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13 results on '"Allegri R"'

1. Patterns and implications of neurological examination findings in autosomal dominant Alzheimer disease

Author

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.

Published
2023

2. Different rates of cognitive decline in autosomal dominant and late-onset Alzheimer disease

Author

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

3. The effect of air pollution on COVID-19 severity in a sample of patients with multiple sclerosis

Author

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

4. Religiosity/Spirituality and Mental Health in Older Adults: A Systematic Review and Meta-Analysis of Observational Studies

Author

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

5. SARS-CoV-2 serology after COVID-19 in multiple sclerosis: An international cohort study

Author

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

6. Amyloid and tau pathology associations with personality traits, neuropsychiatric symptoms, and cognitive lifestyle in the preclinical phases of sporadic and autosomal dominant Alzheimer’s disease

Author

Pichet Binette, A., Vachon-Presseau, É., Morris, J., Bateman, R., Benzinger, T., Collins, D.L., Poirier, J., Breitner, J.C.S., Villeneuve, S., Allegri, R., Amtashar, F., Berman, S., Bodge, C., Brandon, S., Brooks, W., Buck, Jill, Buckles, V., Chea, S., Chhatwal, J., Chrem, P., Chui, H., Cinco, J., Clifford, J., Cruchaga, C., D‘Mello, M., Donahue, T., Douglas, J., Edigo, N., Erekin-Taner, N., Fagan, A., Farlow, M., Farrar, A., Feldman, H., Flynn, G., Fox, N., Franklin, E., Fujii, H., Gant, C., Gardener, S., Ghetti, B., Goate, A., Goldman, J., Gordon, B., Graff-Radford, N., Gray, J., Gurney, J., Hassenstab, J., Hirohara, M., Holtzman, D., Hornbeck, R., DiBari, S.H., Ikeuchi, T., Ikonomovic, S., Jerome, G., Jucker, M., Karch, C., Kasuga, K., Kawarabayashi, T., Klunk, W., Koeppe, R., Kuder-Buletta, E., Laske, C., Lee, J-H, Levin, J., Marcus, D., Martins, R., Mason, N.S., Masters, C., Maue-Dreyfus, D., McDade, E., Montoya, L., Mori, H., Nagamatsu, A., Neimeyer, K., Noble, J., Norton, J., Perrin, R., Raichle, M., Ringman, J., Roh, J.H., Salloway, S., Schofield, P., Shimada, H., Shiroto, T., Shoji, M., Sigurdson, W., Sohrabi, H., Sparks, P., Suzuki, K., Swisher, L., Taddei, K., Wang, J., Wang, P., Weiner, M., Wolfsberger, M., Xiong, C., Xu, X., Tam, A., Labonté, A., Faubert, A-M, Mathieu, A., Madjar, C., Carrier, C.E., Dansereau, C., Kazazian, C., Lepage, C., Picard, C., Maillet, D., Michaud, D., Couture, D., Dea, D., Cuello, C., Barkun, A., Evans, A., Courcot, B., Tardif, C., Debacker, C., Jack, C.R., Fontaine, D., Knopman, D.S., Maultaup, G., Near, J., Leoutsakos, J-M, Maltais, J-R, Brandt, J., Pruessner, J., Morris, J.C., Cheewakriengkrai, L., Münter, L-M, Collins, L., Chakravarty, M., Sager, M.A., Dauar-Tedeschi, M., Eisenberg, M., Rajah, N., Aisen, P., Toussaint, J., Rosa-Neto, P., Bellec, P., Kostopoulos, P., Etienne, P., Tariot, P.N., Orban, P., Sperling, R.A., Hoge, R., Thomas, R.G., Gauthier, S., Craft, S., Montine, T.J., Nair, V., Bohbot, V., Venugopalan, V., Fonov, V., Ituria-Medina, Y., Khachaturian, Z.S., Teigner, E., Anthal, E., Yu, E., Ferdinand, F., Pogossova, G., Mayrand, G., Duclair, G., Gagné, G., Newbold-Fox, H., Leppert, I., Vallée, I., Vogel, J.W., Tremblay-Mercier, J., Frenette, J., Frappier, J., Kat, J., Miron, J., Wan, K., Mahar, L., Carmo, L., Théroux, L., Dadar, M., Dufour, M., Lafaille-Magnan, M-E, Appleby, M., Savard, M., Tuwaig, M., Petkova, M., Rioux, P., Meyer, P-F, El-Khoury, R., Gordon, R., Giles, R., Das, S., Wang, S., Tabrizi, S., Mathotaarachchi, S., Dubuc, S., Lee, T., Beaudry, T., Gervais, V., Pagé, V., Gonneaud, J., Ayranci, G., Pascoal, T.A., Desautels, R., Benbouhoud, F., Saint-Fort, E.F., Verfaillie, S.C.J., Farzin, S., Salaciak, A., Tullo, S., Vachon-Presseau, E., Daoust, L-A, Köbe, T., Spreng, N., McSweeney, M., Nilsson, N., Pishnamazi, M., Bedetti, C., Pichet Binette, A., Vachon-Presseau, É., Morris, J., Bateman, R., Benzinger, T., Collins, D.L., Poirier, J., Breitner, J.C.S., Villeneuve, S., Allegri, R., Amtashar, F., Berman, S., Bodge, C., Brandon, S., Brooks, W., Buck, Jill, Buckles, V., Chea, S., Chhatwal, J., Chrem, P., Chui, H., Cinco, J., Clifford, J., Cruchaga, C., D‘Mello, M., Donahue, T., Douglas, J., Edigo, N., Erekin-Taner, N., Fagan, A., Farlow, M., Farrar, A., Feldman, H., Flynn, G., Fox, N., Franklin, E., Fujii, H., Gant, C., Gardener, S., Ghetti, B., Goate, A., Goldman, J., Gordon, B., Graff-Radford, N., Gray, J., Gurney, J., Hassenstab, J., Hirohara, M., Holtzman, D., Hornbeck, R., DiBari, S.H., Ikeuchi, T., Ikonomovic, S., Jerome, G., Jucker, M., Karch, C., Kasuga, K., Kawarabayashi, T., Klunk, W., Koeppe, R., Kuder-Buletta, E., Laske, C., Lee, J-H, Levin, J., Marcus, D., Martins, R., Mason, N.S., Masters, C., Maue-Dreyfus, D., McDade, E., Montoya, L., Mori, H., Nagamatsu, A., Neimeyer, K., Noble, J., Norton, J., Perrin, R., Raichle, M., Ringman, J., Roh, J.H., Salloway, S., Schofield, P., Shimada, H., Shiroto, T., Shoji, M., Sigurdson, W., Sohrabi, H., Sparks, P., Suzuki, K., Swisher, L., Taddei, K., Wang, J., Wang, P., Weiner, M., Wolfsberger, M., Xiong, C., Xu, X., Tam, A., Labonté, A., Faubert, A-M, Mathieu, A., Madjar, C., Carrier, C.E., Dansereau, C., Kazazian, C., Lepage, C., Picard, C., Maillet, D., Michaud, D., Couture, D., Dea, D., Cuello, C., Barkun, A., Evans, A., Courcot, B., Tardif, C., Debacker, C., Jack, C.R., Fontaine, D., Knopman, D.S., Maultaup, G., Near, J., Leoutsakos, J-M, Maltais, J-R, Brandt, J., Pruessner, J., Morris, J.C., Cheewakriengkrai, L., Münter, L-M, Collins, L., Chakravarty, M., Sager, M.A., Dauar-Tedeschi, M., Eisenberg, M., Rajah, N., Aisen, P., Toussaint, J., Rosa-Neto, P., Bellec, P., Kostopoulos, P., Etienne, P., Tariot, P.N., Orban, P., Sperling, R.A., Hoge, R., Thomas, R.G., Gauthier, S., Craft, S., Montine, T.J., Nair, V., Bohbot, V., Venugopalan, V., Fonov, V., Ituria-Medina, Y., Khachaturian, Z.S., Teigner, E., Anthal, E., Yu, E., Ferdinand, F., Pogossova, G., Mayrand, G., Duclair, G., Gagné, G., Newbold-Fox, H., Leppert, I., Vallée, I., Vogel, J.W., Tremblay-Mercier, J., Frenette, J., Frappier, J., Kat, J., Miron, J., Wan, K., Mahar, L., Carmo, L., Théroux, L., Dadar, M., Dufour, M., Lafaille-Magnan, M-E, Appleby, M., Savard, M., Tuwaig, M., Petkova, M., Rioux, P., Meyer, P-F, El-Khoury, R., Gordon, R., Giles, R., Das, S., Wang, S., Tabrizi, S., Mathotaarachchi, S., Dubuc, S., Lee, T., Beaudry, T., Gervais, V., Pagé, V., Gonneaud, J., Ayranci, G., Pascoal, T.A., Desautels, R., Benbouhoud, F., Saint-Fort, E.F., Verfaillie, S.C.J., Farzin, S., Salaciak, A., Tullo, S., Vachon-Presseau, E., Daoust, L-A, Köbe, T., Spreng, N., McSweeney, M., Nilsson, N., Pishnamazi, M., and Bedetti, C.

Abstract

Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression.

Published
2020

7. A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease

Author

Barthélemy, N.R., Li, Y., Joseph-Mathurin, N., Gordon, B.A., Hassenstab, J., Benzinger, T.L.S., Buckles, V., Fagan, A.M., Perrin, R.J., Goate, A.M., Morris, J.C., Karch, C.M., Xiong, C., Allegri, R., Mendez, P.C., Berman, S.B., Ikeuchi, T., Mori, H., Shimada, H., Shoji, M., Suzuki, K., Noble, J., Farlow, M., Chhatwal, J., Graff-Radford, N.R., Salloway, S., Schofield, P.R., Masters, C.L., Martins, R.N., O’Connor, A., Fox, N.C., Levin, J., Jucker, M., Gabelle, A., Lehmann, S., Sato, C., Bateman, R.J., McDade, E., Bateman, R., Bechara, J., Benzinger, T., Berman, S., Bodge, C., Brandon, S., Brooks, W., Buck, J., Chea, S., Chrem Mendez, P., Chui, H., Cinco, J., Clifford, J., Cruchaga, C., Donahue, T., Douglas, J., Edigo, N., Erekin-Taner, N., Fagan, A., Fitzpatrick, C., Flynn, G., Fox, N., Franklin, E., Fujii, H., Gant, C., Gardener, S., Ghetti, B., Goate, A., Goldman, J., Gordon, B., Graff-Radford, N., Gray, J., Groves, A., Hoechst-Swisher, L., Holtzman, D., Hornbeck, R., Houeland DiBari, S., Ikonomovic, S., Jerome, G., Karch, C., Kasuga, K., Kawarabayashi, T., Klunk, W., Koeppe, R., Kuder-Buletta, E., Laske, C., Lee, J-H, Martins, R., Mason, N.S., Masters, C., Maue-Dreyfus, D., Morris, J., Nagamatsu, A., Neimeyer, K., Norton, J., Perrin, R., Raichle, M., Renton, A., Ringman, J., Roh, J.H., Schofield, P., Sigurdson, W., Sohrabi, H., Sparks, P., Taddei, K., Wang, P., Xu, X., Barthélemy, N.R., Li, Y., Joseph-Mathurin, N., Gordon, B.A., Hassenstab, J., Benzinger, T.L.S., Buckles, V., Fagan, A.M., Perrin, R.J., Goate, A.M., Morris, J.C., Karch, C.M., Xiong, C., Allegri, R., Mendez, P.C., Berman, S.B., Ikeuchi, T., Mori, H., Shimada, H., Shoji, M., Suzuki, K., Noble, J., Farlow, M., Chhatwal, J., Graff-Radford, N.R., Salloway, S., Schofield, P.R., Masters, C.L., Martins, R.N., O’Connor, A., Fox, N.C., Levin, J., Jucker, M., Gabelle, A., Lehmann, S., Sato, C., Bateman, R.J., McDade, E., Bateman, R., Bechara, J., Benzinger, T., Berman, S., Bodge, C., Brandon, S., Brooks, W., Buck, J., Chea, S., Chrem Mendez, P., Chui, H., Cinco, J., Clifford, J., Cruchaga, C., Donahue, T., Douglas, J., Edigo, N., Erekin-Taner, N., Fagan, A., Fitzpatrick, C., Flynn, G., Fox, N., Franklin, E., Fujii, H., Gant, C., Gardener, S., Ghetti, B., Goate, A., Goldman, J., Gordon, B., Graff-Radford, N., Gray, J., Groves, A., Hoechst-Swisher, L., Holtzman, D., Hornbeck, R., Houeland DiBari, S., Ikonomovic, S., Jerome, G., Karch, C., Kasuga, K., Kawarabayashi, T., Klunk, W., Koeppe, R., Kuder-Buletta, E., Laske, C., Lee, J-H, Martins, R., Mason, N.S., Masters, C., Maue-Dreyfus, D., Morris, J., Nagamatsu, A., Neimeyer, K., Norton, J., Perrin, R., Raichle, M., Renton, A., Ringman, J., Roh, J.H., Schofield, P., Sigurdson, W., Sohrabi, H., Sparks, P., Taddei, K., Wang, P., and Xu, X.

Abstract

Development of tau-based therapies for Alzheimer’s disease requires an understanding of the timing of disease-related changes in tau. We quantified the phosphorylation state at multiple sites of the tau protein in cerebrospinal fluid markers across four decades of disease progression in dominantly inherited Alzheimer’s disease. We identified a pattern of tau staging where site-specific phosphorylation changes occur at different periods of disease progression and follow distinct trajectories over time. These tau phosphorylation state changes are uniquely associated with structural, metabolic, neurodegenerative and clinical markers of disease, and some (p-tau217 and p-tau181) begin with the initial increases in aggregate amyloid-β as early as two decades before the development of aggregated tau pathology. Others (p-tau205 and t-tau) increase with atrophy and hypometabolism closer to symptom onset. These findings provide insights into the pathways linking tau, amyloid-β and neurodegeneration, and may facilitate clinical trials of tau-based treatments.

Published
2020

8. Comparing cortical signatures of atrophy between late-onset and autosomal dominant Alzheimer disease

Author

Dincer, A, Gordon, BA, Hari-Raj, A, Keefe, SJ, Flores, S, McKay, NS, Paulick, AM, Lewis, KES, Feldman, RL, Hornbeck, RC, Allegri, R, Ances, BM, Berman, SB, Brickman, AM, Brooks, WS, Cash, DM, Chhatwal, JP, Farlow, MR, la Fougere, C, Fox, NC, Fulham, MJ, Jack, CR, Joseph-Mathurin, N, Karch, CM, Lee, A, Levin, J, Masters, CL, McDade, EM, Oh, H, Perrin, RJ, Raji, C, Salloway, SP, Schofield, PR, Su, Y, Villemagne, VL, Wang, Q, Weiner, MW, Xiong, C, Yakushev, I, Morris, JC, Bateman, RJ, Benzinger, TLS, Dincer, A, Gordon, BA, Hari-Raj, A, Keefe, SJ, Flores, S, McKay, NS, Paulick, AM, Lewis, KES, Feldman, RL, Hornbeck, RC, Allegri, R, Ances, BM, Berman, SB, Brickman, AM, Brooks, WS, Cash, DM, Chhatwal, JP, Farlow, MR, la Fougere, C, Fox, NC, Fulham, MJ, Jack, CR, Joseph-Mathurin, N, Karch, CM, Lee, A, Levin, J, Masters, CL, McDade, EM, Oh, H, Perrin, RJ, Raji, C, Salloway, SP, Schofield, PR, Su, Y, Villemagne, VL, Wang, Q, Weiner, MW, Xiong, C, Yakushev, I, Morris, JC, Bateman, RJ, and Benzinger, TLS

Abstract

Defining a signature of cortical regions of interest preferentially affected by Alzheimer disease (AD) pathology may offer improved sensitivity to early AD compared to hippocampal volume or mesial temporal lobe alone. Since late-onset Alzheimer disease (LOAD) participants tend to have age-related comorbidities, the younger-onset age in autosomal dominant AD (ADAD) may provide a more idealized model of cortical thinning in AD. To test this, the goals of this study were to compare the degree of overlap between the ADAD and LOAD cortical thinning maps and to evaluate the ability of the ADAD cortical signature regions to predict early pathological changes in cognitively normal individuals. We defined and analyzed the LOAD cortical maps of cortical thickness in 588 participants from the Knight Alzheimer Disease Research Center (Knight ADRC) and the ADAD cortical maps in 269 participants from the Dominantly Inherited Alzheimer Network (DIAN) observational study. Both cohorts were divided into three groups: cognitively normal controls (nADRC = 381; nDIAN = 145), preclinical (nADRC = 153; nDIAN = 76), and cognitively impaired (nADRC = 54; nDIAN = 48). Both cohorts underwent clinical assessments, 3T MRI, and amyloid PET imaging with either 11C-Pittsburgh compound B or 18F-florbetapir. To generate cortical signature maps of cortical thickness, we performed a vertex-wise analysis between the cognitively normal controls and impaired groups within each cohort using six increasingly conservative statistical thresholds to determine significance. The optimal cortical map among the six statistical thresholds was determined from a receiver operating characteristic analysis testing the performance of each map in discriminating between the cognitively normal controls and preclinical groups. We then performed within-cohort and cross-cohort (e.g. ADAD maps evaluated in the Knight ADRC cohort) analyses to examine the sensitivity of the optimal cortical signature maps to the amyloid levels

Published
2020

9. Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease

Author

Preische, O., Schultz, S.A., Apel, A., Kuhle, J., Kaeser, S.A., Barro, C., Gräber, S., Kuder-Buletta, E., LaFougere, C., Laske, C., Vöglein, J., Levin, J., Masters, C.L., Martins, R., Schofield, P.R., Rossor, M.N., Graff-Radford, N.R., Salloway, S., Ghetti, B., Ringman, J.M., Noble, J.M., Chhatwal, J., Goate, A.M., Benzinger, T.L.S., Morris, J.C., Bateman, R.J., Wang, G., Fagan, A.M., McDade, E.M., Gordon, B.A., Jucker, M., Allegri, R., Amtashar, F., Bateman, R., Benzinger, T., Berman, S., Bodge, C., Brandon, S., Brooks, W., Buck, J., Buckles, V., Chea, S., Chrem, P., Chui, H., Cinco, J., Clifford, J., Cruchaga, C., D’Mello, M., Donahue, T., Douglas, J., Edigo, N., Erekin-Taner, N., Fagan, A., Farlow, M., Farrar, A., Feldman, H., Flynn, G., Fox, N., Franklin, E., Fujii, H., Gant, C., Gardener, S., Goate, A., Goldman, J., Gordon, B., Graff-Radford, N., Gray, J., Gurney, J., Hassenstab, J., Hirohara, M., Holtzman, D., Hornbeck, R., Houeland DiBari, S., Ikeuchi, T., Ikonomovic, S., Jerome, G., Karch, C., Kasuga, K., Kawarabayashi, T., Klunk, W., Koeppe, R., Lee, J-H, Marcus, D., Mason, N.S., Masters, C., Maue-Dreyfus, D., McDade, E., Montoya, L., Mori, H., Morris, J., Nagamatsu, A., Neimeyer, K., Noble, J., Norton, J., Perrin, R., Raichle, M., Ringman, J., Roh, J-H, Schofield, P., Shimada, H., Shiroto, T., Shoji, M., Sigurdson, W., Sohrabi, H., Sparks, P., Suzuki, K., Swisher, L., Taddei, K., Wang, J., Wang, P., Weiner, M., Wolfsberger, M., Xiong, C., Xu, X., Preische, O., Schultz, S.A., Apel, A., Kuhle, J., Kaeser, S.A., Barro, C., Gräber, S., Kuder-Buletta, E., LaFougere, C., Laske, C., Vöglein, J., Levin, J., Masters, C.L., Martins, R., Schofield, P.R., Rossor, M.N., Graff-Radford, N.R., Salloway, S., Ghetti, B., Ringman, J.M., Noble, J.M., Chhatwal, J., Goate, A.M., Benzinger, T.L.S., Morris, J.C., Bateman, R.J., Wang, G., Fagan, A.M., McDade, E.M., Gordon, B.A., Jucker, M., Allegri, R., Amtashar, F., Bateman, R., Benzinger, T., Berman, S., Bodge, C., Brandon, S., Brooks, W., Buck, J., Buckles, V., Chea, S., Chrem, P., Chui, H., Cinco, J., Clifford, J., Cruchaga, C., D’Mello, M., Donahue, T., Douglas, J., Edigo, N., Erekin-Taner, N., Fagan, A., Farlow, M., Farrar, A., Feldman, H., Flynn, G., Fox, N., Franklin, E., Fujii, H., Gant, C., Gardener, S., Goate, A., Goldman, J., Gordon, B., Graff-Radford, N., Gray, J., Gurney, J., Hassenstab, J., Hirohara, M., Holtzman, D., Hornbeck, R., Houeland DiBari, S., Ikeuchi, T., Ikonomovic, S., Jerome, G., Karch, C., Kasuga, K., Kawarabayashi, T., Klunk, W., Koeppe, R., Lee, J-H, Marcus, D., Mason, N.S., Masters, C., Maue-Dreyfus, D., McDade, E., Montoya, L., Mori, H., Morris, J., Nagamatsu, A., Neimeyer, K., Noble, J., Norton, J., Perrin, R., Raichle, M., Ringman, J., Roh, J-H, Schofield, P., Shimada, H., Shiroto, T., Shoji, M., Sigurdson, W., Sohrabi, H., Sparks, P., Suzuki, K., Swisher, L., Taddei, K., Wang, J., Wang, P., Weiner, M., Wolfsberger, M., Xiong, C., and Xu, X.

Abstract

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer’s disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini–Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer’s disease, which supports its potential utility as a clinically useful biomarker.

Published
2019

10. Seizures as an early symptom of autosomal dominant Alzheimer's disease

Author

Vöglein, J, Noachtar, S, McDade, E, Quaid, KA, Salloway, S, Ghetti, B, Noble, J, Berman, S, Chhatwal, J, Mori, H, Fox, N, Allegri, R, Masters, CL, Buckles, V, Ringman, JM, Rossor, M, Schofield, PR, Sperling, R, Jucker, M, Laske, C, Paumier, K, Morris, JC, Bateman, RJ, Levin, J, Danek, A, Vöglein, J, Noachtar, S, McDade, E, Quaid, KA, Salloway, S, Ghetti, B, Noble, J, Berman, S, Chhatwal, J, Mori, H, Fox, N, Allegri, R, Masters, CL, Buckles, V, Ringman, JM, Rossor, M, Schofield, PR, Sperling, R, Jucker, M, Laske, C, Paumier, K, Morris, JC, Bateman, RJ, Levin, J, and Danek, A

Abstract

Our objective was to assess the reported history of seizures in cognitively asymptomatic mutation carriers for autosomal dominant Alzheimer's disease (ADAD) and the predictive value of seizures for mutation carrier status in cognitively asymptomatic first-degree relatives of ADAD patients. Seizure occurrence in the Dominantly Inherited Alzheimer Network observational study was correlated with mutation carrier status in cognitively asymptomatic subjects. Of 276 cognitively asymptomatic individuals, 11 (4%) had experienced seizures, and nine of these carried an ADAD mutation. Thus, in the Dominantly Inherited Alzheimer Network population, seizure frequency in mutation carriers was significantly higher than in noncarriers (p = 0.04), and the positive predictive value of seizures for the presence of a pathogenic mutation was 81.8%. Among cognitively asymptomatic ADAD family members, the occurrence of seizures increases the a priori risk of 50% mutation-positive status to about 80%. This finding suggests that ADAD mutations increase the risk of seizures.

Published
2019

11. An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations

Author

Dube, U., Del-Aguila, J.L., Li, Z., Budde, J.P., Jiang, S., Hsu, S., Ibanez, L., Fernandez, M.V., Farias, F., Norton, J., Gentsch, J., Wang, F., Allegri, R., Amtashar, F., Benzinger, T., Berman, S., Bodge, C., Brandon, S., Brooks, W., Buck, J., Buckles, V., Chea, S., Chrem, P., Chui, H., Cinco, J., Clifford, J., D'Mello, M., Donahue, T., Douglas, J., Edigo, N., Erekin-Taner, N., Fagan, A., Farlow, M., Farrar, A., Feldman, H., Flynn, G., Fox, N., Franklin, E., Fujii, H., Gant, C., Gardener, S., Ghetti, B., Goate, A., Goldman, J., Gordon, B., Gray, J., Gurney, J., Hassenstab, J., Hirohara, M., Holtzman, D., Hornbeck, R., Houeland DiBari, S., Ikeuchi, T., Ikonomovic, S., Jerome, G., Jucker, M., Kasuga, K., Kawarabayashi, T., Klunk, W., koeppe, R., Kuder-Buletta, E., Laske, C., Levin, J., Marcus, D., Martins, R., Mason, N.S., Maue-Dreyfus, D., McDade, E., Montoya, L., Mori, H., Nagamatsu, A., Neimeyer, K., Noble, J., Perrin, R., Raichle, M., Ringman, J., Roh, J-H, Schofield, P., Shimada, H., Shiroto, T., Shoji, M., Sigurdson, W., Sohrabi, H., Sparks, P., Suzuki, K., Swisher, L., Taddei, K., Wang, J., Wang, P., Weiner, M., Wolfsberger, M., Xiong, C., Xu, X., Dube, U., Del-Aguila, J.L., Li, Z., Budde, J.P., Jiang, S., Hsu, S., Ibanez, L., Fernandez, M.V., Farias, F., Norton, J., Gentsch, J., Wang, F., Allegri, R., Amtashar, F., Benzinger, T., Berman, S., Bodge, C., Brandon, S., Brooks, W., Buck, J., Buckles, V., Chea, S., Chrem, P., Chui, H., Cinco, J., Clifford, J., D'Mello, M., Donahue, T., Douglas, J., Edigo, N., Erekin-Taner, N., Fagan, A., Farlow, M., Farrar, A., Feldman, H., Flynn, G., Fox, N., Franklin, E., Fujii, H., Gant, C., Gardener, S., Ghetti, B., Goate, A., Goldman, J., Gordon, B., Gray, J., Gurney, J., Hassenstab, J., Hirohara, M., Holtzman, D., Hornbeck, R., Houeland DiBari, S., Ikeuchi, T., Ikonomovic, S., Jerome, G., Jucker, M., Kasuga, K., Kawarabayashi, T., Klunk, W., koeppe, R., Kuder-Buletta, E., Laske, C., Levin, J., Marcus, D., Martins, R., Mason, N.S., Maue-Dreyfus, D., McDade, E., Montoya, L., Mori, H., Nagamatsu, A., Neimeyer, K., Noble, J., Perrin, R., Raichle, M., Ringman, J., Roh, J-H, Schofield, P., Shimada, H., Shiroto, T., Shoji, M., Sigurdson, W., Sohrabi, H., Sparks, P., Suzuki, K., Swisher, L., Taddei, K., Wang, J., Wang, P., Weiner, M., Wolfsberger, M., Xiong, C., and Xu, X.

Abstract

Parietal cortex RNA-sequencing (RNA-seq) data were generated from individuals with and without Alzheimer disease (AD; ncontrol = 13; nAD = 83) from the Knight Alzheimer Disease Research Center (Knight ADRC). Using this and an independent (Mount Sinai Brain Bank (MSBB)) AD RNA-seq dataset, cortical circular RNA (circRNA) expression was quantified in the context of AD. Significant associations were identified between circRNA expression and AD diagnosis, clinical dementia severity and neuropathological severity. It was demonstrated that most circRNA–AD associations are independent of changes in cognate linear messenger RNA expression or estimated brain cell-type proportions. Evidence was provided for circRNA expression changes occurring early in presymptomatic AD and in autosomal dominant AD. It was also observed that AD-associated circRNAs co-expressed with known AD genes. Finally, potential microRNA-binding sites were identified in AD-associated circRNAs for miRNAs predicted to target AD genes. Together, these results highlight the importance of analyzing non-linear RNAs and support future studies exploring the potential roles of circRNAs in AD pathogenesis.

Published
2019

12. An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations

Author

Dube, U., Del-Aguila, J.L., Li, Z., Budde, J.P., Jiang, S., Hsu, S., Ibanez, L., Fernandez, M.V., Farias, F., Norton, J., Gentsch, J., Wang, F., Allegri, R., Amtashar, F., Benzinger, T., Berman, S., Bodge, C., Brandon, S., Brooks, W., Buck, J., Buckles, V., Chea, S., Chrem, P., Chui, H., Cinco, J., Clifford, J., D'Mello, M., Donahue, T., Douglas, J., Edigo, N., Erekin-Taner, N., Fagan, A., Farlow, M., Farrar, A., Feldman, H., Flynn, G., Fox, N., Franklin, E., Fujii, H., Gant, C., Gardener, S., Ghetti, B., Goate, A., Goldman, J., Gordon, B., Gray, J., Gurney, J., Hassenstab, J., Hirohara, M., Holtzman, D., Hornbeck, R., Houeland DiBari, S., Ikeuchi, T., Ikonomovic, S., Jerome, G., Jucker, M., Kasuga, K., Kawarabayashi, T., Klunk, W., koeppe, R., Kuder-Buletta, E., Laske, C., Levin, J., Marcus, D., Martins, R., Mason, N.S., Maue-Dreyfus, D., McDade, E., Montoya, L., Mori, H., Nagamatsu, A., Neimeyer, K., Noble, J., Perrin, R., Raichle, M., Ringman, J., Roh, J-H, Schofield, P., Shimada, H., Shiroto, T., Shoji, M., Sigurdson, W., Sohrabi, H., Sparks, P., Suzuki, K., Swisher, L., Taddei, K., Wang, J., Wang, P., Weiner, M., Wolfsberger, M., Xiong, C., Xu, X., Dube, U., Del-Aguila, J.L., Li, Z., Budde, J.P., Jiang, S., Hsu, S., Ibanez, L., Fernandez, M.V., Farias, F., Norton, J., Gentsch, J., Wang, F., Allegri, R., Amtashar, F., Benzinger, T., Berman, S., Bodge, C., Brandon, S., Brooks, W., Buck, J., Buckles, V., Chea, S., Chrem, P., Chui, H., Cinco, J., Clifford, J., D'Mello, M., Donahue, T., Douglas, J., Edigo, N., Erekin-Taner, N., Fagan, A., Farlow, M., Farrar, A., Feldman, H., Flynn, G., Fox, N., Franklin, E., Fujii, H., Gant, C., Gardener, S., Ghetti, B., Goate, A., Goldman, J., Gordon, B., Gray, J., Gurney, J., Hassenstab, J., Hirohara, M., Holtzman, D., Hornbeck, R., Houeland DiBari, S., Ikeuchi, T., Ikonomovic, S., Jerome, G., Jucker, M., Kasuga, K., Kawarabayashi, T., Klunk, W., koeppe, R., Kuder-Buletta, E., Laske, C., Levin, J., Marcus, D., Martins, R., Mason, N.S., Maue-Dreyfus, D., McDade, E., Montoya, L., Mori, H., Nagamatsu, A., Neimeyer, K., Noble, J., Perrin, R., Raichle, M., Ringman, J., Roh, J-H, Schofield, P., Shimada, H., Shiroto, T., Shoji, M., Sigurdson, W., Sohrabi, H., Sparks, P., Suzuki, K., Swisher, L., Taddei, K., Wang, J., Wang, P., Weiner, M., Wolfsberger, M., Xiong, C., and Xu, X.

Abstract

Parietal cortex RNA-sequencing (RNA-seq) data were generated from individuals with and without Alzheimer disease (AD; ncontrol = 13; nAD = 83) from the Knight Alzheimer Disease Research Center (Knight ADRC). Using this and an independent (Mount Sinai Brain Bank (MSBB)) AD RNA-seq dataset, cortical circular RNA (circRNA) expression was quantified in the context of AD. Significant associations were identified between circRNA expression and AD diagnosis, clinical dementia severity and neuropathological severity. It was demonstrated that most circRNA–AD associations are independent of changes in cognate linear messenger RNA expression or estimated brain cell-type proportions. Evidence was provided for circRNA expression changes occurring early in presymptomatic AD and in autosomal dominant AD. It was also observed that AD-associated circRNAs co-expressed with known AD genes. Finally, potential microRNA-binding sites were identified in AD-associated circRNAs for miRNAs predicted to target AD genes. Together, these results highlight the importance of analyzing non-linear RNAs and support future studies exploring the potential roles of circRNAs in AD pathogenesis.

Published
2019

13. Risk factors and clinical characteristics associated with hospitalization for community-acquired bacterial pneumonia in HIV-positive patients according to the presence of liver cirrhosis

Author

Manno, D, Puoti, M, Signorini, L, Lapadula, G, Cadeo, B, Soavi, L, Paraninfo, G, Allegri, R, Cristini, G, Viale, P, Carosi, G, Manno D., Puoti M., Signorini L., Lapadula G., Cadeo B., Soavi L., Paraninfo G., Allegri R., Cristini G., Viale P., Carosi G., Manno, D, Puoti, M, Signorini, L, Lapadula, G, Cadeo, B, Soavi, L, Paraninfo, G, Allegri, R, Cristini, G, Viale, P, Carosi, G, Manno D., Puoti M., Signorini L., Lapadula G., Cadeo B., Soavi L., Paraninfo G., Allegri R., Cristini G., Viale P., and Carosi G.

Abstract

Background: Community-acquired bacterial pneumonia (CABP) represents an important cause of morbidity and mortality for cirrhotic and HIV-infected patients, respectively. However, little is known on CABP in HIV-positive patients with cirrhosis. A study was performed to describev the clinical features and factors predictive of mortality and prolonged hospitalization in cirrhotic HIV-infected patients with a diagnosis of CABP. Methods: Demographic and clinical characteristics of cirrhotic HIV-positive subjects, hospitalized for CABP in our department from June 2000 to December 2006, were compared with those of non-cirrhotic HIV-infected patients with the same diagnosis hospitalized from June 2000 to November 2001. Variables with p < 0.10 in univariate analysis were tested for their predictive value for mortality and length of hospitalization with uni- and multivariate logistic regression analysis. Results: Twenty-nine cirrhotic and 73 non-cirrhotic HIV-positive patients with CABP were compared. Age and alcohol abusewere significantly higher in cirrhotics. At hospital admission, cirrhotic patients had more frequently mental status alterations (7.26 [2.21-23.82], p = 0.001) and milder symptoms and signs (temperature > 37.5 C: 0.27 [0.10-0.75], p = 0.01; respiratory rate > 20: 0.34 [0.13-0.92], p = 0.033; systemic inflammatory response syndrome (SIRS): 0.39 [0.16-0.95], p = 0.038). Adjusting for age, cirrhosis was associated with a higher mortality (5.96 [1.05-33.57]; p = 0.043). Adjusting for age, gender, and concomitant antiretroviral treatment, cirrhosis was also associated with a prolonged hospitalization (> 7 days: 9.30 1.84-46.82]; p = 0.007). Conclusions: The diagnosis of CABP can be difficult in cirrhotic HIV-positive patients because clinical presentation is milder. However, CABP needs to be promptly recognized because mortality is higher in these patients. © 2008 Springer.

Published
2009

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