TY - JOUR

T1 - Prevalence of cerebral amyloid pathology in persons without dementia

T2 - a meta-analysis

AU - Jansen, Willemijn J

AU - Ossenkoppele, Rik

AU - Knol, Dirk L

AU - Tijms, Betty M

AU - Scheltens, Philip

AU - Verhey, Frans R J

AU - Visser, Pieter Jelle

AU - Aalten, Pauline

AU - Aarsland, Dag

AU - Alcolea, Daniel

AU - Alexander, Myriam

AU - Almdahl, Ina S

AU - Arnold, Steven E

AU - Baldeiras, Inês

AU - Barthel, Henryk

AU - van Berckel, Bart N M

AU - Bibeau, Kristen

AU - Blennow, Kaj

AU - Brooks, David J

AU - van Buchem, Mark A

AU - Camus, Vincent

AU - Cavedo, Enrica

AU - Chen, Kewei

AU - Chetelat, Gael

AU - Cohen, Ann D

AU - Drzezga, Alexander

AU - Engelborghs, Sebastiaan

AU - Fagan, Anne M

AU - Fladby, Tormod

AU - Fleisher, Adam S

AU - van der Flier, Wiesje M

AU - Ford, Lisa

AU - Förster, Stefan

AU - Fortea, Juan

AU - Foskett, Nadia

AU - Frederiksen, Kristian S

AU - Freund-Levi, Yvonne

AU - Frisoni, Giovanni B

AU - Froelich, Lutz

AU - Gabryelewicz, Tomasz

AU - Gill, Kiran Dip

AU - Gkatzima, Olymbia

AU - Gómez-Tortosa, Estrella

AU - Gordon, Mark Forrest

AU - Grimmer, Timo

AU - Hampel, Harald

AU - Hausner, Lucrezia

AU - Hellwig, Sabine

AU - Johannsen, Peter

AU - Waldemar, Gunhild

AU - Amyloid Biomarker Study Group

PY - 2015/5/19

Y1 - 2015/5/19

N2 - 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.

AB - 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.

KW - Adult

KW - Age Factors

KW - Aged

KW - Aged, 80 and over

KW - Amyloid beta-Peptides

KW - Apolipoprotein E4

KW - Biomarkers

KW - Brain

KW - Cerebrospinal Fluid

KW - Dementia

KW - Female

KW - Genotype

KW - Humans

KW - Male

KW - Middle Aged

KW - Mild Cognitive Impairment

KW - Positron-Emission Tomography

KW - Prevalence

KW - Risk Factors

U2 - 10.1001/jama.2015.4668

DO - 10.1001/jama.2015.4668

M3 - Journal article

C2 - 25988462

VL - 313

SP - 1924

EP - 1938

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0098-7484

IS - 19

ER -