TY - JOUR
T1 - Intracranial internal carotid artery calcification is not predictive of future cognitive decline
AU - Rahmani, Farzaneh
AU - Nguyen, Marina
AU - Chen, Charles D.
AU - McKay, Nicole
AU - Dincer, Aylin
AU - Joseph-Mathurin, Nelly
AU - Chen, Gengsheng
AU - Liu, Jingxia
AU - Orlowski, Hilary L.P.
AU - Morris, John C.
AU - Benzinger, Tammie L.S.
N1 - Funding Information:
This research was supported by the following: ADRC Center Grant, NIH/NIA P50AG005681, The Barnes-Jewish Hospital Foundation (BJHF), Barnes-Jewish Hospital Foundation (PIB imaging), NIH/NIA P01AG026276, NIA grant T32AG05851804 (M. Nguyen), generous support from Fred Simmons and Olga Mohan, The McDonnell Center for Systems Neuroscience, 22 3922 26239N, NIH/NIA P01AG003991, Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly (florbetapir and AV1451 imaging). For florbetapir (AV45), Avid pharmaceuticals provided the doses and partial support for scanning through an investigator-initiated research grant awarded to Washington University (J.C. Morris, T.L.S. Benzinger). Additional support for image acquisition was provided by CCIR/ICTS Human Imaging Unit (NIH/NCATS UL1TR000448), and support for imaging informatics (CNDA/XNAT) was provided in part by the Neuroimaging Informatics and Analysis Center (1P30NS098577) and R01 EB009352.
Funding Information:
The study was conceived by FR, MN, and TLSB. HLPO, TLSB, and JCM were responsible for funding and data acquisition. Analysis design was conceived, conducted, and interpreted by FR, CDC, NM, and AD with direct supervision from GC and JL. FR and MN contributed to the composition of the manuscript, and all authors contributed to the manuscript preparation and provided substantial revision. All authors have approved the submitted version and have agreed both to be personally accountable for the author’s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated, resolved, and the resolution documented in the literature.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Background: Intracranial internal carotid artery (ICA) calcification is a common incidental finding in non-contrast head CT. We evaluated the predictive value of ICAC (ICAC) for future risk of cognitive decline and compared the results with conventional imaging biomarkers of dementia. Methods: In a retrospective observational cohort, we included 230 participants with a PET-CT scan within 18 months of a baseline clinical assessment and longitudinal imaging assessments. Intracranial ICAC was quantified on baseline CT scans using the Agatson calcium score, and the association between baseline ICA calcium scores and the risk of conversion from a CDR of zero in baseline to a persistent CDR > 0 at any follow-up visit, as well as longitudinal changes in cognitive scores, were evaluated through linear and mixed regression models. We also evaluated the association of conventional imaging biomarkers of dementia with longitudinal changes in cognitive scores and a potential indirect effect of ICAC on cognition through these biomarkers. Results: Baseline ICA calcium score could not distinguish participants who converted to CDR > 0. ICA calcium score was also unable to predict longitudinal changes in cognitive scores, imaging biomarkers of small vessel disease such as white matter hyperintensities (WMH) volume, or AD such as hippocampal volume, AD cortical signature thickness, and amyloid burden. Severity of intracranial ICAC increased with age and in men. Higher WMH volume and amyloid burden as well as lower hippocampal volume and AD cortical signature thickness at baseline predicted lower Mini-Mental State Exam scores at longitudinal follow-up. Baseline ICAC was indirectly associated with longitudinal cognitive decline, fully mediated through WMH volume. Conclusions: In elderly and preclinical AD populations, atherosclerosis of large intracranial vessels as demonstrated through ICAC is not directly associated with a future risk of cognitive impairment, or progression of imaging biomarkers of AD or small vessel disease.
AB - Background: Intracranial internal carotid artery (ICA) calcification is a common incidental finding in non-contrast head CT. We evaluated the predictive value of ICAC (ICAC) for future risk of cognitive decline and compared the results with conventional imaging biomarkers of dementia. Methods: In a retrospective observational cohort, we included 230 participants with a PET-CT scan within 18 months of a baseline clinical assessment and longitudinal imaging assessments. Intracranial ICAC was quantified on baseline CT scans using the Agatson calcium score, and the association between baseline ICA calcium scores and the risk of conversion from a CDR of zero in baseline to a persistent CDR > 0 at any follow-up visit, as well as longitudinal changes in cognitive scores, were evaluated through linear and mixed regression models. We also evaluated the association of conventional imaging biomarkers of dementia with longitudinal changes in cognitive scores and a potential indirect effect of ICAC on cognition through these biomarkers. Results: Baseline ICA calcium score could not distinguish participants who converted to CDR > 0. ICA calcium score was also unable to predict longitudinal changes in cognitive scores, imaging biomarkers of small vessel disease such as white matter hyperintensities (WMH) volume, or AD such as hippocampal volume, AD cortical signature thickness, and amyloid burden. Severity of intracranial ICAC increased with age and in men. Higher WMH volume and amyloid burden as well as lower hippocampal volume and AD cortical signature thickness at baseline predicted lower Mini-Mental State Exam scores at longitudinal follow-up. Baseline ICAC was indirectly associated with longitudinal cognitive decline, fully mediated through WMH volume. Conclusions: In elderly and preclinical AD populations, atherosclerosis of large intracranial vessels as demonstrated through ICAC is not directly associated with a future risk of cognitive impairment, or progression of imaging biomarkers of AD or small vessel disease.
KW - 11C-Pittsburgh compound B
KW - Calcification
KW - Centiloid
KW - Clinical Dementia Rating
KW - Internal carotid artery
KW - Mini-Mental State Exam
KW - PiB
KW - White matter hyperintensities
UR - http://www.scopus.com/inward/record.url?scp=85124499575&partnerID=8YFLogxK
U2 - 10.1186/s13195-022-00972-2
DO - 10.1186/s13195-022-00972-2
M3 - Article
C2 - 35148796
AN - SCOPUS:85124499575
SN - 1758-9193
VL - 14
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
IS - 1
M1 - 32
ER -