Antiphospholipid Antibodies, Brain Infarcts, and Cognitive and Motor Decline in Aging (ABICMA): Design of a Community-Based, Longitudinal, Clinical-Pathological Study

Arvanitakis, Zoe; Brey, Robin L.; Rand, Jacob H.; Schneider, Julie A.; Leurgans, Sue E.; Yu, Lei; Buchman, Aron S.; Arfanakis, Konstantinos; Fleischman, Debra; Boyle, Patricia A.; Bennett, David A.; Levine, Steven R.

doi:10.1159/000342761

Cited by 13 publications

(8 citation statements)

References 52 publications

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“…The study was designed to have 80% power to detect a clinically relevant effect of aPL on infarcts, quantified by an odds ratio of 1.6 or more. 10 In the main finding presented here, we found an OR of 1.08, corresponding to an effect of aPL on infarcts, small enough to be of little clinical relevance. With such as small effect size, we do not recommend that the question be studied in a larger number of subjects.…”

Section: Discussionmentioning

confidence: 42%

“…10 Briefly, aPL data were collected in the first available blood specimen (baseline), and in a subset, in the last available blood specimen (proximate to death, second time point), and in a specimen derived from a third time point in between. Repeated measures of aPL allowed for determination of persistence of aPL positivity over time and may have implications for clinical outcomes, as suggested by the literature and a consensus statement by a panel of aPL experts.…”

Section: Methodsmentioning

confidence: 99%

“…The design of the Antiphospholipid antibodies, Brain Infarcts, and Cognitive and Motor decline in Aging study (ABICMA) has been previously reported in detail. 10 Here, we tested whether aPL are associated with brain infarcts. We used blood specimens, in which we measured aPL, combined with clinical and pathologic data from more than 600 older, community-dwelling persons who were followed longitudinally until death, and underwent a brain autopsy and standardized neuropathologic evaluation.…”

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confidence: 99%

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Relation of Antiphospholipid Antibodies to Postmortem Brain Infarcts in Older People

et al. 2015

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Background-There are few data on the relationship of antiphospholipid antibodies (aPLs) to pathologically proven brain infarcts. We tested the hypothesis that aPLs are associated with a higher odds of brain infarcts among older, communitydwelling individuals who came to autopsy. Methods and Results-Specimens and clinical and pathological data were derived from 607 deceased subjects (mean age at death, 89 years; 66% women) who were participating in 1 of 2 cohort studies of aging (Rush Memory and Aging Project and Religious Orders Study) and had agreed to brain autopsy. Brain infarcts were identified on gross and microscopic examinations, and severity of cerebral vessel disease (atherosclerosis, arteriolosclerosis) was graded. Four clinically used aPLs were measured longitudinally: 3 in serum (anticardiolipin antibodies, β 2-glycoprotein I, and anti-phosphatidylserine) and 1 in plasma (lupus anticoagulant). A quarter of subjects (142 of 607, 23%) had at least 1 aPL present at baseline (median time interval from baseline to death, 4.6 years), and three quarters of these subjects had persistently positive measures over time. In a logistic regression analysis, baseline aPL positivity did not increase the odds of brain infarcts (odds ratio=1.08; 95% confidence interval, 0.74-1.58; P=0.19) or of gross or microscopic infarcts separately. Findings were essentially unchanged when considering number of baseline aPLs, aPLs proximate to death, and persistence of aPLs. Associations did not differ among subjects with increased severity of vessel disease. Conclusion-Overall, we did not find evidence that aPLs increase the odds of pathological brain infarcts in older people. (Circulation. 2015;131:182-189.

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Section: Discussionmentioning

confidence: 42%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Relation of Antiphospholipid Antibodies to Postmortem Brain Infarcts in Older People

et al. 2015

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“…Our observation based on the meta-analysis on case-control studies was also supported by some cohort studies demonstrating the association of aCL positivity with cognitive decline and impaired motor function as follows: (1) Jacobson et al (1999) reported that the frequency of impaired neuropsychologic performance was significantly higher among young individuals with aPLs ( n = 27) as compared with controls ( p < 0.01). (2) Primary data of a longitudinal study demonstrated that aCL was positive up to 19% of subjects with impaired cognitive and motor function ( Arvanitakis et al, 2012 ); (3) Another cohort study on normal population ( n = 1895) without neurological disease including dementia indicated that aCL-positive subjects performed worst on the Mini Mental State Examination (MMSE) cognitive scale, suggesting an aCL-mediated mechanism in cognitive decline ( Homayoon et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Presence of Anticardiolipin Antibodies in Patients with Dementia: A Systematic Review and Meta-Analysis

Islam

Alam

Kamal

et al. 2017

Front. Aging Neurosci.

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Growing evidences are supporting towards the involvement of antiphospholipid antibodies [aPLs e.g., lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β2-glycoprotein I (anti-β2-GPI) antibodies] in various neurological manifestations including migraine, epilepsy and dementia in the presence or absence of autoimmune diseases such as antiphospholipid syndrome or systemic lupus erythematosus. The aim of this systematic review and meta-analysis was to assess the presence of aPLs in dementia patients without a diagnosis of any autoimmune disease. Electronic databases (e.g., PubMed, Web of Science, Scopus, ScienceDirect and Google Scholar) were searched without any year or language restrictions and based on the inclusion criteria, nine prospective case-control studies assessing only aCL were included involving 372 dementia patients and 337 healthy controls. No studies were found to assess the presence of both LA or anti-β2-GPI. The study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects model. We observed the prevalence of aCL in dementia was higher (32.80%) than that of controls (9.50%) e.g., 3.45 times higher risk of presenting with dementia than the controls, and significant presence of aCL antibodies was detected in dementia patients compared to controls (OR: 4.94, 95% CI: 2.66 – 9.16, p < 0.00001; I2 = 32%, p = 0.16). Publication bias was not observed from Egger’s (p = 0.081) and Begg’s tests (p = 0.180). Based on the study quality assessment using modified Newcastle–Ottawa Scale for case-control studies, seven of nine studies were of high methodological quality scoring ≥ 7 (median value). In summary, aCL antibodies were significantly present in dementia patients suggesting that aCL antibodies are generated due to the autoimmune-derived effects of dementia or there might be a potential causative role of this autoantibody in dementia pathogenesis.

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“…The ABICMA study (Antiphospholipid Antibodies, Brain Infarcts, and Cognitive and Motor Decline in Aging study) began in late 2009 and will test the hypothesis that aPL are associated with an increased risk of pathologically proven brain infarcts and are related to cognitive and motor decline in aging. 82…”

Section: Dementiamentioning

confidence: 99%

Antiphospholipid Antibodies: Neuropsychiatric Presentations

Gris

Brenner

2013

Semin Thromb Hemost

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Antiphospholipid antibodies (aPL) are associated with a wide range of neurological, psychological, and psychiatric manifestations. In addition to clearly delineated purely thrombotic manifestations, which define the neurological contribution to the antiphospholipid syndrome, the strength of the other described associations is highly variable, and the underlying pathophysiological mechanisms are not fully understood. Some indications seem to support a psychiatric impact of aPL. The magnitude of the association and cellular and molecular mechanisms involved need to be further elucidated.

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Antiphospholipid Antibodies, Brain Infarcts, and Cognitive and Motor Decline in Aging (ABICMA): Design of a Community-Based, Longitudinal, Clinical-Pathological Study

Cited by 13 publications

References 52 publications

Relation of Antiphospholipid Antibodies to Postmortem Brain Infarcts in Older People

Relation of Antiphospholipid Antibodies to Postmortem Brain Infarcts in Older People

Presence of Anticardiolipin Antibodies in Patients with Dementia: A Systematic Review and Meta-Analysis

Antiphospholipid Antibodies: Neuropsychiatric Presentations

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