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Objective:SQSTM1-variants associated with frontotemporal lobar degeneration have been described recently. In this study, we investigated a heterozygous in-frame duplication c.436_462dup p. (Pro146_Cys154dup) in the SQSTM1 gene in a family with a new phenotype characterized by a personality disorder and behavioral variant frontotemporal dementia (bvFTD). We review the literature on frontotemporal dementia (FTD) associated with SQSTM1. Methods: The index case and relatives were described, and a genetic study through Whole Exome Sequencing was performed. The literature was reviewed using Medline and Web of Science. Case reports, case series, and cohort studies were included if they provided information on SQSTM1 mutations associated with FTD. Results: Our patient is a 70-year-old man with a personality disorder since youth, familial history of dementia, and personality disorders with a 10-year history of cognitive decline and behavioral disturbances. A diagnosis of probable bvFTD was established, and the in-frame duplication c.436_462dup in the SQSTM1 gene was identified. Segregation analysis in the family confirmed that both affected sons with personality disorder were heterozygous carriers, but not his healthy 65-year-old brother. A total of 14 publications about 57 patients with SQSTM1-related FTD were reviewed, in which the bvFTD subtype was the main phenotype described (66.6%), with a predominance in men (63%) and positive family history in 61.4% of the cases. Conclusions: We describe a heterozygous in-frame duplication c.436_462dup p.(Pro146_Cys154dup) in the SQSTM1 gene, which affects the zinc-finger domain of p62, in a family with a personality disorder and bvFTD, expanding the genetics and clinical phenotype related to SQSTM1. © 2021 World Federation of Neurology on behalf of the Research Group on Motor Neuron Diseases.

Background: A protective effect of education on cognitive decline after stroke has been claimed, but evidence from prospective population-based cohorts is very limited. The differential role of literacy and education on dementia after stroke remains unexplored. Objective: This research addresses the role of education and literacy in dementia incidence after stroke and transient ischemic attack (TIA). Methods: 131 participants with stroke or TIA were identified within the population-based NEDICES study (N = 5,278 persons). Participants were fully assessed at baseline (1994–1995) and incident dementia diagnosis was made by expert neurologists (DSM-IV criteria) after a mean follow-up of 3.4 years. Adjusted Cox regression analyses were applied to test the association between education, literacy, and dementia risk. Results: Within the 131 subjects with stroke or TIA, 19 (14%) developed dementia at follow-up. The Cox’s regression model (age and sex adjusted) showed that low education (HR = 3.48, 95% CI = 1.28, 9.42, p = 0.014) and literacy (HR = 3.16, 95% CI = 1.08, 9.22, p = 0.035) were significantly associated with a higher dementia risk. Low education was also associated with dementia when main confounders (i.e., cognitive/functional performance) were considered in the Cox’s model. However, after including stroke recurrence, only low/null literacy (versus education) remained as significant predictor of dementia. Finally, low/null literacy showed an effect over-and-above education on dementia risk when both factors were introduced in the adjusted Cox’s regression. Conclusion: These findings underline the importance of literacy to estimate cognitive decline after stroke in low-educated populations.

Purpose of Review: To provide an updated analysis of the possible use of non-steroidal anti-inflammatory drugs (NSAIDs) as treatments for Alzheimer´s disease (AD). Recent Findings: Neuroinflammation in AD is an active field of research, with increasing evidence from basic and clinical studies for an involvement of innate or adaptive immune responses in the pathophysiology of AD. Few clinical trials with anti-inflammatory drugs have been performed in the last decade, with negative results. Summary: Besides the information gathered from basic research, epidemiological studies have provided conflicting findings, with most case-control or prevalence studies suggesting an inverse relationship between NSAIDs use and AD, but divided results in prospective population-based incident cohort studies. Clinical trials with different NSAIDs are almost unanimous in reporting an absence of clear benefit in AD. Conclusion: The modulation of inflammatory responses is a promising therapeutic strategy in AD. After three decades of research, it seems that conventional NSAIDs are not the best pharmacological option, both for their lack of clear effects and for an unfavorable side-effect profile in long-term treatment. The development of other anti-inflammatory drugs as candidate treatments in AD may benefit from the knowledge acquired with NSAIDs.

Milk and dairy (M&D) is a longstanding human food with widespread use. Many studies showed the preventive capacity of M&D in several human health disorders, but its utility in others is under discussion. Aging has been associated to elderly cognitive decline including dementia-Alzheimer syndrome (Dem-AD). The absence of a therapy to impede or postpone Dem-AD determines the need for its prevention, including nutritional factors. To evaluate the preventive capacity of M&D consumption in elderly Dem-AD we performed a systematic review in the main biomedical databases and information resources, but we present this study as a narrative review to discuss better the complexity of this subject. The elderly Dem-AD has a long pre-symptomatic period and the M&D intake has a widespread use. These determinants and the quality flaws of published studies impeach us to answer whether M&D consumption is preventive for Dem-AD. Moreover, two long Japanese cohorts suggest that M&D intake could prevent Dem-AD. Prospective cohorts beginning in midlife (or early life) could answer this question in the future.

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an autosomal recessive vascular disorder caused by biallellic variants in HTRA1. Recently, it has been reported that several heterozygous mutations in HTRA1 are responsible for a milder late-onset cerebral small vessel disease (CSVD) with an autosomal dominant pattern of inheritance. The majority of them are missense that affects the Htr1A protease activity due to a dominant-negative effect caused by defective trimerization or monomer activation. The molecular mechanism related to the structural destabilization of the protein supports the practical utility of integrating computational stability predictors to prioritize candidate variants in this gene. In this work, we report a family with several members diagnosed with subcortical ischemic events and progressive cognitive impairment caused by the novel c.820C G, p.(Arg274Gly) heterozygous variant in HTRA1 segregating in an autosomal dominant manner and propose its molecular mechanism by a three-dimensional model of the protein's structure.

The causes of the dementia decrease in affluent countries are not well known but health amelioration could probably play a major role. Nevertheless, although many vascular and systemic disorders in adult life are well-known risk factors (RF) for dementia and Alzheimer disease (AD), health status is rarely considered as a single RF.To analyse whether the health status and the self-perceived health (SPH) could be RF for dementia and AD and to discuss its biological basis.We analysed different objective health measures and SPH as RF for dementia and AD incidence in 4569 participants of the NEDICES cohort by means of Cox-regression models. The mean follow-up period was 3.2 (range: 0.03-6.6) years.Ageing, low education, history of stroke, and "poor" SPH were the main RF for dementia and AD incidence, whereas physical activity was protective. "Poor" SPH had a hazard ratio = 1.66 (95% CI 1.17-2.46; p = 0.012) after controlling for different confounders.According to data from NEDICES cohort, SPH is a better predictor of dementia and AD than other more objective health status proxies. SPH should be considered a holistic and biologically rooted indicator of health status, which can predict future development of dementia and AD in older adults.Our data indicate that it is worthwhile to include the SPH status as a RF in the studies of dementia and AD incidence and to explore the effect of its improvement in the evolution of this incidence.

To investigate whether physical activity (PA) is a protective factor for the incidence of Parkinson’s disease (PD) and parkinsonism after three years of follow-up. All participants of this study were obtained from the Neurological Disorders in Central Spain (NEDICES), a prospective population-based cohort survey of older subjects (≥65 years) that comprised 5278 census-based participants at baseline (1994–1995). A modified version of Rosow-Breslau questionnaire was applied to categorize PA into active versus sedentary group. The final diagnosis of PD and parkinsonism was made by an expert neurologist. Cox regression models (CRM) adjusted for several covariates (sex, age, education, alcohol consumption, tobacco, stroke, hypertension and body mass index) were used to calculate the association between PA (active group vs. sedentary) and risk of PD and parkinsonism after three years. 22 incident PD and 25 incident parkinsonism cases were identified among 2943 participants with available PA information (57.1% female; mean age = 73.28 ± 6.24 years) after three years of follow-up. The CRM showed that the active group (vs. sedentary) showed a lower risk of parkinsonism (Hazard ratio (HR) = 0.18; 95% CI [0.07–0.51]; p = 0.0001). However, this effect was restricted to men (HR = 0.34; 95% CI [0.11–0.99], p

Resumen Introduccion La inflamacion relacionada con la angiopatia amiloide es una entidad caracterizada por una respuesta inflamatoria alrededor de los depositos de beta amiloide de la microcirculacion cerebral. Metodos Revision retrospectiva de una serie de pacientes con inflamacion relacionada con angiopatia amiloide, que cumplieran criterios clinico-radiologicos o con diagnostico histopatologico confirmado. Resultados Se incluyeron siete pacientes, cinco varones, con edad media de 79 anos. El inicio fue agudo o subagudo en seis de los casos. La clinica mas frecuente fue deterioro cognitivo (n = 6), alteraciones de conducta (n = 5), crisis epilepticas (n = 5), focalidad neurologica (n = 4) y cefalea (n = 2). El liquido cefalorraquideo fue anormal en tres de cinco casos (pleocitosis linfocitaria e hiperproteinorraquia). Las imagenes de resonancia magnetica cerebral mas frecuentes consistieron en microhemorragias (n = 7), hiperintensidades subcorticales en secuencia T2-FLAIR (n = 7) y realce leptomeningeo (n = 6). La afectacion fue bilateral en tres de los casos, con predominio en regiones parieto-occipitales (n = 5). Se realizo una tomografia por emision de positrones (PET) de amiloide en dos pacientes, resultando positiva en uno. Se obtuvo la confirmacion histopatologica mediante una biopsia en dos de los casos. Todos los sujetos recibieron tratamiento inmunosupresor, objetivandose una respuesta clinica y radiologica inicial favorable, con recaida radiologica en dos de los casos tras la retirada del tratamiento, y mejorando tras la reinstauracion. Conclusiones El diagnostico resulta imprescindible de cara a iniciar un tratamiento precoz, ya que ha demostrado mejorar el pronostico y disminuir las recurrencias. Si bien el diagnostico definitivo es histopatologico, los criterios clinico-radiologicos permiten el diagnostico de esta entidad sin necesidad de biopsia.

Amyloid positron emission tomography (PET) brain imaging with radiotracers like [18F]florbetapir (FBP) or [18F]flutemetamol (FMM) is frequently used for the diagnosis of Alzheimer’s disease. Quantitative analysis is usually performed with standardized uptake value ratios (SUVR), which are calculated by normalizing to a reference region. However, the reference region could present high variability in longitudinal studies. Texture features based on the grey-level co-occurrence matrix, also called Haralick features (HF), are evaluated in this study to discriminate between amyloid-positive and negative cases. A retrospective study cohort of 66 patients with amyloid PET images (30 [18F]FBP and 36 [18F]FMM) was selected and SUVRs and 6 HFs were extracted from 13 cortical volumes of interest. Mann–Whitney U-tests were performed to analyze differences of the features between amyloid positive and negative cases. Receiver operating characteristic (ROC) curves were computed and their area under the curve (AUC) was calculated to study the discriminatory capability of the features. SUVR proved to be the most significant feature among all tests with AUCs between 0.692 and 0.989. All HFs except correlation also showed good performance. AUCs of up to 0.949 were obtained with the HFs. These results suggest the potential use of texture features for the classification of amyloid PET images.

We read with interest the article by De Vleeschhauwer et al1 about touchscreen skills in patients with Parkinson’s disease (PD). We acknowledge that this pioneer and exhaustive effort highlights precisely some of the main difficulties that these patients encounter while interacting with touchscreen devices. One of these examples is the prolonged duration of the sliding tasks performed by the patients. The article reveals that the patients’ accuracy and their intertap interval is similar to those shown by participants without PD. We achieved comparable results in previous research. In previous research, we designed a pilot study focusing on routine outpatient clinics by a trial with a prototype smartphone application (previously used by patients with essential tremor).2 A total of 18 patients with PD and 22 controls matched by age and sex (Table 1) were recruited. They performed 5 repetitions of 4 simple tests that were designed to be common touchscreen activities when using smartphones (further methodological details can be found in Supplementary Material S1). Despite the different methodologies and devices used, both studies shared small sample sizes and easy reaching, sliding, and tapping tasks. In both studies, patients with PD achieved similar accuracy and a similar intertap interval time (Table 1) to healthy participants. In contrast to De Vleeschhauwer et al, we did not find significant differences in the duration test performance between patients with PD and controls. This could be explained by the limited statistical power, more recent onset of the disease, the milder severity of our patients, and fewer repetitions of the tasks and the fact that the most complex sliding tasks were not performed. In addition, there were differences in the touchscreen interface settings3 concerning the type of device, software, button size, and the double-tapping act. We consider that the approach of De Vleeschhauwer et al dealing with more repetitions of the tasks makes the bradykinesia of the patients more obvious. Consequently, it could be useful to detect it in touchscreen interaction as a diagnostic tool.4,5 It may be possible that the most basic touchscreen smartphone tasks do not require multidirection sliding movements or very repetitive tasks and could be performed when accuracy is preserved, reaching the targets displayed on the screen in a slower way, unless dexterity or cognition would be affected.3 Hence, the severity of the disease could affect the touchscreen interaction notably1 ; nevertheless, it should be examined whether the slower performance of the task found in patients with moderate severity really affects the usability of a touchscreen display significantly. As long as this limitation is provided, these issues should be taken into consideration by touchscreen smart device developers to ease the touchscreen interaction process for patients with PD.3 In the case that it is not given, both studies may support the continuation of using touchscreen technology for PD care research in patients with mild to moderate PD., Sara Llamas‐Velasco is supported by the Instituto de Salud Carlos III (ISCIII; Spanish Biomedical Research Institute) through a “Juan Rodés” contract (JR 18/00046). The work presented in this article was carried out with the financial support from the Ministry of Economy and Competitiveness under contract RTC‐2015‐3967‐1, “NetMD‐Plataforma para el seguimiento de Trastornos del Movimiento.” The authors declare that there are no conflicts of interest relevant to this work.

The haploinsufficiency of the methyl-binding domain protein 5 (MBD5) gene has been identified as the determinant cause of the neuropsychiatric disorders grouped under the name MBD5-neurodevelopment disorders (MAND). MAND includes patients with intellectual disability, behavioral problems, and seizures with a static clinical course. However, a few reports have suggested regression. We describe a non-intellectually disabled female, with previous epilepsy and personality disorder, who developed early-onset dementia. The extensive etiologic study revealed a heterozygous nonsense de novo pathogenic variant in the MBD5 gene. This finding could support including the MBD5 gene in the study of patients with atypical early-onset dementia. © 2021 - IOS Press. All rights reserved.

We analyzed the frequency of cognitive impairment (CI) in deceased COVID-19 patients at a tertiary hospital in Spain. Among the 477 adult cases who died after admission from March 1 to March 31, 2020, 281 had confirmed COVID-19. CI (21.1% dementia and 8.9% mild cognitive impairment) was a common comorbidity. Subjects with CI were older, tended to live in nursing homes, had shorter time from symptom onset to death, and were rarely admitted to the ICU, receiving palliative care more often. CI is a frequent comorbidity in deceased COVID-19 subjects and is associated with differences in care.

Background Predementia is a heuristic umbrella concept to classify older adults with cognitive impairment who do not suffer dementia. Many diagnostic entities have been proposed to address this concept, but most of them have not had widespread acceptance. Aims To review clinical definitions, epidemiologic data (prevalence, incidence) and rate of conversion to dementia of the main predementia constructs, with special interest in the two most frequently used: mild cognitive impairment (MCI) and minor neurocognitive disorder (miNCD). Methods We have selected in three databases (MEDLINE, Web of Science and Google scholar) the references from inception to 31 December 2019 of relevant reviews, population and community-based surveys, and clinical series with >500 participants and >3 years follow-up as the best source of evidence. Main results The history of predementia constructs shows that MCI is the most referred entity. It is widely recognized as a clinical syndrome harbinger of dementia of several etiologies, mainly MCI due to Alzheimer's disease. The operational definition of MCI has shortcomings: vagueness of its requirement of "preserved independence in functional abilities" and others. The recent miNCD construct presents analogous difficulties. Current data indicate that it is a stricter predementia condition, with lower prevalence than MCI, less sensitivity to cognitive decline and, possibly, higher conversion rate to dementia. Conclusions MCI is a widely employed research and clinical entity. Preliminary data indicate that the clinical use of miNCD instead of MCI requires more scientific evidence. Both approaches have common limitations that need to be addressed.

IntroductionLittle is known about the relation of cognitive impairment (CI) to COVID-19 mortality. Here, we analyse the frequency of CI in deceased COVID-19 patients.MethodsWe included 477 adult cases that died after admission from March 1 to March 31, 2020: 281 with confirmed COVID-19, 58 probable COVID-19, and 138 who died of other causes.ResultsThe number of comorbidities was high in the confirmed COVID-19, and CI was common (30%: 21.1% dementia; 8.9% mild cognitive impairment). Subjects with CI were older, more lived in nursing homes and had shorter times from symptom onset to death than those without CI. COVID-19 patients with CI were rarely admitted to the ICU and fewer received non-invasive mechanical ventilation, but palliative care was provided more often.ConclusionsDementia is a frequent comorbidity in COVID-19 deceased patients. The burden of COVID-19 in the dementia community will be high.

Background Efforts focused on developing new less invasive biomarkers for early Alzheimer’s disease (AD) diagnosis are substantial. Evidences of infectious pathogens in AD brains may suggest a deteriorated innate immune system in AD pathophysiology. We previously demonstrated reduced salivary levels of Lf in AD patients, one of the major antimicrobial peptides. Methods To assess the clinical utility of salivary Lf for AD diagnosis, we examine the relationship between salivary Lf and cerebral amyloid-β (Aβ) load in two different cross-sectional cohorts including patients with different neurodegenerative disorders. Study participants for cohort 1 (n = 116) were enrolled from the 12 de Octubre University Hospital Neurology Service in Madrid (Spain) and Pablo de Olavide University in Sevilla (Spain). Study participants for cohort 2 (n = 142) were enrolled as part of the Atherobrain - Heart to Head (H2H) project. Participants underwent neurological and neuropsychological examination, saliva sampling, and amyloid-Positron-Emission Tomography (PET) neuroimaging. Results The diagnostic performance of salivary Lf in the cohort 1 had an area under the curve [AUC] of 0.95 (0.911-0.992) for the differentiation of the prodromal AD/AD group positive for amyloid-PET (PET + ) versus healthy group, and 0.97 (0.924-1) versus the frontotemporal dementia (FTD) group. In the cohort 2, salivary Lf had also an excellent diagnostic performance in the health control group versus prodromal AD comparison: AUC 0.93 (95% CI 0.876-0.989). Salivary Lf detected prodromal AD and AD dementia distinguishing them from other dementias as FTD with over 87% sensitivity and 91% specificity. Conclusion Therefore, salivary Lf seems to have a very good diagnostic performance to detect AD. Our findings support the possible utility of salivary Lf as a new non-invasive and cost-effective AD biomarker.

Kynurenic acid (KYNA) is a product of the tryptophan (TRP) metabolism via the kynurenine pathway (KP). This pathway is activated in neurodegenerative disorders, such as Alzheimer´s disease (AD). KYNA is primarily produced by astrocytes and is considered neuroprotective. Thus, altered KYNA levels may suggest an inflammatory response. Very recently, significant increases in KYNA levels were reported in cerebrospinal fluid (CSF) from AD patients compared with normal controls. In this study, we assessed the accuracy of KYNA in CSF for the classification of patients with AD, cognitively healthy controls, and patients with a variety of other neurodegenerative diseases, including frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and progressive supranuclear palsy (PSP). Averaged KYNA concentration in CSF was higher in patients with AD when compared with healthy subjects and with all the other differentially diagnosed groups. There were no significant differences in KYNA levels in CSF between any other neurodegenerative groups and controls. These results suggest a specific increase in KYNA concentration in CSF from AD patients not seen in other neurodegenerative diseases., This research was funded by Instituto de Salud Carlos III (PI18/00118), FEDER, CIBERNED, CIBER-BBN; the Ministry of Science and Innovation (TryKySeNS project, CTQ2011-29163-C03-01); and S2017/BMD-3700 (NEUROMETAB-CM) from Comunidad de Madrid co-financed with the Structural Funds of the European Union. The Nb4D group is a consolidated research group (Grup de Recerca) of the Generalitat de Catalunya and has support from the Departament d’Universitats, Recerca i Societat de la Informació de la Generalitat de Catalunya (expedient: 2017 SGR 1441).

To analyze whether Physical activity (PA) reduces mortality risk at thirteen years' follow-up in a population-based cohort of Spanish older adults. The NEDICES (Neurological Disorders in Central Spain) is a prospective population-based survey of older adults (age ≥ 65 years) that comprised 5278 participants at baseline. A modified version of the Rosow-Breslau questionnaire was applied to categorize the PA (sedentary, light, moderate and high) and dates of death were collected from the Official Spanish Death Registry. Cox regression models adjusted for different covariates (age, sex, marital status, smoking, previous stroke, Parkinson disease, incident dementia, body mass index, comorbidity indexes and functional assessment) were used to evaluate the hazard of death at thirteen years' interval according to different levels of PA. 1710 deaths (52.9% men vs. 47.1% women) were identified among 3633 individuals at thirteen years' follow-up. Hazard ratios (HRs) of the light, moderate, and high PA groups (vs. sedentary group) were 0.64 (95% confidence interval (CI) [0.56, 0.72], p, Highlights • Physical activity is associated with a lower risk of mortality in older adults. • This protective effect seemed slightly higher for women. • Most studies didn't show a dose-effect response. • Promotion of physical activity should be a priority for health agencies.

Semantic variant primary progressive aphasia (svPPA) is a clinical syndrome included in the frontotemporal dementia (FTD) spectrum. Unlike other forms of FTD, it is sporadic in the majority of cases and not commonly associated with motor neuron disease (MND). We describe a case of svPPA associated with MND in the same family, due to a mutation of the transactive response DNA binding protein (TARDBP) gene, and review the literature.

Background The Neurological Disorders in Central Spain, second survey (NEDICES-2) is a population-based, closed-cohort study that will include over 8000 subjects aged ≥55 years. It will also include a biobank. Objective The objective of this study was to evaluate all major aspects of the NEDICES-2 (methods, database, screening instruments, and questionnaires, as well as interexpert rating of the neurological diagnoses) in each one of the planned areas (all of them in central Spain) and to test the possibility of obtaining biological samples from each participant. Methods A selection of patients and participants of the planned NEDICES-2 underwent face-to-face interviews including a comprehensive questionnaire on demographics, current medications, medical conditions, and lifestyle habits. Biological samples (blood, saliva, urine, and hair) were also obtained. Furthermore, every participant was examined by a neurologist. Results In this pilot study, 567 study participants were enrolled (196 from hospitals and 371 from primary care physician lists). Of these 567, 310 completed all study procedures (questionnaires and the neurological evaluation). The study was time-consuming for several primary care physicians. Hence, a few primary care physicians from some areas refused to participate, which led to a reconfiguration of study areas. In addition, the central biobank needed to be supplemented by the biobanks of local Spanish National Health System hospitals. Conclusions Population-based epidemiological surveys, such as the NEDICES-2, require a pilot study to evaluate the feasibility of all aspects of a future field study (population selection, methods and instruments to be used, neurological diagnosis agreement, and data collection)., Our thanks to all collaborators in this feasibility pilot study, the Instituto de Salud Carlos III and the Biomedical Research Networking Center on Neurodegenerative Diseases (CIBERNED), and the two hospital computer experts (Victoria Garcia Baquero and Teresa Garcia Morales), who created the website (http://nedices2.ciberned.com/estudio-de-salud-nedices-2/). We would also like to thank Miss Jennifer Gates for the editing and proofreading of the manuscript.

Background: To assess the diagnostic agreement of cognitive status (dementia, mild cognitive impairment (MCI), normal cognition) among neurologists in the field of neurological disorders in Central Spain 2 study. Methods: Full medical histories of 30 individuals were provided to 27 neurologists: 9 seniors, 10 juniors and 8 residents. For each case, we were asked to assign a diagnosis of dementia, MCI or normal cognition using the National Institute on Aging-Alzheimer's Association workgroup (NIA-AA) core clinical criteria for all-cause dementia, Winblad et al. criteria for MCI, and analyze intensity and etiology if dementia was diagnosed. Inter-rater agreement was assessed both with percent concordance and non-weighted κ statistics. Results: Overall inter-rater agreement on cognitive status was κ = 0.76 (95% CI 0.65-0.86), being slightly higher among junior neurologists (κ = 0.85, 95% CI 0.73-0.95) than among seniors (κ = 0.71, 95% CI 0.59-0.83) and residents (κ = 0.69, 95% CI 0.54-0.81) but without statistical significance among groups. Dementia severity showed an overall κ of 0.34, 0.44 and 0.64 for mild, moderate and severe dementia respectively. Conclusions: Substantial agreement was demonstrated for the diagnosis of cognitive status (dementia, MCI and normal cognition) among neurologists of different levels of experience in a population-based epidemiological study using NIA-AA and Winblad et al. criteria. The agreement rate was lower in the diagnosis of dementia severity.

BACKGROUND The Neurological Disorders in Central Spain, second survey (NEDICES-2) is a population-based, closed-cohort study that will include over 8000 subjects aged ≥55 years. It will also include a biobank. OBJECTIVE The objective of this study was to evaluate all major aspects of the NEDICES-2 (methods, database, screening instruments, and questionnaires, as well as interexpert rating of the neurological diagnoses) in each one of the planned areas (all of them in central Spain) and to test the possibility of obtaining biological samples from each participant. METHODS A selection of patients and participants of the planned NEDICES-2 underwent face-to-face interviews including a comprehensive questionnaire on demographics, current medications, medical conditions, and lifestyle habits. Biological samples (blood, saliva, urine, and hair) were also obtained. Furthermore, every participant was examined by a neurologist. RESULTS In this pilot study, 567 study participants were enrolled (196 from hospitals and 371 from primary care physician lists). Of these 567, 310 completed all study procedures (questionnaires and the neurological evaluation). The study was time-consuming for several primary care physicians. Hence, a few primary care physicians from some areas refused to participate, which led to a reconfiguration of study areas. In addition, the central biobank needed to be supplemented by the biobanks of local Spanish National Health System hospitals. CONCLUSIONS Population-based epidemiological surveys, such as the NEDICES-2, require a pilot study to evaluate the feasibility of all aspects of a future field study (population selection, methods and instruments to be used, neurological diagnosis agreement, and data collection).

We present a 86-year-old woman without relevant medical history and two brothers who died by dementia, who started at 55 years with depression and personality changes with ongoing worsening (30 years) and functional decline. Screening dementia blood test and brain magnetic resonance imaging did not show results that pointed to a secondary cause. The patient met the diagnostic criteria for possible behavioral frontotemporal dementia with a slow progression (bvFTD-SP), suggesting a benign variant. A genetic study confirmed a C9ORF72 hexanucleotide expansion, making this the sixth case mentioned in the literature. We review and discuss the other cases described previously.

Enteroviruses are a common cause of aseptic meningitis and mild infections in childhood. However, in immunocompromised patients they may cause severe neurologic conditions such as encephalitis or polio-like paralysis. Acknowledgment: The authors thank the patient and his family.

The Minimental State Examination (MMSE), created in 1975 as a tool for briefly evaluating the patient's mental state, has been widely used and is the most frequently cited cognitive test on Medline, as well as being the one with the most versions in different languages (over 70). Through a review of the Medline database, this paper aims to analyse its virtues and shortcomings, in addition to determining its current clinical usefulness, in both the original version and any of its modifications, although here we are mainly concerned with its Spanish adaptations. The MMSE (original or versions) is the most commonly used test for standardised cognitive assessment in the clinical setting, especially in the case of the elderly. It is the test with the most data for screening, staging and monitoring dementias. Yet, because filling it in may take over 10 minutes, it has to compete with shorter, more specific screening tests in the primary care and community setting. In the hospital and specialised setting, there is a need for broader standardised neuropsychological tests that make it possible to detect subtle cognitive disorders in patients with incipient dementia or mild cognitive impairment, as well as to establish a cognitive profile of the different subtypes of dementia. This study proposes a series of recommendations on the clinical use of the Spanish versions of the MMSE in different contexts of application.