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European Medical Information Framework
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Prevalence of cerebral amyloid pathology in persons without dementia
Publication . Jansen, Willemijn J.; Ossenkoppele, Rik; Knol, Dirk L.; Tijms, Betty M.; Scheltens, Philip; Verhey, Frans R. J.; Visser, Pieter Jelle; Aalten, Pauline; Aarsland, Dag; Alcolea, Daniel; Alexander, Myriam; Roe, Catherine M.; Rot, Uros; Rowe, Christopher C.; Rüther, Eckart; Sabri, Osama; Sanchez-Juan, Páscual; Santana, Isabel; Sarazin, Marie; Schröder, Johannes; Schütte, Christin; Almdahl, Ina S.; Seo, Sang W.; Soetewey, Femke; Soininen, Hilkka; Spiru, Luiza; Struyfs, Hanne; Teunissen, Charlotte E.; Tsolaki, Magda; Vandenberghe, Rik; Verbeek, Marcel M.; Villemagne, Victor L.; Arnold, Steven E.; Vos, Stephanie J. B.; van Waalwijk van Doorn, Linda J. C.; Waldemar, Gunhild; Wallin, Anders; Wallin, Åsa K.; Wiltfang, Jens; Wolk, David A.; Zboch, Marzena; Zetterberg, Henrik; Baldeiras, Inês; Barthel, Henryk; van Berckel, Bart N. M.; Bibeau, Kristen; Blennow, Kaj; Brooks, David J.; van Buchem, Mark A.; Camus, Vincent; Cavedo, Enrica; Chen, Kewei; Chetelat, Gael; Cohen, Ann D.; Drzezga, Alexander; Engelborghs, Sebastiaan; Fagan, Anne M.; Fladby, Tormod; Fleisher, Adam S.; van der Flier, Wiesje M.; Ford, Lisa; Förster, Stefan; Fortea, Juan; Foskett, Nadia; Frederiksen, Kristian S.; Freund-Levi, Yvonne; Frisoni, Giovanni B.; Froelich, Lutz; Gabryelewicz, Tomasz; Gill, Kiran Dip; Gkatzima, Olymbia; Gómez-Tortosa, Estrella; Gordon, Mark Forrest; Grimmer, Timo; Hampel, Harald; Hausner, Lucrezia; Hellwig, Sabine; Herukka, Sanna-Kaisa; Hildebrandt, Helmut; Ishihara, Lianna; Ivanoiu, Adrian; Jagust, William J.; Johannsen, Peter; Kandimalla, Ramesh; Kapaki, Elisabeth; Klimkowicz-Mrowiec, Aleksandra; Klunk, William E.; Köhler, Sebastian; Koglin, Norman; Kornhuber, Johannes; Kramberger, Milica G.; Van Laere, Koen; Landau, Susan M.; Lee, Dong Young; de Leon, Mony; Lisetti, Viviana; Lleó, Alberto; Madsen, Karine; Maier, Wolfgang; Marcusson, Jan; Mattsson, Niklas; De Mendonça, Alexandre; Meulenbroek, Olga; Meyer, Philipp T.; Mintun, Mark A.; Mok, Vincent; Molinuevo, José Luis; Møllergård, Hanne M.; Morris, John C.; Mroczko, Barbara; Van der Mussele, Stefan; Na, Duk L.; Newberg, Andrew; Nordberg, Agneta; Nordlund, Arto; Novak, Gerald P.; Paraskevas, George P.; Parnetti, Lucilla; Perera, Gayan; Peters, Oliver; Popp, Julius; Prabhakar, Sudesh; Rabinovici, Gil D.; Ramakers, Inez H. G. B.; Rami, Lorena; Resende de Oliveira, Catarina; Rinne, Juha O.; Rodrigue, Karen M.; Rodríguez-Rodríguez, Eloy
Importance: Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
Objective: To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI).
Data sources: Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators.
Study selection: Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity.
Data extraction and synthesis: Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies.
Main outcomes and measures: Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations.
Results: The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOE ε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality.
Conclusions and relevance: Among persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, APOE genotype, and presence of cognitive impairment. These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia.
Prevalence and prognosis of Alzheimer’s disease at the mild cognitive impairment stage
Publication . Vos, Stephanie J. B.; Verhey, Frans; Frölich, Lutz; Kornhuber, Johannes; Wiltfang, Jens; Maier, Wolfgang; Peters, Oliver; Rüther, Eckart; Nobili, Flavio; Morbelli, Silvia; Frisoni, Giovanni B.; Drzezga, Alexander; Didic, Mira; van Berckel, Bart N. M.; Simmons, Andrew; Soininen, Hilkka; Kłoszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon; Muscio, Cristina; Herukka, Sanna-Kaisa; Salmon, Eric; Bastin, Christine; Wallin, Anders; Nordlund, Arto; De Mendonça, Alexandre; Silva, Dina; Santana, Isabel; Lemos, Raquel; Engelborghs, Sebastiaan; Van der Mussele, Stefan; Freund-Levi, Yvonne; Wallin, Åsa K.; Hampel, Harald; van der Flier, Wiesje; Scheltens, Philip; Visser, Pieter Jelle
Three sets of research criteria are available for diagnosis of Alzheimer's disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognitive impairment (n = 1607), 766 of whom had both amyloid and neuronal injury markers, were recruited from 13 cohorts. We used cognitive test performance and available biomarkers to classify subjects as prodromal Alzheimer's disease according to International Working Group-1 and International Working Group-2 criteria and in the high Alzheimer's disease likelihood group, conflicting biomarker groups (isolated amyloid pathology or suspected non-Alzheimer pathophysiology), and low Alzheimer's disease likelihood group according to the National Institute of Ageing-Alzheimer Association criteria. Outcome measures were the proportion of subjects with Alzheimer's disease at the mild cognitive impairment stage and progression to Alzheimer's disease-type dementia. We performed survival analyses using Cox proportional hazards models. According to the International Working Group-1 criteria, 850 (53%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 50% compared to 21% for subjects without prodromal Alzheimer's disease. According to the International Working Group-2 criteria, 308 (40%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 61% compared to 22% for subjects without prodromal Alzheimer's disease. According to the National Institute of Ageing-Alzheimer Association criteria, 353 (46%) subjects were in the high Alzheimer's disease likelihood group, 49 (6%) in the isolated amyloid pathology group, 220 (29%) in the suspected non-Alzheimer pathophysiology group, and 144 (19%) in the low Alzheimer's disease likelihood group. The 3-year progression rate to Alzheimer's disease-type dementia was 59% in the high Alzheimer's disease likelihood group, 22% in the isolated amyloid pathology group, 24% in the suspected non-Alzheimer pathophysiology group, and 5% in the low Alzheimer's disease likelihood group. Our findings support the use of the proposed research criteria to identify Alzheimer's disease at the mild cognitive impairment stage. In clinical settings, the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis. For clinical trials, selection of subjects in the National Institute of Ageing-Alzheimer Association high Alzheimer's disease likelihood group or the International Working Group-2 prodromal Alzheimer's disease group could be considered.
The frequency and influence of dementia risk factors in prodromal Alzheimer's disease
Publication . Bos, Isabelle; Vos, Stephanie J.; Frölich, Lutz; Kornhuber, Johannes; Wiltfang, Jens; Maier, Wolfgang; Peters, Oliver; Rüther, Eckhart; Engelborghs, Sebastiaan; Niemantsverdriet, Ellis; De Roeck, Ellen Elisa; Tsolaki, Magda; Freund-Levi, Yvonne; Johannsen, Peter; Vandenberghe, Rik; Lleó, Alberto; Alcolea, Daniel; Frisoni, Giovanni B.; Galluzzi, Samantha; Nobili, Flavio; Morbelli, Silvia; Drzezga, Alexander; Didic, Mira; van Berckel, Bart N.; Salmon, Eric; Bastin, Christine; Dauby, Solene; Santana, Isabel; Baldeiras, Ines; De Mendonça, Alexandre; Silva, Dina; Wallin, Anders; Nordlund, Arto; Coloma, Preciosa M.; Wientzek, Angelika; Alexander, Myriam; Novak, Gerald P.; Gordon, Mark Forrest; Wallin, Åsa K.; Hampel, Harald; Soininen, Hilkka; Herukka, Sanna-Kaisa; Scheltens, Philip; Verhey, Frans R.; Visser, Pieter Jelle
We investigated whether dementia risk factors were associated with prodromal Alzheimer's disease (AD) according to the International Working Group-2 and National Institute of Aging-Alzheimer's Association criteria, and with cognitive decline. A total of 1394 subjects with mild cognitive impairment from 14 different studies were classified according to these research criteria, based on cognitive performance and biomarkers. We compared the frequency of 10 risk factors between the subgroups, and used Cox-regression to examine the effect of risk factors on cognitive decline. Depression, obesity, and hypercholesterolemia occurred more often in individuals with low-AD-likelihood, compared with those with a high-AD-likelihood. Only alcohol use increased the risk of cognitive decline, regardless of AD pathology. These results suggest that traditional risk factors for AD are not associated with prodromal AD or with progression to dementia, among subjects with mild cognitive impairment. Future studies should validate these findings and determine whether risk factors might be of influence at an earlier stage (i.e., preclinical) of AD.
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Entidade financiadora
European Commission
Programa de financiamento
FP7
Número da atribuição
115372