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 - 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 -