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Background: Major surgery has been associated with perioperative neurocognitive disorders (PND), but the contributing factors and long-term prognosis are uncertain. We hypothesize that preclinical Alzheimer’s disease (AD) might predispose to cognitive deterioration after surgery. Objective: To analyze the effect of amyloid-β on the cognitive trajectory after orthopedic surgery in a sample of non-demented subjects. Methods: Non-demented individuals older than 65 years that were on the waiting list for orthopedic surgery with spinal anesthesia underwent a neuropsychological assessment before and after surgery. During surgery, cerebrospinal fluid samples were obtained to determine AD biomarkers. Results: Cumulative incidence of PND was 55.2%during a mean follow-up of nine months. The most affected cognitive domains were executive function and constructional praxis. The presence of abnormal levels of amyloid-β was associated to a postoperative impairment in verbal and visual memory tests. According to their AD biomarker profile, participants were categorized as either Amyloid Positive (A+) or Amyloid Negative (A-). The incidence of PND did not differ between both groups. The A- group showed a tendency similar to the global sample, worsening in executive function tests and improving on memory scales due to practice effects. In contrast, the A + group showed a notable worsening on memory performance. Conclusion: Our findings support the hypothesis that surgery may promote or accelerate memory decline in cognitively asymptomatic subjects with brain amyloid-β deposits.

Frontotemporal dementia (FTD) is a heterogeneous syndrome characterized by the progressive damage of frontal and temporal brain regions. These networks largely overlap with those involved in pain and temperature processing. Although the impaired perception of pain and temperature has been previously described to be relatively common in patients with FTD, these symptoms are often not consistently assessed by Neurologists. We present the case of a patient with a probable behavioral variant FTD who died due to scalding with hot water in the shower. Impairments in the perception of pain and temperature might have played a fundamental role in this accident.

Objective The structure of the semantic network is constructed and organized during childhood development. Previous publications have hypothesized that neurodegenerative diseases would lead to a disruption of this network reversing the steps acquired in childhood. Semantic Dementia (SD) is a subtype of frontotemporal lobe degeneration in which the main symptom is a specific loss of semantic memory. We aimed to describe the sequential acquisition of concepts in 3-8 years old children evaluated through the production of drawings and, in parallel, their progressive loss in SD patients. Methods 104 children between 40 and 96 months categorized into tertiles according to their age, 21 SD patients categorized into tertiles according to their score on a category fluency task and 34 healthy volunteers were asked to draw 12 items with, a priori, different age of acquisition and familiarity, belonging to four different semantic categories. We employed the drawings of the healthy volunteers to build a scoring scheme. We considered that a concept was acquired in children when 50% or more of its features were present in their drawings, and it was lost in patients when more than 50% were missing. Results Those concepts which the children were able to acquire earlier, according to our scoring scheme, tended to remain in patients with more advanced SD. While the items that children acquired later, were, in general, those that the SD patients lost at earlier disease stages. Conclusion The patterns of concept acquisition in children were the mirror image of the loss in patients with SD. Our study supports the hypothesis that the sequence of concept acquisition in childhood is reversed in SD patients.

There is increasing evidence of the relationship between sleep and neurodegeneration, but this knowledge is not incorporated into clinical practice yet. We aimed to test whether a basic sleep parameter, as total sleep estimated by actigraphy for 1 week, was a valid predictor of CSF Alzheimer’s Disease core biomarkers (amyloid-β-42 and –40, phosphorylated-tau-181, and total-tau) in elderly individuals, considering possible confounders and effect modifiers, particularly the APOE ε4 allele. One hundred and twenty-seven cognitively unimpaired volunteers enrolled in the Valdecilla Study for Memory and Brain Aging participated in this study. Seventy percent of the participants were women with a mean age of 65.5 years. After adjustment for covariates, reduced sleep time significantly predicted higher t-tau and p-tau. This association was mainly due to the APOE ε4 carriers. Our findings suggest that total sleep time, estimated by an actigraphy watch, is an early biomarker of tau pathology and that APOE modulates this relationship. The main limitation of this study is the limited validation of the actigraphy technology used. Sleep monitoring with wearables may be a useful and inexpensive screening test to detect early neurodegenerative changes. This work was supported by grants from the Instituto de Salud Carlos III (Fondo de Investigación Sanitario, PI08/0139, PI12/02288, PI16/01652, and PI20/01011), the JPND (DEMTEST PI11/03028), the CIBERNED, and the Siemens Healthineers

Background Semantic dementia (SD) is a subtype of frontotemporal dementia (FTD) characterized by semantic memory loss and preserved abilities of other cognitive functions. The clinical manifestations of SD require a differential diagnosis with Alzheimer's disease (AD), especially those with early onset, and behavioral variant FTD (bvFTD). Objective The present study aimed to compare cognitive performances and neuropsychiatric symptoms in a population of AD, bvFTD, and left and right SD defined with the support of molecular imaging (amyloid and 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography) and assessed the accuracy of different neuropsychological markers in distinguishing these neurodegenerative diseases. Methods Eighty-seven participants (32 AD, 20 bvFTD, and 35 SD (17 Left-SD and 18 Right-SD) completed a comprehensive neuropsychological battery that included memory, language, attention and executive functions, visuospatial function, visuoconstructional skills, and tasks designed specifically to evaluate prosopagnosia and facial emotions recognition. The Neuropsychiatric Inventory was administered to assess neuropsychiatric symptoms. Results An episodic memory test that included semantic cues, a visuospatial test (both impaired in AD), a naming test and a prosopagnosia task (both impaired in SD) were the four most valuable cognitive metrics for the differential diagnosis between groups. Several behavioral abnormalities were differentially present, of which aggression, self-care (both more frequent in bvFTD), and eating habits, specifically overeating and altered dietary preference (more frequent in SD), were the most valuable in group discrimination. Conclusion Our study highlights the value of a comprehensive neuropsychological and neuropsychiatric evaluation for the differential diagnosis between FTD syndromes and AD.

Oculomotor behavior can provide insight into the integrity of widespread cortical networks, which may contribute to the differential diagnosis between Alzheimer's disease and frontotemporal dementia. Three groups of patients with Alzheimer's disease, behavioral variant of frontotemporal dementia (bvFTD) and semantic variant of primary progressive aphasia (svPPA) and a sample of cognitively unimpaired elders underwent an eye-tracking evaluation. All participants in the discovery sample, including controls, had a biomarker-supported diagnosis. Oculomotor correlates of neuropsychology and brain metabolism evaluated with 18F-FDG PET were explored. Machine-learning classification algorithms were trained for the differentiation between Alzheimer's disease, bvFTD and controls. A total of 93 subjects (33 Alzheimer's disease, 24 bvFTD, seven svPPA, and 29 controls) were included in the study. Alzheimer's disease was the most impaired group in all tests and displayed specific abnormalities in some visually-guided saccade parameters, as pursuit error and horizontal prosaccade latency, which are theoretically closely linked to posterior brain regions. BvFTD patients showed deficits especially in the most cognitively demanding tasks, the antisaccade and memory saccade tests, which require a fine control from frontal lobe regions. SvPPA patients performed similarly to controls in most parameters except for a lower number of correct memory saccades. Pursuit error was significantly correlated with cognitive measures of constructional praxis and executive function and metabolism in right posterior middle temporal gyrus. The classification algorithms yielded an area under the curve of 97.5% for the differentiation of Alzheimer's disease vs. controls, 96.7% for bvFTD vs. controls, and 92.5% for Alzheimer's disease vs. bvFTD. In conclusion, patients with Alzheimer's disease, bvFTD and svPPA exhibit differentiating oculomotor patterns which reflect the characteristic neuroanatomical distribution of pathology of each disease, and therefore its assessment can be useful in their diagnostic work-up. Machine learning approaches can facilitate the applicability of eye-tracking in clinical practice.

ObjectiveTo assess and compare the involvement of choroidal thickness (CT) in patients with mild cognitive impairment (MCI) and dementia due to Alzheimer's disease (AD) defined by amyloid PET and healthy controls (HC).MethodsSixty-three eyes from 34 AD patients [12 eyes (19.0%) with dementia and 51 eyes (80.9%) with MCI], positive to 11C-labelled Pittsburgh Compound-B with positron emission tomography (11C-PiB PET/CT), and the same number of sex- and age-paired HC were recruited. All participants underwent enhanced depth imaging optical coherence tomography (EDI-OCT) assessing CT at 14 measurements from 2 B-scans. Paired Student t-test was used to compare CT measurements between MCI, dementia and sex- and age-paired HC. A univariate generalized estimating equations model (GEE) test was performed to compare MCI and dementia individually with all HC included.ResultsCompared with HC, eyes from patients with positive 11C-PiB PET/CT showed a significant CT thinning in 5 selected locations (in foveal thickness in vertical scan, in temporal scan at 1500μm, in superior scan at 500μm and in inferior scan at 1000μm and 1500μm, p = 0.020-0.045) whilst few significant CT reduction data was reported in MCI or dementia individually versus HC. However, the GEE test identified significant CT thinning in AD compared with all HC included (p = 0.015-0.046).ConclusionsTo our knowledge, the present study is the first measuring CT in eyes from MCI and dementia eyes positive to 11C-PiB PET/CT reporting a significant trend towards CT thinning in MCI patients which became more pronounced in dementia stage. We support further investigation involving larger and prospective OCT studies in AD population characterized with available biomarkers to describe whether choroidal vascular damage occurs specifically in prodromal stages of AD.

Introduction: The objective of this study was to investigate and compare optic nerve and retinal layers in eyes of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) with paired control eyes using optical coherence tomography. Methods: Sixty-three eyes of 34 subjects, 12 eyes with AD and 51 eyes with MCI, positive to 11C-labeled Pittsburgh Compound-B with positron emission tomography (11C-PiB PET/CT), and the same number of sex- and age-paired control eyes underwent optical coherence tomography scanning analyzing retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), Bruch's membrane opening-minimum rim width (BMO-MRW), inner plexiform layer (IPL), outer nuclear layer, and lamina cribrosa (LC). Results: Compared with healthy controls, eyes of patients with positive 11C-PiB PET/CT showed a significant thinning of RNFL (P < .028) and GCL (P < .014). IPL and outer nuclear layer also showed significant thinning in two (P < .025) and one location (P < .010), respectively. No significant differences were found when optic nerve measurements BMO-MRW and LC were compared (P > .131 and P > .721, respectively). Temporal sector GCL, average RNFL, and temporal sector RNFL also exhibited significant thinning when MCI and control eyes were compared (P = .015, P = .005 and P = .050, respectively), and also the greatest area under the curve values (0.689, 0.647, and 0.659, respectively). GCL, IPL, and RNFL tend to be thinner in the AD group compared with healthy controls. Discussion: Our study suggests that RNFL and GCL are useful for potential screening in the early diagnosis of AD. LC and BMO-MRW appear not to be affected by AD. Acknowledgments: P.S.J. was supported by grants from IDIVAL, Instituto de Salud Carlos III (Fondo de Investigacion Sanitario, PI08/0139, PI12/02288, PI16/01652), JPND (DEMTEST PI11/03028) and the CIBERNED program and Siemens Healthineers (Valdecilla Cohort for Memory and Brain Aging). A.C. conducted the statistical analysis.

Background: Semantic dementia (SD) is a subtype of frontotemporal lobe degeneration characterized by semantic loss, with other cognitive functions initially preserved. SD requires differential diagnosis with Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD). Semantic knowledge can be evaluated through different tests; however, most of them depend on language. Objective: We describe the development of a brief drawing task that may be helpful for the differential diagnosis of SD. Methods: Seventy-two patients, including 32 AD, 19 bvFTD, and 21 SD were asked to draw 12 items with different age of acquisition and familiarity, belonging to four different semantic categories. We employed the drawings of healthy volunteers to build a scoring scheme. Results: Turtle, strawberry, train, and envelope were the items of each category that best discriminated between groups and were selected for the Brief drawing task. The discriminatory power of the Brief drawing task between SD versus AD and bvFTD patients, estimated through the area under the curve was 0.84 (95% CI = 0.72-0.96, p = 0.000007). In a logistic model, the Brief drawing task (p = 0.003) and VOSP "number location" subtest (p = 0.016) were significant predictors of the diagnosis of SD versus AD and bvFTD after adjustment by the main covariates. The Brief drawing task provided clinically useful qualitative information. SD drawings were characterized by loss of the distinctive features, intrusions, tendency to prototype, and answers like "I don't know what this is". Conclusion: The Brief drawing task appears to reveal deficits in semantic knowledge among patients with SD that may assist in the differential diagnosis with other neurodegenerative diseases.

Antecedentes y objetivo: La gravedad e inestabilidad de los pacientes, junto con el alto grado de complejidad de la medicación, hacen de las unidades de cuidados intensivos (UCI) un área crítica de problemas relacionados con la medicación. El objetivo de nuestro estudio fue analizar y evaluar la actividad clínica realizada por el farmacéutico clínico integrado en una UCI y conocer la opinión del personal. Material y método: Estudio descriptivo, prospectivo, de 42 meses de duración. El farmacéutico se integró en la actividad diaria del equipo multidisciplinar de una UCI de 12 camas perteneciente al Servicio de Anestesiología y Reanimación. Se registraron todas las intervenciones farmacoterapéuticas (IF) realizadas, el grado de aceptación, el método de comunicación y destinatario de la intervención, así como la evaluación clínica de las intervenciones aceptadas. Posteriormente, se realizó una encuesta al personal de la unidad sobre la seguridad del paciente y la influencia de la integración del farmacéutico en la unidad. Resultados: Se realizaron un total de 2399 IF con un 97,0% de aceptación. De estas, las mayoritarias fueron las relacionadas con la posología (37,8%) y las consultas al farmacéutico (25,7%). De las IF aceptadas, el 53,7% influyeron sobre la eficacia del tratamiento farmacológico y el 35,1% sobre la tolerancia. En la encuesta realizada al personal de la unidad para valorar la percepción de la integración del farmacéutico se obtuvo una valoración global de de 8,58 ± 1,40 sobre 10. Conclusiones: El farmacéutico hospitalario integrado en el equipo multidisciplinar de UCI puede aportar un valor añadido al proceso farmacoterapéutico del paciente crítico., Background and objective: The severity and instability of the patients, together with the high degree of complexity of the medication, make the intensive care units (ICU) a critical area of problems related to medication. The aim of our study was to analyze and assess the activity performed by the clinical pharmacist integrated in an ICU and to know the opinion of the staff about it. Material and method: A 42 month descriptive and prospective study was conducted. The pharmacist was integrated into the daily activity of the multidisciplinary team of a 12-bed ICU belonging to the Anaesthesiology and Resuscitation Department. Every pharmacotherapeutic intervention (PI) carried out, the degree of acceptance, the method of communication and the receiver of the intervention, as well as the clinical evaluation of the accepted interventions were recorded. Subsequently, a survey was carried out to the staff of the unit on the patient´s safety and the influence of the integration of the pharmacist in the unit. Results: A total of 2399 PIs were carried out with a 97.0% of acceptance. Of these, most were those related to posology (37.8%) and consultations with the pharmacist (25.7%). Among the accepted PIs, 53.7% had an influence on the efficacy of drug therapy, and 35.1% on treatment tolerance. In the survey to the unit´s staff in order to assess the perception of the pharmacist´s integration, an overall assessment of 8.58 ± 1.40 out of 10 was obtained. Conclusions: The hospital pharmacist integrated in the ICU multidisciplinary team can add value to the pharmacotherapeutic process of the critical patient.

The interfacial changes associated with a series of polypropylene based composite materials with modified interphases from the reinforcement side, from the matrix side and both were studied by following their dynamic mechanical behavior. Composites consisted in an isotactic polypropylene (iPP) matrix, a series of talc with different surface functionalities (hydroxyl, chloride, n-butyl amine, and silanes) and a commercial interfacial agent form the matrix side (iPP-SA with 5% of grafts). A comprehensive interpretation of the link existing between the dynamic mechanical responses of the series of 75/25 iPP/talc composites and the molecular relaxation spectrum occurring in the polymer phase of the composites is made with emphasis on the role played by the interfacial modifications performed from each and both sides of the interphase. Dynamic mechanical analysis has been used here to study how the intended interfacial modifications affected the behavior of the composites. The efficiency of the interfacial phenomena is discussed from a phenomenological point of view as well as by considering classical criteria such as the glass transition temperature and the glass to rubbery transition. Finally, a correlation between mechanical parameters from the microscopic scale and others from the macroscopic scale appears to emerge.