Publications

BACKGROUND: Serum neurofilament light chain (NfL) is a biomarker of brain injury. We examined the associations of serum NfL concentration with able life and healthy life among older adults.

METHODS: We analyzed Cardiovascular Health Study participants with measured NfL and no history of stroke or transient ischemic attack (TIA). Over 13 years' follow-up, outcomes were years of life (YOL), years of able life (YAL), years of healthy life (YHL), and proportion of follow-up spent able (YAL/YOL%) or healthy (YHL/YOL%). "Able" was defined by independence in all activities of daily living, and "healthy" was defined by self-reported health status. Linear regression and linear spline regression models were used to estimate the difference in each outcome associated with a 50% increment in serum NfL, an increment within the range of the observed data.

RESULTS: Among 1957 participants (mean age 77.8; 61% female), in the adjusted linear model, each 50% increment in NfL was associated with 0.6 fewer YOL (95% CI: -0.7, -0.4), 0.7 fewer YAL (-0.8, -0.5), 0.5 fewer YHL (-0.7, -0.4), 2.9% lower YAL/YOL% (-4.0%, -1.7%) and 1.8% lower YHL/YOL% (-3.1%, -0.6%). Spline analysis showed the strongest associations at NfL of 19.7-33.9 pg/mL, where each 50% increment in NfL was associated with 6.5% lower YAL/YOL% (-9.4%, -3.6%) and 5.6% lower YHL/YOL% (-8.8%, -2.4%).

CONCLUSIONS: Higher serum NfL concentration was associated with less able and healthy life among older adults free of stroke or TIA. Further investigation of NfL, including longitudinal evaluation, is needed to understand its relationship with functional status.

BACKGROUND AND AIMS: Clinical trials using freeze-dried blueberries on measures of cognition or serum brain biomarkers are sparse or lacking. Our primary aim was to test whether an intervention with freeze-dried blueberries reduces serum phosphorylated tau (p-tau181) and neurofilament light (NFL). Secondary outcomes included serum non-esterified fatty acids, glial fibrillary acidic protein (GFAP), blood pressure, and computer-based cognitive tests.

METHODS: This was a randomized double-blind trial where 57 cognitively healthy subjects were assigned either 20 g/d of freeze-dried blueberry powder or matching placebo for 24 weeks. We collected blood samples for biomarker measurements and administered cognitive tests during each of the four study visits spaced by 8 weeks.

RESULTS: Mean (SD) age at baseline was 73.5 (6.6) years among 28 subjects randomized to blueberry powder and 73.3 (5.2) years among 29 subjects assigned to placebo. There was no statistically significant difference in change over time in serum p-tau181 [i.e., baseline and 24-week adjusted mean (95% CI) were 38.5 (21.3-55.7) and 38.9 (21.7-56.1) pg/mL in the placebo group versus 47.2 (28.9-65.5) and 54.7 (36.3-73.0) pg/mL in the blueberry group] (p for interaction between biomarker and time: 0.10)] or serum NFL [i.e., corresponding values were 26.2 (18.2-34.1) and 25.0 (17.1-33.0) pg/mL in the placebo group and 26.6 (18.2-35.0) and 28.0 (19.5-36.5) pg/mL in the blueberry group, p for interaction 0.58]. In secondary aims, blueberry intervention reduced diastolic blood pressure (p interaction with time 0.015) but there was no effect on systolic blood pressure, cognitive tests, and other biomarkers.

CONCLUSION: A 24-week intervention with freeze-dried blueberries had no effect on serum p-tau181 and serum NFL in older adults.

TRIAL REGISTRATION: NCT05764824, https://clinicaltrials.gov/study/NCT05764824.

IMPORTANCE: Postoperative delirium is associated with long-term cognitive decline in older adults. This might be caused by the delirium itself or because delirium is more common in persons who are ill and frail, and these conditions are also associated with cognitive decline.

OBJECTIVE: To determine whether cognitive decline associated with postoperative delirium is mediated by illness and frailty, as measured by recurrent hospitalizations.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included community-dwelling older adults (age ≥70 years), enrolled from June 2010 to August 2013 with 5 years of follow-up data in the ongoing Successful Aging after Elective Surgery longitudinal study. Data were analyzed from November 2022 to May 2026.

EXPOSURES: Incident delirium following major elective surgery, with and without rehospitalizations, combined and by type (rehospitalization alone, rehospitalization with intensive care unit stay, rehospitalization with postacute care stay).

MAIN OUTCOMES AND MEASURES: The main outcome was long-term cognitive decline, measured as change in General Cognitive Performance (GCP) score, a composite measure of 11 neuropsychological tests, between preoperative baseline and 10 repeated assessments over 5 years.

RESULTS: In the cohort of 560 older adults (mean [SD] age, 76.7 [5.2] years; 326 female [58%]), the mean (SD) GCP score at baseline was 57.6 (7.3). Each rehospitalization was associated with a decline of -0.19 (95% CI, -0.31 to -0.09) GCP units per year. Delirium was associated with more marked cognitive decline of -0.33 (95% CI, -0.67 to -0.06) GCP units per year. Rehospitalizations were more common among patients who developed delirium (adjusted incidence rate ratio, 1.42 [95% CI, 1.17 to 1.72]). However, adjustment for combined rehospitalizations and for each type of rehospitalization resulted in only a minimal percentage change that was not statistically significant (-6% to -9%) in the association of delirium with cognitive decline.

CONCLUSIONS AND RELEVANCE: In this cohort study, contrary to expectations, rehospitalization did not mediate the association between delirium and long-term cognitive decline. Future work will be needed to elucidate the pathways by which delirium is associated with long-term cognitive decline.

BACKGROUND: Blood pressure (BP), autonomic function and atherosclerosis are associated with adverse bone-related outcomes. These entities may affect blood pressure variability (BPV). The few studies that have directly investigated the association of BPV with hip fracture or bone mineral density (BMD) were limited to Asian populations and reported few BPV measures.

METHODS: Individuals with BP measurements at ≥4 of the 6 Cardiovascular Health Study (CHS), a large, prospective, observational cohort, visits between 1989 and 90 and 1994-95 and who attended the 1994-95 visit were included. Systolic (SBP), diastolic (DBP) and pulse pressure (PP) variability were estimated as: between-visit mean, between-visit slope (linear trajectory over time) and between-visit standard deviation (SD) of the observed residuals (departure from linear trajectory). Incident hip fractures between 1994 and 95 and 2015 were recorded. The association of BPV with hip fracture was estimated with Cox models (95% confidence intervals, CI). Primary analyses were conducted in individuals not using BP-lowering medications at baseline. Secondary analyses were conducted in those with stable use of BP-lowering medications during look back. Total hip BMD was measured at the 1994-95 study visit in a subset of individuals and analysed for cross-sectional associations with BPV.

RESULTS: Among 1820 individuals not using BP-lowering medications at baseline (60% women; age 76 ± 5 years), 292 incident hip fractures (222 women, 70 men) occurred. After multivariable adjustment, a one SD increase (3.12 mmHg) in DBP residual was associated with an 8.9% increased relative risk (95%CI, 0.4% to 18.2%) in men only. No other BPV measures were associated with hip fractures in men or women. No BPV measure was associated with BMD. Among 1958 individuals with stable BP medication use, 297 incident hip fractures (229 women, 68 men) occurred. In this group, no BPV measure was associated with incident hip fracture or BMD.

CONCLUSION: We found no consistent association of BPV with BMD or hip fracture, which did not validate results from prior studies. Low BPV in this cohort may have limited our ability to identify associations with adverse skeletal outcomes but also may reflect limited clinical importance of BPV for bone.

Hypertension is the most diagnosed condition among adults aged 60 years and older and is a major contributor to morbidity and mortality. In this article, we review current evidence on blood pressure evaluation and management in this population. We incorporate the geriatrics "5 Ms" framework, which includes 5 domains pertinent to geriatrics care. We compare the most recent society guidelines on hypertension management among older adults and discuss both resistant hypertension and deprescribing. This review is meant to equip geriatricians with evidence and resources to inform their approach to hypertension screening and management among older adults.

BACKGROUND: Orthostatic hypotension is thought to be associated with coronary heart disease, falls, and syncope due to low blood pressure (BP) upon standing.

METHODS: The ARIC (Atherosclerosis Risk in Communities) study measured supine and standing BP among adult participants aged 45 to 64 years once at baseline and followed them for over 35 years. We evaluated higher and lower supine and standing systolic BP, diastolic BP, mean arterial pressure, pulse pressure, absolute and relative orthostatic changes in BP after standing, and mean BP across positions. Associations with adjudicated coronary heart disease and mortality events, as well as hospitalizations and medical claims-based falls and syncope, were assessed via adjusted Cox models in strata of antihypertensive treatment.

RESULTS: Among 11 386 participants (mean age, 54 years [SD, 5.7 years]; 56% female; 25% Black adults), drops in systolic BP upon standing (absolute or relative) were associated with coronary heart disease, syncope, and mortality. Higher supine systolic BP and mean arterial pressure were associated with syncope among untreated participants. Increases in systolic BP ≥20 mm Hg upon standing were associated with falls (hazard ratio, 1.52 [95% CI, 1.14-2.02]) and syncope (hazard ratio, 1.40 [95% CI, 1.03-1.92]), particularly among untreated participants. Lower standing systolic BP was associated with a higher risk of syncope among treated participants (hazard ratio, 1.55 [95% CI, 1.14-2.12]). Regardless of treatment status, a higher pulse pressure was associated with coronary heart disease and mortality, but this was not observed for falls or syncope.

CONCLUSIONS: Higher BP, rather than lower standing BP alone, may be an important risk factor for both cardiovascular and hypotension-related events, especially among untreated adults.

OBJECTIVE: Studies and settings designed to identify incident cases of dementia can take advantage of imaging, biomarkers, and specialist clinicians to aid in diagnosis. This is not always feasible for large cohort studies.

DESIGN SETTING AND PARTICIPANTS: The Successful AGing after Elective Surgery (SAGES) study is a long-term, observational study of 560 community-dwelling adults aged ≥70, with serial neuropsychological assessments completed up to 72 months postsurgery.

MEASUREMENT: Mild cognitive impairment (MCI) and dementia diagnoses were determined retrospectively using a rigorous multimodal approach with nested subsamples. This included 1) an expert panel consensus based on serial neuropsychological testing in all participants; 2) diagnosis based on chart review in a subsample of participants; and 3) an in-person neurologist examination in a subsample. An expert adjudication panel then used a Delphi approach to assign research diagnoses incorporating information from all available modalities.

RESULTS: During 72 months of follow-up, 63 incident cases of MCI (11.3%) and four cases of dementia (0.7%) were identified. The most frequent multimodal approach involved combined expert panel consensus and chart review in 41% of MCI (n = 26) diagnoses. Twelve MCI (19%) and three dementia (75%) diagnoses used all three modalities. Eight cases (12%) were diagnosed by a single modality. Diagnostic confidence considered both number and type of information sources used, for example, if agreement by more than one source, or diagnosis only by an in-person exam with a neurologist. Of the 63 MCI and four dementia diagnoses, the expert panel rated their confidence as moderate in four cases (all were MCI) and high in the remaining 63 cases (4 dementia and 59 MCI).

CONCLUSIONS: A novel approach that integrates multiple sources of information and a robust adjudication process to determine incident MCI and dementia in a long-term cohort study may be useful for research applications. Such an approach may be useful when access to expert specialists, biomarkers, advanced neuroimaging and other diagnostic tests may be limited.

PURPOSE: (1) To describe cognitive trajectory patterns over 6 years after major surgery in older adults, and (2) To identify patient characteristics associated with severe cognitive decline.

METHODS: Group-based semiparametric trajectory modeling was performed on longitudinal cognitive data from the SAGES study, which enrolled patients aged ≥ 70 years undergoing major elective noncardiac surgery. Participants received comprehensive neuropsychological testing prior to surgery and postoperatively every 6-12 months up to 72 months. The primary outcome was change in general cognitive performance score, a composite of neuropsychological tests, at each of 11 follow-up timepoints relative to baseline. Generalized linear models were used to assess the associations of pre-surgical patient characteristics and incidence of postoperative delirium with cognitive trajectory.

RESULTS: Of 560 participants, 326 were women (58%) and the average age was 76.7 (standard deviation 5.2) years. They underwent orthopedic (81%), gastrointestinal (13%), and vascular surgeries (6%), and 24% experienced postoperative delirium. We found the 3-group cognitive trajectory model to be optimal, with the groups characterized as severe decline trajectory (SDT) (15% of the cohort), slight decline (59%), or stable (26%). Of pre-surgical factors, age (relative risk [RR]: 1.06, 95% confidence interval [CI] 1.03-1.10 per 1 year increase) and 3MS (Modified-Mini-Mental) score (RR 0.95, 95% CI 0.92-0.99 per one point increase) were significantly associated with SDT. Participants who developed delirium had over two-fold higher risk of SDT compared to those who did not (RR: 2.15, 95% CI: 1.35-3.42).

CONCLUSIONS: Among older adults undergoing major surgery, 15% experienced severe cognitive decline over the ensuing 6 years, 59% experienced slight decline, and 26% remained stable. Older age, baseline cognitive impairment, and delirium were associated with severe decline, with delirium having the strongest association. Our findings provide valuable information for older patients considering major surgery and may help clinicians target interventions.

Wearable technologies have the potential to transform ambulatory and at-home hemodynamic monitoring by providing continuous assessments of cardiovascular health metrics and guiding clinical management. However, existing cuffless wearable devices for blood pressure (BP) monitoring often rely on methods lacking theoretical foundations, such as pulse wave analysis or pulse arrival time, making them vulnerable to physiological and experimental confounders that undermine their accuracy and clinical utility. Here, we developed a smartwatch device with real-time electrical bioimpedance (BioZ) sensing for cuffless hemodynamic monitoring. We elucidate the biophysical relationship between BioZ and BP via a multiscale analytical and computational modeling framework, and identify physiological, anatomical, and experimental parameters that influence the pulsatile BioZ signal at the wrist. A signal-tagged physics-informed neural network incorporating fluid dynamics principles enables estimation of BP and radial and axial blood velocity. We successfully tested our approach with healthy individuals at rest and after physical activity including physical and autonomic challenges, and with patients with hypertension and cardiovascular disease in outpatient and intensive care settings. Our findings demonstrate the feasibility of BioZ technology for cuffless BP and blood velocity monitoring, addressing critical limitations of existing cuffless technologies.