Thal Amyloid Stages Do Not Significantly Impact the Correlation Between Neuropathological Change and Cognition in the Alzheimer Disease Continuum.
The 2012 neuropathological criteria for the diagnosis of Alzheimer disease (AD) summarize the extent of AD neuropathological change with an ABC score, which is a composite of the Thal stage of amyloid deposition (A), the Braak stage of neurofibrillary tangles (NFTs) (B), and the CERAD neuritic plaque score (C). NFTs and neuritic plaques are well-established contributors to cognitive impairment, but whether the Thal amyloid stage independently predicts antemortem cognition remains unknown. We used the National Alzheimer's Coordinating Center autopsy data set to build adjacent-categories logit regression models with CDR-SOB and Mini-Mental State Examination (MMSE) scores as cognitive outcome variables. Increasing CERAD scores were independently associated with higher CDR-SOB scores, whereas increasing Braak NFT stages predicted both higher CDR-SOB and lower MMSE scores. Increasing Thal amyloid stages were not significantly independently associated with either outcome measure. Increasing ABC scores predicted higher CDR-SOB and lower MMSE scores. These results raise the possibility that Thal amyloid stages do not substantially contribute to predicting antemortem cognition compared to CERAD neuritic plaque scores and Braak NFT stages, and suggest that the diffuse amyloid deposits participating in the assignment of Thal amyloid stages are neutral with respect to clinically detectable cognitive and functional changes.
From the Department of Neurology of the University of Iowa Hospitals & Clinics, Iowa City, Iowa (AS-P); Department of Biostatistics and Epidemiology of the University of Massachusetts, Amherst, Massachusetts (JQ); Massachusetts General Hospital Biostatistics Center, Boston, Massachusetts (AM); Department of Biostatistics, University of Washington, Seattle, Washington (SEM); Department of Pathology, School of Medicine of the University of Washington, Seattle, Washington (TJM); C. S. Kubik Laboratory for Neuropathology of the Massachusetts General Hospital (MPF), Department of Neurology of the Massachusetts General Hospital, Boston, Massachusetts (BTH); Department of Biostatistics of the Harvard T. H. Chan School of Public Health, Boston, Massachusetts (RAB); and Massachusetts Alzheimer Disease Research Center, Charlestown, Massachusetts (MPF, RAB, BTH).
Alberto
A
Serrano-Pozo
From the Department of Neurology of the University of Iowa Hospitals & Clinics, Iowa City, Iowa (AS-P); Department of Biostatistics and Epidemiology of the University of Massachusetts, Amherst, Massachusetts (JQ); Massachusetts General Hospital Biostatistics Center, Boston, Massachusetts (AM); Department of Biostatistics, University of Washington, Seattle, Washington (SEM); Department of Pathology, School of Medicine of the University of Washington, Seattle, Washington (TJM); C. S. Kubik Laboratory for Neuropathology of the Massachusetts General Hospital (MPF), Department of Neurology of the Massachusetts General Hospital, Boston, Massachusetts (BTH); Department of Biostatistics of the Harvard T. H. Chan School of Public Health, Boston, Massachusetts (RAB); and Massachusetts Alzheimer Disease Research Center, Charlestown, Massachusetts (MPF, RAB, BTH).
Jing
J
Qian
From the Department of Neurology of the University of Iowa Hospitals & Clinics, Iowa City, Iowa (AS-P); Department of Biostatistics and Epidemiology of the University of Massachusetts, Amherst, Massachusetts (JQ); Massachusetts General Hospital Biostatistics Center, Boston, Massachusetts (AM); Department of Biostatistics, University of Washington, Seattle, Washington (SEM); Department of Pathology, School of Medicine of the University of Washington, Seattle, Washington (TJM); C. S. Kubik Laboratory for Neuropathology of the Massachusetts General Hospital (MPF), Department of Neurology of the Massachusetts General Hospital, Boston, Massachusetts (BTH); Department of Biostatistics of the Harvard T. H. Chan School of Public Health, Boston, Massachusetts (RAB); and Massachusetts Alzheimer Disease Research Center, Charlestown, Massachusetts (MPF, RAB, BTH).
Alona
A
Muzikansky
From the Department of Neurology of the University of Iowa Hospitals & Clinics, Iowa City, Iowa (AS-P); Department of Biostatistics and Epidemiology of the University of Massachusetts, Amherst, Massachusetts (JQ); Massachusetts General Hospital Biostatistics Center, Boston, Massachusetts (AM); Department of Biostatistics, University of Washington, Seattle, Washington (SEM); Department of Pathology, School of Medicine of the University of Washington, Seattle, Washington (TJM); C. S. Kubik Laboratory for Neuropathology of the Massachusetts General Hospital (MPF), Department of Neurology of the Massachusetts General Hospital, Boston, Massachusetts (BTH); Department of Biostatistics of the Harvard T. H. Chan School of Public Health, Boston, Massachusetts (RAB); and Massachusetts Alzheimer Disease Research Center, Charlestown, Massachusetts (MPF, RAB, BTH).
Sarah E
SE
Monsell
From the Department of Neurology of the University of Iowa Hospitals & Clinics, Iowa City, Iowa (AS-P); Department of Biostatistics and Epidemiology of the University of Massachusetts, Amherst, Massachusetts (JQ); Massachusetts General Hospital Biostatistics Center, Boston, Massachusetts (AM); Department of Biostatistics, University of Washington, Seattle, Washington (SEM); Department of Pathology, School of Medicine of the University of Washington, Seattle, Washington (TJM); C. S. Kubik Laboratory for Neuropathology of the Massachusetts General Hospital (MPF), Department of Neurology of the Massachusetts General Hospital, Boston, Massachusetts (BTH); Department of Biostatistics of the Harvard T. H. Chan School of Public Health, Boston, Massachusetts (RAB); and Massachusetts Alzheimer Disease Research Center, Charlestown, Massachusetts (MPF, RAB, BTH).
Thomas J
TJ
Montine
From the Department of Neurology of the University of Iowa Hospitals & Clinics, Iowa City, Iowa (AS-P); Department of Biostatistics and Epidemiology of the University of Massachusetts, Amherst, Massachusetts (JQ); Massachusetts General Hospital Biostatistics Center, Boston, Massachusetts (AM); Department of Biostatistics, University of Washington, Seattle, Washington (SEM); Department of Pathology, School of Medicine of the University of Washington, Seattle, Washington (TJM); C. S. Kubik Laboratory for Neuropathology of the Massachusetts General Hospital (MPF), Department of Neurology of the Massachusetts General Hospital, Boston, Massachusetts (BTH); Department of Biostatistics of the Harvard T. H. Chan School of Public Health, Boston, Massachusetts (RAB); and Massachusetts Alzheimer Disease Research Center, Charlestown, Massachusetts (MPF, RAB, BTH).
Matthew P
MP
Frosch
From the Department of Neurology of the University of Iowa Hospitals & Clinics, Iowa City, Iowa (AS-P); Department of Biostatistics and Epidemiology of the University of Massachusetts, Amherst, Massachusetts (JQ); Massachusetts General Hospital Biostatistics Center, Boston, Massachusetts (AM); Department of Biostatistics, University of Washington, Seattle, Washington (SEM); Department of Pathology, School of Medicine of the University of Washington, Seattle, Washington (TJM); C. S. Kubik Laboratory for Neuropathology of the Massachusetts General Hospital (MPF), Department of Neurology of the Massachusetts General Hospital, Boston, Massachusetts (BTH); Department of Biostatistics of the Harvard T. H. Chan School of Public Health, Boston, Massachusetts (RAB); and Massachusetts Alzheimer Disease Research Center, Charlestown, Massachusetts (MPF, RAB, BTH).
Rebecca A
RA
Betensky
From the Department of Neurology of the University of Iowa Hospitals & Clinics, Iowa City, Iowa (AS-P); Department of Biostatistics and Epidemiology of the University of Massachusetts, Amherst, Massachusetts (JQ); Massachusetts General Hospital Biostatistics Center, Boston, Massachusetts (AM); Department of Biostatistics, University of Washington, Seattle, Washington (SEM); Department of Pathology, School of Medicine of the University of Washington, Seattle, Washington (TJM); C. S. Kubik Laboratory for Neuropathology of the Massachusetts General Hospital (MPF), Department of Neurology of the Massachusetts General Hospital, Boston, Massachusetts (BTH); Department of Biostatistics of the Harvard T. H. Chan School of Public Health, Boston, Massachusetts (RAB); and Massachusetts Alzheimer Disease Research Center, Charlestown, Massachusetts (MPF, RAB, BTH). bhyman@mgh.harvard.edu.
Bradley T
BT
Hyman
D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology* / Q000523:psychology; D000686:Amyloidosis / Q000473:pathology* / Q000523:psychology; D003072:Cognition Disorders / Q000473:pathology* / Q000523:psychology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology*; D058225:Plaque, Amyloid / Q000473:pathology* / Q000523:psychology
ABC score; Alzheimer disease; Amyloid plaques; National Alzheimer’s Coordinating Center; Neuritic plaques; Neurofibrillary tangles; Thal stages.