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The formation of two-dimensional oxide dodecagonal quasicrystals as well as related complex approximant phases was recently reported in thin films derived from BaTiO3 or SrTiO3 perovskites deposited on (111)-oriented Pt single crystals. Here, we use an all-thin-film approach in which the single crystal is replaced by a 10 nm thick Pt(111) buffer layer grown by molecular beam epitaxy on an Al2O3(0001) substrate. An ultra-thin film of SrTiO3 was subsequently deposited by pulsed laser deposition. The film stacking and structure are fully characterized by diffraction and microscopy techniques. We report the discovery of two new complex phases obtained by reduction of this system through high temperature annealing under ultrahigh vacuum conditions. The formation of a new large square approximant with a lattice parameter equal to 44.4 Å is evidenced by low-energy electron diffraction and scanning tunneling microscopy (STM). Additionally, a new 2D hexagonal approximant phase with a lattice parameter of 28 Å has been observed depending on the preparation conditions. Both phases can be described by two different tilings constructed with the same basic square, triangle and rhombus tiles possessing a common edge length of about 6.7 Å. Using the tiling built from high resolution STM images, we propose an atomic model for each approximant which accounts for the experimental observations. Indeed, the STM images simulated using these models are found to be in excellent agreement with the experimental ones, the bright protrusions being attributed to the topmost Sr atoms. In addition our theoretical approach shows that the adhesion of the oxide layer is rather strong (-0.30 eV Å-2). This is attributed to charge transfer, from the most electropositive elements (Sr and Ti) to the most electronegative ones (Pt and O), and to hybridization with Pt-states. Density of states calculations indicate differences in the electronic structure of the two approximants, suggesting different chemical and physical properties. This all-thin-film approach may be useful to explore the formation of complex two-dimensional oxide phases in other metal-oxide combinations.
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BACKGROUND AND PURPOSE: To study the association between Alzheimer's disease and related syndromes (ADRS) and the incidence of short-stay hospitalizations from the year before (Y-1 ) to 4 years after (Y1 -Y4 ) ADRS identification in the healthcare system. METHODS: Among all beneficiaries of the French health insurance general scheme aged 40 years or more, those with an incident ADRS in 2011, identified through long-term disease registry, hospitalization diagnoses or ADRS-specific drug delivery, were matched with beneficiaries without ADRS of the same age, gender and residence area. The annual incidence rates of all-cause hospitalizations (excluding those with a diagnosis code of ADRS) were compared between individuals with or without ADRS using incidence ratios (IRs) globally and by age, gender, deprivation index and modified Charlson score. We also studied cause-specific hospitalizations using patients' diagnoses and procedure codes. RESULTS: A total of 90 871 subjects with and 90 871 subjects without ADRS were included (mean age 79.6 years, 66% females). From Y-1 to Y4 , incidence rates were significantly higher in subjects with ADRS than in those without for all-cause hospitalization [IR(Y-1 ) = 1.73; 95% confidence intervals, 1.71-1.75; IR(Y4 ) = 1.37; 95% confidence intervals, 1.35-1.39], hospitalizations for social reasons [IR(Y-1 ) = 4.28; IR(Y4 ) = 2.70], fall [IR(Y-1 ) = 5.36; IR(Y4 ) = 2.59], injury [IR(Y-1 ) = 2.71; IR(Y4 ) = 2.09] and infection [IR(Y-1 ) = 2.04; IR(Y4 ) = 2.07]. The inverse was observed for hospitalizations for cataract surgery [IR(Y-1 )=0.73; IR(Y4 ) = 0.51] or total hip prosthesis after 2 years [IR(Y4 ) = 0.72]. CONCLUSIONS: Incident ADRS cases were associated with a higher incidence of hospitalization, but these subjects underwent some common non-emergency surgeries less frequently. Future studies need to assess the clinical impact of these differences.
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Enfermedad de Alzheimer , Adulto , Anciano , Enfermedad de Alzheimer/epidemiología , Femenino , Hospitalización , Humanos , Incidencia , Estudios Longitudinales , MasculinoRESUMEN
This corrects the article DOI: 10.1103/PhysRevLett.115.157204.
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Double-barrier heterostructures are model systems for the study of electron tunneling and discrete energy levels in a quantum well (QW). Until now resonant tunneling phenomena in metallic QWs have been observed for limited thicknesses (1-2 nm) under which electron phase coherence is conserved. In the present study we show evidence of QW resonance states in Fe QWs up to 12 nm thick and at room temperature in fully epitaxial double MgAlO_{x} barrier magnetic tunnel junctions. The electron phase coherence displayed in this QW is of unprecedented quality because of a homogenous interface phase shift due to the small lattice mismatch at the Fe-MgAlO_{x} interface. The physical understanding of the critical role of interface strain on QW phase coherence will greatly promote the development of spin-dependent quantum resonant tunneling applications.
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PURPOSE: Despite good to excellent inter-reader agreement in the evaluation of amyloid load on PET scans in subjects with Alzheimer's disease, some equivocal findings have been reported in the literature. We aimed to describe the clinical characteristics of subjects with equivocal PET images. METHODS: Nondemented subjects aged 70 years or more were enrolled from the MAPT trial. Cognitive and functional assessments were conducted at baseline, at 6 months, and annually for 3 years. During the follow-up period, 271 subjects had (18)F-AV45 PET scans. Images were visually assessed by three observers and classified as positive, negative or equivocal (if one observer disagreed). After debate, equivocal images were reclassified as positive (EP+) or negative (EP-). Scans were also classified by semiautomated quantitative analysis using mean amyloid uptake of cortical regions. We evaluated agreement among the observers, and between visual and quantitative assessments using kappa coefficients, and compared the clinical characteristics of the subjects according to their PET results. RESULTS: In 158 subjects (58.30 %) the PET scan was negative for amyloid, in 77 (28.41 %) the scan was positive and in 36 (13.28 %) the scan was equivocal. Agreement among the three observers was excellent (kappa 0.80). Subjects with equivocal images were more frequently men (58 % vs. 37 %) and exhibited intermediate scores on cognitive and functional scales between those of subjects with positive and negative scans. Amyloid load differed between the EP- and negative groups and between the EP+ and positive groups after reclassification. CONCLUSION: Equivocal amyloid PET images could represent a neuroimaging entity with intermediate amyloid load but without a specific neuropsychological pattern. Clinical follow-up to assess cognitive evolution in subjects with equivocal scans is needed.
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Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/fisiopatología , Amiloide/metabolismo , Cognición , Tomografía de Emisión de Positrones , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Variaciones Dependientes del ObservadorRESUMEN
BACKGROUND: Definitions and diagnostic criteria for all medical conditions are regularly subjected to reviews and revisions as knowledge advances. In the field of Alzheimer's disease (AD) research, it has taken almost three decades for diagnostic nomenclature to undergo major re-examination. The shift towards presymptomatic and pre-dementia stages of AD has brought prevention and treatment trials much closer to each other than before. METHODS: Here we discuss: (i) the impact of diagnostic reliability on the possibilities for developing preventive strategies for AD; (ii) the scientific evidence to support moving from observation to action; (iii) ongoing intervention studies; and (iv) the methodological issues and prospects for balancing strategies for high-risk individuals with those for broad population-based prevention. RESULTS: The associations between neuropathology and cognition are still not entirely clear. In addition, the risk factors for AD dementia and the neuropathological hallmarks of AD may not necessarily be the same. Cognitive impairment has a clearer clinical significance and should therefore remain the main focus of prevention. Risk/protective factors for dementia/AD need to be studied from a life-course perspective. New approaches in prevention trials include enrichment strategies based on genetic risk factors or beta-amyloid biomarkers (at least four ongoing pharmacological trials), and multidomain interventions simultaneously targeting various vascular and lifestyle-related risk factors (at least three ongoing trials). Experience from prevention programmes in other chronic diseases can provide additional methodological improvements. CONCLUSIONS: Building infrastructures for international collaborations is necessary for managing the worldwide public health problem of AD and dementia. The International Database on Aging and Dementia (IDAD) and the European Dementia Prevention Initiative (EDPI) are examples of ongoing international efforts aiming to improve the methodology of preventive studies and provide the basis for larger intervention trials.
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Enfermedad de Alzheimer , Demencia , Medicina Preventiva/métodos , Síntomas Prodrómicos , Envejecimiento , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/prevención & control , Biomarcadores/análisis , Ensayos Clínicos como Asunto , Cognición , Demencia/diagnóstico , Demencia/etiología , Demencia/prevención & control , Diagnóstico Precoz , Humanos , Estudios Longitudinales , Factores de RiesgoAsunto(s)
Bioestadística , Congresos como Asunto , Epidemiología , Neoplasias/epidemiología , Congresos como Asunto/organización & administración , Congresos como Asunto/normas , Congresos como Asunto/tendencias , Métodos Epidemiológicos , Epidemiología/organización & administración , Epidemiología/normas , Epidemiología/tendencias , Francia , Historia del Siglo XXI , Humanos , Oncología Médica/organización & administración , Oncología Médica/normas , Oncología Médica/estadística & datos numéricos , Oncología Médica/tendencias , Neoplasias/terapia , Sociedades Médicas/organización & administración , Sociedades Médicas/normas , Sociedades Médicas/tendenciasRESUMEN
The anharmonicity of the potential well confining a magnetic vortex core in a nanodot is measured dynamically with a magnetic resonance force microscope (MRFM). The stray field of the MRFM tip is used to displace the equilibrium core position away from the nanodot center. The anharmonicity is then inferred from the relative frequency shift induced on the eigenfrequency of the vortex core translational mode. An analytical framework is proposed to extract the anharmonic coefficient from this variational approach. Traces of these shifts are recorded while scanning the tip above an isolated nanodot, patterned out of a single crystal FeV film. We observe a +10% increase of the eigenfrequency when the equilibrium position of the vortex core is displaced to about one-third of its radius. This calibrates the tunability of the gyrotropic mode by external magnetic fields.
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BACKGROUND: Frailty has emerged as one of the major risk factors of loss of autonomy and it can be reverted through early and appropriate interventions. A wide range of available frailty screening tools are administered, mainly in clinical settings. However, few frailty instruments are self-administered. OBJECTIVES: The aim of this study was to determine the diagnostic test accuracy of a modified self-administered questionnaire derived from the Study of Osteoporotic Fractures (SOF) index against the Fried frailty phenotype in identifying frailty. DESIGN: Observational, multicenter, diagnostic test accuracy study. PARTICIPANTS: Participants aged 70 and over, living at home or in community-dwelling (n=5134) in two centers in France were contacted. MEASUREMENTS: Participants were mailed self-administered questionnaires derived from the SOF index. Responders who accepted the home evaluation were assessed by trained nurses, blinded to results of the questionnaire, using the Fried frailty phenotype as the reference method. RESULTS: The questionnaire was sent to 5134 participants, of which 1878 (36.6%) met inclusion criteria and returned the questionnaire. Fried frailty assessments were obtained in 691 (35.4%) participants. A total of 639 subjects had a complete evaluation on both the self-administered questionnaire and the Fried phenotype. Mean age was 78.9 (standard deviation [SD]: 5.95) years and 359 (56.2%) participants were women. According to the questionnaire, 159 (24.9%) subjects were considered frail, 172 (26.9%) pre-frail, and 308 (48.2) robust. With the home evaluation, Fried frailty phenotype results were respectively, 114 (17.8%), 295 (46.2%) and 230 (36%). The self-administered questionnaire presented a sensitivity of 66.6% (95% CI: 57.2-75.2) and a specificity of 84.2% (95% CI: 80.8-87.2). CONCLUSIONS: A self-administered questionnaire can be used in elders and represents an opportunity for empowering them in the management of their health in the context of frailty.
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Fragilidad , Humanos , Femenino , Anciano , Masculino , Fragilidad/diagnóstico , Fragilidad/prevención & control , Anciano Frágil , Valor Predictivo de las Pruebas , Servicios Postales , Evaluación Geriátrica/métodos , Vida IndependienteRESUMEN
The A. G. Leventis Foundation International Conference, "Prevention of Alzheimer's Disease and Cognitive Decline with Diet and Lifestyle", was held on May 11-12th, 2022 in Nicosia, Cyprus. This conference examined the role of diet and lifestyle for the prevention and treatment of Alzheimer's Disease and other forms of cognitive decline. Speakers from leading academic institutions presented evidence on healthy dietary patterns, with a particular focus on the traditional Mediterranean diet (MedDiet), in association with cognitive outcomes, mainly cognitive decline, dementia, and Alzheimer's disease, from both observational and interventional studies. Moreover, future directions for the potential use of olive oil, rich in polyphenols, for its therapeutic use as a nutraceutical, as well as nutritional interventions with high-quality dietary patterns (i.e. MedDiet) that support existing primarily observational evidence for the prevention of cognitive decline, as well as challenges in designing rigorous clinical trials are summarized and discussed within the conference proceedings.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Dieta Mediterránea , Humanos , Enfermedad de Alzheimer/prevención & control , Disfunción Cognitiva/prevención & control , Estilo de Vida , Suplementos DietéticosRESUMEN
AIM: To verify the inter-rater agreement of the Integrated Care for Older People (ICOPE) STEP 1 screening tool using the ICOPE Monitor app, comparing self-assessment to a screening performed by a health professional. METHODS: We compared the results of the ICOPE Step 1 obtained by self-screening with those obtained by a professional screening using Gwet's agreement coefficient in two studies. Study 1 tested inter-rater reliability in participants to the INSPIRE-T cohort who agreed to undergo the self-and the professional screening on the same day. Study 2 used data from the INSPIRE-ICOPE care cohort. We included real-life users of the French health system whose first ICOPE Step 1 was a self-assessment followed by a professional Step 1within 130 days (mean=76 days, SD=60). RESULTS: Study 1 included 79 participants (45 aged less than 60, 34 aged 60 and over, 60% female, mean (SD) age of 54.5 (18.5) years). Of the 207 participants in Study 2, 49 were less than 60, and 158 were 60 and over (54% female, mean (SD) age 67 (16.1) years). Agreement coefficients in Study 1 ranged from 0.49 (CI95% 0.24; 0.66) in the cognition domain - moderate agreement) to 0.99 (CI95% 0.96;1.00) in the nutrition domain - very good agreement); and in Study 2 from 0.36 (CI95% 0.23;0.49) in the cognition domain to 0.97 (95% 0.95;1.00) in the nutrition domain. The agreement coefficients for the cognition and hearing domains were higher for the participants aged <60 than those aged 60 and over. The time orientation items (cognition) showed high reliability. CONCLUSION: Our study supports using ICOPE Step 1 as a self-assessment screening tool. High reliability was found for intrinsic capacity's nutrition, psychological, and locomotion domains, regardless of age. We discuss aspects of the self-assessment of cognition, vision, and hearing domains when using the ICOPE monitor app in older adults.
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Aplicaciones Móviles , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Reproducibilidad de los Resultados , Estado NutricionalRESUMEN
Background: Observational studies and some randomized controlled trials have suggested that nutritional supplementation could be a possible intervention pathway to prevent cognitive decline and Alzheimer's disease (AD). As measuring amyloid-ß and tau pathophysiology by positron emission tomography (PET) or cerebrospinal fluid (CSF) analyses may be perceived as complex, plasma versions of such biomarkers have emerged as more accessible alternatives with comparable capacity of predicting cognitive impairment. Objectives: This study aimed to evaluate the effect of a 1-year intervention with a nutritional blend on plasma p-tau181 and glial fibrillary acidic protein (GFAP) levels in community-dwelling older adults. Effects were further assessed in exploratory analyses within sub-cohorts stratified according to p-tau status (with the third tertile considered as high: ≥15.1 pg/ mL) and to apolipoprotein E (APOE) ε4 allele status. Methods: A total of 289 participants ≥70 years (56.4% female, mean age 78.1 years, SD=4.7) of the randomized, double-blind, multicenter, placebo-controlled Nolan trial had their plasma p-tau181 assessed, and daily took either a nutritional blend (composed of thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid, cobalamin, vitamin E, vitamin C, vitamin D, choline, selenium, citrulline, eicosapentaenoic acid - EPA, and docosahexaenoic acid - DHA) or placebo for 1 year. Results: After 1-year, both groups presented a significant increase in plasma p-tau181 and GFAP values, with no effect of the intervention (p-tau181 between-group difference: 0.27pg/mL, 95%CI: -0.95, 1.48; p=0.665; GFAP between-group difference: -3.28 pg/mL, 95%CI: -17.25, 10.69; p=0.644). P-tau-and APOE ε4-stratified analyses provided similar findings. Conclusions: In community-dwelling older adults, we observed an increase in plasma p-tau181 and GFAP levels that was not different between the supplementation groups after one year.
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We perform a spectroscopic study of the collective spin-wave dynamics occurring in a pair of magnetic nanodisks coupled by the magnetodipolar interaction. We take advantage of the stray field gradient produced by the magnetic tip of a ferromagnetic resonance force microscope to continuously tune and detune the relative resonance frequencies between two adjacent nano-objects. This reveals the anticrossing and hybridization of the spin-wave modes in the pair. At the exact tuning, the measured frequency splitting between the binding and antibinding modes corresponds to the strength of the dynamical dipolar coupling Ω. This accurate ferromagnetic resonance force microscope determination of Ω is measured versus the separation between the nanodisks. It agrees quantitatively with calculations of the expected dynamical magnetodipolar interaction in our sample.
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In combining spin- and symmetry-resolved photoemission, magnetotransport measurements and ab initio calculations we detangled the electronic states involved in the electronic transport in Fe(1-x)Co(x)(001)/MgO/Fe(1-x)Co(x)(001) magnetic tunnel junctions. Contrary to previous theoretical predictions, we observe a large reduction in TMR (from 530 to 200% at 20 K) for Co content above 25 atomic% as well as anomalies in the conductance curves. We demonstrate that these unexpected behaviors originate from a minority spin state with Δ(1) symmetry that exists below the Fermi level for high Co concentration. Using angle-resolved photoemission, this state is shown to be a two-dimensional state that occurs at both Fe(1-x)Co(x)(001) free surface, and more importantly at the interface with MgO. The combination of this interface state with the peculiar density of empty states due to chemical disorder allows us to describe in details the complex conduction behavior in this system.
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AIMS: To determine whether diabetes mellitus influences functional status in patients with Alzheimer's disease. METHODS: We studied 608 community-dwelling patients with Alzheimer's disease from a prospective multicenter cohort. Diabetes was assessed at baseline. Functional status was assessed twice yearly with the Activities of Daily Living scale. Each patient had a baseline functional disability if their Activities of Daily Living score was < 6. Progression of functional disability was defined by a decreased Activities of Daily Living score over 4 years of follow-up visits. RESULTS: At baseline, diabetes was present in 63 participants (10.4%) and, compared with those without diabetes, was associated with functional impairment [age- and sex-adjusted OR = 2.73 (95% CI 1.41-5.28)]. After controlling for confounders, the association remained significant [OR = 2.04 (95% CI 1.02-4.11)]. Follow-up demonstrated a significant interaction between duration of Alzheimer's disease and diabetes, which was associated with progression of functional impairment in patients who had been diagnosed with Alzheimer's disease for less than 1 year [age- and sex-adjusted hazard ratio = 1.52 (95% CI 1.01-2.30), P = 0.048], but not in those who had been diagnosed with Alzheimer's disease for more than 1 year [age- and sex-adjusted hazard ratio = 0.78 (95% CI 0.47-1.28), P = 0.32]. Abnormal one-leg balance, polymedication and obesity seem to be important factors explaining the association between diabetes and functional status. CONCLUSIONS: At baseline, the presence of diabetes significantly increases the risk of functional disability in patients with Alzheimer's disease; our longitudinal data confirm that in patients with a recent diagnosis of Alzheimer's disease (but not in those who have had Alzheimer's disease for longer than 1 year), diabetes continues to worsen functional status.
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Actividades Cotidianas , Enfermedad de Alzheimer/fisiopatología , Diabetes Mellitus/fisiopatología , Obesidad/fisiopatología , Equilibrio Postural , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/sangre , Cognición , Estudios de Cohortes , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Obesidad/sangre , Obesidad/complicaciones , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Recent evidence point towards an interaction between omega-3 (n-3) polyunsaturated fatty acids (PUFA) and plasma homocysteine (Hcy). OBJECTIVES: This study tested the hypothesis that effects of red blood cell n-3 PUFA are modified according to baseline plasma Hcy in the large Mulit-domain Alzheimer Prevention Trial (MAPT) throughout the 3-years of treatment with an additional 2 years of observational follow-up. DESIGN: Experimental study. PARTICIPANTS: From the 1680 participants that were randomized in the four groups of the MAPT study (two of which received n-3 PUFA, the other two without n-3 PUFA), 782 were selected because they had baseline data on both Hcy and n-3 PUFA. MEASUREMENTS: Cognitive performance was measured with a broad set of cognitive tests including free and total recall of the cued selective reminding test, digit symbol substitution test, category naming test and Trail-making tests (TMT-A and B) and Clinical dementia rating scale. RESULTS: We found a significant association between TMT-A and red blood cell n-3 PUFA levels in participants with Hcy values ≤16.8 µMol/L after adjustments at baseline (Estimate: -1.3, 95% CI: -2.3; -0.3, p=0.01). Additionally, participants with high Hcy values had a significant worsening after adjustments in TMT-B after a 5-year n-3 PUFA supplementation, compared to low levels of Hcy (Mean difference: 34.8, 95% CI: 7.8;61.7). CONCLUSION: This study shows that Hcy levels could modify the association between red blood cell n-3 PUFA and executive function. People with high Hcy may benefit less from a n-3 PUFA supplementation to prevent cognitive decline.
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Disfunción Cognitiva , Ácidos Grasos Omega-3 , Anciano , Cognición , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/prevención & control , Suplementos Dietéticos , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/uso terapéutico , Homocisteína , HumanosRESUMEN
BACKGROUND: Cardiovascular risk factors and lifestyle factors are associated with an increased risk of cognitive decline and dementia in observational studies, and have been targeted by multidomain interventions. OBJECTIVES: We pooled individual participant data from two multi-domain intervention trials on cognitive function and symptoms of depression to increase power and facilitate subgroup analyses. DESIGN: Pooled analysis of individual participant data. SETTING: Prevention of Dementia by Intensive Vascular Care trial (preDIVA) and Multidomain Alzheimer Preventive Trial (MAPT). PARTICIPANTS: Community-dwelling individuals, free from dementia at baseline. INTERVENTION: Multidomain interventions focused on cardiovascular and lifestyle related risk factors. MEASUREMENTS: Data on cognitive functioning, depressive symptoms and apathy were collected at baseline, 2 years and 3-4 years of follow-up as available per study. We analyzed crude scores with linear mixed models for overall cognitive function (Mini Mental State Examination [MMSE]), and symptoms of depression and apathy (15-item Geriatric Depression Scale). Prespecified subgroup analyses were performed for sex, educational level, baseline MMSE <26, history of hypertension, and history of stroke, myocardial infarction and/or diabetes mellitus. RESULTS: We included 4162 individuals (median age 74 years, IQR 72, 76) with a median follow-up duration of 3.7 years (IQR 3.0 to 4.1 years). No differences between intervention and control groups were observed on change in cognitive functioning scores and symptoms of depression and apathy scores in the pooled study population. The MMSE declined less in the intervention groups in those with MMSE <26 at baseline (N=250; MD: 0.84; 95%CI: 0.15 to 1.54; p<0.001). CONCLUSIONS: We found no conclusive evidence that multidomain interventions reduce the risk of global cognitive decline, symptoms of depression or apathy in a mixed older population. Our results suggest that these interventions may be more effective in those with lower baseline cognitive functioning. Extended follow-up for dementia occurrence is important to inform on the potential long-term effects of multidomain interventions.
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Enfermedad de Alzheimer , Apatía , Anciano , Cognición , Depresión/epidemiología , Depresión/prevención & control , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Interventions simultaneously targeting multiple risk factors and mechanisms are most likely to be effective in preventing cognitive impairment. This was indicated in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) testing a multidomain lifestyle intervention among at-risk individuals. The importance of medical food at the early symptomatic disease stage, prodromal Alzheimer's disease (AD), was emphasized in the LipiDiDiet trial. The feasibility and effects of multimodal interventions in prodromal AD are unclear. OBJECTIVES: To evaluate the feasibility of an adapted FINGER-based multimodal lifestyle intervention, with or without medical food, among individuals with prodromal AD. METHODS: MIND-ADmini is a multinational proof-of-concept 6-month randomized controlled trial (RCT), with four trial sites (Sweden, Finland, Germany, France). The trial targeted individuals with prodromal AD defined using the International Working Group-1 criteria, and with vascular or lifestyle-related risk factors. The parallel-group RCT includes three arms: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); 2) multimodal lifestyle intervention+medical food (Fortasyn Connect); and 3) regular health advice/care (control group). Primary outcomes are feasibility and adherence. Secondary outcomes are adherence to the individual intervention domains and healthy lifestyle changes. RESULTS: Screening began on 28 September 2017 and was completed on 21 May 2019. Altogether 93 participants were randomized and enrolled. The intervention proceeded as planned. CONCLUSIONS: For the first time, this pilot trial tests the feasibility and adherence to a multimodal lifestyle intervention, alone or combined with medical food, among individuals with prodromal AD. It can serve as a model for combination therapy trials (non-pharma, nutrition-based and/or pharmacological interventions).
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Enfermedad de Alzheimer , Trastornos del Conocimiento , Disfunción Cognitiva , Anciano , Enfermedad de Alzheimer/prevención & control , Trastornos del Conocimiento/prevención & control , Disfunción Cognitiva/prevención & control , Humanos , Estilo de Vida , Proyectos PilotoRESUMEN
BACKGROUND: To date, no curative treatment is available for Alzheimer's disease (AD). Therefore, efforts should focus on prevention strategies to improve the efficiency of healthcare systems. OBJECTIVE: Our aim was to assess the cost-effectiveness of three preventive strategies for AD compared to a placebo. DESIGN: The Multidomain Alzheimer Preventive Trial (MAPT) study was a multicenter, randomized, placebo-controlled superiority trial with four parallel groups, including three intervention groups (one group with Multidomain Intervention (MI) plus a placebo, one group with Polyunsaturated Fatty Acids (PFA), one group with a combination of PFA and MI) and one placebo group. SETTING: Participants were recruited and included in 13 memory centers in France and Monaco. PARTICIPANTS: Community-dwelling subject aged 70 years and older were followed during 3 years. INTERVENTIONS: We used data from the MAPT study which aims to test the efficacy of a MI along PFA, the MI plus a placebo, PFA alone, or a placebo alone. MEASUREMENT: Direct medical and non-medical costs were calculated from a payer's perspective during the 3 years of follow-up. The base case incremental Cost-Effectiveness Ratio (ICER) represents the cost per improved cognitive Z-score point. Sensitivity analyses were performed using different interpretation of the effectiveness criteria. RESULTS: Analyses were conducted on 1,525 participants. The ICER at year 3 that compares the MI + PFA and the MI alone to the placebo amounted to 21,443 and 21,543 respectively, per improved Z score point. PFA alone amounted to 111,720 per improved Z score point. CONCLUSION: Our study shows that ICERS of PFA combined with MI and MI alone amounted to 21,443 and 21,543 respectively per improved Z score point compared to the placebo and are below the WTP of 50,000 while the ICER of PFA alone amounted to 111,720 per improved Z score point. This information may help decision makers and serve as a basis for the implementation of a lifetime decision analytic model.
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Enfermedad de Alzheimer , Cognición/fisiología , Análisis Costo-Beneficio/economía , Ácidos Docosahexaenoicos/administración & dosificación , Ejercicio Físico/fisiología , Anciano , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/prevención & control , Femenino , Francia , Humanos , Vida Independiente , Masculino , Mónaco , Proyectos de InvestigaciónRESUMEN
BACKGROUND: The screening tool of the Integrated Care for Older People (ICOPE Step 1), designed to detect declines in the domains of intrinsic capacity, has been incipiently investigated in older adult populations. OBJECTIVES: To retrospectively estimate the frequency of priority conditions associated with declines in intrinsic capacity according to an adaptation of the screening tool ICOPE Step 1 among participants of the Multidomain Alzheimer Preventive Trial (MAPT). DESIGN: A cross-sectional retrospective analysis from the baseline assessment of the MAPT. SETTING: The data was gathered during a preventive consultation for cardiovascular risk factors in memory clinics in France. PARTICIPANTS: Seven hundred fifty-nine older adults aged 70-89 years with memory complaints, allocated to the multidomain groups of the MAPT study. MEASUREMENTS: Five domains of intrinsic capacity (cognition, locomotion, nutrition, sensorial, and psychological) were assessed using a screening tool similar to the ICOPE Step 1 (MAPT Step 1). The frequency of six conditions associated with declines in intrinsic capacity (cognitive decline, limited mobility, malnutrition, visual impairment, hearing loss, and depressive symptoms) was obtained for older adults with memory complaints participating in the MAPT study. RESULTS: Overall, 89.3% of the participants had one or more conditions associated with declines in intrinsic capacity. The overall frequency of each condition was: 52.2% for cognitive decline, 20.2% for limited mobility, 6.6% for malnutrition, 18.1% for visual impairment, 56.2% for hearing loss, and 39% for depressive symptoms. CONCLUSION: After being screened with an adaptation of the ICOPE step 1 (MAPT step 1) tool, 9/10 older adults had one or more conditions associated with declines in intrinsic capacity. The relative frequency differs across conditions and could probably be lower in a population without memory complaints. The frequency of screened conditions associated with declines in IC highlights how relevant it is to develop function-centered care modalities to promote healthy aging.