Neurology August 2012 Volume 79 Issue 7

Objectives: Previous studies have shown that high serum ceramides are associated with memory impairment and hippocampal volume loss, but have not examined dementia as an outcome. The aim of this study was to examine whether serum ceramides and sphingomyelins (SM) were associated with an increased risk of all-cause dementia and Alzheimer disease (AD).Methods: Participants included 99 women without dementia aged 70-79, with baseline serum SM and ceramides, enrolled in a longitudinal population-based study and followed for up to 6 visits over 9 years. Baseline lipids, in tertiles, were examined in relation to all-cause dementia and AD using discrete time Cox proportional survival analysis. Lipids were analyzed using electrospray ionization tandem mass spectrometry.Results: Twenty-seven (27.3%) of the 99 women developed incident dementia. Of these, 18 (66.7%) were diagnosed with probable AD. Higher baseline serum ceramides, but not SM, were associated with an increased risk of AD; these relationships were stronger than with all-cause dementia. Compared to the lowest tertile, the middle and highest tertiles of ceramide d18:1-C16:0 were associated with a 10-fold (95% confidence interval [CI] 1.2-85.1) and 7.6-fold increased risk of AD (95% CI 0.9-62.1), respectively. The highest tertiles of ceramide d18:1-C24:0 (hazard ratio [HR] = 5.1, 95% CI 1.1-23.6) and lactosylceramide (HR = 9.8, 95% CI 1.2-80.1) were also associated with risk of AD. Total and high-density lipoprotein cholesterol and triglycerides were not associated with dementia or AD.Conclusions: Results from this preliminary study suggest that particular species of serum ceramides are associated with incident AD and warrant continued examination in larger studies.GLOSSARY: A[beta]: amyloid-[beta]AD: Alzheimer diseaseamu: atomic mass unitsAPP: amyloid precursor proteinBACE-1: [beta]-site APP cleaving enzyme 1BMI: body mass indexCI: confidence intervalDSM-IV: Diagnostic and Statistical Manual of Mental Disorders, 4th editionESI-MS/MS: electrospray ionization tandem mass spectrometryHDL: high-density lipoproteinHR: hazard ratioMCI: mild cognitive impairmentMMSE: Mini-Mental State ExaminationSM: sphingomyelinWHAS II: Women's Health and Aging Study II.(C)2012 American Academy of Neurology

Objective: The long-chain [omega]-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are potential candidates for interventions to delay Alzheimer disease (AD), but evidence from clinical studies is mixed. We aimed at determining whether plasma levels of EPA or DHA predict atrophy of medial temporal lobe (MTL) gray matter regions in older subjects.Methods: A total of 281 community dwellers from the Three-City Study, aged 65 years or older, had plasma fatty acid measurements at baseline and underwent MRI examinations at baseline and at 4 years. We studied the association between plasma EPA and DHA and MTL gray matter volume change at 4 years.Results: Higher plasma EPA, but not DHA, was associated with lower gray matter atrophy of the right hippocampal/parahippocampal area and of the right amygdala (p < 0.05, familywise error corrected). Based on a mean right amygdala volume loss of 6.0 mm3/y (0.6%), a 1 SD higher plasma EPA (+0.64% of total plasma fatty acids) at baseline was related to a 1.3 mm3 smaller gray matter loss per year in the right amygdala. Higher atrophy of the right amygdala was associated with greater 4-year decline in semantic memory performances and more depressive symptoms.Conclusion: The amygdala, which develops neuropathology in the early stage of AD and is involved in the pathogenesis of depression, may be an important brain structure involved in the association between EPA and cognitive decline and depressive symptoms.GLOSSARY: 3C: Three-CityAD: Alzheimer diseaseCES-D: Center for Epidemiologic Studies-DepressionDHA: docosahexaenoic acidDSM-IV: Diagnostic and Statistical Manual of Mental Disorders, 4th editionEPA: eicosapentaenoic acidGM: gray matterIST: Isaacs Set TestMMSE: Mini-Mental State ExaminationMTL: medial temporal loben-3 PUFA: [omega]-3 polyunsaturated fatty acidsn-6 PUFA: [omega]-6 polyunsaturated fatty acidsTIV: total intracranial volumeWM: white matter(C)2012 American Academy of Neurology

Objective: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown.Methods: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry.Results: In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78-0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14-1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I2 estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD.Conclusion: Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity.GLOSSARY: CI: confidence intervalGEO-PD: Genetic Epidemiology of Parkinson's DiseaseGWAS: genome-wide association studiesHWE: Hardy-Weinberg equilibriumMALDI-TOF: matrix-assisted laser desorption/ionization time-of-flightMSA: multiple system atrophyOR: odds ratioPD: Parkinson diseaseSNP: single nucleotide polymorphism(C)2012 American Academy of Neurology

Objectives: To evaluate disparities in stroke risk factors and outcome among the Native Hawaiians and other Pacific Islanders (NHPI) in Hawaii who are hospitalized with intracerebral hemorrhage (ICH).Methods: We performed a retrospective study on consecutive patients hospitalized for acute ICH at a single tertiary center on Oahu between 2004 and 2010. Clinical data were obtained from the Get With the Guidelines-Stroke database. Multivariable logistic regression was used to assess the predictors for young ICH (age <45).Results: A total of 562 patients hospitalized for acute ICH (Asian 63%, NHPI 18%, white 16%, other 3%) were studied. The NHPI were younger (mean ages, NHPI 55 +/- 16 vs white 66 +/- 16 years, p < 0.0001), and had higher prevalence of diabetes (NHPI 35% vs white 20%, p = 0.01) and history of hypertension (NHPI 77% vs white 64%, p = 0.04) compared to white patients. Independent predictors for young ICH were NHPI race (odds ratio [OR] 3.55; 95% confidence interval [CI] 1.33-9.45), being transferred from another hospital (OR 2.03; 95% CI 1.05-3.93), hypertension (OR 0.49; 95% CI 0.27-0.91), previous stroke or TIA (OR 0.21; 95% CI 0.05-0.91), and dyslipidemia (OR 0.15; 95% CI 0.05-0.50).Conclusions: NHPI with ICH are younger and have higher burden of risk factors compared to white patients. Further studies controlling for socioeconomic modifiers are needed to determine factors contributing to the younger age at presentation in this racial group.GLOSSARY: BMI: body mass indexCAD: coronary artery diseaseCI: confidence intervalGWTG: Get With the GuidelinesHDL: high-density lipoproteinICH: intracerebral hemorrhageIVH: intraventricular hemorrhageLDL: low-density lipoproteinLOS: length of stayMI: myocardial infarctionNHPI: Native Hawaiians and other Pacific IslandersOR: odds ratioQMC: Queen's Medical Center(C)2012 American Academy of Neurology

Objective: To present the results of the nonrandomized arm of the Cervical Artery Dissection in Stroke Study (CADISS-NR) trial, comparing anticoagulation and antiplatelets for prevention of recurrent stroke after carotid and vertebral dissection, and perform a meta-analysis of these results with previously published studies comparing the 2 therapeutic strategies.Methods: A total of 88 patients from 22 centers with extracranial carotid and vertebral dissection were recruited within 1 month of symptom onset. The primary endpoint was recurrent stroke at 3 months. A systematic review was performed, and results of published studies included in a meta-analysis with the CADISS-NR results.Results: In CADISS-NR, one patient in each group had recurrent ischemic stroke (antiplatelet 1/59 [1.69% ], anticoagulation 1/28 [3.57%]). At the primary endpoint of 3 months, 3 (5.08%) antiplatelet patients had recurrent TIA, compared with none in the anticoagulation group. For meta-analysis, there were data from 40 nonrandomized studies including 1,636 patients. There was no significant difference between the 2 treatments in recurrent stroke risk (antiplatelet 13/499 [2.6%], anticoagulant 20/1,137 [1.8%], odds ratio [OR] 1.49) or risk of death (antiplatelet 5/499 [1.00%], anticoagulant 9/1,137 [0.80%], OR 1.27).Conclusion: There is no evidence for superiority of anticoagulation or antiplatelet therapy in prevention of stoke after carotid and vertebral artery dissection; however, all data are from nonrandomized studies and randomized studies are required. The nonrandomized CADISS data show a lower rate of recurrent stroke than reported in some previous studies.Clinical Trial Registration Information: www.dissection.co.uk, ISRNCTN44555237.GLOSSARY: CAD : cervical artery dissectionCADISS-NR : nonrandomized arm of the Cervical Artery Dissection in Stroke StudyOR : odds ratio(C)2012 American Academy of Neurology

Objectives: To determine the immediate and long-term therapeutic efficacies of barbecue rotation and Gufoni maneuvers, a randomized, prospective, and sham-controlled study was conducted in patients with the geotropic type of benign paroxysmal positional vertigo involving the horizontal semicircular canal (HC-BPPV).Methods: In 10 nationwide dizziness clinics in Korea, 170 consecutive patients (107 women, age range 11-97 years, mean age +/- SD 61 +/- 15 years, median = 61 years) with geotropic HC-BPPV were randomly assigned to barbecue rotation (n = 56), Gufoni (n = 64), or sham maneuver (n = 50). An immediate response was determined within 1 hour after a maximum of 2 trials of each maneuver on the visit day. We also assessed the cumulative results of each maneuver by following up the patients for 1 month.Results: After a maximum of 2 maneuvers on the initial visit day, barbecue rotation (38 of 55 [69.1%]) and Gufoni (39 of 64 [60.9%]) maneuvers showed better responses than the sham maneuver (17 of 48 [35.4%]). The cumulative therapeutic effects were also better with barbecue rotation (p = 0.006) and Gufoni (p = 0.031) maneuvers than with the sham maneuver. However, therapeutic efficacies did not differ between the barbecue rotation and Gufoni groups in terms of both immediate (p = 0.46) and long-term (p = 0.10) outcomes.Conclusion: Using a prospective randomized trial, we demonstrated that barbecue rotation and Gufoni maneuvers are effective in treating geotropic HC-BPPV.Classification of evidence: This study provides Class I evidence that barbecue rotation and Gufoni maneuvers are effective in the treatment of geotropic HC-BPPV.GLOSSARY: AAR: absolute risk reductionBPPV: benign paroxysmal positional vertigoCI: confidence intervalHC-BPPV: benign paroxysmal positional vertigo involving the horizontal semicircular canalNNT: number needed to treatOR: odds ratioPC-BPPV: benign paroxysmal positional vertigo involving the posterior semicircular canal(C)2012 American Academy of Neurology