TY - JOUR
T1 - The Spectrum of Alzheimer-Type Pathology in Cognitively Normal Individuals
AU - Walker, Jamie M.
AU - Dehkordi, Shiva Kazempour
AU - Schaffert, Jeff
AU - Goette, William
AU - White, Charles L.
AU - Richardson, Timothy E.
AU - Zare, Habil
N1 - Funding Information:
The NACC database is funded by NIA/NIH Grant U24 AG072122. NACC data are contributed by the NIA-funded ADRCs: P30 AG062429 (PI James Brewer, MD, PhD), P30 AG066468 (PI Oscar Lopez, MD), P30 AG062421 (PI Bradley Hyman, MD, PhD), P30 AG066509 (PI Thomas Grabowski, MD), P30 AG066514 (PI Mary Sano, PhD), P30 AG066530 (PI Helena Chui, MD), P30 AG066507 (PI Marilyn Albert, PhD), P30 AG066444 (PI John Morris, MD), P30 AG066518 (PI Jeffrey Kaye, MD), P30 AG066512 (PI Thomas Wisniewski, MD), P30 AG066462 (PI Scott Small, MD), P30 AG072979 (PI David Wolk, MD), P30 AG072972 (PI Charles DeCarli, MD), P30 AG072976 (PI Andrew Saykin, PsyD), P30 AG072975 (PI David Bennett, MD), P30 AG072978 (PI Neil Kowall, MD), P30 AG072977 (PI Robert Vassar, PhD), P30 AG066519 (PI Frank LaFerla, PhD), P30 AG062677 (PI Ronald Petersen, MD, PhD), P30 AG079280 (PI Eric Reiman, MD), P30 AG062422 (PI Gil Rabinovici, MD), P30 AG066511 (PI Allan Levey, MD, PhD), P30 AG072946 (PI Linda Van Eldik, PhD), P30 AG062715 (PI Sanjay Asthana, MD, FRCP), P30 AG072973 (PI Russell Swerdlow, MD), P30 AG066506 (PI Todd Golde, MD, PhD), P30 AG066508 (PI Stephen Strittmatter, MD, PhD), P30 AG066515 (PI Victor Henderson, MD, MS), P30 AG072947 (PI Suzanne Craft, PhD), P30 AG072931 (PI Henry Paulson, MD, PhD), P30 AG066546 (PI Sudha Seshadri, MD), P20 AG068024 (PI Erik Roberson, MD, PhD), P20 AG068053 (PI Justin Miller, PhD), P20 AG068077 (PI Gary Rosenberg, MD), P20 AG068082 (PI Angela Jefferson, PhD), P30 AG072958 (PI Heather Whitson, MD), P30 AG072959 (PI James Leverenz, MD).
Funding Information:
J.M.W. and T.E.R. are supported in part by National Institute on Aging (NIA) R21 AG078505 and P30 AG066546. J.M.W. is also supported by the San Antonio Claude D. Pepper Older Americans Independence Center, P30 AG044271. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Publisher Copyright:
© 2023-IOS Press. All rights reserved.
PY - 2023
Y1 - 2023
N2 - Background: The strongest risk factor for the development of Alzheimer's disease (AD) is age. The progression of Braak stage and Thal phase with age has been demonstrated. However, prior studies did not include cognitive status. Objective: We set out to define normative values for Alzheimer-Type pathologic changes in individuals without cognitive decline, and then define levels that would qualify them to be resistant to or resilient against these changes. Methods: Utilizing neuropathology data obtained from the National Alzheimer's Coordinating Center (NACC), we demonstrate the age-related progression of Alzheimer-Type pathologic changes in cognitively normal individuals (CDR=0, n=542). With plots generated from these data, we establish standard lines that may be utilized to measure the extent to which an individual's Alzheimer-Type pathology varies from the estimated normal range of pathology. Results: Although Braak stage and Thal phase progressively increase with age in cognitively normal individuals, the Consortium to Establish a Registry for Alzheimer's Disease neuritic plaque score and Alzheimer's disease neuropathologic change remain at low levels. Conclusion: These findings suggest that an increasing burden of neuritic plaques is a strong predictor of cognitive decline, whereas, neurofibrillary degeneration and amyloid-β (diffuse) plaque deposition, both to some degree, are normal pathologic changes of aging that occur in almost all individuals regardless of cognitive status. Furthermore, we have defined the amount of neuropathologic change in cognitively normal individuals that would qualify them to be 'resilient' against the pathology (significantly above the normative values for age, but still cognitively normal) or 'resistant' to the development of pathology (significantly below the normative values for age).
AB - Background: The strongest risk factor for the development of Alzheimer's disease (AD) is age. The progression of Braak stage and Thal phase with age has been demonstrated. However, prior studies did not include cognitive status. Objective: We set out to define normative values for Alzheimer-Type pathologic changes in individuals without cognitive decline, and then define levels that would qualify them to be resistant to or resilient against these changes. Methods: Utilizing neuropathology data obtained from the National Alzheimer's Coordinating Center (NACC), we demonstrate the age-related progression of Alzheimer-Type pathologic changes in cognitively normal individuals (CDR=0, n=542). With plots generated from these data, we establish standard lines that may be utilized to measure the extent to which an individual's Alzheimer-Type pathology varies from the estimated normal range of pathology. Results: Although Braak stage and Thal phase progressively increase with age in cognitively normal individuals, the Consortium to Establish a Registry for Alzheimer's Disease neuritic plaque score and Alzheimer's disease neuropathologic change remain at low levels. Conclusion: These findings suggest that an increasing burden of neuritic plaques is a strong predictor of cognitive decline, whereas, neurofibrillary degeneration and amyloid-β (diffuse) plaque deposition, both to some degree, are normal pathologic changes of aging that occur in almost all individuals regardless of cognitive status. Furthermore, we have defined the amount of neuropathologic change in cognitively normal individuals that would qualify them to be 'resilient' against the pathology (significantly above the normative values for age, but still cognitively normal) or 'resistant' to the development of pathology (significantly below the normative values for age).
KW - Alzheimer's disease
KW - Braak stage
KW - CERAD neuritic plaque score
KW - Thal phase
KW - cognitively normal
KW - resilience
KW - resistance
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U2 - 10.3233/JAD-220898
DO - 10.3233/JAD-220898
M3 - Article
C2 - 36502330
AN - SCOPUS:85147046359
SN - 1387-2877
VL - 91
SP - 683
EP - 695
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 2
ER -