Zoe Arvanitakis1,2, Ana W Capuano3,4, Robin Brey5, Debra A Fleischman3,4,6, Konstantinos Arfanakis3,7, Aron S Buchman3,4, Julie A Schneider3,4,8, Steven R Levine9, David A Bennett3,4. 1. Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA, zarvanit@rush.edu. 2. Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA, zarvanit@rush.edu. 3. Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA. 4. Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA. 5. Department of Neurology, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas, USA. 6. Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois, USA. 7. Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, USA. 8. Department of Pathology, Rush University Medical Center, Chicago, Illinois, USA. 9. Department of Neurology, State University of New York College of Medicine, Downstate Medical Center, and Kings County Hospital Center, Brooklyn, New York, USA.
Abstract
BACKGROUND: Few data are available on associations of antiphospholipid (aPL) antibodies with cognitive and motor decline in aging, and cerebrovascular disease on in vivo neuroimaging and postmortem neuropathology. METHODS: This longitudinal, clinical-pathologic study (aPL antibodies, brain infarcts, and cognitive and motor decline in aging), was derived from 2 ongoing community-based cohort studies. A panel of 3 aPL antibodies was assayed in serum from 956 older individuals (mean age = 81.1 years; 72% women). Serum was also tested in a subset for markers of inflammation (C-reactive protein [CRP]) and blood-brain barrier breakdown (matrix metalloproteinases, MMPs). Annual clinical evaluations documented cognitive (17 neuropsychological tests) and motor function including parkinsonism. Cerebrovascular disease data were derived from in vivo neuroimaging and postmortem neuropathologic evaluations (699 individuals). We examined associations of aPL with cognitive and motor decline, other serum markers, neuroimaging, and neuropathology. RESULTS: Of 956 individuals, 197 (20.6%) had aPL positivity, defined as positivity on any of the assays, at the time of first measurement. During a mean follow-up of 6.6 years (SD 4), overall aPL positivity was not associated with change in global cognition (estimate = -0.005, SE 0.011; p = 0.622) or parkinsonian signs (estimate = -0.003, SE 0.017; p = 0.860). aPL were not associated with serum CRP or MMPs (both p > 0.268). aPL were not associated with in vivo brain magnetic resonance imaging white matter hyperintensities or infarcts (both p > 0.376). Among those autopsied, aPL were not associated with pathologically confirmed brain infarcts, or cerebral atherosclerosis or arteriolosclerosis (all p≥ 0.447). CONCLUSIONS: In older individuals followed longitudinally, aPL do not relate to cognitive or motor decline, inflammation, or cerebrovascular disease on in vivo neuroimaging or postmortem neuropathology.
BACKGROUND: Few data are available on associations of antiphospholipid (aPL) antibodies with cognitive and motor decline in aging, and cerebrovascular disease on in vivo neuroimaging and postmortem neuropathology. METHODS: This longitudinal, clinical-pathologic study (aPL antibodies, brain infarcts, and cognitive and motor decline in aging), was derived from 2 ongoing community-based cohort studies. A panel of 3 aPL antibodies was assayed in serum from 956 older individuals (mean age = 81.1 years; 72% women). Serum was also tested in a subset for markers of inflammation (C-reactive protein [CRP]) and blood-brain barrier breakdown (matrix metalloproteinases, MMPs). Annual clinical evaluations documented cognitive (17 neuropsychological tests) and motor function including parkinsonism. Cerebrovascular disease data were derived from in vivo neuroimaging and postmortem neuropathologic evaluations (699 individuals). We examined associations of aPL with cognitive and motor decline, other serum markers, neuroimaging, and neuropathology. RESULTS: Of 956 individuals, 197 (20.6%) had aPL positivity, defined as positivity on any of the assays, at the time of first measurement. During a mean follow-up of 6.6 years (SD 4), overall aPL positivity was not associated with change in global cognition (estimate = -0.005, SE 0.011; p = 0.622) or parkinsonian signs (estimate = -0.003, SE 0.017; p = 0.860). aPL were not associated with serum CRP or MMPs (both p > 0.268). aPL were not associated with in vivo brain magnetic resonance imaging white matter hyperintensities or infarcts (both p > 0.376). Among those autopsied, aPL were not associated with pathologically confirmed brain infarcts, or cerebral atherosclerosis or arteriolosclerosis (all p≥ 0.447). CONCLUSIONS: In older individuals followed longitudinally, aPL do not relate to cognitive or motor decline, inflammation, or cerebrovascular disease on in vivo neuroimaging or postmortem neuropathology.
Authors: Linda P Fried; Luigi Ferrucci; Jonathan Darer; Jeff D Williamson; Gerard Anderson Journal: J Gerontol A Biol Sci Med Sci Date: 2004-03 Impact factor: 6.053
Authors: Aron S Buchman; Robert S Wilson; Lei Yu; Patricia A Boyle; David A Bennett; Lisa L Barnes Journal: J Gerontol A Biol Sci Med Sci Date: 2015-11-02 Impact factor: 6.053
Authors: S Miyakis; M D Lockshin; T Atsumi; D W Branch; R L Brey; R Cervera; R H W M Derksen; P G DE Groot; T Koike; P L Meroni; G Reber; Y Shoenfeld; A Tincani; P G Vlachoyiannopoulos; S A Krilis Journal: J Thromb Haemost Date: 2006-02 Impact factor: 5.824
Authors: Zoe Arvanitakis; Robin L Brey; Jacob H Rand; Julie A Schneider; Sue E Leurgans; Lei Yu; Aron S Buchman; Konstantinos Arfanakis; Debra A Fleischman; Patricia A Boyle; David A Bennett; Steven R Levine Journal: Neuroepidemiology Date: 2012-10-24 Impact factor: 3.282
Authors: Lisa L Barnes; Futoshi Yumoto; Ana Capuano; Robert S Wilson; David A Bennett; Rochelle E Tractenberg Journal: J Int Neuropsychol Soc Date: 2015-11-13 Impact factor: 2.892
Authors: Zoe Arvanitakis; Robin L Brey; Jacob H Rand; Julie A Schneider; Ana W Capuano; Lei Yu; Sue E Leurgans; David A Bennett; Steven R Levine Journal: Circulation Date: 2014-10-09 Impact factor: 29.690
Authors: David A Bennett; Aron S Buchman; Patricia A Boyle; Lisa L Barnes; Robert S Wilson; Julie A Schneider Journal: J Alzheimers Dis Date: 2018 Impact factor: 4.472
Authors: Aron S Buchman; Sue E Leurgans; Lei Yu; Robert S Wilson; Andrew S Lim; Bryan D James; Joshua M Shulman; David A Bennett Journal: Neurology Date: 2016-08-03 Impact factor: 9.910