Superagers Resist Typical Age-Related White Matter Structural Changes.

Superagers are elderly individuals with the memory ability of people 30 years younger and provide evidence that age-related cognitive decline is not inevitable. In a sample of 64 superagers (mean age, 81.9; 59% women) and 55 typical older adults (mean age, 82.4; 64% women) from the Vallecas Project, we studied, cross-sectionally and longitudinally over 5 years with yearly follow-ups, the global cerebral white matter status as well as region-specific white matter microstructure assessment derived from diffusivity measures. Superagers and typical older adults showed no difference in global white matter health (total white matter volume, Fazekas score, and lesions volume) cross-sectionally or longitudinally. However, analyses of diffusion parameters revealed the better white matter microstructure in superagers than in typical older adults. Cross-sectional differences showed higher fractional anisotropy (FA) in superagers mostly in frontal fibers and lower mean diffusivity (MD) in most white matter tracts, expressed as an anteroposterior gradient with greater group differences in anterior tracts. FA decrease over time is slower in superagers than in typical older adults in all white matter tracts assessed, which is mirrored by MD increases over time being slower in superagers than in typical older adults in all white matter tracts except for the corticospinal tract, the uncinate fasciculus, and the forceps minor. The better preservation of white matter microstructure in superagers relative to typical older adults supports resistance to age-related brain structural changes as a mechanism underpinning the remarkable memory capacity of superagers, while their regional aging pattern is in line with the last-in-first-out hypothesis.

Validez discriminante y concordancia interobservador de 2 métodos de puntuación del test del reloj / Discriminant validity and inter-rater concordance of two scoring systems for the clock test

Objetivos Comparar la validez discriminante y la fiabilidad interobservador de los 2 métodos de corrección del test del reloj más usados en España. Metodología Se han evaluado 2 colecciones de dibujos del reloj obtenidos en un contexto clínico (116 casos; 56,8% mujeres, edad media 73,1±7,7 años) y en una cohorte de voluntarios (2.039 dibujos de 579 sujetos; 59,5% mujeres, edad media 78,3±3,8 años). Todos los sujetos fueron clasificados como sin deterioro cognitivo (DC−) o con deterioro cognitivo (DC+) tras una extensa evaluación clínica y neuropsicológica. Evaluadores expertos han valorado estos dibujos de forma independiente y sin conocimiento del diagnóstico con los métodos de Sunderland y Solomon estandarizados en español por Cacho (rango: 0 a 10) y del Ser (rango: 0 a 7), respectivamente. Se ha calculado la validez discriminante de cada método mediante el área bajo la curva ROC (aROC) en las 2 muestras, y la fiabilidad interobservador mediante el coeficiente de correlación intraclase (CCI) y el coeficiente kappa en la muestra clínica que fue valorada por los 2 evaluadores. Resultados No hay diferencias significativas en la validez discriminante de los métodos de Sunderland y Solomon en ninguna de las muestras (clínica: aROC: 0,73 [IC 95%: 0,64-0,81] y 0,77 [IC 95%: 0,69-0,85], respectivamente, p=0,19; voluntarios: aROC: 0,69 [IC 95%: 0,67-0,71] y 0,72 [IC 95%: 0,69-0,73], respectivamente, p=0,08). Los puntos de corte ≤8 y ≤5 clasifican correctamente al 71 y 73% de la muestra clínica y al 82 y 84% de la muestra de voluntarios, respectivamente. Los 2 métodos tienen una buena concordancia en la muestra clínica (AU)

Objective To compare the discriminant validity and inter-rater reliability of the two scoring systems for the Clock test that are most used in Spain. Methodology Two collections of clock drawings obtained in a clinical context (116 cases; 56.8% women, mean age 73.1±7.7 years) and in a cohort of volunteers (2039 drawings of 579 subjects; 59.5% women, mean age 78.3±3.8 years) have been assessed. All subjects were classified as cognitively normal (CN) or cognitively impaired (CI) after extensive clinical and neuropsychological evaluation. Expert raters have evaluated these drawings independently and without knowledge of the diagnosis using the Sunderland and Solomon systems standardized in Spanish by Cacho (range 0 to 10) and del Ser (range 0 to 7) respectively. The discriminant validity of each method was calculated in the two samples using the area under the ROC curve (aROC), and the inter-rater reliability was calculated in the clinical sample, that was assessed by the two evaluators, using the intraclass correlation coefficient (ICC) and the kappa coefficient. Results There are no significant differences in the discriminant validity of the Sunderland and Solomon systems in any of the samples (clinical: aROC 0.73 [CI95%: 0.64-0.81] and 0.77 [CI95%: 0.69-0.85] respectively, P=.19; volunteers: aROC 0.69 [CI95%: 0.67-0.71] and 0.72 [CI95%: 0.69-0.73] respectively, P=.08). The cut-off points ≤8 and ≤5 correctly classify 71% and 73% of the clinical sample and 82% and 84% of the volunteer sample, respectively. Both systems have good agreement in the clinical sample (Sunderland: ICC 0.90 [CI95%: 0.81-0.93], kappa 0.76 [CI95%: 0.70-0.83]; Solomon: 0.92 [CI95%: 0.88-0.95] and 0.77 [CI95%: 0.71-0.83] respectively), somewhat higher in the second, although the differences are not significant (AU)

[Discriminant validity and inter-rater concordance of two scoring systems for the clock test]. / Validez discriminante y concordancia interobservador de 2 métodos de puntuación del test del reloj.

OBJECTIVE: To compare the discriminant validity and inter-rater reliability of the two scoring systems for the Clock test that are most used in Spain. METHODOLOGY: Two collections of clock drawings obtained in a clinical context (116 cases; 56.8% women, mean age 73.1±7.7 years) and in a cohort of volunteers (2039 drawings of 579 subjects; 59.5% women, mean age 78.3±3.8 years) have been assessed. All subjects were classified as cognitively normal (CN) or cognitively impaired (CI) after extensive clinical and neuropsychological evaluation. Expert raters have evaluated these drawings independently and without knowledge of the diagnosis using the Sunderland and Solomon systems standardized in Spanish by Cacho (range 0 to 10) and del Ser (range 0 to 7) respectively. The discriminant validity of each method was calculated in the two samples using the area under the ROC curve (aROC), and the inter-rater reliability was calculated in the clinical sample, that was assessed by the two evaluators, using the intraclass correlation coefficient (ICC) and the kappa coefficient. RESULTS: There are no significant differences in the discriminant validity of the Sunderland and Solomon systems in any of the samples (clinical: aROC 0.73 [CI95%: 0.64-0.81] and 0.77 [CI95%: 0.69-0.85] respectively, P=.19; volunteers: aROC 0.69 [CI95%: 0.67-0.71] and 0.72 [CI95%: 0.69-0.73] respectively, P=.08). The cut-off points ≤8 and ≤5 correctly classify 71% and 73% of the clinical sample and 82% and 84% of the volunteer sample, respectively. Both systems have good agreement in the clinical sample (Sunderland: ICC 0.90 [CI95%: 0.81-0.93], kappa 0.76 [CI95%: 0.70-0.83]; Solomon: 0.92 [CI95%: 0.88-0.95] and 0.77 [CI95%: 0.71-0.83] respectively), somewhat higher in the second, although the differences are not significant. CONCLUSIONS: The discriminant validity and inter-observer reliability of these two Clock Test correction systems are similar. Solomon's method, shorter and simpler, may be more advisable in pragmatic terms.

Using Explainable Artificial Intelligence in the Clock Drawing Test to Reveal the Cognitive Impairment Pattern.

The prevalence of dementia is currently increasing worldwide. This syndrome produces a deterioration in cognitive function that cannot be reverted. However, an early diagnosis can be crucial for slowing its progress. The Clock Drawing Test (CDT) is a widely used paper-and-pencil test for cognitive assessment in which an individual has to manually draw a clock on a paper. There are a lot of scoring systems for this test and most of them depend on the subjective assessment of the expert. This study proposes a computer-aided diagnosis (CAD) system based on artificial intelligence (AI) methods to analyze the CDT and obtain an automatic diagnosis of cognitive impairment (CI). This system employs a preprocessing pipeline in which the clock is detected, centered and binarized to decrease the computational burden. Then, the resulting image is fed into a Convolutional Neural Network (CNN) to identify the informative patterns within the CDT drawings that are relevant for the assessment of the patient's cognitive status. Performance is evaluated in a real context where patients with CI and controls have been classified by clinical experts in a balanced sample size of [Formula: see text] drawings. The proposed method provides an accuracy of [Formula: see text] in the binary case-control classification task, with an AUC of [Formula: see text]. These results are indeed relevant considering the use of the classic version of the CDT. The large size of the sample suggests that the method proposed has a high reliability to be used in clinical contexts and demonstrates the suitability of CAD systems in the CDT assessment process. Explainable artificial intelligence (XAI) methods are applied to identify the most relevant regions during classification. Finding these patterns is extremely helpful to understand the brain damage caused by CI. A validation method using resubstitution with upper bound correction in a machine learning approach is also discussed.

Applicability of Echocardiographic Strict Negative Criteria for Suspected Infective Endocarditis.

Echocardiography is the cornerstone imaging technique in the diagnosis of infective endocarditis (IE) but is often misused in clinical practice. Recently, strict negative criteria have been proposed to avoid unnecessary follow-up echocardiograms. We aimed to evaluate the use of echocardiography in real-world clinical daily practice and the usefulness of these criteria in the diagnosis of IE. We retrospectively retrieved every echocardiogram performed in our center for suspected IE between 2014 and 2018, including 905 transthoracic echocardiograms (TTEs). Of these, 451 (49.8%) fulfilled the strict negative criteria (group 1). In this group, IE was seldom diagnosed (n = 4, 0.9%). In 338 patients (37.4%) no signs of IE were evident, but they did not fulfill the strict negative criteria (group 2). A follow-up echocardiogram and definitive diagnosis of IE were more frequent (n = 48, 14.2% and n = 20, 5.9%). Finally, in 116 patients (12.8%) the initial TTE showed typical or suggestive signs of IE, in whom the diagnosis was confirmed in 48 patients (41.4%). A definitive diagnosis of IE was established in a minority of the study population (n = 72, 8%). Only 1 readmission for underdiagnosis of IE was noted on group 2. We conclude that in a real-life setting only a minority of patients in whom IE was suspected had a definitive diagnosis. An initial TTE for suspected IE fulfilling the strict negative criteria predicts both a low probability of requesting a follow-up study and of a definitive diagnosis of IE.

MADRID+90 study on factors associated with longevity: Study design and preliminary data.

The progressive aging of the population represents a challenge for society. In particular, a strong increase in the number of people over 90 is expected in the next two decades. As this phenomenon will lead to an increase in illness and age-related dependency, the study of long-lived people represents an opportunity to explore which lifestyle factors are associated with healthy aging and which with the emergence of age-related diseases, especially Alzheimer's type dementia. The project "Factors associated with healthy and pathologically aging in a sample of elderly people over 90 in the city of Madrid" (MADRID+90) brings together a multidisciplinary research team in neurodegenerative diseases that includes experts in epidemiology, neurology, neuropsychology, neuroimaging and computational neuroscience. In the first phase of the project, a stratified random sampling was carried out according to the census of the city of Madrid followed by a survey conducted on 191 people aged 90 and over. This survey gathered information on demographics, clinical data, lifestyles and cognitive status. Here, the main results of that survey are showed. The second phase of the project aims to characterize individual trajectories in the course of either healthy and pathological aging, from a group of 50 subjects over 90 who will undergo a comprehensive clinical examination comprised of neurological and cognitive testing, MRI and EEG. The ultimate goal of the project is to characterize the biophysical and clinical profiles of a population that tends to receive little attention in the literature. A better understanding of the rapidly increasing group of nonagenarians will also help to design new policies that minimize the impact and future social and economic consequences of rapidly aging societies.

Impact of individual and neighborhood dimensions of socioeconomic status on the prevalence of mild cognitive impairment over seven-year follow-up.

Objectives: There is strong evidence about the association between low socioeconomic status (SES) and higher risk of dementia. However, it has not been conveniently addressed so far the role of SES on the incidence of mild cognitive impairment (MCI). This study examines the impact of individual and neighbourhood dimensions of SES, as well as their interaction, on the risk of developing MCI in a sample of older adults.Method: Data from the Vallecas Project cohort, an ongoing community-based longitudinal study for early detection of cognitive impairment and dementia, were used to build two indices of SES namely individual and neighbourhood, as well as a global SES as a combination of both, and to investigate their effects on MCI conversion by means of a multivariate-adjusted Cox proportional hazard model.Results: A total of 1180 participants aged 70 years and older were enrolled in this study. Of these, 199 cases of MCI (16.9%) were diagnosed at any point of the follow-up. The individual and neighbourhood dimensions of SES played different roles in the dynamics of the MCI occurrence through aging. Most importantly, the risk of developing MCI was almost double for lower SES quartiles when compared to the highest one.Conclusion: The incidence of MCI in older adults was related to both individual characteristics and socioeconomic context. Public health strategies should be holistic and focus not only on promoting the classical individual preventive measures, but also on reducing social inequalities to foster healthy aging and reduce dementia burden.

Efecto pronóstico diferencial de la diabetes mellitus tipo 2 en mujeres y varones con insuficiencia cardiaca y fracción de eyección conservada / Differential prognostic impact of type 2 diabetes mellitus in women and men with heart failure with preserved ejection fraction

INTRODUCCIÓN Y OBJETIVOS: La diabetes mellitus tipo 2 (DM2) es una comorbilidad común en pacientes con insuficiencia cardiaca (IC) con fracción de eyección conservada (ICFEP). Estudios anteriores han demostrado que las mujeres diabéticas tienen mayor riesgo de desarrollar insuficiencia cardiaca que los hombres. Sin embargo, el pronóstico a largo plazo de los pacientes diabéticos con insuficiencia cardiaca en función del sexo no se ha explorado ampliamente. En este estudio, nuestro objetivo fue evaluar el impacto diferencial de la DM2 en la mortalidad por todas las causas en hombres frente a mujeres con ICFEP tras un ingreso por IC aguda. MÉTODOS: Se incluyeron prospectivamente 1.019 pacientes consecutivos con ICFEP dados de alta tras un episodio de IC aguda en hospital terciario. Se empleó un análisis de regresión de Cox multivariante para evaluar la interacción entre el sexo y la DM2 con respecto al riesgo de mortalidad total a largo plazo. Las estimaciones de riesgo se expresaron como razones de riesgo (HR). RESULTADOS: La edad media de la cohorte fue de 75,6±9,5 años y 609 (59,8%) eran mujeres. La proporción de DM2 fue similar entre ambos sexos (45,1 frente al 49,1%; p = 0,211). Tras una mediana de seguimiento (intervalo intercuartílico) de 3,6 (1-4-6,8) años, 646 (63,4%) pacientes murieron. Tras ajustar por factores de riesgo, comorbilidades, biomarcadores, parámetros ecográficos y tratamiento al alta, el análisis multivariate mostró un efecto pronóstico diferencial de DM2 (valor de p para la interacción=0,007). La DM2 se asoció con un mayor riesgo de mortalidad por todas las causas en mujeres (HR=1,77; IC95%, 1,41-2,21; p < 0,001) pero no en varones (HR=1,23; IC95%, 0,94-1,61; p = 0,127). CONCLUSIONES: Tras un episodio de IC aguda en pacientes con ICFEF, la DM2 confiere un mayor riesgo de mortalidad en las mujeres. Se requieren más estudios que evalúen el impacto de la DM2 en mujeres con ICFEP

INTRODUCTION AND OBJECTIVES: Type 2 diabetes mellitus (DM2) is a common comorbidity in patients with heart failure (HF) with preserved ejection fraction (HFpEF). Previous studies have shown that diabetic women are at higher risk of developing HF than men. However, the long-term prognosis of diabetic HFpEF patients by sex has not been extensively explored. In this study, we aimed to evaluate the differential impact of DM2 on all-cause mortality in men vs women with HFpEF after admission for acute HF. METHODS: We prospectively included 1019 consecutive HFpEF patients discharged after admission for acute HF in a single tertiary referral hospital. Multivariate Cox regression analysis was used to evaluate the interaction between sex and DM2 regarding the risk of long-term all-cause mortality. Risk estimates were calculated as hazard ratios (HR). RESULTS: The mean age of the cohort was 75.6±9.5 years and 609 (59.8%) were women. The proportion of DM2 was similar between sexes (45.1% vs 49.1%, P=.211). At a median (interquartile range) follow-up of 3.6 (1-4-6.8) years, 646 (63.4%) patients died. After adjustment for risk factors, comorbidities, biomarkers, echo parameters and treatment at discharge, multivariate analysis showed a differential prognostic effect of DM2 (P value for interaction=.007). DM2 was associated with a higher risk of all-cause mortality in women (HR, 1.77; 95%CI, 1.41-2.21; P<.001) but not in men (HR, 1.23; 95%CI, 0.94-1.61; P=.127). CONCLUSIONS: After an episode of acute HF in HFpEF patients, DM2 confers a higher risk of mortality in women. Further studies evaluating the impact of DM2 in women with HFpEF are warranted

CA125 outperforms NT-proBNP in acute heart failure with severe tricuspid regurgitation.

BACKGROUND: In acute heart failure (AHF) with right ventricular dysfunction, the roles of amino-terminal pro-brain natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) are poorly understood, and functional tricuspid regurgitation (TR) severity is thought to indicate a poor prognosis. We examined the prognostic abilities of NT-proBNP and CA125 according to TR status among patients with AHF. METHODS: TR severity was assessed during index hospitalization (108 ± 24 h after admission) and classified as none/trivial, mild, moderate, or severe. Multivariable Cox regression analysis was performed to assess how pre-discharge CA125 and NT-proBNP were associated with long-term all-cause mortality relative to TR severity. RESULTS: We prospectively included 2961 patients discharged following hospitalization for AHF (mean age 74 ± 11 years; 49.0% women; 51.8% with left ventricular ejection fraction >50%). Median NT-proBNP was 4823 ng/L (IQR: 2086-9183) and CA125 was 58.1 U/mL (IQR: 25-129). Severe TR was present in 300 patients (10.1%), and 1821 patients (61.5%) died (mean follow-up, 3.3 ± 3.2 years). Multivariate analysis revealed a differential prognostic effect across TR status for both biomarkers (p-value for both interactions<0.05). NT-proBNP was significantly linearly associated with mortality in non-severe TR (p < 0.001), but not in severe TR (p = 0.308). Higher CA125 values were significantly associated with mortality risk in all patients (HR: 1.09; 95% CI:1.03-1.14; p = 0.001), with a greater effect in those with severe TR (HR: 1.28; 98% CI:1.11-1.48; p = 0.001). CONCLUSIONS: In patients with AHF and severe TR, CA125 outperforms NT-proBNP in predicting long-term mortality. In AHF with right ventricular involvement, CA125 may be the preferred biomarker for risk stratification.

Differential prognostic impact of type 2 diabetes mellitus in women and men with heart failure with preserved ejection fraction.

INTRODUCTION AND OBJECTIVES: Type 2 diabetes mellitus (DM2) is a common comorbidity in patients with heart failure (HF) with preserved ejection fraction (HFpEF). Previous studies have shown that diabetic women are at higher risk of developing HF than men. However, the long-term prognosis of diabetic HFpEF patients by sex has not been extensively explored. In this study, we aimed to evaluate the differential impact of DM2 on all-cause mortality in men vs women with HFpEF after admission for acute HF. METHODS: We prospectively included 1019 consecutive HFpEF patients discharged after admission for acute HF in a single tertiary referral hospital. Multivariate Cox regression analysis was used to evaluate the interaction between sex and DM2 regarding the risk of long-term all-cause mortality. Risk estimates were calculated as hazard ratios (HR). RESULTS: The mean age of the cohort was 75.6±9.5 years and 609 (59.8%) were women. The proportion of DM2 was similar between sexes (45.1% vs 49.1, P=.211). At a median (interquartile range) follow-up of 3.6 (1-4-6.8) years, 646 (63.4%) patients died. After adjustment for risk factors, comorbidities, biomarkers, echo parameters and treatment at discharge, multivariate analysis showed a differential prognostic effect of DM2 (P value for interaction=.007). DM2 was associated with a higher risk of all-cause mortality in women (HR, 1.77; 95%CI, 1.41-2.21; P <.001) but not in men (HR, 1.23; 95%CI, 0.94-1.61; P=.127). CONCLUSIONS: After an episode of acute HF in HFpEF patients, DM2 confers a higher risk of mortality in women. Further studies evaluating the impact of DM2 in women with HFpEF are warranted.

Functional tricuspid regurgitation and recurrent admissions in patients with acute heart failure.

BACKGROUND: Functional tricuspid regurgitation (TR) is a common echocardiographic finding in patients with heart failure (HF), and its role in disease progression and prognosis stratification is becoming increasingly relevant in recent years. However, data regarding its association with the burden of HF-readmission is scarce. In this work, we sought to evaluate the association between TR severity and HF-related readmissions following a hospitalization for acute heart failure (AHF). METHODS: We prospectively included a cohort of 2101 patients admitted with the diagnosis of AHF. TR severity was assessed using a multiparametric integrative approach, and classified as none, mild, moderate, and severe. We used negative binomial regression to identify the association between TR grade and HF-related recurrent admissions. The risk associated to severity of TR was expressed as incidence rate ratio (IRR). RESULTS: At a median follow-up of 2.53 years (IQR: 1.03-4.36), 978 (46.5%) patients died, and 1657 HF-readmissions occurred in 842 patients (40.0%). The proportion of patients with two or more admissions was 18.4%. The proportion of patients with moderate to severe TR was 17.2%. There was a stepwise increase in the incidence of readmissions from none to severe TR. After multivariable adjustment, only patients with severe TR were independently associated with higher risk of recurrent HF admissions (IRR = 1.34, CI 95%: 1.05-1.71; p = .019). CONCLUSIONS: In patients with AHF, severe functional TR is independently associated with an increased risk of long-term recurrent HF hospitalizations.

Comorbidity assessment for mortality risk stratification in elderly patients with acute coronary syndrome.

BACKGROUND: The Charlson's is the most used comorbidity index. It comprises 19 comorbidities, some of which are infrequent in elderly patients with acute coronary syndrome (ACS), while some others are manifestations of cardiac disease rather than comorbidities. Our goal was to simplify comorbidity assessment in elderly non-ST-segment elevation ACS patients. METHODS: The study group consisted of 1 training (n = 920, 76 ±â€¯7 years) and 1 testing (n = 532; 84 ±â€¯4 years) cohorts. The end-point was all-cause mortality at 1-year follow-up. Comorbidities were assessed selecting those medical disorders other than cardiac disease that were independently associated with mortality by multivariable analysis. RESULTS: A total of 130 (14%) patients died in the training cohort. Six comorbidities were predictive: renal failure, anemia, diabetes, peripheral artery disease, cerebrovascular disease and chronic lung disease. The increase in the number of comorbidities yielded a gradient of risk on top of well-known clinical predictors: ≥3 comorbidities (27% mortality, HR = 1.90, 95% CI 1.20-3.03, p = .006); 2 comorbidities (16% mortality, HR = 1.29, 95% CI 0.81-2.04, p = .30); and 0-1 comorbidities (7.6% mortality, reference category). The discrimination accuracy (C-statistic = 0.80) and calibration (Hosmer-Lemeshow test, p = .20) of the predictive model using the 6 comorbidities was comparable to the predictive model using the Charlson index (C-statistic = 0.80; Hosmer-Lemeshow test, p = .70). Similar results were reproduced in the testing cohort (≥3 comorbidities: 24% mortality, HR = 2.37, 95% CI 1.25-4.49, p = .008; 2 comorbidities: 14% mortality, HR = 1.59, 95% CI 0.82-3.07, p = .20; 0-1 comorbidities: 7.5% reference category). CONCLUSION: A simplified comorbidity assessment comprising 6 comorbidities provides useful risk stratification in elderly patients with ACS.

Social robots in advanced dementia.

AIMS: Pilot studies applying a humanoid robot (NAO), a pet robot (PARO) and a real animal (DOG) in therapy sessions of patients with dementia in a nursing home and a day care center. METHODS: In the nursing home, patients were assigned by living units, based on dementia severity, to one of the three parallel therapeutic arms to compare: CONTROL, PARO and NAO (Phase 1) and CONTROL, PARO, and DOG (Phase 2). In the day care center, all patients received therapy with NAO (Phase 1) and PARO (Phase 2). Therapy sessions were held 2 days per week during 3 months. Evaluation, at baseline and follow-up, was carried out by blind raters using: the Global Deterioration Scale (GDS), the Severe Mini Mental State Examination (sMMSE), the Mini Mental State Examination (MMSE), the Neuropsychiatric Inventory (NPI), the Apathy Scale for Institutionalized Patients with Dementia Nursing Home version (APADEM-NH), the Apathy Inventory (AI) and the Quality of Life Scale (QUALID). Statistical analysis included descriptive statistics and non-parametric tests performed by a blinded investigator. RESULTS: In the nursing home, 101 patients (Phase 1) and 110 patients (Phase 2) were included. There were no significant differences at baseline. The relevant changes at follow-up were: (Phase 1) patients in the robot groups showed an improvement in apathy; patients in NAO group showed a decline in cognition as measured by the MMSE scores, but not the sMMSE; the robot groups showed no significant changes between them; (Phase 2) QUALID scores increased in the PARO group. In the day care center, 20 patients (Phase 1) and 17 patients (Phase 2) were included. The main findings were: (Phase 1) improvement in the NPI irritability and the NPI total score; (Phase 2) no differences were observed at follow-up.

Efecto de los fármacos anticolinérgicos en el rendimiento cognitivo de las personas mayores / Effect of anticholinergic drugs on cognitive impairment in the elderly

El empleo de fármacos anticolinérgicos es frecuente en personas mayores, incluso con deterioro cognitivo. Se ha realizado una revisión bibliográfica en PubMed (anticholinergic effects y anticholinergic and dementia) acerca de los efectos de los fármacos anticolinérgicos en población anciana. Se ha enfatizado en determinar patrones de consumo, uso combinado con fármacos inhibidores de la acetilcolinesterasa (IACE), medida de la carga anticolinérgica y efectos cognitivos a corto y a largo plazo. Las conclusiones son que estos fármacos se emplean de forma habitual en población anciana, incluso tras la prescripción de IACE en la enfermedad de Alzheimer. Su empleo puede producir alteraciones cognitivas. Si el consumo es prolongado puede provocar un empeoramiento de la cognición a largo plazo originando falsos diagnósticos de deterioro, o incluso precipitando cuadros de demencia. Los efectos cognitivos son mayores ante un déficit preexistente, pero desaparecen en la demencia avanzada. La presencia de ApoE ¿4 marca una vulnerabilidad a la afectación cognitiva por estos fármacos (AU)

The use of anticholinergic drugs is common in the elderly, even in people with cognitive impairment. A systematic search was conducted in PubMed (anticholinergic effects, anticholinergic and dementia) to define the effects of anticholinergic drugs in the elderly. We emphasized the search in patterns of use, the combined use with AChEIs, the measurement of the Serum Anticholinergic Activity, and the short-term and long-term cognitive effects. The conclusions are that the use of anticholinergic drugs is common in the elderly, even more so than the medical prescription of AChEIs in Alzheimer‘s disease. The use of anticholinergic drugs may result in cognitive impairment. In long-term use it may generate a worsening of cognitive functions. It can lead to a wrong diagnosis of mild cognitive impairment or dementia, and they can also initiate signs of dementia. Greater cognitive effects appear when there is a previous deficit, but cognitive effects from anticholinergic drugs disappear in severe dementia. The presence of ApoE ¿4 increases the vulnerability for cognitive impairment when these drugs are employed (AU)

A blood-based, 7-metabolite signature for the early diagnosis of Alzheimer's disease.

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.

A novel rating scale for the measurement of apathy in institutionalized persons with dementia: the APADEM-NH.

OBJECTIVE: Apathy is one of the most frequent symptoms of dementia, still needing better measurement methods. The objective of this study was to validate a new scale for apathy in institutionalized persons with dementia (APADEM-NH). METHODS: The scale includes 26 items distributed in three dimensions: Deficit of Thinking and Self-Generated behaviors (DT): 13 items, Emotional Blunting (EB): 7 items, and Cognitive Inertia (CI): 6 items. The sample included 100 institutionalized patients (90% female) with probable Alzheimer disease (AD) (57%), possible AD (13%), AD + cerebral vascular disease (17%), Lewy body dementia (11%), and Parkinson associated to dementia (2%), covering all stages of dementia severity according to the Global Deterioration Scale and Clinical Dementia Rating. Additional assessments were the Apathy Inventory, Neuropsychiatric Inventory, Cornell Scale for Depression, and the tested scale. Re-test and inter-rater reliability were carried out in 50 patients. RESULTS: All subscales lacked relevant floor and ceiling effects (<15%). Internal consistency for each dimension was (Cronbach's α): DT = 0.88, EB = 0.83, CI = 0.88; item-total correlations were >0.40; and item homogeneity 0.36-0.51. Test-retest reliability for the items was kW = 0.48-0.92; for the subscales, intraclass correlation coefficient (ICC) = 0.80-0.88; and for the total score, ICC = 0.90. Inter-rater reliability reached kW values of 0.84-1.00; subscales ICC, 0.97-0.99, and total score ICC, 0.99. Standard error of measurement for total score was 6.41 and internal validity ranged from rS = 0.69-0.80. CONCLUSIONS: APADEM-NH proved to be feasible, reliable, and valid for apathy assessment in institutionalized patients suffering mild to severe dementia, discerning well between apathy and depression.

[Effect of anticholinergic drugs on cognitive impairment in the elderly]. / Efecto de los fármacos anticolinérgicos en el rendimiento cognitivo de las personas mayores.

The use of anticholinergic drugs is common in the elderly, even in people with cognitive impairment. A systematic search was conducted in PubMed (anticholinergic effects, anticholinergic and dementia) to define the effects of anticholinergic drugs in the elderly. We emphasized the search in patterns of use, the combined use with AChEIs, the measurement of the Serum Anticholinergic Activity, and the short-term and long-term cognitive effects. The conclusions are that the use of anticholinergic drugs is common in the elderly, even more so than the medical prescription of AChEIs in Alzheimer's disease. The use of anticholinergic drugs may result in cognitive impairment. In long-term use it may generate a worsening of cognitive functions. It can lead to a wrong diagnosis of mild cognitive impairment or dementia, and they can also initiate signs of dementia. Greater cognitive effects appear when there is a previous deficit, but cognitive effects from anticholinergic drugs disappear in severe dementia. The presence of ApoEɛ4 increases the vulnerability for cognitive impairment when these drugs are employed.

Quality of life (QoL) in community-dwelling and institutionalized Alzheimer's disease (AD) patients.

The purpose of this study was to describe and compare QoL and its determinants in two groups of patients with AD that differed in place of residence: community or nursing home. This study covered 200 patients with AD (mean age 79.3 ± 8.2 years, 74% female). Fifty-four per cent of the subjects were living in a nursing home and 46% lived at home. QoL was measured using the Alzheimer's Disease Related Quality of Life Scale (ADRQL). The ADRQL was answered by the family caregiver (community group) or the professional caregiver (nursing home group). Descriptive statistics, Chi-square test, Mann-Whitney test and multiple regression analysis were used to compare sociodemographic and clinical variables between the two study groups. The institutionalized patients were predominantly women (87.0% vs. 58.7%, p<0.001), were older (84 years vs. 74 years, p<0.001), and had more advanced dementia (Global Deterioration Scale (GDS)>5 79.6% vs. 19.6%, p<0.001). ADRQL total score was higher (i.e., better QoL) for patients living at home than for institutionalized patients (72.6 ± 19.9 vs. 64.8 ± 18.2, p<0.01). Neuropsychiatric symptoms, severity of dementia, depression and functional dependence were significant predictors of worst QoL. Once those variables were controlled a marginal effect of setting on QoL was found, which favored the nursing home (ß=0.20, p<0.05).