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5 results on '"Geriatrics/Aging General"'

1. Long-Term Cognitive Safety of Achieving Very Low LDL Cholesterol with Evolocumab.

Author

Zimerman, André, O'Donoghue, Michelle L., Ran, Xinhui, KyungAh Im, Ott, Brian R., Mach, François, Zavitz, Kenton, Kurtz, Christopher E., Monsalvo, Maria Laura, Bei Wang, Atar, Dan, Keech, Anthony, Sabatine, Marc S., and Giugliano, Robert P.

Subjects
THERAPEUTIC use of monoclonal antibodies, PATIENT safety, COGNITIVE testing, EXECUTIVE function, STATISTICAL sampling, LDL cholesterol, ATHEROSCLEROSIS, DESCRIPTIVE statistics, RANDOMIZED controlled trials, LONGITUDINAL method, DRUG efficacy, SHORT-term memory, COGNITION, EVALUATION
Abstract

Background: Concerns persist regarding the cognitive safety of achieving very low levels of low-density lipoprotein (LDL) cholesterol. Although short-term studies are reassuring, the long-term cognitive effects of sustained exposure to very low LDL cholesterol levels through combined proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition and statin therapy remain unknown. Methods: This prospective study enrolled a subset of adults with atherosclerotic cardiovascular disease who had completed a neurocognitive substudy (EBBINGHAUS) of a placebo-controlled randomized trial of evolocumab (FOURIER) and were eligible for a long-term open-label extension. The objective of this current study was to assess the long-term effect of evolocumab on cognitive function. Cognitive function was assessed annually, and the primary end point was change from baseline in executive function within each group, measured using the spatial working memory strategy index score (range, 4-28), with lower scores indicating better performance. Results: A total of 473 patients out of the 1974 patients in the parent EBBINGHAUS study were enrolled and additionally followed for a median of 5.1 years (maximum follow-up since original random assignment 7.2 years). The median age was 62 years; 70% were male, and 91% were White. At 12 weeks into the open-label extension period, median LDL cholesterol across the overall population was 35 mg/dl (interquartile range, 21-55 mg/dl). Treatment with evolocumab was not associated with a change in executive function during the open-label extension in either patients who were originally randomly assigned to and continued evolocumab (mean±standard deviation of 0.1±2.8, P=0.49) or patients originally randomly assigned to placebo who then started on evolocumab (-0.1±2.5, P=0.64). At the final study visit, executive function scores were similar between randomly assigned groups (17.5±3.7 and 17.3±3.7, respectively). Conclusions: Exposure to very low levels of LDL cholesterol, achieved via PCSK9 inhibition and statin therapy, was not associated with cognitive impairment through long-term follow-up. Further studies are needed to assess the generalizability to adults at higher risk of dementia. [ABSTRACT FROM AUTHOR]

Published
2025
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2. Low LDL, High Reassurance? Evolocumab's Long-Term Cognitive Safety Profile.

Author

Zorcic, Katarina and Gill, Sudeep S.

Subjects
DRUG therapy for hyperlipidemia, CARDIOVASCULAR disease prevention, COGNITION disorder risk factors, THERAPEUTIC use of protease inhibitors, RISK assessment, PATIENT safety, ANTILIPEMIC agents, LDL cholesterol, MONOCLONAL antibodies
Abstract

The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) invigorated the cardiology community, refining our understanding of cholesterol metabolism and building on prior successes in the development of effective lipid-lowering medications. In 2003, Abifadel et al. discovered mutations in the PCSK9 gene linked to autosomal dominant hypercholesterolemia. The potential of a novel target for lipid-lowering emerged, and shortly thereafter, the development of PCSK9 inhibitors began. Early clinical trials demonstrated that PCSK9 inhibitors lowered low-density lipoprotein cholesterol (LDL-C) levels by approximately 60%, opening new avenues for potentially reducing adverse cardiovascular events in high-risk populations. [ABSTRACT FROM AUTHOR]

Published
2025
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3. How Should Elevated Blood Pressure Be Managed in Hospital?

Author

Fralick, Michael, Wilson, Linnea M., Abebe, Kaleab Z., and Anderson, Timothy S.

Subjects
HYPERTENSION, MEDICAL care, HOSPITALS, GOAL (Psychology), TREATMENT effectiveness, RANDOMIZED controlled trials, PROFESSIONS, BLOOD pressure measurement, EVALUATION
Abstract

During hospitalization, patients' blood pressure often varies substantially from their outpatient steady state and many patients experience marked fluctuations. Given a lack of guidelines for inpatient blood pressure management, treatment patterns vary and recent observational studies demonstrate intensive inpatient blood pressure treatment may be been associated with harm. This article reviews current knowledge in inpatient blood pressure management and proposes a randomized trial to compare clinical outcomes of more versus less restrictive blood pressure goals. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Trial of Deferiprone in Parkinson’s Disease

Author

Devos, David, Labreuche, Julien, Dušek, Petr, Post, Bart, Bloem, Bastiaan R, Berg, Daniela, Maetzler, Walter, Otto, Markus, Habert, Marie-Odile, Lehericy, Stéphane, Ferreira, Joaquim, Dodel, Richard, Rascol, Olivier, Tranchant, Christine, Eusebio, Alexandre, Thobois, Stéphane, Marques, Ana-Raquel, Meissner, Wassilios G, Ory-Magne, Fabienne, Walter, Uwe, de Bie, Rob M A, Gago, Miguel, Vilas, Dolores, Corvol, Jean-Christophe, Kulisevsky, Jaime, Januario, Cristina, Coelho, Miguel V S, Behnke, Stefanie, Worth, Paul, Seppi, Klaus, Ouk, Thavarak, Potey, Camille, Leclercq, Céline, Viard, Romain, Duhamel, Alain, Kuchcinski, Gregory, Lopes, Renaud, Pruvo, Jean-Pierre, Pigny, Pascal, Garçon, Guillaume, Simonin, Ophélie, Carpentier, Jessica, Rolland, Anne-Sophie, Nyholm, Dag, Scherfler, Christoph, Guyon Delannoy, Pauline, Mangin, Jean-François, Chupin, Marie, Bordet, Régis, Dexter, David T, Fradette, Caroline, Spino, Michael, Tricta, Fernando, Ayton, Scott, Bush, Ashley I, Devedjian, Jean-Christophe, Poewe, Werner, Duce, James A, Cabantchik, Ioav, Defebvre, Luc, Deplanque, Dominique, Moreau, Caroline, Group, FAIRPARK-II Study, Compta, Yaroslau, Pavese, Nicola, Růžička, Evžen, Basenau, Sandra, Beliveau, Vincent, Benchetrit, Eve, Best, Laura, Bloem, Bas, Bonicel, Robin, Boraud, T., Bordet, Regis, Bouca, Raquel, Bourdain, Frédéric, Bouzas, Jimena, Brefel-Courbon, Christine, Bubenheim, Michael, Burn, David, Bush, Ashley I, Cabantchik, Ioav, Calvas, Fabienne, Cámara, Ana, Campolongo, Antonia, Carrière, Nicolas, Chaigneau, Véronique, Matthieu, Collin, Compta, Yaroslau, Connelly, John, Cormier-Dequaire, Florence, Cranston, Amy, Dean, Rory, De Marzi, Roberto, Degos, Bertrand, Demotes, Jacques, Dellapina, Estelle, Deplanque, Dominique, Devedjian, Jean-Christophe, Devos, David, Dexter, David, Dodel, Richard, Dongmo, Carole, Duce, James, Duhamel, Alain, Dupouy, Julia, Dusek, Petr, El Mountassir, Fouzia, Eyvrard, Frédéric, Fernández, Manel, Ferreira, Joaquim, Forni, Gian Luca, Foster, Victoria, Foubert-Samier, Alexandra, Fradette, Caroline, Fréville, Laëtitia, Galitzky, Monique, Gaudebout, Cecile, Gelé, Patrick, Giladi, Nir, Grabli, David, Gleixner, Franck, Grolez, Guillaume, Guyon, Pauline, Habert, Marie-Odile, Harroch, Estelle, Hartmann, Andreas, Hirsch, Denise, Hisbergues, Michael, Hobert, Markus A, Hopfner, Franziska, Jurado, Camille, Kaiser, Andreas, Keen, Gill, Klaus, Seppi, Kouassi, Nadège, Labreuch, Julien, Lacomblez, Lucette, Lagha Boukbiza, Ouhaid, Lanthaler, Barbara, Lechatellier, Gilles, Le Forestier, Nadine, Lehmann, Fred, Lloret, Teresa, Le Naour, J., Le Toullec, Benjamin, Locatelli, Maxime, Löhle, Matthias, Lomeña, F., Longato, Nadine, Lützen, Ulf, McNichol, Ann, Maetzler, Corina, Maetzler, Walter, Mahlknecht, Philipp, Mangone, Graziella, Marín-Lahoz, Juan, Mariani, Louise-Laure, Marques, Ana, Matei, Mihaela, Matthias, Löhle, Maucourt Bacchi, Emilie, Meissner, Wassilios, Michon, Amelie, Moreau, Caroline, Nardocci, Nardo, Nosal, Florence, Nyholm, Dag, Oeckl, Patrick, Oravska, Irena, Ory, Fabienne, Otto, Markus, Ouk, Thavarak, Pagonabarraga, Javier, Pascual-Sedano, Berta, Peball, Marina, Phillips, Clélie, Pineau, Fanny, Planellas, Lluís, Pop-Ilieva, Chiesi, Rabier, Aurélie, Olivier, D., Riedel, Christian, Rodrigues, Maura, Roullet-Solignac, Isabelle, Rose, Christian, Rozova, Anna, Růžička, Evžen, Salis, Alexandra, Schäffer, Eva, Scherfler, Christoph, Schiefermeier, Natalia, Seppi, Klaus, Smagghe, Delphine, Silva, Tânia, Silva, Pedro, Socha, Julie, Souyris, Corinne, Spampinato, Umberto, Spino, Michael, Steel, Alison, Sweta, Bajaj, Thalamas, Claire, Teodor, Danaila, Teresa, Anna, Tison, François, Tolosa, Eduardo, Tricta, Fernando, Trifirò Trifirò, Gianluca, Vidailhet, Marie, Wang, Yi, Werkmann, Mario, Yilmas, Rezzak, You, Hana, Zeuner, Kirsten, Defebvre, Luc, Rascol, Olivier, Tranchant, Christine, Eusebio, Alexandre, Thobois, Stéphane, Corvol, Jean-Christophe, Durif, Franck, Meissner, Wassilos, Yaroslau, Compta, Vilas, Dolores, Kulisevsky, Jaime, Poewe, Werner, Ruzicka, Evzen, Gago, Miguel, Januario, Cristina, Vilhena Soares Coelho, Miguel, Berg, Daniela, Behnke, Stefanie, Walter, Uwe, Worth, Paul, Pavese, Nicola, Post, Bart, de Bie, Rob M A, Abbruzzese, Giovanni, Accart, Bertrand, Allain, Marie-Anne, Anheim, Mathieu, Ardigo, Diego, Aracil-Bolaños, Ignacio, Baba, Paul, Bakker, Martijn, Balzer-Geldsetzer, Monika, Bargalló, Núria, Barone, Paolo, Neurology, ANS - Neurodegeneration, and APH - Aging & Later Life

Subjects
administration & dosage [Deferiprone], Dopamine, Dopamine Agents, Medizin, Administration, Oral, Levodopa, Antiparkinson Agents, therapeutic use [Dopamine Agents], therapeutic use [Deferiprone], Deferiprone, metabolism [Iron], adverse effects [Deferiprone], Geriatrics/Aging, Parkinson Disease, General Medicine, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Hematology/Oncology, chemistry [Substantia Nigra], adverse effects [Dopamine Agents], Disease Progression, administration & dosage [Dopamine Agents], physiopathology [Parkinson Disease], adverse effects [Iron Chelating Agents], Neutropenia, analysis [Iron], administration & dosage [Antiparkinson Agents], Iron, metabolism [Parkinson Disease], Neurology/Neurosurgery, therapeutic use [Levodopa], Iron Chelating Agents, pharmacology [Iron Chelating Agents], Double-Blind Method, adverse effects [Antiparkinson Agents], Genetics, diagnostic imaging [Substantia Nigra], metabolism [Substantia Nigra], Humans, ddc:610, diagnostic imaging [Brain], therapeutic use [Antiparkinson Agents], Brain Chemistry, pharmacology [Antiparkinson Agents], therapeutic use [Iron Chelating Agents], Hematology/Oncology General, chemically induced [Neutropenia], pharmacology [Deferiprone], drug therapy [Parkinson Disease], administration & dosage [Iron Chelating Agents], Geriatrics/Aging General, pharmacology [Dopamine Agents], drug effects [Substantia Nigra], Neuroscience
Abstract

Contains fulltext : 287484.pdf (Publisher’s version ) (Open Access) BACKGROUND: Iron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear. METHODS: We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome. RESULTS: A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P

Published
2022
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5. Challenges Faced and Lessons Learned from Our Trial of VTE Prophylaxis.

Author

Sacks, Chana A., Le Gal, Grégoire, and Mottier, Dominique

Subjects
THROMBOEMBOLISM prevention, VEINS, HOSPITAL care of older people
Abstract

In this Clinical Trials Case Study, the authors describe the challenges faced and lessons learned conducting a trial of venous thromboembolism prophylaxis among hospitalized older adults. [ABSTRACT FROM AUTHOR]

Published
2023
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