Comparison of mortality rate in older adults with and without functional awareness: the Neurological Disorders in Central Spain (NEDICES) population-based study.

OBJECTIVES: 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. STUDY DESIGN: The study design is a longitudinal population-based cohort study. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Association between Parkinson's disease and diabetes: Data from NEDICES study.

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 (<10 years) and long-duration (≥10 years) diabetes. RESULTS: A total of 4998 subjects were included (79 PD and 4919 controls). Univariate analysis did not show any association between prevalence of PD and diabetes (OR 1.89, 95% CI 0.90-3.98, P=.09), although subgroup analysis showed a positive association in those with long-duration diabetes (3.27, 95% CI 1.21-8.85, P=.02). CONCLUSIONS: Diabetes duration might be an important factor in the association between PD and diabetes, and the risk might be limited to those with longer disease duration.

Cognition in non-demented Parkinson's disease vs essential tremor: A population-based study.

OBJECTIVES: Patients with Parkinson's disease (PD) and essential tremor (ET) have a higher risk of cognitive impairment than age-matched controls. Only a few small studies (11-18 subjects per group) have directly compared the cognitive profile of these conditions. Our aim was to compare the cognitive profile of patients with these two conditions to each other and to healthy individuals in a population-based study of non-demented participants. MATERIALS AND METHODS: This investigation was part of the NEDICES study, a survey of the elderly in which 2438 dementia-free participants underwent a short neuropsychological battery. We used nonparametric techniques to evaluate whether there are differences and/or a gradient of impairment across the groups (PD, ET, and controls). Also, we performed a head-to-head comparison of ET and PD, adjusting for age and education. RESULTS: Patients with PD (N=46) and ET (N=180) had poorer cognition than controls (N=2212). An impaired gradient of performance was evident. PD scored lower than ET, and then each of these lower than controls, in memory (P<.05) and verbal fluency (P<.001) tasks. When we compared PD and ET, the former had lower scores in verbal fluency (P<.05), whereas the later had a poorer cognitive processing speed (P<.05). CONCLUSIONS: This large population-based study demonstrates that both conditions influence cognitive performance, that a continuum exists from normal controls to ET to PD (most severe), and that although deficits are in many of the same cognitive domains, the affected cognitive domains do not overlap completely.

Prevención de la enfermedad de Alzheimer: un camino a seguir / Alzheimer's disease prevention: a way forward

Esta revisión propone una visión más optimista de la enfermedad de Alzheimer (EA), en contraposición a la que el envejecimiento poblacional y el fracaso de terapias potencialmente curativas (vacunas y otras) han contribuido a ofrecer. El fracaso terapéutico se debe, verosímilmente, a que la EA se gesta en el cerebro durante décadas, aunque se manifieste en la vejez. En esta revisión se actualiza el concepto de EA y se recogen los resultados de estudios recientes que muestran que la prevención primaria podría reducir la incidencia, o retrasar la aparición de la EA. La mitad de los casos de EA pueden ser potencialmente prevenibles mediante la educación, el control de los factores de riesgo cardiovascular, la promoción de estilos de vida saludables y algunos tratamientos farmacológicos que podrían conseguir una reducción sustancial de su incidencia en el futuro (AU)

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 (AU)

Alzheimer's disease prevention: A way forward. / Prevención de la enfermedad de Alzheimer: un camino a seguir.

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.

Aplicación práctica de los test cognitivos breves / Practical application of brief cognitive tests

Introducción: Los test cognitivos breves (TCB) pueden ayudar a detectar el deterioro cognitivo (DC) en el ámbito asistencial. Se han desarrollado y/o validado varios TCB en nuestro país, pero no existen recomendaciones específicas para su uso. Desarrollo: Revisión de estudios sobre el rendimiento diagnóstico en la detección del DC llevados a cabo en España con TCB que requieran menos de 20 min y recomendaciones de uso consensuadas por expertos, sobre la base de las características de los TCB y de los estudios disponibles. Conclusión: El Fototest, el Memory Impairment Screen (MIS) y el Mini-Mental State Examination (MMSE) son las opciones más recomendables para el primer nivel asistencial, pudiendo añadirse otros test (Test del Reloj [TR] y test de fluidez verbal [TFV]) en caso de resultado negativo y queja o sospecha persistente (aproximación escalonada). En el segundo nivel asistencial es conveniente una evaluación sistemática de las distintas áreas cognitivas, que puede llevarse a cabo con instrumentos como el Montreal Cognitive Assessment, el MMSE, el Rowland Universal Dementia Assessment o el Addenbrooke's Cognitive Examination, o bien mediante el uso escalonado o combinado de herramientas más simples (TR, TFV, Fototest, MIS, Test de Alteración de la Memoria y Eurotest). El uso asociado de cuestionarios cumplimentados por un informador (CCI) aporta valor añadido a los TCB en la detección del DC. La elección de los instrumentos vendrá condicionada por las características del paciente, la experiencia del clínico y el tiempo disponible. Los TCB y los CCI deben reforzar -pero nunca suplantar- el juicio clínico, la comunicación con el paciente y el diálogo interprofesional

Introduction: Brief cognitive tests (BCT) may help detect cognitive impairment (CI) in the clinical setting. Several BCT have been developed and/or validated in our country, but we lack specific recommendations for use. Development: Review of studies on the diagnostic accuracy of BCT for CI, using studies conducted in Spain with BCT which take less than 20 min. We provide recommendations of use based on expert consensus and established on the basis of BCT characteristics and study results. Conclusion: The Fototest, the Memory Impairment Screen (MIS) and the Mini-Mental State Examination (MMSE) are the preferred options in primary care; other BCT (Clock Drawing Test [CDT], test of verbal fluency [TVF]) may also be administered in cases of negative results with persistent suspected CI or concern (stepwise approach). In the specialised care setting, a systematic assessment of the different cognitive domains should be conducted using the Montreal Cognitive Assessment, the MMSE, the Rowland Universal Dementia Assessment, the Addenbrooke's Cognitive Examination, or by means of a stepwise or combined approach involving more simple tests (CDT, TVF, Fototest, MIS, Memory Alteration Test, Eurotest). Associating an informant questionnaire (IQ) with the BCT is superior to the BCT alone for the detection of CI. The choice of instruments will depend on the patient's characteristics, the clinician's experience, and available time. The BCT and IQ must reinforce - but never substitute - clinical judgment, patient-doctor communication, and inter-professional dialogue

The 37 item Version of the Mini-Mental State Examination: Normative Data in a Population-Based Cohort of Older Spanish Adults (NEDICES).

The 37-item version of the Mini-Mental State Examination (MMSE-37) is an extended version of the original test for individuals with low education, which was adapted for different cultures. Despite its favorable psychometric properties, there is a lack of normative data for this instrument. We provide normative data for the MMSE-37 stratified by age, sex, and education in a large population-based cohort of older Spanish adults. The sample consisted of 3,777 participants without dementia (age range: 65-97 years) from different socioeconomic areas of central Spain. Normative data are presented in percentile ranks and divided into nine overlapping age tables with different midpoints, using the overlapping cell procedure. A hierarchical regression was performed to evaluate the effects of sociodemographic variables on MMSE-37 performance. Results showed that age, sex, and education affect test score. The norms presented herein are important for the correct interpretation of MMSE-37 scores when assessing older adults in Spain.

Practical application of brief cognitive tests.

INTRODUCTION: Brief cognitive tests (BCT) may help detect cognitive impairment (CI) in the clinical setting. Several BCT have been developed and/or validated in our country, but we lack specific recommendations for use. DEVELOPMENT: Review of studies on the diagnostic accuracy of BCT for CI, using studies conducted in Spain with BCT which take less than 20 min. We provide recommendations of use based on expert consensus and established on the basis of BCT characteristics and study results. CONCLUSION: The Fototest, the Memory Impairment Screen (MIS) and the Mini-Mental State Examination (MMSE) are the preferred options in primary care; other BCT (Clock Drawing Test [CDT], test of verbal fluency [TVF]) may also be administered in cases of negative results with persistent suspected CI or concern (stepwise approach). In the specialised care setting, a systematic assessment of the different cognitive domains should be conducted using the Montreal Cognitive Assessment, the MMSE, the Rowland Universal Dementia Assessment, the Addenbrooke's Cognitive Examination, or by means of a stepwise or combined approach involving more simple tests (CDT, TVF, Fototest, MIS, Memory Alteration Test, Eurotest). Associating an informant questionnaire (IQ) with the BCT is superior to the BCT alone for the detection of CI. The choice of instruments will depend on the patient's characteristics, the clinician's experience, and available time. The BCT and IQ must reinforce - but never substitute - clinical judgment, patient-doctor communication, and inter-professional dialogue.

No hay razones científicas para jubilar al MMSE / There is no scientific basis for retiring the MMSE

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[Spanish versions of the Minimental State Examination (MMSE). Questions for their use in clinical practice]. / Versiones en español del Minimental State Examination (MMSE). Cuestiones para su uso en la practica clinica.

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.

TITLE: Versiones en español del Minimental State Examination (MMSE). Cuestiones para su uso en la practica clinica.El Minimental State Examination (MMSE), creado en 1975 como instrumento para la evaluacion breve del estado mental, ha tenido una gran difusion, y es el test cognitivo mas citado en Medline y con mayor numero de versiones idiomaticas (superiores a 70). Este articulo pretende, mediante una revision en la base de datos Medline, analizar sus virtudes y limitaciones, ademas de precisar su utilidad clinica actual, tanto de la version original como de sus modificaciones, principalmente de las adaptaciones al español. El MMSE (original o versiones) es el test mas utilizado para la evaluacion cognitiva estandarizada en el ambito clinico, sobre todo en el anciano. Es el que dispone de mas datos para el cribado, estadiaje y seguimiento de las demencias. Sin embargo, dado que su cumplimentacion puede requerir mas de 10 minutos, ha de competir con tests de cribado mas cortos y especificos en atencion primaria y el medio comunitario. En el ambito hospitalario y especializado, se precisan evaluaciones neuropsicologicas estandarizadas mas amplias que permitan detectar alteraciones cognitivas sutiles en pacientes con demencia incipiente o alteracion cognitiva leve, ademas de establecer un perfil cognitivo de los diferentes subtipos de demencias. Este trabajo realiza una serie de recomendaciones sobre el uso clinico de las versiones españolas del MMSE en diferentes contextos de aplicacion.

Cause of death in mild cognitive impairment: a prospective study (NEDICES).

BACKGROUND AND PURPOSE: Previous studies have reported the occurrence of increased mortality rates among individuals with mild cognitive impairment (MCI), but possible links between MCI subtypes and cause-specific mortality need to be explored. To examine short-term mortality (5 years), long-term mortality (13 years) and cause-specific mortality of individuals over 65 years of age suffering from MCI compared with cognitively unimpaired individuals in the Neurological Disorders in Central Spain (NEDICES) cohort. METHODS: Mild cognitive impairment was classified using standardized psychometric and functional assessment in accordance with diagnostic convention. Cox's proportional hazards models, adjusted by sociodemographics and comorbidity factors, were used to assess the risk of death at 5 and 13 years of MCI subtypes compared with a reference group of older people without cognitive impairment (N = 2329). Causes of death were obtained from the National Population Register of Spain. RESULTS: There were 1484 deceased individuals at 13 years. MCI subtypes were defined as amnestic single domain (N = 259), amnestic multiple domain (N = 197) and non-amnestic (N = 641). After adjusting for covariates, only the amnestic multiple domain MCI subtype showed an increased hazard ratio (HR) for mortality at 5 years versus the reference group. However, the HR for mortality at 13 years was increased for all MCI subtypes. The HR by MCI subtype was 1.19 in the non-amnestic subtype (95% CI 1.05-1.36), 1.31 in the amnestic single domain subtype (95% CI 1.10-1.56) and 1.67 in the amnestic multiple domain subtype (95% CI 1.38-2.02). In terms of cause-specific mortality, the chance of death from dementia was statistically higher in all MCI subtypes. CONCLUSION: Amnestic multiple domain MCI showed the greatest risk of mortality in comparison with other MCI subtypes at different intervals. Dementia was the only cause-specific mortality that was increased in MCI individuals.

Cumulative effect of depression on dementia risk.

Objective. To analyze a potential cumulative effect of life-time depression on dementia and Alzheimer's disease (AD), with control of vascular factors (VFs). Methods. This study was a subanalysis of the Neurological Disorders in Central Spain (NEDICES) study. Past and present depression, VFs, dementia status, and dementia due to AD were documented at study inception. Dementia status was also documented after three years. Four groups were created according to baseline data: never depression (nD), past depression (pD), present depression (prD), and present and past depression (prpD). Logistic regression was used. Results. Data of 1,807 subjects were investigated at baseline (mean age 74.3, 59.3% women), and 1,376 (81.6%) subjects were evaluated after three years. The prevalence of dementia at baseline was 6.7%, and dementia incidence was 6.3%. An effect of depression was observed on dementia prevalence (OR [CI 95%] 1.84 [1.01-3.35] for prD and 2.73 [1.08-6.87] for prpD), and on dementia due to AD (OR 1.98 [0.98-3.99] for prD and OR 3.98 [1.48-10.71] for prpD) (fully adjusted models, nD as reference). Depression did not influence dementia incidence. Conclusions. Present depression and, particularly, present and past depression are associated with dementia at old age. Multiple mechanisms, including toxic effect of depression on hippocampal neurons, plausibly explain these associations.

Obesity and impaired cognitive functioning in the elderly: a population-based cross-sectional study (NEDICES).

BACKGROUND AND PURPOSE: Studies of high body mass index (BMI) and cognition in the elderly have shown conflicting results. While some studies have shown a detrimental effect of high BMI on cognitive function, others have observed beneficial effects on cognition. Our aim was to assess cognitive function in a large population-based sample of overweight (BMI 25-29.9 kg/m(2) ) and obese (BMI ≥ 30 kg/m(2) ) community-dwelling elderly participants compared with their counterparts with BMI < 25 kg/m(2) (i.e. controls) living in the same population. METHODS: One-thousand nine-hundred and forty-nine population-dwelling participants aged ≥ 65 years in central Spain [the Neurological Diseases in Central Spain study (NEDICES)] underwent a neuropsychological assessment, including tests of global cognitive performance [measured with a 37-item version of the Mini-Mental State Examination (37-MMSE)], psychomotor speed, verbal fluency, memory and pre-morbid intelligence. RESULTS: There were 507 with BMI < 25 kg/m(2) , 850 overweight and 592 obese participants. In regression analyses that adjusted for age, gender, educational category, intake of medications that potentially affect cognition function, diabetes mellitus, hypertension, dementia, ever smoker, ever drinker and waist circumference, we found that obese/overweight status was associated with the lowest quartiles of the 37-MMSE, Trail Making Test-A (number of errors; indeed more errors), verbal fluency, delayed free recall, immediate logical memory and pre-morbid intelligence. CONCLUSIONS: In this large population sample, overweight and obese participants performed poorer on formal neuropsychological tests than their counterparts with BMI < 25 kg/m(2) . These results support the hypothesis of a detrimental effect of high BMI on impaired cognition in the elderly.

Frailty in elderly persons with essential tremor: a population-based study (NEDICES).

BACKGROUND AND PURPOSE: Essential tremor (ET), one of the most prevalent neurological diseases, has been associated with a variety of comorbidities and, in some studies, a modest increase in risk of mortality. The mechanisms underlying this possible increased mortality have yet to be explored, although one possibility is increased frailty. Frailty has not been studied in ET, and our objective was to address this gap in knowledge. We hypothesized that frailty would be greater in ET cases than in controls. METHODS: A 20-item frailty score assessed comorbid conditions, number of medications, and functional activity. The frailty score was compared in 237 non-demented elderly ET cases and 3903 non-demented age-matched controls from a population-based study in central Spain. RESULTS: The frailty score was higher in ET cases than in controls (8.6 ± 5.2 vs. 6.8 ± 4.6, P < 0.001). Stratifying the frailty score into quartiles and tertiles similarly revealed case-control differences (both P < 0.001). The frailty score also increased with age (r = 0.25, P < 0.001), was higher in women than men (P = 0.02), was correlated with subjective rating of health status (r = 0.42, P < 0.001), and was inversely correlated with body weight (r = -0.06, P < 0.001) and hours/day that participants performed moderate or intensive physical activities (r = -0.16, P < 0.001). CONCLUSION: Essential tremor cases had increased frailty compared to their counterparts without this disease. Whether this increased frailty is a contributor to the increased risk of mortality that has been observed in some studies is a question that deserves further scrutiny.

Revista de Neurología y la neurología española / Revista de Neurología and the Spanish neurology

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Prevalence and European comparison of dementia in a ≥75-year-old composite population in Spain.

OBJECTIVES: To estimate dementia prevalence in Spain. MATERIALS AND METHODS: Nine probabilistic and geographically defined samples participated. A screening design based on the MMSE was implemented. Positively screened individuals underwent clinical evaluation. The total number of cases in Spain was estimated. Prevalence was confronted to that of other European countries. RESULTS: Five hundred and forty-six persons aged ≥75 participated, 49 had dementia (35 with Alzheimer's disease [AD], 10 with vascular dementia [VD], 4 other; 25 first diagnosed in the study). Age- and sex-adjusted prevalence and estimated nationwide cases were 7.5% (95% CI 5.4-9.7), 5.6 (95% CI 3.7-7.5) and 1.4 (95% CI 0.5-2.3), and 290,000 (95% CI 208,000-372,000), 214,000 (95% CI 141,000-288,000) and 54,000 (95% CI 20,000-88,000) for dementia, AD and VD, respectively. CONCLUSIONS: Dementia prevalence in Spain is comparable to other European populations, while a high number of undiagnosed cases live in the community. The potential impact of Mediterranean diet, hypertension control and decreasing vascular risk factors is discussed.

[The effect of donepezil in comparison with conventional treatment on cognitive functioning and the performance of the patient in a prospective cohort of patients with Alzheimer's disease treated in routine clinical practice in Spain]. / Efecto del donepecilo comparado con el tratamiento convencional en la funcion cognitiva y el rendimiento del paciente en una cohorte prospectiva de pacientes con enfermedad de Alzheimer tratados en la practica clinica habitual en Espana.

AIMS: Our aim was to perform a secondary analysis of a 12-month-long, non-blind, multi-centre prospective cost-of-illness study. The analysis assessed the effect of donepezil on cognitive functioning and the performance of patients with possible or probable Alzheimer's disease, compared to that of other drugs for dementia. PATIENTS AND METHODS: A sample of 700 patients took part in the study (76.8 ± 6.6 years of age, 67.3% females): 600 (31.4% drug-naive) received donepezil and 100 (9% drug-naive) were given other drugs for dementia. RESULTS: The mean variations corrected by the baseline values and the centre of the total scores on the Folstein minimental test, the clinical dementia rating and Blessed dementia rating scales at 12 months were significantly lower in patients treated with donepezil: -1.23 ± 3.41 versus -2.26 ± 3.07 (p = 0.006), 0.20 ± 0.68 versus 0.39 ± 1.03 (p = 0.014) and 1.28 ± 3.31 versus 2.04 ± 2.84 (p = 0.027), respectively. CONCLUSIONS: This secondary analysis shows that the deterioration in the cognitive functioning and performance of patients with the passage of time is slower with donepezil than with other drugs for dementia in routine medical practice. Since these results were observed in a post hoc analysis, formal prospective clinical trials should be conducted to confirm these findings.