Objective: Sleep disturbance is common in dementia, although it is unclear whether differences in sleep architecture precede dementia onset. We examined the associations between sleep architecture and the prospective risk of incident dementia in the community-based Framingham Heart Study (FHS). Methods: Our sample comprised a subset of 321 FHS Offspring participants who participated in the Sleep Heart Health Study between 1995 and 1998 and who were aged over 60 years at the time of sleep assessment (mean age 67 ± 5 years, 50% male). Stages of sleep were quantified using home-based polysomnography. Participants were followed for a maximum of 19 years for incident dementia (mean follow-up 12 ± 5 years). Results: We observed 32 cases of incident dementia; 24 were consistent with Alzheimer disease dementia. After adjustments for age and sex, lower REM sleep percentage and longer REM sleep latency were both associated with a higher risk of incident dementia. Each percentage reduction in REM sleep was associated with approximately a 9% increase in the risk of incident dementia (hazard ratio 0.91; 95% confidence interval 0.86, 0.97). The magnitude of association between REM sleep percentage and dementia was similar following adjustments for multiple covariates including vascular risk factors, depressive symptoms, and medication use, following exclusions for persons with mild cognitive impairment at baseline and following exclusions for early converters to dementia. Stages of non-REM sleep were not associated with dementia risk. Conclusions: Despite contemporary interest in slow-wave sleep and dementia pathology, our findings implicate REM sleep mechanisms as predictors of clinical dementia.

Background: Age-adjusted stroke incidence has decreased over the past 50 years, likely as a result of changes in the prevalence and impact of various stroke risk factors. An updated version of the Framingham Stroke Risk Profile (FSRP) might better predict current risks in the FHS (Framingham Heart Study) and other cohorts. We compared the accuracy of the standard (old) and of a revised (new) version of the FSRP in predicting the risk of all-stroke and ischemic stroke and validated this new FSRP in 2 external cohorts, the 3C (3 Cities) and REGARDS (Reasons for Geographic and Racial Differences in Stroke) studies. Methods: We computed the old FSRP as originally described and a new model that used the most recent epoch-specific risk factor prevalence and hazard ratios for individuals ≥55 years of age and for the subsample ≥65 years of age (to match the age range in REGARDS and 3C studies, respectively) and compared the efficacy of these models in predicting 5- and 10-year stroke risks. Results: The new FSRP was a better predictor of current stroke risks in all 3 samples than the old FSRP (calibration χ ² of new/old FSRP: in men: 64.0/12.1, 59.4/30.6, and 20.7/12.5; in women: 42.5/4.1, 115.4/90.3, and 9.8/6.5 in FHS, REGARDS, and 3C, respectively). In the REGARDS, the new FSRP was a better predictor among whites compared with blacks. Conclusions: A more contemporaneous, new FSRP better predicts current risks in 3 large community samples and could serve as the basis for examining geographic and racial differences in stroke risk and the incremental diagnostic utility of novel stroke risk factors.

The discovery of minimally invasive and cost-effective blood-based biomarkers for dementia has the potential to transform clinical research and practice by permitting widespread low-cost screening, risk stratification, and efficient identification of persons with the greatest dementia risk for inclusion in dementia prevention trials. Single-molecule array technology permits the detection of total tau (t-tau) from plasma with a greater than 1000-fold improvement in sensitivity over conventional enzyme-linked immunosorbent assay (ELISA).^1,2 Plasma t-tau level measured with this technology is greater in persons with Alzheimer disease (AD) dementia or mild cognitive impairment (MCI) compared with control participants.^3-5 However, the usefulness of plasma t-tau as a diagnostic biomarker is limited by the large overlap in values observed between diagnostic groups, which may signal a lack of specificity for AD. The latest National Institute on Aging–Alzheimer Association Research Framework (NIA-AA) describes t-tau as a biomarker of neuronal injury rather than of neurofibrillary tangle burden, noting that an elevated t-tau level reflects neuronal injury from various causes.⁶ Nevertheless, plasma t-tau shows early promise as a predictive biomarker for dementia with 2 longitudinal studies demonstrating that plasma t-tau is associated with endophenotypes of dementia, including cognitive decline.^7,8 However, evidence from representative community-based studies is limited, and studies to date have not been powered to examine the association with risk for dementia. Further studies are required to evaluate plasma t-tau as a predictive biomarker for incident dementia, permitting risk stratification in the setting where blood-based biomarkers would be most useful—in the general community and the age groups of relevance to early dementia prevention trials. Accordingly, we examined the association of plasma t-tau level as a predictive biomarker for dementia of any cause (all dementia) and incident dementia of the Alzheimer type (AD dementia) in the large community-based Framingham Heart Study (FHS), with replication performed in an independent multicenter cohort from France. We also examined endophenotypes associated with dementia, including cognitive function, hippocampal volume, and tau neurofibrillary tangle burden.

Background and Purpose—: Sugar- and artificially-sweetened beverage intake have been linked to cardiometabolic risk factors, which increase the risk of cerebrovascular disease and dementia. We examined whether sugar- or artificially sweetened beverage consumption was associated with the prospective risks of incident stroke or dementia in the community-based Framingham Heart Study Offspring cohort. Methods—: We studied 2888 participants aged >45 years for incident stroke (mean age 62 [SD, 9] years; 45% men) and 1484 participants aged >60 years for incident dementia (mean age 69 [SD, 6] years; 46% men). Beverage intake was quantified using a food-frequency questionnaire at cohort examinations 5 (1991–1995), 6 (1995–1998), and 7 (1998–2001). We quantified recent consumption at examination 7 and cumulative consumption by averaging across examinations. Surveillance for incident events commenced at examination 7 and continued for 10 years. We observed 97 cases of incident stroke (82 ischemic) and 81 cases of incident dementia (63 consistent with Alzheimer’s disease). Results—: After adjustments for age, sex, education (for analysis of dementia), caloric intake, diet quality, physical activity, and smoking, higher recent and higher cumulative intake of artificially sweetened soft drinks were associated with an increased risk of ischemic stroke, all-cause dementia, and Alzheimer’s disease dementia. When comparing daily cumulative intake to 0 per week (reference), the hazard ratios were 2.96 (95% confidence interval, 1.26–6.97) for ischemic stroke and 2.89 (95% confidence interval, 1.18–7.07) for Alzheimer’s disease. Sugar-sweetened beverages were not associated with stroke or dementia. Conclusions—: Artificially sweetened soft drink consumption was associated with a higher risk of stroke and dementia.

Background: A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort. Methods: This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups. Results: Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140–720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51–1.73]; P =0.84), death (aHR, 0.78 [95% CI, 0.22–2.76]; P =0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48–1.73]; P =0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15–0.82]; P =0.02). Conclusions: In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies.