Elisabeth Solana

Decreased Default Mode Network connectivity correlates with age-associated structural and cognitive changes.

Ageing entails cognitive and motor decline as well as brain changes such as loss of gray (GM) and white matter (WM) integrity, neurovascular and functional connectivity alterations. Regarding connectivity, reduced resting-state fMRI connectivity between anterior and posterior nodes of the Default Mode Network (DMN) relates to cognitive function and has been postulated to be a hallmark of ageing. However, the relationship between age-related connectivity changes and other neuroimaging-based measures in ageing is fragmentarily investigated. In a sample of 116 healthy elders we aimed to study the relationship between antero-posterior DMN connectivity and measures of WM integrity, GM integrity and cerebral blood flow (CBF), assessed with an arterial spin labeling sequence. First, we replicated previous findings demonstrating DMN connectivity decreases in ageing and an association between antero-posterior DMN connectivity and memory scores. The results showed that the functional connectivity between posterior midline structures and the medial prefrontal cortex was related to measures of WM and GM integrity but not to CBF. Gray and WM correlates of anterio-posterior DMN connectivity included, but were not limited to, DMN areas and cingulum bundle. These results resembled patterns of age-related vulnerability which was studied by comparing the correlates of antero-posterior DMN with age-effect maps. These age-effect maps were obtained after performing an independent analysis with a second sample including both young and old subjects. We argue that antero-posterior connectivity might be a sensitive measure of brain ageing over the brain. By using a comprehensive approach, the results provide valuable knowledge that may shed further light on DMN connectivity dysfunctions in ageing.

Cognitive and motor improvement after retesting in normal-pressure hydrocephalus: a real change or merely a learning effect?

OBJECT The test-retest method is commonly used in the management of patients with normal-pressure hydrocephalus (NPH). One of the most widely used techniques in the diagnosis of this condition is evaluation of the patients response to CSF evacuation by lumbar puncture (a so-called tap test or spinal tap). However, interpretation of improved results in subsequent evaluations is controversial because higher scores could reflect a real change in specific abilities or could be simply the result of a learning effect. METHODS To determine the effect of testing-retesting in patients with NPH, the authors analyzed changes documented on 5 neuropsychological tests (the Toulouse-Pieron, Trail Making Test A, Grooved Pegboard, Word Fluency, and Bingley Memory tests) and several motor ability scales (motor performance test, length of step, and walking speed tests) in a series of 32 patients with NPH who underwent the same battery on 4 consecutive days. The same tests were also applied in 30 healthy volunteers. In both groups, the authors used the generalized least-squares regression method with random effects to test for learning effects. To evaluate possible differences in response depending on the degree of cognitive impairment at baseline, the results were adjusted by using the Mini-Mental State Examination scores of patients and controls when these scores were significant in the model. RESULTS In patients with NPH there were no statistically significant differences in any of the neuropsychological or motor tests performed over the 4 consecutive days, except in the results of the Toulouse-Pieron test, which were significantly improved on Day 3. In contrast, healthy volunteers had statistically significant improvement in the results of the Toulouse-Pieron test, Trail Making Test A, and Grooved Pegboard test but not in the remaining neuropsychological tests. Patients in the healthy volunteer group also exhibited statistically significant improvement in the motor performance test but not in step length or walking speed. CONCLUSIONS No learning effect was found in patients with NPH on any of the neuropsychological or motor tests. Clinical improvement after retesting in these patients reflects real changes, and this strategy can therefore be used in both the diagnosis and evaluation of surgical outcomes.

Neuroanatomical correlates of olfactory loss in normal aged subjects.

In non-demented older persons, smell dysfunction, measured premortem, has been associated with postmortem brain degeneration similar to that of Alzheimers disease. We hypothesized that distinct measures of gray and white matter integrity evaluated through magnetic resonance imaging (MRI) techniques could detect degenerative changes associated with age-related olfactory dysfunction. High-resolution T1-weighted images and diffusion-tensor images (DTI) of 30 clinically healthy subjects aged 51-77 were acquired with a 3-Tesla MRI scanner. Odor identification performance was assessed by means of the University of Pennsylvania Smell Identification Test (UPSIT). UPSIT scores correlated with right amygdalar volume and bilateral perirhinal and entorhinal cortices gray matter volume. Olfactory performance also correlated with postcentral gyrus cortical thickness and with fractional anisotropy and mean diffusivity levels in the splenium of the corpus callosum and the superior longitudinal fasciculi. Our results suggest that age-related olfactory loss is accompanied by diffuse degenerative changes that might correspond to the preclinical stages of neurodegenerative processes.

Idiopathic normal pressure hydrocephalus: results of a prospective cohort of 236 shunted patients.

AIM To describe the outcomes and complication rates in 236 patients with idiopathic normal pressure hydrocephalus (INPH) after treatment. PATIENTS AND METHODS Among a cohort of 257 patients with suspected INPH, 244 were shunted and 236 were followed up at 6 months after shunting (145 men [61.4%] and 91 women [38.6%] with a median age of 75 years). The study protocol of these patients included clinical, radiological, neuropsychological and functional assessment. The decision to shunt patients was based on continuous intracranial pressure monitoring and CSF dynamics studies. A differential low-pressure valve system, always combined with a gravity compensating device, was implanted in 99% of the patients. RESULTS After shunting, 89.9% of the patients showed clinical improvement (gait improved in 79.3% of patients, sphincter control in 82.4%, and dementia in 63.7%). Two patients (0.8%) died. Early postsurgical complications were found in 13 of the 244 shunted patients (5.3%). Six months after shunting, the follow-up CT showed asymptomatic hygromas in 8 of the 236 (3.4%). Additional postsurgical complications were found in 7 patients (3%), consisting of 6 subdural hematomas (3 acute and 3 chronic) and 1 distal catheter infection. CONCLUSIONS Currently, a high percentage of patients with INPH can improve after shunting, with early and late complication rates of less than 12%.

Cognitive disturbances and neuropsychological changes after surgical treatment in a cohort of 185 patients with idiopathic normal pressure hydrocephalus.

Although idiopathic normal pressure hydrocephalus (iNPH) is considered a treatable dementia, there is still some controversy regarding the cognitive improvement in these patients. The main aims of this study were to analyze baseline cognitive status and to study the neuropsychological changes after surgical treatment in a sample of 185 consecutive iNPH patients. An additional aim was to identify the variables that influenced the cognitive outcome. Specific tests assessing memory, attention, visual scanning, executive functions (EFs), and motor speed were used before and 6 months after shunting. The cognitive domains most affected at baseline were memory, EFs, attention, and psychomotor speed. After shunting, significant differences in the group as a whole were found in all tests except Digits Forward and Trail Making Part B. However, less than 50% of patients showed a significant improvement when analyzed individually. Previous global cognitive status assessed by Mini-Mental State Examination baseline scores was the best predictor for the cognitive outcome.

Structural networks involved in attention and executive functions in multiple sclerosis

Attention and executive deficits are disabling symptoms in multiple sclerosis (MS) that have been related to disconnection mechanisms. We aimed to investigate changes in structural connectivity in MS and their association with attention and executive performance applying an improved framework that combines high order probabilistic tractography and anatomical exclusion criteria postprocessing. We compared graph theory metrics of structural networks and fractional anisotropy (FA) of white matter (WM) connections or edges between 72 MS subjects and 38 healthy volunteers (HV) and assessed their correlation with cognition. Patients displayed decreased network transitivity, global efficiency and increased path length compared with HV (p < 0.05, corrected). Also, nodal strength was decreased in 26 of 84 gray matter regions. The distribution of nodes with stronger connections or hubs of the network was similar among groups except for the right pallidum and left insula, which became hubs in patients. MS subjects presented reduced edge FA widespread in the network, while FA was increased in 24 connections (p < 0.05, corrected). Decreased integrity of frontoparietal networks, deep gray nuclei and insula correlated with worse attention and executive performance (r between 0.38 and 0.55, p < 0.05, corrected). Contrarily, higher strength in the right transverse temporal cortex and increased FA of several connections (mainly from cingulate, frontal and occipital cortices) were associated with worse functioning (r between − 0.40 and − 0.47, p < 0.05 corrected). In conclusion, structural brain connectivity is disturbed in MS due to widespread impairment of WM connections and gray matter structures. The increased edge connectivity suggests the presence of reorganization mechanisms at the structural level. Importantly, attention and executive performance relates to frontoparietal networks, deep gray nuclei and insula. These results support the relevance of network integrity to maintain optimal cognitive skills.

[Cognitive event-related brain potentials (P300) in patients with normal pressure hydrocephalus. Results of a prospective study].

OBJECTIVE To determine the response to cognitive event-related potentials (P300) in patients with normal-pressure hydrocephalus (NPH) and their relationship with clinical and cognitive status before and after shunt surgery. METHODS We performed a prospective study in a series of 26 patients with NPH who underwent clinical and cognitive assessment before surgery and 6 months afterwards. Visual P300 potentials obtained before and after treatment were also compared with those obtained in 18 healthy volunteers. RESULTS Before shunting, the P300 wave was detected in 11 (42.3%) NPH patients, compared with the 18 (100%) volunteers. Six months after shunting, the P300 wave was found in 20 (76.9%) NPH patients. P300 latency was significantly longer in NPH patients than in the control group before surgery, but not at 6 months after surgery. No significant differences in neuropsychological studies or in the level of dependence for daily life activities were found between the subgroups of NPH patients with and without pre-surgical P300 waves, or between changes in P300 parameters and clinical and cognitive changes. CONCLUSIONS The P300 wave was delayed or undetectable in a substantial percentage of patients with NPH before surgery. These alterations can be reversed by shunting. P300 analysis and neuropsychological tests could be complementary measures to evaluate functional status in patients with NPH.

Normal Hypocretin-1 (Orexin A) Levels in Cerebrospinal Fluid in Patients with Idiopathic Intracranial Hypertension

AIM Low levels of hypocretin-1 (HC-1) have been associated with hypersomnia, obesity, depression, and chronic headaches. These conditions are frequently present in patients with idiopathic intracranial hypertension (IIH) and may be associated with abnormalities of the hypocretin system. The aim of this study was to determine HC-1 concentrations in cerebrospinal fluid (CSF) in a series of patients with IIH and to compare these concentrations with those in a control group with no neurological alterations. PATIENTS AND METHODS This prospective study included a cohort of 26 consecutive patients with IIH who were mostly women (25 vs. 1) with a mean age of 42.5 ± 13.2. CSF samples were obtained from a lumbar puncture performed between 08:00 and 10:00 a.m. HC-1 was determined by a competitive radioimmunoassay (RIA) using I(125) as the isotope. Samples of normal CSF were obtained during spinal anesthesia for urological, general or vascular surgery from 40 patients (10 women and 30 men with a mean age of 63.7 ± 14.8) with no previous neurological or psychiatric history, a normal neurological examination, and MMSE scores of ≥ 24. RESULTS No statistically significant differences were found between HC-1 levels in the CSF of patients with IIH (119.61 ± 21.63 pg/mL) and those of the control group (119.07 ± 20.30 pg/mL; p = 0.918). CONCLUSIONS HC-1 is not associated with the clinical symptoms present in patients with IIH.

Potenciales evocados cognitivos (P300) en pacientes con hidrocefalia de presión normal

Resumen Objetivos Determinar la respuesta a los potenciales evocados visuales (P300) en pacientes con hidrocefalia de presion normal (NPH) antes y despues de la implantacion de una derivacion de liquido cefalorraquideo (LCR) y establecer su relacion con la situacion clinica y cognitiva antes y despues del tratamiento quirurgico. Metodos Estudio prospectivo en una serie de 26 pacientes con NPH a los que se realizo una valoracion clinica y neuropsicologica y se analizo la P300 antes y 6 meses despues del tratamiento quirurgico. Los resultados de la P300 de los pacientes antes y despues del tratamiento se compararon con los de un grupo control de 18 voluntarios sanos. Resultados Once de los pacientes con una NPH (42,3%) presentaron onda P300 antes del tratamiento quirurgico, mientras que esta onda estaba presente en los 18 individuos del grupo control (100%). La latencia de la onda fue significativamente superior en los pacientes que en el grupo control. Seis meses despues de la implantacion de la derivacion de LCR, 20 (76,9%) de los pacientes con NPH presentaron la onda P300, sin que hubiera diferencias significativas en las latencias de la onda entre ambos grupos. No hubo diferencias en los estudios neuropsicologicos y en el grado de independencia en la realizacion de las actividades de la vida diaria entre los pacientes que presentaron la P300 antes de la cirugia y los que no la presentaron, ni entre los cambios de la P300 y los cambios clinicos o cognitivos despues del tratamiento quirurgico. Conclusiones Un porcentaje importante de pacientes con una NPH no presentan onda P300 o su latencia esta incrementada. Estas alteraciones pueden revertirse en muchos pacientes al implantar una derivacion de LCR

Adaptability and reproducibility of a memory disruption rTMS protocol in the PharmaCog IMI European project

Transcranial magnetic stimulation (TMS) can interfere with cognitive processes, such as transiently impairing memory. As part of a multi-center European project, we investigated the adaptability and reproducibility of a previously published TMS memory interfering protocol in two centers using EEG or fMRI scenarios. Participants were invited to attend three experimental sessions on different days, with sham repetitive TMS (rTMS) applied on day 1 and real rTMS on days 2 and 3. Sixty-eight healthy young men were included. On each experimental day, volunteers were instructed to remember visual pictures while receiving neuronavigated rTMS trains (20 Hz, 900 ms) during picture encoding at the left dorsolateral prefrontal cortex (L-DLPFC) and the vertex. Mixed ANOVA model analyses were performed. rTMS to the L-DLPFC significantly disrupted recognition memory on experimental day 2. No differences were found between centers or between fMRI and EEG recordings. Subjects with lower baseline memory performances were more susceptible to TMS disruption. No stability of TMS-induced memory interference could be demonstrated on day 3. Our data suggests that adapted cognitive rTMS protocols can be implemented in multi-center studies incorporating standardized experimental procedures. However, our center and modality effects analyses lacked sufficient statistical power, hence highlighting the need to conduct further studies with larger samples. In addition, inter and intra-subject variability in response to TMS might limit its application in crossover or longitudinal studies.