness index and pressure-strain elastic modulus were higher, and distensibility was significantly lower in the AD group compared to the control. Interatrial electromechanical delay was significantly longer in the AD group. CONCLUSION: Our findings suggest that patients with AD are more likely to have diastolic dysfunction, higher atrial conduction times, and increased arterial stiffness compared to the controls of same sex and similar age.

Ischemia modified albumin and plasma oxidative stress markers in Alzheimer's disease.

OBJECTIVES: The objective of this study was to determine ischemia modified albumin (IMA) and oxidant status in Alzheimer's disease (AD). Therefore, we evaluated the IMA and oxidant status by measuring serum uric acid, albumin and gamma-glutamyltransferase (GGT) in AD. METHODS: The plasma albumin, uric acid, GGT and IMA levels were measured by spectrophotometric methods in 32 AD patients and 32 healthy controls. The Mini Mental Status Examination and Clinical Dementia Rating Scale were used to evaluate the cognitive functions of AD patients. RESULTS: AD patients had significantly higher IMA levels as compared to those of the controls respectively. Uric acid concentrations were significantly decreased and GGT values were significantly increased in AD when compared with control group. Albumin levels of the patients were also compared and no significant difference was detected. CONCLUSION: Oxidative stress and IMA levels rise in AD. However, large prospective studies are required to understand the mechanisms leading to increased IMA levels during AD, whether preceded or not by AD.

Screening for Patients with Mild Alzheimer Disease Using Frequency Doubling Technology Perimetry.

We compared the visual field performances of patients with mild Alzheimer disease (AD) with normal subjects and detected visual field impairment attributable to the magnocellular pathway using frequency doubling technology-Matrix (FDT-Matrix). We recruited 43 patients with mild AD (mean age: 68.0 ± 7.2 years) and 33 controls who are visually and cognitively normal (mean age: 64.1 ± 6.4 years). All participants had at least two reliable FDT-Matrix 30-2 tests. Reliability indices, global indices (mean deviation and pattern standard deviation), and glaucoma hemifield test results were measured with FDT-Matrix. The mean test duration was significantly longer in patient group compared with controls (p = 0.002). Among the reliability indices, false negatives were higher in patient group than controls (p = 0.003). There were statistically significant differences in mean deviation and pattern standard deviation values (p < 0.0001 and p < 0.0001, respectively) and glaucoma hemifield test results (p < 0.001) between the patient and the control group. Our results imply that the pathogenesis of cognitive deterioration may not only be confined to the cortical area but also to the magnocellular pathway. We underline that FDT testing can be useful for the identification of early impairment and the follow-up of patients with AD.

DNA repair genes in Parkinson's disease.

AIMS: There is a growing interest in the understanding of a possible role of DNA repair systems in ageing and neurodegenerative diseases after DNA damage is observed in the brain of individuals affected by neurodegenerative diseases. In the light of these findings, we investigated whether DNA repair gene polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met XPD Lys751Gln, XPG Asp1104His, APE1 Asp148Glu, and HOGG1 Ser326Cys) account for an increased risk of Parkinson's disease (PD). METHODS: The present analyses are based on 60 case subjects with PD and 108 unrelated healthy controls. Genotyping of DNA repair gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We, for the first time, demonstrated the positive association of APE1, XRCC1, and XRCC3 DNA repair gene variants with PD risk. In our study, the frequencies of Glu/Glu genotype in APE1, Gln+ genotype of XRCC1, and Thr+ genotype of XRCC3 are higher in patients than in controls (p=0.028, p=0.002 and p=0.046, respectively). CONCLUSIONS: In conclusion, our findings have suggested that APE1, XRCC1, and XRCC3 genetic variants may be a risk factor by increasing oxidative stress that might cause the loss of dopaminergic cells in the substantiata nigra and locus caeruleus, leading to abnormal signal transmittion, and ultimately, the development of PD. In addition, generation of reactive oxygen species from dopamine might affect the other DNA repair pathway proteins that we did not examine in the current study. Further studies with larger sample groups are necessary to clarify the role of DNA repair genes and the development of PD.

Treatment of homocystinuria-related dystonia with deep brain stimulation: a case report.

A 23-year-old woman with the medical history of homocystinuria that had been diagnosed at the age of 14 has been non-responsive to treatment. The patient presented with the symptoms of dysphonia, dysarthria and severe dystonia of the neck and left extremities. Blood and urine biochemistry revealed high levels of homocystine. Brain magnetic resonance imaging was normal with no detectable pathologies. Medical treatment strategies were used and repeated injections of botulinum toxin A were administered, but the symptoms showed no significant improvement. The patient was then operated, and deep brain stimulators targeting the bilateral globus pallidus internus were implanted. After the activation of the electrodes, dystonia symptoms showed a remarkable improvement. Good outcome was documented during the follow-up period of 7 months. To our best knowledge, this is the first reported case of homocystinuria-related dystonia symptoms that were successfully treated with deep brain stimulation.

Different phenotypy in three siblings with homocystinuria.

INTRODUCTION: Movement disorders associated with homocystinuria have been reported as rare cases. Their physiopathology has not yet been clarified. METHODS: Three siblings in the same family have been described, all with homocystinuria but possessing phenotypic differences. RESULT: The first case presented oromandibular dyskinesia, spasmodic dysphonia, tremor, bradykinesia, and generalized dystonia along with the classic findings of homocystinuria. The second case had marfanoid features and ophthalmic complications of homocystinuria, and also evidence of mild rigidity of which the patient did not complain. The third case had only marfanoid features. The most severely affected family member was the first case who also had increased thyroid peroxidase antibodies, antithyroglobulin antibodies, and thyroiditis. CONCLUSION: The most severely affected sibling presented movement disorders and evidence of autoimmune thyroiditis. These findings have led us to think that research on the relations between movement disorders, basal ganglia, immunity, autoimmune thyroid diseases, and homocysteine should be continued.

Neurotoxicity following chronic intravenous use of "Russian cocktail".

INTRODUCTION: Recently, neurological abnormalities in methcathinone users have been attributed to manganese. We report similar toxicity in three patients following the use of a mixture similar to methcathinone: potassium permanganate, ephedrine, and aspirin. CASE REPORTS: Three teenagers (15 to 19 years old) presented with extrapyramidal abnormalities and movement disorders following chronic intravenous use of a mixture known as "Russian Cocktail". All three patients had multiple movement disorders. One patient had normal blood manganese concentration (<19 microg/L) and MRI. The other two had elevated blood manganese (2100 microg/L and 3176 microg/L) and MRIs showing bilateral symmetric hyper-intensities on T1-weighted-images in the dentate nucleus, subcortical white substance of cerebellar hemisphere, globus pallidus, and putamen. Abstinence and treatment with EDTA, levodopa, and para-aminosalicylic acid was associated with decreasing blood manganese concentrations and subjective improvement, but no change in objective findings. DISCUSSION: The "Russian Cocktail" likely contains manganese as a result of the oxidation of ephedrine by potassium permanganate in water acidified by acetylsalicylic acid. We believe that manganese with the possible contribution of methcathinone caused the neurological impairments. CONCLUSIONS: Three toxic substances have been made into a mixture administered intravenously, similar to methcathinone. Our patients learned of this mixture, called "Russian Cocktail", from their friends. The toxicity from repeated use of this mixture is one of extrapyramidal abnormalities and movement disorders. Standard therapies were unsuccessful in reversing the clinical toxicity.