TY - JOUR

T1 - Weighting and standardization of frequencies to determine prevalence of AD imaging biomarkers

AU - Roberts, Rosebud O.

AU - Knopman, David S.

AU - Syrjanen, Jeremy A.

AU - Aakre, Jeremiah A.

AU - Vassilaki, Maria

AU - Kremers, Walter K.

AU - Mielke, Michelle M.

AU - Machulda, Mary M.

AU - Graff-Radford, Jonathan

AU - Geda, Yonas E.

AU - Vemuri, Prashanthi

AU - Lowe, Val

AU - Jack, Clifford R.

AU - Petersen, Ronald C.

N1 - Funding Information:
The study was funded by the NIH (P50 AG016574, U01 AG006786, R01 AG041851, R01 NS097495, R01 AG011378), the Elsie and Marvin Dekelboum Family Foundation, the GHR Foundation, and the Mayo Foundation for Medical Education and Research, and was made possible by the Rochester Epidemiology Project (R01 AG034676).
Funding Information:
R. Roberts receives research funding from the NIH/NIA and Roche. D. Knopman serves on a Data Safety Monitoring Board for Lundbeck Pharmaceuticals and for the DIAN study; is an investigator in clinical trials sponsored by Biogen, TauRX Pharmaceuticals, Lilly Pharmaceuticals, and the Alzheimer’s Disease Cooperative Study; and receives research support from the NIH. J. Syrjanen and J. Aakre report no disclosures relevant to the manuscript. M. Vassilaki receives research funding from Roche. W. Kremers receives research funding from NIH and Roche. M. Mielke consults for Eli Lilly and Lysosomal Therapeutics, Inc., receives unrestricted research grants from Biogen and Roche, and receives research funding from the NIH/NIA and the Department of Defense. M. Machulda receives research support from the NIH/NIA & NIDCD. J. Graff-Radford reports no disclosures relevant to the manuscript. Y. Geda receives funding from NIH and Roche. P. Vemuri receives NIH funding. V. Lowe serves on scientific advisory boards for Bayer Schering Pharma, Piramal Life Sciences, and Merck Research, and receives research support from GE Healthcare, Siemens Molecular Imaging, Avid Radiopharmaceuticals, and the NIH (NIA, NCI). C. Jack serves on a scientific advisory board for Eli Lilly & Company; receives research support from the NIH/NIA and the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Foundation; and holds stock in Johnson & Johnson. R. Petersen is a consultant for Roche, Inc., Biogen, Inc., Merck, Inc., Eli Lilly and Company, and Genentech, Inc.; receives publishing royalties from Mild Cognitive Impairment (Oxford University Press, 2003); and receives research support from the NIH. Go to Neurology.org for full disclosures.

PY - 2017

Y1 - 2017

N2 - Objective: To estimate the prevalence of elevated brain amyloid and reduced cortical thickness (as a marker for neurodegeneration) in a defined population. Methods: Mayo Clinic Study of Aging participants underwent MRI to assess a composite Alzheimer disease (AD) signature cortical thickness measure and PET to assess brain amyloid accumulation. Participants were characterized as having elevated amyloid (A+/A-), reduced cortical thickness (N+/N-), and A+N+, A+N-, A-N+, or A-N-. The prevalence of AD biomarkers was derived by adjusting for nonparticipation and standardizing to the Olmsted County, Minnesota, population. Results: Among 1,646 participants without dementia (mean age 70.8 years; 53.2% men), the prevalence (95% confidence interval) of amyloidosis was 21.1% (19.1%-23.2%): women, 24.3%; men, 17.5%. The prevalence of reduced cortical thickness was 28.9% (26.4%-31.5%): women, 27.9%; men, 30.2%. The prevalence estimates of biomarker categories were as follows: A-N-: 61.4%; A+N-: 9.7%; A-N+: 17.4%; and A+N+: 11.5%, and varied by sex and by APOE ϵ4 carrier status. In men, prevalence estimates were as follows: A-N-: 62.6%; A+N-: 7.3%; A-N+: 19.9%; and A+N+: 10.2%. In women, prevalence estimates were as follows: A-N-: 60.4%; A+N-: 11.7%; A-N+: 15.3%; and A+N+: 12.6%. In ϵ4 carriers, prevalence estimates were as follows: A-N-: 54.6%; A+N-: 16.6%; A-N+: 12.4%; and A+N+: 16.4%. In non-ϵ4 carriers, prevalence estimates were as follows: A-N-: 63.3%; A+N-: 6.9%; A-N+: 19.9%; and A+N+: 10.0%. Conclusions: These prevalence estimates are important for understanding age-related trends in amyloid positivity and AD signature cortical thickness in the population, and for potentially projecting the future burden of biomarkers in elderly persons.

AB - Objective: To estimate the prevalence of elevated brain amyloid and reduced cortical thickness (as a marker for neurodegeneration) in a defined population. Methods: Mayo Clinic Study of Aging participants underwent MRI to assess a composite Alzheimer disease (AD) signature cortical thickness measure and PET to assess brain amyloid accumulation. Participants were characterized as having elevated amyloid (A+/A-), reduced cortical thickness (N+/N-), and A+N+, A+N-, A-N+, or A-N-. The prevalence of AD biomarkers was derived by adjusting for nonparticipation and standardizing to the Olmsted County, Minnesota, population. Results: Among 1,646 participants without dementia (mean age 70.8 years; 53.2% men), the prevalence (95% confidence interval) of amyloidosis was 21.1% (19.1%-23.2%): women, 24.3%; men, 17.5%. The prevalence of reduced cortical thickness was 28.9% (26.4%-31.5%): women, 27.9%; men, 30.2%. The prevalence estimates of biomarker categories were as follows: A-N-: 61.4%; A+N-: 9.7%; A-N+: 17.4%; and A+N+: 11.5%, and varied by sex and by APOE ϵ4 carrier status. In men, prevalence estimates were as follows: A-N-: 62.6%; A+N-: 7.3%; A-N+: 19.9%; and A+N+: 10.2%. In women, prevalence estimates were as follows: A-N-: 60.4%; A+N-: 11.7%; A-N+: 15.3%; and A+N+: 12.6%. In ϵ4 carriers, prevalence estimates were as follows: A-N-: 54.6%; A+N-: 16.6%; A-N+: 12.4%; and A+N+: 16.4%. In non-ϵ4 carriers, prevalence estimates were as follows: A-N-: 63.3%; A+N-: 6.9%; A-N+: 19.9%; and A+N+: 10.0%. Conclusions: These prevalence estimates are important for understanding age-related trends in amyloid positivity and AD signature cortical thickness in the population, and for potentially projecting the future burden of biomarkers in elderly persons.

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U2 - 10.1212/WNL.0000000000004652

DO - 10.1212/WNL.0000000000004652

M3 - Article

C2 - 29030451

AN - SCOPUS:85037714814

VL - 89

SP - 2039

EP - 2048

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 20

ER -