The Apathy Evaluation Scale (AES-C): Psychometric Properties and Invariance of Italian Version in Mild Cognitive Impairment and Alzheimer's Disease.

Apathy is a neuropsychiatric symptom observed in different neurological and psychiatric disorders. Although apathy is considered a symptom, it has been recently reconsidered as a syndrome characterised by three dimensions: cognitive symptoms, affective symptoms and behavioural symptoms. Recent studies have shown that apathy can be considered as a prodromal symptom of Alzheimer's disease (AD), but also an indicator of the transition from mild cognitive impairment to AD. According to this scenario, an early detection of apathy in subjects with Mild Cognitive Impairment (MCI) and Mild AD can be a valid psychometric strategy to improve an early diagnosis and promote a prompt intervention. The Apathy Evaluation Scale is a validated tool composed of 18 items that assess and quantify emotional, behavioural and cognitive aspects of apathy. The aim of this study is to assess the specific reliability and validity of the Italian version of the Apathy Evaluation Scale-Clinician Version (AES-C) to detect apathy both in amnestic MCI and mild AD patients. In the present paper, we therefore examined the psychometric properties and the invariance of the Italian Version of the AES-C conducted on a sample composed of an experimental group of amnestic MCI and AD patients (N = 107) and a control group (N = 107) constituted by Age- and Sex-matched healthy controls. Results confirm the goodness of the scale. Confirmatory factory analysis confirmed that the AES-C Italian Version presents the same stability of one second-order factor and three first-order factors identified in the original version, and all items are predicted by a single general factor. Moreover, the scale was found to be invariant across both populations. Moreover, reliability and discriminant analysis showed good values. We found in the experimental group a negative correlation between the AES-C and Frontal Assessment Battery (FAB) (rs = -0.21, p < 0.001) and Mini Mental State Examination (MMSE) (rs = -0.04, p < 0.001), while a positive correlation was found between the AES-C and Hamilton psychiatric Rating scale for Depression (HAM-D) scores (rs = 0.58, p < 0.001) Overall, our data demonstrated the validity of the Italian version of the AES-C for the assessment of apathy both in MCI and in AD patients.

Executive Functions During Submaximal Exercises in Male Athletes: Role of Blood Lactate.

The present study was carried out among 20 healthy young male athletes to determine whether aerobic exercise performed at two different intensities is able to affect executive functions. For this purpose, we used the Stroop Color Word Test (SCWT) to evaluate the ability to inhibit cognitive interference and the Trail Making Test (TMT) to assess organized visual search, set shifting, and cognitive flexibility. Simple Reaction Time (RT), as a measure of perception and response execution, was also evaluated. The experimental protocol included the measure of blood lactate levels with the aim of assessing possible relations between lactate blood values and selected executive functions after a 30-min steady-state test performed at 60% and at 80% of VO2max. The results showed that a 30-min aerobic exercise is not associated with a worsening of executive functions as long as the blood lactate levels stay within the 4 mmol/l threshold.

Effects of a Bout of Intense Exercise on Some Executive Functions.

The present study examined the effects of an exhaustive exercise on executive functions by using the Stroop Color Word Test (SCWT), Trail Making Test (TMT), A and B, and simple Reaction Time (RT). Thirty adults agreed to participate; 15 participants had a mean age of 24.7 years ± 3.2 Standard Deviation (SD, Standard Deviation) (group YOUNG), while the remaining 15 had a mean age of 58.9 years ± 2.6 SD (group OLD). Each subject performed the cognitive tasks at rest and blood lactate was measured (pre); each subject executed the acute exhaustive exercise and, immediately after the conclusion, executed the cognitive tasks and blood lactate was again measured (end). Cognitive tests were repeated and blood lactate measured 15 min after its conclusion of the exhaustive exercise (post). We observed: (1) a significant positive correlation between blood lactate levels and RT levels; (2) a significant negative relationship between levels of blood lactate and the SCWT mean score; (3) no significant correlation between blood lactate levels and TMT scores (time and errors), both A and B; (4) variations in blood lactate levels, due to exhaustive exercise, and parallel deterioration in the execution of RT and SCWT are significantly more pronounced in the group YOUNG than in the group OLD. The present study supports the possibility that high levels of blood lactate induced by an exhaustive exercise could adversely affect the executive functions pertaining to the prefrontal cortex.

Cognitive Deficits and White Matter Alterations in Highly Trained Scuba Divers.

Nitrogen gas (N2), present in the normal atmospheric air, is a potential source of risk for scuba divers. It seems probable that myelin can represent, in hyperbaric conditions, a preferential site for the accumulation of N2 in central nervous system (CNS). The purpose of this study is to verify whether the practice of the scuba diving is capable to determine a damage of the brain white matter (WM) in a dose dependent manner and, consequently, possible deficiency of their cognitive abilities. For this purpose, 54 professional scuba divers (35 men and 19 women), with at least 2,000 dives in their careers, were studied. Possible alterations of brain WM were evaluated in terms of Fractional anisotropy (FA) by using Diffusion Tensor Imaging, whereas possible cognitive impairments were verified by means of neuropsychological testing, by studying: (1) General mental capability (2) Executive functioning; (3) Visuospatial construction such as Rey Complex Figure; (4) Attention and orientation: (5) Selective attention capacity and processing speed ability; (6) Memory. The results showed alteration of the WM in terms of changes in FA; these alterations, statistically significant but quantitatively quite modest, were mainly observed in the WM of the anterior part of the brain, whereas no differences were observed between left and right hemisphere. The alterations of the WM were associated with changes, also in this case statistically significant but quantitatively quite modest, of the cognitive functions, in particular of those dependent on the prefrontal cortex, such as attention and memory function. The present study leads to the conclusion that repeated dives, even performed in compliance with the current decompression tables, can progressively lead in the CNS to the formation of micro-lesions in the myelin sheet capable of altering the functioning of the neuron.

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 Alzheimer's 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.

Working memory and blood lactate levels.

The accumulation of lactate in the blood after a high-intensity exercise is associated with an increase of lactate extractions by the brain. Previously, a negative influence of blood lactate on attentional processes has been observed. The present study was carried out to examine the association of high blood lactate levels, induced with a maximal cycling, with another cognitive domain: working memory. For evaluation of working memory two different protocols were used: the first (Self-Ordered Pointing Task) capable of analyzing non-spatial working memory requiring the ability to generate and monitor a sequence of responses and the second for evaluating motor working memory necessary to perform a motor task. The study was carried out in 30 students (15 males and 15 females) who performed exhaustive exercise. In each subject, blood lactate was measured and motor as well as non-motor forms of working memory were evaluated before the exercise, at its end as well as 15 min after the exhaustion. It was observed that an increase of blood lactate levels is associated with a worsening of both types of working memory.

Executive dysfunctions in migraine with and without aura: what is the role of white matter lesions?

OBJECTIVE/BACKGROUND: Executive dysfunctions and white matter lesions on magnetic resonance imaging have been reported in migraine. The aim of this study was to determine whether any correlation between these 2 variables exists. MATERIALS AND METHODS: Forty-four subjects affected by migraine with or without aura were compared with 16 healthy subjects. A battery of neuropsychological tests assessing executive functions was administered to all subjects. Number and total volume of white matter lesions were assessed in the whole brain and in the frontal lobe. RESULTS: The performances of both groups of migraineurs, with and without aura, were significantly worse when compared with controls on Boston Scanning Test. Moreover, we found lower performances compared with controls respectively on Frontal Assessment Battery in patients with migraine with aura and on Controlled Oral Word Association Test in patients with migraine without aura. Nineteen patients (43.2%) and one control subject (6.2%) had white matter lesions. We did not find any significant correlation between white matter lesions load and neuropsychological performances. CONCLUSIONS: On the basis of our results, white matter lesions load on magnetic resonance imaging do not seem to contribute to neuropsychological performances deficit in migraineurs.

Attentional processes during submaximal exercises.

Blood levels of lactate and glucose were measured in 15 healthy male athletes with the purpose of evaluating possible correlation between their blood values and intensity and selectivity of attention, after a 30-min steady-state test performed at 60 and 80% of maximal oxygen consumption (VO2max). On the basis of the results, we conclude that, during aerobic exercise, a worsening of attentional capabilities does not occur unless there is an increase of blood lactate above 4 mmol/l.

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.

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.

Lack of interaction between LRP1 and A2M polymorphisms for the risk of Alzheimer disease.

Alzheimer disease (AD) has a heterogeneous aetiology, involving genetic and environmental factors. Low-density lipoprotein receptor-related protein 1 (LRP1), alpha-2-macroglobulin (A2M) and apolipoprotein E (APOE) are involved in molecular pathways leading to beta-amyloid deposition. Three polymorphic sites in these genes (APOE-epsilon 2/epsilon 3/epsilon 4, A2M-Ile/Val and LRP1-C/T) have been associated with AD, but the results were not univocal. We carried out a case-control study to investigate the association between these polymorphisms and the risk of developing AD and their possible interaction. We recruited 125 AD patients who fulfilled the diagnostic criteria proposed by NINCDS-ADRDA for probable or possible AD and 310 controls subjects. PCR was used to detect the polymorphisms. ORs and 95% CIs were estimated using logistic regression analysis. The OR for subjects carrying at least one allele Val (A2M-Val+) in their genotypes was 1.52 (95% CI 1.00-2.31; p=0.05); for subjects carrying at least one allele C (LRP1-C+), 1.58 (95% CI 1.00-2.50; p=0.05); for subjects carrying at least one allele epsilon 4 (APOE-epsilon 4+), 3.1 (95%CI 1.87-5.00; p<0.001). The coexistence of at least one allele Val (A2M-Val+) and one allele C (LRP1-C+) increased up two times the risk of AD (OR 2.32; 95% CI 1.23-4.35; p<0.009). No evidence of significant interaction has been found between the studied polymorphisms (p>0.05). In conclusion our study suggests that LRP1-C/T, A2M-Ile/Val and APOE-epsilon 2/epsilon 3/epsilon 4 polymorphisms are associated with AD.

Neuronal NOS expression in rat's cuneate nuclei following passive forelimb movements and median nerve stimulation.

Nitric oxide (NO) synthase (NOS) has been observed in the Cuneate Nuclei (CN), suggesting a role for NO in the modulation of their neurons' activity. The present study was undertaken to evaluate whether passive movement of forelimb as well as electric stimulation of medial nerve modulate the expression of neuronal isoform of NOS (nNOS) within CN. The experiments were carried out on 21 male Wistar rats, by using two different protocols. In the first group of rats the median nerve was stimulated with high frequency trains (phasic stimulation) or at constant frequency (tonic stimulation); as a control, in the third group, no stimulus was delivered. Moreover, in the second group of rats, we imposed to the animal's left forepaw circular paths at a roughly constant speed (continuous movement), or rapid flexions and extensions of the wrist (sudden movement); as a control, in the third group, no movement was imposed. After the experimental session, free-floating frontal sections of medulla oblongata were processed for nNOS or glutamate (GLU) immunohistochemistry. Phasic stimulation of the median nerve or sudden movements of the forelimb determines a significant decrement of the nNOS-positive neurons within the ipsilateral CN, whereas no effects were observed on GLU positive cells. We have also found a peculiar topographical distribution within IN of nNOS-positive neurons: positive cells were clustered at periphery of some "niches" having circular or elliptical form, with GLU positive cells at center.

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.

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.

Influence of nitric oxide on the activity of cuneate neurons in the rat.

Some neurons of main and external cuneate nuclei are immunoreactive for nitric oxide (NO) synthase, suggesting a role for endogenous NO in the early stages of somatosensory processing. We tested this hypothesis by investigating the possibility that NO modulates cuneate discharge. We observed that both spontaneous and N-methyl-D-aspartate-evoked activities of cuneate neurons were decreased by NO precursor L-arginine. The inhibition of NO synthase, by application of N-nitro-L-arginine methyl ester, instead, abolished the depressant effect induced by L-arginine. Our data suggest a NO modulation of cuneate neurons and provide support for a physiologic role not only in increasing the signal-to-noise ratio in the excited cells but also in a form of surround inhibition.

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.

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

Twenty Alzheimer's 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.