Publications

BackgroundPatients with Alzheimer's disease and related dementias (ADRD) have an increased risk for delirium and subsequent complications. Rating delirium severity in the presence of co-occurring dementia is challenging due to overlapping features of delirium and ADRD. The multi-site prospective Better ASsessment of ILlness (BASIL)-II study will develop and validate a new delirium severity instrument for use in patients with and without ADRD.ObjectiveDescribe an expert panel process used to rate delirium severity.MethodsClinical assessors conducted standardized cognitive tests. A separate panel of experts independently reviewed assessors' reports, rated delirium severity using a 0-10 scale, and assigned dementia diagnoses using DSM-5 criteria. Panel agreement was defined using a priori criteria. Cases without agreement after initial review were discussed as a group and re-rated using a modified Delphi approach until achieving consensus.ResultsPatients (N = 488) were on average 79 years old, 58% female, and 75% White. After initial review, 80% of cases were in agreement for delirium severity. Kappa was 0.86 (95% CI, 0.78, 0.82) before expert panel discussion and 0.90 (95%CI, 0.89, 0.92) after consensus. Final delirium severity ratings were no delirium (48%); subsyndromal (22%), mild-moderate (25%), or severe (6%). Disagreement in delirium severity was associated with ADRD (OR 3.02), nursing home setting (2.63), and vision impairment (2.42).ConclusionsThis rigorous process provides confidence that delirium severity can be rated accurately in patients with and without ADRD. We will use this expert panel adjudication to provide the reference standard for validation of a future delirium severity instrument.

IMPORTANCE: There is limited research on the long-term associations of plasma phosphorylated tau 217 (p-tau217) with mild cognitive impairment (MCI) and dementia. No study has evaluated whether such associations vary by race or hormone therapy (HT) use.

OBJECTIVE: To examine associations of baseline plasma p-tau217 with incident MCI and dementia and determine whether associations vary by age, race, APOE ε4 carrier status, or HT use.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined women recruited from 39 US clinical sites between 1996 and 1999 into the Women's Health Initiative Memory Study who were randomized to either estrogen alone vs placebo or estrogen plus progestin vs placebo. Women were assessed for up to 25 years through 2021. Baseline plasma p-tau217 was measured in 2024 and analyzed between February and August 2025. Women aged 65 to 79 years who were cognitively unimpaired at baseline were included for this analysis.

EXPOSURE: Plasma p-tau217, quantified using the ALZpath Simoa assay.

MAIN OUTCOMES AND MEASURES: The primary outcome was the combined end point of incident MCI or probable dementia. Secondary outcomes included MCI and dementia examined separately. Cause-specific hazard ratios (HRs) and 95% CIs for the association of p-tau217 with MCI or dementia were estimated using Cox proportional hazards regression models.

RESULTS: Among 2766 participants (mean [SD] age, 69.9 [3.8] years; 486 [17.9%] Black, 196 [7.1%] Hispanic, and 2007 [73.9%] White), 1311 developed the combined end point of MCI or dementia (849 participants with MCI and 752 participants with dementia). Every 1-SD increase in log2-transformed p-tau217 was associated with incident MCI or dementia (HR, 2.43; 95% CI, 2.18-2.71) and each individual outcome (MCI: HR, 1.94; 95% CI, 1.72-2.20; dementia: HR, 3.17; 95% CI, 2.79-3.61). Associations of p-tau217 with dementia were larger in magnitude for women randomized to estrogen plus progestin (HR, 4.18; 95% CI, 3.41-5.13) vs placebo (HR, 3.07; 95% CI, 2.41-3.91) (P for interaction = .04) but did not significantly vary by estrogen alone vs placebo. P-tau217 associations with MCI or dementia were larger in magnitude for women older than 70 years (P for interaction = .04), APOE ε4 carriers (P for interaction = .02), and White women compared with Black women (P for interaction < .001). However, the combination of p-tau217 and age performed similarly in White women (area under the curve = 72.0%; 95% CI, 70.3%-73.6%) and Black women (area under the curve = 70.4%; 95% CI, 64.0%-78.0%). P-tau217 was not associated with incident MCI in Black women.

CONCLUSIONS AND RELEVANCE: In this cohort study of cognitively unimpaired older women, p-tau217 was associated with incident MCI or dementia up to 25 years later. These findings suggest that age, race, APOE ε4, and HT use should be considered when examining associations of p-tau217 with cognitive outcomes.

UNLABELLED: Background. The use of colorectal cancer (CRC) screening decision aids (DAs) increases patient knowledge and engagement in decision making. Thus, we aimed to implement a CRC DA in a Boston-area health system informed by the Theory of Change quality improvement framework. Methods. Following international standards, an interdisciplinary working group developed a 2-page CRC screening DA, readable on smartphones, for adults ages 45 to 75 y. Prior to DA implementation, we texted a study survey to 8,641 adults age 45 to 75 y seen in primary care at our health system (baseline). Between January 2022 and April 2023, we texted the DA to 21,522 patients due for CRC screening and scheduled with their primary care provider (PCP). In August 2022 and in May 2023 (follow-up), we texted a study survey to patients who had been texted the DA in prior months. We used linear regression to examine the DA's effects on shared decision-making (SDM) quality (using the 4-item SDM Process Scale, for which scores range from 0-4), knowledge (2 questions), and reported discussions with PCPs of screening modalities. Results. Of 30,163 texted study surveys, 1,692 (5.6%, 697 baseline and 995 follow-up) were completed; 77.1% of participants were non-Hispanic White and 45.3% were aged 60 to 75 y. Overall, 30.6% (n = 304) of follow-up survey respondents reported reviewing the DA. Compared with baseline participants, these patients reported higher SDM quality (SDM process scores = 2.5 v. 2.1, P < 0.001) and more knowledge about CRC screening and were more likely to have discussed stool-based testing with PCPs. Limitations. Low response rate with no sociodemographic data for nonresponders. Conclusions/Implications. Patients who read a CRC screening DA texted to them before primary care visits may experience improved SDM quality. However, a more intensive implementation strategy may be needed for more patients to read DAs.

HIGHLIGHTS: It is feasible for large health systems to automatize text messaging of colorectal cancer (CRC) screening decision aids (DAs) to patients due for CRC screening before a visit with their primary care practitioner.Patients who review a texted CRC screening DA report higher shared decision-making quality and knowledge about CRC screening.Use of CRC DAs may decrease screening via colonoscopy but not overall screening rates.A more intensive intervention than text messaging is likely needed to increase the number of patients who review a CRC screening DA.

BACKGROUND: Resistant hypertension is associated with adverse cardiovascular outcomes and mortality. In the past decade, management guidelines have shifted to target lower blood pressures (BP). Current prevalence and prescribing patterns among adults with resistant hypertension are not well characterized.

METHODS: We used data from the National Health and Nutrition Examination Survey from 2003 to 2020. Apparent treatment-resistant hypertension (aTRH) was defined as patients on a diuretic, either with a systolic BP ≥130 or diastolic BP ≥80 mm Hg while on 3 medications or those on ≥4 medications regardless of BP. Medications were identified through pill bottle review.

RESULTS: Of 24 579 adults with hypertension, 1939 had aTRH (42.4% male, 19.9% Black), corresponding to a weighted total of 6 989 821 US patients. Among hypertensive adults, the prevalence of aTRH was 6.41% (95% CI, 5.97%-6.88%) and remained stable over time. Over the study duration, aTRH prevalence among adults on treatment decreased from 17.7% to 12.6%. The overall prevalence of hypertension rose from 50.1% to 54.0%, while the prevalence of uncontrolled BP decreased from 75.0% to 68.7%. Over time, use of 3 drug regimens for aTRH decreased (57.8%-42.9%), while 4 drug regimens increased (34.0%-51.8%). aTRH was most strongly associated with older patients, those of Black race, higher body mass index, and more advanced cardiovascular comorbidities.

CONCLUSION: The prevalence of aTRH has remained stable over the past 2 decades despite the rising incidence of hypertension. Use of multidrug treatment regimens has increased, aligning with national guidelines. However, uncontrolled hypertension remains high.

BACKGROUND: Low-carbohydrate diet (LCD) and low-fat diet (LFD) patterns are practiced by many in the United States, although their health effects, as well as the role of diet quality in the effects, are not fully understood.

OBJECTIVES: This study aimed to prospectively examine the associations of these diets, which emphasize different quantities and qualities of macronutrients, as well as their objective metabolomic indices, with coronary heart disease (CHD) risk in U.S.

METHODS: We followed 42,720 men in the Health Professionals Follow-Up Study (HPFS) (1986-2016), 64,164 women in the Nurses' Health Study (NHS) (1986-2018), and 91,589 women in NHSII (1991-2019) for CHD incidence. Five LCD and 5 LFD indices were derived based on food frequency questionnaire (FFQ) assessments, each emphasizing different sources and qualities of macronutrients (animal products vs plant-based foods, whole grains vs refined carbohydrates, etc). Multimetabolite scores of LCD and LFD indices assessed using FFQ assessments were developed through elastic net regressions among 1,146 healthy participants in the lifestyle validation studies (LVS), substudies embedded in the NHS/NHSII/HPFS.

RESULTS: During 5,248,916 person-years of follow-up, we documented 20,033 CHD cases. When comparing individuals with the highest LCD scores (emphasizing lower carbohydrate contents) and those with the lowest, the pooled multivariable-adjusted hazard ratios (95% CIs) for CHD were 1.05 (1.01-1.10) for overall LCD, 1.07 (1.02-1.12) for animal LCD, 0.94 (0.90-0.99) for vegetable LCD, 1.14 (1.09-1.20) for unhealthy LCD, and 0.85 (0.82-0.89) for healthy LCD. These estimates were 0.93 (0.89-0.98) for overall LFD, 0.94 (0.90-0.98) for animal LFD, 0.87 (0.83-0.91) for vegetable LFD, 1.12 (1.07-1.17) for unhealthy LFD, and 0.87 (0.83-0.91) for healthy LFD. The healthy versions of the LCD and LFD patterns were also linked to lower triglycerides, higher high-density lipoprotein cholesterol, and lower high-sensitivity C-reactive protein levels, as well as favorable metabolomic profiles, including increased 3-indolepropionic acid and decreased valine. Unhealthy patterns showed opposite associations. Multimetabolite scores of LCD and LFD indices were developed in the LVS (Spearman r = 0.57-0.68) and replicated in NHS, NHSII, and HPFS (r = 0.21-0.38). They showed associations with CHD risk highly consistent with those based on FFQ assessments.

CONCLUSIONS: These findings highlight the critical role of diet quality in determining health effects of low-carbohydrate and low-fat diets on CHD risk. The healthy versions of these diets may exert their health benefits through some common pathways that together entail favorable cardiovascular risk profile and lower CHD risk.

BACKGROUND: Home blood pressure (BP) monitoring (HBPM) is increasingly used as an alternative to office BP. However, factors influencing agreement between office and home BP among very old adults remain unclear.

METHODS: During ARIC (Atherosclerosis Risk in Communities) visit 10, participants underwent 3 automated office BP (AOBP) measurements using an Omron HEM-907XL and performed HBPM twice daily for 8 days using an Omron BP7450. Discordance was defined as a systolic BP difference of ±10 mm Hg between mean AOBP and HBPM. Multivariable regression models evaluated demographic, anthropometric, and clinical factors associated with discordance.

RESULTS: Among 792 participants (58% female; mean age, 84±3.7 years), mean systolic BP was 130.6 mm Hg (AOBP) and 129.6 mm Hg (HBPM). Despite a minimal average difference (1.0±15.7 mm Hg), 49% had ≥10 mm Hg systolic BP discordance. Higher AOBP was associated with greater discordance. Compared with females, males had lower AOBP relative to HBPM (-4.69 mm Hg [95% CI, -6.86 to -2.51]). Smaller arm circumference was associated with higher discordance (β=14.4 mm Hg [95% CI, 4.78-24.04]). Frail adults had lower AOBP relative to HBPM (β, -5.1 mm Hg [95% CI, -11.0 to 0.9]). Baseline AOBP systolic BP ≥140 mm Hg strongly predicted discordance ≥+10 mm Hg (odds ratio, 8.27 [95% CI, 5.52-12.40]). Participants aged 91 to 100 years had lower AOBP than those aged 78 to 80 years (β, -5.0 mm Hg [95% CI, -10.06 to 0.001]).

CONCLUSIONS: Among very old adults, substantial BP discordance between AOBP and HBPM was common and influenced by higher BP, age, male sex, arm circumference, and frailty.