Abstract. While APOE ε4 is the major genetic risk factor for Alzheimer's disease (AD), amyloid dysmetabolism is an initial or early event predicting clinical disease and is an important focus for secondary intervention trials. To improve identification of cases with increased AD risk, we evaluated recruitment procedures using pathological CSF concentrations of A␤ 42 (pA␤) and APOE ε4 as risk markers in a multi-center study in Norway. In total, 490 subjects aged 40-80 y were included after response to advertisements and media coverage or memory clinics referrals. Controls (n = 164) were classified as normal controls without first-degree relatives with dementia (NC), normal controls with first-degree relatives with dementia (NCFD), or controls scoring below norms on cognitive screening. Patients (n = 301) were classified as subjective cognitive decline or * Correspondence to: Lene Pålhaugen, P.B. 1000, N-1478 Lørenskog, Norway. Tel.: +47 95832775; E-mail: lene. palhaugen@gmail.com. 98 T. Fladby et al. / Detecting At-Risk AD Casesmild cognitive impairment. Subjects underwent a clinical and cognitive examination and MRI according to standardized protocols. Core biomarkers in CSF from 411 and APOE genotype from 445 subjects were obtained. Cases (both self-referrals (n = 180) and memory clinics referrals (n = 87)) had increased fractions of pA␤ and APOE ε4 frequency compared to NC. Also, NCFD had higher APOE ε4 frequencies without increased fraction of pA␤ compared to NC, and cases recruited from memory clinics had higher fractions of pA␤ and APOE ε4 frequency than self-referred. This study shows that memory clinic referrals are pA␤ enriched, whereas self-referred and NCFD cases more frequently are pA␤ negative but at risk (APOE ε4 positive), suitable for primary intervention.

White matter hyperintensities (WMHs) are associated with vascular risk and Alzheimer’s disease. In this study, we examined relations between WMH load and distribution, amyloid pathology and vascular risk in 339 controls and cases with either subjective (SCD) or mild cognitive impairment (MCI). Regional deep (DWMH) and periventricular (PWMH) WMH loads were determined using an automated algorithm. We stratified on Aβ1-42 pathology (Aβ+/−) and analyzed group differences, as well as associations with Framingham Risk Score for cardiovascular disease (FRS-CVD) and age. Occipital PWMH ( p = 0.001) and occipital DWMH ( p = 0.003) loads were increased in SCD-Aβ+ compared with Aβ− controls. In MCI-Aβ+ compared with Aβ− controls, there were differences in global WMH ( p = 0.003), as well as occipital DWMH ( p = 0.001) and temporal DWMH ( p = 0.002) loads. FRS-CVD was associated with frontal PWMHs ( p = 0.003) and frontal DWMHs ( p = 0.005), after adjusting for age. There were associations between global and all regional WMH loads and age. In summary, posterior WMH loads were increased in SCD-Aβ+ and MCI-Aβ+ cases, whereas frontal WMHs were associated with vascular risk. The differences in WMH topography support the use of regional WMH load as an early-stage marker of etiology.

PurposeTo compare left ventricular (LV) torsion represented as the circumferential-longitudinal (CL) shear angle between 2D and 3D quantification, using cardiovascular magnetic resonance (CMR).MethodsCMR tagging was performed in six healthy volunteers. From this, LV torsion was calculated using a 2D and a 3D method. The cross-correlation between both methods was evaluated and comparisons were made using Bland-Altman analysis.ResultsThe cross-correlation between the curves was r2 = 0.97 ± 0.02. No significant time-delay was observed between the curves. Bland-Altman analysis revealed a significant positive linear relationship between the difference and the average value of both analysis methods, with the 2D results showing larger values than the 3D. The difference between both methods can be explained by the definition of the 2D method.ConclusionLV torsion represented as CL shear quantified by the 2D and 3D analysis methods are strongly related. Therefore, it is suggested to use the faster 2D method for torsion calculation.

Purpose: To extend the harmonic phase (HARP) tracking method in order to track the myocardial tissue that appears near the epicardial contour during systole and reappears near the endocardial contour during diastole, due to the longitudinal motion and conical shape of the heart. Materials and Methods:A mathematical model of myocardial deformation was used to quantify the accuracy of the extended HARP tracking and of the strain computation. For six healthy volunteers, the number of tracked points and the two-dimensional strain components were computed with the extended and with the original HARP tracking version.Results: High accuracy was obtained for the circumferential strain (maximum error is 0.5% relative to analytical strain). The extended version tracked 22 Ϯ 7%, 51 Ϯ 19%, and 67 Ϯ 20% more points than the original version on the basal, mid, and apical slices, respectively (P Յ 0.001 for each slice), and yielded a decreased circumferential shortening (relative decrease: 2 Ϯ 4%, 9 Ϯ 4%, and 12 Ϯ 5% for the three slices; P Ͻ 0.005 for mid and apex), at end systole. These differences in circumferential strain were related to the more complete coverage of the myocardial wall with tracked points. Conclusion:The extended HARP tracking also provides strain values from myocardial regions that were not covered by the original HARP tracking. SINCE THE FIRST articles on MRI and myocardial tagging (1,2) were published, myocardial strain analysis with MR has become a more common procedure. The postprocessing performed on the tagged images can go from simple visual inspection of the tag pattern deformation to the exhaustive computation of strain maps. Important efforts have been made during the past few years in the latter field. The published methods include active contour models (3), optical flow methods (4,5), template matching methods (6), and harmonic phase (HARP) MR (7). Due to its automatic nature, HARP tracking is a promising tool for clinical application. HARP tracking is a phase-sensitive method to determine the tag line displacement by tracking its angle value over the cardiac cycle, normally starting at the time frame with an undeformed tag pattern.Due to the combination of the conical shape of the heart and its longitudinal motion, new tag lines appear during the systolic phase near the epicardial contour and other tag lines disappear near the endocardial contour. Since these new tag lines are not present during the time frame with the undeformed tag pattern, their angle values are not available and, consequently, these lines are not tracked. However, disregarding these tag lines can lead to systematic errors in the strain results, due to the transmural gradient in the strain (8).In this work, an extended HARP tracking method is proposed, which tracks the new tag lines that enter into the image plane during the systolic phase and recovers the tag lines that reappear at the endocardial contour during the diastolic phase. With this extended method, all parts of the myocardium are completely tracked during all ...