Oxidative Stress in Cerebral Small Vessel Disease Dizziness Patients, Basally and After Polyphenol Compound Supplementation.

BACKGROUND: Leukoaraiosis (LA) is a common radiological finding in elderly, frequently associated with several clinical disorders, including unexplained dizziness. The pathogenesis of LA is multifactorial, with a dysfunction of cerebral microcirculation resulting in chronic hypoperfusion and tissue loss, with oxidative stress involved in this cascade. OBJECTIVE: The aim of this study was to analyse some oxidative stress biomarkers in a cohort of LA patients. METHOD: Fifty-five consecutive patients (33 males, median age 75 years) with LA were recruited. In a subgroup of 33 patients with LA and unexplained dizziness, we have then performed an open study to evaluate if 60-day supplementation with a polyphenol compound may modify these biomarkers and influence quality of life, analysed with the Dizziness Handicap Inventory (DHI) scale. RESULTS: At baseline, blood oxidative stress parameters values were outside normal ranges and compared to matched healthy controls. After the two months supplementation, we observed a significant decrement of advanced oxidation protein products values and a significant improvement of DHI. CONCLUSION: Oxidative stress biomarkers may be useful to detect redox imbalance in LA and to provide non-invasive tools to monitor disease status and response to therapy.

Is high oral dose L-arginine intake effective in leukoaraiosis? Preliminary data, study protocol and expert's opinion.

BACKGROUND: Leukoraraiosis is worldwide considered as a part of the normal aging process, although it is strongly associated with dementia and other disabilities. The pathogenesis of leukoaraiosis still has not been thoroughly acknowledged, even though chronic ischemia with consequent arteriolosclerosis probably due to endothelial dysfunction has been suggested. Treatment focuses on prevention of lesion formation and progression by aggressive control of risk factors, which should begin at an early age and continue on regular basis. Aim of our protocol is to evaluate the effect of long-term oral administration of high-dose L-arginine (6 g/day at least for 24 months) on white matter lesions and neurological and cognitive functions. MATERIALS AND METHODS: Patients affected by mild to moderate leukoaraiosis will be enrolled in the study. After a complete neurovascular assessment (i.e. accurate blood test examinations, Echocardiography, Doppler ultrasound of the neck and peripheral arteries), they will undergo MRI, specific neuropsychological tests and gait analysis. Patients will be evaluated at baseline, at 6, 12, 18 and 24 month-follow up. Statistical Analysis will be performed using the software R. A significant level of P<0.05 will be set for all the tests. PRELIMINARY DATA: Two of the 4 patients currently enrolled in the study presented a mild improvement in cognitive function. DISCUSSION: Because of its high prevalence in over-65-year-old subjects, we hypothesized that treatment with 6 gr of Larginine, as supplementary dietary option, could be helpful in patients affected by leukoaraiosis to improve the cognitive and gait impairment often observed in these subjects (as demonstrated by the LADIS study).

Abnormalities of magnetic resonance spectroscopy and diffusion tensor imaging are correlated with executive dysfunction in patients with ischemic leukoaraiosis.

Abnormal diffusion tensor imaging (DTI) results have been observed in the periventricular white matter in patients with ischemic leukoaraiosis (ILA). However, the underlying pathological changes and their relationship to cognitive impairments are obscure. In addition, damage in the thalamus, an important structure in the executive function network, has been suggested in ILA, but is poorly understood. Twenty patients with ILA and 20 healthy volunteers with similar ages and educational histories underwent DTI, magnetic resonance spectroscopy (MRS) and a neuropsychological assessment. In patients with ILA, we observed an increased mean diffusivity (MD) and decreased levels of N-acetylaspartate (NAA)/creatine (Cr) in the anterior and posterior periventricular region and the thalamus, as well as decreased fractional anisotropy (FA) in the anterior and posterior periventricular regions. MD and NAA/Cr levels in the anterior and posterior periventricular white matter and NAA/Cr levels in the thalamus were correlated with executive function. DTI and MRS abnormalities were consistent with axonal and/or neuronal loss and dysfunction in the anterior and posterior periventricular white matter and the thalamus. This study demonstrates that DTI and MRS techniques can be used to investigate pathological changes in the anterior and posterior periventricular white matter and the thalamus; these changes may be correlated with executive functional changes in patients with ILA.

Mild cognitive impairment and event-related potentials in patients with cerebral atrophy and leukoaraiosis.

OBJECTIVE: The influence of cerebral atrophy and leukoaraiosis (LA) on the degree and profile of cognitive impairment remains unclear. DESIGN: The aim of the study was to assess neuropsychological features of cognitive performance and parameters of event-related potentials (ERP) in subjects with generalised cerebral atrophy and LA. SETTING: Department of Neurology, University of Medicine. PATIENTS AND PARTICIPANTS: Forty-two patients with LA and/or cerebral atrophy and twenty controls. MEASUREMENTS AND RESULTS: Neuropsychological testing (NT) included Mini Mental State Examination (MMSE), Auditory Verbal Learning Test (AVLT) and Trail Making Test (TMT). Auditory ERPs were performed and parameters of the N2 and P3 components were compared in the patients and controls. Relationships were analysed between radiological indices of atrophy and LA, and NT and ERP results. Results of NT suggested generalised mild cognitive impairment in all the patients. P3 and N2 latencies were longer in the patients than in controls, especially in the LA subgroup. Correlations were found for indices of atrophy, AVLT and ERP parameters. There was a predominant influence of age upon ERP parameters and radiological indices. CONCLUSIONS: Cerebral atrophy and LA result in deficits in memory and attention. NT and ERP may be used as complementary methods in the assessment of cognitive impairment in patients with cerebral atrophy and LA.