Relationship Between Sarcopenia and Intensive Blood Pressure Control Efficacy and Safety: A Secondary Analysis of SPRINT.

BACKGROUND: Sarcopenia and hypertension are independently associated with worse cardiovascular disease (CVD) risk and survival. While individuals with sarcopenia may benefit from intensive blood pressure (BP) control, the increased vulnerability of this population raises concerns for potential harm. This study aimed to evaluate clinical and safety outcomes with intensive (target <120 mm Hg) versus standard (<140 mm Hg) systolic BP targets in older hypertensive adults with sarcopenia compared with nonsarcopenic counterparts in the SPRINT (Systolic Blood Pressure Intervention Trial). METHODS: Sarcopenia was defined using surrogates of the lowest sex-stratified median of the sarcopenia index (serum creatinine/cystatin C×100) for muscle wasting and gait speed ≤0.8 m/s for muscle weakness. Outcomes included CVD events, all-cause mortality, and serious adverse events. RESULTS: Of 2571 SPRINT participants with sarcopenia index and gait speed data available (aged ≥75 years), 502 (19.5%) met the criteria for sarcopenia, which was associated with higher risks of CVD events (adjusted hazard ratio, 1.49 [95% CI, 1.15-1.94]; P=0.003) and all-cause mortality (adjusted hazard ratio, 1.46 [95% CI, 1.09-1.94]; P=0.010). In participants with sarcopenia, intensive (versus standard) BP control nearly halved the risk of CVD events (adjusted hazard ratio, 0.57 [95% CI, 0.36-0.88]; P=0.012) without increasing serious adverse events. Similar risk reduction was seen for all-cause mortality in participants with sarcopenia (adjusted hazard ratio, 0.66 [95% CI, 0.41-1.08]; P=0.102), but the effect was only significant in those without chronic kidney disease. CONCLUSIONS: Older hypertensive adults with sarcopenia randomized to intensive BP control experienced a lower risk of CVD without increased adverse events compared with standard BP control. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

The impact of incident stroke on cognitive trajectories in later life.

BACKGROUND: Cognitive impairment is common after stroke, and a large proportion of stroke patients will develop dementia. However, there have been few large prospective studies which have assessed cognition both prior to and after stroke. This study aims to determine the extent to which incident stroke impacts different domains of cognitive function in a longitudinal cohort of older community-dwelling individuals. METHODS: 19,114 older individuals without cardiovascular disease or major cognitive impairment were recruited and followed over a maximum 11 years. Stroke included ischaemic and haemorrhagic stroke and was adjudicated by experts. Cognitive function was assessed regularly using Modified Mini-Mental State Examination (3MS), Hopkins Verbal Learning Test-Revised (HVLT-R), Symbol Digit Modalities Test (SDMT), and Controlled Oral Word Association Test (COWAT). Linear mixed models were used to investigate the change in cognition at the time of stroke and decline in cognitive trajectories following incident stroke. RESULTS: During a median follow-up period of 8.4 [IQR: 7.2, 9.6] years, 815 (4.3%) participants experienced a stroke. Over this time, there was a general decline observed in 3MS, HVLT-R delayed recall, and SDMT scores across participants. However, for individuals who experienced a stroke, there was a significantly greater decline across all cognitive domains immediately after the event immediately after the event (3MS: -1.03 [95%CI: -1.45, -0.60]; HVLT-R: -0.47 [-0.70, -0.24]; SDMT: -2.82 [-3.57, -2.08]; COWAT: -0.67 [-1.04, -0.29]) and a steeper long-term decline for three of these domains (3MS -0.62 [-0.88, -0.35]; COWAT: -0.30 [-0.46, -0.14]); HVLT-R: -0.12 [95%CI, -0.70, -0.24]). However individuals with stroke experienced no longer-term decline in SDMT compared to the rest of the participants. CONCLUSIONS: These findings highlight the need for comprehensive neuropsychology assessments for ongoing monitoring of cognition following incident stroke; and potential early intervention.

Intensive Blood Pressure Treatment and Subclinical Brain Infarcts: A Secondary Analysis of SPRINT (Systolic Pressure Intervention Trial).

OBJECTIVE: Subclinical brain infarcts (SBI) increase the risk for stroke and dementia, but whether they should be considered equivalent to symptomatic stroke when determining blood pressure targets remains unclear. We tested whether intensive systolic blood pressure (SBP) treatment reduced the risk of new SBI or stroke and determined the association between SBI and cognitive impairment. METHODS: In this secondary analysis of SPRINT (Systolic Pressure Intervention Trial), participants ≥50 years old, with SBP 130-180mmHg and elevated cardiovascular risk but without known clinical stroke, dementia, or diabetes, were randomized to intensive (<120mmHg) or standard (<140mmHg) SBP treatment. Brain magnetic resonance images collected at baseline and follow-up were read for SBI. The occurrence of mild cognitive impairment (MCI) or probable dementia (PD) was evaluated. RESULTS: For 667 participants at baseline, SBI were identified in 75 (11%). At median 3.9 years follow-up, 12 of 457 had new SBI on magnetic resonance imaging (5 intensive, 7 standard), whereas 8 had clinical stroke (4 per group). Baseline SBI (subhazard ratio [sHR] = 3.90; 95% CI 1.49 to 10.24; p = 0.006), but not treatment group, was associated with new SBI or stroke. For participants with baseline SBI, intensive treatment reduced their risk for recurrent SBI or stroke (sHR = 0.050; 95% CI 0.0031 to 0.79; p = 0.033). Baseline SBI also increased risk for MCI or PD during follow-up (sHR = 2.38; 95% CI 1.23 to 4.61; p = 0.010). INTERPRETATION: New cerebral ischemic events were infrequent, but intensive treatment mitigated the increased risk for participants with baseline SBI, indicating primary prevention SBP goals are still appropriate when SBI are present. ANN NEUROL 2024;95:866-875.

The dementia care study (D-CARE): Recruitment strategies and demographic characteristics of participants in a pragmatic randomized trial of dementia care.

INTRODUCTION: Pragmatic research studies that include diverse dyads of persons living with dementia (PLWD) and their family caregivers are rare. METHODS: Community-dwelling dyads were recruited for a pragmatic clinical trial evaluating three approaches to dementia care. Four clinical trial sites used shared and site-specific recruitment strategies to enroll health system patients. RESULTS: Electronic health record (EHR) queries of patients with a diagnosis of dementia and engagement of their clinicians were the main recruitment strategies. A total of 2176 dyads were enrolled, with 80% recruited after the onset of the pandemic. PLWD had a mean age of 80.6 years (SD 8.5), 58.4% were women, and 8.8% were Hispanic/Latino, and 11.9% were Black/African American. Caregivers were mostly children of the PLWD (46.5%) or spouses/partners (45.2%), 75.8% were women, 9.4% were Hispanic/Latino, and 11.6% were Black/African American. DISCUSSION: Health systems can successfully enroll diverse dyads in a pragmatic clinical trial.

Self-Measured Blood Pressure-Guided Pharmacotherapy: A Systematic Review and Meta-Analysis of United States-Based Telemedicine Trials.

BACKGROUND: The optimal approach to implementing telemedicine hypertension management in the United States is unknown. METHODS: We examined telemedicine hypertension management versus the effect of usual clinic-based care on blood pressure (BP) and patient/clinician-related heterogeneity in a systematic review/meta-analysis. We searched United States-based randomized trials from Medline, Embase, CENTRAL, CINAHL, PsycINFO, Compendex, Web of Science Core Collection, Scopus, and 2 trial registries. We used trial-level differences in BP and its control rate at ≥6 months using random-effects models. We examined heterogeneity in univariable metaregression and in prespecified subgroups (clinicians leading pharmacotherapy [physician/nonphysician], self-management support [pharmacist/nurse], White versus non-White patient predominant trials [>50% patients/trial], diabetes predominant trials [≥25% patients/trial], and White patient predominant but not diabetes predominant trials versus both non-White and diabetes patient predominant trials]. RESULTS: Thirteen, 11, and 7 trials were eligible for systolic and diastolic BP difference and BP control, respectively. Differences in systolic and diastolic BP and BP control rate were -7.3 mm Hg (95% CI, -9.4 to -5.2), -2.7 mm Hg (-4.0 to -1.5), and 10.1% (0.4%-19.9%), respectively, favoring telemedicine. Greater BP reduction occurred in trials where nonphysicians led pharmacotherapy, pharmacists provided self-management support, White patient predominant trials, and White patient predominant but not diabetes predominant trials, with no difference by diabetes predominant trials. CONCLUSIONS: Telemedicine hypertension management is more effective than clinic-based care in the United States, particularly when nonphysicians lead pharmacotherapy and pharmacists provide self-management support. Non-White patient predominant trials achieved less BP reduction. Equity-conscious, locally informed adaptation of telemedicine interventions is needed before wider implementation.

Study design and methods: U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER).

INTRODUCTION: The U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER) is conducted to confirm and expand the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in Americans. METHODS: U.S. POINTER was planned as a 2-year randomized controlled trial of two lifestyle interventions in 2000 older adults at risk for dementia due to well-established factors. The primary outcome is a global cognition composite that permits harmonization with FINGER. RESULTS: U.S. POINTER is centrally coordinated and conducted at five clinical sites (ClinicalTrials.gov: NCT03688126). Outcomes assessments are completed at baseline and every 6 months. Both interventions focus on exercise, diet, cognitive/social stimulation, and cardiovascular health, but differ in intensity and accountability. The study partners with a worldwide network of similar trials for harmonization of methods and data sharing. DISCUSSION: U.S. POINTER is testing a potentially sustainable intervention to support brain health and Alzheimer's prevention for Americans. Impact is strengthened by the targeted participant diversity and expanded scientific scope through ancillary studies.

Effects of the implementation of the dynamic silver code in the emergency department.

BACKGROUND: Older persons accessing the Emergency Department (ED) spend more time and are at increased risk of poor outcomes. The Dynamic Silver Code (DSC), based on administrative data, predicts mortality of 75+ subjects visiting the ED. OBJECTIVE: To evaluate the effects of the implementation of the DSC in the ED. METHODS: A pre-post comparison was conducted in the ED of a community hospital in Florence, Italy before and after the DSC was fully implemented. In the post-DSC phase, a clinical decision tree was applied: patients at low-mild risk (DSC class I and II) were assigned to Internal Medicine, those at moderate risk (class III) to Geriatrics, and those at high risk (class IV) required geriatric consultation before assignment. Outcome measures were ED length of stay (LOS) and, in patients admitted to Geriatrics, weight of the Diagnosis Related Groups (DRG), hospital LOS, and mortality. RESULTS: 7,270 patients were enrolled in the pre-DSC and 4,725 in the post-DSC phase. ED LOS decreased from a median of 380 [206, 958] in the pre-DSC to 318 [178, 655] min in the post-DSC period (p<0.001). Class III represented the largest share of admissions to Geriatrics in the post-DSC period (57.7 % vs. 38.3 %; p<0.001). In patients admitted to Geriatrics, hospital LOS decreased by one day (p = 0.006) between the two study periods, with greater DRG weight and comparable mortality. CONCLUSIONS: Application of the DSC seemed to ease patient flow and to reduce LOS of older patients in the ED and increased appropriateness of admissions to Geriatrics.

Low-Density-Lipoprotein Cholesterol and Mortality Outcomes Among Healthy Older Adults: A Post Hoc Analysis of ASPREE Trial.

BACKGROUND: The prognostic implication of cholesterol levels in older adults remains uncertain. This study aimed to examine the relationship between low-density-lipoprotein cholesterol (LDL-c) and mortality outcomes in older individuals. METHODS: This post hoc analysis examined the associations of LDL-c levels with mortality risks from all-cause, cardiovascular disease (CVD), cancer, and combined non-CVD/noncancer conditions in a cohort of individuals aged ≥65 years from the ASPirin in Reducing Events in the Elderly trial (NCT01038583). At baseline, participants had no diagnosed dementia, physical disability, or CVD, and were not taking lipid-lowering agents. Outcome analyses were performed using multivariable Cox models. RESULTS: We analyzed 12 334 participants (mean age: 75.2 years). Over a median 7-year follow-up, 1 250 died. Restricted cubic splines found a U-shaped relation for LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVE mortality (nadir: 3.3-3.4 mmol/L); the risk of CVD mortality was similar at LDL-c below 3.3 mmol/L and increased above 3.3 mmol/L. Similar trends were observed in analyses modeling LDL-c by quartiles. When modeling LDL-c as a continuous variable, the risk of all-cause mortality, cancer mortality, and noncancer/non-CVD mortality was decreased by 9%, 16%, and 18%, respectively, per 1-mmol/L higher LDL-c, and the risk of CVD mortality was increased by 19% per 1-mmol/L higher LDL-c. Reduced all-cause and non-CVD/noncancer mortality risks were only significant in males but not females (pinteraction < .05). CONCLUSIONS: There were U-shaped relationships between LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVD mortality in healthy older adults. Higher LDL-c levels were associated with an increased risk of CVD mortality. Future studies are warranted to confirm our results.

Cerebrovascular reactivity in Alzheimer's disease signature regions is associated with mild cognitive impairment in adults with hypertension.

INTRODUCTION: Vascular risk factors contribute to cognitive decline suggesting that maintaining cerebrovascular health could reduce dementia risk. The objective of this study is to evaluate the association of cerebrovascular reactivity (CVR), a measure of brain blood vessel elasticity, with mild cognitive impairment (MCI) and dementia. METHODS: Participants were enrolled in the Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension (SPRINT-MIND) magnetic resonance imaging substudy. Baseline CVR in Alzheimer's disease (AD) signature regions were primary variables of interest. The occipital pole and postcentral gyrus were included as control regions. RESULTS: Higher AD composite CVR was associated with lower MCI risk. No significant associations between inferior temporal gyrus, occipital pole, or postcentral gyrus CVR and MCI risk, or any regional CVR-combined risk associations were observed. DISCUSSION: CVR in AD signature regions is negatively associated with occurrence of MCI, implicating CVR in AD signature regions as a potential mechanism leading to cognitive impairment.

The relationship between visual function and physical performance in the Study of Muscle, Mobility and Aging (SOMMA).

PURPOSE: The relationship of types of visual function to different aspects of physical function, especially strength and coordination, has been understudied, but delineation of these relationships could suggest potentially modifiable targets prior to the onset of disability. METHODS: Cross-sectional analysis of visual function (self-reported eyesight and eye disease, visual acuity, contrast sensitivity) and physical function tests in 877 older adults (mean age 76.36±5.01 years, 59.2% women, and 13.3% Black race). Separate linear regression models were constructed for short physical performance battery (SPPB), expanded SPPB (eSPPB), their components (gait speed, chair stand, balance, narrow walk), stair climb, four-square step, leg extension peak power and strength, and grip strength. RESULTS: In adjusted models, worse acuity, worse contrast sensitivity, and self-reported poor vision were significantly associated with worse performance on the eSPPB and four-square step test. Worse contrast sensitivity, but not acuity, was significantly associated with shorter balance times, slower chair stand pace, longer stair climb time, and worse SPPB score. Associations of worse acuity and contrast sensitivity with weaker leg extension power, leg strength, and grip strength were attenuated by covariate adjustment. Self-reported macular degeneration, but not cataract or glaucoma, was associated with worse performance on SPPB, eSPPB, balance, stair climb, and four-square step tests in adjusted models. Worse contrast sensitivity and macular degeneration remained associated with worse SPPB and balance after controlling for visual acuity and self-reported eyesight. CONCLUSIONS: Poor contrast sensitivity was more strongly associated with worse physical performance than acuity, especially for complex tasks that dynamically challenge coordination and balance. Future studies should examine if older adults with contrast sensitivity impairment would benefit from targeted intervention to decrease their risk of disability.

Heterogeneity of the Effect of Telemedicine Hypertension Management Approach on Blood Pressure: A Systematic Review and Meta-analysis of US-based Clinical Trials.

Background: Telemedicine management of hypertension (TM-HTN) uses home blood pressure (BP) to guide pharmacotherapy and telemedicine-based self-management support (SMS). Optimal approach to implementing TM-HTN in the US is unknown. Methods: We conducted a systematic review and a meta-analysis to examine the effect of TM-HTN vs. usual clinic-based care on BP and assessed heterogeneity by patient- and clinician-related factors. We searched US-based randomized clinical trials among adults from Medline, Embase, CENTRAL, CINAHL, PsycInfo, and Compendex, Web of Science Core Collection, Scopus, and two trial registries to 7/7/2023. Two authors extracted, and a third author confirmed data. We used trial-level differences in systolic BP (SBP), diastolic BP (DBP) and BP control rate at ≥6 months using random-effects models. We examined heterogeneity of effect in univariable meta-regression and in pre-specified subgroups [clinicians leading pharmacotherapy (physician vs. non-physician), SMS (pharmacist vs. nurse), White vs. non-White patient predominant trials (>50% patients/trial), diabetes predominant trials (≥25% patients/trial) and in trials that have majority of both non-White patients and patients with diabetes vs. White patient predominant but not diabetes predominant trials. Results: Thirteen, 11 and 7 trials were eligible for SBP, DBP and BP control, respectively. Differences in SBP, DBP and BP control rate were -7.3 mmHg (95% CI: - 9.4, -5.2), -2.7 mmHg (-4.0, -1.5) and 10.1% (0.4%, 19.9%), respectively, favoring TM-HTN. More BP reduction occurred in trials with non-physician vs. physician led pharmacotherapy (9.3/4.0 mmHg vs. 4.9/1.1 mmHg, P<0.01 for both SBP/DBP), pharmacist vs. nurses provided SMS (9.3/4.1 mmHg vs. 5.6/1.0 mmHg, P=0.01 for SBP, P<0.01 for DBP), and White vs. non-White patient predominant trials (9.3/4.0 mmHg vs. 4.4/1.1 mmHg, P<0.01 for both SBP/DBP), with no difference by diabetes predominant trials. Lower BP reduction occurred in both diabetes and non-White patient predominant trials vs. White patient predominant but not diabetes predominant trials (4.5/0.9 mmHg vs. 9.5/4.2 mmHg, P<0.01 for both SBP/DBP). Conclusions: TM-HTN is more effective than clinic-based care in the US, particularly when non-physician led pharmacotherapy and pharmacist provided SMS. Non-White patient predominant trials seemed to achieve lesser BP reduction. Equity conscious, locally informed adaptation of TM-HTN is needed before wider implementation. Clinical Perspective: What Is New?: In this systematic review and meta-analysis of US-based clinical trials, we found that telemedicine management of hypertension (TM-HTN) was more effective in reducing and controlling blood pressure (BP) compared with clinic based hypertension (HTN) care.The BP reduction was more evident when pharmacotherapy was led by non-physician compared with physicians and HTN self-management support was provided by clinical pharmacists compared with nurses,Non-White patient predominant trials achieved lesser BP reductions than White patient predominant trials.What Are the Clinical Implications?: Before wider implementation of TM-HTN intervention in the US, locally informed adaptation, such as optimizing the team-based HTN care approach, can provide more effective BP control.Without equity focused tailoring, TM-HTN intervention implemented as such can exacerbate inequities in BP control among non-White patients in the US.

Low-Dose Aspirin and the Risk of Stroke and Intracerebral Bleeding in Healthy Older People: Secondary Analysis of a Randomized Clinical Trial.

Importance: Low-dose aspirin has been widely used for primary and secondary prevention of stroke. The balance between potential reduction of ischemic stroke events and increased intracranial bleeding has not been established in older individuals. Objective: To establish the risks of ischemic stroke and intracranial bleeding among healthy older people receiving daily low-dose aspirin. Design, Setting, and Participants: This secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized, double-blind, placebo-controlled trial of daily low-dose aspirin was conducted among community-dwelling people living in Australia or the US. Participants were older adults free of symptomatic cardiovascular disease. Recruitment took place between 2010 and 2014, and participants were followed up for a median (IQR) of 4.7 (3.6-5.7) years. This analysis was completed from August 2021 to March 2023. Interventions: Daily 100-mg enteric-coated aspirin or matching placebo. Main Outcomes and Measures: Stroke and stroke etiology were predetermined secondary outcomes and are presented with a focus on prevention of initial stroke or intracranial bleeding event. Outcomes were assessed by review of medical records. Results: Among 19 114 older adults (10 782 females [56.4%]; median [IQR] age, 74 [71.6-77.7] years), 9525 individuals received aspirin and 9589 individuals received placebo. Aspirin did not produce a statistically significant reduction in the incidence of ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.71-1.11). However, a statistically significant increase in intracranial bleeding was observed among individuals assigned to aspirin (108 individuals [1.1%]) compared with those receiving placebo (79 individuals [0.8%]; HR, 1.38; 95% CI, 1.03-1.84). This occurred by an increase in a combination of subdural, extradural, and subarachnoid bleeding with aspirin compared with placebo (59 individuals [0.6%] vs 41 individuals [0.4%]; HR, 1.45; 95% CI, 0.98-2.16). Hemorrhagic stroke was recorded in 49 individuals (0.5%) assigned to aspirin compared with 37 individuals (0.4%) in the placebo group (HR, 1.33; 95% CI, 0.87-2.04). Conclusions and Relevance: This study found a significant increase in intracranial bleeding with daily low-dose aspirin but no significant reduction of ischemic stroke. These findings may have particular relevance to older individuals prone to developing intracranial bleeding after head trauma. Trial Registration: ISRCTN.org Identifier: ISRCTN83772183.

Clinical trials in vascular cognitive impairment following SPRINT-MIND: An international perspective.

A large interventional trial, the Systolic Blood Pressure Intervention Trial sub-study termed Memory and Cognition in Decreased Hypertension (SPRINT-MIND), found reduced risk of cognitive impairment in older adults with intensive, relative to standard, blood-pressure-lowering targets (systolic BP < 120 vs. <140 mm Hg). In this perspective, we discuss key questions and make recommendations for clinical practice and for clinical trials, following SPRINT-MIND. Future trials should embody cognitive endpoints appropriate to the participant group, ideally with adaptive designs that ensure robust answers for cognitive and cardiovascular endpoints. Reliable data from diverse populations, including the oldest-old (age > 80 years), will maximize external validity and global implementation of trial findings. New biomarkers will improve phenotyping to stratify patients to optimal treatments. Currently no antihypertensive drug class stands out for dementia risk reduction. Multi-domain interventions, incorporating lifestyle change (exercise, diet) alongside medications, may maximize global impact. Given the low cost and wide availability of antihypertensive drugs, intensive BP reduction may be a cost-effective means to reduce dementia risk in diverse, aging populations worldwide.

Health Characteristics and Aspirin Use in Participants at the Baseline of the ASPirin in Reducing Events in the Elderly - eXTension (ASPREE-XT) Observational Study.

BACKGROUND: Aspirin as a primary preventative in healthy older adults did not prolong disability-free survival in the ASPREE randomized trial. Observational studies following randomized trials allow assessment of benefits and harms which may not appear during the trial. We describe health characteristics, physical function, and aspirin use in the ASPREE-eXTension (ASPREE-XT) observational study cohort. METHODS: Descriptive statistics compared health characteristics of those consented to ASPREE-XT at their first post-trial baseline (XT01) to corresponding ASPREE baseline values, and to those not consented. Likelihood of an indication for aspirin was assessed in participants reporting aspirin use at XT01. RESULTS: 16,317 (93%) of the remaining and eligible 17,546 ASPREE participants were consented into ASPREE-XT; 14,894 completed XT01. Mean participant age had increased from 74.9 to 80.6 years. Overall health and physical function declined from the original ASPREE baseline; more participants were living alone, there was higher prevalence of chronic kidney disease, diabetes, and frailty, grip strength was lower and gait speed slower. Those not consented into ASPREE-XT were slightly older, and had lower cognitive scores and higher prevalence of age-related conditions than those who continued. 1015/11,717 (8.7%) participants without an apparent indication for aspirin reported using aspirin at XT01. CONCLUSIONS: The ASPREE-XT cohort was slightly less healthy at the XT01 visit than at ASPREE trial initiation, and rates of aspirin use without indication were similar to ASPREE baseline. Participants will be followed long-term to investigate aspirin's potential legacy towards dementia and cancer prevention and explore determinants of healthy aging.

Older Adults' Perspectives on Screening for Cognitive Impairment Following Critical Illness: Pre-Implementation Qualitative Study.

Screening for cognitive impairment following ICU discharge is recommended but not part of routine care. We sought to understand older adults' perspectives on screening for cognitive impairment following an ICU admission to inform the design and delivery of a cognitive screening intervention. DESIGN: Qualitative study using semi-structured interviews. SUBJECTS: Adults 60 years and older within 3 months of discharge from an ICU in an academic health system. INTERVENTIONS: Interviews were conducted via telephone, audio recorded and transcribed verbatim. All transcripts were coded in duplicate. Discrepancies were resolved by consensus. Codes were organized into themes and subthemes inductively. MEASUREMENTS AND MAIN RESULTS: We completed 22 interviews. The mean age of participants was 71 ± 6 years, 14 (63.6%) were men, 16 (72.7%) were White, and 6 (27.3%) were Black. Thematic analysis was organized around four themes: 1) receptivity to screening, 2) communication preferences, 3) information needs, and 4) provider involvement. Most participants were receptive to cognitive screening; this was influenced by trust in their providers and prior experience with cognitive screening and impairment. Participants preferred simple, direct, compassionate communication. They wanted to understand the screening procedure, the rationale for screening, and expectations for recovery. Participants desired input from their primary care provider to have their cognitive screening results placed in the context of their overall health, because they had a trusted relationship, and for convenience. CONCLUSIONS: Participants demonstrated limited understanding of and exposure to cognitive screening but see it as potentially beneficial following an ICU stay. Providers should use simple, straightforward language and place emphasis on expectations. Resources may be needed to assist primary care providers with capacity to provide cognitive screening and interpret results for ICU survivors. Implementation strategies can include educational materials for clinicians and patients on rationale for screening and recovery expectations.

Identifying Patients for Intensive Blood Pressure Treatment Based on Cognitive Benefit: A Secondary Analysis of the SPRINT Randomized Clinical Trial.

Importance: Intensive vs standard treatment to lower systolic blood pressure (SBP) reduces risk of mild cognitive impairment (MCI) or dementia; however, the magnitude of cognitive benefit likely varies among patients. Objective: To estimate the magnitude of cognitive benefit of intensive vs standard systolic BP (SBP) treatment. Design, Setting, and Participants: In this ad hoc secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), 9361 randomized clinical trial participants 50 years or older with high cardiovascular risk but without a history of diabetes, stroke, or dementia were followed up. The SPRINT trial was conducted between November 1, 2010, and August 31, 2016, and the present analysis was completed on October 31, 2022. Intervention: Systolic blood pressure treatment to an intensive (<120 mm Hg) vs standard (<140 mm Hg) target. Main Outcomes and Measures: The primary outcome was a composite of adjudicated probable dementia or amnestic MCI. Results: A total of 7918 SPRINT participants were included in the analysis; 3989 were in the intensive treatment group (mean [SD] age, 67.9 [9.2] years; 2570 [64.4%] men; 1212 [30.4%] non-Hispanic Black) and 3929 were in the standard treatment group (mean [SD] age, 67.9 [9.4] years; 2570 [65.4%] men; 1249 [31.8%] non-Hispanic Black). Over a median follow-up of 4.13 (IQR, 3.50-5.88) years, there were 765 and 828 primary outcome events in the intensive treatment group and standard treatment group, respectively. Older age (hazard ratio [HR] per 1 SD, 1.87 [95% CI, 1.78-1.96]), Medicare enrollment (HR per 1 SD, 1.42 [95% CI, 1.35-1.49]), and higher baseline serum creatinine level (HR per 1 SD, 1.24 [95% CI, 1.19-1.29]) were associated with higher risk of the primary outcome, while better baseline cognitive functioning (HR per 1 SD, 0.43 [95% CI, 0.41-0.44]) and active employment status (HR per 1 SD, 0.44 [95% CI, 0.42-0.46]) were associated with lower risk of the primary outcome. Risk of the primary outcome by treatment goal was estimated accurately based on similar projected and observed absolute risk differences (C statistic = 0.79). Higher baseline risk for the primary outcome was associated with greater benefit (ie, larger absolute reduction of probable dementia or amnestic MCI) of intensive vs standard treatment across the full range of estimated baseline risk. Conclusions and Relevance: In this secondary analysis of the SPRINT trial, participants with higher baseline projected risk of probable dementia or amnestic MCI gained greater absolute cognitive benefit from intensive vs standard SBP treatment in a monotonic fashion. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Evidence for Age Bias Contributing to Therapeutic Inertia in Blood Pressure Management: A Secondary Analysis of SPRINT.

BACKGROUND: Despite evidence supporting the cardiovascular and cognitive benefits of intensive blood pressure management, older adults have the lowest rates of blood pressure control. We determined the association between age and therapeutic inertia (TI) in SPRINT (Systolic Blood Pressure Intervention Trial), and whether frailty, cognitive function, or gait speed moderate or mediate these associations. METHODS: We performed a secondary analysis of SPRINT of participant visits with blood pressure above randomized treatment goal. We categorized baseline age as <60, 60 to <70, 70 to <80, and ≥80 years and TI as no antihypertensive medication intensification per participant visit. Generalized estimating equations generated odds ratios for TI associated with age, stratified by treatment group based on nested models adjusted for baseline frailty index score (fit [frailty index, ≤0.10], less fit [0.100.10). CONCLUSIONS: Older age is associated with greater TI independent of physical or cognitive function, implying age bias in hypertension management.

Pragmatic evaluation of events and benefits of lipid lowering in older adults (PREVENTABLE): Trial design and rationale.

Whether initiation of statins could increase survival free of dementia and disability in adults aged ≥75 years is unknown. PREVENTABLE, a double-blind, placebo-controlled randomized pragmatic clinical trial, will compare high-intensity statin therapy (atorvastatin 40 mg) with placebo in 20,000 community-dwelling adults aged ≥75 years without cardiovascular disease, disability, or dementia at baseline. Exclusion criteria include statin use in the prior year or for >5 years and inability to take a statin. Potential participants are identified using computable phenotypes derived from the electronic health record and local referrals from the community. Participants will undergo baseline cognitive testing, with physical testing and a blinded lipid panel if feasible. Cognitive testing and disability screening will be conducted annually. Multiple data sources will be queried for cardiovascular events, dementia, and disability; survival is site-reported and supplemented by a National Death Index search. The primary outcome is survival free of new dementia or persisting disability. Co-secondary outcomes are a composite of cardiovascular death, hospitalization for unstable angina or myocardial infarction, heart failure, stroke, or coronary revascularization; and a composite of mild cognitive impairment or dementia. Ancillary studies will offer mechanistic insights into the effects of statins on key outcomes. Biorepository samples are obtained and stored for future study. These results will inform the benefit of statins for increasing survival free of dementia and disability among older adults. This is a pioneering pragmatic study testing important questions with low participant burden to align with the needs of the growing population of older adults.

Association of Intensive vs Standard Blood Pressure Control With Regional Changes in Cerebral Small Vessel Disease Biomarkers: Post Hoc Secondary Analysis of the SPRINT MIND Randomized Clinical Trial.

Importance: Little is known about the associations of strict blood pressure (BP) control with microstructural changes in small vessel disease markers. Objective: To investigate the regional associations of intensive vs standard BP control with small vessel disease biomarkers, such as white matter lesions (WMLs), fractional anisotropy (FA), mean diffusivity (MD), and cerebral blood flow (CBF). Design, Setting, and Participants: The Systolic Blood Pressure Intervention Trial (SPRINT) is a multicenter randomized clinical trial that compared intensive systolic BP (SBP) control (SBP target <120 mm Hg) vs standard control (SBP target <140 mm Hg) among participants aged 50 years or older with hypertension and without diabetes or a history of stroke. The study began randomization on November 8, 2010, and stopped July 1, 2016, with a follow-up duration of approximately 4 years. A total of 670 and 458 participants completed brain magnetic resonance imaging at baseline and follow-up, respectively, and comprise the cohort for this post hoc analysis. Statistical analyses for this post hoc analysis were performed between August 2020 and October 2022. Interventions: At baseline, 355 participants received intensive SBP treatment and 315 participants received standard SBP treatment. Main Outcomes and Measures: The main outcomes were regional changes in WMLs, FA, MD (in white matter regions of interest), and CBF (in gray matter regions of interest). Results: At baseline, 355 participants (mean [SD] age, 67.7 [8.0] years; 200 men [56.3%]) received intensive BP treatment and 315 participants (mean [SD] age, 67.0 [8.4] years; 199 men [63.2%]) received standard BP treatment. Intensive treatment was associated with smaller mean increases in WML volume compared with standard treatment (644.5 mm3 vs 1258.1 mm3). The smaller mean increases were observed specifically in the deep white matter regions of the left anterior corona radiata (intensive treatment, 30.3 mm3 [95% CI, 16.0-44.5 mm3]; standard treatment, 80.5 mm3 [95% CI, 53.8-107.2 mm3]), left tapetum (intensive treatment, 11.8 mm3 [95% CI, 4.4-19.2 mm3]; standard treatment, 27.2 mm3 [95% CI, 19.4-35.0 mm3]), left superior fronto-occipital fasciculus (intensive treatment, 3.2 mm3 [95% CI, 0.7-5.8 mm3]; standard treatment, 9.4 mm3 [95% CI, 5.5-13.4 mm3]), left posterior corona radiata (intensive treatment, 26.0 mm3 [95% CI, 12.9-39.1 mm3]; standard treatment, 52.3 mm3 [95% CI, 34.8-69.8 mm3]), left splenium of the corpus callosum (intensive treatment, 45.4 mm3 [95% CI, 25.1-65.7 mm3]; standard treatment, 83.0 mm3 [95% CI, 58.7-107.2 mm3]), left posterior thalamic radiation (intensive treatment, 53.0 mm3 [95% CI, 29.8-76.2 mm3]; standard treatment, 106.9 mm3 [95% CI, 73.4-140.3 mm3]), and right posterior thalamic radiation (intensive treatment, 49.5 mm3 [95% CI, 24.3-74.7 mm3]; standard treatment, 102.6 mm3 [95% CI, 71.0-134.2 mm3]). Conclusions and Relevance: This study suggests that intensive BP treatment, compared with standard treatment, was associated with a slower increase of WMLs, improved diffusion tensor imaging, and FA and CBF changes in several brain regions that represent vulnerable areas that may benefit from more strict BP control. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Association Between Contrast Sensitivity and Physical Function in Cognitively Healthy Older Adults: The Brain Networks and Mobility Function Study.

BACKGROUND: To evaluate whether contrast sensitivity is associated with lower extremity physical function in cognitively intact older adults. METHODS: Cross-sectional analysis of the relationship of binocular and worse eye log contrast sensitivity (LCS) to expanded Short Physical Performance Battery (eSPPB) and its components (gait speed, narrow walking speed, chair stand pace, and balance) in 192 cognitively healthy older adults. The association of LCS with postural sway and gait was also tested with tasks that further challenged functional reserve. RESULTS: Mean age was 76.4 years with 56% identifying as female and over 98.5% having good corrected visual acuity. Lower LCS was significantly associated with worse performance on the eSPPB, 4-M gait speed, narrow walking speed, and balance time in unadjusted and adjusted models. The relationship between worse eye LCS and larger postural sway was 3 times greater on a foam surface (beta 1.07, 95% CI [0.35, 1.80]) than a firm surface (beta 0.35, 95% CI [0.05, 0.65]), and both were robust to adjustment for confounders; similar findings were observed with binocular LCS. Lower binocular LCS had a greater decremental effect on gait velocity during the fast pace (beta -0.58, 95% CI [-0.90, -0.27]) than the usual pace (Beta -0.39 [-0.63, -0.15]) gait task. CONCLUSIONS: These findings suggest that cognitively unimpaired older adults without significant visual acuity impairment can have subtle preclinical deficits in contrast sensitivity and physical function that could place them at risk of mobility and balance issues. Future studies should determine whether this subset of older adults may benefit from targeted intervention to prevent disability.