Tiziana Maci

Attentional processes and blood lactate levels

The accumulation of lactate in the blood after a high-intensity exercise is associated to an increase of lactate extractions by the brain. However, no information has been provided about the influences of blood lactate on cognitive performances and, in particular, on attention. The present study was carried out to examine the association of high blood lactate levels, induced with a maximal cycling, with two different attentional tasks. The study was carried out on 17 male sprinters who performed exhaustive exercise. Before the exercise, as well as 5 and 10 min after the exhaustion, blood lactate was measured and intensity as well as selectivity of attention of each subject were evaluated. Same measurements were performed on 6 out of 17 subjects who accepted to receive an intravenous infusion of a lactate solution. In both experimental conditions, an inverse relation between scores in both aspects of attention and blood lactate levels was observed.

Physical and Cognitive Stimulation in Alzheimer Disease. The GAIA Project A Pilot Study

Several data suggest that physical activity and cognitive stimulation have a positive effect on the quality of life (QoL) of people with Alzheimer’s disease (AD), slowing the decline due to the disease. A pilot project was undertaken to assess the effect of cognitive stimulation, physical activity, and socialization on patients with AD and their informal caregiver’s QoL and mood. Fourteen patients with AD were randomly divided into active treatment group and control group. At the end of treatment, a significant improvement in apathy, anxiety, depression, and QoL in the active treatment group was found. Considering caregivers, those of the active treatment group exhibited a significant improvement in their mood and in their perception of patients’ QoL. This study provides evidence that a combined approach based on cognitive stimulation, physical activity, and socialization is a feasible tool to improve mood and QoL in patients with AD and their caregivers.

Motor cortex excitability in Alzheimer's disease and in subcortical ischemic vascular dementia.

Twenty Alzheimers disease (AD) patients, 20 subcortical ischemic vascular dementia (SIVD) patients and 20 neurologically and cognitively normal subjects underwent transcranial magnetic stimulation to study motor cortex excitability changes. Motor threshold (MT), amplitude of motor evoked potentials, silent period and the H/M ratio (amplitude of maximal Hoffman reflex vs. that of maximal motor response) were considered. MT was lower in SIVD patients when compared with AD patients (P = 0.003) and the control group (P < 0.001) and lower in AD patients when compared with the control group (P < 0.001). The increment of motor cortex excitability in AD and SIVD did not lead us to distinguish clearly the two types of dementia. It is likely that the electrophysiological similarity between AD and SIVD could represent another common mechanism shared from these forms of dementia.

CSF N-glycoproteomics for early diagnosis in Alzheimer's disease

This work aims at exploring the human CSF (Cerebrospinal fluid) N-glycome by MALDI MS techniques, in order to assess specific glycosylation pattern(s) in patients with Alzheimers disease (n:24) and in subjects with mild cognitive impairment (MCI) (n:11), these last as potential AD patients at a pre-dementia stage. For comparison, 21 healthy controls were studied. We identified a group of AD and MCI subjects (about 40-50% of the studied sample) showing significant alteration of CSF N-glycome profiling, consisting of a decrease in the overall sialylation degree and an increase in species bearing bisecting GlcNAc. Noteworthy, all the MCI patients that converted to AD within the clinical follow-up, had an abnormal CSF glycosylation profile. Based on the studied cohort, CSF glycosylation changes may occur before an AD clinical onset. Previous studies specifically focused on the key role of glycosyltransferase GnT-III on AD-pathogenesis, addressing the patho-mechanism to specific sugar modification of BACE-1 glycoprotein with bisecting GlcNAc. Our patients addressed protein N-glycosylation changes at an early phase of the whole biomolecular misregulation on AD, pointing to CSF N-glycome analyses as promising tool to enhance early detection of AD and also suggesting alternative therapeutics target molecules, such as specific glyco-enzymes.

The second-to-fourth digit ratio correlates with the rate of academic performance in medical school students

Prenatal androgens have important organizing effects on the development and future behavior of the brain. The second-to-fourth digit length ratio (2D:4D) has been proposed as a marker of these prenatal androgen effects, with a relatively longer fourth finger indicating higher prenatal androgen exposure. 2D:4D has been shown to predict the success of men who play sports and of financial traders. However, to date little is known regarding the effects of prenatal androgens on academic performance, for example, admission to and success in a highly competitive university system such as the state-run Italian medical schools. Here, we report the findings of a study conducted at the University of Catania Medical School, Italy, in which the 2D:4D ratio was sampled in a group of 48 male students. The 2D:4D ratios were found to be correlated with the performance of the students on the admission test to the medical school, their salivary testosterone levels and their aggressiveness; however, no correlation was observed with the mean score on exams during the course of study. Our results suggest that pre and/or postnatal androgens increase performance in situations that require prompt decision-making and the ability to take risks, but do not influence performance when a more analytical and planned approach is called for.

Gender differences in changes of motor cortex excitability during elevated blood lactate levels

Gender differences in cortical excitability have been detected by using transcranial magnetic stimulation (TMS). The present study was carried out to compare the effects of high blood lactate levels, induced by performing a maximal exhausting exercise, on the excitability of the primary motor cortex in young male and female athletes. The study was carried out on 21 young males and 20 females from the Middle Distance Track Team of our university. Before the exercise, at the end, as well as 5 and 10 min after the conclusion, venous blood lactate and glucose were measured and excitability of the motor cortex was evaluated by using TMS. We observed a similar enhancement of excitability of primary motor cortex, concomitantly with an increase of blood lactate, in both young male and female athletes. However, the improvement was significantly higher (p < 0.05) in women (37.4% ± 3.97) than in men (42.0% ± 6.43), suggesting a greater sensitiveness of female cerebral cortex to blood lactate.

Changes of blood lactate levels after repetitive transcranial magnetic stimulation.

The objective was to study whether repetitive transcranial magnetic stimulation (rTMS) of the motor cortex could induce modification of peripheral blood lactate values. Nineteen young healthy volunteers were included; during the study, all subjects were at rest, sitting on a comfortable armchair. The muscular activation was evaluated by continuous electromyographic record. TMS was performed by using a circular coil at the vertex. Resting motor threshold (rMT) was defined as the lowest TMS intensity able to induce motor responses of an amplitude >50 microV in the relaxed contralateral target muscle in approximately 50% of 20 consecutive stimuli. Venous blood lactate values were measured before, immediately after and 10 min after a single session of low frequencies (1Hz for 15 min) rTMS (LF rTMS) or high frequency (20 Hz for 15 min) rTMS (HF rTMS). As expected, LF rTMS induced a decrease of motor cortex excitability, whereas HF rTMS evoked an increase of motor cortex excitability. However, in the present investigation we observed that both conditions are associated to a significant increase of blood lactate. Since in our experimental conditions we can exclude a muscular production of lactate, the significant increment of peripheral blood lactate values, observed 10 min after the end of the rTMS session, is probably due to the crossing by brain-produced lactate of the blood-brain barrier.

Effects of Gabapentin and Topiramate in primary rat astrocyte cultures.

We studied in vitro the effects of anticonvulsant drugs Gabapentin and Topiramate on the production of reactive oxygen species and nitric oxide (NO), the activity of glutamine synthetase (GS), and cell viability in primary cultures of rat cortical astrocytes which are intimately involved in the normal functioning of neurons. We investigated the effects of these drugs at concentrations within the therapeutic range (1, 10 and 50 μg/ml). We observed that, in cultured astrocytes, Gabapentin induced a weak increase in the biosynthesis of NO, a mild decrease in GS activity and cell viability, and minor induction of a stress condition. Topiramate was observed to induce even greater stressor effects on these cells.

Cognitive Findings After Transient Global Amnesia: Role of Prefrontal Cortex

The aim of this study is to verify, after recovery, the presence of specific patterns of cognitive dysfunctions in Transient Global Amnesia (TGA). Fourteen patients with the diagnosis of TGA were submitted to a battery of neuropsychological tests and compared to a matched control group. We found significant qualitative and quantitative differences between TGA patients and controls in the California Verbal Learning Test (CLVT) and Rey-Osterrieth Complex Figure Test. Our data support the presence of selective cognitive dysfunctions after the clinical recovery. Moreover, for Verbal Fluency, Digit Span Backward, and Number of Clusters in the CVLT short-term memory test, the relation resulted as positively related with the temporal interval from the TGA episode. Reduction of categorical learning, attention, and qualitative alterations of spatial strategy seem to postulate a planning defect due to a prefrontal impairment.

Dissociation between motor and cognitive impairments in SCA2: Evidence from a follow-up study.

Sirs: Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease in which, besides motor disturbances, cognition could also be impaired [2–4, 7–9]. Nevertheless, it is unclear whether the cognitive functions of SCA2 patients worsen over time as observed for motor disturbances. Ten subjects (6 men and 4 women; age 57.5 ± 13.7 years, mean ± SD) with SCA2 were re-evaluated 8.5 ± 0.5 years after the first visit. They belonged to a larger sample of 18 subjects previously described [8]: 8 patients were lost to followup (3 subjects deceased, 4 refused to participate and one patient was not traced) and could not be reevaluated. Disease duration at the last visit was 14.4 ± 6.8 years. The pathological expanded alleles ranged from 35 to 46 CAG repeat numbers (mean 40.1 ± 2.8). Clinical and cognitive conditions were assessed by using the same scoring systems used in the seminal paper [8]. In particular, cerebellar motor disturbances were scored using a scale ranging from 0 (absent) to 5 (most severe) [6]. A battery of neuropsychological tests assessing working memory (digit span and Corsi Block-tapping Test), verbal memory (California Verbal Learning Test, CVLT), visuo-spatial memory (immediate and delayed copy of Rey Complex Figure), executive functions (verbal fluency assessed by Controlled Oral Association Test, COWAT), constructive abilities (copy of Rey Complex Figure) and conceptual abilities (Raven’s Progressive Matrices ‘47, RPM) was administered to all patients. Affective conditions were scored by using Hamilton Depression Scale. The motor scores significantly deteriorated during the follow-up period and the worsening was more evident for postural ataxia (Table 1). At the follow-up visit, other extracerebellar signs had become evident in some patients (spasticity in two, dysphagia in one and double vision in other three subjects). Moreover, two patients were wheelchair-bound and one patient could walk with a bilateral support, whereas at baseline only two patients used a walking aid. Most of the neuropsychological performances did not show a significant deterioration during the follow-up period (Table 2), including verbal memory (assessed by CVLT) and executive functions (assessed by COWAT and RPM) that were impaired at baseline, as previously reported [8]. The only significant changes were observed for depression scores and for nonverbal memory, which deteriorated at the follow-up visit as compared to baseline. To our knowledge this is the first follow-up study conducted in SCA2 patients, even if the small number of examined patients could not allow definitive conclusions. Nevertheless, our results indicate a clear dissociation between motor and cognitive impairments during the progression of the disease. Indeed we showed that the cognitive defects found at baseline did not change significantly over time, at variance with motor disturbances that, as expected, worsened during the observation period. It has been suggested that the cognitive deficits observed in SCA2 patients could result from disruption of a cerebro-cerebellar circuitry presumably at the pontine level [3]. This process should occur early in the course of SCA2, because we found cognitive defects even in the milder stages of the disease [8]. Nevertheless, this damage LETTER TO THE EDITORS