Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.

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; Almdahl, Ina S; Arnold, Steven E; 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; Forster, 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; Roe, Catherine M; Rot, Uros; Rowe, Christopher C; Rüther, Eckart; Sabri, Osama; Sanchez-Juan, Páscual; Santana, Isabel; Sarazin, Marie; Schröder, Johannes; Schütte, Christin; Seo, Sang W; Soetewey, Femke; Soininen, Hilkka; Spiru, Luiza; Struyfs, Hanne; Teunissen, Charlotte E; Tsolaki, Magda; Vandenberghe, Rik; Verbeek, Marcel M; Villemagne, Victor L; 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     «

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; Almdahl, Ina S; Arnold, Steven E; 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,...     »

Cerebral amyloid-? 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.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).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.Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity.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.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.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-?4 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 ?4?4 carriers, 50 years for ?2?4 carriers, 55 years for ?3?4 carriers, 65 years for ?3?3 carriers, and 95 years for ?2?3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality.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.     «

Cerebral amyloid-? 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.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 cog...     »