BACKGROUND AND AIMS:We aimed to study subclinical non-invasive vascular markers as predictors of incident long-term cognitive impairment in a longitudinal population-based study. METHODS:The Barcelona-Asymptomatic Intracranial Atherosclerosis (AsIA) study is a population-based study that included a random sample of 933 Caucasian subjects (mean age 66 years, 64% male) with a moderate-high vascular risk and without history of stroke or dementia. Subclinical carotid and intracranial stenosis was assessed at baseline visit by cervical and transcranial color-coded duplex (TCCD) and confirmed by magnetic resonance angiography. Cervico-cerebral stenosis (CCS) was defined as the presence of extra and/or intracranial stenosis >50%. Baseline middle cerebral artery pulsatility index (MCA-PI) was measured bilaterally by TCCD, and mean PI of both sides was considered for analyses. Subjects were followed-up to determine incident long-term cognitive impairment (mild cognitive impairment or dementia). RESULTS:After a median of 7.16 [6.91-7.75] years of follow-up, 91 subjects (9.7%) developed cognitive impairment, 27 of them mild cognitive impairment, and 64 dementia. Incidence of cognitive impairment was significantly higher among subjects with subclinical CCS (21.4% versus 9% in those without CCS) and among those with mean MCA-PI>1 (13.5% versus 7.4% in those with MCA-PI<1). In multivariate Cox regression analyses, both CCS and MCA-PI>1 were independently associated with incident cognitive impairment with HR of 2.07 [1.11-3.88] and 1.58 [1.02-2.46], respectively. CONCLUSIONS:Subclinical cervico-cerebral stenosis and higher MCA-PI are non-invasive neurosonological markers of incident long-term cognitive impairment in our population.

Introduction: Numerous diagnostic criteria have tried to tackle the variability in clinical manifestations and problematic diagnosis of vascular cognitive impairment (VCI) but none have been universally accepted. These criteria have not been readily comparable, impacting on clinical diagnosis rates and in turn prevalence estimates, research, and treatment.Methods: The Vascular Impairment of Cognition Classification Consensus Study (VICCCS) involved participants (81% academic researchers) from 27 countries in an online Delphi consensus study. Participants reviewed previously proposed concepts to develop new guidelines.Results: VICCCS had a mean of 122 (98-153) respondents across the study and a 67% threshold to represent consensus. VICCCS redefined VCI including classification of mild and major forms of VCI and subtypes. It proposes new standardized VCI-associated terminology and future research priorities to address gaps in current knowledge.Discussion: VICCCS proposes a consensus-based updated conceptualization of VCI intended to facilitate standardization in research. (C) 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Resting-state studies conducted with stroke patients are scarce. First objective was to explore whether patients with good cognitive recovery showed differences in resting-state functional patterns of brain activity when compared to patients with poor cognitive recovery. Second objective was to determine whether such patterns were correlated with cognitive performance. Third objective was to assess the existence of prognostic factors for cognitive recovery. Eighteen right-handed stroke patients and eighteen healthy controls were included in the study. Stroke patients were divided into two groups according to their cognitive improvement observed at three months after stroke. Probabilistic independent component analysis was used to identify resting-state brain activity patterns. The analysis identified six networks: frontal, fronto-temporal, default mode network, secondary visual, parietal, and basal ganglia. Stroke patients showed significant decrease in brain activity in parietal and basal ganglia networks and a widespread increase in brain activity in the remaining ones when compared with healthy controls. When analyzed separately, patients with poor cognitive recovery (n=10) showed the same pattern as the whole stroke patient group, while patients with good cognitive recovery (n=8) showed increased activity only in the default mode network and fronto-temporal network, and decreased activity in the basal ganglia. We observe negative correlations between basal ganglia network activity and performance in Semantic Fluency test and Part A of the Trail Making Test for patients with poor cognitive recovery. A reverse pattern was observed between frontal network activity and the abovementioned tests for the same group. (C) 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.

Resting-state studies conducted with stroke patients are scarce. The study of brain activity and connectivity at rest provides a unique opportunity for the investigation of brain rewiring after stroke and plasticity changes. This study sought to identify dynamic changes in the functional organization of the default mode network (DMN) of stroke patients at three months after stroke. Eleven patients (eight male and three female; age range: 48-72) with right cortical and subcortical ischemic infarctions and 17 controls (eleven males and six females; age range: 57-69) were assessed by neurological and neuropsychological examinations and scanned with resting-state functional magnetic ressonance imaging. First, we explored group differences in functional activity within the DMN by means of probabilistic independent component analysis followed by a dual regression approach. Second, we estimated functional connectivity between 11 DMN nodes both locally by means of seed-based connectivity analysis, as well as globally by means of graph-computation analysis. We found that patients had greater DMN activity in the left precuneus and the left anterior cingulate gyrus when compared with healthy controls (P<0.05 family-wise error corrected). Seed-based connectivity analysis showed that stroke patients had significant impairment (P=0.014; threshold=2.00) in the connectivity between the following five DMN nodes: left superior frontal gyrus (lSFG) and posterior cingulate cortex (t=2.01); left parahippocampal gyrus and right superior frontal gyrus (t=2.11); left parahippocampal gyrus and lSFG (t=2.39); right parietal and lSFG (t=2.29). Finally, mean path length obtained from graph-computation analysis showed positive correlations with semantic fluency test (r(s)=0.454; P=0.023), phonetic fluency test (r(s)=0.523; P=0.007) and the mini mental state examination (r(s)=0.528; P=0.007). In conclusion, the ability to regulate activity of the DMN appears to be a central part of normal brain function in stroke patients. Our study expands the understanding of the changes occurring in the brain after stroke providing a new avenue for investigating lesion-induced network plasticity. Hum Brain Mapp 36:577-590, 2015. (c) 2014 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Resumen: Objetivos: Determinar la respuesta a los potenciales evocados visuales (P300) en pacientes con hidrocefalia de presión normal (NPH) antes y después de la implantación de una derivación de líquido cefalorraquídeo (LCR) y establecer su relación con la situación clínica y cognitiva antes y después del tratamiento quirúrgico. Métodos: Estudio prospectivo en una serie de 26 pacientes con NPH a los que se realizó una valoración clínica y neuropsicológica y se analizó la P300 antes y 6 meses después del tratamiento quirúrgico. Los resultados de la P300 de los pacientes antes y después 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 quirúrgico, 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 después de la implantación de la derivación 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 neuropsicológicos y en el grado de independencia en la realización de las actividades de la vida diaria entre los pacientes que presentaron la P300 antes de la cirugía y los que no la presentaron, ni entre los cambios de la P300 y los cambios clínicos o cognitivos después del tratamiento quirúrgico. Conclusiones: Un porcentaje importante de pacientes con una NPH no presentan onda P300 o su latencia está incrementada. Estas alteraciones pueden revertirse en muchos pacientes al implantar una derivación de LCR Abstract: 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. Palabras clave: Hidrocefalia de presión normal, Neuropsicología, Potenciales evocados cognitivos, Potenciales evocados visuales, P300, Keywords: Normal pressure hydrocephalus, Neuropsychology, Cognitive event-related brain potentials, Visual event-related potentials, P300

Martínez S, Cáceres C, Mataró M, Escudero D, Latorre P, Dávalos A. Is there progressive cognitive dysfunction in Sjögren Syndrome? A preliminary study.
Acta Neurol Scand: 122: 182–188.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard.

INTRODUCTION:Vascular risk factors (VRF) have been related to cognitive deficits and an increased risk of dementia. Cognitive impairment is considered to be one of the earliest manifestations of cerebrovascular disease. In Spain there is a high prevalence of VRF, but also one of the lowest incidences of cerebrovascular disease in Europe. This is the first study that investigates the relationship between VRF and cognition in a Spanish sample. METHODS:A total of 90 people aged between 50-65 years with a low-to-moderate cardiovascular risk underwent a neuropsychological evaluation. None of them had a history of cardiovascular disease. The battery included tests assessing executive, attentional, mnesic, visuospatial and motor-speed/coordination functions. We used correlation and inter-groups comparison to relate VRF to multiple cognitive domains0120. RESULTS:Higher stroke risk was significantly related to a lowered profile in visuo-constructive functions and motor-speed/coordination. Moreover, the group with moderate cardiovascular risk showed a lower performance in visuoconstructive functions compared to the low-risk group. After statistical adjustment for age, sex and years of scholarship VRF were only related to motor-speed/coordination. CONCLUSIONS:In healthy, middle-aged adults, VRF are related with impairment in two cognitive domains. This effect is slight and tends to appear in people with moderate cardiovascular risk.

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. (C) 2009 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L. All rights reserved.

Introduction: Vascular risk factors (VRF) have been related to cognitive deficits and an increased risk of dementia. Cognitive impairment is considered to be one of the earliest manifestations of cerebrovascular disease. In Spain there is a high prevalence of VRF, but also one of the lowest incidences of cerebrovascular disease in Europe. This is the first study that investigates the relationship between VRF and cognition in a Spanish sample.Methods: A total of 90 people aged between 50-65 years with a low-to-moderate cardiovascular risk underwent a neuropsychological evaluation. None of them had a history of cardiovascular disease. The battery included tests assessing executive, attentional, mnesic, visuospatial and motor-speed/coordination functions. We used correlation and inter-groups comparison to relate VRF to multiple cognitive domains(24).Results: Higher stroke risk was significantly related to a lowered profile in visuo-constructive functions and motor-speed/coordination. Moreover, the group with moderate cardiovascular risk showed a lower performance in visuoconstructive functions compared to the low-risk group. After statistical adjustment for age, sex and years of scholarship VRF were only related to motor-speed/coordination.Conclusions: In healthy, middle-aged adults, VRF are related with impairment in two cognitive domains. This effect is slight and tends to appear in people with moderate cardiovascular risk. (C) 2009 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L. All rights reserved.

Aim: To analyse the influence of apolipoprotein (APOE) is an element of 4 status on the cognitive and behavioural functions usually impaired after moderate and severe traumatic brain injury (TBI).Methods: In all, 77 patients with TBI selected from 140 consecutive admissions were genotyped for APOE. Each patient was subjected to neuropsychological and neurobehavioural assessment at least 6 months after injury.Results: Performance of participants carrying the is an element of 4 allele was notably worse on verbal memory (Auditory Verbal Learning Test), motor speed, fine motor coordination, visual scanning, attention and mental flexibility (Grooved Pegboard, Symbol Digit Modalities Test and part B of the Trail Making Test) and showed considerably more neurobehavioural disturbances (Neurobehavioral Rating Scale Revised) than the group without the is an element of 4 allele.Conclusions: In particular, performance on neuropsychological tasks that are presumed to be related to temporal lobe, frontal lobe and white matter integrity is worse in patients with the APOE is an element of 4 allele than in those without it. More neurobehavioural disturbances are observed in APOE is an element of 4 carriers than in APOE is an element of 2 and is an element of 3 carriers.

The primary goal of this study was to determine the incidence of post-traumatic ventriculomegaly (Evans' index >= 0.30) in 95 head-injured patients with a Glasgow Coma Scale (GCS) score of <= 13 at admission. Additional objectives were to determine the relationship between an increase in ventricular size and several clinical and radiological features and outcome. A planimetric study was carried out in the sequential control computed tomography (CT) scans of 34 moderately head-injured (GCS 9-13) and 61 severely head-injured (GCS 3-8) patients with a minimum follow-up of 2 months. Between two and six CT scans were evaluated in each patient. The presence of subarachnoid hemorrhage (SAH) was registered. Evans' index was determined in all CT scans. In the final CT scan of each patient, ventricular size was related to the admission GCS score, age, the presence of SAH in the initial CT scans, type of brain lesion (classified according to the final diagnosis in the Traumatic Coma Data Bank classification), and outcome. Ventriculomegaly was found in 39.3% of patients with severe head injury and in 27.3 % of those with a moderate head injury. Increased ventricular size was evident 4 weeks after injury in 57.6% and 2 months after injury in 69.7%. No relationship was found between post-traumatic ventriculomegaly and age, initial GCS score, the presence of SAH, or type of lesion (focal or diffuse). Post-traumatic ventriculomegaly was significantly correlated with outcome. Post-traumatic ventriculomegaly is a frequent and early finding in patients with moderate or severe traumatic brain injury.

OBJECTIVES:Our aim was to evaluate corpus callosum functioning in a group of patients with normal pressure hydrocephalus (NPH) before and after shunting.METHODS:Left ear-extinction under a dichotic listening task was evaluated in twenty-three patients with NPH, 30 patients with Alzheimer's disease and 30 aged controls.RESULTS:Patients with NPH had higher levels of left ear extinction than the control and Alzheimer's groups. Sixty-one percent of NPH patients exhibited left ear suppression, compared with 13% of Alzheimer's patients and 17% of controls. Following surgery, NPH patients showed a significant change in the degree of asymmetry in the dichotic listening task.CONCLUSIONS:Hydrocephalus was associated with left-ear extinction,which diminished after surgery. Our results may indicate reversible functional damage in the corpus callosum.

Object. The authors set out to describe the outcome in a subgroup of patients with normal-pressure hydrocephalus (NPH) in whom prognostic factors were poor. This subgroup of patients who had received shunts was selected according to strict criteria.Methods. From a cohort of 56 patients with NPH in whom shunts were placed, the authors selected a subgroup with four of the factors traditionally considered to indicate poor prognosis: idiopathic type, cortical atrophy, longstanding symptoms, and presence of dementia in addition to old age. Twelve patients met the inclusion criteria.After receiving shunts, 92% of the patients showed clinical improvement on the NPH scale; gait improved in 100% of patients, sphincter control in 90%, and dementia in 33%. Improvement was significant for gait and sphincter control, general NPH score, and most daily life activity scales. No significant differences regarding clinical, cognitive, or functional changes following surgery were found in comparison with the rest of patients (the good prognosis subgroup).Conclusions. The clinical condition of patients with NPH who present with traditionally accepted markers of poor prognosis can improve after surgery, especially as regards gait and sphincter control. The authors assert that the presence of these markers should not be considered to be an absolute criterion for ruling out shunt surgery in cases of NPH syndrome.

OBJECTData from many studies have demonstrated that shunt insertion in patients with idiopathic normal-pressure hydrocephalus (NPH) is associated with high morbidity and a lack of significant improvement; however, the use of strict diagnostic and treatment protocols can improve the results of surgery in these patients. The primary aim in this prospective study was to analyze the results of shunt placement in 43 patients with idiopathic NPH. A secondary aim was to determine the relationship between several clinical and neuroimaging factors, and patient outcome after surgery.METHODSThirty men and 13 women with a mean age of 71.1 +/- 6.9 years participated in this study. All patients underwent clinical, neuropsychological, and radiological assessment before and 6 months after surgery. In all patients continuous monitoring of intracranial pressure was performed using a fiberoptic extradural sensor. In 31 patients cerebrospinal fluid dynamics were also determined. Eighty-six percent of patients showed clinical improvement after shunt insertion, 11.6% showed no change, and 2.3% exhibited some worsening. Gait improved in 81.4% of the patients, sphincter control in 69.8%, and cognitive dysfunction in 39.5%. There was no treatment-related death. Early or late postsurgical complications occurred in six patients (14%), although all of these complications were minor or were satisfactorily resolved. The complete clinical triad, cortical sulci size, and periventricular lucencies were related to outcome, whereas patient age, symptom duration, ventricular dilation, and the degree of presurgical dementia were unrelated to outcome.CONCLUSIONSGiven the correct diagnosis, shunt insertion can produce marked improvement in patients with idiopathic NPH syndrome, causing few deaths and few clinically relevant complications.

Extraneurological insults secondary to TBI such as hypotension or hypoxia have been associated with mortality and morbidity. The purpose of this study was to investigate the influence of systemic complications on both neuropsychological outcome and cerebral atrophy. Fifty-seven patients selected from 122 consecutive admissions were studied. Data on the type and severity of injury as well as other systemic insults were collected prior to and during the first 3 days of hospitalization. These data included the presence or absence of a hypoxic episode during the pre-hospital period, the presence and degree of hypoxia, hypercapnia, anemia, hypotension and intracranial hypertension, pupillary reactivity, Glasgow Coma Scale score and coma duration. From the last control CT scan image, performed 6 months post-injury, four different indexes of ventricular dilatation were calculated. Neuropsychological assessment at 6 months included tests of verbal and visual memory, visuoconstructive functions, fine motor speed, and frontal lobe functions. Our results showed that hypoxia and hypotension were related to neuropsychological outcome and long-term ventricular enlargement. Hypoxic episodes prior to hospitalization were related to third ventricle dilatation and to adverse neurological and cognitive outcomes, especially to attention, motor speed, mental flexibility, fluency and verbal memory impairments, suggesting fronto-striatal and hippocampal dysfunction. We conclude that the effect of extraneurological insults on brain structure and function may be as important as the severity of the primary injury.

BACKGROUND:Proton magnetic resonance spectroscopy can assess neurochemical sequelae in traumatic brain injury. Metabolic abnormalities are present in the acute or subacute period in patients with traumatic brain injury and correlate with outcome on clinical scales.OBJECTIVE:To investigate the use of proton magnetic resonance spectroscopy in detecting possible gray subcortical neurochemical impairments and their relationship with neuropsychological performance.DESIGN:Group comparisons and correlations of brain metabolites with clinical and neuropsychological variables.PATIENTS AND METHODS:Metabolite concentrations were acquired from voxels localized to the basal ganglia and medial temporal region in 20 patients with long-term moderate and severe traumatic brain injury and 20 matched control subjects. Both groups underwent neuropsychological assessment.RESULTS:N-acetylaspartate-choline-containing compounds ratios were decreased in patients in the basal ganglia (t = -3.28, P =.002) and medial temporal region (t = -3.52, P =.001). The basal ganglia ratio correlated to measures of speed, motor scanning, and attention.CONCLUSION:Patients with long-term TBI present a regional correlation pattern that may help identify the neurological basis of cognitive sequelae in traumatic brain injury.

Background: “Normal” pressure hydrocephalus (NPH) is associated with injury to neurotransmitter and neuropeptide systems that recovers after surgery. This could be linked to changes in galanin, a neuropeptide with inhibitory effects on basal forebrain cognitive function. Objective: To examine changes in CSF galanin concentrations in patients with normal pressure hydrocephalus undergoing shunt surgery, and to investigate the relation between these changes and cognitive functioning. Methods: Eight patients underwent surgery for idiopathic normal pressure hydrocephalus. Lumbar CSF galanin determinations, cognitive status, and clinical status were quantified before operation and six months after. Cognition was assessed by an extensive battery of tests measuring attention, memory, speed of mental processing, visuospatial function, and frontal lobe function. Results: CSF galanin concentration decreased after surgery. This reduction correlated with improved clinical and cognitive functioning, specifically with attention and visuomotor speed, visuoconstructive and frontal functioning, and clinical status according to the NPH scale, including the sphincter and cognitive components. Conclusions: The cognitive and clinical improvement after shunt implantation correlated with CSF galanin levels, suggesting that the distribution or function of this agent involves cerebral structures that have some potential for recovery. In this study, galanin was related to several cognitive functions that may be associated with the fronto-subcortical deficits underlying cognitive dysfunction in normal pressure hydrocephalus.

UNLABELLED:Our goal was to study cerebral blood flow (CBF) changes after surgery in a group of 15 patients with idiopathic normal pressure hydrocephalus (NPH).METHODS:We used hexamethylpropyleneamine oxime SPECT and statistical parametric mapping (SPM), an image analysis method that does not require prior selection of regions of interest.RESULTS:Our study showed areas of significant increase in perfusion in specific regions of both frontal lobes and the right parietal lobe. Regions of increased perfusion were found in the left prefrontal dorsolateral areas (Brodmann's areas 9 and 45 or 47), right frontal premotor area (Brodmann's area 44), right medial prefrontal region (Brodmann's area 10 or 32), right frontal white matter area (superior longitudinalis fasciculus), and right basal ganglia (lenticular nucleus, putamen, and globus pallidus). In the right hemisphere, another region of increased perfusion was found in the inferior parietal lobule (Brodmann's area 40). The 2 areas most related to clinical improvement were Brodmann's area 32 and the frontal part of the left lobule of Reil insula.CONCLUSION:The results obtained with the SPM method of image analysis confirm and expand on previous CBF literature in NPH, with specific CBF regions located in frontal and parietal areas that improve after surgery in idiopathic NPH.

Objectives. The aims of the study were 1) to assess the degree of agreement between CSF flow dynamics determined by MR and ICP monitoring in the diagnosis of NPH, and 2) to determine the sensitivity and specificity of CSF flow dynamics studied by MR in predicting improvement after shunting.Patients and Methods. A prospective study was carried out in 35 consecutive patients with suspected NPH. CSF velocity (Phase Contrast) through the aqueduct was determined in sagittal plane. Patients were classified as "normal" or hyperdynamic in comparison with a control group of 27 healthy volunteers. Continuous extradural ICP monitoring was performed for at least 72 hours and patients were classified as having active, compensated, or ex-vacuo hydrocephalus. Patients with active or compensated hydrocephalus were shunted.Results. The degree of agreement between MR dynamics and ICP monitoring was 82%. Sensitivity of CSF velocity was 90% and specificity was 50%.Conclusions. The degree of agreement between ICP monitoring and CSF velocity is high. High CSF velocity through the aqueduct is a good predictor of improvement after surgery. However, patients with normal velocity in MR required additional tests before a diagnosis of NPH is ruled out.