Intelligent digital tools for screening of brain connectivity and dementia risk estimation in people affected by mild cognitive impairment: the AI-Mind clinical study protocol.

More than 10 million Europeans show signs of mild cognitive impairment (MCI), a transitional stage between normal brain aging and dementia stage memory disorder. The path MCI takes can be divergent; while some maintain stability or even revert to cognitive norms, alarmingly, up to half of the cases progress to dementia within 5 years. Current diagnostic practice lacks the necessary screening tools to identify those at risk of progression. The European patient experience often involves a long journey from the initial signs of MCI to the eventual diagnosis of dementia. The trajectory is far from ideal. Here, we introduce the AI-Mind project, a pioneering initiative with an innovative approach to early risk assessment through the implementation of advanced artificial intelligence (AI) on multimodal data. The cutting-edge AI-based tools developed in the project aim not only to accelerate the diagnostic process but also to deliver highly accurate predictions regarding an individual's risk of developing dementia when prevention and intervention may still be possible. AI-Mind is a European Research and Innovation Action (RIA H2020-SC1-BHC-06-2020, No. 964220) financed between 2021 and 2026. First, the AI-Mind Connector identifies dysfunctional brain networks based on high-density magneto- and electroencephalography (M/EEG) recordings. Second, the AI-Mind Predictor predicts dementia risk using data from the Connector, enriched with computerized cognitive tests, genetic and protein biomarkers, as well as sociodemographic and clinical variables. AI-Mind is integrated within a network of major European initiatives, including The Virtual Brain, The Virtual Epileptic Patient, and EBRAINS AISBL service for sensitive data, HealthDataCloud, where big patient data are generated for advancing digital and virtual twin technology development. AI-Mind's innovation lies not only in its early prediction of dementia risk, but it also enables a virtual laboratory scenario for hypothesis-driven personalized intervention research. This article introduces the background of the AI-Mind project and its clinical study protocol, setting the stage for future scientific contributions.

Complexity analysis of spontaneous brain activity in Alzheimer disease and mild cognitive impairment: an MEG study.

Nonlinear analyses have shown that Alzheimer disease (AD) patients' brain activity is characterized by a reduced complexity and connectivity. The aim of this study is to define complexity patterns of mild cognitive impairment (MCI) patients. Whole-head magnetoencephalography recordings were obtained from 18 diagnosed AD patients, 18 MCI patients, and 18 healthy controls during resting conditions. Lempel-Ziv complexity (LZC) values were calculated. MCI patients exhibited intermediary LZC scores between AD patients and controls. A combination of age and posterior LZC scores allowed ADs-MCIs discrimination with 94.4% sensitivity and specificity, whereas no LZC score allowed MCIs---controls discrimination. AD patients and controls showed a parallel tendency to diminished LZC scores as a function of age, but MCI patients did not exhibit such "normal" tendency. Accordingly, anterior LZC scores allowed MCIs-controls discrimination for subjects below 75 years. MCIs exhibited a qualitatively distinct relationship between aging and complexity reduction, with scores higher than controls in older individuals. This fact might be considered a new example of compensatory mechanism in MCI before fully established dementia.

Structural and functional patterns in healthy aging, mild cognitive impairment, and Alzheimer disease.

The aim of this study was to analyze the combined contribution of magnetic resonance imaging and magnetoencephalography (MEG) to the diagnosis of mild cognitive impairment (MCI) and AD. To whole-head MEG recordings were obtained from three diagnosis groups: Alzheimer disease (AD), MCI, and control. Magnetic resonance imaging volumetric data of global brain, temporal lobe, and hippocampal volumes, were also obtained. Results indicated that a reduction of volume in the hippocampal structure allowed the discrimination between AD and MCI patients as compared with controls. The percentage of correct classification was 91.3% when AD versus controls was compared, and 83.3% when we compared MCI versus control. MEG data showed that AD patients exhibit higher theta and delta activity than MCI and controls. Such higher activity was significant in parietal, temporal, and occipital areas. Left parietal theta classified controls versus MCIs with 78.3% rate of correct classification. Right occipital theta and the left parietal delta allowed the discrimination of controls versus ADs, with 81.8% rate of correct classification. Left parietal theta discriminated between ADs and MCIs with 56.6% rate of correct classification. In addition, the combination of both techniques significantly improved the rate of correct classification, thus indicating that a multidisciplinary perspective of techniques may improve the diagnostic capabilities.

[Prognostic value of functional assessment at admission in an emergency short-stay unit]. / Valor pronóstico de la valoración funcional al ingreso en una unidad de corta estancia de Urgencias.

INTRODUCTION: To determine the prognostic value of functional impairment on the final destination of elders admitted for acute medical illness to an emergency short-stay unit (ESSU). MATERIAL AND METHODS: We performed a prospective analysis of patients aged more than 65 years old admitted to the ESSU of Hospital Clínico San Carlos in Madrid in April 2008. A protocol was designed that included epidemiologic variables (age and gender), clinical variables (reason for admission, comorbidity measured by the Charlson Index [CI]) and functional variables (previous, admission and functional decline [FD] measured with the Barthel [BI] and Lawton Indexes [LI]). The prognostic value of FD on the decision to admit patients was analyzed through ROC curves and the cut points that maximized sensitivity and specificity were determined. RESULTS: Sixty patients were included with a mean age of 80.7 (SD 8.2) years and 71.7% were women. The reasons for admission were acute infections in 31.7%, heart failure in 23.3%, syncope in 15.0%, intestinal obstruction in 11.7%, gastrointestinal bleeding in 10.0%, and arrhythmias in 8.3%. The mean CI was 2.27 (1.45). Functional assessment was as follows: mean previous BI score: 79.25 (SD 25) and at admission: 62.92 (SD 28.19). Mean previous LI score: 4.85 (SD 2.45) and at admission: 2.98 (SD 2.42).): BI-FD: 20% (1.25-38.23), LI-FD 37.5% (16.7-70.2%). FD was found in 100% of the patients. The mean length of stay was 1.70 (SD 0.62) days. Discharge destination was home discharge in 46.7% and hospitalization unit in 53.3%. Multivariate analysis according to discharge destination (home vs hospitalization) provided the following results : BI-FI > or = 16% (OR=7.99 [1.1-60.5], p=0.037), LI-FI > or =35% (OR=19.6 [0.04-0.52], p <0.0001). CONCLUSIONS: Patients with significant FD in the emergency room should not be admitted to an ESSU since significant FD is a prognostic factor for transfer to a conventional ward.

[Oral anticoagulation therapy in the elderly population with atrial fibrillation. A review article]. / Anticoagulación en población anciana con fibrilación auricular no valvular. Artículo de revisión.

Aging is an important risk factor for patients with atrial fibrillation. The estimated prevalence of atrial fibrillation in patients aged ≥80 years is 9-10%, and is associated with a four to five fold increased risk of embolic stroke, and with an estimated increased stroke risk of 1.45-fold per decade in aging. Older age is also associated with an increased risk of major bleeding with oral anticoagulant therapy. This review will focus on the role of oral anticoagulation with new oral anticoagulants, non-vitamin K antagonist in populations with common comorbid conditions, including age, chronic kidney disease, coronary artery disease, on multiple medication, and frailty. In patients 75 years and older, randomised trials have shown new oral anticoagulants to be as effective as warfarin, or in some cases superior, with an overall better safety profile, consistently reducing rates of intracranial haemorrhages. Prior to considering oral anticoagulant therapy in an elderly frail patient, a comprehensive assessment should be performed to include the risks and benefits, stroke risk, baseline kidney function, cognitive status, mobility and fall risk, multiple medication, nutritional status assessment, and life expectancy.

[Clinical assessment and diagnostic tools]. / Evaluación clínica y herramientas diagnósticas.

The presence of cognitive impairment generates important changes in both affected individuals and their families and the health staff who must provide adequate care. Early identification of this alteration allows appropriate diagnosis and treatment and psychosocial and educational support, as well as the possibility of establishing care, life and financial plans. The interest of the scientific community in age-related cognitive alterations is demonstrated by the abundance of criteria and classifications. Obviously, there is a need to unify these criteria and implement longitudinal studies in order to reach reliable conclusions. Clinical assessment of the distinct cognitive domains should include careful history-taking and the use of diagnostic neuropsychological batteries. First, the ideal screening test would be one that could be administered in a few minutes, with a cut-off point that would identify patients requiring further assessment for correct diagnosis. The use of dynamic biomarkers is based on the hypothesis that they have a specific time-dependent model. These biomarkers include, firstly, markers of amyloidosis and, secondly, markers of neurodegeneration. Cognitive frailty is an emerging term inspired by a potential parallel with physical frailty syndrome. A subgroup of patients with cognitive impairment show a reduced capacity for recovery and functional decline that interact with physical frailty. The evidence suggests that cognitive status represents an important dimension of frailty syndrome.

[Breakthrough cancer pain in the elderly]. / Dolor irruptivo oncológico en el anciano.

Breakthrough pain is defined as an acute exacerbation of pain with rapid onset, short duration and moderate or high intensity, which occurs spontaneously or in connection with a predictable or unpredictable event despite there being stabilised and controlled baseline pain. However, there are doubts about the definition, terminology, epidemiology, and assessment of breakthrough pain, with no clear answers or consensus, especially in the elderly population. This non-systematic review summarises the most important aspects of breakthrough pain in the elderly, based on the limited publications there are in that population group.

MEG spectral profile in Alzheimer's disease and mild cognitive impairment.

OBJECTIVE: In this study, we applied a novel procedure to calculate the mean frequency from the Magnetoencephalography (MEG) signals of 22 patients with Alzheimer's Disease (AD), 22 patients with mild cognitive impairment (MCI), and 21 healthy controls. A significant mean frequency decrease was expected in pathological groups. MCI subjects are expected to show intermediate mean frequency values between AD patients and controls. METHODS: MEG signal was obtained from a whole-head 148 channels magnetometer in a resting condition. We estimated the power spectral density from the MEG signal by means of the Fourier transform of the autocorrelation function. Then, we computed the mean frequency for each subject. RESULTS: Mean frequency was higher in controls (12.46 +/- 2.00 Hz, mean +/- SD) than in MCI subjects (10.82 +/- 2.21 Hz) with significant differences (P < 0.05). Moreover, mean frequency values in MCI subjects were higher than in AD patients (9.06 +/- 2.48 Hz, P < 0.05). We also detected a decrease of 0.17 Hz per year in mean frequency from normal subjects' MEG (P < 0.05) CONCLUSIONS: Results demonstrated that the approach adopted for the calculation of a mean frequency score seems to be adequate and sensitive to detect differences between normal aging, cognitive deterioration and AD. In addition, data may contribute to the theoretical discussion on the nature of mild cognitive impairment and its similitudes with Alzheimer's disease. SIGNIFICANCE: This paper may be considered a first step to obtain a reliable measure which summarizes spectral information, and might be of a potential clinical interest.

[Diagnostic criteria. Benefits of early diagnosis]. / Criterios diagnósticos. Beneficios del diagnóstico precoz.

Almost 36 million persons live with dementia worldwide. This figure is set to double by 2030, with 66 million patients, and by 2050 there will be 116 million affected persons. Dementia has an economic impact on individuals and health services and affects the global economy. It is important to evaluate costs to plan social services and healthcare and to provide information on the cost-effectiveness of treatments. The economic cost of dementia was around 604 billion dollars in 2010 and estimates are obviously set to rise.

[Clinical profile and 90-day mortality in centenarian patients attended in emergency departments]. / Perfil clínico y mortalidad a 90días de los pacientes centenarios atendidos en servicios de urgencias hospitalarios.

OBJECTIVES: To determine the clinical profile and to develop a model to predict 90-day mortality in centenarian patients attended in emergency departments (ED). METHODOLOGY: This was an observational, retrospective, multicentre cohort study including patients >99years attended in 5 ED in the Community of Madrid from January to December 2012. Demographic variables were recorded, as well as, comorbidities, cognitive, functional, social basal status, geriatric syndromes, acute episode, and hospital and social resources use, and 90-day mortality. RESULTS: The study included 209patients aged 101years (SD 1.7) of whom 161 (77.0%) were female. Sixty four (32.5%) had severe comorbidity (Charlson index≥3), 101 (49.8%) on multiple medication, 100 (52.6%) had cognitive impairment, 82 (42.3%) had severe functional dependence, 85 (40.7%) were institutionalised, and 190 (94.5%) had a geriatric syndrome. Dyspnoea (26.8%), followed by falls (12.4%) were the most common causes of attendance. One hundred and eighteen (56.5%) were admitted, and 58 out of 174 (33.3%) died in the first 90days. The model to predict 90-day overall mortality included male sex (OR 2.42 95% CI=0.97-6.04; P=.059), emergency care in the previous 3months (OR 4.08 95% CI=1.26-13.16; P=.019) and the hospitalization by index event (OR 8.63 95% CI=3.25-22.9; P<.001) and this model had an area under ROC curve of 0.776 (95% CI=0.70-0.85; P<.001). CONCLUSIONS: Centenarian patients attended in ED had a significant frailty and one in three cases died in the first 90days after being attended, and this was associated with male sex, emergency care in the previous 3months, and hospitalisation.

Frailty in elderly people with chronic kidney disease. / La fragilidad en el anciano con enfermedad renal crónica.

In recent years, the concept of frailty as a "state of pre-disability" has been widely accepted by those involved in the care of the elderly. Its importance lies not only in its high prevalence - more than 25% in people over 85 years of age - but it is also considered an independent risk factor of disability, institutionalisation and mortality amongst the elderly. The study of renal function is relevant in patients with major comorbidities. Studies have shown a significant association between chronic kidney disease and the development of adverse clinical outcomes such as heart disease, heart failure, end-stage renal disease, increased susceptibility to infections and greater functional impairment. Frailty can be reversed, which is why a study of frailty in patients with chronic kidney disease is of particular interest. This article aims to describe the association between ageing, frailty and chronic kidney disease in light of the most recent and relevant scientific publications.

[Update on oncological pain in the elderly]. / Actualización del dolor oncológico en el anciano.

Pain is a prevalent symptom in cancer geriatric patients, appearing in up to 90% of patients with terminal cancer. This requires a multidimensional approach, as there is a high percentage of inappropriate assessments and treatments. Unrecognized or poorly treated pain in the geriatric population, especially in cancer patients, leads to the development of disabling symptoms such as depression, anxiety, isolation, sleep disturbances, and appetite, and very especially, loss of functional capacity and quality of life. In this review an analysis is made on the most relevant studies on the diagnosis and management of cancer pain in the geriatric population.

Time-modulated enhancing of the fronto-parietal circuits in the very-old elders.

Several studies have shown that memory circuits can be reorganised as a function of age. Brain magnetic activity evoked by a memory task was recorded in 19 healthy elderly subjects divided into two groups, a young-elder group (mean age of 62) and senior-elder group (mean age of 76). The young-elder group showed greater activity over the left medial temporal lobe in the late latency windows (between 400 and 800 ms) than the senior-elder group. The senior-elder group showed an initial increased activity (between 150 and 400 ms) over the complex of motor areas, followed by an increased activity in the left temporo-parietal cortex at the late latency window. These results revealed a reorganization of brain networks supporting memory in the eldest subjects. Furthermore, these circuits are reorganised in a time-dependent manner, meaning the rehearsal articulatory process active in the early time window followed by a phonological storage and recognition process in the late latency window.

Correlations of hippocampal atrophy and focal low-frequency magnetic activity in Alzheimer disease: volumetric MR imaging-magnetoencephalographic study.

BACKGROUND AND PURPOSE: Patients with Alzheimer disease (AD) have more low-frequency activity on conventional EEG and increased focal magnetoencephalographic (MEG) dipole density (DD) in delta and theta bands. This activity concurs with atrophy and reduced metabolic and perfusion rates, particularly in temporoparietal structures. The relationship between functional and structural measures and their conjoined capability to improve the diagnosis of AD were assessed in this study. METHODS: Whole-head MEG recordings were obtained in 15 patients in whom the diagnosis of AD had been made and in 16 healthy control subjects during a resting condition. MR imaging volumetric data were also obtained; these included global cerebral, temporal lobe, and hippocampal volumes. RESULTS: DD in the delta and theta bands was enhanced in the AD group compared with the healthy control subjects. Slow-wave activity differed significantly between the groups in the temporoparietal regions of both hemispheres. Left hippocampal volume was correlated with left temporal and parietal delta DD and left temporal theta DD. A combination of left hippocampal volume and left temporal theta DD enabled correct classification in 87.1% of the patients with AD or control subjects. CONCLUSION: Results support the predominant role of temporoparietal hypofunction as defined by DD and hippocampal structural deficits shown on MR images in patients with AD. A multidisciplinary perspective of different techniques may improve our understanding of the disease and our diagnostic abilities.

Recommendations for vaccination against pneumococcus in kidney patients in Spain.

UNLABELLED: Invasive pneumococcal disease (IPD) is a serious problem in some risk groups: patients with stage 4 and 5 chronic kidney disease, stage 3 CKD undergoing immunosuppressive treatment, nephrotic syndrome or diabetes. These individuals are more susceptible to infections and more prone to suffering more severe and worsening symptoms. Vaccination is one of the strategies for preventing IPD, although vaccination coverage in this group at present is lower than desired. Currently, there are two vaccinations for adults. The polysaccharide vaccine (PPSV23), used for decades in patients over the age of 2, includes most serotypes (23), but it does not generate immune memory, causing the immune tolerance phenomenon and it does not act on nasopharyngeal colonisation. The conjugate vaccine (VNC13) can be used from infancy until adulthood (advice in patients over 18 years old received approval from the European Medicines Agency in July 2013) and generates a more powerful immune response than PPSV23 against the majority of the 13 serotypes that it includes. The 16 scientific societies most directly associated with the groups at risk of IPD have discussed and drafted a series of vaccination recommendations based on scientific evidence related to pneumococcal vaccination in adults with underlying conditions and pathologies, which are the subject of the document “ CONSENSUS: Pneumococcal vaccination in adults with underlying pathology”. This text sets out the vaccination recommendations for the chronic kidney disease population.

MEG delta mapping along the healthy aging-Alzheimer's disease continuum: diagnostic implications.

New diagnostic criteria for Alzheimer's disease (AD) stress the role of in vivo biomarkers. Neurophysiological markers are usually not considered as such criteria, although theoretical and practical reasons would justify them. In order to assess the value of neurophysiology as an AD biomarker, whole-head magnetoencephalographic (MEG) resting state recordings were obtained from 35 AD patients, 23 mild cognitive impairment (MCI) patients, and 24 healthy controls. The AD group was further split into two groups differing in severity according to the GDS/FAST criteria. A Minimum Norm Estimation procedure was utilized to estimate the cortical origin of slow brain oscillatory activity in the delta band (2-4 Hz). Eight regions of interest (ROIs) discriminated between AD patients and controls. Delta current density (DCD) in all ROIs showed a significant negative correlation with cognitive status (p < 0.001). DCD values in posterior parietal, occipital, prerolandic, and precuneus cortices distinguished reliably between MCI patients, AD patients with different severity scores, and controls. Importantly, an increase of DCD in right parietal cortex and precuneus indexed the transition from MCI to mild dementia and from mild to more severe dementia. MEG delta mapping might be a serious candidate for a "neural degeneration" marker of AD reflecting dysfunctional synaptic transmission. More importantly, the localization of DCD values is in line with functional imaging markers of AD. However, MEG delta mapping is a totally non-invasive technique that directly measures neural activity. We propose that individuals with enhanced DCD in posterior parietal and precuneus cortices are at risk of progression to full dementia.

[Key points in healthcare of frail elders in the Emergency Department]. / Puntos clave en la asistencia al anciano frágil en Urgencias.

Patients older than 65 years are increasingly attended in the Emergency Department (ED). This means that internists working in ED are responsible for improving their geriatric training. The frail elders are the one who have the higher probability to suffer an adverse event. The detection of this profile is very important for making a decision in ED. A possible geriatric emergency model would be the one that screens frailty among all patients older than 65 years old in ED by nurses, and, in those triaged as of high risk, a geriatric assessment must be done by a geriatric trained doctor or nurse. All this information will be helpful for the final location and discharge follow-up plan.

Anticoagulantes orales en pacientes frágiles con fibrilación auricular: moviéndose en la incertidumbre en la práctica clínica diaria / Oral anticoagulants in frail patients with atrial fibrillation: moving in the uncertainty of daily clinical practice

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