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.

Associations among vascular risk factors, neuroimaging biomarkers, and cognition: Preliminary analyses from the Multi-Ethnic Study of Atherosclerosis (MESA).

INTRODUCTION: Little is known about how antecedent vascular risk factor (VRF) profiles impact late-life brain health. METHODS: We examined baseline VRFs, and cognitive testing and neuroimaging measures (ß-amyloid [Aß] PET, MRI) in a diverse longitudinal cohort (N = 159; 50% African-American, 50% White) from Wake Forest's Multi-Ethnic Study of Atherosclerosis Core. RESULTS: African-Americans exhibited greater baseline Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE), Framingham stroke risk profile (FSRP), and atherosclerotic cardiovascular disease risk estimate (ASCVD) scores than Whites. We observed no significant racial differences in Aß positivity, cortical thickness, or white matter hyperintensity (WMH) volume. Higher baseline VRF scores were associated with lower cortical thickness and greater WMH volume, and FSRP and CAIDE were associated with Aß. Aß was cross-sectionally associated with cognition, and all imaging biomarkers were associated with greater 6-year cognitive decline. DISCUSSION: Results suggest the convergence of multiple vascular and Alzheimer's processes underlying neurodegeneration and cognitive decline.

Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial.

Importance: There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia. Objective: To evaluate the effect of intensive blood pressure control on risk of dementia. Design, Setting, and Participants: Randomized clinical trial conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diabetes or history of stroke. Randomization began on November 8, 2010. The trial was stopped early for benefit on its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. The final date for follow-up of cognitive outcomes was July 22, 2018. Interventions: Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683). Main Outcomes and Measures: The primary cognitive outcome was occurrence of adjudicated probable dementia. Secondary cognitive outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia. Results: Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 8563 (91.5%) completed at least 1 follow-up cognitive assessment. The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio [HR], 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97). Conclusions and Relevance: Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Association of Intensive vs Standard Blood Pressure Control With Cerebral White Matter Lesions.

Importance: The effect of intensive blood pressure lowering on brain health remains uncertain. Objective: To evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain volumes. Design, Setting, and Participants: A substudy of a multicenter randomized clinical trial of hypertensive adults 50 years or older without a history of diabetes or stroke at 27 sites in the United States. Randomization began on November 8, 2010. The overall trial was stopped early because of benefit for its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. Brain magnetic resonance imaging (MRI) was performed on a subset of participants at baseline (n = 670) and at 4 years of follow-up (n = 449); final follow-up date was July 1, 2016. Interventions: Participants were randomized to a systolic blood pressure (SBP) goal of either less than 120 mm Hg (intensive treatment, n = 355) or less than 140 mm Hg (standard treatment, n = 315). Main Outcomes and Measures: The primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome. Results: Among 670 recruited patients who had baseline MRI (mean age, 67.3 [SD, 8.2] years; 40.4% women), 449 (67.0%) completed the follow-up MRI at a median of 3.97 years after randomization, after a median intervention period of 3.40 years. In the intensive treatment group, based on a robust linear mixed model, mean white matter lesion volume increased from 4.57 to 5.49 cm3 (difference, 0.92 cm3 [95% CI, 0.69 to 1.14]) vs an increase from 4.40 to 5.85 cm3 (difference, 1.45 cm3 [95% CI, 1.21 to 1.70]) in the standard treatment group (between-group difference in change, -0.54 cm3 [95% CI, -0.87 to -0.20]). Mean total brain volume decreased from 1134.5 to 1104.0 cm3 (difference, -30.6 cm3 [95% CI, -32.3 to -28.8]) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm3 (difference, -26.9 cm3 [95% CI, 24.8 to 28.8]) in the standard treatment group (between-group difference in change, -3.7 cm3 [95% CI, -6.3 to -1.1]). Conclusions and Relevance: Among hypertensive adults, targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Using Kotter's Change Management Framework to Redesign Departmental GME Recruitment.

Background: In light of the COVID-19 pandemic, dramatic change in the graduate medical education (GME) trainee recruitment process was required. Kotter's 8-Step Change Model is a change management framework that has been successfully applied to a variety of GME initiatives but not for recruitment redesign. Objective: To implement major change in program recruitment during the COVID-19 pandemic while maintaining Match outcomes and a high-quality candidate experience. Methods: In 2020, we applied Kotter's 8 steps to implement major changes to program recruitment for a department of internal medicine including 15 GME programs (1 internal medicine residency and 14 subspecialty fellowships). We collected each program's Match fill rates and used Google Analytics to collect monthly website traffic for the year prior to our change process and the subsequent 2 years. Standardized post-interview survey questions were created, and these results were reviewed for descriptive analysis. Results: We successfully used Kotter's 8 steps to change recruitment to a virtual format. Program fill rates remained high after implementation. Website engagement improved with peak monthly page rates doubling over previous values. During the highest traffic month, the average time on site increased for 7 programs, while the bounce rate decreased by more than half for 10 programs. Candidate descriptive feedback was positive. Conclusions: The application of Kotter's 8 steps guided major changes to GME recruitment for 15 programs and was associated with maintained Match fill rates and increased website engagement.

Vascular and microstructural markers of cognitive pathology.

Introduction: Arterial stiffness may play a role in the development of dementia through poorly understood effects on brain microstructural integrity and perfusion. Methods: We examined markers of arterial stiffness (carotid-femoral pulse wave velocity [cfPWV]) and elevated systolic blood pressure (SBP) in relation to cognitive function and brain magnetic resonance imaging macrostructure (gray matter [GM] and white matter [WM] volumes), microstructure (diffusion based free water [FW] and fractional anisotropy [FA]), and cerebral blood flow (CBF) in WM and GM in models adjusted for age, race, sex, education, and apolipoprotein E ε4 status. Results: Among 460 participants (70 ± 8 years; 44 dementia, 158 mild cognitive impairment, 258 normal cognition), higher cfPWV and SBP were independently associated with higher FW, higher WM hyperintensity volume, and worse cognition (global and executive function). Higher SBP alone was significantly associated with lower WM and GM CBF. Discussion: Arterial stiffness is associated with impaired WM microstructure and global and executive cognitive function.

Hypertensive Aspects of Cardiometabolic Disorders Are Associated with Lower Brain Microstructure, Perfusion, and Cognition.

BACKGROUND: Cardiometabolic disorders (hypertension, diabetes) are key modifiable risk factors for Alzheimer's disease and related disorders. They often co-occur; yet, the extent to which they independently affect brain structure and function is unclear. OBJECTIVE: We hypothesized their combined effect is greater in associations with cognitive function and neuroimaging biomarkers of white matter (WM) health and cerebral perfusion in a diverse older adult cohort. METHODS: Participants aged 50-85 years received: clinical evaluation, oral glucose tolerance testing, neuroimaging, cognitive testing, and adjudication. Neuroimaging included: T1 (gray [GM]/WM segmentation, regional volumes/thicknesses); FLAIR (WM hyperintensity volume [WMHv]; arterial spin labeling (cerebral blood flow); diffusion tensor imaging (fractional anisotropy [FA]); and neurite orientation dispersion and density imaging (Free Water). Hypertension (HTN) and impaired glucose tolerance (IGT) were staged and cardiometabolic status was categorized (HTN only, IGT only, IGT+HTN, neither). Multivariable linear regression modeled associations with cognitive and neuroimaging measures (covariates: age, gender, race). RESULTS: MRI was available for 478 participants (35% mild cognitive impairment, 10% dementia) with mean age 70±8 years, 74% with HTN, 61% with IGT, and 15% self-identified as Black/African-American. IGT+HTN was significantly associated with cognitive impairment, higher WM Free Water and WMHv, lower FA, and lower GM perfusion compared to neither factor. HTN alone was associated with poorer cognition and lower GM perfusion. Cardiometabolic factors were not associated with GM macrostructure (volumes, temporal lobe cortical thickness) or cognitive status. CONCLUSION: HTN and its co-occurrence with IGT (HTN+IGT) were associated with lower global cognitive performance and reduced GM perfusion and impaired WM microstructure.

Effect of intensive blood pressure control on subtypes of mild cognitive impairment and risk of progression from SPRINT study.

BACKGROUND: To examine the effect of intensive blood pressure control on the occurrence of subtypes of mild cognitive impairment (MCI) and determine the risk of progression to dementia or death. METHODS: Secondary analysis of a randomized trial of community-dwelling adults (≥50 years) with hypertension. Participants were randomized to a systolic blood pressure (SBP) goal of <120 mm Hg (intensive treatment; n = 4678) or <140 mm Hg (Standard treatment; n = 4683). Outcomes included adjudicated MCI, MCI subtype (amnestic, non-amnestic, multi-domain, single domain), and probable dementia. Multistate survival models were used to examine transitions in cognitive status accounting for the competing risk of death. RESULTS: Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 640 participants met the protocol definition for MCI, with intensive treatment reducing the risk of MCI overall (hazard ratio [HR], 0.81 [95% confidence interval {CI}, 0.69-0.94]), as previously reported. This effect was largely reflected in amnestic subtypes (HR, 0.78 [95% CI, 0.66-0.92]) and multi-domain subtypes (HR, 0.78 [95% CI, 0.65-0.93]). An adjudication of MCI, as compared with normal cognitive function, substantially increased the probability of progressing to probable dementia (5.9% [95% CI: 4.5%-7.7%] vs. 0.6% [95% CI: 0.3%-0.9%]) and to death (10.0% [95% CI: 8.3%-11.9%] vs. 2.3% [95% CI: 2.0%-2.7%]) within 2 years. CONCLUSIONS: Intensive treatment reduced the risk for amnestic and multi-domain subtypes of MCI. An adjudication of MCI was associated with increased risk of progression to dementia and death, highlighting the relevance of MCI as a primary outcome in clinical and research settings.

Preserving Cognition, Preventing Dementia.

Dementia incidence continues to rise in the United States and around the world. Although age is the single biggest risk factor for the development of dementia, it is not considered normal sequelae of aging. Although there has been little to no progress made in the past couple of decades in the treatment or cure of Alzheimer disease, there has been significant progress made in prevention. Single factors, such as hearing loss or cardiovascular risk factors, may increase the risk for cognitive decline. The opportunity to mitigate these risk factors provides an exciting new healthy aging approach to dementia prevention.

Effects of intensive versus standard blood pressure control on domain-specific cognitive function: a substudy of the SPRINT randomised controlled trial.

BACKGROUND: Results from the Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive control of systolic blood pressure significantly reduced the occurrence of mild cognitive impairment, but not probable dementia. We investigated the effects of intensive lowering of systolic blood pressure on specific cognitive functions in a preplanned substudy of participants from SPRINT. METHODS: SPRINT was an open-label, multicentre, randomised controlled trial undertaken at 102 sites, including academic medical centres, Veterans Affairs medical centres, hospitals, and independent clinics, in the USA and Puerto Rico. Participants were adults aged 50 years or older with systolic blood pressure higher than 130 mm Hg, but without diabetes, history of stroke, or dementia. Participants were randomly assigned (1:1) to a systolic blood pressure goal of less than 120 mm Hg (intensive treatment) versus less than 140 mm Hg (standard treatment). All major classes of antihypertensive agents were included. A subgroup of randomly assigned participants including, but not limited to, participants enrolled in an MRI substudy was then selected for a concurrent substudy of cognitive function (target 2800 participants). Each individual was assessed with a screening cognitive test battery and an extended cognitive test battery at baseline and biennially during the planned 4-year follow-up. The primary outcomes for this substudy were standardised composite scores for memory (Logical Memory I and II, Modified Rey-Osterrieth Complex Figure [immediate recall], and Hopkins Verbal Learning Test-Revised [delayed recall]) and processing speed (Trail Making Test and Digit Symbol Coding). SPRINT was registered with ClinicalTrials.gov, NCT01206062. FINDINGS: From Nov 23, 2010, to Dec 28, 2012, 2921 participants (mean age 68·4 years [SD 8·6], 1080 [37%] women) who had been randomly assigned in SPRINT were enrolled in the substudy (1448 received intensive treatment and 1473 received standard treatment). SPRINT was terminated early due to benefit observed in the primary outcome (composite of cardiovascular events). After a median follow-up of 4·1 years (IQR 3·7-5·8), there was no between-group difference in memory, with an annual decline in mean standardised domain score of -0·005 (95% CI -0·010 to 0·001) in the intensive treatment group and -0·001 (-0·006 to 0·005) in the standard treatment group (between-group difference -0·004, 95% CI -0·012 to 0·004; p=0·33). Mean standardised processing speed domain scores declined more in the intensive treatment group (between-group difference -0·010, 95% CI -0·017 to -0·002; p=0·02), with an annual decline of -0·025 (-0·030 to -0·019) for the intensive treatment group and -0·015 (-0·021 to 0·009) for the standard treatment group. INTERPRETATION: Intensive treatment to lower systolic blood pressure did not result in a clinically relevant difference compared with standard treatment in memory or processing speed in a subgroup of participants from SPRINT. The effect of blood pressure lowering might not be evident in specific domains of cognitive function, but instead distributed across multiple domains. FUNDING: National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Alzheimer's Association.

Ten Things Every Geriatrician Should Know About House Calls.

Home-based primary care (HBPC) is experiencing a reemergence to meet the needs of homebound older adults. This brief review based on existing literature and expert opinion discusses 10 key facts about HBPC that every geriatrician should know: (1) the team-based nature of HBPC is key to its success; (2) preparations and after-hour access for house calls are required; (3) home safety for the clinician and patient must be considered; (4) being homebound is an independent mortality risk factor with a high symptom burden; (5) home care medicine presents unique benefits and challenges; (6) a systems-based approach to care is essential; (7) HBPC is a sustainable model within value-based care proven by the Department of Veterans Affairs and the Independence at Home Medicare Demonstration Project; (8) HBPC has an educational mission; (9) national organizations for HBPC include American Academy of Home Care Medicine and Home Centered Care Institute; and (10) practicing HBPC is a privilege. HBPC is a dynamic and unique practice model that will continue to grow in the future. J Am Geriatr Soc 67:139-144, 2019.

Healthy Aging: American Geriatrics Society White Paper Executive Summary.

In July 2015, the Journal of the American Geriatrics Society published a manuscript titled, "Failing to Focus on Healthy Aging: A Frailty of Our Discipline?" In response, the American Geriatrics Society (AGS) Clinical Practice and Models of Care Committee and Public Education Committee developed a white paper calling on the AGS and its members to play a more active role in promoting healthy aging. The executive summary presented here summarizes the recommendations from that white paper. The full version is published online at GeriatricsCareOnline.org. Life expectancy has increased dramatically over the last century. Longer life provides opportunity for personal fulfillment and contributions to community but is often associated with illness, discomfort, disability, and dependency at the end of life. Geriatrics has focused on optimizing function and quality of life as we age and reducing morbidity and frailty, but there is evidence of earlier onset of chronic disease that is likely to affect the health of future generations of older adults. The AGS is committed to promoting the health, independence, and engagement of all older adults as they age. Geriatrics as an interprofessional specialty is well positioned to promote healthy aging. We draw from decades of accumulated knowledge, skills, and experience in areas that are central to geriatric medicine, including expertise in complexity and the biopsychosocial model; attention to function and quality of life; the ability to provide culturally competent, person-centered care; the ability to assess people's preferences and values; and understanding the importance of systems in optimizing outcomes. J Am Geriatr Soc 67:17-20, 2019.