COVID-19 after two years: trajectories of different components of mental health in the Spanish population.

AIMS: Our study aimed to (1) identify trajectories on different mental health components during a two-year follow-up of the COVID-19 pandemic and contextualise them according to pandemic periods; (2) investigate the associations between mental health trajectories and several exposures, and determine whether there were differences among the different mental health outcomes regarding these associations. METHODS: We included 5535 healthy individuals, aged 40-65 years old, from the Barcelona Brain Health Initiative (BBHI). Growth mixture models (GMM) were fitted to classify individuals into different trajectories for three mental health-related outcomes (psychological distress, personal growth and loneliness). Moreover, we fitted a multinomial regression model for each outcome considering class membership as the independent variable to assess the association with the predictors. RESULTS: For the outcomes studied we identified three latent trajectories, differentiating two major trends, a large proportion of participants was classified into 'resilient' trajectories, and a smaller proportion into 'chronic-worsening' trajectories. For the former, we observed a lower susceptibility to the changes, whereas, for the latter, we noticed greater heterogeneity and susceptibility to different periods of the pandemic. From the multinomial regression models, we found global and cognitive health, and coping strategies as common protective factors among the studied mental health components. Nevertheless, some differences were found regarding the risk factors. Living alone was only significant for those classified into 'chronic' trajectories of loneliness, but not for the other outcomes. Similarly, secondary or higher education was only a risk factor for the 'worsening' trajectory of personal growth. Finally, smoking and sleeping problems were risk factors which were associated with the 'chronic' trajectory of psychological distress. CONCLUSIONS: Our results support heterogeneity in reactions to the pandemic and the need to study different mental health-related components over a longer follow-up period, as each one evolves differently depending on the pandemic period. In addition, the understanding of modifiable protective and risk factors associated with these trajectories would allow the characterisation of these segments of the population to create targeted interventions.

Healthy minds from 0-100 years: Optimising the use of European brain imaging cohorts ("Lifebrain").

The main objective of "Lifebrain" is to identify the determinants of brain, cognitive and mental (BCM) health at different stages of life. By integrating, harmonising and enriching major European neuroimaging studies across the life span, we will merge fine-grained BCM health measures of more than 5,000 individuals. Longitudinal brain imaging, genetic and health data are available for a major part, as well as cognitive and mental health measures for the broader cohorts, exceeding 27,000 examinations in total. By linking these data to other databases and biobanks, including birth registries, national and regional archives, and by enriching them with a new online data collection and novel measures, we will address the risk factors and protective factors of BCM health. We will identify pathways through which risk and protective factors work and their moderators. Exploiting existing European infrastructures and initiatives, we hope to make major conceptual, methodological and analytical contributions towards large integrative cohorts and their efficient exploitation. We will thus provide novel information on BCM health maintenance, as well as the onset and course of BCM disorders. This will lay a foundation for earlier diagnosis of brain disorders, aberrant development and decline of BCM health, and translate into future preventive and therapeutic strategies. Aiming to improve clinical practice and public health we will work with stakeholders and health authorities, and thus provide the evidence base for prevention and intervention.

Active and placebo transcranial magnetic stimulation effects on external and internal auditory hallucinations of schizophrenia.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) over the left temporo-parietal region has been proposed as a treatment for resistant auditory verbal hallucinations (AVH), but which patients are more likely to benefit from rTMS is still unclear. This study sought to assess the effects of rTMS on AVH, with a focus on hallucination phenomenology. METHOD: Twenty-seven patients with schizophrenia and medication-resistant AVH participated to a randomized, double-blind, placebo-controlled, add-on rTMS study. The stimulation targeted a language-perception area individually determined using functional magnetic resonance imaging and a language recognition task. AVH were assessed using the hallucination subscale of the Scale for the Assessment of Positive Symptoms (SAPS). The spatial location of AVH was assessed using the Psychotic Symptom Rating Scales. RESULTS: A significant improvement in SAPS hallucination subscale score was observed in both actively treated and placebo-treated groups with no difference between both modalities. Patients with external AVH were significantly more improved than patients with internal AVH, with both modalities. CONCLUSIONS: A marked placebo effect of rTMS was observed in patients with resistant AVH. Patients with prominent external AVH may be more likely to benefit from both active and placebo interventions. Cortical effects related to non-magnetic stimulation of the auditory cortex are suggested.

Clinical and biomarker profiling of prodromal Alzheimer's disease in workpackage 5 of the Innovative Medicines Initiative PharmaCog project: a 'European ADNI study'.

BACKGROUND: In the field of Alzheimer's disease (AD), the validation of biomarkers for early AD diagnosis and for use as a surrogate outcome in AD clinical trials is of considerable research interest. OBJECTIVE: To characterize the clinical profile and genetic, neuroimaging and neurophysiological biomarkers of prodromal AD in amnestic mild cognitive impairment (aMCI) patients enrolled in the IMI WP5 PharmaCog (also referred to as the European ADNI study). METHODS: A total of 147 aMCI patients were enrolled in 13 European memory clinics. Patients underwent clinical and neuropsychological evaluation, magnetic resonance imaging (MRI), electroencephalography (EEG) and lumbar puncture to assess the levels of amyloid ß peptide 1-42 (Aß42), tau and p-tau, and blood samples were collected. Genetic (APOE), neuroimaging (3T morphometry and diffusion MRI) and EEG (with resting-state and auditory oddball event-related potential (AO-ERP) paradigm) biomarkers were evaluated. RESULTS: Prodromal AD was found in 55 aMCI patients defined by low Aß42 in the cerebrospinal fluid (Aß positive). Compared to the aMCI group with high Aß42 levels (Aß negative), Aß positive patients showed poorer visual (P = 0.001), spatial recognition (P < 0.0005) and working (P = 0.024) memory, as well as a higher frequency of APOE4 (P < 0.0005), lower hippocampal volume (P = 0.04), reduced thickness of the parietal cortex (P < 0.009) and structural connectivity of the corpus callosum (P < 0.05), higher amplitude of delta rhythms at rest (P = 0.03) and lower amplitude of posterior cingulate sources of AO-ERP (P = 0.03). CONCLUSION: These results suggest that, in aMCI patients, prodromal AD is characterized by a distinctive cognitive profile and genetic, neuroimaging and neurophysiological biomarkers. Longitudinal assessment will help to identify the role of these biomarkers in AD progression.

Evaluation of symptomatic drug effects in Alzheimer's disease: strategies for prediction of efficacy in humans.

In chronic diseases such as Alzheimer's disease (AD), the arsenal of biomarkers available to determine the effectiveness of symptomatic treatment is very limited. Interpretation of the results provided in literature is cumbersome and it becomes difficult to predict their standardization to a larger patient population. Indeed, cognitive assessment alone does not appear to have sufficient predictive value of drug efficacy in early clinical development of AD treatment. In recent years, research has contributed to the emergence of new tools to assess brain activity relying on innovative technologies of imaging and electrophysiology. However, the relevance of the use of these newer markers in treatment response assessment is waiting for validation. This review shows how the early clinical assessment of symptomatic drugs could benefit from the inclusion of suitable pharmacodynamic markers. This review also emphasizes the importance of re-evaluating a step-by-step strategy in drug development.

[Posterior cortical atrophy. Its neuropsychological profile and differences from typical Alzheimer's disease]. / Atrofia cortical posterior. Perfil neuropsicológico y diferencias con la enfermedad de Alzheimer típica.

INTRODUCTION: The term 'posterior cortical atrophy' (PCA) refers to a neurodegenerative syndrome that is characterised by progressive alteration of the higher visual-perceptual and/or visual-spatial functions, which often presents Alzheimer's disease (AD). AIM: To describe the value of neuropsychological tests in the differential diagnosis of patients with PCA versus patients with typical AD. SUBJECTS AND METHODS: The sample was made up of four patients with PCA, four patients with initial typical AD with no significant differences in the degree of cognitive impairment according to the Minimental State Examination and seven cognitively healthy controls. Subjects were administered a full neuropsychological battery of tests for memory, language, praxias, executive functions, and visual-perceptual and visual-spatial capacities. The statistical analysis was performed using the Mann-Whitney U test for non-parametric tests and independent samples. RESULTS: In the neuropsychological study, scores were significantly lower in the group with PCA compared to the control group in verbal comprehension, praxias and visual gnosias (p < 0.05), and significantly higher with respect to the group with typical AD in episodic memory tests (p < 0.05). In contrast, patients with PCA had a significantly lower score in comparison to typical AD in visual-perceptive and visual-spatial tests (p < 0.05), and in constructive praxias (p < 0.05). CONCLUSIONS: Results in the neuropsychological tests show subjects with PCA and typical AD have different cognitive profiles, and are useful in the differential diagnosis of the two clinical variants.

Atrofia cortical posterior. Perfil neuropsicológico y diferencias con la enfermedad de Alzheimer típica / Posterior Cortical Atrophy. Its Neuropsychological profile and differences form typical alzheimer´s disease

Introducción. El término 'atrofia cortical posterior' (ACP) hace referencia a un síndrome neurodegenerativo caracterizado or una alteración progresiva de las funciones visuoperceptivas y/o visuoespaciales superiores, que frecuentemente presenta patología de enfermedad de Alzheimer (EA). Objetivo. Describir la utilidad de las pruebas neuropsicológicas en el diagnóstico diferencial de los pacientes con ACP frente a pacientes con EA típica. Sujetos y métodos. La muestra estaba formada por cuatro pacientes con ACP, cuatro pacientes con EA típica inicial sin diferencias significativas en el grado de deterioro cognitivo según el Minimental State Examination y siete controles cognitivamente sanos. Se administró una batería neuropsicológica completa que incluía test de memoria, lenguaje, praxias, función ejecutiva y las capacidades visuoperceptivas y visuoespaciales. En el análisis estadístico se utilizó la U de Mann-Whitney para pruebas no paramétricas y muestras independientes. Resultados. El estudio neuropsicológico mostró puntuaciones significativamente inferiores del grupo con ACP frente al grupo control en comprensión verbal, praxias y gnosias visuales (p < 0,05), y significativamente superiores respecto al grupo de EA típica en pruebas de memoria episódica (p < 0,05). Por el contrario, los pacientes con ACP tuvieron una puntuación significativamente inferior frente a la EA típica en pruebas visuoperceptivas y visuoespaciales (p < 0,05) y en las praxias constructivas (p < 0,05). Conclusión. Los resultados en las pruebas neuropsicológicas muestran diferentes perfiles cognitivos entre los sujetos con ACP y EA típica, y son útiles en el diagnóstico diferencial entre ambas variantes clínicas (AU)

Introduction. The term 'posterior cortical atrophy' (PCA) refers to a neurodegenerative syndrome that is characterised by progressive alteration of the higher visual-perceptual and/or visual-spatial functions, which often presents Alzheimer’s disease (AD). Aim. To describe the value of neuropsychological tests in the differential diagnosis of patients with PCA versus patients with typical AD. Subjects and methods. The sample was made up of four patients with PCA, four patients with initial typical AD with no significant differences in the degree of cognitive impairment according to the Minimental State Examination and seven cognitively healthy controls. Subjects were administered a full neuropsychological battery of tests for memory, language, praxias, executive functions, and visual-perceptual and visual-spatial capacities. The statistical analysis was performed using the Mann-Whitney U test for non-parametric tests and independent samples. Results. In the neuropsychological study, scores were significantly lower in the group with PCA compared to the control group in verbal comprehension, praxias and visual gnosias (p < 0.05), and significantly higher with respect to the group with typical AD in episodic memory tests (p < 0.05). In contrast, patients with PCA had a significantly lower score in comparison to typical AD in visual-perceptive and visual-spatial tests (p < 0.05), and in constructive praxias (p < 0.05). Conclusions. Results in the neuropsychological tests show subjects with PCA and typical AD have different cognitive profiles, and are useful in the differential diagnosis of the two clinical variants (AU)

Higher severity of frontal periventricular white matter and basal ganglia hyperintensities in first-ever lacunar stroke with multiple silent lacunes.

BACKGROUND AND PURPOSE: We investigated whether patients with a lacunar infarct (LI) syndrome exhibiting unique LI or multiple LI on magnetic resonance imaging (MRI) examinations differed in terms of topography and severity of white matter hyperintensities (WMH) ratings. METHODS: Forty consecutive patients with a first-ever acute LI, who presented a lacunar syndrome according to Miller-Fisher's classification were recruited and were classified into a group presenting isolated LI on MRI (n = 17) or multiple LI (n = 23). RESULTS: Despite equivalent demographic, clinical and cognitive characteristics, patients with multiple LI had increased ratings of WMH in frontal, occipital and subcortical regions. No significant correlations could be evidenced between the number of LI and WMH ratings. CONCLUSIONS: Present findings provide support to previous hypothesis considering single and multiple LI MRI presentations of lacunar infarct patients as distinct entities.

Increased cerebral activity in Parkinson's disease patients carrying the DRD2 TaqIA A1 allele during a demanding motor task: a compensatory mechanism?

Previous studies suggest that neuroimaging techniques are useful for detecting the effects of functional genetic polymorphisms on brain function in healthy subjects or in patients presenting with psychiatric or neurodegenerative conditions. Former evidence showed that individuals carrying risk alleles displayed broader patterns of brain activity during behavioural and cognitive tasks, despite being clinically comparable to non-carriers. This suggests the presence of compensatory brain mechanisms. In the present study, we investigated this effect in Parkinson's disease (PD) patients carrying the DRD2 TaqIA A1 allelic variant. This variant may confer an increased risk of developing the disease and/or influence the clinical presentation. During a complex sequential motor task, we evidenced by functional magnetic resonance imaging that A1 allele carriers activated a larger network of bilateral cerebral areas than non-carriers, including cerebellar and premotor regions. Both groups had similar clinical and demographic measures. In addition, their motor performance during the functional magnetic resonance experiment was comparable. Therefore, our conclusions, pending replication in a larger sample, seem to reflect the recruitment of compensatory cerebral resources during motor processing in PD patients carrying the A1 allele.

Posibilidades y limitaciones de un seguro de cuidados de larga duración para mayores dependientes en España / The possibilities and constrains of long term care insurance in Spain

En este articulo se examina la problemática de la financiaciónde la dependencia en España. Se revisa la evidencia empíricarelevante con en fin de evaluar los instrumentos de financiaciónal alcance, y en especial un seguro de dependencia comomecanismo de cobertura de los gastos asociados a cuidados delarga duración. Se argumenta que el riesgo de dependencia esun riesgo asegurable, si bien la existencia de fallos de mercadoapunta a la necesidad de instrumentalizar un seguro obligatorio.El rol del seguro privado un papel complementario o suplementario.La evidencia empírica apunta a que la opción preferidapor la población española es una financiación pública

This paper examines the financial policy constrains andpossibilities of funding long term care in Spain. To this end, werevise the existing empirical evidence to evaluate the financingtools available , and specially the applicability of a long term careinsurance as a means to insure the costs of long term care. Weargue that the dependency risks are insurable risks subjected tomarket failures that justify the need for a compulsory insurance.The role of the private long-term care insurance in that caseis restricted to a complementary or a supplementary role. Evidencefrom Spanish social attitudes suggests that the public prefersa publicly funded system to private alternatives

Polimorfismo T102C del receptor 5HT2A y rendimiento cognitivo en la alteración cognitiva leve / T102C polymorphism in the 5HT2A gene and cognition in mild cognitive impairment

La Alteración Cognitiva Leve es un estado de transición entreel envejecimiento normal y la enfermedad de Alzheimer y espor ello una condición de riesgo para la demencia. La serotoninay sus receptores tienen un papel importante en los procesosde aprendizaje y memoria. El receptor 5HT2A está localizadopredominantemente en áreas frontales e hipocampales. En esteestudio hemos valorado la influencia del genotipo del polimorfismoT102C del gen 5HT2A en el rendimiento cognitivo de unamuestra de 59 sujetos con Alteración Cognitiva Leve. Los sujetosheterocigotos (T102/C102) para este polimorfismo puntuabansignificativamente menos en el Mini-Mental, pruebas dememoria visual y verbal y en funciones premotoras, sugiriendoque este genotipo sería un nuevo marcador genético de riesgoen la alteración cognitiva

Mild Cognitive Impairment (MCI) is a transitional statebetween normal aging and Alzheimer’s disease and thus, it is ahigh-risk condition for dementia. Serotonin and its receptorsare associated with memory and learning processes. The5HT2A receptor is expressed in prefrontal cortex and hippocampus,above all. We have studied the role of the polymorphismT102C in the 5HT2A gene in cognition in a sample of 59MCI subjects. Those individuals carrying the heterozygous variant(T102/C102) performed significantly worse in the Mini-Mental State Examination, visual and verbal memory tests aswell as premotor functions. These results suggest that this genotypecould be a new genetic risk factor for cognitive impairmentin the elderly

Alteraciones neuropsicológicas en los infartos cerebrales de tipo lacunar / Neuropsychological dysfunction associated to lacunar stroke

Introducción: Hasta el momento se han realizado múltiples trabajos sobre los infartos lacunares (ILs), su etiología y los factores de riesgo para padecerlos, pero se han realizado muy pocos sobre las secuelas neuropsicológicas que éstos pueden comportar. Objetivo: Correlacionar la topografía de los infartos lacunares con diferentes perfiles de afectación cognitiva, relacionando la clínica neurológica con los parámetros de resonáncia magnética (RM anatómica) y los hallazgos obtenidos mediante la administración de pruebas neuropsicológicas. Material y método: Los pacientes que formaron parte del estudio fueron 20 pacientes consecutivos que ingresaron en el Servicio de Neurología del Hospital Sagrat Cor de Barcelona, presentando un síndrome lacunar según la clasificación de Miller Fisher: hemiparesia motora pura, síndrome sensitivo puro, hemiparesiaataxia, disartria-mano torpe y síndrome sensitivo-motriz. De los sujetos seleccionados se obtuvieron imágenes de RM cerebral potenciadas en T1, FLAIR y en densidad protónica (DP) para distinguir entre los infartos lacunares agudos y los existentes con anterioridad al ingreso. Posteriormente, a todos los pacientes se les realizó una exploración neuropsicológica completa. Resultados y conclusiones: Los resultados hallados son los siguientes: a) no hay ningún grupo sindrómico que se caracterice por presentar una mayor o menor representación de infartos únicos o múltiples. b) la diferencia entre la proporción de casos que presentaban o no leucoaraiosis no fue significativa para ninguno de los grupos clinicos. c) hallamos una diferencia significativa en el rendimiento en el Test de orientación de líneas de Benton, en la que los sujetos que presentaban un síndrome de Disartria-mano torpe puntuaban mejor que los que tenían un Sd.Sensitivo puro. d) el rendimiento neuropsicológico de los sujetos con un único o múltiples ILs difería en las pruebas de fluencia fonética (PMR) y semántica (animales en 1 minuto), obteniendo mejores puntuaciones los sujetos con un único IL. e) los resultados hallados no mostraron diferencias significativas en cuanto al rendimiento neuropsicológico y la presencia/ausencia de leucoaraiosis. Estos resultados indican que los infartos lacunares, clásicamente considerados desde una perspectiva neurológica «silente», se pueden asociar a una disfunción neuropsicológica significativa. En estudios posteriores se podría investigar si los pacientes que presentan una disfunción cognitiva causada por infartos lacunares, tienen un mayor riesgo de desarrollar demencia, particularmente de tipo vascularsubcortical (AU)

Introduction: A number of investigations have been developed to date, to study the causes and risk factors leading to lacunar infarcts. However only few works were addressed to investigate the neuropsychological correlates of these cerebrovascular lesions. Objective: To correlate lacunar infarct topography with distinct patterns of cognitive dysfunction relating clinic aspects with magnetic resonance parameters and neuropsychological assessment. Methods: Twenty consecutive patients from the Neurology Service at the Sagrat Cor Hospital in Barcelona were included in the study. Al patients were diagnosed as presenting a lacunar syndrome according to Miller’s and Fisher’s classification: pure motor hemiparesis, pure sensitive syndrome, ataxia-hemiparesia, disartria-clumsy hand and sensitive-motor syndrome. Structural magnetic resonance images were acquired from all cases using T1 weighted, FLAIR and proton density (PD) sequences to distinguish between acute and chronic lacunar infarcts. Finally, all patients were assessed by means of an exhaustive neuropsychological battery. Results and conclusions: The following results were obtained: a) any syndrome group is characterized by presenting increased or reduced severity of lacunar infarcts, b) similarly, clinical groups did not differ in the amount of white matter damage as reflected by the presence of leuko-araiosis. C) Significant differences were found on the Benton’s Line Orientation Test where patients with a disartriaclumsy hand syndrome exhibited better performance as compared to patients with pure sensitive syndrome. D) Significant differences were found in category and phonetic fluency tests between patients presenting with a single lacunar infarct and multiple infarct patients. E) Leuko-araiosis was not related to cognitive performance among patients. Present results indicate that lacunar infarcts, classically considered as ‘silent’ from a neurological perspective, may associate with significant neuropsychological dysfunction. Future studies should investigate whether patients exhibiting cognitive impairment caused by lacunar infarcts are at increased risk for developing dementia, particularly of a subcortical vascular type (AU)

Apolipoproteins E and C1 and brain morphology in memory impaired elders.

Previous research has shown that polymorphisms of the apolipoproteins E ( APOE) and APOC1 represent genetic risk factors for dementia and for cognitive impairment in the elderly. The brain mechanisms by which these genetic variations affect behavior or clinical severity are poorly understood. We studied the effect of APOE and APOC1 genes on magnetic resonance imaging measures in a sample of 50 subjects with age-associated memory impairment. The APOE E4 allele was associated with reduced left hippocampal volumes and APOE*E3 status was associated with greater frontal lobe white matter volumes. However, no APOE effects were observed when analyses accounted for other potential confounding variables. The effects of APOC1 on hippocampal volumes appeared to be more robust than those of the APOE polymorphism. However, no modulatory effects on brain morphology outside the medial temporal lobe region were observed when demographic variables, clinical status, and other anatomical brain measurements were taken into consideration. Our results suggest that the role of the APOC1 polymorphism in brain morphology of the cognitively impaired elderly should be examined in further studies.

Relation of Apo E and ACE genes to cognitive performance in chronic alcoholic patients.

Apolipoprotein E epsilon4 and ACE genes have been related to several conditions involving cognitive impairment, including Alzheimer's disease, normal ageing and cerebrovascular disease. However, it has not been established whether their genotypes are associated with alcoholism or its cognitive functioning. Genotypic distributions of 140 chronic alcoholic patients were compared with a non-alcoholic sample, and the cognitive performance of a subsample of the alcoholic subjects was assessed with standard neuropsychological tests. No differences in allele or genotype distributions of Apo E or ACE genes were found when comparing controls and alcoholics (Apo E epsilon2/2; patients 1.4%, controls 0% p < 0.06; epsilon2/epsilon3; patients 9.3%, controls 6.6% p < 0.29; epsilon2/epsilon4; patients 0%, controls 1% p < 0.31; epsilon3/epsilon3 patients 71.4%, controls 72% p < 0.89; epsilon3/epsilon4; patients 15.7%, controls 19.2%, p < 0.36; epsilon4/epsilon4; patients 2.1%, controls 1.2% p < 0.44; ACE D/D; patients 35%, controls 28.5% p < 0.14; I/D; patients 47.5%, controls 51.1% p < 0.51; I/I; patients 14.5%, controls 20.4% p < 0.19). In terms of cognitive performance, epsilon4/epsilon3 patients did better on visuoconstructive (p < 0.001) and visual memory (p < 0.04) functions compared with epsilon2/epsilon3 bearers. Furthermore, ACE D/D patients performed better on a test of abstract reasoning (p < 0.03) compared with the ACE I/I homozygous group. The cognitive results suggest that Apo E or ACE genotypes may modify the effects of ethanol on cognitive deterioration in alcoholic patients. However, the data do not support an association between the Apo E epsilon4 allele and reduced cognitive performance in alcoholism.

APOE and APOC1 genetic polymorphisms in age-associated memory impairment.

We studied the distribution of two genetic polymorphisms (APOE and APOC1) in a sample of 100 subjects fulfilling the NIMH criteria for age-associated memory impairment (AAMI) and 124 controls. We found significant associations both for APOE and APOC1 loci and their combinations with the AAMI condition. The findings in our sample suggest that memory-impaired subjects as described by the NIMH may be genetically differentiated from normally aging subjects in relation to these two polymorphisms and indicate the interest of considering variations in the APOC1 gene for further studies in cognitive aging.

[White matter changes and cognitive performance in aging]. / Cambios en la sustancia blanca y rendimiento cognitivo en el envejecimiento.

OBJECTIVE: In this paper we review the main magnetic resonance studies to show a possible relationship between changes in the white matter of the brain or leukoaraiosis, and the neuropsychological profile of elderly persons without dementia. DEVELOPMENT: The articles published to date show contradictory data, and in nearly half the cases reviewed no clear relationship could be established between leukoaraiosis and conduct. However, by using sensitive cognitive tests it is possible to detect and association between the presence and degree of change in the white matter and decline in frontal function such as speed of processing information, visuomotor function, verbal fluency, classification and mental sequences. Other cognitive areas such as language, memory or visuospatial, visuoconstructive and visuoperceptive functions appear less frequently related to the presence or intensity of lesions of the white matter of the brain. From a neuropsychological point of view, periventricular localization of the leukoaraiosis seems to be more important than subcortical localization. CONCLUSIONS: The neuropsychological functions most frequently associated with the presence of leukoaraiosis are those dependent on the frontal lobes, and are a disconnection favoured by the presence of the white matter of the brain, the most probable underlying physiopathological mechanism. Although there is evidence showing a genetic effect in the appearance of the white matter of the brain, study of the genes associated with cognitive deterioration in normal ageing has not given conclusive findings.

[Study of the long term sequelae of traumatic brain injury: evaluation of declarative and procedural memory, and its neuroanatomic substrate]. / Estudio de las secuelas a largo plazo de los traumatismos craneoencefálicos: evaluación de la memoria declarativa y procedimental y de su sustrato neuroanatómico.

INTRODUCTION AND OBJECTIVES: The hippocampus and the striatum have been proposed as respectively cerebral substrates of declarative and procedural memory. Both structures are vulnerable to traumatic brain injury. Although declarative and procedural memory have been reported to be impaired in traumatic brain injury (TBI), volumetric measures have so far failed to associate this impairment with atrophy of hippocampal and striatal structures. In our study, we investigated the profile of declarative and procedural memory in children who suffered from moderate to severe traumatic brain injury during childhood (injury test interval: 9.42+/-1.98 years). PATIENTS AND METHODS: Nineteen patients and matched controls were evaluated on tests of declarative memory and motor learning. Results showed that TBI subjects exhibit poorer performance in both tasks. Moreover, structural magnetic resonance images were obtained from TBI subjects. In order to relate neuropsychological performance with hippocampal and neostriatal volumetric data, correlation analyses were performed. RESULTS: Significant positive correlations were obtained between hippocampal volume and memory for objects. Striatal volume correlated positively with motor learning and with verbal memory. CONCLUSIONS: It thus seems that plasticity does not completely compensate for the memory deficits resultant from neural loss in the immature brain.

Neuropsychological and genetic differences between age-associated memory impairment and mild cognitive impairment entities.

OBJECTIVE: To neuropsychologically and genetically compare age-associated memory impairment (AAMI) and mild cognitive impairment (MCI) entities and to determine what proportion of AAMI diagnosed individuals could also receive a MCI diagnosis. To compare the distribution of a previously known genetic risk factor for Alzheimer's disease (apolipoprotein E common polymorphism) associated with these two conditions with a sample of the normal aging. DESIGN: Neuropsychological and genetic assessments in AAMI and MCI individuals. Genetic assessment in AAMI, MCI, and control subjects. SETTING: General health centers and geriatric homes from northeastern Spain (Catalunya). PARTICIPANTS: One hundred and four subjects presenting subjective memory complaints were selected and the AAMI and MCI criteria were applied. One hundred and twenty-four healthy Spanish subjects age 50 and older were defined as controls. MEASUREMENTS: Memory, language, and frontal lobe functions were assessed using standard neuropsychological tests. The apolipoprotein E (apo E) polymorphism was obtained by using polymerase chain reaction (PCR) and HhaI restriction endonuclease. RESULTS: Sixty-seven percent of previously diagnosed AAMI individuals could also be identified as MCI subjects. These MCI cases differed from those only-AAMI individuals both in neuropsychological and genetic analyses, performing worse not only on memory but also on language and frontal lobe tests and presenting high and low prevalences of the apo E epsilon 3/epsilon 4 and epsilon 3/epsilon 3 genotypes, respectively. The general AAMI sample of 93 individuals also differed from controls in the apo E genotype and allele distributions but these differences were no longer present after subtracting the MCI cases (63 subjects). These findings reflect that the differences between the memory impaired sample and the control sample regarding the apo E polymorphism were mainly attributable to MCI individuals and not to those who received only a diagnosis of AAMI alone. CONCLUSIONS: Our findings suggest that among AAMI subjects, those who also fulfill the MCI criteria present a neuropsychological and genetic profile closer to that previously related to Alzheimer's disease than those individuals only eligible for a diagnosis of AAMI. However, our findings also suggest that using only the AAMI criteria still appears to select a population that differs genetically from the normal older population.