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Clinical predictors of severe cerebral amyloid angiopathy and influence of APOE genotype in persons with pathologically verified Alzheimer disease.
JAMA Neurol. 2014 Jul 01; 71(7):878-83.JN

Abstract

IMPORTANCE

Although cerebral amyloid angiopathy (CAA) has important clinical implications, our understanding of it and ability to diagnose it are limited.

OBJECTIVE

To determine pathological correlates and clinical factors identifiable during life that predict the presence of severe CAA in persons with pathologically confirmed Alzheimer disease (AD).

DESIGN, SETTING, AND PARTICIPANTS

We compared demographic and clinical variables at the earliest visit during life at which participants were found to have cognitive impairment and compared pathological variables between persons ultimately found to have no or severe CAA at autopsy using logistic regression. Analyses were repeated separately for carriers and noncarriers of the APOE ε4 allele. Data were obtained from the Uniform Data Set, which comprises longitudinal clinical assessments performed in the Alzheimer's Disease Centers funded by the National Institute on Aging. Participants included 193 persons with AD and severe CAA and 232 persons with AD and no CAA. All participants had cognitive impairment and met National Institute on Aging-Reagan Institute neuropathological criteria for AD.

MAIN OUTCOMES AND MEASURES

Prevalence of demographic characteristics and the APOE ε4 allele and odds ratios (ORs) of clinical variables for the prediction of severe CAA.

RESULTS

Persons with severe CAA compared with those without CAA were more likely to carry an APOE ε4 allele (64.9% vs 42.8%, respectively; P < .001), to be Hispanic (6.8% vs 1.3%, respectively; P = .003), to have had a transient ischemic attack (12.5% vs 6.1%, respectively; OR = 2.1; 95% CI, 1.0-4.4), and to have lower degrees of diffuse amyloid plaque pathology (mean [SD] Consortium to Establish a Registry for Alzheimer's Disease score, 1.2 [0.5] vs 1.4 [0.8], respectively; P = .01). Those with CAA compared with those without CAA more commonly had intracerebral hemorrhage (9.3% vs 3.5%, respectively; P = .01), cortical microinfarcts (20.7% vs 12.9%, respectively; P = .03), and subcortical leukoencephalopathy (20.5% vs 12.1%, respectively; P = .02). Noncarriers of the APOE ε4 allele with severe CAA compared with those without CAA had a higher prevalence of stroke (11.1% vs 3.9%, respectively; OR = 3.8; 95% CI, 1.0-14.6) and hypercholesterolemia (50.0% vs 32.7%, respectively; OR = 2.3; 95% CI, 1.1-4.7).

CONCLUSIONS AND RELEVANCE

Being Hispanic and having had a transient ischemic attack-like episode were predictors of CAA in persons with AD. Less diffuse parenchymal amyloid pathology in persons with severe CAA suggests a difference in β-amyloid trafficking.

Authors+Show Affiliations

Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles2Mary S. Easton Center for Alzheimer's Disease Research, University of California, Los Angeles.National Alzheimer's Coordinating Center, University of Washington, Seattle.Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles2Mary S. Easton Center for Alzheimer's Disease Research, University of California, Los Angeles.National Alzheimer's Coordinating Center, University of Washington, Seattle.Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles.Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles2Mary S. Easton Center for Alzheimer's Disease Research, University of California, Los Angeles4Division of Neuropathology, Department of Pathology and Laborator.

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

24797962

Citation

Ringman, John M., et al. "Clinical Predictors of Severe Cerebral Amyloid Angiopathy and Influence of APOE Genotype in Persons With Pathologically Verified Alzheimer Disease." JAMA Neurology, vol. 71, no. 7, 2014, pp. 878-83.
Ringman JM, Sachs MC, Zhou Y, et al. Clinical predictors of severe cerebral amyloid angiopathy and influence of APOE genotype in persons with pathologically verified Alzheimer disease. JAMA Neurol. 2014;71(7):878-83.
Ringman, J. M., Sachs, M. C., Zhou, Y., Monsell, S. E., Saver, J. L., & Vinters, H. V. (2014). Clinical predictors of severe cerebral amyloid angiopathy and influence of APOE genotype in persons with pathologically verified Alzheimer disease. JAMA Neurology, 71(7), 878-83. https://doi.org/10.1001/jamaneurol.2014.681
Ringman JM, et al. Clinical Predictors of Severe Cerebral Amyloid Angiopathy and Influence of APOE Genotype in Persons With Pathologically Verified Alzheimer Disease. JAMA Neurol. 2014 Jul 1;71(7):878-83. PubMed PMID: 24797962.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical predictors of severe cerebral amyloid angiopathy and influence of APOE genotype in persons with pathologically verified Alzheimer disease. AU - Ringman,John M, AU - Sachs,Michael C, AU - Zhou,Yan, AU - Monsell,Sarah E, AU - Saver,Jeffrey L, AU - Vinters,Harry V, PY - 2014/5/7/entrez PY - 2014/5/7/pubmed PY - 2014/9/10/medline SP - 878 EP - 83 JF - JAMA neurology JO - JAMA Neurol VL - 71 IS - 7 N2 - IMPORTANCE: Although cerebral amyloid angiopathy (CAA) has important clinical implications, our understanding of it and ability to diagnose it are limited. OBJECTIVE: To determine pathological correlates and clinical factors identifiable during life that predict the presence of severe CAA in persons with pathologically confirmed Alzheimer disease (AD). DESIGN, SETTING, AND PARTICIPANTS: We compared demographic and clinical variables at the earliest visit during life at which participants were found to have cognitive impairment and compared pathological variables between persons ultimately found to have no or severe CAA at autopsy using logistic regression. Analyses were repeated separately for carriers and noncarriers of the APOE ε4 allele. Data were obtained from the Uniform Data Set, which comprises longitudinal clinical assessments performed in the Alzheimer's Disease Centers funded by the National Institute on Aging. Participants included 193 persons with AD and severe CAA and 232 persons with AD and no CAA. All participants had cognitive impairment and met National Institute on Aging-Reagan Institute neuropathological criteria for AD. MAIN OUTCOMES AND MEASURES: Prevalence of demographic characteristics and the APOE ε4 allele and odds ratios (ORs) of clinical variables for the prediction of severe CAA. RESULTS: Persons with severe CAA compared with those without CAA were more likely to carry an APOE ε4 allele (64.9% vs 42.8%, respectively; P < .001), to be Hispanic (6.8% vs 1.3%, respectively; P = .003), to have had a transient ischemic attack (12.5% vs 6.1%, respectively; OR = 2.1; 95% CI, 1.0-4.4), and to have lower degrees of diffuse amyloid plaque pathology (mean [SD] Consortium to Establish a Registry for Alzheimer's Disease score, 1.2 [0.5] vs 1.4 [0.8], respectively; P = .01). Those with CAA compared with those without CAA more commonly had intracerebral hemorrhage (9.3% vs 3.5%, respectively; P = .01), cortical microinfarcts (20.7% vs 12.9%, respectively; P = .03), and subcortical leukoencephalopathy (20.5% vs 12.1%, respectively; P = .02). Noncarriers of the APOE ε4 allele with severe CAA compared with those without CAA had a higher prevalence of stroke (11.1% vs 3.9%, respectively; OR = 3.8; 95% CI, 1.0-14.6) and hypercholesterolemia (50.0% vs 32.7%, respectively; OR = 2.3; 95% CI, 1.1-4.7). CONCLUSIONS AND RELEVANCE: Being Hispanic and having had a transient ischemic attack-like episode were predictors of CAA in persons with AD. Less diffuse parenchymal amyloid pathology in persons with severe CAA suggests a difference in β-amyloid trafficking. SN - 2168-6157 UR - https://www.unboundmedicine.com/medline/citation/24797962/Clinical_predictors_of_severe_cerebral_amyloid_angiopathy_and_influence_of_APOE_genotype_in_persons_with_pathologically_verified_Alzheimer_disease_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2014.681 DB - PRIME DP - Unbound Medicine ER -