Clinical application of plasma P-tau217 to assess eligibility for amyloid-lowering immunotherapy in memory clinic patients with early Alzheimer's disease.

BACKGROUND: With the approval of disease-modifying treatments (DMTs) for early Alzheimer's disease (AD), there is an increased need for efficient and non-invasive detection methods for cerebral amyloid-ß (Aß) pathology. Current methods, including positron emission tomography (PET) and cerebrospinal fluid (CSF) analysis, are costly and invasive methods that may limit access to new treatments. Plasma tau phosphorylated at threonine-217 (P-tau217) presents a promising alternative, yet optimal cutoffs for treatment eligibility with DMTs like aducanumab require further investigation. This study evaluates the efficacy of one- and two-cutoff strategies for determining DMT eligibility at the Butler Hospital Memory & Aging Program (MAP). METHODS: In this retrospective, cross-sectional diagnostic cohort study, we first developed P-tau217 cutoffs using site-specific and BioFINDER-2 training data, which were then tested in potential DMT candidates from Butler MAP (total n = 150). ROC analysis was used to calculate the area under the curve (AUC) and accuracy of P-tau217 interpretation strategies, using Aß-PET/CSF testing as the standard of truth. RESULTS: Potential DMT candidates at Butler MAP (n = 50), primarily diagnosed with mild cognitive impairment (n = 29 [58%]) or mild dementia (21 [42%]), were predominantly Aß-positive (38 [76%]), and half (25 [50%]) were subsequently treated with aducanumab. Elevated P-tau217 predicted cerebral Aß positivity in potential DMT candidates (AUC = 0.97 [0.92-1]), with diagnostic accuracy ranging from 0.88 (0.76-0.95, p = 0.028) to 0.96 (0.86-1, p < .001). When using site-specific cutoffs, a subset of DMT candidates (10%) exhibited borderline P-tau217 (between 0.273 and 0.399 pg/mL) that would have potentially required confirmatory testing. CONCLUSIONS: This study, which included participants treated with aducanumab, confirms the utility of one- and two-cutoff strategies for interpreting plasma P-tau217 in assessing DMT eligibility. Using P-tau217 could potentially replace more invasive diagnostic methods, and all aducanumab-treated participants would have been deemed eligible based on P-tau217. However, false positives remain a concern, particularly when applying externally derived cutoffs that exhibited lower specificity which could have led to inappropriate treatment of Aß-negative participants. Future research should focus on prospective validation of P-tau217 cutoffs to enhance their generalizability and inform standardized treatment decision-making across diverse populations.

Clinical application of plasma P-tau217 to assess eligibility for amyloid-lowering immunotherapy in memory clinic patients with early Alzheimer's disease.

Background: With the approval of disease-modifying treatments (DMTs) for early Alzheimer's disease (AD), there is an increased need for efficient and non-invasive detection methods for cerebral amyloid-ß (Aß) pathology. Current methods, including positron emission tomography (PET) and cerebrospinal fluid (CSF) analysis, are costly and invasive methods that may limit access to new treatments. Plasma tau phosphorylated at threonine-217 (P-tau217) presents a promising alternative, yet optimal cutoffs for treatment eligibility with DMTs like aducanumab require further investigation. This study evaluates the efficacy of one- and two-cutoff strategies for determining DMT eligibility at the Butler Hospital Memory & Aging Program (MAP). Methods: In this retrospective, cross-sectional diagnostic cohort study, we first developed P-tau217 cutoffs using site-specific training data and BioFINDER-2, which were then tested in potential DMT candidates from Butler MAP (total n = 150). ROC analysis was used to calculate the area under the curve (AUC) and accuracy of P-tau217 interpretation strategies, using Aß-PET/CSF testing as the standard of truth. Results: Potential DMT candidates at Butler MAP (n = 50), primarily diagnosed with mild cognitive impairment (n = 29 [58%]) or mild dementia (21 [42%]), were predominantly Aß-positive (38 [76%]), and half (25 [50%]) were subsequently treated with aducanumab. Elevated P-tau217 predicted cerebral Aß positivity in potential DMT candidates (AUC = 0.97 [0.92-1]), with diagnostic accuracy ranging from 0.88 (0.76-0.95, p = 0.028) to 0.96 (0.86-1, p < .001). When using site-specific cutoffs, a subset of DMT candidates (10%) exhibited borderline P-tau217 (between 0.273 and 0.399 pg/mL) that would have potentially required from confirmatory testing. Conclusions: This study, which included participants treated with aducanumab, confirms the utility of one- and two-cutoff strategies for interpreting plasma P-tau217 in assessing DMT eligibility. Using P-tau217 could potentially replace more invasive diagnostic methods, and all aducanumab-treated participants would have been deemed eligible based on P-tau217. However, false positives remain a concern, particularly when applying externally derived cutoffs that exhibited lower specificity which could have led to inappropriate treatment of Aß-negative participants. Future research should focus on prospective validation of P-tau217 cutoffs to enhance their generalizability and inform standardized treatment decision-making across diverse populations.

The effects of universal pre-K on cognitive development.

In this study of Oklahoma's universal pre-K program, the authors relied on a strict birthday eligibility criterion to compare "young" kindergarten children who just completed pre-K to "old" pre-K children just beginning pre-K. This regression-discontinuity design reduces the threat of selection bias. Their sample consisted of 1,567 pre-K children and 1,461 kindergarten children who had just completed pre-K. The authors estimated the impact of the pre-K treatment on Woodcock-Johnson Achievement test scores. The authors found test impacts of 3.00 points (0.79 of the standard deviation for the control group) for the Letter-Word Identification score, 1.86 points (0.64 of the standard deviation of the control group) for the Spelling score, and 1.94 points (0.38 of the standard deviation of the control group) for the Applied Problems score. Hispanic, Black, White, and Native American children all benefit from the program, as do children in diverse income brackets, as measured by school lunch eligibility status. The authors conclude that Oklahoma's universal pre-K program has succeeded in enhancing the school readiness of a diverse group of children.

Teenagers in the United States: sexual activity, contraceptive use, and childbearing, 2002.

OBJECTIVE: This report presents national estimates of sexual activity, contraceptive use, and births among males and females 15-19 years of age in the United States in 2002 from the National Survey of Family Growth (NSFG). Data are also presented from the 1988 and 1995 NSFGs, and from the 1988 and 1995 National Survey of Adolescent Males (NSAM). METHODS: Descriptive tables of numbers and percents are presented and interpreted. Data were collected through in-person interviews of the civilian noninstitutionalized population in the United States. Interviews were conducted with 7,643 females, 1,150 of whom were teenagers, and 4,928 males, 1,121 of whom were teenagers. RESULTS: In 2002, about 47 percent of female teenagers (4.6 million), and about 46 percent of male teenagers (4.7 million) had had sexual intercourse at least once. For never-married males, there was a significant decline from 55 percent in 1995 to 46 percent in 2002. Among never-married females, for those aged 15-17 there was a significant decline in the percent sexually experienced, and for those aged 18-19 there was no significant change. Teenagers showed increases in the use of contraceptives. About 3 out of 4 teens used a method of contraception at their first intercourse. About 91 percent of males and 83 percent of females used a method at their last (most recent) sex. Hispanic teens are most likely to have a birth before age 20 and non-Hispanic whites are least likely, with non-Hispanic black teens in the middle. CONCLUSION: This report documents findings that may be helpful in understanding trends in teen birth and pregnancy, and STD rates.