Trina A. Johnson, PhD; Yves Lapierre, MD; Amit Bar-Or, MD; et al.
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Arch Neurol. 2010;67(12):1449-1455. doi:10.1001/archneurol.2010.312
Cheryl D. Bushnell, MD, MHS; Louise O. Zimmer, MA, MPH; Wenqin Pan, PhD; et al.
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Arch Neurol. 2010;67(12):1456-1463. doi:10.1001/archneurol.2010.190
ObjectiveTo measure longitudinal use of stroke prevention medications following stroke hospital discharge. We hypothesized that a combination of patient-, provider-, and system-level factors influence medication-taking behavior.DesignObservational cohort design.SettingOne hundred six US hospitals participating in the American Heart Association Get With The Guidelines鈥揝troke program.PatientsTwo thousand eight hundred eighty-eight patients 18 years or older admitted with ischemic stroke or transient ischemic attack.Main Outcome MeasureRegimen persistence, including use of antiplatelet therapies, warfarin, antihypertensive therapies, lipid-lowering therapies, or diabetes medications, from discharge to 3 months. Reasons for nonpersistence were also ascertained.ResultsTwo thousand five hundred ninety-eight patients (90.0%) were eligible for analysis. At 3 months, 75.5% of subjects continued taking all secondary prevention medications prescribed at discharge. Persistence at 3 months was associated with decreasing number of medication classes prescribed, increasing age, medical history, less severe stroke disability, having insurance, working status, understanding why medications are prescribed and how to refill them, increased quality of life, financial hardship, geographic region, and hospital size.ConclusionsOne-quarter of stroke patients reported discontinuing 1 or more of their prescribed regimen of secondary prevention medications within 3 months of hospitalization for an acute stroke. Several modifiable factors associated with regimen persistence were identified and could be targets for improving long-term secondary stroke prevention.
Lydia Alvarez-Erviti, PhD; Maria C. Rodriguez-Oroz, MS, PhD; J. Mark Cooper, PhD; et al.
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Arch Neurol. 2010;67(12):1464-1472. doi:10.1001/archneurol.2010.198
ObjectiveTo investigate chaperone-mediated autophagy in the pathogenesis of Parkinson disease (PD).DesignPostmortem observational study.SettingUniversity Department of Clinical Neuroscience, Institute of Neurology, University College London.SubjectsPostmortem samples from 7 PD, 6 Alzheimer disease (AD), and 8 control brains.Main Outcome MeasureLysosomal-associated membrane protein 2A (LAMP2A) and heat shock cognate 70 (hsc70) protein levels were compared in the substantia nigra pars compacta and amygdala of PD, AD, and control brain samples. To provide insight into the turnover of 伪-synuclein, degradation pathways for this protein were studied in a dopaminergic cell line.ResultsThe expression levels of the chaperone-mediated autophagy proteins LAMP2A and hsc70 were significantly reduced in the substantia nigra pars compacta and amygdala of PD brains compared with age-matched AD and control brain samples. Lewy bodies in these regions contained autophagy-related proteins. We demonstrated that decreased LAMP2A levels in dopaminergic cell lines reduced chaperone-mediated autophagy activity and increased the half-life of 伪-synuclein.ConclusionsThese findings suggest that there is reduced chaperone-mediated autophagy activity in the PD brain, provide evidence for the role of autophagy in PD pathogenesis and Lewy body formation, and suggest that this pathway may be a suitable therapeutic target in PD.
Gyungah Jun, PhD; Adam C. Naj, PhD; Gary W. Beecham, PhD; et al.
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Arch Neurol. 2010;67(12):1473-1484. doi:10.1001/archneurol.2010.201
ObjectivesTo determine whether genotypes at CLU, PICALM, and CR1 confer risk for Alzheimer disease (AD) and whether risk for AD associated with these genes is influenced by apolipoprotein E (APOE) genotypes.DesignAssociation study of AD and CLU, PICALM, CR1, and APOE genotypes.SettingAcademic research institutions in the United States, Canada, and Israel.ParticipantsSeven thousand seventy cases with AD, 3055 with autopsies, and 8169 elderly cognitively normal controls, 1092 with autopsies, from 12 different studies, including white, African American, Israeli-Arab, and Caribbean Hispanic individuals.ResultsUnadjusted, CLU (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.85-0.96 for single-nucleotide polymorphism [SNP] rs11136000), CR1 (OR, 1.14; 95% CI, 1.07-1.22; SNP rs3818361), and PICALM (OR, 0.89; 95% CI, 0.84-0.94, SNP rs3851179) were associated with AD in white individuals. None were significantly associated with AD in the other ethnic groups. APOE 蔚4 was significantly associated with AD (ORs, 1.80-9.05) in all but 1 small white cohort and in the Arab cohort. Adjusting for age, sex, and the presence of at least 1 APOE 蔚4 allele greatly reduced evidence for association with PICALM but not CR1 or CLU. Models with the main SNP effect, presence or absence of APOE 蔚4, and an interaction term showed significant interaction between presence or absence of APOE 蔚4 and PICALM.ConclusionsWe confirm in a completely independent data set that CR1, CLU, and PICALM are AD susceptibility loci in European ancestry populations. Genotypes at PICALM confer risk predominantly in APOE 蔚4鈥損ositive subjects. Thus, APOE and PICALM synergistically interact.
Stephanie A. Cosentino, PhD; Yaakov Stern, PhD; Elisaveta Sokolov, MSc; et al.
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Arch Neurol. 2010;67(12):1485-1490. doi:10.1001/archneurol.2010.189
ObjectivesTo determine if plasma 尾-amyloid (A尾) levels (1) can be linked to specific cognitive changes that constitute conversion to Alzheimer disease (AD) and (2) correspond to cognitive change independent of dementia.DesignLongitudinal study including 3 visits during approximately 4陆 years (2000-2006).SettingNorthern Manhattan community.ParticipantsEight hundred eighty individuals from a population-based and ethnically diverse sample who had 2 plasma A尾 measurements and were dementia free at the time of the first A尾 sample; 481 remained cognitively healthy, 329 were cognitively or functionally impaired but not demented at any point, and 70 developed AD.Main Outcome MeasuresGeneral estimating equations tested the association between plasma A尾 (baseline and change in values) and cognitive change (composite score and memory, language, and visuospatial indices).ResultsHigh baseline plasma A尾42 (P聽=聽.01) and A尾40 (P聽=聽.01) and decreasing/relatively stable A尾42 (P聽=聽.01) values were associated with faster decline in multiple cognitive domains. In those who remained cognitively healthy, high baseline plasma A尾42 (P聽=聽.01) and decreasing/relatively stable plasma A尾42 (P聽=聽.01) was associated with faster cognitive decline, primarily in memory.ConclusionsThe association between plasma A尾 and multiple aspects of cognition more clearly specifies the previously documented downward trajectory of plasma A尾 with AD onset. The predominant association with memory seen only in healthy elderly individuals also suggests that plasma A尾 is linked with even earlier neurologic changes that may or may not culminate in dementia.
Christiane Reitz, MD, PhD; Ming-Xin Tang, PhD; Nicole Schupf, PhD; et al.
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Arch Neurol. 2010;67(12):1491-1497. doi:10.1001/archneurol.2010.297
Sara Benedetti, PhD; Stefano Carlo Previtali, MD, PhD; Silvia Coviello, PhD; et al.
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Arch Neurol. 2010;67(12):1498-1505. doi:10.1001/archneurol.2010.303
Matthew J. Gabel, PhD; Norman L. Foster, MD; Judith L. Heidebrink, MD; et al.
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Arch Neurol. 2010;67(12):1506-1512. doi:10.1001/archneurol.2010.301