Search

Objective: to conduct a systematic review and meta-analyses of the effect of socio-behavioral cognitive reserve (CR) proxies on cognitive decline after stroke. Method: three journal search and indexing databases (PubMed, Scopus and Web of Sciences) were crossed to examine the scientific evidence systematically. In addition, meta-analytic techniques, using mixed-effect methods, were carried out to estimate the impact (pooled effect size) of CR proxies on either dementia incidence or cognitive decline after stroke. Results: twenty-two studies were included in the systematic revision, whereas nineteen of them were eligible for the meta-analysis. The findings showed that high education is associated with a decreased rate of post-stroke dementia. Moreover, other CR proxies (e.g., occupation, bilingualism or social interaction) demonstrate a protective effect against non-dementia cognitive decline after stroke, although some inconsistencies were found in the literature. Regarding the meta-analysis, occupational attainment and education) showed a protective effect against post-stroke cognitive impairment diagnosis in comparison with a mixed category of different CR proxies. Second, a main cognitive change effect was found, pointing to greater cognitive change after stroke in those with low vs. high CR. Conclusions: Our findings emphasize that CR may prevent cognitive decline after stroke, but this effect can be modulated by different factors such the CR proxy and individual characteristics such as age or type of lesion. The methodological divergences of the studies (i.e., follow-up intervals, cognitive outcomes) need unification to diminish external sources of variability for predicting rates of cognitive decline after stroke.

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.

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.

Aims To analyze the incidence of type 2 diabetes (T2D) in Central Spain and its association with the socioeconomic status (SES), educational level, and other risk factors (RF) in the elderly population of three communities. Methods Data for 5278 elderly participants (≥65 years old) were obtained using a census population-based survey. There was a first and a second survey three years later. The association between SES, educational level, RF, and T2D incidence was analyzed. Results The incidence rate for T2D was 9.8/1000 person-years without gender differences. Incident T2D was associated with low SES and lower educational levels. Baseline and follow-up BMI were also the main RFs for T2D. Communities’ incidence rates were: (1) Margarita, working-class area: 11.3/1000 person-years; (2) Arévalo, agricultural region: 10.1/1000 person-years and; (3) Lista, professional high-income class area: 7.6/1000 person-years. Conclusion We found an incidence rate of 9.8/1000 person-years of T2D in the elderly population. The risk of T2D was associated with a lower income and educational level. An increase in BMI may mediate this association. Our results emphasize the necessity of strategies for the prevention of diabetes that includes an approach to SES, educational levels, and other RF among older individuals in Spanish community settings.

Objective: We aim to explain why salivary lactoferrin (Lf) levels are reduced in patients suffering mild cognitive impairment (MCI) and sporadic Alzheimer’s disease (sAD).1 We also will discuss if such Lf decrease could be due to a downregulation of the sAD associated systemic immunity. Background: Several non-neurological alterations have been described in sAD, mainly in skin, blood cell, and immunological capacities. We reviewed briefly the main pathophysiological theories of sAD (amyloid cascade, tau, unfolder protein tau, and amyloid deposits) emphasizing the most brain based hypotheses such as the updated tau-related neuron skeletal hypothesis; we also comment on the systemic theories that emphasize the fetal origin of the complex disorders that include the low inflammatory and immunity theories of sAD. New/updated hypothesis: Lf has important anti-infectious and immunomodulatory roles in health and disease. We present the hypothesis that the reduced levels of saliva Lf could be an effect of immunological disturbances associated to sAD. Under this scenario, two alternative pathways are possible: first, whether sAD could be a systemic disorder (or disorders) related to early immunological and low inflammatory alterations; second, if systemic immunity alterations of sAD manifestations could be downstream of early sAD brain affectations. Major challenges for the hypothesis: The major challenge of the Lf as early sAD biomarker would be its validation in other clinical and population-based studies. It is possible the decreased salivary Lf in early sAD could be related to immunological modulation actions, but other different unknown mechanisms could be the origin of such reduction. Linkage to other major theories:This hypothesis is in agreement with two physiopathological explanations of the sAD as a downstream process determined by the early lesions of the hypothalamus and autonomic vegetative system (neurodegeneration), or as a consequence of low neuroinflammation and dysimmunity since the early life aggravated in the elderly (immunosenescence)

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

Objective The recent advances in technology are opening a new opportunity to remotely evaluate motor features in people with Parkinson's disease (PD). We hypothesized that typing on an electronic device, a habitual behavior facilitated by the nigrostriatal dopaminergic pathway, could allow for objectively and nonobtrusively monitoring parkinsonian features and response to medication in an at-home setting. Methods We enrolled 31 participants recently diagnosed with PD who were due to start dopaminergic treatment and 30 age-matched controls. We remotely monitored their typing pattern during a 6-month (24 weeks) follow-up period before and while dopaminergic medications were being titrated. The typing data were used to develop a novel algorithm based on recursive neural networks and detect participants' responses to medication. The latter were defined by the Unified Parkinson's Disease Rating Scale-III (UPDRS-III) minimal clinically important difference. Furthermore, we tested the accuracy of the algorithm to predict the final response to medication as early as 21 weeks prior to the final 6-month clinical outcome. Results The score on the novel algorithm based on recursive neural networks had an overall moderate kappa agreement and fair area under the receiver operating characteristic (ROC) curve with the time-coincident UPDRS-III minimal clinically important difference. The participants classified as responders at the final visit (based on the UPDRS-III minimal clinically important difference) had higher scores on the novel algorithm based on recursive neural networks when compared with the participants with stable UPDRS-III, from the third week of the study onward. Conclusions This preliminary study suggests that remotely gathered unsupervised typing data allows for the accurate detection and prediction of drug response in PD. © 2019 International Parkinson and Movement Disorder Society.

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.

The main aim of the study was to compare the rates of mortality in older adults with and without functional unawareness (FU). We also tested a possible interaction effect between levels of awareness and education, as a single cognitive reserve proxy, on mortality.The study design is a longitudinal population-based cohort study.The Neurological Disorders in Central Spain is epidemiological study to detect main age-associated conditions in people aged 65 years and older. Participants were collected from updated population-based registers of residents in three areas of central Spain. Awareness of functional limitations was established in accordance with the discrepancy between two sources of information on functional impairments: reliable informants versus the participants themselves. Three mutually exclusive groups were formed, namely, Functional Limitation Complaints (FCs), FU, and Functional Awareness (FA). Cox's regression models, adjusted by different covariates, were used to calculate the risk of mortality for each group at 5-year follow-up (vs. reference group without limitations).Of 1818 selected individuals, 229 (12.5%) showed FA, 254 (13.9%) showed FC, and 96 (5%) were classified as FU. All these groups showed an increased risk of mortality at 5-year follow-up [adjusted hazard ratio (HR) for FC FU FA]. However, the association of FU with mortality remained significant only for highly educated individuals.Functional impairment was associated with increased mortality rates, regardless of the presence of unawareness. This study extends the role of education in modulating the symptoms and prognosis of individuals at very mild or preclinical dementia stages.

The aim of this study was to establish reliable change and regression-based change score norms on the 37-item version of MMSE in older Spanish adults at the three-year follow-up.All subjects of this research were selected from the Neurological Disorders in Central Spain (NEDICES), a prospective population-based cohort study of older adults (65 years and over). Of the 4208 individuals free from neurological disorders in this cohort, 2073 participants completed the MMSE-37 at baseline and at the three-year follow-up. Reliable Change Indices were computed for the 80, 90% and 95 confidence intervals (CIs). Multiple regression analyses were used to derive equations for predicting MMSE-37 post-test scores taking into account baseline scores, time to follow-up and sociodemographic factors.The MMSE-37 obtained a marginal test-retest reliability (.70). The results showed significant effects of education, age, and sex on the MMSE-37 change scores. After correcting for regression to the mean, at least a 6-point change on MMSE-37 (three-years follow-up) is required to be classified as reliable (90% CI).These findings demonstrate that the MMSE-37 is a reliable test-retest measure whose change scores are significantly influenced by sociodemographic factors. Importantly, small changes on this measure require a cautious interpretation.

High education has been associated with faster cognitive decline after diagnosis of Alzheimer's disease (AD), but it is unclear whether these findings extend to other dementia subtypes. OBJECTIVE: We investigated whether educational attainment influences the cognitive trajectories of older adults with different dementia subtypes. METHODS: All participants were selected from NEDICES, a prospective population-based cohort study of Spanish older adults. A total sample of 53 individuals with dementia completed the MMSE-37 at Times 1 and 2 (mean follow-up=2.8±0.5 years) to assess cognitive decline. RESULTS: At follow-up, MMSE-37 scores had decreased by 3.34±4.98 points in low-educated individuals with dementia versus 7.90±4.88 points in high-educated subjects (effect size (r)=0.32, p=0.02). CONCLUSION: Educational level influenced the cognitive trajectories of patients with dementia assessed by the MMSE-37. RESUMO A educação mais alta tem sido associada com um declínio cognitive mais rápido após o diagnóstico de doença de Alzheimer (DA), mas não está claro se estes achados podem ser extendidos a outros subtipos de demência. OBJETIVO: Nós investigamos se o nível educacional alcançado influencia as trajetórias cognitivas de adultos idosos com diferentes subtipos de demência. MÉTODOS: Todos os participantes foram selecionados do NEDICES, um estudo de coorte prospectivo de base populacional de idosos adultos espanhóis. Uma amostra total de 53 indivíduos com demência completaram o MEEM-37 nos momentos 1 e 2 (acompanhamento médio de 2.8± 0.5 anos) para avaliação do declínio cognitive. RESULTADOS: No seguimento, o MEEM-37 declinou 3.34±4.98 pontos em indivíduos de baixa escolaridade com demência versus 7.90±4.88 pontos entre os altamente escolarizados (tamanho do efeito (r)=0.32, p=0.02). CONCLUSÃO: O nível educacional influenciou as trajetórias cognitivas de pacientes com demência avaliados pelo MEEM-37.

Objective The association between higher education and increased mortality in Alzheimer's disease (AD) is controversial. Further it is unknown whether education predicts survival in all dementia subtypes. We assessed mortality rates and death causes of persons with dementia compared to participants without dementia. Methods Participants derive from the Neurological Disorders in Central Spain, a prospective population- based cohort study of older adults. We compared 269 persons with dementia to 2944 participants without dementia. We carried out Cox regression models to predict the risk of mortality dependent on the educational attainment adjusting for covariates. Reasons of death were obtained from the National Population Register. Results During a median follow-up of 5.4 years, 400 individuals died (171 with dementia, 229 without dementia). Among the participants with dementia, those with higher educational attainment had an increased risk of death than those with lower education; the adjusted hazard ratio (HRa) was 1.40 (95% confidence interval [CI], 1.01 to 1.94). When the analysis was restricted to patients with AD the HRa increased to 1.51 (95% CI = 1.01-2.24). By contrast, educational attainment was not associated with increased mortality among participants without dementia (HRa = 0.92, 95% CI = 0.71-1.20, p = 0.55), whereas education did not influence mortality in QD. Conclusion Our findings suggest that high educational attainment is associated with increased mortality risk in people with dementia. This observation implies that neuropathology is more advanced in patients with higher education at any level of clinical severity, leading these individuals to an earlier death after diagnosis.

Objective: We aimed to analyse the clinical utility of the Mattis Dementia Rating Scale (MDRS-2) for early detection of Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI) in a sample of Spanish older adults. Methods: A total of 125 participants (age = 75.12 ± 6.83, years of education =7.08 ± 3.57) were classified in three diagnostic groups: 45 patients with mild AD, 37 with amnestic MCI—single and multiple domain and 43 cognitively healthy controls (HCs). Reliability, criterion validity and diagnostic accuracy of the MDRS-2 (total and subscales) were analysed. The MDRS-2 scores, adjusted by socio-demographic characteristics, were calculated through hierarchical multiple regression analysis. Results: The global scale had adequate reliability (α = 0.736) and good criterion validity (r = 0.760, p

This review proposes a more optimistic view of Alzheimer's disease (AD), in contrast to that contributed by the ageing of the population and the failure of potentially curative therapies (vaccines and others). Treatment failure is likely due to the fact that AD gestates in the brain for decades but manifests in old age. This review updates the concept of AD and presents the results of recent studies that show that primary prevention can reduce the incidence and delay the onset of the disease. Half of all cases of AD are potentially preventable through education, the control of cardiovascular risk factors, the promotion of healthy lifestyles and specific drug treatments. These approaches could substantially reduce the future incidence rate of this disease.

Resumen Esta revision propone una vision mas optimista de la enfermedad de Alzheimer (EA), en contraposicion a la que el envejecimiento poblacional y el fracaso de terapias potencialmente curativas (vacunas y otras) han contribuido a ofrecer. El fracaso terapeutico se debe, verosimilmente, a que la EA se gesta en el cerebro durante decadas, aunque se manifieste en la vejez. En esta revision se actualiza el concepto de EA y se recogen los resultados de estudios recientes que muestran que la prevencion primaria podria reducir la incidencia, o retrasar la aparicion de la EA. La mitad de los casos de EA pueden ser potencialmente prevenibles mediante la educacion, el control de los factores de riesgo cardiovascular, la promocion de estilos de vida saludables y algunos tratamientos farmacologicos que podrian conseguir una reduccion sustancial de su incidencia en el futuro.

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.

Alzheimer disease (AD) mortality risk in a large cohort of subjects treated or not with non-steroidal anti-inflammatory drugs (NSAIDs) is unknown. Our objective was to determine whether NSAIDs use is associated with decreased risk of AD mortality. In this prospective, population-based study (Neurological Disorders in Central Spain [NEDICES]) of 5,072 people without AD (aged 65 years and older), sociodemographic, comorbidity factors, and current medications were recorded at baseline. Community-dwelling older adults were followed for a median of 12.7 years, after which the death certificates of deceased participants were examined. 2,672 (52.7%) of 5,072 participants died, including 504 (18.9%) NSAIDs users and 2,168 (81.1%) non-users. Of the 2,672 deceased participants, 113 (4.2%) had AD as a cause of death (8 [1.6%] among NSAIDs users and 105 [4.8%] among non-users, chi-square = 10.70, p = 0.001). In an unadjusted Cox model, risk of AD mortality was decreased in NSAIDs users (hazard ratio [HR] for AD mortality = 0.35, 95% confidence interval [CI] 0.17–0.72, p = 0.004) when compared to non-users. After adjusting for numerous demographic factors and co-morbidities, the HR for AD mortality in NSAIDs users was 0.29, 95% CI 0.12–0.73, p = 0.009. Stratified analyses showed a significantly decreased risk of AD mortality with aspirin, whereas non-aspirin NSAIDs only showed a statistical trend toward significance in the adjusted Cox regression models. NSAIDs use was associated with 71% decreased risk of AD mortality in older adults. Our results support the hypothesis that NSAIDs use is a protective factor of developing AD.

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 and Objectives: The existence of different patterns of functional impairment in older adults has scarcely been addressed. This research investigates major patterns of functional impairme...

The effect of different educational indices on clinical diagnosis of dementia requires more investigation.We compared the differential influence of two educational indices (EIs): years of schooling and level of education (i.e., null/low literacy, can read and write, primary school, and secondary school) on global cognition, functional performance, and the probability of having a dementia diagnosis.A total of 3,816 participants were selected from the population-based study of older adults "Neurological Disorders in Central Spain" (NEDICES). The 37-item version of the Mini-Mental State Examination (MMSE-37) and the Pfeffer's questionnaire were applied to assess cognitive and functional performance, respectively. The diagnosis of dementia was performed by expert neurologists according to Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) criteria. Logistic regression models adjusted for potential confounders were carried out to test the association between the two EIs and dementia diagnosis.Both EIs were significantly associated with cognitive and functional scores, but individuals with null/low literacy performed significantly worse on MMSE-37 than literates when these groups were compared in terms of years of schooling. The two EIs were also related to an increased probability of dementia diagnosis in logistic models, but the association's strength was stronger for level of education than for years of schooling.Literacy predicted cognitive performance over and above the years of schooling. Lower education increases the probability of having a dementia diagnosis but the impact of different EIs is not uniform.

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.

Objective We investigated the mortality rates of three subtypes of disability and their specific explanatory factors in older adults. Methods Our data come from NEDICES, a population-based longitudinal cohort study of Spanish older adults. We examined 3816 participants without dementia who completed the Pfeffer's Functional Activities Questionnaire (FAQ) and an assessment of self-perceived functional limitations (SFL) associated with health conditions. Subjects were classified into mutually exclusive subtypes of disability: subtype 1 (SFL), subtype 2 (impaired FAQ), and subtype 3 (impaired FAQ plus SFL). Factors related to all disability subtypes were analyzed using a multinomial logistic regression (MLR), whereas Cox regression (CR) models adjusted by covariates were applied to compare survival rates between groups at the 5-year follow up. Results The CR models indicated that SFL and FAQ scores were associated with higher risk of mortality at 5-years. After stratifying by subtypes of disability, mortality was significantly higher in subtype 3 than in subtypes 1 and 2. All models were consistent after adjusting by different covariates. The MLR showed that subtype 1 was specifically associated with the number of comorbidities, whereas subtype 2 was associated with lower MMSE scores depression and living in nursing homes. Conclusions Our results show that the combination of impaired FAQ plus SFL have an increased differential predictive utility for mortality than approaches based on unique measures. They also indicate that both measures of disability are associated with different explanatory factors.

Objective: Although the cerebello-thalamo-cortical network has often been suggested to be of importance in the pathogenesis of essential tremor (ET), the origins of tremorgenic activity in this disease are not fully understood. We used a combination of cortical thickness imaging and neurophysiological studies to analyze whether the severity of tremor was associated with anatomical changes in the brain in ET patients. Methods: Magnetic resonance imaging (MRI) and a neurophysiological assessment were performed in 13 nondemented ET patients. High field structural brain MRI images acquired in a 3T scanner and analyses of cortical thickness and surface were carried out. Cortical reconstruction and volumetric segmentation was performed with the FreeSurfer image analysis software. We used high-density surface electromyography (hdEMG) and inertial measurement units (IMUs) to quantify the tremor severity in upper extrimities of patients. In particular, advanced computer tool was used to reliably identify discharge patterns of individual motor units from surface hdEMG and quantify motor unit synchronization. Results: We found significant association between increased motor unit synchronization (i.e., more severe tremor) and cortical changes (i.e., atrophy) in widespread cerebral cortical areas, including the left medial orbitofrontal cortex, left isthmus of the cingulate gyrus, right paracentral lobule, right lingual gyrus, as well as reduced left supramarginal gyrus (inferior parietal cortex), right isthmus of the cingulate gyrus, left thalamus, and left amygdala volumes. Interpretation: Given that most of these brain areas are involved in controlling movement sequencing, ET tremor could be the result of an involuntary activation of a program of motor behavior used in the genesis of voluntary repetitive movements., This work was funded by FEDER grant ; National Institutes of Health grant ; NINDS grants R01 NS39422;, R01 NS094607;, R01 NS085136;, R01 NS073872;, and R01 NS088257; European Commission grant ICT‐2011‐287739; Ministry of Economy and Competitiveness grant RTC‐2015‐3967‐1; Spanish Health Research Agency grants FIS PI12/01602; and FIS PI16/00451; Spanish Ministry of Economy and Competitiveness grants DPI‐2015‐68664‐C4‐1‐R; and DPI2015‐72638‐EXP; Claire O'Neil Essential Tremor Research grant ; Slovenian Research Agency grant J2‐7357.

There remains much to learn about the changes in cortical anatomy that are associated with tremor severity in Parkinson's disease (PD). For this reason, we used a combination of structural neuroimaging to measure cortical thickness and neurophysiological studies to analyze whether PD tremor was associated with cortex integrity. Magnetic resonance imaging and neurophysiological assessment were performed in 13 nondemented PD patients (9 women, 69.2%) with a clearly tremor-dominant phenotype. Cortical reconstruction and volumetric segmentation were performed with the Freesurfer image analysis software. Assessment of tremor was performed by means of high-density surface electromyography (hdEMG) and inertial measurement units (IMUs). Individual motor unit discharge patterns were identified from surface hdEMG and tremor metrics quantifying motor unit synchronization from IMUs. Increased motor unit synchronization (i.e., more severe tremor) was associated with cortical changes (i.e., atrophy) in wide-spread cortical areas, including caudal middle frontal regions bilaterally (dorsal premotor cortices), left inferior parietal lobe (posterior parietal cortex), left lateral orbitofrontal cortex, cingulate cortex bilaterally, left posterior and transverse temporal cortex, and left occipital lobe, as well as reduced left middle temporal volume. Given that the majority of these areas are involved in controlling movement sequencing, our results support Albert's classic hypothesis that PD tremor may be the result of an involuntary activation of a program of motor behavior used in the genesis of rapid voluntary alternating movements.

Early separation of mild cognitive impairment (MCI) from normal aging and mild cases of dementia remains a challenge, especially in the general population. We aimed to analyze the diagnostic accuracy of a brief neuropsychological battery (BNB) in dementia and MCI cases from the Neurological Disorders in Central Spain (NEDICES) population-based cohort study. We screened 3,891 participants into dementia and non-dementia groups using a two-phase procedure: screening (MMSE-37 and Pfeffer-11) and clinical diagnosis by specialists (DSM-IV criteria). We selected subsequently a subsample of dementia (nA¢Â€ÂŠ=A¢Â€ÂŠ98), MCI (nA¢Â€ÂŠ=A¢Â€ÂŠ71), and cognitively healthy (nA¢Â€ÂŠ=A¢Â€ÂŠ123) participants matched in socio-demographic characteristics. The clinical validity of each test of the BNB was determined by the area under the ROC curve. We determined the best combination of tests to classify individuals into the diagnostic groups by logistic regression analyses. The results indicated that dementia and MCI groups could be best discriminated from the healthy control group on the basis of their scores on the semantic verbal fluency and delayed recall subtests of the BNB. As for discriminating the MCI group from the dementia group, immediate recall tasks (stories and pictures) yielded the highest level of accuracy. Probably the most interesting finding is that the verbal fluency task consistently allowed discrimination among the diagnostic groups. Overall, subtests of the BNB are more accurate in differentiating dementia patients than MCI patients from healthy controls. In this population-based sample, a more fine-grained discrimination that includes MCI patients should follow a systematic subtest-wise analysis and decision.

Background An association between head trauma and essential tremor (ET) has not been formally assessed. Our purpose was to assess the association between serious head trauma and ET. Methods History of head trauma was assessed in 274 ET cases and 3201 controls in the Neurological Disorders in Central Spain (NEDICES) study, a population-based study in central Spain. Head trauma was defined as serious only if the subject reported that the trauma resulted in loss of consciousness, hospitalization, or a visit to the emergency department. Results Thirty-two (11.7%) of 274 ET cases vs. 260 (8.1%) of 3201 controls reported a history of serious head trauma (p = 0.04). In an adjusted logistic regression analysis, participants who reported serious head trauma were 52% more likely to have ET (odds ratio [OR] 1.52; 95% confidence interval [CI] 1.02–2.27, p = 0.04). The odds of ET increased with increasing age of head trauma: adjusted ORs = 1.23 (95% CI 0.43–3.46, p = 0.70) for serious head trauma that occurred before age 18 years, adjusted OR = 1.49 (95% CI 0.62–3.55, p = 0.37) for serious head trauma between ages 18 to 39 years, and adjusted OR = 1.61 (95% CI 1.00–2.57, p = 0.04) for serious head trauma at age 40 years or older. Conclusions Our study suggests that serious head trauma, especially when it occurs after 40 years, is associated with increased odds of ET. Additional studies are needed to reproduce this novel finding.

Background Essential tremor (ET), a highly-prevalent, progressive, aging-associated neurological disease, poses a significant public health challenge. Aside from its associated motor features, the disease affects cognition in some patients, mood, and morale, and has been associated with increased risk of mortality in the elderly. Studies have not investigated the relationship between self-rated health and risk of ET. We determined whether baseline poor self-rated health was associated with increased risk of incident ET. Methods In this prospective, population-based study of people ≥65 years of age, subjects were evaluated at baseline and 3 years later. At baseline, subjects were asked to rate their health using a single-item health question. Hazard ratios (HR) of ET according to baseline self-rated health (very good, good, fair, poor, and very poor) were estimated with Cox models. Results The 3853 subjects had a median follow-up duration of 3.2 years. There were 82 incident ET cases. Compared to subjects who rated their health as good or very good, the risk of ET was increased for subjects who rated their health as fair (HR = 1.69, p = 0.03), and for subjects who rated their health as poor or very poor (HR = 2.12, p = 0.02). In a fully adjusted model, the risk remained increased for subjects who rated their health as poor or very poor (HR = 2.34, p = 0.01). Conclusions Subjects rating their health as poor/very poor at baseline were at increased risk of incident ET at follow-up. Premotor and/or early motor symptoms of ET could negatively influence self-perceptions of health status.

Objective. This research aims to determine whether residence (rural vs. urban) at different life stages (childhood, adulthood, and late life) is associated with increased risk of incident dementia in a population-based cohort of older Spaniards. Methods. In this prospective study, 2,711 participants aged 65 years and older were assessed at baseline and 3 years later. All cases of incident dementia were diagnosed using DSM-IV criteria. The relationship between residence and the relative risk of dementia was analysed using Cox's regression models. Demographics, comorbidity index, consumption (tobacco / alcohol) and doubtful dementia diagnosis were considered as possible confounders. Results. At the three-year follow-up, 91 cases of dementia were detected. Lower education and occupational attainment were associated with a higher incidence of dementia three years later. Rural residence in adulthood was associated with a significantly higher risk of dementia at the follow-up. Childhood rural residence revealed a marked trend for risk of dementia (p = 0.08), but it was nonsignificant in later life. The risk of dementia was considerably higher for the rural/low-education group than for the urban/high-education group, for both childhood and adulthood residence. Finally, people from areas with the lowest socio- economic status Arevalo (rural, blue-collar) and Margaritas (urban, blue-collar) showed higher risk of dementia than people from Lista (urban, mixed white/blue collar). Conclusion. In this cohort, early and mid-life stages rural residence was a risk factor for dementia, but not later-life rural residence. The rural residence effect was noticeably higher in people with a lower educational level.

Accurate blood-based biomarkers of Alzheimer's disease (AD) could constitute simple, inexpensive, and non-invasive tools for the early diagnosis and treatment of this devastating neurodegenerative disease. We sought to develop a robust AD biomarker panel by identifying alterations in plasma metabolites that persist throughout the continuum of AD pathophysiology. Using a multicenter, cross-sectional study design, we based our analysis on metabolites whose levels were altered both in AD patients and in patients with amnestic mild cognitive impairment (aMCI), the earliest identifiable stage of AD. UPLC coupled to mass spectrometry was used to independently compare the levels of 495 plasma metabolites in aMCI (n = 58) and AD (n = 100) patients with those of normal cognition controls (NC, n = 93). Metabolite alterations common to both aMCI and AD patients were used to generate a logistic regression model that accurately distinguished AD from NC patients. The final panel consisted of seven metabolites: three amino acids (glutamic acid, alanine, and aspartic acid), one non-esterified fatty acid (22:6n-3, DHA), one bile acid (deoxycholic acid), one phosphatidylethanolamine [PE(36:4)], and one sphingomyelin [SM(39:1)]. Detailed analysis ruled out the influence of potential confounding variables, including comorbidities and treatments, on each of the seven biomarkers. The final model accurately distinguished AD from NC patients (AUC, 0.918). Importantly, the model also distinguished aMCI from NC patients (AUC, 0.826), indicating its potential diagnostic utility in early disease stages. These findings describe a sensitive biomarker panel that may facilitate the specific detection of early-stage AD through the analysis of plasma samples.

The influence of education and oral word-reading ability on cognitive performance was examined in a sample of 1510 nondemented elders differing in socioeconomic status (SES) from three Spanish communities.All individuals were enrolled in the Neurological Disorders in Central Spain, a population-based epidemiological study in central Spain. They completed a detailed demographic survey and a short standardized neuropsychological battery assessing psychomotor speed, attention, language, and memory. The Word Accentuation Test (WAT) was used as measure of oral reading ability. The influence of education and oral reading on cognitive performance was determined by multiple linear regression models, first controlling for demographics (age and sex), and subsequently for the WAT score and education. The contribution of socioeconomic conditions was addressed by stratifying the sample into groups of high and low SES.The WAT showed a significant independent effect on cognitive scores, generally greater than that predicted by demographics. The higher predictive power of oral word reading on cognitive scores compared to education was consistent across the three communities. Although the variance explained by WAT was very similar in areas with diverse SES (low vs. high), WAT scores accounted for slightly more variance in naming and memory tasks in low SES areas. In contrast, the variance explained by WAT was higher for verbal fluency and the Trail-Making Test in areas with high SES.Oral word-reading ability predicts cognitive performance better than years of education across individuals with different SES. The influence of WAT may be modulated by SES and cognitive task properties.

Background: Little information is available on the potential association between polypharmacy and risk of mortality. Objective: To determine in a population-based study whether polypharmacy is associated with increased risk of mortality in elderly persons. Methods: In this population-based, prospective study of 5,052 people aged 65 years and older (Neurological Disorders in Central Spain), current medications were recorded. Cox proportional hazards models, adjusted for sociodemographics and comorbidity factors, were used to assess the risk of death up to 13.3 years later, comparing the polypharmacy group (≥6 drugs) to those who were taking 1-5 drugs and those in a nonmedicated group (0 drugs). Results: Out of 5,052 participants, 2,550 (50.5%) died over a median follow-up of 6.5 years, including 361 (28.8%) deaths among 931 nonmedicated participants, 1,946 (51.4%) deaths among 3,787 participants taking 1-5 drugs daily, and 243 (72.8%) among 334 participants on polypharmacy. In an unadjusted Cox model, risk of mortality was increased in participants on polypharmacy [hazard ratio (HR) = 2.78, 95% confidence interval [CI]: 2.36-3.27, p < 0.001) and in those taking between 1 and 5 drugs (HR = 1.47, 95% CI: 1.31-1.64, p < 0.001) versus those who were nonmedicated (reference group). In a Cox model that adjusted for a variety of demographic factors and comorbidities, HR remained increased in participants on polypharmacy (HR = 1.83, 95% CI: 1.51-2.21, p < 0.001). Conclusion: This study provides evidence that polypharmacy is associated with increased risk of mortality in elderly people. The extent to which polypharmacy is the proximate cause rather than a marker of this increase risk remains to be determined.

Diffusion tensor imaging (DTI) studies have detected white matter microstructural changes in essential tremor (ET). However, it is still unclear whether these changes are related to cognitive deficits, which have been described in ET patients. DTI-derived fractional anisotropy, mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity measures were compared between 23 ET patients and 23 age-, gender-, and education-matched healthy individuals, using whole-brain tract-based spatial statistics. Correlations of white matter changes with scores obtained from a detailed neuropsychological assessment were subsequently examined. ET patients demonstrated increases in MD in the bilateral posterior corona radiata, bilateral superior longitudinal fasciculus, bilateral fornix (cres)/stria terminalis, genu and splenium of the corpus callosum, bilateral anterior and posterior limbs of internal capsule, bilateral retrolenticular region part of internal capsule, and left posterior thalamic radiation. Except for the genu of the corpus callosum, an increase in AD values was also found in these same tracts. Furthermore, increased MD and AD values in different white matter areas was negatively correlated with performance on language and verbal memory and positively with visuospatial ability. These correlations suggest that white matter changes might be involved in the pathogenesis of cognitive deficits in ET.

Background Despite growing evidence showing an association between Parkinson's disease (PD) and diabetes, epidemiological studies have shown conflicting results. Aims of the study To evaluate the association between PD and diabetes and the impact of diabetes duration in this association in an elderly (≥65 years) Spanish population. Methods Data for this cross-sectional population-based analysis were obtained from NEDICES study. Subjects were identified from census list. Diagnosis of PD was confirmed by neurological examination. Diabetes was defined by self-report, being on antidiabetic medication or diagnosis on medical records. Logistic regression analysis adjusted by potential confounders was performed to estimate the association between both conditions and also after dividing patients into short-duration (