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BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) is testing whether a lower systolic blood pressure (BP) target of 120mm Hg leads to a reduction in cardiovascular morbidity and mortality among hypertensive, nondiabetic adults. Because there may be detrimental effects of intensive BP control, particularly in older, frail adults, we sought to characterize frailty within SPRINT to address ongoing questions about the ability of large-scale trials to enroll representative samples of noninstitutionalized, community-dwelling, older adults. METHODS: We constructed a 36-item frailty index (FI) in 9,306 SPRINT participants, classifying participants as fit (FI ≤ 0.10), less fit (0.10 0.21). Recurrent event models were used to evaluate the association of the FI with the incidence of self-reported falls, injurious falls, and all-cause hospitalizations. RESULTS: The distribution of the FI was comparable with what has been observed in population studies, with 2,570 (27.6%) participants classified as frail. The median FI was 0.18 (interquartile range = 0.14 to 0.24) in participants aged 80 years and older (N = 1,159), similar to the median FI of 0.17 reported for participants in the Hypertension in the Very Elderly Trial. In multivariable analyses, a 1% increase in the FI was associated with increased risk for self-reported falls (hazard ratio [HR] = 1.030), injurious falls (HR = 1.035), and all-cause hospitalizations (HR = 1.038) (all p values CONCLUSIONS: Large clinical trials assessing treatments to reduce cardiovascular disease risk, such as SPRINT, can enroll heterogeneous populations of older adults, including the frail elderly, comparable with general population cohorts. Language: en

This review summarizes evidence from studies of blood pressure and dementia-related biomarkers into our understanding of cognitive health and highlights the challenges facing studies, particularly randomized trials, of hypertension and cognition. Several lines of research suggest that elevated blood pressure, especially at midlife, is associated with cognitive decline and dementia and that treatment of hypertension could prevent these conditions. Further, studies of hypertension and brain structure show that blood pressure is associated with several forms of small vessel disease that can result in vascular dementia or interact with Alzheimer's pathology to lower the pathologic threshold at which Alzheimer's signs and symptoms manifest. In addition, recent studies of hypertension and Alzheimer's biomarkers show that elevated blood pressure and pulse pressure are associated with the extent of brain beta amyloid (Aβ) deposition and altered cerebral spinal fluid profiles of Aβ and tau indicative of Alzheimer's pathology. However, in spite of strong evidence of biological mechanisms, results from randomized trials of antihypertensive therapy for the prevention of cardiovascular or cerebrovascular disease that include cognitive endpoints do not strongly support the observational evidence that treatment of hypertension should be better for cognition. We propose that future clinical trials should consider including dementia biomarkers and assess genetic and cardiometabolic risk factors that have been associated with progression of the underlying disease pathology to help bridge these gaps.

Cognitive impairment (CI) can develop during the course of ageing and is a feature of many neurological and neurodegenerative diseases. Many individuals with CI have substantial, sustained, and complex health care needs, which frequently include pain. However, individuals with CI can have difficulty communicating the features of their pain to others, which in turn presents a significant challenge for effective diagnosis and treatment of their pain. Herein, we review the literature on responsivity of individuals with CI to experimental pain stimuli. We discuss pain responding across a large number of neurological and neurodegenerative disorders in which CI is typically present. Overall, the existing data suggest that pain processing is altered in most individuals with CI compared with cognitively intact matched controls. The precise nature of these alterations varies with the type of CI (or associated clinical condition) and may also depend on the type of pain stimulation used and the type of pain responses assessed. Nevertheless, it is clear that regardless of the etiology of CI, patients do feel noxious stimuli, with more evidence for hypersensitivity than hyposensitivity to these stimuli compared with cognitively unimpaired individuals. Our current understanding of the neurobiological mechanisms underpinning these alterations is limited but may be enhanced through the use of animal models of CI, which also exhibit alterations in nociceptive responding. Further research using additional behavioural indices of pain is warranted. Increased understanding of altered experimental pain processing in CI will facilitate the development of improved diagnostic and therapeutic approaches for pain in individuals with CI.

Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions., Late-onset Alzheimer's disease (LOAD) is a complex multi-factorial disorder. Here, the authors perform a data-driven analysis of LOAD progression, including multimodal brain imaging, plasma and CSF biomarkers, and find vascular dysfunction is among the earliest and strongest altered events.

The Systolic Blood Pressure Intervention Trial (SPRINT) will compare treatment to a systolic blood pressure goal of

Importance Apolipoprotein E ( APOE ) e4 is an established risk factor for cognitive decline and the development of dementia, but other factors may help to minimize its effects. Objective Using APOE e4 as an indicator of high risk, we investigated factors associated with cognitive resilience among black and white older adults who are APOE e4 carriers. Design, Setting, and Participants Participants included 2487 community-dwelling older (aged 69-80 years at baseline) black and white adults examined at 2 community clinics in the prospective cohort Health, Aging, and Body Composition (Health ABC) study. The baseline visits occurred from May 1997 through June 1998. Our primary analytic cohort consisted of 670 APOE e4 carriers (329 black and 341 white participants) who were free of cognitive impairment at baseline and underwent repeated cognitive testing during an 11-year follow-up (through 2008) using the Modified Mini-Mental State Examination. Main Outcomes and Measures We stratified all analyses by race. Using the Modified Mini-Mental State Examination scores, we assessed normative cognitive change in the entire cohort (n = 2487) and classified the APOE e4 carriers as being cognitively resilient vs nonresilient by comparing their cognitive trajectories with those of the entire cohort. We then conducted bivariate analyses and multivariable random forest and logistic regression analyses to explore factors predictive of cognitive resilience in APOE e4 carriers. Results Among white APOE e4 carriers, the strongest predictors of cognitive resilience were, in relative order of importance, no recent negative life events, a higher literacy level, advanced age, a higher educational level, and more time spent reading. Among black APOE e4 carriers, the strongest predictors of cognitive resilience were, in relative order of importance, a higher literacy level, a higher educational level, female sex, and the absence of diabetes mellitus. In follow-up logistic regression models, higher literacy level (adjusted odds ratio [OR], 9.50 [95% CI, 2.67-60.89]), a higher educational level (adjusted OR for college graduate vs less than high school, 3.81 [95% CI, 1.13-17.56]), and age (adjusted OR for 73-76 vs 69-72 years, 2.01 [95% CI, 1.13-3.63]) had significant independent effects in predicting cognitive resilience among white APOE e4 carriers. Among black APOE e4 carriers, a higher literacy level (adjusted OR, 2.27 [95% CI, 1.29-4.06]) and a higher educational level (adjusted OR for high school graduate/some college vs less than high school, 2.86 [95% CI, 1.54-5.49]; adjusted OR for college graduate vs less than high school, 2.52 [95% CI, 1.14-5.62]) had significant independent effects in predicting cognitive resilience. Conclusions and Relevance Although APOE e4 carriers are at high risk for cognitive decline, our findings suggest possible intervention targets, including the enhancement of cognitive reserve and improvement of other psychosocial and health factors, to promote cognitive resilience among black and white APOE e4 carriers.

OBJECTIVES: To determine whether caregiver characteristics are independently associated with neuropsychiatric symptoms of dementia (NPS) after accounting for patient characteristics. DESIGN: Cross-sectional analysis of data from the Medicare Alzheimer's Disease Demonstration and Evaluation study. SETTING: Community-dwelling residents in eight U.S. cities. PARTICIPANTS: Five thousand seven hundred eighty-eight patients with dementia and their caregivers. MEASUREMENTS: Caregivers were asked about the presence of 12 NPS in patients with dementia. Caregiver predictors included age, sex, education, income, marital status, relationship to the patient, whether they lived with patient, number of hours per week spent caregiving, self-reported health, dependency in activities of daily living (ADLs) and instrumental activities of daily living (IADLs), depression, and burden. Multivariate linear regression was used to determine which caregiver characteristics were independently associated with reports of more NPS in patients after controlling for the patient's age, sex, dementia severity, level of ADL dependency, and dementia type. RESULTS: Caregivers were on average 64 years old, 72% female, and 49% were the spouse of the patient (32% wives, 17% husbands). The mean burden score of caregivers was 15 (range 0–32, with higher scores indicating more burden), and 32% had significant depressive symptoms. Patients were on average 79 years old, 60% were female, and most had moderate to severe dementia. The mean number of NPS±standard deviation was 4.8±2.8. After adjusting for patient characteristics, caregivers who were younger, less educated, more depressed, more burdened, or spent more hours per week giving care reported more NPS in care recipients (all P≤.005). CONCLUSION: Certain caregiver characteristics are associated with NPS, independent of patient characteristics, including dementia severity. Clinicians should consider the dynamics between patients and caregivers when managing NPS. Understanding how different caregiver characteristics influence NPS may help tailor caregiver education and interventions.

Kaycee M Sink,1 Mark A Espeland,2 Julia Rushing,2 Cynthia M Castro,3 Timothy S Church,4 Ronald Cohen,5 Thomas M Gill,6 Leora Henkin,2 Janine M Jennings,7 Diana R Kerwin,8 Todd M Manini,5 Valerie Myers,9 Marco Pahor,5 Kieran F Reid,10 Nancy Woolard,1 Stephen R Rapp,11 Jeff D Williamson1 On behalf of LIFE Investigators 1Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA; 4Pennington Biomedical, Louisiana State University, Baton Rouge, LA, USA; 5Institute on Aging and Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA; 6Yale School of Medicine, Department of Internal Medicine, New Haven, CT, USA; 7Department of Psychology, Wake Forest University, Winston-Salem, NC, USA; 8Texas Alzheimer’s and Memory Disorders, Texas Health Presbyterian Hospital Dallas, TX, USA; 9Klein Buendel, Inc., Golden, CO, USA; 10Nutrition, Exercise Physiology and Sarcopenia Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA; 11Department of Psychiatry and Behavioral Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA Abstract: Observational studies have shown beneficial relationships between exercise and cognitive function. Some clinical trials have also demonstrated improvements in cognitive function in response to moderate–high intensity aerobic exercise; however, these have been limited by relatively small sample sizes and short durations. The Lifestyle Interventions and Independence for Elders (LIFE) Study is the largest and longest randomized controlled clinical trial of physical activity with cognitive outcomes, in older sedentary adults at increased risk for incident mobility disability. One LIFE Study objective is to evaluate the effects of a structured physical activity program on changes in cognitive function and incident all-cause mild cognitive impairment or dementia. Here, we present the design and baseline cognitive data. At baseline, participants completed the modified Mini Mental Status Examination, Hopkins Verbal Learning Test, Digit Symbol Coding, Modified Rey–Osterrieth Complex Figure, and a computerized battery, selected to be sensitive to changes in speed of processing and executive functioning. During follow up, participants completed the same battery, along with the Category Fluency for Animals, Boston Naming, and Trail Making tests. The description of the mild cognitive impairment/dementia adjudication process is presented here. Participants with worse baseline Short Physical Performance Battery scores (prespecified at ≤7) had significantly lower median cognitive test scores compared with those having scores of 8or 9 with modified Mini Mental Status Examination score of 91versus (vs) 93, Hopkins Verbal Learning Test delayed recall score of 7.4vs 7.9, and Digit Symbol Coding score of 45vs 48, respectively (all P

COGNITION AND BIOMARKERS IN ADULTS WITH A DOUBLE-HIT RISK FOR DEMENTIA: MILD COGNITIVE IMPAIRMENTAND PREDIABETES Laura D. Baker, Angela Hansen, Brenna Cholerton, Jeannine Skinner, Kaycee Sink, Maureen Callaghan, Suzanne Craft, Valerie Wilson, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States; VA Puget Sound Health Care System, Seattle, Seattle, Washington, United States; 3 University of Washington Health Sciences, Seattle, Washington, United States; 4 Vanderbilt School of Medicine, Nashville, Tennessee, United States; Wake Forest School of Medicine, Winston-Salem, North Carolina, United States; VA Puget Sound Health Care System, Seattle, Tacoma, Washington, United States; 7 Wake Forest School of Medicine, Winston-Salem, North Carolina, United States. Contact e-mail: ldbaker@wakehealth.edu

Aims: Albuminuria and reduced estimated glomerular filtration rate (eGFR) are linked with poorer cognitive performance in European-ancestry populations with advanced nephropathy; relationships in African Americans (AAs) with type 2 diabetes (T2D) are less clear. Tests of cognitive performance, urine albumin:creatinine ratio (UACR), and CKD-EPI eGFR were performed in unrelated AAs with T2D to determine relationships. Methods: Cross-sectional analysis of 263 unrelated AAs with T2D recruited in the African American-Diabetes Heart Study (AA-DHS) MIND. Global cognitive function (mini-mental state exam [3MSE] and Montreal Cognitive Assessment [MoCA]), memory (Rey Auditory Verbal Learning Test [RAVLT]), executive function (Stroop, verbal fluency for animals, and Digit Symbol Copy [DSC]), UACR, and eGFR were determined. Relationships between cognitive tests and renal parameters were assessed using multivariate models, adjusted for age, gender, body mass index, hemoglobin A1c, level of education, hypertension, and LDL cholesterol. Results: Participants had a mean ± SD age of 60.2 ± 9.7 years, 62.7% were female, T2D duration was 14.3 ± 8.9 years, eGFR 86.0 ± 23.2 ml/min/1.73 m2, and UACR 155.8 ± 542.1 (median 8.1) mg/g. In adjusted models, higher UACR was associated with worse 3MSE (p = 0.014), MoCA (p = 0.0089), DSC (p = 0.0004), Stroop performance time (p = 0.003), Stroop errors (p = 0.032), and Stroop interference (p = 0.026). Higher eGFR was associated with better performance on DSC (p = 0.0071). Conclusions: In AAs with T2D, albuminuria and eGFR were associated with cognitive function, even in mild kidney disease. These data stress the need for interventions to prevent cognitive decline well before the late stages of kidney disease.

Individuals with dementia and their family caregivers have higher rates of stress and mental health concerns than the general population. Gerontological nurses have unique and valuable opportunities to conduct therapeutic interactions that support the mental health and well-being of patients and family members. Information regarding dementia patient and family caregiver stressors are presented, followed by engaging strategies for opening therapeutic conversations about these topics. Ways in which gerontological nurses can facilitate coping skills and strengths identification are also outlined. [ Journal of Gerontological Nursing, 39 (11), 7–10.]

Objectives: The aim of this study was to determine whether use of diuretics, angiotensin-1 receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), or β-blockers (BB) was associated with a reduced risk of Alzheimer disease (AD) dementia in participants with normal cognition or mild cognitive impairment (MCI). Methods: Secondary longitudinal data analysis of the Ginkgo Evaluation of Memory Study in older adults at least 75 years of age with normal cognition (n = 1,928) or MCI (n = 320) over a median 6.1-year period using Cox proportional hazard models after adjusting for confounders. Results: Diuretic use was reported by 15.6%, ARB 6.1%, ACE-I 15.1%, CCB 14.8%, and BB 20.5%. Of the 2,248 participants, 290 (13%) developed AD dementia. Hazard ratio for incident AD dementia among participants with normal cognition was 0.51 in diuretic (95% confidence interval [CI] 0.31–0.82), 0.31 in ARB (95% CI 0.14–0.68), 0.50 in ACE-I (95% CI 0.29–0.83), 0.62 in CCB (95% CI 0.35–1.09), and 0.58 in BB (95% CI 0.36–0.93) users and was not significantly altered when mean systolic blood pressure was above 140 mm Hg. In participants with MCI, only diuretic use was associated with decreased risk (hazard ratio = 0.38, 95% CI 0.20–0.73). Conclusions: Diuretic, ARB, and ACE-I use was, in addition to and/or independently of mean systolic blood pressure, associated with reduced risk of AD dementia in participants with normal cognition, while only diuretic use was associated with reduced risk in participants with MCI.

The Association of American Medical Colleges (AAMC) and the John A. Hartford Foundation published geriatrics competencies for medical students in 2008 defining specific knowledge and skills that medical students should be able to demonstrate before graduation. Medical schools, often with limited geriatrics faculty resources, face challenges in teaching and assessing these competencies. As an initial step to facilitate more-efficient implementation of the competencies, a 1-week geriatrics rotation was developed for the third year using clinical, community, and self-directed learning resources. The Wake Forest University School of Medicine Acute Care for the Elderly Unit serves as home base, and each student selects a half-day outpatient or long-term care experience. Students also perform a home-based falls-risk assessment with a Meals-on-Wheels client. The objectives for the rotation include 20 of the 26 individual AAMC competencies and specific measurable tracking tasks for seven individual competencies. In the evaluation phase, 118 students completed the rotation. Feedback was positive, with an average rating of 7.1 (1 = worst, 10 = best). Students completed a 23-item pre- and post-knowledge test, and average percentage correct improved by 15% (P < .001); this improvement persisted at graduation (2 years after the pretest). On a 12-item survey of attitudes toward older adults, improvement was observed immediately after the rotation that did not persist at graduation. Ninety-seven percent of students documented completion of the competency-based tasks. This article provides details of development, structure, evaluation, and lessons learned that will be useful for other institutions considering a brief, concentrated geriatrics experience in the third year of medical school.

Background and Purpose— Arterial stiffness is a measure of subclinical cardiovascular disease and increases with age. This study examines the association between arterial stiffness and cognitive decline in a cohort of older adults. Methods— A total of 2488 subjects with baseline measure of arterial stiffness (mean age, 74.2 years; 52.3% women) were prospectively followed over 9 years in the Health, Aging, and Body Composition Study. Arterial stiffness was measured as pulse wave velocity (PWV) and analyzed in tertiles. Cognitive function was assessed using the Modified Mini-Mental State examination at baseline and repeated at years 3, 5, 8, and 10. Lower Modified Mini-Mental State examination scores indicate worse function. We fit linear mixed models to examine longitudinal changes in cognitive function over the 9 years of follow-up and logistic regression models, restricted to 1331 participants, to examine cognitive impairment defined as a decrease of ≥5 points after 9 years. We adjusted for sociodemographics, Apoe4, and cardiovascular disease risk factors. Results— The annual decrease in Modified Mini-Mental State examination scores was 0.30 points at low PWV (95% confidence interval [CI], −0.37 to −0.22), 0.46 points at middle PWV (95% CI, −0.54 to −0.39), and 0.45 points at high PWV (95% CI, −0.53 to −0.38), from fully adjusted linear mixed models. In fully adjusted models, the odds of cognitive impairment after 9 years of follow-up was 40% greater for subjects with middle PWV (odds ratio [OR], 1.40; 95% CI, 1.03–1.92) and 59% greater for subjects with high PWV (OR, 1.59; 95% CI, 1.16–2.18), compared with low PWV. Conclusions— High arterial stiffness was modestly associated with cognitive decline and impairment. Interventions to prevent arterial stiffness may be effective in delaying cognitive decline.

Objective To test whether a long term, structured physical activity program compared with a health education program reduces the risk of serious fall injuries among sedentary older people with functional limitations. Design Multicenter, single blinded randomized trial (Lifestyle Interventions and Independence for Elders (LIFE) study). Setting Eight centers across the United States, February 2010 to December 2011. Participants 1635 sedentary adults aged 70-89 years with functional limitations, defined as a short physical performance battery score ≤9, but who were able to walk 400 m. Interventions A permuted block algorithm stratified by field center and sex was used to allocate interventions. Participants were randomized to a structured, moderate intensity physical activity program (n=818) conducted in a center (twice a week) and at home (3-4 times a week) that included aerobic, strength, flexibility, and balance training activities, or to a health education program (n=817) consisting of workshops on topics relevant to older people and upper extremity stretching exercises. Main outcome measures Serious fall injuries, defined as a fall that resulted in a clinical, non-vertebral fracture or that led to a hospital admission for another serious injury, was a prespecified secondary outcome in the LIFE Study. Outcomes were assessed every six months for up to 42 months by staff masked to intervention assignment. All participants were included in the analysis. Results Over a median follow-up of 2.6 years, a serious fall injury was experienced by 75 (9.2%) participants in the physical activity group and 84 (10.3%) in the health education group (hazard ratio 0.90, 95% confidence interval 0.66 to 1.23; P=0.52). These results were consistent across several subgroups, including sex. However, in analyses that were not prespecified, sex specific differences were observed for rates of all serious fall injuries (rate ratio 0.54, 95% confidence interval 0.31 to 0.95 in men; 1.07, 0.75 to 1.53 in women; P = 0.043 for interaction), fall related fractures (0.47, 0.25 to 0.86 in men; 1.12, 0.77 to 1.64 in women; P = 0.017 for interaction), and fall related hospital admissions (0.41, 0.19 to 0.89 in men; 1.10, 0.65 to 1.88 in women; P=0.039 for interaction). Conclusions In this trial, which was underpowered to detect small, but possibly important reductions in serious fall injuries, a structured physical activity program compared with a health education program did not reduce the risk of serious fall injuries among sedentary older people with functional limitations. These null results were accompanied by suggestive evidence that the physical activity program may reduce the rate of fall related fractures and hospital admissions in men. Trial registration ClinicalsTrials.gov NCT01072500.

Computer-administered assessment of cognitive function is being increasingly incorporated in clinical trials; however, its performance in these settings has not been systematically evaluated.The Seniors Health and Activity Research Program pilot trial (N = 73) developed a computer-based tool for assessing memory performance and executive functioning. The Lifestyle Interventions and Independence for Elders investigators incorporated this battery in a full-scale multicenter clinical trial (N = 1635). We describe relationships that test scores have with those from interviewer-administered cognitive function tests and risk factors for cognitive deficits and describe performance measures (completeness, intraclass correlations [ICC]).Computer-based assessments of cognitive function had consistent relationships across the pilot and full-scale trial cohorts with interviewer-administered assessments of cognitive function, age, and a measure of physical function. In the Lifestyle Interventions and Independence for Elders cohort, their external validity was further demonstrated by associations with other risk factors for cognitive dysfunction: education, hypertension, diabetes, and physical function. Acceptable levels of data completeness (83%) were achieved on all computer-based measures; however, rates of missing data were higher among older participants (odds ratio = 1.06 for each additional year; p0.001) and those who reported no current computer use (odds ratio = 2.71; p0.001). ICCs among clinics were at least as low (ICC0.013) as for interviewer measures (ICC0.023), reflecting good standardization. All cognitive measures loaded onto the first principal component (global cognitive function), which accounted for 40% of the overall variance.Our results support the use of computer-based tools for assessing cognitive function in multicenter clinical trials of older individuals.

Previous studies involving inner city populations detected higher cerebral white matter hyperintensity (WMH) scores in African Americans (AAs) compared with European Americans (EAs). This finding might be attributable to the higher prevalence of cardiovascular disease (CVD) risk factors and poorer access to healthcare in AAs. Despite racial differences in CVD risk factor profiles, AAs have paradoxically lower levels of subclinical CVD. We hypothesized that AAs with diabetes and good access to healthcare would have comparable or lower levels of WMH as EAs. Racial differences in the distribution of WMH were analyzed in 46 AAs and 156 EAs with type 2 diabetes enrolled in the Diabetes Heart Study (DHS)-Mind, and replicated in a sample of 113 AAs and 61 EAs patients who had clinically indicated cerebral magnetic resonance imaging. Wilcoxon 2-sample tests and linear models were used to compare the distribution of WMH in AAs and EAs and to test for association between WMH and race. The unadjusted mean WMH score from the Diabetes Heart Study–Mind was 1.9 in AAs and 2.3 in EAs ( P = .3244). Among those with clinically indicated magnetic resonance imaging, the mean WMH score was 2.9 in AAs and 3.9 in EAs ( P = .0503). Adjustment for age and sex produced no statistically significant differences in WMH score between AAs and EAs. These independent datasets reveal comparable WMH scores in AAs and EAs, suggesting that disparities in access to healthcare and environmental exposures likely underlie the previously reported excess burden of WMH in AAs.

Background: To investigate the association between diuretics, angiotensin-converting enzyme inhibitors (ACE-I), angiotensin II receptor blockers (AT2RB), and cognitive function. Methods: This post hoc analysis of the randomized controlled Ginkgo Evaluation of Memory Study trial focuses on 3069 nondemented community-dwelling participants aged >75 years. At baseline visit, detailed information about medication use was collected and five cognitive domains were assessed. Multivariate linear regression analyses were used to assess cross-sectional associations between medication use and cognitive function. Results: In all, 36% of participants reported history of hypertension and 53% reported antihypertensive medication use, with 17% reporting diuretic, 11% ACE-I, and 2% AT2RB use. Potassium-sparing diuretic use (N = 192) was associated with better verbal learning and memory measured by California Verbal Learning Test as compared with no antihypertensive medication users (β = 0.068, P =.01; β = 0.094, P

Objective: To investigate predictors of missing data in a longitudinal study of Alzheimer disease (AD). Methods: The Alzheimer9s Disease Neuroimaging Initiative (ADNI) is a clinic-based, multicenter, longitudinal study with blood, CSF, PET, and MRI scans repeatedly measured in 229 participants with normal cognition (NC), 397 with mild cognitive impairment (MCI), and 193 with mild AD during 2005–2007. We used univariate and multivariable logistic regression models to examine the associations between baseline demographic/clinical features and loss of biomarker follow-ups in ADNI. Results: CSF studies tended to recruit and retain patients with MCI with more AD-like features, including lower levels of baseline CSF Aβ 42 . Depression was the major predictor for MCI dropouts, while family history of AD kept more patients with AD enrolled in PET and MRI studies. Poor cognitive performance was associated with loss of follow-up in most biomarker studies, even among NC participants. The presence of vascular risk factors seemed more critical than cognitive function for predicting dropouts in AD. Conclusion: The missing data are not missing completely at random in ADNI and likely conditional on certain features in addition to cognitive function. Missing data predictors vary across biomarkers and even MCI and AD groups do not share the same missing data pattern. Understanding the missing data structure may help in the design of future longitudinal studies and clinical trials in AD.

Background The efficacy of non-pharmacological intervention approaches such as physical activity, strength, and cognitive training for improving brain health has not been established. Before definitive trials are mounted, important design questions on participation/adherence, training and interventions effects must be answered to more fully inform a full-scale trial. Methods SHARP-P was a single-blinded randomized controlled pilot trial of a 4-month physical activity training intervention (PA) and/or cognitive training intervention (CT) in a 2 × 2 factorial design with a health education control condition in 73 community-dwelling persons, aged 70-85 years, who were at risk for cognitive decline but did not have mild cognitive impairment. Results Intervention attendance rates were higher in the CT and PACT groups: CT: 96%, PA: 76%, PACT: 90% (p=0.004), the interventions produced marked changes in cognitive and physical performance measures (p≤0.05), and retention rates exceeded 90%. There were no statistically significant differences in 4-month changes in composite scores of cognitive, executive, and episodic memory function among arms. Four-month improvements in the composite measure increased with age among participants assigned to physical activity training but decreased with age for other participants (intervention*age interaction p = 0.01). Depending on the choice of outcome, two-armed full-scale trials may require fewer than 1,000 participants (continuous outcome) or 2,000 participants (categorical outcome). Conclusions Good levels of participation, adherence, and retention appear to be achievable for participants through age 85 years. Care should be taken to ensure that an attention control condition does not attenuate intervention effects. Depending on the choice of outcome measures, the necessary sample sizes to conduct four-year trials appear to be feasible. Trial Registration Clinicaltrials.gov Identifier: NCT00688155

To examine the performance of the Telephone Interview for Cognitive Status (TICS) for identifying participants appropriate for trials of physical activity and cognitive training interventions.Volunteers (N=343), ages 70-85 years, who were being recruited for a pilot clinical trial on approaches to prevent cognitive decline, were administered TICS and required to score ≥ 31 prior to an invitation to attend clinic-based assessments. The frequencies of contraindications for physical activity and cognitive training interventions were tallied for individuals grouped by TICS scores. Relationships between TICS scores and other measures of cognitive function were described by scatterplots and correlation coefficients.Eligibility criteria to identify candidates who were appropriate candidates for the trial interventions excluded 51.7% of the volunteers with TICS31. TICS scores above this range were not strongly related to cognition or attendance at screening visits, however overall enrollment yields were approximately half for participants with TICS=31 versus TICS=41, and increased in a graded fashion throughout the range of scores.Use of TICS to define eligibility criteria in trials of physical activity and cognitive training interventions may not be worthwhile in that many individuals with low scores would already be eliminated by intervention-specific criteria and the relationship of TICS with clinic-based tests of cognitive function among appropriate candidates for these interventions may be weak. TICS may be most useful in these trials to identify candidates for oversampling in order to obtain a balanced cohort of participants at risk for cognitive decline.

You are asked to conduct a preoperative assessment of an 86-year-old woman recently admitted to hospital with a fractured right hip. She reports having fallen while getting out of her bathtub but denies any prior history of falls. She has no other injuries. She lives alone at home and was

The herbal product Ginkgo biloba is taken frequently with the intention of improving cognitive health in aging. However, evidence from adequately powered clinical trials is lacking regarding its effect on long-term cognitive functioning.To determine whether G. biloba slows the rates of global or domain-specific cognitive decline in older adults.The Ginkgo Evaluation of Memory (GEM) study, a randomized, double-blind, placebo-controlled clinical trial of 3069 community-dwelling participants aged 72 to 96 years, conducted in 6 academic medical centers in the United States between 2000 and 2008, with a median follow-up of 6.1 years.Twice-daily dose of 120-mg extract of G. biloba (n = 1545) or identical-appearing placebo (n = 1524).Rates of change over time in the Modified Mini-Mental State Examination (3MSE), in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog), and in neuropsychological domains of memory, attention, visual-spatial construction, language, and executive functions, based on sums of z scores of individual tests.Annual rates of decline in z scores did not differ between G. biloba and placebo groups in any domains, including memory (0.043; 95% confidence interval [CI], 0.034-0.051 vs 0.041; 95% CI, 0.032-0.050), attention (0.043; 95% CI, 0.037-0.050 vs 0.048; 95% CI, 0.041-0.054), visuospatial abilities (0.107; 95% CI, 0.097-0.117 vs 0.118; 95% CI, 0.108-0.128), language (0.045; 95% CI, 0.037-0.054 vs 0.041; 95% CI, 0.033-0.048), and executive functions (0.092; 95% CI, 0.086-0.099 vs 0.089; 95% CI, 0.082-0.096). For the 3MSE and ADAS-Cog, rates of change varied by baseline cognitive status (mild cognitive impairment), but there were no differences in rates of change between treatment groups (for 3MSE, P = .71; for ADAS-Cog, P = .97). There was no significant effect modification of treatment on rate of decline by age, sex, race, education, APOE*E4 allele, or baseline mild cognitive impairment (P.05).Compared with placebo, the use of G. biloba, 120 mg twice daily, did not result in less cognitive decline in older adults with normal cognition or with mild cognitive impairment.clinicaltrials.gov Identifier: NCT00010803.

Background Hypertension (HTN) is a risk factor for dementia, and animal studies suggest that centrally active angiotensin-converting enzyme (ACE) inhibitors (those that cross the blood-brain barrier) may protect against dementia beyond HTN control. Methods Participants in the Cardiovascular Health Study Cognition Substudy with treated HTN and no diagnosis of congestive heart failure (n = 1054; mean age, 75 years) were followed up for a median of 6 years to determine whether cumulative exposure to ACE inhibitors (as a class and by central activity), compared with other anti-HTN agents, was associated with a lower risk of incident dementia, cognitive decline (by Modified Mini-Mental State Examination [3MSE]), or incident disability in instrumental activities of daily living (IADLs). Results Among 414 participants who were exposed to ACE inhibitors and 640 who were not, there were 158 cases of incident dementia. Compared with other anti-HTN drugs, there was no association between exposure to all ACE inhibitors and risk of dementia (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.88-1.15), difference in 3MSE scores (−0.32 points per year; P = .15), or odds of disability in IADLs (odds ratio [OR], 1.06; 95% CI, 0.99-1.14). Adjusted results were similar. However, centrally active ACE inhibitors were associated with 65% less decline in 3MSE scores per year of exposure ( P = .01), and noncentrally active ACE inhibitors were associated with a greater risk of incident dementia (adjusted HR, 1.20; 95% CI, 1.00-1.43 per year of exposure) and greater odds of disability in IADLs (adjusted OR, 1.16; 95% CI, 1.03-1.30 per year of exposure) compared with other anti-HTN drugs. Conclusions While ACE inhibitors as a class do not appear to be independently associated with dementia risk or cognitive decline in older hypertensive adults, there may be within-class differences in regard to these outcomes. These results should be confirmed with a randomized clinical trial of a centrally active ACE inhibitor in the prevention of cognitive decline and dementia.

Importance Epidemiological evidence suggests that physical activity benefits cognition, but results from randomized trials are limited and mixed. Objective To determine whether a 24-month physical activity program results in better cognitive function, lower risk of mild cognitive impairment (MCI) or dementia, or both, compared with a health education program. Design, Setting, and Participants A randomized clinical trial, the Lifestyle Interventions and Independence for Elders (LIFE) study, enrolled 1635 community-living participants at 8 US centers from February 2010 until December 2011. Participants were sedentary adults aged 70 to 89 years who were at risk for mobility disability but able to walk 400 m. Interventions A structured, moderate-intensity physical activity program (n = 818) that included walking, resistance training, and flexibility exercises or a health education program (n = 817) of educational workshops and upper-extremity stretching. Main Outcomes and Measures Prespecified secondary outcomes of the LIFE study included cognitive function measured by the Digit Symbol Coding (DSC) task subtest of the Wechsler Adult Intelligence Scale (score range: 0-133; higher scores indicate better function) and the revised Hopkins Verbal Learning Test (HVLT-R; 12-item word list recall task) assessed in 1476 participants (90.3%). Tertiary outcomes included global and executive cognitive function and incident MCI or dementia at 24 months. Results At 24 months, DSC task and HVLT-R scores (adjusted for clinic site, sex, and baseline values) were not different between groups. The mean DSC task scores were 46.26 points for the physical activity group vs 46.28 for the health education group (mean difference, −0.01 points [95% CI, −0.80 to 0.77 points], P = .97). The mean HVLT-R delayed recall scores were 7.22 for the physical activity group vs 7.25 for the health education group (mean difference, −0.03 words [95% CI, −0.29 to 0.24 words], P = .84). No differences for any other cognitive or composite measures were observed. Participants in the physical activity group who were 80 years or older (n = 307) and those with poorer baseline physical performance (n = 328) had better changes in executive function composite scores compared with the health education group ( P = .01 for interaction for both comparisons). Incident MCI or dementia occurred in 98 participants (13.2%) in the physical activity group and 91 participants (12.1%) in the health education group (odds ratio, 1.08 [95% CI, 0.80 to 1.46]). Conclusions and Relevance Among sedentary older adults, a 24-month moderate-intensity physical activity program compared with a health education program did not result in improvements in global or domain-specific cognitive function. Trial Registration clinicaltrials.gov Identifier:NCT01072500

9560 Background: This abstract uses the National Institute on Aging/Alzheimer’s (NIA/AA) criteria to report the prevalence of MCI in a cohort of breast cancer survivors who received adjuvant chemot...