Visual assessment of [¹⁸F]flutemetamol PET images can detect early amyloid pathology and grade its extent

PURPOSE: To investigate the sensitivity of visual read (VR) to detect early amyloid pathology and the overall utility of regional VR. METHODS: [¹⁸F]flutemetamol PET images of 497 subjects (ALFA+ N = 352; ADC N = 145) were included. Scans were visually assessed according to product guidelines, recording the number of positive regions (0-5) and a final negative/positive classification. Scans were quantified using the standard and regional Centiloid (CL) method. The agreement between VR-based classification and published CL-based cut-offs for early (CL = 12) and established (CL = 30) pathology was determined. An optimal CL cut-off maximizing Youden's index was derived. Global and regional CL quantification was compared to VR. Finally, 28 post-mortem cases from the [¹⁸F]flutemetamol phase III trial were included to assess the percentage agreement between VR and neuropathological classification of neuritic plaque density. RESULTS: VR showed excellent agreement against CL = 12 (κ = .89, 95.2%) and CL = 30 (κ = .88, 95.4%) cut-offs. ROC analysis resulted in an optimal CL = 17 cut-off against VR (sensitivity = 97.9%, specificity = 97.8%). Each additional positive VR region corresponded to a clear increase in global CL. Regional VR was also associated with regional CL quantification. Compared to mCERAD_{SOT}-based classification (i.e., any region mCERAD_{SOT} > 1.5), VR was in agreement in 89.3% of cases, with 13 true negatives, 12 true positives, and 3 false positives (FP). Regional sparse-to-moderate neuritic and substantial diffuse Aβ plaque was observed in all FP cases. Regional VR was also associated with regional plaque density. CONCLUSION: VR is an appropriate method for assessing early amyloid pathology and that grading the extent of visual amyloid positivity could present clinical value

Age differentiation in the effect of household situation on first-time homeownership

To become a homeowner, it is necessary to have sufficient resources and stability in the household situation. In existing studies, household type is often used as a proxy forlevel of stability. Household types with a highlevel of commitment (married couples without and with children) are regarded as stable households, and singles and cohabitors as less stable households. In this paper, it is argued that stability can be reached not only by making a commitment, but also by growing older. Increasing age brings stability into the lives of singles and cohabitors. Age also matters for the structure of resources and costs of different household types. From a combination of theory on age and theory on homeownership in the life course, five hypotheses are derived.They are tested on retrospective data by using discrete-time event-history analysis. From a model with interaction effects, it can be seen whether the probability of becoming a homeowner differs between household types in differentage groups. The results show that married couples have the highest probability of becoming homeowners in age group 18-24, whereas the probability is highest for cohabitors inage group 25-29, and in age group 30-34 for singles. This supports the idea that people become homeowners either when they make a commitment, or when stability is created through the passage of time in a less committing household type

Cohabitation, marriage, and first birth: the interrelationship of family formation events in Spain

In this paper, we investigate (1) the mutual causal relationship between first union formation and first childbirth, and (2) the existence of constant unmeasured determinants shared by these two events. We argue that these determinants mainly consist of value orientations that are heterogeneous in the population. We apply event-history techniques to retrospective survey data on Spain, allowing for unobserved heterogeneity components which simultaneously affect the two processes. Our findings confirm the existence of a strong selection effect, which influences both union formation and first birth. When controlling for these shared factors, we find that the risk of conception increases immediately at marriage, and it continues to be high during the following four years. Entry into cohabitation, in contrast, produces a much smaller increase in the relative risk of conception. The effect of conception on union formation is particularly strong during pregnancy, but it declines sharply after delivery