30 results on '"Allegri R"'
Search Results
2. Patterns and implications of neurological examination findings in autosomal dominant Alzheimer disease
- Author
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Voeglein, J, Franzmeier, N, Morris, JC, Dieterich, M, McDade, E, Simons, M, Preische, O, Hofmann, A, Hassenstab, J, Benzinger, TL, Fagan, A, Noble, JM, Berman, SB, Graff-Radford, NR, Ghetti, B, Farlow, MR, Chhatwal, JP, Salloway, S, Xiong, C, Karch, CM, Cairns, N, Perrin, RJ, Day, G, Martins, R, Sanchez-Valle, R, Mori, H, Shimada, H, Ikeuchi, T, Suzuki, K, Schofield, PR, Masters, CL, Goate, A, Buckles, V, Fox, NC, Chrem, P, Allegri, R, Ringman, JM, Yakushev, I, Laske, C, Jucker, M, Hoglinger, G, Bateman, RJ, Danek, A, Levin, J, Voeglein, J, Franzmeier, N, Morris, JC, Dieterich, M, McDade, E, Simons, M, Preische, O, Hofmann, A, Hassenstab, J, Benzinger, TL, Fagan, A, Noble, JM, Berman, SB, Graff-Radford, NR, Ghetti, B, Farlow, MR, Chhatwal, JP, Salloway, S, Xiong, C, Karch, CM, Cairns, N, Perrin, RJ, Day, G, Martins, R, Sanchez-Valle, R, Mori, H, Shimada, H, Ikeuchi, T, Suzuki, K, Schofield, PR, Masters, CL, Goate, A, Buckles, V, Fox, NC, Chrem, P, Allegri, R, Ringman, JM, Yakushev, I, Laske, C, Jucker, M, Hoglinger, G, Bateman, RJ, Danek, A, and Levin, J
- Abstract
INTRODUCTION: As knowledge about neurological examination findings in autosomal dominant Alzheimer disease (ADAD) is incomplete, we aimed to determine the frequency and significance of neurological examination findings in ADAD. METHODS: Frequencies of neurological examination findings were compared between symptomatic mutation carriers and non mutation carriers from the Dominantly Inherited Alzheimer Network (DIAN) to define AD neurological examination findings. AD neurological examination findings were analyzed regarding frequency, association with and predictive value regarding cognitive decline, and association with brain atrophy in symptomatic mutation carriers. RESULTS: AD neurological examination findings included abnormal deep tendon reflexes, gait disturbance, pathological cranial nerve examination findings, tremor, abnormal finger to nose and heel to shin testing, and compromised motor strength. The frequency of AD neurological examination findings was 65.1%. Cross-sectionally, mutation carriers with AD neurological examination findings showed a more than two-fold faster cognitive decline and had greater parieto-temporal atrophy, including hippocampal atrophy. Longitudinally, AD neurological examination findings predicted a significantly greater decline over time. DISCUSSION: ADAD features a distinct pattern of neurological examination findings that is useful to estimate prognosis and may inform clinical care and therapeutic trial designs.
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- 2023
3. Different rates of cognitive decline in autosomal dominant and late-onset Alzheimer disease
- Author
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Buckles, VD, Xiong, C, Bateman, RJ, Hassenstab, J, Allegri, R, Berman, SB, Chhatwal, JP, Danek, A, Fagan, AM, Ghetti, B, Goate, A, Graff-Radford, N, Jucker, M, Levin, J, Marcus, DS, Masters, CL, McCue, L, McDade, E, Mori, H, Moulder, KL, Noble, JM, Paumier, K, Preische, O, Ringman, JM, Fox, NC, Salloway, S, Schofield, PR, Martins, R, Voglein, J, Morris, JC, Buckles, VD, Xiong, C, Bateman, RJ, Hassenstab, J, Allegri, R, Berman, SB, Chhatwal, JP, Danek, A, Fagan, AM, Ghetti, B, Goate, A, Graff-Radford, N, Jucker, M, Levin, J, Marcus, DS, Masters, CL, McCue, L, McDade, E, Mori, H, Moulder, KL, Noble, JM, Paumier, K, Preische, O, Ringman, JM, Fox, NC, Salloway, S, Schofield, PR, Martins, R, Voglein, J, and Morris, JC
- Abstract
As prevention trials advance with autosomal dominant Alzheimer disease (ADAD) participants, understanding the similarities and differences between ADAD and “sporadic” late-onset AD (LOAD) is critical to determine generalizability of findings between these cohorts. Cognitive trajectories of ADAD mutation carriers (MCs) and autopsy-confirmed LOAD individuals were compared to address this question. Longitudinal rates of change on cognitive measures were compared in ADAD MCs (n = 310) and autopsy-confirmed LOAD participants (n = 163) before and after symptom onset (estimated/observed). LOAD participants declined more rapidly in the presymptomatic (preclinical) period and performed more poorly at symptom onset than ADAD participants on a cognitive composite. After symptom onset, however, the younger ADAD MCs declined more rapidly. The similar but not identical cognitive trajectories (declining but at different rates) for ADAD and LOAD suggest common AD pathologies but with some differences.
- Published
- 2022
4. The effect of air pollution on COVID-19 severity in a sample of patients with multiple sclerosis
- Author
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Bergamaschi, R., Ponzano, M., Schiavetti, I., Carmisciano, L., Cordioli, C., Filippi, M., Radaelli, M., Immovilli, P., Capobianco, M., De Rossi, N., Brichetto, G., Cocco, E., Scandellari, C., Cavalla, P., Pesci, I., Zito, A., Confalonieri, P., Marfia, G. A., Perini, P., Inglese, M., Trojano, M., Brescia Morra, V., Pisoni, E., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., Sormani, M. P., Abbadessa, G., Aguglia, U., Allegorico, L., Allegri, R. B. M., Alteno, A., Amato, M. P., Annovazzi, P., Antozzi, C., Appendino, L., Arena, S., Baione, V., Balgera, R., Barcella, V., Baroncini, D., Barrilà, C., Bellacosa, A., Bellucci, G., Bergamaschi, V., Bezzini, D., Biolzi, B., Bisecco, A., Bonavita, S., Borriello, G., Bosa, C., Bosco, A., Bovis, F., Bozzali, M., Brambilla, L., Brescia, M. V., Buccafusca, M., Bucciantini, E., Bucello, S., Buscarinu, M. C., Cabboi, M. P., Calabrese, M., Calabria, F., Caleri, F., Camilli, F., Caniatti, L. M., Cantello, R., Capra, R., Capuano, R., Carta, P., Celani, M. G., Cellerino, M., Cerqua, R., Chisari, C., Clerici, R., Clerico, M., Cola, G., Conte, A., Conti, M. Z., Cordano, C., Cordera, S., Corea, F., Correale, C., Cottone, S., Crescenzo, F., Curti, E., D'Ambrosio, A., D'Amico, E., Danni, M. C., D'Arma, A., Dattola, V., de Biase, S., De Luca, G., De Mercanti, S. F., De Mitri, P., De Stefano, N., Della, C. M., Mirabella, Massimiliano, MuSC-19 study, Group., Mirabella M. (ORCID:0000-0002-7783-114X), Bergamaschi, R., Ponzano, M., Schiavetti, I., Carmisciano, L., Cordioli, C., Filippi, M., Radaelli, M., Immovilli, P., Capobianco, M., De Rossi, N., Brichetto, G., Cocco, E., Scandellari, C., Cavalla, P., Pesci, I., Zito, A., Confalonieri, P., Marfia, G. A., Perini, P., Inglese, M., Trojano, M., Brescia Morra, V., Pisoni, E., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., Sormani, M. P., Abbadessa, G., Aguglia, U., Allegorico, L., Allegri, R. B. M., Alteno, A., Amato, M. P., Annovazzi, P., Antozzi, C., Appendino, L., Arena, S., Baione, V., Balgera, R., Barcella, V., Baroncini, D., Barrilà, C., Bellacosa, A., Bellucci, G., Bergamaschi, V., Bezzini, D., Biolzi, B., Bisecco, A., Bonavita, S., Borriello, G., Bosa, C., Bosco, A., Bovis, F., Bozzali, M., Brambilla, L., Brescia, M. V., Buccafusca, M., Bucciantini, E., Bucello, S., Buscarinu, M. C., Cabboi, M. P., Calabrese, M., Calabria, F., Caleri, F., Camilli, F., Caniatti, L. M., Cantello, R., Capra, R., Capuano, R., Carta, P., Celani, M. G., Cellerino, M., Cerqua, R., Chisari, C., Clerici, R., Clerico, M., Cola, G., Conte, A., Conti, M. Z., Cordano, C., Cordera, S., Corea, F., Correale, C., Cottone, S., Crescenzo, F., Curti, E., D'Ambrosio, A., D'Amico, E., Danni, M. C., D'Arma, A., Dattola, V., de Biase, S., De Luca, G., De Mercanti, S. F., De Mitri, P., De Stefano, N., Della, C. M., Mirabella, Massimiliano, MuSC-19 study, Group., and Mirabella M. (ORCID:0000-0002-7783-114X)
- Abstract
Background and purpose Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 mu g/m(3) (PM2.5), may contribute to severe COVID-19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID-19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID-19 severity amongst PwMS. Methods Data were retrieved from an Italian web-based platform (MuSC-19) which includes PwMS with COVID-19. PM2.5 2016-2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID-19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID-19 severity. Results In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID-19 course (odds ratio 1.90; p = 0.009). Conclusions Even if several other factors explain the unfavourable course of COVID-19 in PwMS, the role of air pollutants must be considered and further investigated.
- Published
- 2022
5. Religiosity/Spirituality and Mental Health in Older Adults: A Systematic Review and Meta-Analysis of Observational Studies
- Author
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Coelho-Junior, H. J., Calvani, Riccardo, Panza, F., Allegri, R. F., Picca, A., Marzetti, Emanuele, Alves, V. P., Calvani R. (ORCID:0000-0001-5472-2365), Marzetti E. (ORCID:0000-0001-9567-6983), Coelho-Junior, H. J., Calvani, Riccardo, Panza, F., Allegri, R. F., Picca, A., Marzetti, Emanuele, Alves, V. P., Calvani R. (ORCID:0000-0001-5472-2365), and Marzetti E. (ORCID:0000-0001-9567-6983)
- Abstract
Objectives: The present study investigated the association between religious and spiritual (RS) practices with the prevalence, severity, and incidence of mental health problems in older adults. Methods: We conducted a systematic review and meta-analysis of cross-sectional and longitudinal studies that investigated older adults aged 60+ years and assessed RS using valid scales and questions from valid scales, and mental health according to validated multidimensional or specific instruments. Studies were retrieved from MEDLINE, LILACS, SCOPUS, CINAHL, and AgeLine databases until July 31, 2021. The risk of bias was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS). A pooled effect size was calculated based on the log odds ratio (OR) and Z-scores. This study is registered on PROSPERO. Results: One hundred and two studies that investigated 79.918 community-dwellers, hospitalized, and institutionalized older adults were included. Results indicated that high RS was negatively associated with anxiety and depressive symptoms, while a positive association was observed with life satisfaction, meaning in life, social relations, and psychological well-being. Specifically, people with high spirituality, intrinsic religiosity, and religious affiliation had a lower prevalence of depressive symptoms. In relation to longitudinal analysis, most studies supported that high RS levels were associated with a lower incidence of depressive symptoms and fear of death, as well as better mental health status. Conclusion: Findings of the present study suggest that RS are significantly associated with mental health in older adults. People with high RS levels had a lower prevalence of anxiety and depressive symptoms, as well as reported greater life satisfaction and psychological well-being, better social relations, and more definite meaning in life. Data provided by an increasing number of longitudinal studies have supported most of these findings.
- Published
- 2022
6. SARS-CoV-2 serology after COVID-19 in multiple sclerosis: An international cohort study
- Author
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Sormani, M. P., Schiavetti, I., Landi, D., Carmisciano, L., De Rossi, N., Cordioli, C., Moiola, L., Radaelli, M., Immovilli, P., Capobianco, M., Brescia Morra, V., Trojano, M., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Fragoso, Y. D., Sen, S., Siva, A., Furlan, R., Salvetti, M., Abbadessa, G., Aguglia, U., Allegorico, L., Allegri, R. B. M., Amato, M. P., Annovazzi, P., Antozzi, C., Appendino, L., Arena, S., Baione, V., Balgera, R., Barcella, V., Baroncini, D., Barrila, C., Bellacosa, A., Bellucci, G., Bergamaschi, R., Bergamaschi, V., Bezzini, D., Biolzi, B., Bisecco, A., Bonavita, S., Borriello, G., Bosa, C., Bosco, A., Bovis, F., Bozzali, M., Brambilla, L., Brescia, M. V., Brichetto, G., Buccafusca, M., Bucciantini, E., Bucello, S., Buscarinu, M. C., Cabboi, M. P., Calabrese, M., Calabria, F., Caleri, F., Camilli, F., Caniatti, L. M., Cantello, R., Capra, R., Capuano, R., Carta, P., Cavalla, P., Celani, M. G., Cellerino, M., Cerqua, R., Chisari, C., Clerici, R., Clerico, M., Cocco, E., Cola, G., Confalonieri, P., Conte, A., Conti, M. Z., Cordano, C., Cordera, S., Corea, F., Correale, C., Cottone, S., Crescenzo, F., Curti, E., D'Ambrosio, A., D'Amico, E., Danni, M. C., D'Arma, A., Dattola, V., de Biase, S., De Luca, G., De Mercanti, S. F., De Mitri, P., De Stefano, N., Della Cava, M., di Napoli, M., Di Sapio, A., Docimo, R., Dutto, A., Evangelista, L., Fanara, S., Ferraro, D., Ferro, M. T., Filippi, M., Fioretti, C., Fratta, M., Frau, J., Fronza, M., Gajofatto, A., Gallo, A., Gallo, P., Gasperini, C., Ghazaryan, A., Giometto, B., Gobbin, F., Govone, F., Granella, F., Grange, E., Grasso, M. G., Guareschi, A., Guaschino, C., Guerrieri, S., Guidetti, D., Iaffaldano, P., Ianniello, A., Iasevoli, L., Imperiale, D., Infante, M. T., Inglese, M., Iodice, R., Iovino, A., Konrad, G., Lanzillo, R., Lapucci, C., Lavorgna, L., L'Episcopo Maria, R., Leva, S., Liberatore, G., Lo Re, M., Longoni, M., Lopiano, L., Lorefice, L., Lucchini, Matteo, Lus, G., Maimone, D., Malentacchi, M., Mallucci, G., Malucchi, S., Mancinelli, C. R., Mancinelli, L., Manganotti, P., Maniscalco, T. G., Mantero, V., Marangoni, S., Marastoni, D., Marfia, A. G., Marinelli, F., Marti, A., Martinelli Boneschi, F., Masserano Zoli, F., Matta, F., Mendozzi, L., Meucci, G., Miante, S., Miele, G., Milano, E., Mirabella, Massimiliano, Missione, R., Moccia, M., Montepietra, S., Monti Bragadin, M., Montini, F., Motta, R., Nardone, R., Nicoletti, C. G., Nobile-Orazio, E., Nozzolillo, A., Onofrj, M., Orlandi, R., Palmieri, A., Paolicelli, D., Pasquali, L., Pasto, L., Pedrazzoli, E., Perini, P., Pesci, I., Petracca, M., Petrone, A., Piantadosi, C., Pietroboni, A. M., Pinardi, F., Ponzano, M., Portaccio, E., Pozzato, M., Pozzilli, C., Prosperini, L., Protti, A., Ragonese, P., Rasia, S., Realmuto, S., Repice, A., Rigoni, E., Rilla, M. T., Rinaldi, F., Romano, C. M., Ronzoni, M., Rovaris, M., Ruscica, F., Sabattini, L., Salemi, G., Saraceno, L., Sartori, A., Sbragia, E., Scandellari, C., Scarano Giuditta, I., Scarano, V., Schillaci, V., Sessa, M., Sgarito, C., Sibilia, G., Siciliano, G., Signori, A., Signoriello, E., Sinisi, L., Sireci, F., Sola, P., Solaro, C., Sotgiu, S., Sparaco, M., Stromillo, M. L., Strumia, S., Susani, L. E., Tabiadon, G., Teatini, F., Tomassini, V., Tonietti, S., Torri, C. V., Tortorella, C., Toscano, S., Totaro, R., Trotta, M., Turano, G., Ulivelli, M., Valentino, M., Vaula, G., Vecchio, D., Vercellino, M., Verrengia, E. P., Vianello, M., Virgilio, E., Vitetta, F., Vollaro, S., Zaffaroni, M., Zampolini, M., Zarbo, I. R., Zito, A., Zuliani, L., Lucchini M. (ORCID:0000-0002-0447-2297), Mirabella M. (ORCID:0000-0002-7783-114X), Sormani, M. P., Schiavetti, I., Landi, D., Carmisciano, L., De Rossi, N., Cordioli, C., Moiola, L., Radaelli, M., Immovilli, P., Capobianco, M., Brescia Morra, V., Trojano, M., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Fragoso, Y. D., Sen, S., Siva, A., Furlan, R., Salvetti, M., Abbadessa, G., Aguglia, U., Allegorico, L., Allegri, R. B. M., Amato, M. P., Annovazzi, P., Antozzi, C., Appendino, L., Arena, S., Baione, V., Balgera, R., Barcella, V., Baroncini, D., Barrila, C., Bellacosa, A., Bellucci, G., Bergamaschi, R., Bergamaschi, V., Bezzini, D., Biolzi, B., Bisecco, A., Bonavita, S., Borriello, G., Bosa, C., Bosco, A., Bovis, F., Bozzali, M., Brambilla, L., Brescia, M. V., Brichetto, G., Buccafusca, M., Bucciantini, E., Bucello, S., Buscarinu, M. C., Cabboi, M. P., Calabrese, M., Calabria, F., Caleri, F., Camilli, F., Caniatti, L. M., Cantello, R., Capra, R., Capuano, R., Carta, P., Cavalla, P., Celani, M. G., Cellerino, M., Cerqua, R., Chisari, C., Clerici, R., Clerico, M., Cocco, E., Cola, G., Confalonieri, P., Conte, A., Conti, M. Z., Cordano, C., Cordera, S., Corea, F., Correale, C., Cottone, S., Crescenzo, F., Curti, E., D'Ambrosio, A., D'Amico, E., Danni, M. C., D'Arma, A., Dattola, V., de Biase, S., De Luca, G., De Mercanti, S. F., De Mitri, P., De Stefano, N., Della Cava, M., di Napoli, M., Di Sapio, A., Docimo, R., Dutto, A., Evangelista, L., Fanara, S., Ferraro, D., Ferro, M. T., Filippi, M., Fioretti, C., Fratta, M., Frau, J., Fronza, M., Gajofatto, A., Gallo, A., Gallo, P., Gasperini, C., Ghazaryan, A., Giometto, B., Gobbin, F., Govone, F., Granella, F., Grange, E., Grasso, M. G., Guareschi, A., Guaschino, C., Guerrieri, S., Guidetti, D., Iaffaldano, P., Ianniello, A., Iasevoli, L., Imperiale, D., Infante, M. T., Inglese, M., Iodice, R., Iovino, A., Konrad, G., Lanzillo, R., Lapucci, C., Lavorgna, L., L'Episcopo Maria, R., Leva, S., Liberatore, G., Lo Re, M., Longoni, M., Lopiano, L., Lorefice, L., Lucchini, Matteo, Lus, G., Maimone, D., Malentacchi, M., Mallucci, G., Malucchi, S., Mancinelli, C. R., Mancinelli, L., Manganotti, P., Maniscalco, T. G., Mantero, V., Marangoni, S., Marastoni, D., Marfia, A. G., Marinelli, F., Marti, A., Martinelli Boneschi, F., Masserano Zoli, F., Matta, F., Mendozzi, L., Meucci, G., Miante, S., Miele, G., Milano, E., Mirabella, Massimiliano, Missione, R., Moccia, M., Montepietra, S., Monti Bragadin, M., Montini, F., Motta, R., Nardone, R., Nicoletti, C. G., Nobile-Orazio, E., Nozzolillo, A., Onofrj, M., Orlandi, R., Palmieri, A., Paolicelli, D., Pasquali, L., Pasto, L., Pedrazzoli, E., Perini, P., Pesci, I., Petracca, M., Petrone, A., Piantadosi, C., Pietroboni, A. M., Pinardi, F., Ponzano, M., Portaccio, E., Pozzato, M., Pozzilli, C., Prosperini, L., Protti, A., Ragonese, P., Rasia, S., Realmuto, S., Repice, A., Rigoni, E., Rilla, M. T., Rinaldi, F., Romano, C. M., Ronzoni, M., Rovaris, M., Ruscica, F., Sabattini, L., Salemi, G., Saraceno, L., Sartori, A., Sbragia, E., Scandellari, C., Scarano Giuditta, I., Scarano, V., Schillaci, V., Sessa, M., Sgarito, C., Sibilia, G., Siciliano, G., Signori, A., Signoriello, E., Sinisi, L., Sireci, F., Sola, P., Solaro, C., Sotgiu, S., Sparaco, M., Stromillo, M. L., Strumia, S., Susani, L. E., Tabiadon, G., Teatini, F., Tomassini, V., Tonietti, S., Torri, C. V., Tortorella, C., Toscano, S., Totaro, R., Trotta, M., Turano, G., Ulivelli, M., Valentino, M., Vaula, G., Vecchio, D., Vercellino, M., Verrengia, E. P., Vianello, M., Virgilio, E., Vitetta, F., Vollaro, S., Zaffaroni, M., Zampolini, M., Zarbo, I. R., Zito, A., Zuliani, L., Lucchini M. (ORCID:0000-0002-0447-2297), and Mirabella M. (ORCID:0000-0002-7783-114X)
- Abstract
Background: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available. Objective: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test. Methods: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model. Results: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p = 0.002). Conclusion: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.
- Published
- 2022
7. Nuevos criterios diagnósticos clínico y neuropatológicos de la encefalopatía traumática crónica: una revisión narrativa.
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Russo MJ, Salvat F, F Allegri R, and Sevlever GE
- Abstract
La encefalopatía traumática crónica es una enfermedad neurodegenerativa resultante de la acumulación de numerosos traumatismos craneoencefálicos, para la cual no existe un diagnóstico en vida definitivo ni un tratamiento específico. Entre los factores de riesgo asociados se encuentran: la exposición a deportes de contacto que predisponen a traumatismos craneoencefálicos clínicos y subclínicos reiterados, la presencia de la apolipoproteína E4 y la edad. A escala microscópica, la lesión patognomónica de la enfermedad implica agregados de proteína tau fosforilada en neuronas, con o sin astrocitos en forma de espina, en las profundidades del surco cortical alrededor de un pequeño vaso sanguíneo, en lo profundo del parénquima y con un patrón irregular, que pueden estar acompañado en ocasiones de otros depósitos de proteínas anormales y prevalentes en otras entidades como placas de beta-amiloide, TDP-43 y/o alfa-sinucleína. Desde el punto de vista clínico se caracteriza por un curso lento e insidioso que se inicia con síntomas cognitivos leves, alteraciones del comportamiento y desregulación emocional, y progresa hacia la aparición de síntomas motores tipo parkinsonianos y demencia. La única forma de diagnosticar definitivamente la ETC es después de la muerte, durante una autopsia del cerebro. A pesar de que se han propuesto criterios diagnósticos prometedores, no están actualmente validados. Se están desarrollando biomarcadores que determinen en vida los cambios fisiopatológicos de la entidad sin necesidad de la biopsia.
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- 2024
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8. Need to adapt Alzheimer's disease criteria in Latin America.
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Custodio N, Allegri R, Lopera F, and Caramelli P
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- 2024
- Full Text
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9. Impact on the nervous system of long COVID-19 infection in children.
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Granana N, Tarulla A, Calandri I, Carli A, Rivas B, Festa JM, Vacirca S, Lis M, Worff I, and Allegri R
- Subjects
- Humans, Child, Female, Male, Adolescent, Child, Preschool, SARS-CoV-2, Nervous System Diseases virology, Risk Factors, Time Factors, Pandemics, Infant, Post-Acute COVID-19 Syndrome, COVID-19 complications
- Abstract
Background: The coronavirus disease 2019 (COVID-19) pandemic has had a profound global impact, raising concerns about its long-term effects, particularly neurological complications. While studies have highlighted such complications in adults, there is a paucity of research focusing on children., Objective: To examine the medium- to long-term neurological and cognitive symptoms in 18 year old children and below with positive versus negative COVID-19 antigens and to identify the probable risk factors to promote specific health actions., Methods: An observational study was carried out to determine neurological symptoms in the medium and long terms after COVID 19. A random sample of 124 children, both symptomatic or asymptomatic, tested positive or negative for COVID-19 through swab tests., Results: Neurological symptoms were assessed between 6 to 12 months and 2 years after the infection. Acute symptoms, including headache, anosmia, ageusia, and myalgia, were observed in more than 20% of the children, but they generally resolved within 6 to 12 months. Persistent functional difficulties, such as in studying, paying attention, and socializing, were reported in 3% of the cases. Behavioral symptoms at baseline were noted in 7.8% of children, but they were remitted in most cases, except for those with prior involvement., Conclusion: These findings underscore the need for continued monitoring of children following COVID-19 infection and the importance of tailored health interventions., Competing Interests: The authors have no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)
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- 2024
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10. Long Non-Coding RNAs and Alzheimer's Disease: Towards Personalized Diagnosis.
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Mosquera-Heredia MI, Vidal OM, Morales LC, Silvera-Redondo C, Barceló E, Allegri R, Arcos-Burgos M, Vélez JI, and Garavito-Galofre P
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- Humans, Female, Male, Aged, Precision Medicine methods, Biomarkers, Machine Learning, Aged, 80 and over, Case-Control Studies, Gene Expression Profiling methods, Computational Biology methods, Alzheimer Disease diagnosis, Alzheimer Disease genetics, RNA, Long Noncoding genetics
- Abstract
Alzheimer's disease (AD), a neurodegenerative disorder characterized by progressive cognitive decline, is the most common form of dementia. Currently, there is no single test that can diagnose AD, especially in understudied populations and developing countries. Instead, diagnosis is based on a combination of medical history, physical examination, cognitive testing, and brain imaging. Exosomes are extracellular nanovesicles, primarily composed of RNA, that participate in physiological processes related to AD pathogenesis such as cell proliferation, immune response, and neuronal and cardiovascular function. However, the identification and understanding of the potential role of long non-coding RNAs (lncRNAs) in AD diagnosis remain largely unexplored. Here, we clinically, cognitively, and genetically characterized a sample of 15 individuals diagnosed with AD (cases) and 15 controls from Barranquilla, Colombia. Advanced bioinformatics, analytics and Machine Learning (ML) techniques were used to identify lncRNAs differentially expressed between cases and controls. The expression of 28,909 lncRNAs was quantified. Of these, 18 were found to be differentially expressed and harbored in pivotal genes related to AD. Two lncRNAs, ENST00000608936 and ENST00000433747, show promise as diagnostic markers for AD, with ML models achieving > 95% sensitivity, specificity, and accuracy in both the training and testing datasets. These findings suggest that the expression profiles of lncRNAs could significantly contribute to advancing personalized AD diagnosis in this community, offering promising avenues for early detection and follow-up.
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- 2024
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11. Molecular neuroimaging in dominantly inherited versus sporadic early-onset Alzheimer's disease.
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Iaccarino L, Llibre-Guerra JJ, McDade E, Edwards L, Gordon B, Benzinger T, Hassenstab J, Kramer JH, Li Y, Miller BL, Miller Z, Morris JC, Mundada N, Perrin RJ, Rosen HJ, Soleimani-Meigooni D, Strom A, Tsoy E, Wang G, Xiong C, Allegri R, Chrem P, Vazquez S, Berman SB, Chhatwal J, Masters CL, Farlow MR, Jucker M, Levin J, Salloway S, Fox NC, Day GS, Gorno-Tempini ML, Boxer AL, La Joie R, Bateman R, and Rabinovici GD
- Abstract
Approximately 5% of Alzheimer's disease patients develop symptoms before age 65 (early-onset Alzheimer's disease), with either sporadic (sporadic early-onset Alzheimer's disease) or dominantly inherited (dominantly inherited Alzheimer's disease) presentations. Both sporadic early-onset Alzheimer's disease and dominantly inherited Alzheimer's disease are characterized by brain amyloid-β accumulation, tau tangles, hypometabolism and neurodegeneration, but differences in topography and magnitude of these pathological changes are not fully elucidated. In this study, we directly compared patterns of amyloid-β plaque deposition and glucose hypometabolism in sporadic early-onset Alzheimer's disease and dominantly inherited Alzheimer's disease individuals. Our analysis included 134 symptomatic sporadic early-onset Alzheimer's disease amyloid-Positron Emission Tomography (PET)-positive cases from the University of California, San Francisco, Alzheimer's Disease Research Center (mean ± SD age 59.7 ± 5.6 years), 89 symptomatic dominantly inherited Alzheimer's disease cases (age 45.8 ± 9.3 years) and 102 cognitively unimpaired non-mutation carriers from the Dominantly Inherited Alzheimer Network study (age 44.9 ± 9.2). Each group underwent clinical and cognitive examinations,
11 C-labelled Pittsburgh Compound B-PET and structural MRI.18 F-Fluorodeoxyglucose-PET was also available for most participants. Positron Emission Tomography scans from both studies were uniformly processed to obtain a standardized uptake value ratio (PIB50-70 cerebellar grey reference and FDG30-60 pons reference) images. Statistical analyses included pairwise global and voxelwise group comparisons and group-independent component analyses. Analyses were performed also adjusting for covariates including age, sex, Mini-Mental State Examination, apolipoprotein ε4 status and average composite cortical of standardized uptake value ratio. Compared with dominantly inherited Alzheimer's disease, sporadic early-onset Alzheimer's disease participants were older at age of onset (mean ± SD, 54.8 ± 8.2 versus 41.9 ± 8.2, Cohen's d = 1.91), with more years of education (16.4 ± 2.8 versus 13.5 ± 3.2, d = 1) and more likely to be apolipoprotein ε4 carriers (54.6% ε4 versus 28.1%, Cramer's V = 0.26), but similar Mini-Mental State Examination (20.6 ± 6.1 versus 21.2 ± 7.4, d = 0.08). Sporadic early-onset Alzheimer's disease had higher global cortical Pittsburgh Compound B-PET binding (mean ± SD standardized uptake value ratio, 1.92 ± 0.29 versus 1.58 ± 0.44, d = 0.96) and greater global cortical18 F-fluorodeoxyglucose-PET hypometabolism (mean ± SD standardized uptake value ratio, 1.32 ± 0.1 versus 1.39 ± 0.19, d = 0.48) compared with dominantly inherited Alzheimer's disease. Fully adjusted comparisons demonstrated relatively higher Pittsburgh Compound B-PET standardized uptake value ratio in the medial occipital, thalami, basal ganglia and medial/dorsal frontal regions in dominantly inherited Alzheimer's disease versus sporadic early-onset Alzheimer's disease. Sporadic early-onset Alzheimer's disease showed relatively greater18 F-fluorodeoxyglucose-PET hypometabolism in Alzheimer's disease signature temporoparietal regions and caudate nuclei, whereas dominantly inherited Alzheimer's disease showed relatively greater hypometabolism in frontal white matter and pericentral regions. Independent component analyses largely replicated these findings by highlighting common and unique Pittsburgh Compound B-PET and18 F-fluorodeoxyglucose-PET binding patterns. In summary, our findings suggest both common and distinct patterns of amyloid and glucose hypometabolism in sporadic and dominantly inherited early-onset Alzheimer's disease., Competing Interests: Y.L., E.T., B.G., and G.W. report no conflict of interest relevant to this manuscript. J.J.L.-G.’s research is supported by NIH-NIA (K01AG073526), the Alzheimer’s Association (AARFD-21-851415, SG-20-690363), the Michael J. Fox Foundation (MJFF-020770), the Foundation for Barnes-Jewish Hospital and the McDonnell Academy. T.L.S.B., MD, PhD, has investigator-initiated research funding from the NIH, the Alzheimer’s Association, the Barnes-Jewish Hospital Foundation and Avid Radiopharmaceuticals. T.L.S.B. participates as a site investigator in clinical trials sponsored by Avid Radiopharmaceuticals, Eli Lilly and Company, Biogen, Eisai, Janssen and F. Hoffmann-La Roche, Ltd. She serves as an unpaid consultant to Eisai and Siemens. She is on the Speaker’s Bureau for Biogen. J.C.M., MD, is the Friedman Distinguished Professor of Neurology, Director, Knight ADRC; Associate Director of DIAN and Founding Principal Investigator of DIAN. He is funded by NIH grants # P30 AG066444, P01AG003991, P01AG026276, U19 AG032438 and U19 AG024904. Neither J.C.M. nor his family owns stock or has equity interest (outside of mutual funds or other externally directed accounts) in any pharmaceutical or biotechnology company. Carlos Cruchaga, PhD, receives research support from Biogen, EISAI, Alector and Parabon. The funders of the study had no role in the collection, analysis or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. Dr. Cruchaga is a member of the advisory board of Vivid Genetics, Halia Therapeutics and Adx Healthcare. G.S.D.’s research is supported by NIH (K23AG064029, U01AG057195 and U19AG032438), the Alzheimer’s Association and the Chan Zuckerberg Initiative. He serves as a consultant for Parabon NanoLabs, Inc., as a Topic Editor (Dementia) for DynaMed (EBSCO), and as the clinical director of the Anti-NMDA Receptor Encephalitis Foundation, Inc. (Canada; uncompensated). He is the co-project PI for a clinical trial in anti-NMDAR encephalitis, which receives support from Horizon Pharmaceuticals. He has developed educational materials for PeerView Media, Inc., and Continuing Education, Inc. He owns stock in ANI Pharmaceuticals. R.J.B., MD, is the director and principal investigator of the DIAN and DIAN-TU-001. He receives research support from the National Institute on Aging of the National Institutes of Health, DIAN-TU Trial Pharmaceutical Partners (Eli Lilly and Company, F. Hoffman-La Roche, Ltd. and Avid Radiopharmaceuticals), Alzheimer’s Association, GHR Foundation, Anonymous Organization, DIAN-TU Pharma Consortium (Active: Biogen, Eisai, Eli Lilly and Company, Janssen, F. Hoffmann-La Roche, Ltd./Genentech, United Neuroscience. Previous: AbbVie, Amgen, AstraZeneca, Forum, Mithridion, Novartis, Pfizer, Sanofi). He has been an invited speaker and consultant for AC Immune, F. Hoffman La Roche, Ltd. and Janssen and a consultant for Amgen and Eisai. J.L., MD, reports speaker fees from Bayer Vital, Biogen and Roche, consulting fees from Axon Neuroscience and Biogen and author fees from Thieme Medical Publishers and W. Kohlhammer GmbH Medical Publishers. In addition, he reports compensation for serving as chief medical officer for MODAG GmbH, is a beneficiary of the phantom share program of MODAG GmbH and is an inventor in a patent ‘Pharmaceutical Composition and Methods of Use’ (EP 22 159 408.8) filed by MODAG GmbH, all activities outside the submitted work. L.I. is currently a full-time employee of Eli Lilly and Company/Avid Radiopharmaceuticals and a minor shareholder of Eli Lilly and Company. His contribution to the work presented in this manuscript was performed while he was affiliated with the University of California San Francisco. G.D.R., MD, receives research support from NIA P30-AG062422, U01 AG057195, R35 AG072362, R56-AG075744, NINDS R21-NS120629, Alzheimer’s Association ZEN-21-848216, American College of Radiology, Rainwater Charitable Foundation, Shenandoah Foundation, Avid Radiopharmaceuticals, Life Molecular Imaging, GE HealthCare and Genentech. He has served as a consultant for Alector, Eli Lilly, Genentech, GE HealthCare, Roche, Johnson & Johnson and Merck. He serves as an associate editor for JAMA Neurology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)- Published
- 2024
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12. Estimation of cognitive reserve and its impact on cognitive performance in older adults.
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Feldberg C, Barreyro JP, Tartaglini MF, Hermida PD, Moya García L, Benetti L, Somale MV, and Allegri R
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- Humans, Aged, Cognition, Executive Function, Life Style, Educational Status, Neuropsychological Tests, Cognitive Reserve
- Abstract
Objectives: Cognitive reserve provides evidence in the search for answers regarding the role that lifestyle has in the protection of cognition in old age. Through a structural equations model, different things were analyzed: the relative weight of education, occupational complexity, free time activities and the intelligence quotient in cognitive reserve; and its impact on three cognitive domains: memory, language and executive functions., Design: A trail analysis was executed, using structural equations procedure., Participants: 167 older participants (mean = 76.74 years, standard deviation = 6.8 years)., Measurements: Participants were assessed with: Sociodemographic Questionnaire, Occupational Activity Agency Questionnaire, Social Participation Questionnaire and Neuropsychological Evaluation Battery for: memory, language and executive functions., Results: The cognitive reserve factor is well represented by the measures included, with values between .43 and .86, and shows a direct effect on language ( β = .52, p < .001), executive functions ( β = .77, p <.001), and memory ( β = .36, p = .003)., Conclusions: In conclusion, lifestyle factors, such as education, occupational complexity, leisure time activities and intelligence quotient have an impact on the conformation of cognitive reserve and performance in some psychological processes.
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- 2024
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13. Longitudinal clinical, cognitive and biomarker profiles in dominantly inherited versus sporadic early-onset Alzheimer's disease.
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Llibre-Guerra JJ, Iaccarino L, Coble D, Edwards L, Li Y, McDade E, Strom A, Gordon B, Mundada N, Schindler SE, Tsoy E, Ma Y, Lu R, Fagan AM, Benzinger TLS, Soleimani-Meigooni D, Aschenbrenner AJ, Miller Z, Wang G, Kramer JH, Hassenstab J, Rosen HJ, Morris JC, Miller BL, Xiong C, Perrin RJ, Allegri R, Chrem P, Surace E, Berman SB, Chhatwal J, Masters CL, Farlow MR, Jucker M, Levin J, Fox NC, Day G, Gorno-Tempini ML, Boxer AL, La Joie R, Rabinovici GD, and Bateman R
- Abstract
Approximately 5% of Alzheimer's disease cases have an early age at onset (<65 years), with 5-10% of these cases attributed to dominantly inherited mutations and the remainder considered as sporadic. The extent to which dominantly inherited and sporadic early-onset Alzheimer's disease overlap is unknown. In this study, we explored the clinical, cognitive and biomarker profiles of early-onset Alzheimer's disease, focusing on commonalities and distinctions between dominantly inherited and sporadic cases. Our analysis included 117 participants with dominantly inherited Alzheimer's disease enrolled in the Dominantly Inherited Alzheimer Network and 118 individuals with sporadic early-onset Alzheimer's disease enrolled at the University of California San Francisco Alzheimer's Disease Research Center. Baseline differences in clinical and biomarker profiles between both groups were compared using t -tests. Differences in the rates of decline were compared using linear mixed-effects models. Individuals with dominantly inherited Alzheimer's disease exhibited an earlier age-at-symptom onset compared with the sporadic group [43.4 (SD ± 8.5) years versus 54.8 (SD ± 5.0) years, respectively, P < 0.001]. Sporadic cases showed a higher frequency of atypical clinical presentations relative to dominantly inherited (56.8% versus 8.5%, respectively) and a higher frequency of APOE-ε4 (50.0% versus 28.2%, P = 0.001). Compared with sporadic early onset, motor manifestations were higher in the dominantly inherited cohort [32.5% versus 16.9% at baseline ( P = 0.006) and 46.1% versus 25.4% at last visit ( P = 0.001)]. At baseline, the sporadic early-onset group performed worse on category fluency ( P < 0.001), Trail Making Test Part B ( P < 0.001) and digit span ( P < 0.001). Longitudinally, both groups demonstrated similar rates of cognitive and functional decline in the early stages. After 10 years from symptom onset, dominantly inherited participants experienced a greater decline as measured by Clinical Dementia Rating Sum of Boxes [3.63 versus 1.82 points ( P = 0.035)]. CSF amyloid beta-42 levels were comparable [244 (SD ± 39.3) pg/ml dominantly inherited versus 296 (SD ± 24.8) pg/ml sporadic early onset, P = 0.06]. CSF phosphorylated tau at threonine 181 levels were higher in the dominantly inherited Alzheimer's disease cohort (87.3 versus 59.7 pg/ml, P = 0.005), but no significant differences were found for t-tau levels ( P = 0.35). In summary, sporadic and inherited Alzheimer's disease differed in baseline profiles; sporadic early onset is best distinguished from dominantly inherited by later age at onset, high frequency of atypical clinical presentations and worse executive performance at baseline. Despite these differences, shared pathways in longitudinal clinical decline and CSF biomarkers suggest potential common therapeutic targets for both populations, offering valuable insights for future research and clinical trial design., Competing Interests: J.J.L.-G.’s research is supported by NIH-NIA (K01AG073526), the Alzheimer’s Association (AARFD-21-851415 and SG-20-690363), the Michael J. Fox Foundation (MJFF-020770), the Foundation for Barnes-Jewish Hospital and the McDonnell Academy. A.M.F., PhD, is the Biomarker Core Leader of the DIAN-TU. She is a member of the scientific advisory boards for Roche Diagnostics, Genentech and AbbVie and also consults for Araclon/Grifols, DiademRes, DiamiR and Otsuka Pharmaceuticals. T.L.S.B., MD, PhD, has investigator-initiated research funding from the NIH, the Alzheimer’s Association, the Barnes-Jewish Hospital Foundation and Avid Radiopharmaceuticals. T.L.S.B. participates as a site investigator in clinical trials sponsored by Avid Radiopharmaceuticals, Eli Lilly and Company, Biogen, Eisai, Jaansen and F. Hoffmann-La Roche, Ltd. She serves as an unpaid consultant to Eisai and Siemens. She is on the Speaker’s Bureau for Biogen. J.C.M., MD, is the Friedman Distinguished Professor of Neurology, Director, Knight ADRC, Associate Director of DIAN and Founding Principal Investigator of DIAN. He is funded by NIH grants # P30 AG066444, P01AG003991, P01AG026276, U19 AG032438 and U19 AG024904. Neither J.C.M. nor his family owns stock or has equity interest (outside of mutual funds or other externally directed accounts) in any pharmaceutical or biotechnology company. A.J.A., PhD, has served as a consultant for Biogen Inc and H. Lundbeck HS. J.H., PhD, is a paid consultant for F. Hoffmann-La Roche, Ltd., Takeda, and Lundbeck and is on the Data Safety and Monitoring Board for Eisai. J.L., MD, reports speaker fees from Bayer Vital, Biogen and Roche, consulting fees from Axon Neuroscience and Biogen and author fees from Thieme Medical Publishers and W. Kohlhammer GmbH Medical Publishers. In addition, he reports compensation for serving as chief medical officer for MODAG GmbH, is a beneficiary of the phantom share program of MODAG GmbH and is an inventor in a patent ‘Pharmaceutical Composition and Methods of Use’ (EP 22 159 408.8) filed by MODAG GmbH, all activities outside the submitted work. L.I. is currently a full-time employee of Eli Lilly and Company/Avid Radiopharmaceuticals and a minor shareholder of Eli Lilly and Company. His contribution to the work presented in this manuscript was performed while he was affiliated with the University of California San Francisco. G.D.R., MD, receives research support from NIA P30-AG062422, U01-AG057195, R35 AG072362, R56-AG075744, NINDS R21-NS120629, Alzheimer’s Association ZEN-21-848216, American College of Radiology, Rainwater Charitable Foundation, Shenandoah Foundation, Avid Radiopharmaceuticals, Life Molecular Imaging, GE Healthcare and Genentech. He has served as a consultant for Alector, Eli Lilly, Genentech, GE Healthcare, Roche, Johnson & Johnson and Merck. He serves as associate editor for JAMA Neurology. All other authors report no conflict of interest relevant to this manuscript., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2023
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14. Change in Cerebrospinal Fluid Tau Microtubule Binding Region Detects Symptom Onset, Cognitive Decline, Tangles, and Atrophy in Dominantly Inherited Alzheimer's Disease.
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Horie K, Li Y, Barthélemy NR, Gordon B, Hassenstab J, Benzinger TLS, Fagan AM, Morris JC, Karch CM, Xiong C, Allegri R, Mendez PC, Ikeuchi T, Kasuga K, Noble J, Farlow M, Chhatwal J, Day G, Schofield PR, Masters CL, Levin J, Jucker M, Lee JH, Roh JH, Sato C, Sachdev P, Koyama A, Reyderman L, Bateman RJ, and McDade E
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- Humans, Cross-Sectional Studies, tau Proteins metabolism, Amyloid beta-Peptides metabolism, Positron-Emission Tomography methods, Atrophy pathology, Biomarkers cerebrospinal fluid, Disease Progression, Microtubules metabolism, Microtubules pathology, Alzheimer Disease diagnostic imaging, Alzheimer Disease genetics, Alzheimer Disease metabolism, Cognitive Dysfunction diagnostic imaging, Cognitive Dysfunction genetics, Cognitive Dysfunction cerebrospinal fluid
- Abstract
Objective: Identifying cerebrospinal fluid measures of the microtubule binding region of tau (MTBR-tau) species that reflect tau aggregation could provide fluid biomarkers that track Alzheimer's disease related neurofibrillary tau pathological changes. We examined the cerebrospinal fluid (CSF) MTBR-tau species in dominantly inherited Alzheimer's disease (DIAD) mutation carriers to assess the association with Alzheimer's disease (AD) biomarkers and clinical symptoms., Methods: Cross-sectional and longitudinal CSF from 229 DIAD mutation carriers and 130 mutation non-carriers had sequential characterization of N-terminal/mid-domain phosphorylated tau (p-tau) followed by MTBR-tau species and tau positron emission tomography (tau PET), other soluble tau and amyloid biomarkers, comprehensive clinical and cognitive assessments, and brain magnetic resonance imaging of atrophy., Results: CSF MTBR-tau species located within the putative "border" region and one species corresponding to the "core" region of aggregates in neurofibrillary tangles (NFTs) increased during the presymptomatic stage and decreased during the symptomatic stage. The "border" MTBR-tau species were associated with amyloid pathology and CSF p-tau; whereas the "core" MTBR-tau species were associated stronger with tau PET and CSF measures of neurodegeneration. The ratio of the border to the core species provided a continuous measure of increasing amounts that tracked clinical progression and NFTs., Interpretation: Changes in CSF soluble MTBR-tau species preceded the onset of dementia, tau tangle increase, and atrophy in DIAD. The ratio of 4R-specific MTBR-tau (border) to the NFT (core) MTBR-tau species corresponds to the pathology of NFTs in DIAD and change with disease progression. The dynamics between different MTBR-tau species in the CSF may serve as a marker of tau-related disease progression and target engagement of anti-tau therapeutics. ANN NEUROL 2023;93:1158-1172., (© 2023 American Neurological Association.)
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- 2023
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15. COVID-19 Pneumonia with Migratory Pattern in Agammaglobulinemic Patients: A Report of Two Cases and Review of Literature.
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Degli Antoni M, Crosato V, Pennati F, Borghesi A, Cristini G, Allegri R, Capone S, Bergamasco A, Soresina A, Badolato R, Maroldi R, Quiros-Roldan E, Matteelli A, Castelli F, and Focà E
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- Humans, COVID-19 complications, Pneumonia, Genetic Diseases, X-Linked, Agammaglobulinemia complications, Agammaglobulinemia diagnostic imaging
- Abstract
X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by marked reduction in serum immunoglobulins and early-onset infections. Coronavirus Disease-2019 (COVID-19) pneumonia in immunocompromised patients presents clinical and radiological peculiarities which have not yet been completely understood. Very few cases of agammaglobulinemic patients with COVID-19 have been reported since the beginning of the pandemic in February 2020. We report two cases of migrant COVID-19 pneumonia in XLA patients.
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- 2023
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16. Axonal damage and astrocytosis are biological correlates of grey matter network integrity loss: a cohort study in autosomal dominant Alzheimer disease.
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Vermunt L, Sutphen C, Dicks E, de Leeuw DM, Allegri R, Berman SB, Cash DM, Chhatwal JP, Cruchaga C, Day G, Ewers M, Farlow M, Fox NC, Ghetti B, Graff-Radford N, Hassenstab J, Jucker M, Karch CM, Kuhle J, Laske C, Levin J, Masters CL, McDade E, Mori H, Morris JC, Perrin RJ, Preische O, Schofield PR, Suárez-Calvet M, Xiong C, Scheltens P, Teunissen CE, Visser PJ, Bateman RJ, Benzinger TLS, Fagan AM, Gordon BA, and Tijms BM
- Abstract
Brain development and maturation leads to grey matter networks that can be measured using magnetic resonance imaging. Network integrity is an indicator of information processing capacity which declines in neurodegenerative disorders such as Alzheimer disease (AD). The biological mechanisms causing this loss of network integrity remain unknown. Cerebrospinal fluid (CSF) protein biomarkers are available for studying diverse pathological mechanisms in humans and can provide insight into decline. We investigated the relationships between 10 CSF proteins and network integrity in mutation carriers (N=219) and noncarriers (N=136) of the Dominantly Inherited Alzheimer Network Observational study. Abnormalities in Aβ, Tau, synaptic (SNAP-25, neurogranin) and neuronal calcium-sensor protein (VILIP-1) preceded grey matter network disruptions by several years, while inflammation related (YKL-40) and axonal injury (NfL) abnormalities co-occurred and correlated with network integrity. This suggests that axonal loss and inflammation play a role in structural grey matter network changes., Key Points: Abnormal levels of fluid markers for neuronal damage and inflammatory processes in CSF are associated with grey matter network disruptions.The strongest association was with NfL, suggesting that axonal loss may contribute to disrupted network organization as observed in AD.Tracking biomarker trajectories over the disease course, changes in CSF biomarkers generally precede changes in brain networks by several years.
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- 2023
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17. The Nairobi Declaration-Reducing the burden of dementia in low- and middle-income countries (LMICs): Declaration of the 2022 Symposium on Dementia and Brain Aging in LMICs.
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Maestre G, Carrillo M, Kalaria R, Acosta D, Adams L, Adoukonou T, Akinwande K, Akinyemi J, Akinyemi R, Akpa O, Alladi S, Allegri R, Arizaga R, Arshad F, Arulogun O, Babalola D, Baiyewu O, Bak T, Bellaj T, Boshe J, Brayne C, Brodie-Mends D, Brown R, Cahn J, Cyrille N, Damasceno A, de Silva R, de Silva R, Djibuti M, Dreyer AJ, Ellajosyula R, Farombi T, Fongang B, Forner S, Friedland R, Garza N, Gbessemehlan A, Georgiou EE, Gouider R, Govia I, Grinberg L, Guerchet M, Gugssa S, Gumikiriza-Onoria JL, Gustafson D, Hogervorst E, Hornberger M, Ibanez A, Ihara M, Ismail O, Issac T, Jönsson L, Kaputu C, Karanja W, Karungi J, Tshala-Katumbay D, Kunkle B, Lee JH, Leroi I, Lewis R, Livingston G, Lopera F, Lwere K, Manes F, Mbakile-Mahlanza L, Mena P, Miller B, Millogo A, Mohamed A, Musyimi C, Mutiso V, Nakasujja N, Ndetei D, Nightingale S, Njamnshi AK, Novotni G, Nyamayaro P, Nyame S, Ogeng'o J, Ogunniyi A, Okada De Oliveira M, Okubadejo N, Orrell M, Orunmuyi A, Owolabi M, Paddick S, A Pericak-Vance M, Pirtosek Z, Potocnik F, Preston B, Raman R, Ranchod K, Rizig M, Rosselli M, Deepa R, Roy U, Salokhiddinov M, Sano M, Sarfo F, Satizabal CL, Sepulveda-Falla D, Seshadri S, Sexton C, Skoog I, St George-Hyslop P, Suemoto C, Tanner J, Thapa P, Toure K, Ucheagwu V, Udeh-Momoh C, Valcour V, Vance J, Varghese M, Vera J, Walker R, Weidner W, Sebastian W, Whitehead Gay P, Zetterberg H, and Zewde Y
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- 2023
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18. Emergence of Pandemic Clonal Lineage Sequence Types 131 and 69 of Extraintestinal Escherichia coli as a Cause of Meningitis: Is It Time To Revise Molecular Assays?
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De Francesco MA, Bertelli A, Corbellini S, Scaltriti E, Risso F, Allegri R, Tiecco G, Castelli F, and Caruso A
- Abstract
Two Escherichia coli strains, respectively responsible for neonatal and adult meningitis, were isolated and their phenotypic antibiotic susceptibility and genomic features characterized by whole-genome sequencing (WGS). Multiplex real-time PCR targeting the principal microorganisms involved in meningitis etiology failed to identify either isolate. Afterwards, matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry was used to identify the isolates as E. coli strains. Genomic analysis showed that they belonged to sequence types 131 and 69 (ST131 and ST69). Neither of the isolates harbored the K1 capsular antigen or belonged to other capsular serotypes, but they shared different virulence factors, including ibe genes, responsible for invasion of brain endothelial cells. IMPORTANCE The extraintestinal pathogenic Escherichia coli group is characterized by the presence of uropathogenic E. coli (UPEC), sepsis-associated E. coli (SEPEC), and neonatal meningitis E. coli (NMEC). All of these members exhibit many virulence factors, such as lipopolysaccharides, toxins, iron acquisition factors, invasins, fimbriae, and capsules. Urinary infections are the most common infections caused by this group, followed by globally increasing numbers of both community- and nosocomially acquired bloodstream infections, associated with considerable patient morbidity and mortality. Some lineages tend to become dominant; in addition to enhanced fitness, this epidemiological success stems from increased virulence, antibiotic resistance, gut colonization, and greater host-to-host transmission. Our results underline the importance of continuous surveillance of these new emerging lineages and the need to develop new meningitis molecular assay panels able to identify them.
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- 2023
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19. Biomarkers for dementia in Latin American countries: Gaps and opportunities.
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Parra MA, Orellana P, Leon T, Victoria CG, Henriquez F, Gomez R, Avalos C, Damian A, Slachevsky A, Ibañez A, Zetterberg H, Tijms BM, Yokoyama JS, Piña-Escudero SD, Cochran JN, Matallana DL, Acosta D, Allegri R, Arias-Suárez BP, Barra B, Behrens MI, Brucki SMD, Busatto G, Caramelli P, Castro-Suarez S, Contreras V, Custodio N, Dansilio S, la Cruz-Puebla M, de Souza LC, Diaz MM, Duque L, Farías GA, Ferreira ST, Guimet NM, Kmaid A, Lira D, Lopera F, Meza BM, Miotto EC, Nitrini R, Nuñez A, O'Neill S, Ochoa J, Pintado-Caipa M, Resende EPF, Risacher S, Rojas LA, Sabaj V, Schilling L, Sellek AF, Sosa A, Takada LT, Teixeira AL, Unaucho-Pilalumbo M, and Duran-Aniotz C
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- Humans, Latin America, Dementia diagnosis
- Abstract
Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a great potential to advance dementia biomarkers research. Considering the unique contributions that LAC could make to this growing field, we highlight the urgent need to expand biomarker research. These insights allowed us to propose an action plan that addresses the recommendations for a biomarker framework recently proposed by regional experts., (© 2022 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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20. Pattern and implications of neurological examination findings in autosomal dominant Alzheimer disease.
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Vöglein J, Franzmeier N, Morris JC, Dieterich M, McDade E, Simons M, Preische O, Hofmann A, Hassenstab J, Benzinger TL, Fagan A, Noble JM, Berman SB, Graff-Radford NR, Ghetti B, Farlow MR, Chhatwal JP, Salloway S, Xiong C, Karch CM, Cairns N, Perrin RJ, Day G, Martins R, Sanchez-Valle R, Mori H, Shimada H, Ikeuchi T, Suzuki K, Schofield PR, Masters CL, Goate A, Buckles V, Fox NC, Chrem P, Allegri R, Ringman JM, Yakushev I, Laske C, Jucker M, Höglinger G, Bateman RJ, Danek A, and Levin J
- Subjects
- Humans, Neurologic Examination, Alzheimer Disease pathology, Cognitive Dysfunction genetics
- Abstract
Introduction: As knowledge about neurological examination findings in autosomal dominant Alzheimer disease (ADAD) is incomplete, we aimed to determine the frequency and significance of neurological examination findings in ADAD., Methods: Frequencies of neurological examination findings were compared between symptomatic mutation carriers and non mutation carriers from the Dominantly Inherited Alzheimer Network (DIAN) to define AD neurological examination findings. AD neurological examination findings were analyzed regarding frequency, association with and predictive value regarding cognitive decline, and association with brain atrophy in symptomatic mutation carriers., Results: AD neurological examination findings included abnormal deep tendon reflexes, gait disturbance, pathological cranial nerve examination findings, tremor, abnormal finger to nose and heel to shin testing, and compromised motor strength. The frequency of AD neurological examination findings was 65.1%. Cross-sectionally, mutation carriers with AD neurological examination findings showed a more than two-fold faster cognitive decline and had greater parieto-temporal atrophy, including hippocampal atrophy. Longitudinally, AD neurological examination findings predicted a significantly greater decline over time., Discussion: ADAD features a distinct pattern of neurological examination findings that is useful to estimate prognosis and may inform clinical care and therapeutic trial designs., (© 2022 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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21. Autosomal dominant and sporadic late onset Alzheimer's disease share a common in vivo pathophysiology.
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Morris JC, Weiner M, Xiong C, Beckett L, Coble D, Saito N, Aisen PS, Allegri R, Benzinger TLS, Berman SB, Cairns NJ, Carrillo MC, Chui HC, Chhatwal JP, Cruchaga C, Fagan AM, Farlow M, Fox NC, Ghetti B, Goate AM, Gordon BA, Graff-Radford N, Day GS, Hassenstab J, Ikeuchi T, Jack CR, Jagust WJ, Jucker M, Levin J, Massoumzadeh P, Masters CL, Martins R, McDade E, Mori H, Noble JM, Petersen RC, Ringman JM, Salloway S, Saykin AJ, Schofield PR, Shaw LM, Toga AW, Trojanowski JQ, Vöglein J, Weninger S, Bateman RJ, and Buckles VD
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- Humans, Amyloid beta-Peptides, Magnetic Resonance Imaging methods, Biomarkers, Alzheimer Disease diagnostic imaging, Alzheimer Disease genetics, Amyloidosis
- Abstract
The extent to which the pathophysiology of autosomal dominant Alzheimer's disease corresponds to the pathophysiology of 'sporadic' late onset Alzheimer's disease is unknown, thus limiting the extrapolation of study findings and clinical trial results in autosomal dominant Alzheimer's disease to late onset Alzheimer's disease. We compared brain MRI and amyloid PET data, as well as CSF concentrations of amyloid-β42, amyloid-β40, tau and tau phosphorylated at position 181, in 292 carriers of pathogenic variants for Alzheimer's disease from the Dominantly Inherited Alzheimer Network, with corresponding data from 559 participants from the Alzheimer's Disease Neuroimaging Initiative. Imaging data and CSF samples were reprocessed as appropriate to guarantee uniform pipelines and assays. Data analyses yielded rates of change before and after symptomatic onset of Alzheimer's disease, allowing the alignment of the ∼30-year age difference between the cohorts on a clinically meaningful anchor point, namely the participant age at symptomatic onset. Biomarker profiles were similar for both autosomal dominant Alzheimer's disease and late onset Alzheimer's disease. Both groups demonstrated accelerated rates of decline in cognitive performance and in regional brain volume loss after symptomatic onset. Although amyloid burden accumulation as determined by PET was greater after symptomatic onset in autosomal dominant Alzheimer's disease than in late onset Alzheimer's disease participants, CSF assays of amyloid-β42, amyloid-β40, tau and p-tau181 were largely overlapping in both groups. Rates of change in cognitive performance and hippocampal volume loss after symptomatic onset were more aggressive for autosomal dominant Alzheimer's disease participants. These findings suggest a similar pathophysiology of autosomal dominant Alzheimer's disease and late onset Alzheimer's disease, supporting a shared pathobiological construct., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2022
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22. Different rates of cognitive decline in autosomal dominant and late-onset Alzheimer disease.
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Buckles VD, Xiong C, Bateman RJ, Hassenstab J, Allegri R, Berman SB, Chhatwal JP, Danek A, Fagan AM, Ghetti B, Goate A, Graff-Radford N, Jucker M, Levin J, Marcus DS, Masters CL, McCue L, McDade E, Mori H, Moulder KL, Noble JM, Paumier K, Preische O, Ringman JM, Fox NC, Salloway S, Schofield PR, Martins R, Vöglein J, and Morris JC
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- Humans, Alzheimer Disease pathology, Alzheimer Disease physiopathology, Cognitive Dysfunction physiopathology
- Abstract
As prevention trials advance with autosomal dominant Alzheimer disease (ADAD) participants, understanding the similarities and differences between ADAD and "sporadic" late-onset AD (LOAD) is critical to determine generalizability of findings between these cohorts. Cognitive trajectories of ADAD mutation carriers (MCs) and autopsy-confirmed LOAD individuals were compared to address this question. Longitudinal rates of change on cognitive measures were compared in ADAD MCs (n = 310) and autopsy-confirmed LOAD participants (n = 163) before and after symptom onset (estimated/observed). LOAD participants declined more rapidly in the presymptomatic (preclinical) period and performed more poorly at symptom onset than ADAD participants on a cognitive composite. After symptom onset, however, the younger ADAD MCs declined more rapidly. The similar but not identical cognitive trajectories (declining but at different rates) for ADAD and LOAD suggest common AD pathologies but with some differences., (© 2021 the Alzheimer's Association.)
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- 2022
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23. Predicting brain age from functional connectivity in symptomatic and preclinical Alzheimer disease.
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Millar PR, Luckett PH, Gordon BA, Benzinger TLS, Schindler SE, Fagan AM, Cruchaga C, Bateman RJ, Allegri R, Jucker M, Lee JH, Mori H, Salloway SP, Yakushev I, Morris JC, and Ances BM
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- Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Brain physiology, Humans, Magnetic Resonance Imaging methods, Middle Aged, Neuroimaging, Young Adult, Alzheimer Disease pathology
- Abstract
"Brain-predicted age" quantifies apparent brain age compared to normative neuroimaging trajectories. Advanced brain-predicted age has been well established in symptomatic Alzheimer disease (AD), but is underexplored in preclinical AD. Prior brain-predicted age studies have typically used structural MRI, but resting-state functional connectivity (FC) remains underexplored. Our model predicted age from FC in 391 cognitively normal, amyloid-negative controls (ages 18-89). We applied the trained model to 145 amyloid-negative, 151 preclinical AD, and 156 symptomatic AD participants to test group differences. The model accurately predicted age in the training set. FC-predicted brain age gaps (FC-BAG) were significantly older in symptomatic AD and significantly younger in preclinical AD compared to controls. There was minimal correspondence between networks predictive of age and AD. Elevated FC-BAG may reflect network disruption during symptomatic AD. Reduced FC-BAG in preclinical AD was opposite to the expected direction, and may reflect a biphasic response to preclinical AD pathology or may be driven by inconsistency between age-related vs. AD-related networks. Overall, FC-predicted brain age may be a sensitive AD biomarker., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interests. JC Morris is funded by NIH grants # P30 AG066444; P01AG003991; P01AG026276; U19 AG032438; and U19 AG024904. Neither Dr. Morris nor his family owns stock or has equity interest (outside of mutual funds or other externally directed accounts) in any pharmaceutical or biotechnology company. Dr. Salloway reports personal fees from EISAI, NOVARTIS, GENENTECH, ROCHE, GEMVAX, AVID, and LILLY. Dr. Bateman is on the scientific advisory board of C2N Diagnostics and reports research support from Abbvie, Avid Radiopharmaceuticals, Biogen, Centene, Eisai, Eli Lilly and Company, Genentech, Hoffman-LaRoche, Janssen, and United Neuroscience., (Copyright © 2022. Published by Elsevier Inc.)
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- 2022
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24. CSF Tau phosphorylation at Thr205 is associated with loss of white matter integrity in autosomal dominant Alzheimer disease.
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Strain JF, Barthelemy N, Horie K, Gordon BA, Kilgore C, Aschenbrenner A, Cruchaga C, Xiong C, Joseph-Mathurin N, Hassenstab J, Fagan AM, Li Y, Karch CM, Perrin RJ, Berman SB, Chhatwal JP, Graff-Radford NR, Mori H, Levin J, Noble JM, Allegri R, Schofield PR, Marcus DS, Holtzman DM, Morris JC, Benzinger TLS, McDade EM, Bateman RJ, and Ances BM
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- Amyloid beta-Peptides cerebrospinal fluid, Biomarkers cerebrospinal fluid, Diffusion Tensor Imaging, Humans, Phosphorylation, tau Proteins metabolism, Alzheimer Disease cerebrospinal fluid, Alzheimer Disease diagnostic imaging, Alzheimer Disease genetics, Cognitive Dysfunction diagnostic imaging, White Matter metabolism
- Abstract
Background: Hyperphosphorylation of tau leads to conformational changes that destabilize microtubules and hinder axonal transport in Alzheimer's disease (AD). However, it remains unknown whether white matter (WM) decline due to AD is associated with specific Tau phosphorylation site(s)., Methods: In autosomal dominant AD (ADAD) mutation carriers (MC) and non-carriers (NC) we compared cerebrospinal fluid (CSF) phosphorylation at tau sites (pT217, pT181, pS202, and pT205) and total tau with WM measures, as derived from diffusion tensor imaging (DTI), and cognition. A WM composite metric, derived from a principal component analysis, was used to identify spatial decline seen in ADAD., Results: The WM composite explained over 70% of the variance in MC. WM regions that strongly contributed to the spatial topography were located in callosal and cingulate regions. Loss of integrity within the WM composite was strongly associated with AD progression in MC as defined by the estimated years to onset (EYO) and cognitive decline. A linear regression demonstrated that amyloid, gray matter atrophy and phosphorylation at CSF tau site pT205 each uniquely explained a reduction in the WM composite within MC that was independent of vascular changes (white matter hyperintensities), and age. Hyperphosphorylation of CSF tau at other sites and total tau did not significantly predict WM composite loss., Conclusions: We identified a site-specific relationship between CSF phosphorylated tau and WM decline within MC. The presence of both amyloid deposition and Tau phosphorylation at pT205 were associated with WM composite loss. These findings highlight a primary AD-specific mechanism for WM dysfunction that is tightly coupled to symptom manifestation and cognitive decline., (Copyright © 2022. Published by Elsevier Inc.)
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- 2022
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25. Diabetic patients treated with metformin during early stages of Alzheimer's disease show a better integral performance: data from ADNI study.
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Pomilio C, Pérez NG, Calandri I, Crivelli L, Allegri R, Sevlever G, and Saravia F
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- Biomarkers, Humans, Alzheimer Disease drug therapy, Diabetes Mellitus, Type 2 drug therapy, Metformin therapeutic use
- Abstract
We evaluated the effect of the antidiabetic drug metformin on patients enrolled in the ADNI study considering patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD). Employing data from this observational study, we performed a principal component analysis focusing on the cognitive sphere by evaluating data from neuropsychological tests included in a modified version of the Alzheimer's Disease Cooperative Study-Preclinical Alzheimer Cognitive Composite (ADCS-PACC). Second, we included the levels of amyloid-β, tau, and phosphorylated tau in CSF. We found that MCI metformin-treated patients were globally characterized as subjects with a better cognitive performance and CSF biomarkers profile than the mean population of MCI patients. On the other hand, control subjects and type 2 diabetes patients (T2D) were paired by age, gender, ApoE allele, and years of education, defining three groups: MCI, MCI + T2D, and MCI + T2D + metformin. We evaluated the effect of T2D and metformin treatment employing the PACC score and composites defined from standardized ADNI variables to evaluate the memory and learning function. We found that MCI + T2D patients had a worse cognitive performance than MCI patients, but this deleterious effect was not observed in MCI + T2D + metformin patients. These cognitive variations were associated with changes in cortical thickness and hippocampal volume. Finally, no differences were found in metabolic plasmatic parameters (glycemia, cholesterol, triglycerides). Our study-employing different strategies for data analysis from the global study ADNI-shows a beneficial effect of metformin treatment on cognitive performance, CSF biomarkers profile, and neuroanatomical measures in MCI due to AD patients., (© 2022. The Author(s), under exclusive licence to American Aging Association.)
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- 2022
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26. Acute and post-acute neurological manifestations of COVID-19: present findings, critical appraisal, and future directions.
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Beghi E, Giussani G, Westenberg E, Allegri R, Garcia-Azorin D, Guekht A, Frontera J, Kivipelto M, Mangialasche F, Mukaetova-Ladinska EB, Prasad K, Chowdhary N, and Winkler AS
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- Hospital Mortality, Humans, SARS-CoV-2, Post-Acute COVID-19 Syndrome, COVID-19 complications, Nervous System Diseases epidemiology, Nervous System Diseases etiology
- Abstract
Acute and post-acute neurological symptoms, signs and diagnoses have been documented in an increasing number of patients infected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes Coronavirus Disease 2019 (COVID-19). In this review, we aimed to summarize the current literature addressing neurological events following SARS-CoV-2 infection, discuss limitations in the existing literature and suggest future directions that would strengthen our understanding of the neurological sequelae of COVID-19. The presence of neurological manifestations (symptoms, signs or diagnoses) both at the onset or during SARS-CoV-2 infection is associated with a more severe disease, as demonstrated by a longer hospital stay, higher in-hospital death rate or the continued presence of sequelae at discharge. Although biological mechanisms have been postulated for these findings, evidence-based data are still lacking to clearly define the incidence, range of characteristics and outcomes of these manifestations, particularly in non-hospitalized patients. In addition, data from low- and middle-income countries are scarce, leading to uncertainties in the measure of neurological findings of COVID-19, with reference to geography, ethnicity, socio-cultural settings, and health care arrangements. As a consequence, at present a specific phenotype that would specify a post-COVID (or long-COVID) neurological syndrome has not yet been identified., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)
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- 2022
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27. A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects.
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Acosta-Uribe J, Aguillón D, Cochran JN, Giraldo M, Madrigal L, Killingsworth BW, Singhal R, Labib S, Alzate D, Velilla L, Moreno S, García GP, Saldarriaga A, Piedrahita F, Hincapié L, López HE, Perumal N, Morelo L, Vallejo D, Solano JM, Reiman EM, Surace EI, Itzcovich T, Allegri R, Sánchez-Valle R, Villegas-Lanau A, White CL 3rd, Matallana D, Myers RM, Browning SR, Lopera F, and Kosik KS
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- Colombia, Founder Effect, Humans, Mutation, Alzheimer Disease genetics, Frontotemporal Lobar Degeneration genetics, Neurodegenerative Diseases genetics
- Abstract
Background: The Colombian population, as well as those in other Latin American regions, arose from a recent tri-continental admixture among Native Americans, Spanish invaders, and enslaved Africans, all of whom passed through a population bottleneck due to widespread infectious diseases that left small isolated local settlements. As a result, the current population reflects multiple founder effects derived from diverse ancestries., Methods: We characterized the role of admixture and founder effects on the origination of the mutational landscape that led to neurodegenerative disorders under these historical circumstances. Genomes from 900 Colombian individuals with Alzheimer's disease (AD) [n = 376], frontotemporal lobar degeneration-motor neuron disease continuum (FTLD-MND) [n = 197], early-onset dementia not otherwise specified (EOD) [n = 73], and healthy participants [n = 254] were analyzed. We examined their global and local ancestry proportions and screened this cohort for deleterious variants in disease-causing and risk-conferring genes., Results: We identified 21 pathogenic variants in AD-FTLD related genes, and PSEN1 harbored the majority (11 pathogenic variants). Variants were identified from all three continental ancestries. TREM2 heterozygous and homozygous variants were the most common among AD risk genes (102 carriers), a point of interest because the disease risk conferred by these variants differed according to ancestry. Several gene variants that have a known association with MND in European populations had FTLD phenotypes on a Native American haplotype. Consistent with founder effects, identity by descent among carriers of the same variant was frequent., Conclusions: Colombian demography with multiple mini-bottlenecks probably enhanced the detection of founder events and left a proportionally higher frequency of rare variants derived from the ancestral populations. These findings demonstrate the role of genomically defined ancestry in phenotypic disease expression, a phenotypic range of different rare mutations in the same gene, and further emphasize the importance of inclusiveness in genetic studies., (© 2022. The Author(s).)
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- 2022
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28. Cognitive consequences of COVID-19: results of a cohort study from South America.
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Crivelli L, Calandri I, Corvalán N, Carello MA, Keller G, Martínez C, Arruabarrena M, and Allegri R
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- Activities of Daily Living, Adult, Cognition, Cohort Studies, Humans, SARS-CoV-2, COVID-19 complications, Cognitive Dysfunction diagnosis, Cognitive Dysfunction etiology
- Abstract
Background: Neurological and psychiatric manifestations associated with SARS-CoV-2 infection have been reported throughout the scientific literature. However, studies on post-COVID cognitive impairment in people with no previous cognitive complaint are scarce., Objective: We aim to investigate the impact of COVID-19 on cognitive functions in adults without cognitive complaints before infection and to study cognitive dysfunction according to disease severity and cognitive risk factors., Methods: Forty-five post-COVID-19 patients and forty-five controls underwent extensive neuropsychological evaluation, which assessed cognitive domains such as memory, language, attention, executive functions, and visuospatial skills, including psychiatric symptomatology scales. Data were collected on the severity of infection, premorbid medical conditions, and functionality for activities of daily living before and after COVID-19., Results: Significant differences between groups were found in cognitive composites of memory (p=0.016, Cohen's d= 0.73), attention (p<0.001, Cohen's d=1.2), executive functions (p<0.001, Cohen's d=1.4), and language (p=0.002, Cohen's d=0.87). The change from premorbid to post-infection functioning was significantly different between severity groups (WHODAS, p=0.037). Self-reported anxiety was associated with the presence of cognitive dysfunction in COVID-19 subjects (p=0.043)., Conclusion: Our results suggest that the presence of cognitive symptoms in post-COVID-19 patients may persist for months after disease remission and argue for the inclusion of cognitive assessment as a protocolized stage of the post-COVID examination. Screening measures may not be sufficient to detect cognitive dysfunction in post-COVID-19 patients.
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- 2022
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29. Detection of emerging neurodegeneration using Bayesian linear mixed-effect modeling.
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Cobigo Y, Goh MS, Wolf A, Staffaroni AM, Kornak J, Miller BL, Rabinovici GD, Seeley WW, Spina S, Boxer AL, Boeve BF, Wang L, Allegri R, Farlow M, Mori H, Perrin RJ, Kramer J, and Rosen HJ
- Subjects
- Humans, Bayes Theorem, Brain diagnostic imaging, Magnetic Resonance Imaging, Alzheimer Disease diagnostic imaging, Neurodegenerative Diseases diagnostic imaging, Frontotemporal Dementia diagnostic imaging, Frontotemporal Lobar Degeneration
- Abstract
Early detection of neurodegeneration, and prediction of when neurodegenerative diseases will lead to symptoms, are critical for developing and initiating disease modifying treatments for these disorders. While each neurodegenerative disease has a typical pattern of early changes in the brain, these disorders are heterogeneous, and early manifestations can vary greatly across people. Methods for detecting emerging neurodegeneration in any part of the brain are therefore needed. Prior publications have described the use of Bayesian linear mixed-effects (BLME) modeling for characterizing the trajectory of change across the brain in healthy controls and patients with neurodegenerative disease. Here, we use an extension of such a model to detect emerging neurodegeneration in cognitively healthy individuals at risk for dementia. We use BLME to quantify individualized rates of volume loss across the cerebral cortex from the first two MRIs in each person and then extend the BLME model to predict future values for each voxel. We then compare observed values at subsequent time points with the values that were expected from the initial rates of change and identify voxels that are lower than the expected values, indicating accelerated volume loss and neurodegeneration. We apply the model to longitudinal imaging data from cognitively normal participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI), some of whom subsequently developed dementia, and two cognitively normal cases who developed pathology-proven frontotemporal lobar degeneration (FTLD). These analyses identified regions of accelerated volume loss prior to or accompanying the earliest symptoms, and expanding across the brain over time, in all cases. The changes were detected in regions that are typical for the likely diseases affecting each patient, including medial temporal regions in patients at risk for Alzheimer's disease, and insular, frontal, and/or anterior/inferior temporal regions in patients with likely or proven FTLD. In the cases where detailed histories were available, the first regions identified were consistent with early symptoms. Furthermore, survival analysis in the ADNI cases demonstrated that the rate of spread of accelerated volume loss across the brain was a statistically significant predictor of time to conversion to dementia. This method for detection of neurodegeneration is a potentially promising approach for identifying early changes due to a variety of diseases, without prior assumptions about what regions are most likely to be affected first in an individual., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)
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- 2022
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30. Music Based Assessment for Cognitive Functions for Spanish-Speaking Adults With Acquired Brain Injury (ECMUS): A Pilot-Validation Study.
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Pfeiffer CF, Hanser S, Russo MJ, Goyheneix M, Oliva M, Codding P, and Allegri R
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- Adult, Cognition, Humans, Pilot Projects, Psychometrics, Reproducibility of Results, Brain Injuries, Music, Music Therapy
- Abstract
Acquired brain injury (ABI) commonly causes cognitive dysfunction that needs to be assessed and treated to maximize rehabilitation outcomes. Research suggests that music, emotion, and cognition are intimately linked, and that music can contribute to the assessment and treatment of cognitive functions of adults who have suffered from ABI. To this date, no standardized music based assessment tool exists to identify and measure cognitive functioning and mood states of Spanish-speaking persons with ABI at treatment intake and over time. The objective of this study was to develop such a scale and determine its psychometric properties in terms of internal consistency, reliability, and concurrent validity. The "Evaluación de la Cognición Musical para Adultos con Lesión Cerebral Adquirida" (in English "Music Based Assessment for Cognitive Functions of Adults with Acquired Brain Injury - ECMUS") was developed and tested at a neurorehabilitation institute in Argentina. Twenty-four healthy adults and 20 adults with ABI were recruited and assessed with the ECMUS. Despite the limited number of participants, this preliminary psychometric examination shows promising results. The tool has an acceptable internal consistency, excellent test-retest and inter-rater reliability, and, depending on the subscale, weak to strong correlations to related, nonmusical constructs. Overall, this pilot study opens the possibility to further explore the inclusion of music in assessment procedures of Spanish-speaking individuals with ABI in rehabilitation settings. It is clinically derived and emphasizes evidence-based contributions of the field of music therapy to interdisciplinary assessment and treatment in rehabilitation settings., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Music Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2021
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