Peak Width of Skeletonized Mean Diffusivity as Neuroimaging Biomarker in Cerebral Amyloid Angiopathy.

BACKGROUND AND PURPOSE: Whole-brain network connectivity has been shown to be a useful biomarker of cerebral amyloid angiopathy and related cognitive impairment. We evaluated an automated DTI-based method, peak width of skeletonized mean diffusivity, in cerebral amyloid angiopathy, together with its association with conventional MRI markers and cognitive functions. MATERIALS AND METHODS: We included 24 subjects (mean age, 74.7 [SD, 6.0] years) with probable cerebral amyloid angiopathy and mild cognitive impairment and 62 patients with MCI not attributable to cerebral amyloid angiopathy (non-cerebral amyloid angiopathy-mild cognitive impairment). We compared peak width of skeletonized mean diffusivity between subjects with cerebral amyloid angiopathy-mild cognitive impairment and non-cerebral amyloid angiopathy-mild cognitive impairment and explored its associations with cognitive functions and conventional markers of cerebral small-vessel disease, using linear regression models. RESULTS: Subjects with Cerebral amyloid angiopathy-mild cognitive impairment showed increased peak width of skeletonized mean diffusivity in comparison to those with non-cerebral amyloid angiopathy-mild cognitive impairment (P < .001). Peak width of skeletonized mean diffusivity values were correlated with the volume of white matter hyperintensities in both groups. Higher peak width of skeletonized mean diffusivity was associated with worse performance in processing speed among patients with cerebral amyloid angiopathy, after adjusting for other MRI markers of cerebral small vessel disease. The peak width of skeletonized mean diffusivity did not correlate with cognitive functions among those with non-cerebral amyloid angiopathy-mild cognitive impairment. CONCLUSIONS: Peak width of skeletonized mean diffusivity is altered in cerebral amyloid angiopathy and is associated with performance in processing speed. This DTI-based method may reflect the degree of white matter structural disruption in cerebral amyloid angiopathy and could be a useful biomarker for cognition in this population.

Apolipoprotein D: a potential biomarker for cerebral amyloid angiopathy.

AIMS: We investigated the potential of apolipoprotein D (apoD) as cerebrospinal fluid (CSF) biomarker for cerebral amyloid angiopathy (CAA) after confirmation of its association with CAA pathology in human brain tissue. METHODS: The association of apoD with CAA pathology was analysed in human occipital lobe tissue of CAA (n = 9), Alzheimer's disease (AD) (n = 11) and healthy control cases (n = 11). ApoD levels were quantified in an age- and sex-matched CSF cohort of CAA patients (n = 31), AD patients (n = 27) and non-neurological controls (n = 67). The effects of confounding factors (age, sex, serum levels) on apoD levels were studied using CSF of non-neurological controls (age range 16-85 years), and paired CSF and serum samples. RESULTS: ApoD was strongly associated with amyloid deposits in vessels, but not with parenchymal plaques in human brain tissue. CSF apoD levels correlated with age and were higher in men than women in subjects >50 years. The apoD CSF/serum ratio correlated with the albumin ratio. When controlling for confounding factors, CSF apoD levels were significantly lower in CAA patients compared with controls and compared with AD patients (P = 0.0008). CONCLUSIONS: Our data show that apoD is specifically associated with CAA pathology and may be a CSF biomarker for CAA, but clinical application is complicated due to dependency on age, sex and blood-CSF barrier integrity. Well-controlled follow-up studies are required to determine whether apoD can be used as reliable biomarker for CAA.

Effect of CTA Tube Current on Spot Sign Detection and Accuracy for Prediction of Intracerebral Hemorrhage Expansion.

BACKGROUND AND PURPOSE: Reduction of CT tube current is an effective strategy to minimize radiation load. However, tube current is also a major determinant of image quality. We investigated the impact of CTA tube current on spot sign detection and diagnostic performance for intracerebral hemorrhage expansion. MATERIALS AND METHODS: We retrospectively analyzed a prospectively collected cohort of consecutive patients with primary intracerebral hemorrhage from January 2001 to April 2015 who underwent CTA. The study population was divided into 2 groups according to the median CTA tube current level: low current (<350 mA) and high current (≥350 mA). CTA first-pass readings for spot sign presence were independently analyzed by 2 readers. Baseline and follow-up hematoma volumes were assessed by semiautomated computer-assisted volumetric analysis. Sensitivity, specificity, positive and negative predictive values, and accuracy of spot sign in predicting hematoma expansion were calculated. RESULTS: This study included 709 patients (288 and 421 in the low- and high-current groups, respectively). A higher proportion of low-current scans identified at least 1 spot sign (20.8% versus 14.7%, P = .034), but hematoma expansion frequency was similar in the 2 groups (18.4% versus 16.2%, P = .434). Sensitivity and positive and negative predictive values were not significantly different between the 2 groups. Conversely, high-current scans showed superior specificity (91% versus 84%, P = .015) and overall accuracy (84% versus 77%, P = .038). CONCLUSIONS: CTA obtained at high levels of tube current showed better diagnostic accuracy for prediction of hematoma expansion by using spot sign. These findings may have implications for future studies using the CTA spot sign to predict hematoma expansion for clinical trials.

Decoupling of structural and functional brain connectivity in older adults with white matter hyperintensities.

Age-related impairments in the default network (DN) have been related to disruptions in connecting white matter tracts. We hypothesized that the local correlation between DN structural and functional connectivity is negatively affected in the presence of global white matter injury. In 125 clinically normal older adults, we tested whether the relationship between structural connectivity (via diffusion imaging tractography) and functional connectivity (via resting-state functional MRI) of the posterior cingulate cortex (PCC) and medial prefrontal frontal cortex (MPFC) of the DN was altered in the presence of white matter hyperintensities (WMH). A significant correlation was observed between microstructural properties of the cingulum bundle and MPFC-PCC functional connectivity in individuals with low WMH load, but not with high WMH load. No correlation was observed between PCC-MPFC functional connectivity and microstructure of the inferior longitudinal fasciculus, a tract not passing through the PCC or MPFC. Decoupling of connectivity, measured as the absolute difference between structural and functional connectivity, in the high WMH group was related to poorer executive functioning and memory performance. These results suggest that such decoupling may reflect reorganization of functional networks in response to global white matter pathology and may provide an early marker of clinically relevant network alterations.

Genetic variation at CR1 increases risk of cerebral amyloid angiopathy.

OBJECTIVE: Accumulated evidence suggests that a variant within the CR1 gene (single nucleotide polymorphism rs6656401), known to increase risk for Alzheimer disease (AD), influences ß-amyloid (Aß) deposition in brain tissue. Given the biologic overlap between AD and cerebral amyloid angiopathy (CAA), a leading cause of intracerebral hemorrhage (ICH) in elderly individuals, we investigated whether rs6656401 increases the risk of CAA-related ICH and influences vascular Aß deposition. METHODS: We performed a case-control genetic association study of 89 individuals with CAA-related ICH and 280 individuals with ICH unrelated to CAA and compared them with 324 ICH-free control subjects. We also investigated the effect of rs6656401 on risk of recurrent CAA-ICH in a prospective longitudinal cohort of ICH survivors. Finally, association with severity of histopathologic CAA was investigated in 544 autopsy specimens from 2 longitudinal studies of aging. RESULTS: rs6656401 was associated with CAA-ICH (odds ratio [OR] = 1.61, 95% confidence interval [CI] 1.19-2.17, p = 8.0 × 10(-4)) as well as with risk of recurrent CAA-ICH (hazard ratio = 1.35, 95% CI 1.04-1.76, p = 0.024). Genotype at rs6656401 was also associated with severity of CAA pathology at autopsy (OR = 1.34, 95% CI 1.05-1.71, p = 0.009). Adjustment for parenchymal amyloid burden did not cancel this effect, suggesting that, despite the correlation between parenchymal and vascular amyloid pathology, CR1 acts independently on both processes, thus increasing risk of both AD and CAA. CONCLUSION: The CR1 variant rs6656401 influences risk and recurrence of CAA-ICH, as well as the severity of vascular amyloid deposition.

Warfarin-related intraventricular hemorrhage: imaging and outcome.

OBJECTIVE: Oral anticoagulation therapy (OAT) with warfarin increases mortality and disability after intracerebral hemorrhage (ICH), the result of increased ICH volume and risk of hematoma expansion. We investigated whether OAT also influences risk of development of intraventricular hemorrhage (IVH), the volume of IVH and IVH expansion, and whether IVH is a substantive mediator of the overall effect of OAT on ICH outcome. METHODS: We performed a retrospective analysis of a prospectively collected single-center cohort of 1,879 consecutive ICH cases (796 lobar, 865 deep, 153 cerebellar, 15 multiple location, 50 primary IVH) from 1999 to 2009. ICH and IVH volumes at presentation, as well as hematoma expansion (>33% or >6 mL increase) and IVH expansion (>2 mL increase), were determined using established semiautomated methods. Outcome was assessed at 90 days using either the modified Rankin Scale or Glasgow Outcome Scale. RESULTS: Warfarin use was associated with IVH risk, IVH volume at presentation, and IVH expansion in both lobar and deep ICH (all p < 0.05) in a dose-response relationship with international normalized ratio. Warfarin was associated with poor outcome in both lobar and deep ICH (p < 0.01), and >95% of this effect was accounted for by baseline ICH and IVH volumes, as well as ICH and IVH expansion. CONCLUSION: Warfarin increases IVH volume and risk of IVH expansion in lobar and deep ICH. These findings (along with effects on ICH volume and expansion) likely represent the mechanisms by which anticoagulation worsens ICH functional outcome.

Cerebral microbleeds and cognitive functioning in the PROSPER study.

OBJECTIVES: Cerebral microbleeds (MBs) are an important indicator of cerebral small-vessel disease, and their prevalence increases with increasing age. Little is known about the functional consequences of MBs in the aging population. In this study we investigated whether the presence and location of MBs are associated with cognition in the PROSPER study. METHODS: For 439 subjects the number and location (cortico-subcortical, deep white matter, basal ganglia, and infratentorial) of the MBs was recorded. Difference in cognitive performance between subjects with and without MBs was calculated by entering the variables sex, age, white matter hyperintensity volume, infarction, and MBs in a linear mixed model. Differences in cognition between subjects with and without one or more MBs at different anatomic locations were assessed using the same model. RESULTS: We found that after correction for sex, age, white matter hyperintensity volume, and infarction, subjects with infratentorial MBs had a significantly lower score on the Immediate Picture-Word Learning test, Delayed Picture-Word Learning, and Instrumental Activities of Daily Living. CONCLUSIONS: Our data demonstrate that in elderly individuals at increased vascular risk, infratentorial MBs are associated with loss in cognitive functioning.

Statin use and outcome after intracerebral hemorrhage: case-control study and meta-analysis.

OBJECTIVES: Intracerebral hemorrhage (ICH) is a highly lethal disease of the elderly. Use of statins is increasingly widespread among the elderly, and therefore common in patients who develop ICH. Accumulating data suggests that statins have neuroprotective effects, but their association with ICH outcome has been inconsistent. We therefore performed a meta-analysis of all available evidence, including unpublished data from our own institution, to determine whether statin exposure is protective for patients who develop ICH. METHODS: In our prospectively ascertained cohort, we compared 90-day functional outcome in 238 pre-ICH statin cases and 461 statin-free ICH cases. We then meta-analyzed results from our cohort along with previously published studies using a random effects model, for a total of 698 ICH statin cases and 1,823 non-statin-exposed subjects. RESULTS: Data from our center demonstrated an association between statin use before ICH and increased probability of favorable outcome (odds ratio [OR] = 2.08, 95% confidence interval [CI] 1.37-3.17) and reduced mortality (OR = 0.47, 95% CI 0.32-0.70) at 90 days. No compound-specific statin effect was identified. Meta-analysis of all published evidence confirmed the effect of statin use on good outcome (OR = 1.91, 95% CI 1.38-2.65) and mortality (OR = 0.55, 95% CI 0.42-0.72) after ICH. CONCLUSION: Antecedent use of statins prior to ICH is associated with favorable outcome and reduced mortality after ICH. This phenomenon appears to be a class effect of statins. Further studies are required to clarify the biological mechanisms underlying these observations.

Correlations between MRI white matter lesion location and executive function and episodic memory.

OBJECTIVES: MRI white matter hyperintensity (WMH) volume is associated with cognitive impairment. We hypothesized that specific loci of WMH would correlate with cognition even after accounting for total WMH volume. METHODS: Subjects were identified from a prospective community-based study: 40 had normal cognition, 94 had mild impairment (defined here as a Clinical Dementia Rating [CDR] score of 0.5 without dementia), and 11 had mild Alzheimer's dementia. Factor analysis of a 22-item neuropsychological battery yielded 4 factors (episodic memory, executive function, spatial skills, and general knowledge). MRI WMH segmentation and analysis was performed using FreeSurfer software. RESULTS: Higher WMH volume was independently associated with lower executive function and episodic memory factor scores. Voxel-based general linear models showed loci where WMH was strongly inversely associated with specific cognitive factor scores (p < 0.001), controlling for age, education, sex, APOE genotype, and total WMH volume. For episodic memory, clusters were observed in bilateral temporal-occipital and right parietal periventricular white matter, and the left anterior limb of the internal capsule. For executive function, clusters were observed in bilateral inferior frontal white matter, bilateral temporal-occipital and right parietal periventricular white matter, and the anterior limb of the internal capsule bilaterally. CONCLUSIONS: Specific WMH loci are closely associated with executive function and episodic memory, independent of total WMH volume. The anatomic locations suggest that WMH may cause cognitive impairment by affecting connections between cortex and subcortical structures, including the thalamus and striatum, or connections between the occipital lobe and frontal or parietal lobes.

White matter hyperintensity volume is increased in small vessel stroke subtypes.

OBJECTIVE: White matter hyperintensity (WMH) may be a marker of an underlying cerebral microangiopathy. Therefore, we hypothesized that WMH would be most severe in patients with lacunar stroke and intracerebral hemorrhage (ICH), 2 types of stroke in which cerebral small vessel (SV) changes are pathophysiologically relevant. METHODS: We determined WMH volume (WMHV) in cohorts of prospectively ascertained patients with acute ischemic stroke (AIS) (Massachusetts General Hospital [MGH], n = 628, and the Ischemic Stroke Genetics Study [ISGS], n = 263) and ICH (MGH, n = 122). RESULTS: Median WMHV was 7.5 cm³ (interquartile range 3.4-14.7 cm³) in the MGH AIS cohort (mean age 65 ± 15 years). MGH patients with larger WMHV were more likely to have lacunar stroke compared with cardioembolic (odds ratio [OR] = 1.87 per SD normally transformed WMHV), large artery (OR = 2.25), undetermined (OR = 1.87), or other (OR = 1.85) stroke subtypes (p < 0.03). These associations were replicated in the ISGS cohort (p = 0.03). In a separate analysis, greater WMHV was seen in ICH compared with lacunar stroke (OR = 1.2, p < 0.02) and in ICH compared with all ischemic stroke subtypes combined (OR = 1.34, p < 0.007). CONCLUSIONS: Greater WMH burden was associated with SV stroke compared with other ischemic stroke subtypes and, even more strongly, with ICH. These data, from 2 independent samples, support the model that increasing WMHV is a marker of more severe cerebral SV disease and provide further evidence for links between the biology of WMH and SV stroke.

Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review.

OBJECTIVES: Antiplatelet therapy (APT) promotes bleeding; therefore, APT might worsen outcome in patients with intracerebral hemorrhage (ICH). We performed a systematic review and meta-analysis to address the hypothesis that pre-ICH APT use is associated with mortality and poor functional outcome following ICH. METHODS: The Medline and Embase databases were searched in February 2008 using relevant key words, limited to human studies in the English language. Cohort studies of consecutive patients with ICH reporting mortality or functional outcome according to pre-ICH APT use were identified. Of 2,873 studies screened, 10 were judged to meet inclusion criteria by consensus of 2 authors. Additionally, we solicited unpublished data from all authors of cohort studies with >100 patients published within the last 10 years, and received data from 15 more studies. Univariate and multivariable-adjusted odds ratios (ORs) for mortality and poor functional outcome were abstracted as available and pooled using a random effects model. RESULTS: We obtained mortality data from 25 cohorts (15 unpublished) and functional outcome data from 21 cohorts (14 unpublished). Pre-ICH APT users had increased mortality in both univariate (OR 1.41, 95% confidence interval [CI] 1.21 to 1.64) and multivariable-adjusted (OR 1.27, 95% CI 1.10 to 1.47) pooled analyses. By contrast, the pooled OR for poor functional outcome was no longer significant when using multivariable-adjusted estimates (univariate OR 1.29, 95% CI 1.09 to 1.53; multivariable-adjusted OR 1.10, 95% CI 0.93 to 1.29). CONCLUSIONS: In cohort studies, APT use at the time of ICH compared to no APT use was independently associated with increased mortality but not with poor functional outcome.

Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy.

BACKGROUND: Cerebral amyloid angiopathy (CAA) typically presents with lobar intracerebral macrohemorrhages (ICH) or microbleeds (MBs). Several case reports also found superficial siderosis (SS) in patients with CAA. We aimed to assess the value of SS for the in vivo diagnosis of CAA, and tested whether the inclusion of SS as a criterion alters the sensitivity and specificity of the Boston criteria for CAA-related hemorrhage. METHODS: We retrospectively analyzed the T2*-weighted MRIs of 38 patients with histopathologically proven CAA and of 22 control patients with histopathologically proven non-CAA ICHs regarding the presence of ICHs, MBs, and SS. We compared the sensitivity and specificity of the classic Boston criteria to that of modified criteria, which included SS as a criterion. RESULTS: ICHs were present in 71% of the patients with CAA, and in all control patients. MBs were found in 47.4% of patients with CAA and in 22.7% of controls. SS was detected in 60.5% of patients with CAA, but in none of the controls. The classic criteria had a sensitivity of 89.5% for CAA-related hemorrhage, while inclusion of SS increased their sensitivity to 94.7% (not significant). On the contrary, the specificity of the Boston criteria was 81.2% both for the classic and for the modified criteria. CONCLUSIONS: Superficial siderosis (SS) occurs with high prevalence in cerebral amyloid angiopathy (CAA) and is rare in non-CAA forms of intracerebral hemorrhages. Thus, we propose that inclusion of SS in the Boston criteria might enhance their sensitivity for CAA-related hemorrhage without loss of specificity.

Silent ischemic infarcts are associated with hemorrhage burden in cerebral amyloid angiopathy.

BACKGROUND: Neuropathologic studies suggest an association between cerebral amyloid angiopathy (CAA) and small ischemic infarctions as well as hemorrhages. We examined the prevalence and associated risk factors for infarcts detected by diffusion-weighted imaging (DWI). METHODS: We performed retrospective analysis of MR images from 78 subjects with a diagnosis of probable CAA and a similar aged group of 55 subjects with Alzheimer disease or mild cognitive impairment (AD/MCI) for comparison. DWI and apparent diffusion coefficient (ADC) maps were inspected for acute or subacute infarcts. We also examined the association between DWI lesions and demographic variables, conventional vascular risk factors, and radiographic markers of CAA severity such as number of hemorrhages on gradient-echo MRI and volume of T2-hyperintense white matter lesions. RESULTS: Twelve of 78 subjects with CAA (15%) had a total of 17 DWI-hyperintense lesions consistent with subacute cerebral infarctions vs 0 of 55 subjects with AD/MCI (p = 0.001). The DWI lesions were located primarily in cortex and subcortical white matter. CAA subjects with DWI lesions had a higher median number of total hemorrhages (22 vs 4, p = 0.025) and no difference in white matter hyperintensity volume or conventional vascular risk factors compared to subjects with CAA without lesions. CONCLUSIONS: MRI evidence of small subacute infarcts is present in a substantial proportion of living patients with advanced cerebral amyloid angiopathy (CAA). The presence of these lesions is associated with a higher burden of hemorrhages, but not with conventional vascular risk factors. This suggests that advanced CAA predisposes to ischemic infarction as well as intracerebral hemorrhage.

Plasma Abeta, homocysteine, and cognition: the Vitamin Intervention for Stroke Prevention (VISP) trial.

BACKGROUND: Amyloid-beta protein (Abeta) plays a key role in Alzheimer disease (AD) and is also implicated in cerebral small vessel disease. Serum total homocysteine (tHcy) is a risk factor for small vessel disease and cognitive impairment and correlates with plasma Abeta levels. To determine whether this association results from a common pathophysiologic mechanism, we investigated whether vitamin supplementation-induced reduction of tHcy influences plasma Abeta levels in the Vitamin Intervention in Stroke Prevention (VISP) study. METHODS: Two groups of 150 patients treated with either the high-dose or low-dose formulation of pyridoxine, cobalamin, and folic acid in a randomized, double-blind fashion were selected among the participants in the VISP study without recurrent stroke during follow-up and in the highest 10% of the distribution for baseline tHcy levels. Concentrations of plasma Abeta with 40 (Abeta40) and 42 (Abeta42) amino acids were measured at baseline and at the 2-year visit. RESULTS: tHcy levels significantly decreased with vitamin supplementation in both groups. tHcy were strongly correlated with Abeta40 but not Abeta42 concentrations. There was no difference in the change in Abeta40, Abeta42 (p = 0.40, p = 0.35), or the Abeta42/Abeta40 ratio over time (p = 0.86) between treatment groups. Abeta measures were not associated with cognitive change. CONCLUSIONS: This double-blind randomized controlled trial of vitamin therapy demonstrates a strong correlation between serum tHcy and plasma Abeta40 concentrations in subjects with ischemic stroke. Treatment with high dose vitamins does not, however, influence plasma levels of Abeta, despite their effect on lowering tHcy. Our results suggest that although tHcy is associated with plasma Abeta40, they may be regulated by independent mechanisms.

MR imaging detection of cerebral microbleeds: effect of susceptibility-weighted imaging, section thickness, and field strength.

BACKGROUND AND PURPOSE: The emergence of cerebral microbleeds (CMB) as common MR imaging findings raises the question of how MR imaging parameters influence CMB detection. To evaluate the effects of modified gradient recalled-echo (GRE) MR imaging methods, we performed an analysis of sequence, section thickness, and field strength on CMB imaging properties and detection in subjects with cerebral amyloid angiopathy (CAA), a condition associated with microhemorrhage. MATERIALS AND METHODS: Multiple MR images were obtained from subjects with probable CAA, with varying sequences (GRE versus susceptibility-weighted imaging [SWI]), section thicknesses (1.2-1.5 versus 5 mm), and magnetic field strengths (1.5T versus 3T). Individual CMB were manually identified and analyzed for contrast index (lesion intensity normalized to normal-appearing white matter signal intensity) and diameter. CMB counts were compared between 1.5T thick-section GRE and thin-section SWI for 3 subjects who underwent both protocols in the same scanning session. RESULTS: With other parameters constant, use of SWI, thinner sections, and a higher field strength yielded medium-to-large gains in CMB contrast index (CI; Cohen d 0.71-1.87). SWI was also associated with small increases in CMB diameter (Cohen d <0.3). Conventional thick-section GRE identified only 33% of CMB (103 of 310) seen on thin-section SWI. Lesions prospectively identified on GRE had significantly greater CI and diameter measured on the GRE image than those not prospectively identified. CONCLUSIONS: The examined alternatives to conventional GRE MR imaging yield substantially improved CMB contrast and sensitivity for detection. Future studies based on these techniques will most likely yield even higher prevalence estimates for CMB.

Feeding, oviposition and survival of Liriomyza trifolii (Diptera: Agromyzidae) on Bt and non-Bt cottons.

The effects of Bt transgenic cottons (Bt-I expressing cry1Ac and Bt-II expressing cry1Ab and cry2Ab or cry1Ab and cry1Fa) and non-Bt cottons on feeding, oviposition and longevity of adults, and development and survival of Liriomyza trifolii larvae were studied under laboratory conditions; and infestation on four Bt and two non-Bt cotton traits were investigated under field conditions. Laboratory choice and no-choice tests showed that L. trifolii adults were capable of distinguishing between Bt cottons and non-Bt cottons. In a choice test on younger plants (4-5 leaves), the adults were found more often and made more feeding punctures (FP) on non-Bt cottons than on Bt cottons. On older plants (8-9 leaves), adults made the most FP on non-Bt cotton followed by those on Bt-II cottons and the least on Bt-I cotton. The females oviposited more eggs (6.7 eggs per leaf) on non-Bt cotton than on Bt-I (1.7 eggs per leaf) and Bt-II (0.8 eggs per leaf) cottons on younger plants and oviposited similar numbers of eggs (0.7-1.3 eggs per leaf) on non-Bt and Bt cottons on older plants. In a no-choice test, the females also fed more FP on non-Bt cottons than on Bt cottons on both younger and older plants. The females oviposited more eggs (15.6 eggs per leaf) on non-Bt cotton than on Bt-I (8.2 eggs per leaf) and Bt-II (6.5 eggs per leaf) cottons on younger plants and similar numbers of eggs (2.5-3.3 eggs per leaf) on non-Bt and Bt cottons on older plants. Larval and puparial survivals were not different among Bt and non-Bt cottons. The occurrence and damage of leafminers on cottons in the field showed that L. trifolii infested more plants and leaves and had more mines on non-Bt cotton than on Bt cottons.

Impaired visual evoked flow velocity response in cerebral amyloid angiopathy.

OBJECTIVE: Animal models of cerebral amyloid angiopathy (CAA) exhibit abnormal vascular reactivity. We determined whether vascular reactivity, measured by transcranial Doppler ultrasound (TCD), is reduced in humans with CAA. METHODS: Cases were recruited from an established prospective study of CAA. Healthy controls were recruited from a study of normal aging. Evoked mean flow velocity increase in the posterior cerebral artery (PCA) was measured while subjects viewed a flashing alternating checkerboard stimulus. In a separate but partially overlapping cohort we measured the mean flow velocity increase in the middle cerebral artery (MCA) while subjects inhaled carbon dioxide. RESULTS: The visual evoked mean flow velocity increase was 8.0 +/- 6.1% in CAA (n = 11) compared to 17.4 +/- 5.7% in controls (n = 9, p = 0.002). The PCA pulsatility index, a marker of distal vascular resistance, was higher in CAA (CAA 1.35 +/- 0.35, control 1.04 +/- 0.14, p = 0.03). Among CAA subjects, lower visual evoked mean flow velocity increase was associated with a higher number of hemorrhages seen on MRI (r = -0.87, p = 0.0005) and higher MRI white matter hyperintensity volume (r = -0.67, p = 0.02). The MCA response to carbon dioxide did not differ between CAA and control in 20 subjects (9 CAA, 11 control, p = 0.54). CONCLUSIONS: Cerebral amyloid angiopathy (CAA) was associated with decreased vascular reactivity in response to visual stimulation, possibly reflecting the occipital predilection of the disease. The association of posterior cerebral artery (PCA) evoked flow velocity response with elevated PCA pulsatility index and MRI markers of small vessel disease suggests that abnormal PCA evoked flow velocity in CAA is caused by pathology of the distal resistance vessels.

Effects of photoperiod on boll weevil (Coleoptera: Curculionidae) development, survival, and reproduction.

Effects of photoperiod on development, survival, feeding, and oviposition of boll weevils, Anthonomus grandis grandis Boheman, were assessed under five different photophases (24, 14, 12, 10, and 0 h) at a constant 27 degrees C temperature and 65% RH in the laboratory. Analyses of our results detected positive relationships between photoperiod and puncturing (mean numbers of oviposition and feeding punctures per day), and oviposition (oviposition punctures/oviposition+feeding punctures) activities, and the proportion of squares attacked by boll weevil females. When boll weevil females developed in light:darkness cycles, they produced a significantly higher percentage of eggs developing to adulthood than those developed in 24-h light or dark conditions. In long photoperiod (24:0 and 14:10 h), the number of female progeny was significantly higher and their development time was significantly shorter than those developed in short photoperiod (0:24 and 10:14 h). Lifetime oviposition was significantly highest at 12- and 14-h photophase, lowest at 0- and 10-h photophase, and intermediate at 24 h of light. Life table calculations indicated that boll weevil populations developed in a photoperiod of 14:10 and 12:12 (L:D) h will increase an average of two-fold each generation (Ro) compared with boll weevils developed in 24:0- and 10:14-h photoperiods and 15-fold compared with those at 0:24 h. Knowledge of the photoperiod-dependent population growth potential is critical for understanding population dynamics to better develop sampling protocols and timing insecticide applications.

Course of cerebral amyloid angiopathy-related inflammation.

BACKGROUND: A subset of patients with cerebral amyloid angiopathy (CAA) present with cognitive symptoms, seizures, headaches, T2-hyperintense MRI lesions, and neuropathologic evidence of CAA-associated vascular inflammation. OBJECTIVE: To analyze the risk factors, diagnostic characteristics, and long-term course of this disorder. METHODS: We assessed 14 consecutive patients with pathologically diagnosed CAA-related inflammation, 12 with available neuroimaging and follow-up data. Patients were evaluated for MRI appearance, APOE genotype, and clinical course over a 46.8 +/- 29.1-month follow-up. RESULTS: Baseline MRI scans were characterized by asymmetric T2-hyperintense lesions extending to the subcortical white matter and occasionally the overlying gray matter, with signal properties suggesting vasogenic edema. Subjects could be divided into three groups based on response to immunosuppressive treatment: monophasic improvement (7/12), initial improvement followed by symptomatic relapse (3/12), and no evident response to treatment (2/12). The volume of MRI hyperintensities correlated with the severity of clinical symptoms. One patient experienced symptomatic intracerebral hemorrhage within a region of recurrent MRI hyperintensity. The APOE epsilon4/epsilon4 genotype was strongly associated with CAA-related inflammation, present in 76.9% (10/13) of subjects vs 5.1% (2/39) with symptomatic but noninflammatory CAA (p < 0.0001). CONCLUSION: Cerebral amyloid angiopathy-related inflammation represents a clinically, pathologically, radiographically, and genetically distinct disease subtype with implications for clinical practice and ongoing immunotherapeutic approaches to Alzheimer disease.

Reproductive potential of overwintering, F1, and F2 female boll weevils (Coleoptera: Curculionidae) in the Lower Rio Grande Valley of Texas.

The feeding and oviposition activity of overwintering boll weevils, Anthonomus grandis grandis (Boheman), and seasonal fluctuations in development, survival, and reproduction of progeny of overwintering and first- and second-generation boll weevil females were determined in the laboratory at 27 degrees C, 65% RH, and a photoperiod of 12:12 (L:D) h. During the cotton-free period in the Lower Rio Grande Valley, female boll weevils without access to cotton resorb their unlaid eggs and enter reproductive diapause. However, when they were provided daily with greenhouse-grown cotton squares, commencement of oviposition began after 7, 15, or 20 d, depending on when they were captured. Females captured later in the winter fed longer before laying eggs than those captured in the early fall, suggesting that it may take females longer to terminate diapause the longer they have been dormant. The rate of feeding by females was significantly less during the winter months, and this may have affected the rate of diet-mediated termination of dormancy. Females of the first and second generations after the overwintering generation produced a significantly higher percentage of progeny surviving to adulthood and a higher proportion of these progeny were females. Offspring development time from overwintering female parents was significantly longer than that from first and second generations under the same laboratory conditions. The total number of lifetime eggs produced by females of the second generation during the cotton-growing season were approximately 9.9-fold higher than for overwintering females and 1.5-fold higher than for first-generation females. Life table calculations indicated that the population of second-generation boll weevils increased an average of 1.5-fold higher each generation than for females of the first generation and 22.6-fold higher than for overwintering females. Our data showed variation in boll weevil survival, development, and reproductive potential among the overwintering and first- and second-generation females, suggesting inherent seasonal fluctuations in these parameters.