105 results on '"Altuna M"'
Search Results
2. Mechanisms Involved in Epileptogenesis in Alzheimer's Disease and Their Therapeutic Implications
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Altuna, M, Olmedo-Saura, G, Carmona-Iragui, M, and Fortea, J
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hyperexcitability ,epilepsy ,Alzheimer's disease ,antiseizure medications ,seizures - Abstract
Epilepsy and Alzheimer's disease (AD) incidence increases with age. There are reciprocal relationships between epilepsy and AD. Epilepsy is a risk factor for AD and, in turn, AD is an independent risk factor for developing epilepsy in old age, and abnormal AD biomarkers in PET and/or CSF are frequently found in late-onset epilepsies of unknown etiology. Accordingly, epilepsy and AD share pathophysiological processes, including neuronal hyperexcitability and an early excitatory-inhibitory dysregulation, leading to dysfunction in the inhibitory GABAergic and excitatory glutamatergic systems. Moreover, both beta-amyloid and tau protein aggregates, the anatomopathological hallmarks of AD, have proepileptic effects. Finally, these aggregates have been found in the resection material of refractory temporal lobe epilepsies, suggesting that epilepsy leads to amyloid and tau aggregates. Some epileptic syndromes, such as medial temporal lobe epilepsy, share structural and functional neuroimaging findings with AD, leading to overlapping symptomatology, such as episodic memory deficits and toxic synergistic effects. In this respect, the existence of epileptiform activity and electroclinical seizures in AD appears to accelerate the progression of cognitive decline, and the presence of cognitive decline is much more prevalent in epileptic patients than in elderly patients without epilepsy. Notwithstanding their clinical significance, the diagnosis of clinical seizures in AD is a challenge. Most are focal and manifest with an altered level of consciousness without motor symptoms, and are often interpreted as cognitive fluctuations. Finally, despite the frequent association of epilepsy and AD dementia, there is a lack of clinical trials to guide the use of antiseizure medications (ASMs). There is also a potential role for ASMs to be used as disease-modifying drugs in AD.
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- 2022
3. Role of Biomarkers for the Diagnosis of Prion Diseases: A Narrative Review
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Altuna, M, Ruiz, I, Zelaya, MV, and Mendioroz, M
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diagnosis ,prion disease ,neurodegeneration ,biomarkers ,dementia - Abstract
Prion diseases are progressive and irreversible neurodegenerative disorders with a low incidence (1.5-2 cases per million per year). Genetic (10-15%), acquired (anecdotal) and sporadic (85%) forms of the disease have been described. The clinical spectrum of prion diseases is very varied, although the most common symptoms are rapidly progressive dementia, cerebellar ataxia and myoclonus. Mean life expectancy from the onset of symptoms is 6 months. There are currently diagnostic criteria based on clinical phenotype, as well as neuroimaging biomarkers (magnetic resonance imaging), neurophysiological tests (electroencephalogram and polysomnogram), and cerebrospinal fluid biomarkers (14-3-3 protein and real-time quaking-induced conversion (RT-QuIC)). The sensitivity and specificity of some of these tests (electroencephalogram and 14-3-3 protein) is under debate and the applicability of other tests, such as RT-QuIC, is not universal. However, the usefulness of these biomarkers beyond the most frequent prion disease, sporadic Creutzfeldt-Jakob disease, remains unclear. Therefore, research is being carried out on new, more efficient cerebrospinal fluid biomarkers (total tau, ratio total tau/phosphorylated tau and neurofilament light chain) and potential blood biomarkers (neurofilament light chain, among others) to try to universalize access to early diagnosis in the case of prion diseases.
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- 2022
4. The A beta 1-42/A beta 1-40 ratio in CSF is more strongly associated to tau markers and clinical progression than A beta 1-42 alone
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Delaby, C, Estelles, T, Zhu, NU, Arranz, J, Barroeta, I, Carmona-Iragui, M, Illan-Gala, I, Santos-Santos, MA, Altuna, M, Sala, I, Sanchez-Saudinos, MB, Videla, L, Valldeneu, S, Subirana, A, Tondo, M, Blanco-Vaca, F, Lehmann, S, Belbin, O, Blesa, R, Fortea, J, Lleo, A, and Alcolea, D
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Amyloid ,A beta 1-40 ,Cerebrospinal fluid ,A beta 1-42 ,Tau ,Biomarkers - Abstract
Background: Cerebrospinal fluid (CSF) A beta 1-42 levels and the A beta 1-42/A beta 1-40 ratio are markers of amyloid pathology, but previous studies suggest that their levels might be influenced by additional pathophysiological processes. Aims: To compare A beta 1-42 and the A beta 1-42/A beta 1-40 ratio in CSF in different neurodegenerative disorders and study their association with other biomarkers (tTau, pTau181, and NfL) and with cognitive and functional progression. Methods: We included all participants from the Sant Pau Initiative on Neurodegeneration (SPIN) with CSF A beta 1-42 and A beta 1-42/A beta 1-40. Participants had diagnoses of Alzheimer's disease (AD), dementia with Lewy bodies, frontotemporal lobar degeneration-related syndromes, non-neurodegenerative conditions, or were cognitively normal. We classified participants as"positive" or"negative" according to each marker. We compared CSF levels of tTau, pTau181, and NfL between concordant and discordant groups through ANCOVA and assessed differences in cognitive (MMSE, FCSRT) and functional (GDS, CDR-SOB) progression using Cox regression and linear-mixed models. Results: In the 1791 participants, the agreement between A beta 1-42 and A beta 1-42/A beta 1-40 was 78.3%. The A beta 1-42/A beta 1-40 ratio showed a stronger correlation with tTau and pTau181 than A beta 1-42 and an agreement with tTau and pTau181 of 73.1% and 77.1%, respectively. Participants with a low A beta 1-42/A beta 1-40 ratio showed higher tTau and pTau181 and worse cognitive and functional prognosis, regardless of whether they were positive or negative for A beta 1-42. The results were consistent across stages, diagnostic categories, and use of different cutoffs. Conclusion: Although A beta 1-42 and A beta 1-42/A beta 1-40 are considered markers of the same pathophysiological pathway, our findings provide evidence favoring the use of the A beta 1-42/A beta 1-40 ratio in clinical laboratories in the context of AD.
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- 2022
5. Y-Chromosomal Evidence for a Founder Effect in Mbyá-Guaraní Amerindians from Northeast Argentina
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ALTUNA, M. EUGENIA, MODESTI, NIDIA M., and DEMARCHI, DARÍO A.
- Published
- 2006
6. Precipitation of Nb in Ferrite After Austenite Conditioning. Part I: Microstructural Characterization
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Iza-Mendia, A., Altuna, M. A., Pereda, B., and Gutiérrez, I.
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- 2012
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7. Precipitation of Nb in Ferrite After Austenite Conditioning. Part II: Strengthening Contribution in High-Strength Low-Alloy (HSLA) Steels
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Altuna, M. A., Iza-Mendia, Amaia, and Gutiérrez, I.
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- 2012
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8. Metabolite Signature of Alzheimer's Disease in Adults with Down Syndrome
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Montal, V, Barroeta, I, Bejanin, A, Pegueroles, J, Carmona-Iragui, M, Altuna, M, Benejam, B, Videla, L, Fernandez, S, Padilla, C, Aranha, MR, Iulita, MF, Vidal-Pineiro, D, Alcolea, D, Blesa, R, Lleo, A, and Fortea, J
- Abstract
Objective The purpose of this study was to examine the Alzheimer's disease metabolite signature through magnetic resonance spectroscopy in adults with Down syndrome and its relation with Alzheimer's disease biomarkers and cortical thickness. Methods We included 118 adults with Down syndrome from the Down Alzheimer Barcelona Imaging Initiative and 71 euploid healthy controls from the Sant Pau Initiative on Neurodegeneration cohort. We measured the levels of myo-inositol (a marker of neuroinflammation) and N-acetyl-aspartate (a marker of neuronal integrity) in the precuneus using magnetic resonance spectroscopy. We investigated the changes with age and along the disease continuum (asymptomatic, prodromal Alzheimer's disease, and Alzheimer's disease dementia stages). We assessed the relationship between these metabolites and A beta(42)/A beta(40) ratio, phosphorylated tau-181, neurofilament light (NfL), and YKL-40 cerebrospinal fluid levels as well as amyloid positron emission tomography uptake using Spearman correlations controlling for multiple comparisons. Finally, we computed the relationship between cortical thickness and metabolite levels using Freesurfer. Results Asymptomatic adults with Down syndrome had a 27.5% increase in the levels of myo-inositol, but equal levels of N-acetyl-aspartate compared to euploid healthy controls. With disease progression, myo-inositol levels increased, whereas N-acetyl-aspartate levels decreased in symptomatic stages of the disease. Myo-inositol was associated with amyloid, tau, and neurodegeneration markers, mainly at symptomatic stages of the disease, whereas N-acetyl-aspartate was related to neurodegeneration biomarkers in symptomatic stages. Both metabolites were significantly associated with cortical thinning, mainly in symptomatic participants. Interpretation Magnetic resonance spectroscopy detects Alzheimer's disease related inflammation and neurodegeneration, and could be a good noninvasive disease-stage biomarker in Down syndrome. ANN NEUROL 2021
- Published
- 2021
9. Sleep Disorders in Adults with Down Syndrome
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Gimenez, S, Altuna, M, Blessing, E, Osorio, RM, and Fortea, J
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Down syndrome ,insomnia ,aging ,sleep disorders ,Alzheimer's disease ,obstructive sleep apnea - Abstract
Sleep disorders, despite being very frequent in adults with Down syndrome (DS), are often overlooked due to a lack of awareness by families and physicians and the absence of specific clinical sleep guidelines. Untreated sleep disorders have a negative impact on physical and mental health, behavior, and cognitive performance. Growing evidence suggests that sleep disruption may also accelerate the progression to symptomatic Alzheimer's disease (AD) in this population. It is therefore imperative to have a better understanding of the sleep disorders associated with DS in order to treat them, and in doing so, improve cognition and quality of life, and prevent related comorbidities. This paper reviews the current knowledge of the main sleep disorders in adults with DS, including evaluation and management. It highlights the existing gaps in knowledge and discusses future directions to achieve earlier diagnosis and better treatment of sleep disorders most frequently found in this population.
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- 2021
10. Epilepsy in Down Syndrome: A Highly Prevalent Comorbidity
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Altuna, M, Gimenez, S, and Fortea, J
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down syndrome ,aging ,epilepsy ,Alzheimer's disease ,seizures - Abstract
Individuals with Down syndrome (DS) have an increased risk for epilepsy during the whole lifespan, but especially after age 40 years. The increase in the number of individuals with DS living into late middle age due to improved health care is resulting in an increase in epilepsy prevalence in this population. However, these epileptic seizures are probably underdiagnosed and inadequately treated. This late onset epilepsy is linked to the development of symptomatic Alzheimer's disease (AD), which is the main comorbidity in adults with DS with a cumulative incidence of more than 90% of adults by the seventh decade. More than 50% of patients with DS and AD dementia will most likely develop epilepsy, which in this context has a specific clinical presentation in the form of generalized myoclonic epilepsy. This epilepsy, named late onset myoclonic epilepsy (LOMEDS) affects the quality of life, might be associated with worse cognitive and functional outcomes in patients with AD dementia and has an impact on mortality. This review aims to summarize the current knowledge about the clinical and electrophysiological characteristics, diagnosis and treatment of epileptic seizures in the DS population, with a special emphasis on LOMEDS. Raised awareness and a better understanding of epilepsy in DS from families, caregivers and clinicians could enable earlier diagnoses and better treatments for individuals with DS.
- Published
- 2021
11. Hepatic 11 beta-hydroxysteroid dehydrogenase 1 involvement in alterations of glucose metabolism produced by acidotic stress in rat
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Altuna, M. E., Mazzetti, M. B., Rago, L. F., San Martín de Viale, L. C., and Damasco, M. C.
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- 2009
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12. Differential levels of Neurofilament Light protein in cerebrospinal fluid in patients with a wide range of neurodegenerative disorders
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Delaby, Constance, Alcolea, Daniel, Carmona Iragui, María, Illán-Gala, Ignacio, Morenas-Rodríguez, E., Barroeta, Isabel, Altuna, M., Estellés, T., Santos-Santos, M., Turon-Sans, J., Muñoz, L., Ribosa-Nogué, Roser, Sala-Matavera, I., Sánchez-Saudinós, María Belén, Subirana, A., Videla, L., Benejam, Bessy, Sirisi Dolcet, Sonia, Lehmann, S., Belbin, Olivia, Clarimón, Jordi, Blesa, Rafael, Pagonabarraga Mora, Javier, Rojas-Garcia, Ricard, Fortea, Juan, Lleó, Alberto, Universitat Autònoma de Barcelona, Delaby, Constance, Alcolea, Daniel, Carmona Iragui, María, Illán-Gala, Ignacio, Morenas-Rodríguez, E., Barroeta, Isabel, Altuna, M., Estellés, T., Santos-Santos, M., Turon-Sans, J., Muñoz, L., Ribosa-Nogué, Roser, Sala-Matavera, I., Sánchez-Saudinós, María Belén, Subirana, A., Videla, L., Benejam, Bessy, Sirisi Dolcet, Sonia, Lehmann, S., Belbin, Olivia, Clarimón, Jordi, Blesa, Rafael, Pagonabarraga Mora, Javier, Rojas-Garcia, Ricard, Fortea, Juan, Lleó, Alberto, and Universitat Autònoma de Barcelona
- Abstract
Altres ajuts: "Marató TV3" grant (20141210, 044412, 20143710)., Cerebrospinal fluid (CSF) biomarkers are useful in the diagnosis and the prediction of progression of several neurodegenerative diseases. Among them, CSF neurofilament light (NfL) protein has particular interest, as its levels reflect neuroaxonal degeneration, a common feature in various neurodegenerative diseases. In the present study, we analyzed NfL levels in the CSF of 535 participants of the SPIN (Sant Pau Initiative on Neurodegeneration) cohort including cognitively normal participants, patients with Alzheimer disease (AD), Down syndrome (DS), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We evaluated the differences in CSF NfL accross groups and its association with other CSF biomarkers and with cognitive scales. All neurogenerative diseases showed increased levels of CSF NfL, with the highest levels in patients with ALS, FTD, CBS and PSP. Furthermore, we found an association of CSF NfL levels with cognitive impairment in patients within the AD and FTD spectrum and with AD pathology in DLB and DS patients. These results have implications for the use of NfL as a marker in neurodegenerative diseases.
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- 2020
13. Differential levels of Neurofilament Light protein in cerebrospinal fluid in patients with a wide range of neurodegenerative disorders
- Author
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Delaby, C., primary, Alcolea, D., additional, Carmona-Iragui, M., additional, Illán-Gala, I., additional, Morenas-Rodríguez, E., additional, Barroeta, I., additional, Altuna, M., additional, Estellés, T., additional, Santos-Santos, M., additional, Turon-Sans, J., additional, Muñoz, L., additional, Ribosa-Nogué, R., additional, Sala-Matavera, I., additional, Sánchez-Saudinos, B., additional, Subirana, A., additional, Videla, L., additional, Benejam, B., additional, Sirisi, S., additional, Lehmann, S., additional, Belbin, O., additional, Clarimon, J., additional, Blesa, R., additional, Pagonabarraga, J., additional, Rojas-Garcia, R., additional, Fortea, J., additional, and Lleó, A., additional
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- 2020
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14. Trends in Outcomes for Neonates Born Very Preterm and Very Low Birth Weight in 11 High-Income Countries
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Lui K, Lee S, Kusuda S, Adams M, Vento M, Reichman B, Darlow B, Lehtonen L, Modi N, Norman M, Hakansson S, Bassler D, Rusconi F, Lodha A, Yang J, Shah P, Marshall P, Schmidt P, Dhawan A, Craven P, de Waal K, Simmer K, Gill A, Pillow J, Stack J, Birch P, Cooke L, Casalaz D, Holberton J, Stewart A, Downe L, Stewart M, Bajuk B, Berry A, Hunt R, Kilburn C, De Paoli T, Bolisetty S, Paradisis M, Rieger I, Koorts P, Kuschel C, Doyle L, Numa A, Carlisle H, Badawi N, Loughran-Fowlds A, Koh G, Davis J, Luig M, Andersen C, Chambers G, Austin N, Lynn A, Edmonds L, Mildenhall L, Buksh M, Battin M, van den Boom J, Bourchier D, Richardson V, Dineen F, Rajadurai V, Lam S, Fung G, Harrison A, Synnes A, Cieslak Z, Sherlock R, Yee W, Aziz K, Fajardo C, Kalapesi Z, Sankaran K, Daspal S, Seshia M, Alvaro R, Mukerji A, Da Silva O, Nwaesei C, Lee K, Dunn M, Lemyre B, Dow K, Pelausa E, Barrington K, Drolet C, Piedboeuf B, Claveau M, Beltempo M, Bertelle V, Masse E, Canning R, Makary H, Ojah C, Monterrosa L, Deshpandey A, Afifi J, Kajetanowicz A, Andersson S, Tammela O, Sankilampi U, Saarela T, Prazad P, Noguchi A, McWan K, Button B, Stratton W, Hamvus A, Raghaven A, Derrick M, Hadley R, Covert R, Lablanc O, Weiss M, Bell A, Shareef M, Silvestri J, Heymann E, Zangen S, Smolkin T, Mimouni F, Bader D, Rothschild A, Strauss Z, Felszer C, Omari H, Tov-Friedman S, Bar-Oz B, Feldman M, Saad N, Flidel-Rimon O, Weisbrod M, Lubin D, Litmanovitz I, Kugelman A, Shinwell E, Klinger G, Nijim Y, Bin-Nun A, Golan A, Mandel D, Fleisher-Sheffer V, Kohelet D, Bakhrakh L, Hattori S, Shirai M, Ishioka T, Mori T, Amizuka T, Huchimukai T, Yoshida H, Sasaki A, Shimizu J, Nakamura T, Maruyama M, Matsumoto H, Hosokawa S, Taki A, Nakagawa M, Ko K, Uozumi A, Nakata S, Shimazaki A, Yoda T, Numata O, Imamura H, Kobayashi A, Tokuriki S, Uchida Y, Arai T, Ito M, Ieda K, Ono T, Hayashi M, Maki K, Yamakawa M, Kawai M, Fujii N, Shiomi K, Nozaki K, Wada H, Kim T, Tokunaga Y, Takatera A, Oshima T, Sumida H, Michinomae Y, Kusumoto Y, Yoshimoto S, Morisawa T, Ohashi T, Takahashi Y, Sugimoto M, Ono N, Miyagawa S, Saijo T, Yamagami T, Koyano K, Kobayashi S, Kanda T, Sakemi Y, Aoki M, Iida K, Goshi M, Maruyama Y, Avila-Alvarez A, Ting J, Toye J, Fernandez-Trisac J, Pico M, Seara M, Gutierrez A, Vizcaino C, Iglesias M, Zaplana H, Colomer B, Lopez J, Mozo R, Martinez M, Sebastian M, Carbonell M, Barnusell J, Puiggros M, Aloy J, Mussons F, Sanz I, Galiana G, Coroleu W, Iriondo M, Vilella L, Porta R, Demestre X, Nadal S, Martinez C, Cuesta M, Mora D, Tardio J, Benavente I, Alonso A, Olmos R, Cabezas M, Jimenez M, Caballero P, Diaz M, Fagundo A, Canals L, Rodrigo F, Marti L, Galdo M, Suazo J, Lopez E, Fernandez J, Altuna M, Muga O, Navarro D, Dominguez M, del Prado M, Diez I, Benavides M, Lapena S, Prada T, Mir E, Sanchez A, Vega E, del Prado N, Fernandez C, Vilaplana L, Perez I, Gomez L, Comeche L, Martin I, Armengod C, Labian C, Munoz M, Bravo D, Perez V, Fernandez M, Gonzalez C, Segura S, Azorin M, Jimenez A, Sanchez-Tamayo T, Moreno E, Gonzalez M, Martinez J, Garcia J, Orayen C, Gonzalez J, Albo M, Colmenero E, Gonzalez E, del Arco B, Gordillo L, Asensio M, Diaz C, Albujar R, Jorge P, Romero S, Falero M, Izquierdo A, Capell J, Vicente M, Caballero R, Euba A, Serna A, Goya J, Legorburu A, Amoros A, Isabel V, Gonzalez N, Gracia S, Faci P, Villagrasa M, Macian M, Kofron J, Brodd K, Odlind A, Alberg L, Arwehed S, Hafstrom O, Kasemo A, Nederman K, Ahman L, Ingemarsson F, Petersson H, Thurn P, Albinsson E, Selander B, Abrahamsson T, Heimdahl I, Sveinsdottir K, Wejryd E, Hedlund A, Soderberg M, Hallberg B, Brune T, Backstrom J, Robinson J, Farooqi A, Normann E, Fredriksson M, Palm A, Rosenqvist U, Walde B, Hagman C, Ohlin A, Florell R, Smedsaas-Lofvenberg A, Meyer P, Anderegg C, Schulzke S, Nelle M, Wagner B, Riedel T, Kaczala G, Pfister R, Tolsa J, Roth M, Stocker M, Laubscher B, Malzacher A, Micallef J, Hegi L, Arlettaz R, Bernet V, Fiorini P, Boldrini A, Tomasini B, Kefas J, Kamalanathan A, Jayachandran, Yoxall B, McBride T, Webb D, Garr R, Hassan A, Ambadkar P, Dyke M, McDevitt K, Rewitzky G, D'Amore A, Panasa N, Settle P, Maddock N, Edi-Osagie N, Zipitis C, Heal C, Birch J, Hasib A, Soe A, Kumar N, Kisat H, Vasu V, Lama M, Gupta R, Rawlingson C, Wickham T, Theron M, Kendall G, Gupta A, Aladangady N, Ali I, Alsford L, Lopez W, Murthy V, Sullivan C, Thomas M, Bate T, Godambe S, Watts T, Kuna J, Chang J, Pai V, Huddy C, Yasin S, Nicholl R, Pandey P, Cusack J, Kairamkonda V, Muogbo D, Harry L, Simmons P, Nycyk J, Gallagher A, Pillay T, Deshpande S, Mahadevan, Moore A, Clark S, Garbash M, Lal M, Abu-Harb M, Dani C, Mittal A, Allwood A, Selter M, Munyard P, Bartle D, Paul S, Whincup G, Mallik A, Amess P, Godden C, Reynolds P, Misra I, De Halpert P, Salgia S, Sanghavi R, Wigfield R, Deketelaere A, Khashu M, Hall M, Groves C, Brown N, Brennan N, Vamvakiti K, McIntyre J, Pirie S, Jones S, Mannix P, Cairns P, Eaton M, Schwarz K, Gibson D, Miall L, Krishnamurthy, and Int Network Evaluation Outcomes iN
- Abstract
Objective To evaluate outcome trends of neonates born very preterm in 11 high-income countries participating in the International Network for Evaluating Outcomes of neonates. Study design In a retrospective cohort study, we included 154 233 neonates admitted to 529 neonatal units between January 1, 2007, and December 31, 2015, at 24(0/7) to 31(6/7) weeks of gestational age and birth weight
- Published
- 2019
15. Origin of paternal lineages in an admixed population of Northern Argentina (La Esperanza, Jujuy)
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Altuna, M. Eugenia, García, Angelina, Ramallo, Virginia, Bailliet, Graciela, Modesti, Nidia M., and Demarchi, Darío A.
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- 2009
- Full Text
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16. Aplicación de técnicas de nanoindentación y EBSD en aceros con microestructuras complejas
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Altuna, M. A. and Gutiérrez, I.
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lcsh:TN1-997 ,Mining engineering. Metallurgy ,ebsd ,Strengthening of ferrite ,TN1-997 ,Martensite ,Nanoindentation ,lcsh:Mining engineering. Metallurgy ,martensita ,nanoindentación ,endurecimiento ferrita - Abstract
In the present work, the mechanical behaviour of ferritic-perlitic and ferritic-martensitic steels has been studied. These microstructures have been obtained with different thermic treatments. For this study, the volumetric fraction of each phase and the ferrite grain size have been quantified by metallography. For mechanical characterization, tensile tests have been carried out and the nanoindentation technique has been used to analize the mechanical behaviour of each phase. The nanohardness of ferrite increases when the ferrite is surraunding by the martensite instead of the pearlite. In order to study the effect of the martensite in the ferrite, the misorientations inside the ferrite grain have been analyzed by the technique EBSD/OIM.En el presente trabajo, se ha estudiado el comportamiento mecánico de aceros con microestructuras ferrito-perlíticas y ferrito-martensíticas y la relación de estas con la microestructura. Se han obtenido las diferentes microestructuras mediante tratamientos térmicos. Mediante metalografía cuantitativa se ha determinado la fracción volumétrica de cada fase y el tamaño de grano de la ferrita. Para la caracterización mecánica, se han realizado ensayos de tracción. Con el fin de analizar el comportamiento mecánico de cada fase, se ha utilizado la técnica de nanoindentación. Se ha observado que la ferrita tiene mayor dureza si se encuentra en una microestructura ferrito-martensítica que si está en una ferrito-perlítica. Por ello, se ha estudiado el efecto que tiene la presencia de martensita en las características de la ferrita. En este estudio se han aplicado técnicas de EBSD/OIM, con las que se han analizado las desorientaciones presentes en el interior de los granos de ferrita
- Published
- 2008
17. Validando buenas prácticas en la docencia de Trabajo Social. En el camino de la innovación didáctica
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Feijòo, C. Ramos, Altuna, M. Arino, Correa, A. Berasaluze, Dellavalle, Marilena, García, J. Lorenzo, Gómez, P. Munuera, and Fernández, M. T. Pascual
- Subjects
supervision ,Social Work ,formazione alle competenze professionali ,Social Work Education ,Trabajo social ,ricerca ,competencias profesionales ,Social Work, Social Work Education, Trabajo social, competencias profesionales, supervision, Servizio sociale, formazione alle competenze professionali, ricerca ,Servizio sociale - Published
- 2015
18. Buenas prácticas en la docencia de Trabajo Social
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Ramos Feijóo, C., Dellavalle, Marilena, Ariño Altuna, M., and Munuera Gómez, M.
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Qualità della formazione ,innovazione didattica ,Competenze ,raccordo teoria/prassi - Published
- 2013
19. Relación microestructura - comportamiento mecánico en estructuras bainíticas
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Altuna, M. A. and Gutiérrez, E. I.
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Bainite ,tratamientos isotérmicos ,EBSD ,isothermal treatments ,Bainita ,comportamiento mecánico ,mechanical behaviour - Abstract
In the present work, the microestructures and their mechanical properties have been studied in different bainitic structures. Therefore, different bainitic morphologies have been produced by isothermal treatments carried out at different temperatures. For these steels, 400-450 °C is the optimum range of temperatures in order to obtain bainitic structures. If the Temperature is higher, perlite is also formed and if it is lower, martensite is obtained during quenching. SEM and EBSD/OIM techniques were applied in order to study the microstructure. Tensile tests were carried out for mechanical characterization. En el presente trabajo, se ha estudiado la microestructura de distintos tipos de estructuras bainíticas y las correspondientes propiedades mecánicas. Con el fin de generar diferentes microestructuras de tipo bainítico se han realizado tratamientos térmicos a distintas temperaturas. Para los aceros analizados, se ha obtenido que el rango óptimo, a la hora de obtener estructuras baíniticas, es aproximadamente 400-450 °C. Si la temperatura de tratamiento es más alta, se favorece la formación de perlita y, en cambio, si la temperatura es más baja, tiene lugar la formación de martensita durante el temple final. La microestructura se ha analizado mediante SEM y EBSD/OIM. La caracterización mecánica de los aceros sé ha llevado a cabo mediante ensayos de tracción.
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- 2005
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20. I Jornadas Regionales del Jabalí del Cono Sur de América.
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Castro, G., Lozano, A., and Altuna, M.
- Abstract
Copyright of Suiform Soundings is the property of IUCN SSC Wild Pig Specialist Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2017
21. Aplication of nanoindentation and EBSD techniques in complex microstructures steels.
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Altuna, M. A., primary and Gutiérrez, I., additional
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- 2008
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22. APOEpolymorphism distribution among Native Americans and related populations
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Demarchi, Darío A., primary, Salzano, Francisco M., additional, Eugenia Altuna, M., additional, Fiegenbaum, Marilu, additional, Hill, K., additional, Hurtado, A. M., additional, Tsunetto, Luiza T., additional, Petzl-Erler, M. L., additional, and Hutz, Mara H., additional
- Published
- 2005
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23. Perfil de ácidos grasos a los dos meses de vida en niños alimentados con lactancia materna frente a varias fórmulas artificiales disponibles comercialmente en España
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Benito Fernández, J., primary, Ruiz Sanz, J.I., additional, Aquino Fariña, L., additional, Pijoán Zubizarret, J.I., additional, Sasieta Altuna, M., additional, and Sanjurjo Crespo, P., additional
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- 2002
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24. APOE polymorphism distribution among Native Americans and related populations.
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Demarchi, Darío A., Salzano, Francisco M., Eugenia Altuna, M., Fiegenbaum, Marilu, Hill, K., Hurtado, A. M., Tsunetto, Luiza T., Petzl-Erler, M. L., and Hutz, Mara H.
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APOLIPOPROTEIN E ,LIPID metabolism ,CARDIOVASCULAR diseases ,GENETIC polymorphisms ,ETHNIC groups - Abstract
Background : Apolipoprotein E (apoE, protein; APOE , gene) plays a central role in lipid metabolism. Three common alleles, E *2, E *3 and E *4 have quantitative effects on lipid and lipoproteins levels, which are major risk determinants of cardiovascular diseases in several populations. Given their clinical significance, it is of interest to know the distribution of APOE variants in populations from diverse ethnic groups, as well as to determine if this polymorphism presents variations that might be associated with given evolutionary factors. Aim : We report the distribution of APOE polymorphisms in Native American populations from South America, comparing it with other native populations of the Americas and Siberia. Subjects and methods : The sample consisted of 315 individuals from nine Native American populations living at subtropical latitudes of Argentina, Brazil and Paraguay. The extended analysis included 50 populations across South and North America, Greenland and Siberia. The geographic patterns of the variation were investigated through correlation analysis, spatial autocorrelation and analysis molecular of variance (AMOVA). Results : The incidence of the most common allele ( APOE *3) in the sample analysed ranged from 0.78 to 0.98. The second allele in prevalence, APOE *4, varied from 0.00 to 0.17. The rare allele APOE *2 was found in five of the nine populations investigated. This variant was found in a male with both maternal and paternal Native American lineages, suggesting that this allele is present in Native Americans and hence should not be used as an indicator of admixture. APOE *3 and APOE *4 present, respectively, positive and negative associations with latitude, although the pattern is much more pronounced in the Northern Hemisphere than in South America. APOE *2 increases its frequency with latitude but this pattern is statistically significant only in South America. Conclusion : The overall APOE spatial pattern seems, in general, compatible with a directional demographic expansion which occurred in north-eastern Asia and much of the New World. The APOE *2 allele shows this pattern in South America but a random distribution in the Northern Hemisphere, suggesting that the possibility of selection should not be discarded. [ABSTRACT FROM AUTHOR]
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- 2005
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25. Precipitation strengthening produced by the formation in ferrite of Nb carbides
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Altuna, M. A., Iza-Mendia, A., and Isabel Gutierrez
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A Nb microalloyed steel has been thermomechanically processed at laboratory through the use of plane straincompression sequences followed by simulated coiling. Tensile samples have been machined from the obtainedspecimens in order to investigate the effect of different variables: recrystallisation or accumulated strain beforetransformation, holding in austenite and coiling temperature on the final mechanical behaviour. Transmissionelectron microscopy observation of the precipitates has been carried out after coiling at different temperatures.It has been shown that when Nb remains in solution in austenite after hot deformation, it can precipitate inferrite, leading to an important strengthening effect which is directly related to the concentration of Nb insolution before transformation and coiling temperature.
26. High mountain lakes: Extreme habitats and witnesses of environmental changes
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Catalan, J., Lluís Camarero, Felip, M., Pla, S., Ventura, M., Buchaca, T., Bartumeus, F., Mendoza, G., Miró, A., Casamayor, E. O., Medina-Sánchez, J. M., Bacardit, M., Altuna, M., Bartrons, M., and Quijano, D. D.
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Alpine lakes ,Vida en hábitats extremos ,Lagos alpinos ,Vida en hàbitats extrems ,Contaminación atmosférica difusa ,Extreme habitats ,Llacs alpins ,Relaciones cuenca-lago ,Relacions conca-llac ,Contaminació atmosfèrica difusa ,Canvi climàtic ,Cambio climático ,Long-range atmospheric pollution ,Climate change ,Catchment-lake relationships - Abstract
33 páginas, 14 figuras, 3 tablas., [EN]High mountain lakes offer research opportunities beyond what could be expected from their quantitative relevance in the Earth system. In this article we present a brief summary of the research carried out in the lakes of the Pyrenees in the last twenty years by the group of limnology of the Centre for High Mountain Research (CRAM) of the University of Barcelona. The studies can be included in three main topics: life in extreme conditions, catchment-lake relationships and environmental changes., [ES]Los lagos de montaña ofrecen oportunidades de estudio que van mucho más allá de lo que su disposición en el territorio y abundancia pudieran sugerir. En este artículo presentamos un breve resumen de los temas que hemos abordado a lo largo de poco más de veinte años de investigación en los lagos de los Pirineos por parte del grupo de limnología del Centro de Investigaciones de Alta Montaña (CRAM) de la Universidad de Barcelona. Los estudios se enmarcan fundamentalmente en tres líneas generales: la vida en condiciones extremas, las relaciones cuenca-lago y los cambios ambientales.
27. Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer's disease in the EMIF-AD study.
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Smith RG, Pishva E, Kouhsar M, Imm J, Dobricic V, Johannsen P, Wittig M, Franke A, Vandenberghe R, Schaeverbeke J, Freund-Levi Y, Frölich L, Scheltens P, Teunissen CE, Frisoni G, Blin O, Richardson JC, Bordet R, Engelborghs S, de Roeck E, Martinez-Lage P, Altuna M, Tainta M, Lleó A, Sala I, Popp J, Peyratout G, Winchester L, Nevado-Holgado A, Verhey F, Tsolaki M, Andreasson U, Blennow K, Zetterberg H, Streffer J, Vos SJB, Lovestone S, Visser PJ, Bertram L, and Lunnon K
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- Humans, Female, Male, Aged, Middle Aged, Genome-Wide Association Study, Alzheimer Disease genetics, Alzheimer Disease blood, Alzheimer Disease cerebrospinal fluid, DNA Methylation genetics, Chitinase-3-Like Protein 1 cerebrospinal fluid, Chitinase-3-Like Protein 1 genetics, Chitinase-3-Like Protein 1 blood, Biomarkers cerebrospinal fluid, Biomarkers blood, Neurofilament Proteins cerebrospinal fluid, Neurofilament Proteins blood
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Introduction: We investigated blood DNA methylation patterns associated with 15 well-established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathophysiology, neuroinflammation, and neurodegeneration., Methods: We assessed DNA methylation in 885 blood samples from the European Medical Information Framework for Alzheimer's Disease (EMIF-AD) study using the EPIC array., Results: We identified Bonferroni-significant differential methylation associated with CSF YKL-40 (five loci) and neurofilament light chain (NfL; seven loci) levels, with two of the loci associated with CSF YKL-40 levels correlating with plasma YKL-40 levels. A co-localization analysis showed shared genetic variants underlying YKL-40 DNA methylation and CSF protein levels, with evidence that DNA methylation mediates the association between genotype and protein levels. Weighted gene correlation network analysis identified two modules of co-methylated loci correlated with several amyloid measures and enriched in pathways associated with lipoproteins and development., Discussion: We conducted the most comprehensive epigenome-wide association study (EWAS) of AD-relevant CSF biomarkers to date. Future work should explore the relationship between YKL-40 genotype, DNA methylation, and protein levels in the brain., Highlights: Blood DNA methylation was assessed in the EMIF-AD MBD study. Epigenome-wide association studies (EWASs) were performed for 15 Alzheimer's disease (AD)-relevant cerebrospinal fluid (CSF) biomarker measures. Five Bonferroni-significant loci were associated with YKL-40 levels and seven with neurofilament light chain (NfL). DNA methylation in YKL-40 co-localized with previously reported genetic variation. DNA methylation potentially mediates the effect of single-nucleotide polymorphisms (SNPs) in YKL-40 on CSF protein levels., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
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- 2024
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28. Characterization of white matter hyperintensities in Down syndrome.
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Morcillo-Nieto AO, Zsadanyi SE, Arriola-Infante JE, Carmona-Iragui M, Montal V, Pegueroles J, Aranha MR, Vaqué-Alcázar L, Padilla C, Benejam B, Videla L, Barroeta I, Fernandez S, Altuna M, Giménez S, González-Ortiz S, Bargalló N, Ribas L, Arranz J, Torres S, Iulita MF, Belbin O, Camacho V, Alcolea D, Lleó A, Fortea J, and Bejanin A
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- Humans, Male, Female, Adult, Middle Aged, Gray Matter pathology, Gray Matter diagnostic imaging, Brain pathology, Brain diagnostic imaging, Aged, Down Syndrome pathology, Down Syndrome diagnostic imaging, White Matter pathology, White Matter diagnostic imaging, Magnetic Resonance Imaging, Biomarkers cerebrospinal fluid, Alzheimer Disease pathology, Alzheimer Disease cerebrospinal fluid, Alzheimer Disease diagnostic imaging
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Introduction: In Down syndrome (DS), white matter hyperintensities (WMHs) are highly prevalent, yet their topography and association with sociodemographic data and Alzheimer's disease (AD) biomarkers remain largely unexplored., Methods: In 261 DS adults and 131 euploid controls, fluid-attenuated inversion recovery magnetic resonance imaging scans were segmented and WMHs were extracted in concentric white matter layers and lobar regions. We tested associations with AD clinical stages, sociodemographic data, cerebrospinal fluid (CSF) AD biomarkers, and gray matter (GM) volume., Results: In DS, total WMHs arose at age 43 and showed stronger associations with age than in controls. WMH volume increased along the AD continuum, particularly in periventricular regions, and frontal, parietal, and occipital lobes. Associations were found with CSF biomarkers and temporo-parietal GM volumes., Discussion: WMHs increase 10 years before AD symptom onset in DS and are closely linked with AD biomarkers and neurodegeneration. This suggests a direct connection to AD pathophysiology, independent of vascular risks., Highlights: White matter hyperintensities (WMHs) increased 10 years before Alzheimer's disease symptom onset in Down syndrome (DS). WMHs were strongly associated in DS with the neurofilament light chain biomarker. WMHs were more associated in DS with gray matter volume in parieto-temporal areas., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
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- 2024
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29. Visual Deficit Related to Cataracts-A Potential Modifiable Risk Factor for Vascular Dementia.
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Altuna M
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- Humans, Risk Factors, Female, Male, Aged, Vision Disorders etiology, Aged, 80 and over, Middle Aged, Cataract complications, Dementia, Vascular etiology, Dementia, Vascular prevention & control, Dementia, Vascular epidemiology
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- 2024
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30. Unlocking Preclinical Alzheimer's: A Multi-Year Label-Free In Vitro Raman Spectroscopy Study Empowered by Chemometrics.
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Lopez E, Etxebarria-Elezgarai J, García-Sebastián M, Altuna M, Ecay-Torres M, Estanga A, Tainta M, López C, Martínez-Lage P, Amigo JM, and Seifert A
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- Humans, Machine Learning, Male, Female, Biomarkers cerebrospinal fluid, Aged, Early Diagnosis, Spectrum Analysis, Raman methods, Alzheimer Disease diagnosis, Alzheimer Disease cerebrospinal fluid
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Alzheimer's disease is a progressive neurodegenerative disorder, the early detection of which is crucial for timely intervention and enrollment in clinical trials. However, the preclinical diagnosis of Alzheimer's encounters difficulties with gold-standard methods. The current definitive diagnosis of Alzheimer's still relies on expensive instrumentation and post-mortem histological examinations. Here, we explore label-free Raman spectroscopy with machine learning as an alternative to preclinical Alzheimer's diagnosis. A special feature of this study is the inclusion of patient samples from different cohorts, sampled and measured in different years. To develop reliable classification models, partial least squares discriminant analysis in combination with variable selection methods identified discriminative molecules, including nucleic acids, amino acids, proteins, and carbohydrates such as taurine/hypotaurine and guanine, when applied to Raman spectra taken from dried samples of cerebrospinal fluid. The robustness of the model is remarkable, as the discriminative molecules could be identified in different cohorts and years. A unified model notably classifies preclinical Alzheimer's, which is particularly surprising because of Raman spectroscopy's high sensitivity regarding different measurement conditions. The presented results demonstrate the capability of Raman spectroscopy to detect preclinical Alzheimer's disease for the first time and offer invaluable opportunities for future clinical applications and diagnostic methods.
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- 2024
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31. Down Syndrome-Basque Alzheimer Initiative (DS-BAI): Clinic-Biological Cohort.
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Altuna M, Estanga A, Garrido A, Saldias J, Cañada M, Echeverria M, Larrea JÁ, Ayo P, Fiz A, Muñoz M, Santa-Inés J, García-Landarte V, and García-Sebastián M
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Background: Down syndrome (DS) is the most common genetically determined intellectual disability. In recent decades, it has experienced an exponential increase in life expectancy, leading to a rise in age-related diseases, including Alzheimer's disease (AD). Specific health plans for the comprehensive care of the DS community are an unmet need, which is crucial for the early and accurate diagnosis of main medical comorbidities. We present the protocol of a newly created clinical and research cohort and its feasibility in real life., Methods: The Down Syndrome-Basque Alzheimer Initiative (DS-BAI) is a population-based, inclusive, multidisciplinary initiative for the clinical-assistance and clinical-biological research approach to aging in DS led by the CITA-Alzheimer Foundation (Donostia, Basque Country). It aims to achieve the following: (1) provide comprehensive care for adults with DS, (2) optimize access to rigorous and quality training for socio-family and healthcare references, and (3) create a valuable multimodal clinical-biological research platform., Results: During the first year, 114 adults with DS joined the initiative, with 36% of them showing symptoms indicative of AD. Furthermore, adherence to training programs for healthcare professionals and families has been high, and the willingness to collaborate in basic and translational research has been encouraging., Conclusion: Specific health plans for DS and conducting clinical and translational research on the challenges of aging, including AD, are necessary and feasible.
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- 2024
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32. Basal forebrain atrophy along the Alzheimer's disease continuum in adults with Down syndrome.
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Rozalem Aranha M, Iulita MF, Montal V, Pegueroles J, Bejanin A, Vaqué-Alcázar L, Grothe MJ, Carmona-Iragui M, Videla L, Benejam B, Arranz J, Padilla C, Valldeneu S, Barroeta I, Altuna M, Fernández S, Ribas L, Valle-Tamayo N, Alcolea D, González-Ortiz S, Bargalló N, Zetterberg H, Blennow K, Blesa R, Wisniewski T, Busciglio J, Cuello AC, Lleó A, and Fortea J
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- Humans, Adult, Atrophy pathology, Biomarkers cerebrospinal fluid, Alzheimer Disease pathology, Down Syndrome diagnostic imaging, Down Syndrome complications, Basal Forebrain
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Background: Basal forebrain (BF) degeneration occurs in Down syndrome (DS)-associated Alzheimer's disease (AD). However, the dynamics of BF atrophy with age and disease progression, its impact on cognition, and its relationship with AD biomarkers have not been studied in DS., Methods: We included 234 adults with DS (150 asymptomatic, 38 prodromal AD, and 46 AD dementia) and 147 euploid controls. BF volumes were extracted from T-weighted magnetic resonance images using a stereotactic atlas in SPM12. We assessed BF volume changes with age and along the clinical AD continuum and their relationship to cognitive performance, cerebrospinal fluid (CSF) and plasma amyloid/tau/neurodegeneration biomarkers, and hippocampal volume., Results: In DS, BF volumes decreased with age and along the clinical AD continuum and significantly correlated with amyloid, tau, and neurofilament light chain changes in CSF and plasma, hippocampal volume, and cognitive performance., Discussion: BF atrophy is a potentially valuable neuroimaging biomarker of AD-related cholinergic neurodegeneration in DS., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
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- 2023
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33. New Community and Sociohealth Challenges Arising from the Early Diagnosis of Mild Cognitive Impairment (MCI).
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López C and Altuna M
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Population aging increases the risk of developing neurodegenerative diseases that cause cognitive impairment. Advances in clinical practice and greater social awareness of the importance of cognitive impairment have led to an increase in the number of people with early diagnosis, predementia. Increasing access to biomarkers to assess whether Alzheimer's disease (AD) is the underlying cause of mild cognitive impairment (MCI) has undoubted clinical benefits (access to potentially disease-modifying treatments, among others) but is also responsible for new social-health care challenges. Understanding the psychosocial impact of a diagnosis of MCI due to AD or another neurodegenerative disease is essential to create future strategies to reduce the emotional overload of patients, their risk of discrimination and stigmatization, and to favor their social inclusion. We present a narrative review of the diagnostic process of mild cognitive impairment in clinical practice, with a holistic person-centered approach, and discuss the implications of such diagnosis (benefits and risks) and strategies on how to address them.
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- 2023
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34. Cross-sectional versus longitudinal cognitive assessments for the diagnosis of symptomatic Alzheimer's disease in adults with Down syndrome.
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Videla L, Benejam B, Carmona-Iragui M, Barroeta I, Fernández S, Arranz J, Azzahchi SE, Altuna M, Padilla C, Valldeneu S, Pegueroles J, Montal V, Aranha MR, Vaqué-Alcázar L, Iulita MF, Alcolea D, Bejanin A, Videla S, Blesa R, Lleó A, and Fortea J
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- Adult, Humans, Longitudinal Studies, Cross-Sectional Studies, Neuropsychological Tests, Cognition, Alzheimer Disease diagnosis, Alzheimer Disease psychology, Down Syndrome complications, Down Syndrome diagnosis, Down Syndrome genetics, Cognitive Dysfunction diagnosis, Cognitive Dysfunction psychology
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Background: Down syndrome (DS) is a genetic form of Alzheimer's disease (AD). However, clinical diagnosis is difficult, and experts emphasize the need for detecting intra-individual cognitive decline., Objective: To compare the performance of baseline and longitudinal neuropsychological assessments for the diagnosis of symptomatic AD in DS., Methods: Longitudinal cohort study of adults with DS. Individuals were classified as asymptomatic, prodromal AD, or AD dementia. We performed receiver operating characteristic curve analyses to compare baseline and longitudinal changes of CAMCOG-DS and mCRT., Results: We included 562 adults with DS. Baseline assessments showed good to excellent diagnostic performance for AD dementia (AUCs between 0.82 and 0.99) and prodromal AD, higher than the 1-year intra-individual cognitive decline (area under the ROC curve between 0.59 and 0.79 for AD dementia, lower for prodromal AD). Longer follow-ups increased the diagnostic performance of the intra-individual cognitive decline., Discussion: Baseline cognitive assessment outperforms the 1-year intra-individual cognitive decline in adults with DS., (© 2023 the Alzheimer's Association.)
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- 2023
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35. Correction: Plasma glial fibrillary acidic protein and neurofilament light chain for the diagnostic and prognostic evaluation of frontotemporal dementia.
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Zhu N, Santos-Santos M, Illán-Gala I, Montal V, Estellés T, Barroeta I, Altuna M, Arranz J, Muñoz L, Belbin O, Sala I, Sánchez-Saudinós MB, Subirana A, Videla L, Pegueroles J, Blesa R, Clarimón J, Carmona-Iragui M, Fortea J, Lleó A, and Alcolea D
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- 2023
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36. Association of biological sex with clinical outcomes and biomarkers of Alzheimer's disease in adults with Down syndrome.
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Iulita MF, Bejanin A, Vilaplana E, Carmona-Iragui M, Benejam B, Videla L, Barroeta I, Fernández S, Altuna M, Pegueroles J, Montal V, Valldeneu S, Giménez S, González-Ortiz S, Torres S, El Bounasri El Bennadi S, Padilla C, Rozalem Aranha M, Estellés T, Illán-Gala I, Belbin O, Valle-Tamayo N, Camacho V, Blessing E, Osorio RS, Videla S, Lehmann S, Holland AJ, Zetterberg H, Blennow K, Alcolea D, Clarimón J, Zaman SH, Blesa R, Lleó A, and Fortea J
- Abstract
The study of sex differences in Alzheimer's disease is increasingly recognized as a key priority in research and clinical development. People with Down syndrome represent the largest population with a genetic link to Alzheimer's disease (>90% in the 7th decade). Yet, sex differences in Alzheimer's disease manifestations have not been fully investigated in these individuals, who are key candidates for preventive clinical trials. In this double-centre, cross-sectional study of 628 adults with Down syndrome [46% female, 44.4 (34.6; 50.7) years], we compared Alzheimer's disease prevalence, as well as cognitive outcomes and AT(N) biomarkers across age and sex. Participants were recruited from a population-based health plan in Barcelona, Spain, and from a convenience sample recruited via services for people with intellectual disabilities in England and Scotland. They underwent assessment with the Cambridge Cognitive Examination for Older Adults with Down Syndrome, modified cued recall test and determinations of brain amyloidosis (CSF amyloid-β 42 / 40 and amyloid-PET), tau pathology (CSF and plasma phosphorylated-tau181) and neurodegeneration biomarkers (CSF and plasma neurofilament light, total-tau, fluorodeoxyglucose-PET and MRI). We used within-group locally estimated scatterplot smoothing models to compare the trajectory of biomarker changes with age in females versus males, as well as by apolipoprotein ɛ4 carriership. Our work revealed similar prevalence, age at diagnosis and Cambridge Cognitive Examination for Older Adults with Down Syndrome scores by sex, but males showed lower modified cued recall test scores from age 45 compared with females. AT(N) biomarkers were comparable in males and females. When considering apolipoprotein ɛ4, female ɛ4 carriers showed a 3-year earlier age at diagnosis compared with female non-carriers (50.5 versus 53.2 years, P = 0.01). This difference was not seen in males (52.2 versus 52.5 years, P = 0.76). Our exploratory analyses considering sex, apolipoprotein ɛ4 and biomarkers showed that female ɛ4 carriers tended to exhibit lower CSF amyloid-β 42/amyloid-β 40 ratios and lower hippocampal volume compared with females without this allele, in line with the clinical difference. This work showed that biological sex did not influence clinical and biomarker profiles of Alzheimer's disease in adults with Down syndrome. Consideration of apolipoprotein ɛ4 haplotype, particularly in females, may be important for clinical research and clinical trials that consider this population. Accounting for, reporting and publishing sex-stratified data, even when no sex differences are found, is central to helping advance precision medicine., Competing Interests: O.B. reported receiving personal fees from ADx NeuroSciences outside the submitted work. H.Z. declares that he has served on scientific advisory boards and/or as a consultant for Abbvie, Alector, Annexon, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Pinteon Therapeutics, Red Abbey Labs, Passage Bio, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen and Roche and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, which is a part of the GU Ventures Incubator Program, outside the submitted work. K.B. declares that he has served as a consultant, on advisory boards, or data monitoring committees for Abcam, Axon, BioArctic, Biogen, JOMDD/Shimadzu, Julius Clinical, Lilly, MagQu, Novartis, Pharmatrophix, Prothena, Roche Diagnostics and Siemens Healthineers and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, which is a part of the GU Ventures Incubator Program, outside the submitted work. D.A. reported receiving personal fees for advisory board services and/or speaker honoraria from Fujirebio-Europe, Roche, Nutricia, Krka Farmacéutica and Esteve, outside the submitted work. A.L. has served as a consultant or on advisory boards for Fujirebio-Europe, Roche, Biogen and Nutricia, outside the submitted work. J.F. reported receiving personal fees for service on the advisory boards, adjudication committees or speaker honoraria from AC Immune, Novartis, Lundbeck, Roche, Fujirebio and Biogen, outside the submitted work. 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Topography of neurofibrillary tangles and granulovacuoles in hippocampi of patients with Down's syndrome: Quantitative comparison with normal ageing and Alzheimer's disease. Neuropathol Appl Neurobiol. 1981;7(1):13–20.645330161MotteJ, WilliamsRS. Age-related changes in the density and morphology of plaques and neurofibrillary tangles in Down syndrome brain. Acta Neuropathol. 1989;77(5):535–546.252415062Vila-CastelarC, Guzman-VelezE, Pardilla-DelgadoE, et alExamining sex differences in markers of cognition and neurodegeneration in autosomal dominant Alzheimer's disease: Preliminary findings from the Colombian Alzheimer's prevention initiative biomarker study. J Alzheimers Dis. 2020;77(4):1743–1753.3292506763OssenkoppeleR, LyooCH, Jester-BromsJ, et alAssessment of demographic, genetic, and imaging variables associated with brain resilience and cognitive resilience to pathological tau in patients with Alzheimer disease. JAMA Neurol. 2020;77(5):632–642.3209154964BejaninA, IulitaMF, VilaplanaE, et alAssociation of apolipoprotein E varepsilon4 allele with clinical and multimodal biomarker changes of Alzheimer disease in adults with Down syndrome. JAMA Neurol. 2021;78(8):937–947.3422804265CacciagliaR, SalvadoG, MolinuevoJL, et alAge, sex and APOE-epsilon4 modify the balance between soluble and fibrillar beta-amyloid in non-demented individuals: Topographical patterns across two independent cohorts. Mol Psychiatry. 2022;27(4):2010–2018.3523695866ChoSH, WooS, KimC, et alDisease progression modelling from preclinical Alzheimer's disease (AD) to AD dementia. Sci Rep. 2021;11(1):4168.3360301567MathysH, Davila-VelderrainJ, PengZ, et alSingle-cell transcriptomic analysis of Alzheimer's disease. Nature. 2019;570(7761):332–337.3104269768AndrewsEJ, MartiniAC, HeadE. Exploring the role of sex differences in Alzheimer's disease pathogenesis in Down syndrome. Front Neurosci. 2022;16:954999.69SchupfN, ZigmanW, KapellD, LeeJH, KlineJ, LevinB. Early menopause in women with Down's syndrome. J Intellect Disabil Res. 1997;41(Pt 3):264–267.921907670CoppusA, EvenhuisH, VerberneGJ, et alEarly age at menopause is associated with increased risk of dementia and mortality in Down syndrome. J Appl Res Intellect Disabil. 2010;23(5):408–408.71AlmeyA, MilnerTA, BrakeWG. Estrogen receptors in the central nervous system and their implication for dopamine-dependent cognition in females. Horm Behav. 2015;74:125–138.2612229472SpampinatoSF, MolinaroG, MerloS, et alEstrogen receptors and type 1 metabotropic glutamate receptors are interdependent in protecting cortical neurons against beta-amyloid toxicity. Mol Pharmacol. 2012;81(1):12–20.2198425373LiangK, YangL, YinC, et alEstrogen stimulates degradation of beta-amyloid peptide by up-regulating neprilysin. J Biol Chem. 2010;285(2):935–942.1989748574AmtulZ, WangL, WestawayD, RozmahelRF. Neuroprotective mechanism conferred by 17beta-estradiol on the biochemical basis of Alzheimer's disease. Neuroscience. 2010;169(2):781–786.2049392875Batallan BurrowesAA, OlajideOJ, IasenzaIA, ShamsWM, CarterF, ChapmanCA. Ovariectomy reduces cholinergic modulation of excitatory synaptic transmission in the rat entorhinal cortex. PLoS One. 2022;17(8):e0271131.76TaxierLR, PhilippiSM, FleischerAW, YorkJM, LaDuMJ, FrickKM. APOE4 homozygote females are resistant to the beneficial effects of 17beta-estradiol on memory and CA1 dendritic spine density in the EFAD mouse model of Alzheimer's disease. Neurobiol Aging. 2022;118:13–24.3584310977BrintonRD. Cellular and molecular mechanisms of estrogen regulation of memory function and neuroprotection against Alzheimer's disease: Recent insights and remaining challenges. Learn Mem. 2001;8(3):121–133.1139063278Garcia-SeguraLM, AzcoitiaI, DonCarlosLL. Neuroprotection by estradiol. Prog Neurobiol. 2001;63(1):29–60.1104041779CosgraveMP, TyrrellJ, McCarronM, GillM, LawlorBA. Age at onset of dementia and age of menopause in women with Down's syndrome. J Intellect Disabil Res. 1999;43(Pt 6):461–465.1062236180SchupfN, WinstenS, PatelB, et alBioavailable estradiol and age at onset of Alzheimer's disease in postmenopausal women with Down syndrome. Neurosci Lett. 2006;406(3):298–302.1692606781SchupfN, LeeJH, WeiM, et alEstrogen receptor-alpha variants increase risk of Alzheimer's disease in women with Down syndrome. Dement Geriatr Cogn Disord. 2008;25(5):476–482.1840836682de Gonzalo-CalvoD, BarroetaI, NanMN, et alEvaluation of biochemical and hematological parameters in adults with Down syndrome. Sci Rep. 2020;10(1):13755.3279261983StartinCM, D'SouzaH, BallG, et alHealth comorbidities and cognitive abilities across the lifespan in Down syndrome. 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37. Neural correlates of episodic memory in adults with Down syndrome and Alzheimer's disease.
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Benejam B, Aranha MR, Videla L, Padilla C, Valldeneu S, Fernández S, Altuna M, Carmona-Iragui M, Barroeta I, Iulita MF, Montal V, Pegueroles J, Bejanin A, Giménez S, González-Ortiz S, Videla S, Bartrés-Faz D, Alcolea D, Blesa R, Lleó A, and Fortea J
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- Adult, Atrophy, Cross-Sectional Studies, Female, Humans, Magnetic Resonance Imaging methods, Male, Memory Disorders diagnostic imaging, Memory Disorders etiology, Middle Aged, Neuropsychological Tests, Alzheimer Disease complications, Alzheimer Disease diagnostic imaging, Alzheimer Disease pathology, Down Syndrome complications, Down Syndrome diagnostic imaging, Memory, Episodic
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Background: Adults with Down syndrome are at an ultra-high risk of developing early-onset Alzheimer's disease. Episodic memory deficits are one of the earliest signs of the disease, but their association with regional brain atrophy in the population with Down syndrome has not been explored. We aimed to investigate the neuroanatomical correlates of episodic memory in adults with Down syndrome and symptomatic Alzheimer's disease., Methods: Single-center, cross-sectional study. A total of 139 adults with Down syndrome (85 asymptomatic and 54 with symptomatic Alzheimer's disease) were included in the study (mean age 43.6 ± 10.9 years, 46% female). Episodic memory was assessed using the modified Cued Recall Test. Immediate (trial 1 free immediate recall, trial 3 free immediate recall, total free immediate recall score, and total immediate score) and delayed scores (free delayed recall score and total delayed score) were examined. Cortical thickness from magnetic resonance imaging was determined with surface-based morphometry using the FreeSurfer 6.0 software package. The clusters of reduced cortical thickness were compared between symptomatic and asymptomatic participants to create a cortical atrophy map. Then, the correlation between cortical thickness and the modified Cued Recall Test subscores were separately assessed in symptomatic and asymptomatic subjects, controlling for age, sex, and severity of intellectual disability., Results: Compared with asymptomatic participants, those with symptomatic Alzheimer's disease showed a pattern of cortical atrophy in posterior parieto-temporo-occipital cortices. In symptomatic subjects, trial 1 immediate free recall significantly correlated with cortical atrophy in lateral prefrontal regions. Trial 3 free immediate recall and total free immediate recall were associated with the most widespread cortical atrophy. Total immediate score was related to posterior cortical atrophy, including lateral parietal and temporal cortex, posterior cingulate cortex, precuneus, and medial temporal lobe areas. Delayed memory scores were associated with cortical atrophy in temporoparietal and medial temporal lobe regions. No significant relationships were observed between episodic memory measures and cortical atrophy in asymptomatic subjects., Conclusions: Different episodic memory measures were associated with cortical atrophy in specific brain regions in adults with Down syndrome and Alzheimer's disease. These results overlap with those described in sporadic Alzheimer's disease and further support the similarities between Down syndrome-associated Alzheimer's disease and that in the general population., (© 2022. The Author(s).)
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38. Progressive cognitive impairment and familial spastic paraparesis due to PRESENILIN 1 mutation: anatomoclinical characterization.
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Altuna M, Larumbe R, Zelaya MV, Moreno S, García-Solaesa V, Mendioroz M, Ramos MA, and Erro ME
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- Atrophy complications, Female, Humans, Mutation genetics, Plaque, Amyloid, Seizures, Alzheimer Disease, Cognitive Dysfunction etiology, Cognitive Dysfunction genetics, Movement Disorders complications, Paraparesis, Spastic complications, Paraparesis, Spastic genetics, Presenilin-1 genetics
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Introduction: Autosomal dominant Alzheimer's disease (ADAD) due to presenilin 1 (PSEN1) mutation can induce atypical neurological symptoms such as movement disorders and epileptic seizures in the context of early-onset progressive cognitive impairment., Methods: This study includes the anatomoclinical description of three patients of two generations of the same family with movement disorders and progressive cognitive impairment. All were evaluated by trained neurologists, underwent protocolized neuropsychological evaluation, and were assessed by structural (magnetic resonance) and functional (SPECT, PET-18FDG, or PET-18F-Florbetapir) brain imaging tests. A molecular genetic study was performed for all patients, and post-mortem confirmatory anatomopathological evaluation for one of them., Results: The three female patients had an age of onset of symptoms of 38-51 years. All developed progressive multidomain cognitive impairment, paraparesis, and dysarthria, two with ophthalmoparesis and one with untriggered epileptic seizures since early stages. Bilateral cortical fronto-parietal atrophy and global cortical hypoperfusion or posterior bilateral hypometabolism were detected. PET-18F-Florbetapir, when performed, was positive for amyloid cortical deposit. The molecular genetic study confirmed the PSEN1 mutation c.869-2 A>G. Postmortem study of one of them confirmed Alzheimer's disease anatomopathological features with classic cotton wool plaques (CWP), including coexistence of amyloid angiopathy and Lewy body co-pathology., Discussion: The phenotype of ADAD due to PSEN1 mutations is very heterogeneous between and across the same family. Family history assessment should include information not only about cognitive decline, but also about movement disorders and untriggered epileptic seizures. Further studies are needed to identify genetic or epigenetic factors that determine phenotypic diversity in this disease., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)
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39. Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome.
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Videla L, Benejam B, Pegueroles J, Carmona-Iragui M, Padilla C, Fernández S, Barroeta I, Altuna M, Valldeneu S, Garzón D, Ribas L, Montal V, Arranz Martínez J, Rozalem Aranha M, Alcolea D, Bejanin A, Iulita MF, Videla Cés S, Blesa R, Lleó A, and Fortea J
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- Adult, Aged, Cognition, Cohort Studies, Female, Humans, Neuropsychological Tests, Alzheimer Disease epidemiology, Down Syndrome psychology, Intellectual Disability complications
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Importance: Alzheimer disease (AD) is the main medical problem in adults with Down syndrome (DS). However, the associations of age, intellectual disability (ID), and clinical status with progression and longitudinal cognitive decline have not been established., Objective: To examine clinical progression along the AD continuum and its related cognitive decline and to explore the presence of practice effects and floor effects with repeated assessments., Design, Setting, and Participants: This is a single-center cohort study of adults (aged >18 years) with DS with different ID levels and at least 6 months of follow-up between November 2012 and December 2021. The data are from a population-based health plan designed to screen for AD in adults with DS in Catalonia, Spain. Individuals were classified as being asymptomatic, having prodromal AD, or having AD dementia., Exposures: Neurological and neuropsychological assessments., Main Outcomes and Measures: The main outcome was clinical change along the AD continuum. Cognitive decline was measured by the Cambridge Cognitive Examination for Older Adults With Down Syndrome and the modified Cued Recall Test., Results: A total of 632 adults with DS (mean [SD] age, 42.6 [11.4] years; 292 women [46.2%]) with 2847 evaluations (mean [SD] follow-up, 28.8 [18.7] months) were assessed. At baseline, there were 436 asymptomatic individuals, 69 patients with prodromal AD, and 127 with AD dementia. After 5 years of follow-up, 17.1% (95% CI, 12.5%-21.5%) of asymptomatic individuals progressed to symptomatic AD in an age-dependent manner (0.6% [95% CI, 0%-1.8%] for age <40 years; 21.1% [95% CI, 8.0%-32.5%] for age 40-44 years; 41.4% [95% CI, 23.1%-55.3%] for age 45-49 years; 57.5% [95% CI, 38.2%-70.8%] for age ≥50 years; P < .001), and 94.1% (95% CI, 84.6%-98.0%) of patients with prodromal AD progressed to dementia with no age dependency. Cognitive decline in the older individuals was most common among those who progressed to symptomatic AD and symptomatic individuals themselves. Importantly, individuals with mild and moderate ID had no differences in longitudinal cognitive decline despite having different performance at baseline. This study also found practice and floor effects, which obscured the assessment of longitudinal cognitive decline., Conclusions and Relevance: This study found an association between the development of symptomatic AD and a high risk of progressive cognitive decline among patients with DS. These results support the need for population health plans to screen for AD-related cognitive decline from the fourth decade of life and provide important longitudinal data to inform clinical trials in adults with DS to prevent AD.
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40. DYRK1A and Activity-Dependent Neuroprotective Protein Comparative Diagnosis Interest in Cerebrospinal Fluid and Plasma in the Context of Alzheimer-Related Cognitive Impairment in Down Syndrome Patients.
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Moreau M, Carmona-Iragui M, Altuna M, Dalzon L, Barroeta I, Vilaire M, Durand S, Fortea J, Rebillat AS, and Janel N
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Down syndrome (DS) is a complex genetic condition due to an additional copy of human chromosome 21, which results in the deregulation of many genes. In addition to the intellectual disability associated with DS, adults with DS also have an ultrahigh risk of developing early onset Alzheimer's disease dementia. DYRK1A, a proline-directed serine/threonine kinase, whose gene is located on chromosome 21, has recently emerged as a promising plasma biomarker in patients with sporadic Alzheimer's disease (AD). The protein DYRK1A is truncated in symptomatic AD, the increased truncated form being associated with a decrease in the level of full-length form. Activity-dependent neuroprotective protein (ADNP), a key protein for the brain development, has been demonstrated to be a useful marker for symptomatic AD and disease progression. In this study, we evaluated DYRK1A and ADNP in CSF and plasma of adults with DS and explored the relationship between these proteins. We used mice models to evaluate the effect of DYRK1A overexpression on ADNP levels and then performed a dual-center cross-sectional human study in adults with DS in Barcelona (Spain) and Paris (France). Both cohorts included adults with DS at different stages of the continuum of AD: asymptomatic AD (aDS), prodromal AD (pDS), and AD dementia (dDS). Non-trisomic controls and patients with sporadic AD dementia were included for comparison. Full-form levels of DYRK1A were decreased in plasma and CSF in adults with DS and symptomatic AD (pDS and dDS) compared to aDS, and in patients with sporadic AD compared to controls. On the contrary, the truncated form of DYRK1A was found to increase both in CSF and plasma in adults with DS and symptomatic AD and in patients with sporadic AD with respect to aDS and controls. ADNP levels showed a more complex structure. ADNP levels increased in aDS groups vs. controls, in agreement with the increase in levels found in the brains of mice overexpressing DYRK1A. However, symptomatic individuals had lower levels than aDS individuals. Our results show that the comparison between full-length and truncated-form levels of DYRK1A coupled with ADNP levels could be used in trials targeting pathophysiological mechanisms of dementia in individuals with DS.
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41. Association of Alzheimer Disease With Life Expectancy in People With Down Syndrome.
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Iulita MF, Garzón Chavez D, Klitgaard Christensen M, Valle Tamayo N, Plana-Ripoll O, Rasmussen SA, Roqué Figuls M, Alcolea D, Videla L, Barroeta I, Benejam B, Altuna M, Padilla C, Pegueroles J, Fernandez S, Belbin O, Carmona-Iragui M, Blesa R, Lleó A, Bejanin A, and Fortea J
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- Aged, Cohort Studies, Female, Humans, Life Expectancy, Longitudinal Studies, Male, Middle Aged, Alzheimer Disease complications, Alzheimer Disease epidemiology, Down Syndrome complications, Down Syndrome epidemiology
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Importance: People with Down syndrome have a high risk of developing Alzheimer disease dementia. However, penetrance and age at onset are considered variable, and the association of this disease with life expectancy remains unclear because of underreporting in death certificates., Objective: To assess whether the variability in symptom onset of Alzheimer disease in Down syndrome is similar to autosomal dominant Alzheimer disease and to assess its association with mortality., Design, Setting, and Participants: This study combines a meta-analysis with the assessment of mortality data from US death certificates (n = 77 347 case records with a International Classification of Diseases code for Down syndrome between 1968 to 2019; 37 900 [49%] female) and from a longitudinal cohort study (n = 889 individuals; 46% female; 3.2 [2.1] years of follow-up) from the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI)., Main Outcomes and Measures: A meta-analysis was conducted to investigate the age at onset, age at death, and duration of Alzheimer disease dementia in Down syndrome. PubMed/Medline, Embase, Web of Science, and CINAHL were searched for research reports, and OpenGray was used for gray literature. Studies with data about the age at onset or diagnosis, age at death, and disease duration were included. Pooled estimates with corresponding 95% CIs were calculated using random-effects meta-analysis. The variability in disease onset was compared with that of autosomal dominant Alzheimer disease. Based on these estimates, a hypothetical distribution of age at death was constructed, assuming fully penetrant Alzheimer disease. These results were compared with real-world mortality data., Results: In this meta-analysis, the estimate of age at onset was 53.8 years (95% CI, 53.1-54.5 years; n = 2695); the estimate of age at death, 58.4 years (95% CI, 57.2-59.7 years; n = 324); and the estimate of disease duration, 4.6 years (95% CI, 3.7-5.5 years; n = 226). Coefficients of variation and 95% prediction intervals of age at onset were comparable with those reported in autosomal dominant Alzheimer disease. US mortality data revealed an increase in life expectancy in Down syndrome (median [IQR], 1 [0.3-16] years in 1968 to 57 [49-61] years in 2019), but with clear ceiling effects in the highest percentiles of age at death in the last decades (90th percentile: 1990, age 63 years; 2019, age 65 years). The mortality data matched the limits projected by a distribution assuming fully penetrant Alzheimer disease in up to 80% of deaths (corresponding to the highest percentiles). This contrasts with dementia mentioned in 30% of death certificates but is in agreement with the mortality data in DABNI (78.9%). Important racial disparities persisted in 2019, being more pronounced in the lower percentiles (10th percentile: Black individuals, 1 year; White individuals, 30 years) than in the higher percentiles (90th percentile: Black individuals, 64 years; White individuals, 66 years)., Conclusions and Relevance: These findings suggest that the mortality data and the consistent age at onset were compatible with fully penetrant Alzheimer disease. Lifespan in persons with Down syndrome will not increase until disease-modifying treatments for Alzheimer disease are available.
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42. Mechanisms Involved in Epileptogenesis in Alzheimer's Disease and Their Therapeutic Implications.
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Altuna M, Olmedo-Saura G, Carmona-Iragui M, and Fortea J
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- Aged, Amyloid beta-Peptides, Humans, Seizures, tau Proteins metabolism, Alzheimer Disease, Cognitive Dysfunction etiology, Epilepsy diagnosis, Epilepsy drug therapy, Epilepsy etiology, Epilepsy, Temporal Lobe drug therapy, Epilepsy, Temporal Lobe etiology
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Epilepsy and Alzheimer's disease (AD) incidence increases with age. There are reciprocal relationships between epilepsy and AD. Epilepsy is a risk factor for AD and, in turn, AD is an independent risk factor for developing epilepsy in old age, and abnormal AD biomarkers in PET and/or CSF are frequently found in late-onset epilepsies of unknown etiology. Accordingly, epilepsy and AD share pathophysiological processes, including neuronal hyperexcitability and an early excitatory-inhibitory dysregulation, leading to dysfunction in the inhibitory GABAergic and excitatory glutamatergic systems. Moreover, both β-amyloid and tau protein aggregates, the anatomopathological hallmarks of AD, have proepileptic effects. Finally, these aggregates have been found in the resection material of refractory temporal lobe epilepsies, suggesting that epilepsy leads to amyloid and tau aggregates. Some epileptic syndromes, such as medial temporal lobe epilepsy, share structural and functional neuroimaging findings with AD, leading to overlapping symptomatology, such as episodic memory deficits and toxic synergistic effects. In this respect, the existence of epileptiform activity and electroclinical seizures in AD appears to accelerate the progression of cognitive decline, and the presence of cognitive decline is much more prevalent in epileptic patients than in elderly patients without epilepsy. Notwithstanding their clinical significance, the diagnosis of clinical seizures in AD is a challenge. Most are focal and manifest with an altered level of consciousness without motor symptoms, and are often interpreted as cognitive fluctuations. Finally, despite the frequent association of epilepsy and AD dementia, there is a lack of clinical trials to guide the use of antiseizure medications (ASMs). There is also a potential role for ASMs to be used as disease-modifying drugs in AD.
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43. Feasibility and Long-Term Compliance to Continuous Positive Airway Pressure Treatment in Adults With Down Syndrome, a Genetic Form of Alzheimer's Disease.
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Giménez S, Farre A, Morente F, Videla L, Gutiérrez M, Clos S, Fernández A, Blanco M, Altuna M, Pegueroles J, Asensio A, Benejam B, Batista M, Barroeta I, Fortuna A, Fortea J, and Mayos M
- Abstract
Background: Down syndrome (DS) is a genetic form of Alzheimer's disease (AD) with a high prevalence of obstructive sleep apnea (OSA). These characteristics place the DS population as an optimal model to study the relationship between sleep and AD and to design clinical trials of preventive sleep therapies for AD. Regrettably, OSA treatment with continuous positive airway pressure (CPAP) is often neglected in adults with DS. In both clinical practice and research trials, it is usually presumed that these patients will not adapt to or tolerate the therapy., Study Objective: We aimed to evaluate the feasibility and long-term CPAP compliance in this population and their capacity to be enrolled in CPAP research studies., Methods: We prospectively compared the CPAP compliance of 17 OSA patients with DS and 19 age and sex matched OSA euploid patients. CPAP management and follow-up schedules were prescribed according to the habitual clinical practice. We compared group differences in tolerance, objective, and subjective hours of nightly CPAP usage at the 1st, 3rd, 6th, 12th, 24th, and 36th month visits. Good compliance was defined as at least 4 h use per night. We also investigated predictive factors of long-term CPAP compliance., Results: The percentage of DS subjects with good CPAP compliance (81.2 vs. 78.9%) and the objective CPAP use (5 vs. 6 h, p = 0.92) did not differ from the control group (CG). Subjective CPAP compliance was significantly higher in OSA patients with DS than in controls in all the follow-up visits (8 vs. 6.75 h, p = 0.001). The DS group had a significantly higher number of visits (9 vs. 5; p = 0.021) and mask changes (2.5 vs. 2; p = 0.05) than controls. Objective hours of CPAP use at the first follow-up visit predicted long-term CPAP compliance ( p < 0.005)., Conclusion: CPAP treatment is feasible and has good long-term compliance in OSA patients with DS. It should be recommended to improve health and prevent comorbidities. The DS population is indeed suitable to participate in longitudinal preventive sleep clinical trials for AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Giménez, Farre, Morente, Videla, Gutiérrez, Clos, Fernández, Blanco, Altuna, Pegueroles, Asensio, Benejam, Batista, Barroeta, Fortuna, Fortea and Mayos.)
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- 2022
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44. Role of Biomarkers for the Diagnosis of Prion Diseases: A Narrative Review.
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Altuna M, Ruiz I, Zelaya MV, and Mendioroz M
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- 14-3-3 Proteins cerebrospinal fluid, Biomarkers cerebrospinal fluid, Humans, Sensitivity and Specificity, Creutzfeldt-Jakob Syndrome cerebrospinal fluid, Creutzfeldt-Jakob Syndrome diagnosis, Prion Diseases cerebrospinal fluid, Prion Diseases diagnosis
- Abstract
Prion diseases are progressive and irreversible neurodegenerative disorders with a low incidence (1.5-2 cases per million per year). Genetic (10-15%), acquired (anecdotal) and sporadic (85%) forms of the disease have been described. The clinical spectrum of prion diseases is very varied, although the most common symptoms are rapidly progressive dementia, cerebellar ataxia and myoclonus. Mean life expectancy from the onset of symptoms is 6 months. There are currently diagnostic criteria based on clinical phenotype, as well as neuroimaging biomarkers (magnetic resonance imaging), neurophysiological tests (electroencephalogram and polysomnogram), and cerebrospinal fluid biomarkers (14-3-3 protein and real-time quaking-induced conversion (RT-QuIC)). The sensitivity and specificity of some of these tests (electroencephalogram and 14-3-3 protein) is under debate and the applicability of other tests, such as RT-QuIC, is not universal. However, the usefulness of these biomarkers beyond the most frequent prion disease, sporadic Creutzfeldt-Jakob disease, remains unclear. Therefore, research is being carried out on new, more efficient cerebrospinal fluid biomarkers (total tau, ratio total tau/phosphorylated tau and neurofilament light chain) and potential blood biomarkers (neurofilament light chain, among others) to try to universalize access to early diagnosis in the case of prion diseases.
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- 2022
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45. The Aβ1-42/Aβ1-40 ratio in CSF is more strongly associated to tau markers and clinical progression than Aβ1-42 alone.
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Delaby C, Estellés T, Zhu N, Arranz J, Barroeta I, Carmona-Iragui M, Illán-Gala I, Santos-Santos MÁ, Altuna M, Sala I, Sánchez-Saudinós MB, Videla L, Valldeneu S, Subirana A, Tondo M, Blanco-Vaca F, Lehmann S, Belbin O, Blesa R, Fortea J, Lleó A, and Alcolea D
- Subjects
- Biomarkers cerebrospinal fluid, Humans, Peptide Fragments cerebrospinal fluid, Alzheimer Disease cerebrospinal fluid, Amyloid beta-Peptides cerebrospinal fluid, tau Proteins cerebrospinal fluid
- Abstract
Background: Cerebrospinal fluid (CSF) Aβ1-42 levels and the Aβ1-42/Aβ1-40 ratio are markers of amyloid pathology, but previous studies suggest that their levels might be influenced by additional pathophysiological processes., Aims: To compare Aβ1-42 and the Aβ1-42/Aβ1-40 ratio in CSF in different neurodegenerative disorders and study their association with other biomarkers (tTau, pTau181, and NfL) and with cognitive and functional progression., Methods: We included all participants from the Sant Pau Initiative on Neurodegeneration (SPIN) with CSF Aβ1-42 and Aβ1-42/Aβ1-40. Participants had diagnoses of Alzheimer's disease (AD), dementia with Lewy bodies, frontotemporal lobar degeneration-related syndromes, non-neurodegenerative conditions, or were cognitively normal. We classified participants as "positive" or "negative" according to each marker. We compared CSF levels of tTau, pTau181, and NfL between concordant and discordant groups through ANCOVA and assessed differences in cognitive (MMSE, FCSRT) and functional (GDS, CDR-SOB) progression using Cox regression and linear-mixed models., Results: In the 1791 participants, the agreement between Aβ1-42 and Aβ1-42/Aβ1-40 was 78.3%. The Aβ1-42/Aβ1-40 ratio showed a stronger correlation with tTau and pTau181 than Aβ1-42 and an agreement with tTau and pTau181 of 73.1% and 77.1%, respectively. Participants with a low Aβ1-42/Aβ1-40 ratio showed higher tTau and pTau181 and worse cognitive and functional prognosis, regardless of whether they were positive or negative for Aβ1-42. The results were consistent across stages, diagnostic categories, and use of different cutoffs., Conclusion: Although Aβ1-42 and Aβ1-42/Aβ1-40 are considered markers of the same pathophysiological pathway, our findings provide evidence favoring the use of the Aβ1-42/Aβ1-40 ratio in clinical laboratories in the context of AD., (© 2022. The Author(s).)
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- 2022
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46. Plasma glial fibrillary acidic protein and neurofilament light chain for the diagnostic and prognostic evaluation of frontotemporal dementia.
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Zhu N, Santos-Santos M, Illán-Gala I, Montal V, Estellés T, Barroeta I, Altuna M, Arranz J, Muñoz L, Belbin O, Sala I, Sánchez-Saudinós MB, Subirana A, Videla L, Pegueroles J, Blesa R, Clarimón J, Carmona-Iragui M, Fortea J, Lleó A, and Alcolea D
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- Cross-Sectional Studies, Humans, Intermediate Filaments, Prognosis, Frontotemporal Dementia diagnostic imaging, Glial Fibrillary Acidic Protein analysis
- Abstract
Background: Astrocytes play an essential role in neuroinflammation and are involved in the pathogenesis of neurodenegerative diseases. Studies of glial fibrillary acidic protein (GFAP), an astrocytic damage marker, may help advance our understanding of different neurodegenerative diseases. In this study, we investigated the diagnostic performance of plasma GFAP (pGFAP), plasma neurofilament light chain (pNfL) and their combination for frontotemporal dementia (FTD) and Alzheimer's disease (AD) and their clinical utility in predicting disease progression., Methods: pGFAP and pNfL concentrations were measured in 72 FTD, 56 AD and 83 cognitively normal (CN) participants using the Single Molecule Array technology. Of the 211 participants, 199 underwent cerebrospinal (CSF) analysis and 122 had magnetic resonance imaging. We compared cross-sectional biomarker levels between groups, studied their diagnostic performance and assessed correlation between CSF biomarkers, cognitive performance and cortical thickness. The prognostic performance was investigated, analyzing cognitive decline through group comparisons by tertile., Results: Unlike pNfL, which was increased similarly in both clinical groups, pGFAP was increased in FTD but lower than in AD (all P < 0.01). Combination of both plasma markers improved the diagnostic performance to discriminate FTD from AD (area under the curve [AUC]: combination 0.78; pGFAP 0.7; pNfL 0.61, all P < 0.05). In FTD, pGFAP correlated with cognition, CSF and plasma NfL, and cortical thickness (all P < 0.05). The higher tertile of pGFAP was associated with greater change in MMSE score and poor cognitive outcome during follow-up both in FTD (1.40 points annually, hazard ratio [HR] 3.82, P < 0.005) and in AD (1.20 points annually, HR 2.26, P < 0.005)., Conclusions: pGFAP and pNfL levels differ in FTD and AD, and their combination is useful for distinguishing between the two diseases. pGFAP could also be used to track disease severity and predict greater cognitive decline during follow-up in patients with FTD., (© 2021. The Author(s).)
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- 2021
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47. Use of plasma biomarkers for AT(N) classification of neurodegenerative dementias.
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Alcolea D, Delaby C, Muñoz L, Torres S, Estellés T, Zhu N, Barroeta I, Carmona-Iragui M, Illán-Gala I, Santos-Santos MÁ, Altuna M, Sala I, Sánchez-Saudinós MB, Videla L, Valldeneu S, Subirana A, Pegueroles J, Hirtz C, Vialaret J, Lehmann S, Karikari TK, Ashton NJ, Blennow K, Zetterberg H, Belbin O, Blesa R, Clarimón J, Fortea J, and Lleó A
- Subjects
- Adult, Aged, Aged, 80 and over, Alzheimer Disease blood, Biomarkers blood, Cognitive Dysfunction blood, Female, Frontotemporal Dementia blood, Humans, Lewy Body Disease blood, Male, Middle Aged, Phosphorylation, Alzheimer Disease diagnosis, Amyloid beta-Peptides blood, Cognitive Dysfunction diagnosis, Frontotemporal Dementia diagnosis, Lewy Body Disease diagnosis, Neurofilament Proteins blood, tau Proteins blood
- Abstract
Objectives: All categories included in the AT(N) classification can now be measured in plasma. However, their agreement with cerebrospinal fluid (CSF) markers is not fully established. A blood signature to generate the AT(N) classification would facilitate early diagnosis of patients with Alzheimer's disease (AD) through an easy and minimally invasive approach., Methods: We measured Aβ, pTau181 and neurofilament light (NfL) in 150 plasma samples of the Sant Pau Initiative on Neurodegeneration cohort including patients with mild cognitive impairment, AD dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal participants. We classified participants in the AT(N) categories according to CSF biomarkers and studied the diagnostic value of plasma biomarkers within each category individually and in combination., Results: The plasma Aβ composite, pTau181 and NfL yielded areas under the curve (AUC) of 0.75, 0.78 and 0.88 to discriminate positive and negative participants in their respective A, T and N categories. The combination of all three markers did not outperform pTau181 alone (AUC=0.81) to discriminate A+T+ from A-T- participants. There was a moderate correlation between plasma Aβ composite and CSF Aβ1-42/Aβ1-40 (Rho=-0.5, p<0.001) and between plasma pTau181 and CSF pTau181 in the entire cohort (Rho=0.51, p<0.001). NfL levels in plasma showed high correlation with those in CSF (Rho=0.78, p<0.001)., Conclusions: Plasma biomarkers are useful to detect the AT(N) categories, and their use can differentiate patients with pathophysiological evidence of AD. A blood AT(N) signature may facilitate early diagnosis and follow-up of patients with AD through an easy and minimally invasive approach., Competing Interests: Competing interests: DA is employed by Hospital de la Santa Creu i Sant Pau and received research grants from Pla Estratègic de Recerca i Innovació en Salut (PERIS SLT006/17/125), and from Instituto de Salud Carlos III (PI18/00435 and INT19/00016). He participated in advisory boards from Fujirebio-Europe and Roche Diagnostics and received speaker honoraria from Fujirebio-Europe, Roche Diagnostics, Nutricia, Esteve and from Krka Farmacéutica S.L. CD is employed by Université de Montpellier and CHU de Montpellier. LM is employed by Biomedical Research Institute Sant Pau. ST is employed by Biomedical Research Institute Sant Pau. TE is employed by Biomedical Research Institute Sant Pau. Declarations of interest: Dr Estellés is funded by a 'Río Hortega' research grant from the Institute of Health Carlos III. NZ is employed by Hospital de la Santa Creu i Sant Pau. IB is employed by Hospital de la Santa Creu i Sant Pau. MC-I is employed by Hospital de la Santa Creu i Sant Pau. II-G is supported by the Global Brain Health Institute (Atlantic Fellow for Equity in Brain Health and pilot award for global brain health leaders GBHI ALZ UK-21-720973) and the 'Juan Rodés' grant from the Institute of Health Carlos III (JR20/00018). MAS-S is employed by Hospital de la Santa Creu i Sant Pau. He is funded by a 'Juan Rodés' research grant from the Institute of Health Carlos III. MA is employed by Biomedical Research Institute Sant Pau. Dr Altuna is funded by a 'Río Hortega' research grant from the Institute of Health Carlos III. IS is employed by Hospital de la Santa Creu i Sant Pau. MBS-S is employed by Biomedical Research Institute Sant Pau. LV is employed by Fundació Catalana Síndrome de Down. SV is employed by Biomedical Research Institute Sant Pau. AS is employed by Biomedical Research Institute Sant Pau. JP is employed by Biomedical Research Institute Sant Pau. CH is employed by Université de Montpellier et CHU de Montpellier. JV is employed by CHU de Montpellier. SL is employed by the University and the Hospital of Montpellier. He participated in advisory boards from Fujirebio-Europe and Roche. TKK is employed by the University of Gothenburg. NA is employed by the University of Gothenburg. KB is employed by Gothenburg University and Sahlgrenska University Hospital. KB has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. HZ is employed by the University of Gothenburg, Sahlgrenska University Hospital and University College London. HZ has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. OB is employed by Biomedical Research Institute Sant Pau. Dr Belbin is funded by a 'Miguel Servet' research grant from the Institute of Health Carlos III. RB is employed by Hospital de la Santa Creu i Sant Pau and received research grants from Institute of Health Carlos III, Fundació Bancària Obra Social La Caixa and Fundació La Marató de TV3. He participated in advisory boards from Lilly and Nutricia, and he received speaker honoraria and travel funding from Novartis and Nutricia. JC is employed by Biomedical Research Institute Sant Pau and received research grants from Generalitat de Catalunya and from Institute of Health Carlos III. JF is employed by Hospital de la Santa Creu i Sant Pau and received research grants from Institute of Health Carlos III, Fundació La Marató de TV3, and Pla Estratègic de Recerca i Innovació en Salut (PERIS). AL is employed by Hospital de la Santa Creu i Sant Pau and received research grants from CIBERNED, Institute of Health Carlos III and Fundación BBVA. He participated in advisory boards from Fujirebio-Europe, Nutricia, Biogen, and received speaker honoraria from Lilly., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2021
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48. Metabolite Signature of Alzheimer's Disease in Adults with Down Syndrome.
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Montal V, Barroeta I, Bejanin A, Pegueroles J, Carmona-Iragui M, Altuna M, Benejam B, Videla L, Fernández S, Padilla C, Aranha MR, Iulita MF, Vidal-Piñeiro D, Alcolea D, Blesa R, Lleó A, and Fortea J
- Subjects
- Adult, Alzheimer Disease epidemiology, Aspartic Acid analogs & derivatives, Aspartic Acid metabolism, Biomarkers metabolism, Cross-Sectional Studies, Down Syndrome epidemiology, Female, Humans, Inositol metabolism, Magnetic Resonance Imaging methods, Magnetic Resonance Spectroscopy methods, Male, Middle Aged, Positron-Emission Tomography methods, Alzheimer Disease diagnostic imaging, Alzheimer Disease metabolism, Down Syndrome diagnostic imaging, Down Syndrome metabolism, Metabolomics methods
- Abstract
Objective: The purpose of this study was to examine the Alzheimer's disease metabolite signature through magnetic resonance spectroscopy in adults with Down syndrome and its relation with Alzheimer's disease biomarkers and cortical thickness., Methods: We included 118 adults with Down syndrome from the Down Alzheimer Barcelona Imaging Initiative and 71 euploid healthy controls from the Sant Pau Initiative on Neurodegeneration cohort. We measured the levels of myo-inositol (a marker of neuroinflammation) and N-acetyl-aspartate (a marker of neuronal integrity) in the precuneus using magnetic resonance spectroscopy. We investigated the changes with age and along the disease continuum (asymptomatic, prodromal Alzheimer's disease, and Alzheimer's disease dementia stages). We assessed the relationship between these metabolites and Aβ
42 /Aβ40 ratio, phosphorylated tau-181, neurofilament light (NfL), and YKL-40 cerebrospinal fluid levels as well as amyloid positron emission tomography uptake using Spearman correlations controlling for multiple comparisons. Finally, we computed the relationship between cortical thickness and metabolite levels using Freesurfer., Results: Asymptomatic adults with Down syndrome had a 27.5% increase in the levels of myo-inositol, but equal levels of N-acetyl-aspartate compared to euploid healthy controls. With disease progression, myo-inositol levels increased, whereas N-acetyl-aspartate levels decreased in symptomatic stages of the disease. Myo-inositol was associated with amyloid, tau, and neurodegeneration markers, mainly at symptomatic stages of the disease, whereas N-acetyl-aspartate was related to neurodegeneration biomarkers in symptomatic stages. Both metabolites were significantly associated with cortical thinning, mainly in symptomatic participants., Interpretation: Magnetic resonance spectroscopy detects Alzheimer's disease related inflammation and neurodegeneration, and could be a good noninvasive disease-stage biomarker in Down syndrome. ANN NEUROL 2021;90:407-416., (© 2021 American Neurological Association.)- Published
- 2021
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49. Association of Apolipoprotein E ɛ4 Allele With Clinical and Multimodal Biomarker Changes of Alzheimer Disease in Adults With Down Syndrome.
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Bejanin A, Iulita MF, Vilaplana E, Carmona-Iragui M, Benejam B, Videla L, Barroeta I, Fernandez S, Altuna M, Pegueroles J, Montal V, Valldeneu S, Giménez S, González-Ortiz S, Muñoz L, Padilla C, Aranha MR, Estellés T, Illán-Gala I, Belbin O, Camacho V, Wilson LR, Annus T, Osorio RS, Videla S, Lehmann S, Holland AJ, Zetterberg H, Blennow K, Alcolea D, Clarimon J, Zaman SH, Blesa R, Lleó A, and Fortea J
- Subjects
- Adult, Alleles, Alzheimer Disease complications, Amyloid beta-Peptides genetics, Apolipoproteins E, Atrophy, Biomarkers, Cohort Studies, Down Syndrome complications, Female, Glucose metabolism, Heterozygote, Hippocampus pathology, Humans, Male, Middle Aged, Peptide Fragments genetics, tau Proteins genetics, Alzheimer Disease genetics, Apolipoprotein E4 genetics, Down Syndrome genetics
- Abstract
Importance: Alzheimer disease (AD) is the leading cause of death in individuals with Down syndrome (DS). Previous studies have suggested that the APOE ɛ4 allele plays a role in the risk and age at onset of dementia in DS; however, data on in vivo biomarkers remain scarce., Objective: To investigate the association of the APOE ɛ4 allele with clinical and multimodal biomarkers of AD in adults with DS., Design, Setting, and Participants: This dual-center cohort study recruited adults with DS in Barcelona, Spain, and in Cambridge, UK, between June 1, 2009, and February 28, 2020. Included individuals had been genotyped for APOE and had at least 1 clinical or AD biomarker measurement; 2 individuals were excluded because of the absence of trisomy 21. Participants were either APOE ɛ4 allele carriers or noncarriers., Main Outcomes and Measures: Participants underwent a neurological and neuropsychological assessment. A subset of participants had biomarker measurements: Aβ1-42, Aβ1-40, phosphorylated tau 181 (pTau181) and neurofilament light chain (NfL) in cerebrospinal fluid (CSF), pTau181, and NfL in plasma; amyloid positron emission tomography (PET); fluorine 18-labeled-fluorodeoxyglucose PET; and/or magnetic resonance imaging. Age at symptom onset was compared between APOE ɛ4 allele carriers and noncarriers, and within-group local regression models were used to compare the association of biomarkers with age. Voxelwise analyses were performed to assess topographical differences in gray matter metabolism and volume., Results: Of the 464 adults with DS included in the study, 97 (20.9%) were APOE ɛ4 allele carriers and 367 (79.1%) were noncarriers. No differences between the 2 groups were found by age (median [interquartile range], 45.9 [36.4-50.2] years vs 43.7 [34.9-50.2] years; P = .56) or sex (51 male carriers [52.6%] vs 199 male noncarriers [54.2%]). APOE ɛ4 allele carriers compared with noncarriers presented with AD symptoms at a younger age (mean [SD] age, 50.7 [4.4] years vs 52.7 [5.8] years; P = .02) and showed earlier cognitive decline. Locally estimated scatterplot smoothing curves further showed between-group differences in biomarker trajectories with age as reflected by nonoverlapping CIs. Specifically, carriers showed lower levels of the CSF Aβ1-42 to Aβ1-40 ratio until age 40 years, earlier increases in amyloid PET and plasma pTau181, and earlier loss of cortical metabolism and hippocampal volume. No differences were found in NfL biomarkers or CSF total tau and pTau181. Voxelwise analyses showed lower metabolism in subcortical and parieto-occipital structures and lower medial temporal volume in APOE ɛ4 allele carriers., Conclusions and Relevance: In this study, the APOE ɛ4 allele was associated with earlier clinical and biomarker changes of AD in DS. These results provide insights into the mechanisms by which APOE increases the risk of AD, emphasizing the importance of APOE genotype for future clinical trials in DS.
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- 2021
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50. Phosphorylated tau181 in plasma as a potential biomarker for Alzheimer's disease in adults with Down syndrome.
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Lleó A, Zetterberg H, Pegueroles J, Karikari TK, Carmona-Iragui M, Ashton NJ, Montal V, Barroeta I, Lantero-Rodríguez J, Videla L, Altuna M, Benejam B, Fernandez S, Valldeneu S, Garzón D, Bejanin A, Iulita MF, Camacho V, Medrano-Martorell S, Belbin O, Clarimon J, Lehmann S, Alcolea D, Blesa R, Blennow K, and Fortea J
- Subjects
- Adult, Alzheimer Disease blood, Alzheimer Disease pathology, Amyloid beta-Peptides metabolism, Area Under Curve, Atrophy, Biomarkers blood, Biomarkers metabolism, Cerebral Cortex diagnostic imaging, Cerebral Cortex metabolism, Cerebral Cortex pathology, Cognition, Cross-Sectional Studies, Disease Progression, Down Syndrome blood, Down Syndrome pathology, Female, Humans, Male, Middle Aged, Neurofilament Proteins blood, Phosphorylation, tau Proteins metabolism, Alzheimer Disease diagnosis, Down Syndrome diagnosis, tau Proteins blood
- Abstract
Plasma tau phosphorylated at threonine 181 (p-tau181) predicts Alzheimer's disease (AD) pathology with high accuracy in the general population. In this study, we investigated plasma p-tau181 as a biomarker of AD in individuals with Down syndrome (DS). We included 366 adults with DS (240 asymptomatic, 43 prodromal AD, 83 AD dementia) and 44 euploid cognitively normal controls. We measured plasma p-tau181 with a Single molecule array (Simoa) assay. We examined the diagnostic performance of p-tau181 for the detection of AD and the relationship with other fluid and imaging biomarkers. Plasma p-tau181 concentration showed an area under the curve of 0.80 [95% CI 0.73-0.87] and 0.92 [95% CI 0.89-0.95] for the discrimination between asymptomatic individuals versus those in the prodromal and dementia groups, respectively. Plasma p-tau181 correlated with atrophy and hypometabolism in temporoparietal regions. Our findings indicate that plasma p-tau181 concentration can be useful to detect AD in DS., (© 2021. The Author(s).)
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- 2021
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