TY - JOUR
T1 - Cerebrospinal fluid dynamics and discordant amyloid biomarkers
AU - Graff-Radford, Jonathan
AU - Jones, David T.
AU - Wiste, Heather J.
AU - Cogswell, Petrice M.
AU - Weigand, Stephen D.
AU - Lowe, Val
AU - Elder, Benjamin D.
AU - Vemuri, Prashanthi
AU - Van Harten, Argonde
AU - Mielke, Michelle M.
AU - Knopman, David S.
AU - Graff-Radford, Neill R.
AU - Petersen, Ronald C.
AU - Jack, Clifford R.
AU - Gunter, Jeffrey L.
N1 - Publisher Copyright:
© 2021
PY - 2022/2
Y1 - 2022/2
N2 - Do MRI-based metrics of a CSF-dynamics disorder, disproportionately enlarged subarachnoid-space hydrocephalus (DESH), correlate with discordant amyloid biomarkers (low CSF β-amyloid 1–42, normal Aβ-PET scan)? Individuals ≥50 years from the Mayo Clinic Study of Aging, with MRI, 11C-Pittsburgh compound B (Aβ) PET scans, and CSF phosphorylated-tau protein and Aβ42, were categorized into 4 groups: normal and/or abnormal by CSF β-amyloid 1–42 and Aβ amyloid PET. Within groups, we noted MRI patterns of CSF-dynamics disorders and Aβ-PET accumulation-change rate. One-hundred participants (21%) in the abnormal-CSF and/or normal-PET group had highest DESH-pattern scores and lowest CSF-phosphorylated-tau levels. Among normal amyloid-PET individuals, a 1-unit DESH-pattern score increase correlated with 30%-greater odds of abnormal amyloid CSF after age, and sex adjustment. Mean rate over time of amyloid-PET accumulation in abnormal-CSF and/or normal-PET individuals approximated individuals with normal amyloid values. Adjusting for phosphorylated-tau, abnormal CSF-amyloid and/or normal amyloid-PET individuals had higher mean amyloid-PET accumulation rates than normal individuals. CSF dynamics disorders confound β-amyloid and phosphorylated-tau CSF-biomarker interpretation.
AB - Do MRI-based metrics of a CSF-dynamics disorder, disproportionately enlarged subarachnoid-space hydrocephalus (DESH), correlate with discordant amyloid biomarkers (low CSF β-amyloid 1–42, normal Aβ-PET scan)? Individuals ≥50 years from the Mayo Clinic Study of Aging, with MRI, 11C-Pittsburgh compound B (Aβ) PET scans, and CSF phosphorylated-tau protein and Aβ42, were categorized into 4 groups: normal and/or abnormal by CSF β-amyloid 1–42 and Aβ amyloid PET. Within groups, we noted MRI patterns of CSF-dynamics disorders and Aβ-PET accumulation-change rate. One-hundred participants (21%) in the abnormal-CSF and/or normal-PET group had highest DESH-pattern scores and lowest CSF-phosphorylated-tau levels. Among normal amyloid-PET individuals, a 1-unit DESH-pattern score increase correlated with 30%-greater odds of abnormal amyloid CSF after age, and sex adjustment. Mean rate over time of amyloid-PET accumulation in abnormal-CSF and/or normal-PET individuals approximated individuals with normal amyloid values. Adjusting for phosphorylated-tau, abnormal CSF-amyloid and/or normal amyloid-PET individuals had higher mean amyloid-PET accumulation rates than normal individuals. CSF dynamics disorders confound β-amyloid and phosphorylated-tau CSF-biomarker interpretation.
KW - Alzheimer's disease
KW - Amyloid PET accumulation
KW - Biomarkers
KW - Disproportionately enlarged subarachnoid-space hydrocephalus (DESH)
KW - Mayo Clinic Study of Aging (MCSA)
KW - Normal-pressure hydrocephalus
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U2 - 10.1016/j.neurobiolaging.2021.10.017
DO - 10.1016/j.neurobiolaging.2021.10.017
M3 - Article
C2 - 34844077
AN - SCOPUS:85119956065
SN - 0197-4580
VL - 110
SP - 27
EP - 36
JO - Neurobiology of aging
JF - Neurobiology of aging
ER -