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.

[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.

[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.

[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.

[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.

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.

[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.

[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.

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.

[Which patients benefit the most from hospital geriatric care in the opinion of the geriatricians?]. / ¿Qué pacientes se benefician más de la atención geriátrica hospitalaria en opinión de los especialistas en Geriatría?

OBJECTIVE: To assess the most appropriate criteria considered by geriatricians to select patients who might benefit the most from geriatric hospital care. MATERIAL AND METHODS: We carried out a survey that consisted of various socio-demographic, clinical, functional and mental criteria included in the definition of the geriatric and frail elderly patient. The survey was sent to all specialists in geriatrics in the different hospitals of the Madrid Health Service. They were asked to answer to each criterion indicating whether they considered it as high priority, priority, low priority or no priority. The responses were clustered by type of hospital: acute hospitals with or without a post-graduate geriatric program for medical residents, and medium and long stay hospitals. RESULTS: A total of 83 questionnaires were completed (70% of the study population): 42 teaching hospitals a post-graduate geriatric program (74% of possible), 20 of those with an emergency department but without a post-graduate geriatric program (56% of possible), and 21 medium and long stay hospitals (84% of potential). All proposed criteria were considered individually as priority or high-priority by more than 50% of respondents. An age 85 years and over, admission for hip fracture, the presence of severe cognitive or functional impairment, frailty, and unexplained deterioration of health status, were considered individually as criteria for selecting high-priority target population by more than 85% of respondents. CONCLUSIONS: Certain criteria, such as advanced age, or the presence of geriatrics-specific conditions, such as hip fracture or severe functional or cognitive impairment, are identified by geriatricians as useful to select patients to receive geriatric specialist hospital care.

Differential patterns of connectivity in progressive mild cognitive impairment.

It is now widely accepted that Alzheimer's disease is characterized by a functional disconnection between brain regions. The disease appears to begin up to decades prior to clinical diagnosis. Therefore, in the present study, we combined magnetoencephalography, a memory task, and functional connectivity analysis in mild cognitive impairment subjects in order to identify functional connectivity patterns that could characterize subjects who would eventually go on to develop the disease. We monitored 19 subjects and finally 5 of them developed Alzheimer's disease. These progressive patients showed a differential profile of functional connectivity values compared with those patients who remained stable over time. Specifically there were higher synchronization values over the parieto-occipital region in α and ß frequency bands. The involvement of this brain region in amyloid-ß accumulation and its possible association with hyper-synchronization are also discussed.

[Spontaneous electroencephalographic and magneto-encephalographic activity as a marker of Alzheimer's disease and mild cognitive impairment]. / Actividad espontánea electroencefalográfica y magnetoencefalográfica como marcador de la enfermedad de Alzheimer y el deterioro cognitivo leve.

The association between the electroencephalogram (EEG) and the study of cognitive impairment was observed from the beginning of using this technique. The introduction of the magnetoencephalogram (MEG) has enabled new lines of research to be developed with a potential for significant clinical applicability. Both techniques have a series of advantages, such as the direct detection of neuronal activity. The EEG-MEG spectral variations in Alzheimer's disease (AD) and mild cognitive impairment (MCI) are also linked to essential physiological processes, such as neuronal disconnection or the deficiency in certain neurotransmitters. These spectral variations are basically characterised by a slowing down of the trace when spontaneous activity is registered, with an increase in the power of low frequency bands (delta and theta) and a decrease in the high frequency bands (alpha, beta, gamma). The spectral analysis gives sensitivity-specificity results of around 80%. By using MEG, it has been possible to specifically locate the sources of this low frequency activity, which has enabled the sensitivity of the test to be increased to 93.3%, particularly when combined with the nuclear resonance data. However, the most promising results come from longitudinal studies which attempt to predict those MCI patients with a higher risk of developing AD. In this case, some EEG studies have shown a sensitivity of 85% when detecting these patients. Even more important, some longitudinal MEG studies have been able to determine that high parietal delta activity increases the relative risk of developing AD by 350%.

Brain activity patterns in stable and progressive mild cognitive impairment during working memory as evidenced by magnetoencephalography.

It has been reported that mild cognitive impairment (MCI) patients, when compared with controls, show increased activity in different brain regions within the ventral pathway during memory tasks. A key question is whether this profile of increased activity could be useful to predict which patients will develop dementia. Herein, we present profiles of brain magnetic activity during a memory task recorded with magnetoencephalography from MCI patients (N = 10), Alzheimer's disease (AD) patients (N = 10), and healthy volunteers (N = 17). After 2½ years of follow-up, five of the MCI patients developed AD. Patients who progressed to AD (PMCI) showed higher activity than those who remained stable (SMCI), AD patients and controls. This increased activity in PMCI patients involves regions within the ventral and dorsal pathways. In contrast, SMCI patients showed higher activation than controls only along the ventral pathway. This increase in both the ventral and dorsal pathways in PMCI patients may reflect a compensatory mechanism for the loss in efficiency in memory networks, which would be absent in AD patients as they showed lower activity levels than the rest of the groups.