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INTRODUCTION: Neighborhood disadvantage may be an important determinant of cardiometabolic health and cognitive aging. However, less is known about relationships among individuals with mild cognitive impairment (MCI). METHODS: The objective of this study is to investigate the relationship between neighborhood disadvantage measured by national Area Deprivation Index (ADI) rank with measures of cardiometabolic health and cognition among Wake Forest (WF) Alzheimer's Disease Research Center (ADRC) participants, with and without MCI. RESULTS: ADI was positively associated with blood pressure and cardiometabolic index (CMI), and negatively associated with global and Preclinical Alzheimer's Cognitive Composite (PACC5) scores, in cognitively unimpaired (CU) individuals. ADI was only positively associated with hemoglobin A1c (HbA1c) in MCI. DISCUSSION: Neighborhood disadvantage is associated more strongly with measures of cardiometabolic health and cognition among CU individuals rather than MCI. These findings demonstrate a need for structural solutions to address social determinants of health in an attempt to reduce cardiometabolic and cognitive risks. [ABSTRACT FROM AUTHOR]

Background: The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) will determine whether interventions that simultaneously include multiple risk reduction strategies can protect cognitive health in older adults. The primary outcome, a global cognitive composite score derived from the POINTER‐Modified Neuropsychological Test Battery (PmNTB), was developed to allow for outcome harmonization with its forerunner, the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) and other large trials (e.g., A4, EXERT). Here we describe the PmNTB and its initial validation in the baseline U.S. POINTER sample. Method: U.S. POINTER is a Phase 3, multicenter, randomized 2‐year clinical trial of two interventions varying in intensity and format, in older adults at increased risk for cognitive decline and dementia. The PmNTB includes performance from 7 cognitive tests and is computed as the mean of three domain‐specific composites: Episodic Memory, Processing Speed, and Executive Function. The Episodic Memory Composite includes Free and Cued Selective Reminding Test, Story Recall, and Visual Paired Associates. The Processing Speed Composite includes Trail Making Test (TMTA) and Digit Symbol Substitution Test. The Executive Function Composite includes Number Span, Word Fluency, and TMTB. PmNTB was assessed in relation to age, clinical status (Clinical Dementia Rating‐CDR), and other cognitive composites able to be computed in the current sample using overlapping measures (i.e., FINGER NTB, Preclinical Alzheimer's Cognitive Composite‐PACC‐5). Result: 2094 participants completed the baseline assessment (mean age = 68.2±5.2 years; 68.8% female, 69.1% non‐hispanic white, mean MMSE = 28.9± 1.3). Global CDR was 0 for 79.5% of participants, and 0.5 for 20.5% of participants. After adjusting for education, race, ethnicity, and sex, each additional year in age was associated with a drop in PmNTB z‐score by ‐0.064 (95%CI = ‐0.071,‐0.056, p<0.001). Likewise, global CDR = 0.5 (questionable dementia) was associated with a lower PmNTB score (z = ‐0.549) compared with global CDR = 0 (‐0.134 z‐scores). PmNTB correlated with the FINGER NTB (r = 0.858, p<0.001) and the PACC‐5 (r = 0.876, p<0.001). Conclusion: The PmNTB is a valid measure of cognitive functioning, capturing age‐related cognitive decrements and is associated with clinically relevant, functional outcomes. It also exhibits convergent validity with established cognitive outcomes. [ABSTRACT FROM AUTHOR]

In this article, the 3‐methacryloxypropyltrimethoxy silane (KH570) was deposited onto the surface of the polyurethane (PU) membrane to prepare pervaporation (PV) desulfurization membrane. The modified membrane was characterized by Fourier transform infrared spectrum, scanning electron microscopy, and atomic force microscope and so forth. After modification, the surface exhibited a special morphology with cracks which was micro‐controlled by adjusting the hydrolysis time, the concentration and the deposition time of KH570. Through the PV performance of the modified membrane, it was found that the surface morphology with cracks effectively reduced the mass transfer resistance and enlarged contact area, which played a key role in the increase of flux. Under the optimal modification conditions, the flux of the membrane was 2.41 kg m−2 h−1, which increased by 154% in comparison with the pristine PU membrane, while the enrichment factor maintained a satisfactory level of 7.35. Therefore, this study provided a new insight to fabricate a high performance PV desulfurization membrane. [ABSTRACT FROM AUTHOR]

Background: The brain is particularly sensitive to excessive pressure and flow pulsatility. Disproportionate stiffening of the aorta can reduce wave reflection at the aorta‐carotid interface and facilitate transmission of excessive pulsatile energy into the cerebral microcirculation, leading to impaired cognitive function. The U.S. POINTER Neurovascular (POINTER‐NV) ancillary study is an ongoing study designed to evaluate vascular structure and function in participants from the U.S. POINTER trial. Here we describe the baseline characteristics of the POINTER‐NV participants, focusing on aortic and carotid variables and their association with cognitive function. Method: Ultrasound and tonometry were used to assess aortic and carotid measures. Hemodynamic and structural variables were compared according to cognitive status using the baseline Clinical Dementia Rating Scale Sum of Boxes (CDR‐SB) score categorized as normal (CDR‐SB = 0) or possibly impaired (CDR‐SB>0). Linear regression was used to assess cross‐sectional associations between aortic and carotid variables and composite scores for global cognition, executive function, memory, and processing speed, with and without adjustment for age, sex, race, and ethnicity. Result: Aortic and carotid hemodynamics were available for 165 POINTER‐NV participants (mean age: 67.9±5.1 years, 70% female, 37% people of color). A large proportion of the participants had evidence of subclinical cardiovascular disease based on a carotid intima‐media thickness ≥1.0 mm (n = 109/165, 66.1%) or increased aortic stiffness based on a carotid‐femoral pulse wave velocity >10 m/s (n = 70/131, 53.4%). There were no significant differences in aortic or carotid structure and function between participants with normal cognition (n = 109) and those with possible cognitive impairment (n = 56). Higher carotid‐femoral pulse wave velocity was associated with lower global cognition, executive function, and processing speed, even after adjustment for age, sex, race, and ethnicity (all p<0.05). Although there was some suggestion that higher carotid pulsatility, higher carotid transmission, and lower aorta‐carotid reflection may be associated with worse cognition, these associations were not consistent across cognitive domains and did not hold up after covariate adjustment. Conclusion: Age‐related changes in vascular structure and function can promote cognitive decline and dementia. Our data are consistent with prior evidence suggesting that higher aortic stiffness may be particularly important in this regard. [ABSTRACT FROM AUTHOR]

Background: The arterial baroreflex maintains stable blood flow to the brain. Reduced baroreflex sensitivity for modulation of heart rate (BRS) has been observed in patients with Alzheimer's disease (AD) and mild cognitive impairment and may be impacted by race, ethnicity, sex, and socioeconomic factors such as the Area Deprivation Index (ADI), a validated, neighborhood‐level composite index that incorporates 17 social determinants of health. However, these relationships have not been well described. Method: This study utilized baseline data from 196 participants enrolled in the U.S. POINTER Neurovascular study, an ancillary to the parent U.S. POINTER multi‐site lifestyle intervention trial that adds assessments of autonomic function and vascular structure and function. BRS was calculated from continuous blood pressure and electrocardiogram recording using the slope of the regression line between changes in systolic blood pressure and RR interval values in the same direction, with higher BRS indicating better autonomic function. ADI scores ranging from 1 to 10 were calculated using 9‐digit zip codes, with 10 indicating the greatest disadvantage. Analysis of variance and linear regression were used to evaluate associations between measures of interest. Result: The average age of the study population was 67.9 ± 5.4 years, 64 (17%) were males, and 60 (30.6%) identified as people of color (POC). Overall, the mean BRS was 9.2 ± 4.6 ms/mmHg, and the average ADI score was 4.56 ± 2.69 (range: 1 to 10), corresponding to a national ADI percentile of 40.7 ± 26.1 (range: 3 to 100). Less than a quarter of participants (n = 42, 21.4%) had an ADI percentile >67, indicating a moderate to high level of neighborhood disadvantage. White participants had lower BRS compared to POC (8.60 ± 4.49 vs. 10.60 ± 4.61 ms/mmHg, p = 0.0048). In a multiple regression model adjusting for demographics and ADI, sex (p = 0.0283), race and ethnicity (p = 0.0049), and education (p = 0.0196) were significantly associated with BRS, indicating better autonomic function in men, POC, and those with higher education. ADI was not associated with BRS. Conclusion: Race, ethnicity, and education impact autonomic function. Further investigations are needed to assess the impact of other demographic and socioeconomic factors on neurovascular health. [ABSTRACT FROM AUTHOR]

Background: Sleep disordered breathing (SDB) leads to nocturnal hypoxemia and sleep disruption, which are linked to adverse health conditions, particularly in older adults at risk for dementia. Few prospective studies of SDB examine cognitive decline among those at increased risk for cognitive impairment and dementia. POINTER‐zzz, a sleep ancillary study of U.S. study to PrOtect brain health through lifestyle INTErvention to Reduce risk (U.S. POINTER), allows us to examine the role of lifestyle intervention on sleep quality, and potential moderating effects of sleep on cognition to the intervention in medically and cognitively vulnerable older adults. Method: U.S. POINTER was designed to investigate the effects of two 2‐year lifestyle interventions on cognitive trajectories in 2,000 older, cognitively normal adults (aged 60‐79 yrs) at increased risk for cognitive decline and dementia due to physical inactivity, poor diet and cardiovascular disease. POINTER‐zzz enrolled a subset of parent trial participants and administered in‐home sleep assessments using WatchPAT (1 night) and ActiGraph (6 nights) devices. We summarize participants' baseline characteristics including apnea hypopnea index (AHI), sleep duration and sleep efficiency. Result: To date, 688 POINTER‐zzz participants enrolled and completed baseline WatchPAT and/or Actigraph assessments. Participant ages averaged 68.6 years old (standard deviation, 5.13); 21% of participants self‐identified as Black/African American, 4% Hispanic/Latino, and 66% White. More than half (68%) were female, and 69% had a Bachelor's degree or higher. Overall, 87% of participants had at least mild sleep apnea (AHI>5). Severe sleep apnea (AHI≥30) was observed in 14% of participants overall, and 21% of those aged ≥75 yrs. Severe sleep apnea was more prevalent among males (19%) than females (11%). Overall, nightly sleep duration for the cohort averaged 6.6 hours, with 83% sleep efficiency, and an average of 79.3 minutes awake after sleep onset. Conclusion: POINTER‐zzz participants have sleep characteristics that align with expectations for a cohort that is broadly representative of a diverse older adult population in the US. POINTER‐zzz provides an unparalleled opportunity to test the effects of a multi‐domain lifestyle intervention on sleep disturbances that are linked to cognitive decline and AD in a well‐characterized, diverse cohort of at‐risk older adults. [ABSTRACT FROM AUTHOR]

Background: The U.S. POINTER study is a phase 3, multicenter, 2‐year randomized controlled trial (RCT) of two lifestyle interventions varying in intensity and format, conducted in older adults living in the U.S. who do not have objective cognitive impairment at study entry, but have increased risk of cognitive decline and dementia. Inclusion criteria included specific risk factors (e.g., family history of dementia, vascular risk factors) but not subjective cognitive concerns (SCCs). However, SCCs are likely to be common in this group of at‐risk individuals. U.S. POINTER provides a unique opportunity to evaluate the prevalence of SCCs and their demographic and clinical correlates in an at‐risk group. Methods: Recruitment for the U.S. POINTER study is still ongoing, and the following is based on a partial sample. The sample includes 1811 U.S. POINTER participants with complete baseline data (collected by December 2022), mean age = 68.2y (SD = 5.2), 73.5% are female, 70.2% have18+ years education, and 29.3% are from underrepresented groups. SCCs were measured by the brief 12‐item Everyday Cognition (ECog) questionnaire which includes two items in each of 6 domains: everyday memory, language, visuospatial abilities, planning, organization and divided attention. Responses on the ECog range from 0 = no change/better compared to baseline, 1 = questionably/inconsistently worse, 2 = consistently a little worse, 3 = much worse. Neuropsychological performance was measured using a global composite and episodic memory, executive functioning, and processing speed composites. Other variables included demographics, depression (Geriatric Depression Scale total score; GDS) and sleep (Insomnia severity index (ISI)) and vascular disease burden index. Results: Thirty‐five percent of the cohort endorsed having a subjective complaint on the ECog (score ≥2 on any item). The most frequent complaint was "Remembering where I have placed objects" (23%). SCCs did not differ by age, sex or education. ECog‐12 Total were related to insomnia and depression (p<.0001). After adjusting for age, sex, education, vascular risk burden, GDS and ISI, greater SCC (ECog‐12 Total) was still associated with the global composite and all three domains (ps < 0.003). Conclusions: SCCs, particularly everyday memory complaints, were relatively common in this at‐risk cohort. While SCCs were related to depression and sleep, they were also independently associated with slightly worse cognitive function. [ABSTRACT FROM AUTHOR]

Background: Cognitive dispersion refers to the within‐person variability across tasks. Relative to the normative approach, cognitive dispersion may be more sensitive to subtle changes in preclinical Alzheimer's disease. Greater dispersion has been associated with increased risk for conversion to mild cognitive impairment and faster rates of medial temporal lobe atrophy. This metric can be derived from a regular neuropsychological assessment and complement traditional outcome approaches, particularly in those underrepresented in normative data. This study evaluated cognitive dispersion as an independent predictor of clinical status across racial and ethnic groups. Method: Baseline data on 1811 cognitively unimpaired older adults with high vascular risk from the U.S. POINTER multisite lifestyle intervention study were examined. Sample characteristics included mean age of 68 (SD = 5.2), 70% female, 30% less‐than‐college education, and 29% underrepresented groups (301 Black, 231 Other). Correlations between cognitive dispersion and other brain health risks (vascular, subjective cognitive decline (SCD), physical activity) were tested. Cognitive dispersion was defined as the standard deviation of individuals' z‐transformed scores of 8 cognitive tests. Vascular risk burden was the sum of 5 conditions (hypertension, diabetes, hypercholesterolemia, heart disease, obesity). Self‐report SCD was measured by the Cognitive Function Instrument (CFI) and Measurement of Everyday Cognition (ECOG12). Logistic Regression Models were fitted to predict Clinical Dementia Global Ratings (CDR 0.5 vs. 0) to evaluate cognitive dispersion as an independent predictor in the whole sample, White participants and Black participants, controlled for demographics, vascular risk, and physical activity. Logistic Regression Models were also evaluated with CFI or ECOG12 as additional covariate. Result: Greater cognitive dispersion was correlated with older age, greater vascular burden and less physical activity, but not SCD. Cognitive dispersion was significantly higher in men, Black participants, and participants with less education. Cognitive dispersion predicted CDR in Black participants (OR = 4.7, p<0.01), and trended in the whole sample (OR = 1.6, p = 0.05), but was not significant in White participants (OR = 1.2, p = 0.63). Results hold when controlled for SCD (Table 1). Conclusion: Results supported cognitive dispersion as a sensitive objective metric, in addition to self‐report SCD, to identify individuals showing the earliest clinical signs of decline, particularly among those underrepresented in traditional norms. [ABSTRACT FROM AUTHOR]

Background: Autonomic regulation plays a major role in maintaining stable blood supply to the brain. Impaired autonomic function, as evidenced by high blood pressure variability (BPV) and/or low heart rate variability (HRV), is common in older adults and is associated with reduced perfusion, which can ultimately lead to impaired cognitive function. The U.S. POINTER Neurovascular (POINTER‐NV) ancillary study is an ongoing study designed to evaluate autonomic function in participants from the U.S. POINTER trial. Here we describe the baseline characteristics of the POINTER‐NV participants, focusing on autonomic measures and their relationship to cognitive function. Method: Continuous blood pressure and ECG recordings were used to assess BPV, HRV, and sympathovagal balance. Autonomic variables were compared according to cognitive status using the baseline Clinical Dementia Rating Scale Sum of Boxes (CDR‐SB) score. Linear regression was used to assess cross‐sectional associations between sympathovagal balance and BPV variables and composite scores for global cognition, executive function, memory, and processing speed, with and without adjustment for age, sex, and race/ethnicity. Result: Autonomic measures were available for 212 POINTER‐NV participants (mean age: 67.9 ± 5.4 years, 67% female, 33% people of color). There were no significant differences in BPV or HRV measures between participants with normal cognition (CDR‐SB score = 0) and those with possible cognitive impairment (CDR‐SB score = 0.5–1.0). Higher sympathovagal balance was significantly associated with higher scores of global cognition, executive function, and processing speed; however, this association became statistically insignificant after adjustment for age, sex, and race/ethnicity. Higher BPV measured as standard deviation of mean arterial pressure (SDMAP) was associated with lower scores for episodic memory after adjustment for age, sex, and race/ethnicity (p = 0.03). There was some suggestion that lower HRV might be associated with worse cognition, however, these associations were inconsistent across cognitive domains and did not remain after covariate adjustment. Conclusion: Age‐related changes in autonomic function can promote cognitive decline and dementia. Our data are consistent with prior evidence suggesting a role for sympathovagal balance and blood pressure variability in modulating cognitive function [ABSTRACT FROM AUTHOR]

Objective: This study examined the short- and long-term effects of adding caloric restriction to 5 months of aerobic exercise training on executive function in sedentary older adults with obesity.Methods: Sedentary adults with obesity aged 65 to 79 years completed a randomized trial investigating the cardiorespiratory benefits of adding moderate (~ 250 kcal) or high (~ 600 kcal) caloric restriction to a 20-week aerobic exercise program. Approximately half (n = 88) completed a cognitive assessment battery at baseline, post intervention, and 18 to 24 months after intervention completion. The primary outcome was an executive function composite score.Results: In the overall sample, the executive function composite increased 0.114 from baseline to postintervention (P = 0.01). Randomization to caloric restriction did not significantly alter executive function over aerobic exercise alone, nor were there between-group differences on any individual executive function test following the intervention or at long-term follow-up. Adding caloric restriction to exercise was associated with a modest increase in Mini-Mental State Examination score (P = 0.04). In the overall sample, increases from baseline at long-term follow-up were noted in digit symbol and word list recall performance as well.Conclusions: Adding caloric restriction to a 20-week aerobic exercise program does not worsen or improve executive function more than exercise alone assessed up to 24 months post randomization. [ABSTRACT FROM AUTHOR]

Background: U.S. POINTER is testing whether multidomain lifestyle interventions focused on physical exercise, nutrition, cognitive challenge, and risk factor management reduces risk of cognitive decline in a heterogeneous population of at‐risk older adults in America. The study adapts the FINGER (Finnish Intervention Geriatric Study to Prevent Cognitive Impairment and Disability) interventions to fit the United States culture and delivers the intervention within the community at 5 sites across the country. Method: U.S. POINTER is a 2‐year RCT that will enroll 2000 cognitively unimpaired older adults who are at risk for cognitive decline due sedentary lifestyle, poor diet and other factors. Participants are randomized to one of two lifestyle intervention groups that differ in format and intensity. In 2020, the COVID‐19 pandemic presented a number of challenges for the study that affected recruitment, assessment schedules, and intervention delivery. Result: As of March 2020, when COVID‐19 incidence was on an exponential rise in the US, 240 participants had been enrolled in U.S. POINTER. In response to local and national safety mandates, study activities were paused from March 23rd to July 13th. During the pause, sites remained in contact with study candidates and enrolled participants to provide ongoing support to keep them engaged in the trial. Enrollees also received regular telephone calls to encourage continued adherence to their assigned lifestyle intervention. In response to the multiple pandemic‐related challenges, study protocols and procedures were adapted to facilitate and encourage participant adherence to intervention activities. At study re‐start, retention was 98%. Despite climbing COVID‐19 infection rates nationwide, enrollment at all 5 sites has continued at a steady rate (N=540 as of Jan2021), virtual Team Meeting attendance for both lifestyle groups exceeds 80%, and participants continue to successfully work toward their intervention goals. Conclusion: The COVID‐19 pandemic presented unprecedented challenges, but it also provided a unique opportunity to adapt intervention delivery so that a nonpharmacological community‐based trial could continue – even during a debilitating global health crisis. U.S. POINTER's adaptations to pandemic‐related challenges may ultimately increase the resilience of its interventions to even the most challenging of circumstances that older adults will face now and in the future. [ABSTRACT FROM AUTHOR]

Introduction Consistent evidence linking habitual sleep duration with risks of mild cognitive impairment (MCI) and dementia is lacking. Methods We conducted a prospective study on 7444 community-dwelling women (aged 65–80 y) with self-reported sleep duration, within the Women's Health Initiative Memory Study in 1995–2008. Incident MCI/dementia cases were ascertained by validated protocols. Cox models were used to adjust for multiple sociodemographic and lifestyle factors, depression, cardiovascular disease (CVD), and other clinical characteristics. Results We found a statistically significant ( P = .03) V-shaped association with a higher MCI/dementia risk in women with either short (≤6 hours/night) or long (≥8 hours/night) sleep duration (vs. 7 hours/night). The multicovariate-adjusted hazard for MCI/dementia was increased by 36% in short sleepers irrespective of CVD, and by 35% in long sleepers without CVD. A similar V-shaped association was found with cognitive decline. Discussion In older women, habitual sleep duration predicts the future risk for cognitive impairments including dementia, independent of vascular risk factors. [ABSTRACT FROM AUTHOR]

Objectives To describe the interindividual variability in physical function responses to supervised resistance and aerobic exercise training interventions in older adults. Design Data analysis of two randomized, controlled exercise trials. Setting Community-based research centers. Participants Overweight and obese (body mass index ( BMI) ≥27.0 kg/m2) sedentary men and women aged 65 to 79 (N = 95). Intervention Five months of 4 d/wk of aerobic training ( AT, n = 40) or 3 d/wk of resistance training ( RT, n = 55). Measurements Physical function assessments: global measure of lower extremity function (Short Physical Performance Battery ( SPPB)), 400-m walk, peak aerobic capacity ( VO2peak), and knee extensor strength. Results On average, both exercise interventions significantly improved physical function. For AT, there was a 7.9% increase in VO2peak; individual absolute increases varied from 0.4 to 4.3 mL/kg per minute, and four participants (13%) showed no change or a decrease in VO2peak. For RT, knee extensor strength improved an average of 8.1%; individual increases varied from 1.2 to 63.7 Nm, and 16 participants (30%) showed no change or a decrease in strength. Usual gait speed, 400-m walk time, chair rise time, and SPPB improved for the majority of AT participants and usual gait speed, chair rise time, and SPPB improved for the majority of RT participants, but there was wide variation in the magnitude of improvement. Only change in 400-m walk time with RT was related to exercise adherence (correlation coefficient = −0.31, P = .004). Conclusion Despite sufficient levels of adherence to both exercise interventions, some participants did not improve function, and the magnitude of improvement varied widely. Additional research is needed to identify factors that optimize responsiveness to exercise to maximize its functional benefits in older adults. [ABSTRACT FROM AUTHOR]

Objective To assess the long-term effects of an intensive lifestyle intervention on physical function using a randomized post-test design in the Look AHEAD trial. Methods Overweight and obese (BMI ≥ 25 kg m−2) middle-aged and older adults (aged 45-76 years at enrollment) with type 2 diabetes ( n = 964) at four clinics in Look AHEAD, a trial evaluating an intensive lifestyle intervention (ILI) designed to achieve weight loss through caloric restriction and increased physical activity compared to diabetes support and education (DSE), underwent standardized assessments of performance-based physical function including an expanded short physical performance battery (SPPBexp), 20-m and 400-m walk, and grip and knee extensor strength 8 years post-randomization, during the trial's weight maintenance phase. Results Eight years post-randomization, individuals randomized to ILI had better SPPBexp scores [adjusted mean (SE) difference: 0.055 (0.022), P = 0.01] and faster 20-m and 400-m walk speeds [0.032 (0.012) m s−1, P = 0.01, and 0.025 (0.011) m s−1, P = 0.02, respectively] compared to those randomized to DSE. Achieved weight loss greatly attenuated the group differences in physical function, and the intervention effect was no longer significant. Conclusions An intensive lifestyle intervention has long-term benefits for mobility function in overweight and obese middle-aged and older individuals with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective The objective was to determine whether adding a self-regulatory intervention (SRI) focused on self-monitoring of spontaneous physical activity (SPA) and sedentary behavior to a standard weight loss intervention improved maintenance of lost weight. Methods Older (65-79 years), obese (BMI = 30-40 kg/m2) adults ( n = 48) were randomized to a 5-month weight loss intervention involving a hypocaloric diet (DIET) and aerobic exercise (EX) with or without the SRI to promote SPA and decrease sedentary behavior (SRI + DIET + EX compared with DIET + EX). Following the weight loss phase, both groups transitioned to self-selected diet and exercise behavior during a 5-month follow-up. Throughout the 10-months, the SRI + DIET + EX group utilized real-time accelerometer feedback for self-monitoring. Results There was an overall group by time effect of the SRI ( P < 0.01); DIET + EX lost less weight and regained more weight than SRI + DIET + EX. The average weight regain during follow-up was 1.3 kg less in the SRI + DIET + EX group. Individuals in this group maintained approximately 10% lower weight than baseline compared with those in the DIET + EX group whom maintained approximately 5% lower weight than baseline. Conclusions Addition of a SRI, designed to increase SPA and decrease sedentary behavior, to a standard weight loss intervention enhanced successful maintenance of lost weight. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis In previous studies, we consistently found that approximately 30% of asymptomatic healthy older adults silently aspirated liquids during a flexible endoscopic evaluation of swallowing (FEES) and that their aspiration status was stable for the following year. However, no studies have systematically evaluated effects of silent aspiration on lung parenchyma and airways. We used computed tomography (CT) to compare lungs of healthy older adult aspirators versus nonaspirators. We hypothesized that CT images would show pulmonary differences in healthy older adult aspirators versus nonaspirators. Study Design Prospective study. Methods Fifty healthy older adults (25 aspirators and 25 nonaspirators) who participated in a previous FEES were randomly selected. CT scans were performed; on inspiration, lung views were taken at 1.25 mm and 2.5 mm windows, and on expiration, lung views were taken at 2.5 mm. CT scans were reviewed by radiologists blinded to group assignment. Outcomes included bronchiectasis, bronchiolectasis, bronchial wall thickening, parenchymal band, fibrosis, air trapping, intraluminal airway debris, and tree-in-bud pattern. Results χ2 analyses between aspirators and nonaspirators found no statistically significant differences between aspirators and nonaspirators for any outcomes ( P > .05). Logistic regression analyses adjusted for smoking did not change the results. Conclusions There were no differences in pulmonary CT findings between healthy older adult aspirators and nonaspirators. This study adds to the evidence that some aspiration may be within the range of normal for older adults, or at least does not contribute to a change in pulmonary appearance on CT images. Level of Evidence 3b Laryngoscope, 124:494-497, 2014 [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To identify treatable risk factors for aspiration in older adults, particularly those associated with sarcopenia, we examined tongue composition. We hypothesized that isometric and swallowing posterior tongue strength would positively correlate with posterior tongue adiposity, and healthy older adults who aspirate would have greater tongue adiposity than healthy older adults who did not aspirate. Study Design: Prospective. Methods: Participants were 40 healthy adults, comprised of 20 aspirators (mean age, 78 years) and 20 nonaspirators (mean age, 81 years), as identified via flexible endoscopic evaluation of swallowing. Measures of maximal isometric posterior tongue strength and posterior swallowing tongue strength were acquired via tongue manometry. An index of posterior tongue adiposity was acquired via computed tomography for a 1-cm region of interest. Results: Posterior tongue adiposity was correlated with posterior tongue isometric ( r = 0.32, P = .05) but not swallowing pressures ( P > .05) as examined with separate partial correlation analyses. Tongue adiposity did not significantly differ as a function of age, gender, or aspiration status ( P > .05). Conclusions: Lower posterior isometric tongue strength was associated with greater posterior tongue adiposity. However, aspiration in healthy older adults was not affected by posterior tongue adiposity. This finding offers insight into the roles of tongue composition and strength in healthy older adults. [ABSTRACT FROM AUTHOR]

Objectives: This analysis delineates the predisposing, need, and enabling factors that are associated with regular and recent dental care in a multiethnic sample of rural older adults. Methods: A cross-sectional, comprehensive, oral-health survey conducted with a random, multiethnic (African American, American Indian, white) sample of 635 community-dwelling adults aged 60 years and older was completed in two rural southern counties. Logistic regression models assessed the simultaneous associations of dental care with predisposing, enabling, and need factors. Results: Almost no edentulous rural older adults received dental care; 27.1 percent of dentate rural older adults had received regular dental care, and 36.7 percent had received recent dental care. Predisposing (less than high-school education, dental anxiety), enabling (no regular place for dental care), and need factors (no filled teeth) reduced the odds of regular dental, while predisposing (dental anxiety), enabling (no regular place for dental care), and need factors (no filled teeth) reduced the odds of recent dental care. Having excellent, very good, or good self-rated oral health increased the odds of receiving regular and recent dental care. Conclusions: Regular and recent dental care are infrequent among rural older adults. Contrary to expectations, those not receiving dental care are those who most need care; this has been referred to as the Paradox of Dental Need. Community access to dental care and the ability of older adults to pay for dental care must be addressed by public-health policy to improve the health and quality of life of older adults in rural communities. [ABSTRACT FROM AUTHOR]

Objective To better understand the contribution of age to the development of osteoarthritis (OA). Methods Surgical destabilization of the medial meniscus (DMM) was used to model OA in 12-week-old and 12-month-old male C57BL/6 mice. OA severity was evaluated histologically. RNA used for microarray and real-time polymerase chain reaction analysis was isolated from joint tissue collected from the medial side of the joint, including cartilage, meniscus, subchondral bone, and the joint capsule with synovium. Computational analysis was used to identify patterns of gene expression, and immunohistochemistry was used to evaluate tissue distribution of selected proteins. Results OA was more severe in older mice than in young mice. Only 55 genes showed a similar expression with DMM-induced OA in the 2 age groups, while 493 genes showed differential expression, the majority having increased expression in older mice. Functional categories for similarly expressed genes included extracellular matrix- and cell adhesion-related genes; differentially expressed genes included those related to muscle structure and development and immune response genes. Comparison of expression in sham-operated control joints revealed an age-related decrease in matrix gene expression and an increase in immune and defense response gene expression. Interleukin-33 was present in multiple joint tissue cells, while CCL21 was more localized to chondrocytes and meniscal cells. Periostin was found in the extracellular matrix of cartilage and meniscus. Conclusion Age affects both the basal pattern of gene expression in joint tissues and the response to surgically induced OA. Examining tissue from the joint beyond only cartilage revealed novel genes and proteins that would be important to consider in OA. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Scant data exist on normal bolus dwell time assessed during flexible endoscopic evaluation of swallowing (FEES). The purpose of this study was to examine bolus dwell time in healthy older adults. Because it has been previously reported that some healthy older adults aspirate, we also sought to determine if bolus dwell time varied as a function of aspiration status. Study Design: Prospective. Methods: Seventy-six healthy volunteers from the seventh, eighth, and ninth decades of life participated. Dwell times were analyzed via FEES as a function of pharyngeal location, liquid type, delivery method, purée type, viscosity, age, and gender. Results: Longer dwell times were evidenced with the eldest participants, straw delivery, and the smallest volume. Adults in the ninth decade were 4.8 ( P = .01) and 3.8 ( P = .02) times more likely to have longer dwell times at the vallecula and 7.1 ( P = .002) and 3.8 ( P = 0.02) at the pyriform sinus than those in the seventh and eighth decades, respectively. Longer dwell times at the vallecula and pyriform sinuses were 2 and 2.38 times ( P < .0001) more likely for straw than cup delivery, respectively. Boluses of 5 mL were 1.5 times ( P < .05) more likely to result in longer dwell times than larger volumes. Bolus dwell times did not significantly differ as a function of aspiration status. Conclusions: Advanced age, straw delivery, and small volumes yielded longer dwell times. These variables should be considered before diagnosing an abnormal bolus dwell time in elder patients. [ABSTRACT FROM AUTHOR]

To quantify prevalence of dry mouth, association between dry mouth and beverage intake and dietary quality, and association between dry mouth and self-reported dietary accommodations to oral health deficits. Cross-sectional study; data from self-reports. Rural North Carolina counties with substantial African-American and American Indian populations. Six hundred twenty-two participants aged 60 and older. Data included the 11-item Xerostomia Inventory (higher scores connote greater effect from dry mouth), a food frequency questionnaire (converted into Health Eating Index-2005 scores), and survey items on foods modified before consumption or avoided because of oral health problems. Dry mouth was associated with being female, lower education, and income below the poverty level. Although overall beverage consumption did not vary with dry mouth, consumption of certain sugar-sweetened beverages was positively associated with dry mouth. Overall dietary quality did not differ with dry mouth, but more-severe dry mouth was associated with lower intake of whole grains and higher intakes of fruits. Dry mouth was strongly associated with self-reported modification and avoidance of foods. Those in the highest tertile of dry mouth were more likely to modify several foods than those in the lowest tertile and were more likely to avoid three or more foods. Older adults appear to modify foods or selectively avoid foods in response to perceived dry mouth. Despite these behaviors, dry mouth does not result in poorer dietary quality. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To quantify the association between food avoidance and modification due to oral health problems, to examine the association between food practices and dietary quality, and to determine foods associated with these self-management behaviors. DESIGN: Cross-sectional. SETTING: Rural North Carolina. PARTICIPANTS: Six hundred thirty-five community-dwelling adults aged 60 and older. MEASUREMENTS: Demographic and food frequency data and oral health assessments were obtained during home visits. Avoidance (0, 1–2 foods, 3–14 foods) and modification (0–3 foods, 4–5 foods) due to oral health problems were assessed for foods representing oral health challenges. Food frequency data were converted into Healthy Eating Index-2005 (HEI-2005) scores. Linear regression models tested the significance of associations between HEI-2005 measures and food avoidance and modification. RESULTS: Thirty-five percent of participants avoided three to 14 foods, and 28% modified four to five foods. After adjusting for age, sex, ethnicity, poverty, education, and tooth loss, total HEI-2005 score was lower ( P<.001) for persons avoiding more foods and higher for persons modifying more foods ( P<.001). Those avoiding three to 14 foods consumed more saturated fat and energy from solid fat and added sugar and less nonhydrogenated fat than those avoiding fewer than three foods. Those who modified four to five foods consumed less saturated fat and solid fat and added sugar but more total grains than those modifying fewer than four foods. CONCLUSION: Food avoidance and modification due to oral health problems are associated with significant differences in dietary quality. Approaches to minimize food avoidance and promote food modification by persons having eating difficulties due to oral health conditions are needed. [ABSTRACT FROM AUTHOR]

The medical and personal circumstances of older persons present challenges for designing and analyzing clinical research studies in which they participate. These challenges that elderly study samples present are not unique, but they are sufficiently distinctive to warrant deliberate and systematic attention. Their distinctiveness originates in the multifactorial etiologies of geriatric health syndromes and the multiple morbidities accruing with aging at the end of life. The objective of this article is to identify a set of statistical challenges arising in research with older persons that should be considered conjointly in the practice of clinical research and addressed systematically in the training of biostatisticians intending to work with gerontologists, geriatricians, and older study participants. The statistical challenges include design and analytical strategies for multicomponent interventions, multiple outcomes, state transition models, floor and ceiling effects, missing data, and mixed methods. The methodological and pedagogical themes of this article will be integrated by a description of a proposed subdiscipline of “gerontologic biostatistics” and supported by the introduction of new set of statistical resources for researchers working in this area. These conceptual and methodological resources have been developed in the context of several collaborating Claude D. Pepper Older Americans Independence Centers. [ABSTRACT FROM AUTHOR]

Background: We have developed an animal model of alcohol self-administration that initially employs schedule-induced polydipsia (SIP) to establish reliable ethanol consumption under open access (22 h/d) conditions with food and water concurrently available. SIP is an adjunctive behavior that is generated by constraining access to an important commodity (e.g., flavored food). The induction schedule and ethanol polydipsia generated under these conditions affords the opportunity to investigate the development of drinking typologies that lead to chronic, excessive alcohol consumption. Methods: Adult male cynomolgus monkeys (Macaca fascicularis) were induced to drink water and 4% (w/v in water) ethanol by a Fixed-Time 300 seconds (FT-300 seconds) schedule of banana-flavored pellet delivery. The FT-300 seconds schedule was in effect for 120 consecutive sessions, with daily induction doses increasing from 0.0 to 0.5 g/kg to 1.0 g/kg to 1.5 g/kg every 30 days. Following induction, the monkeys were allowed concurrent access to 4% (w/v) ethanol and water for 22 h/day for 12 months. Results: Drinking typographies during the induction of drinking 1.5 g/kg ethanol emerged that were highly predictive of the daily ethanol intake over the next 12 months. Specifically, the frequency in which monkeys ingested 1.5 g/kg ethanol without a 5-minute lapse in drinking (defined as a bout of drinking) during induction strongly predicted (correlation 0.91) subsequent ethanol intake over the next 12 months of open access to ethanol. Blood ethanol during induction were highly correlated with intake and with drinking typography and ranged from 100 to 160 mg% when the monkeys drank their 1.5 g/kg dose in a single bout. Forty percent of the population became heavy drinkers (mean daily intakes >3.0 g/kg for 12 months) characterized by frequent “spree” drinking (intakes >4.0 g/kg/d). Conclusion: This model of ethanol self-administration identifies early alcohol drinking typographies (gulping the equivalent of 6 drinks) that evolve into chronic heavy alcohol consumption in primates (drinking the equivalent of 16 to 20 drinks per day). The model may aid in identifying biological risks for establishing harmful alcohol drinking. [ABSTRACT FROM AUTHOR]

Background: U.S. POINTER aims to test whether a multidomain lifestyle intervention focused on physical and cognitive activity, nutrition, and risk factor management reduces risk of cognitive decline in a heterogeneous population of older adults in the U.S. The study adapts the FINGER (Finnish Intervention Geriatric Study to Prevent Cognitive Impairment and Disability) interventions to fit American culture and works with community partners at 5 sites across the country to develop sustainable community‐based intervention programs. Methods: U.S. POINTER is a 2‐year RCT that is enrolling 2000 cognitively normal older adults (60‐79 years) who are at risk for decline due sedentary lifestyle, poor diet and other factors such as family history of memory impairment and suboptimum cardiovascular health. Recruitment utilizes electronic health records, as well as grassroots approaches to engage traditionally underrepresented groups. Participants are randomized to one of two lifestyle intervention groups – Self‐Guided or Structured Lifestyle Intervention – that differ in format, intensity and accountability. U.S. POINTER includes partnerships with local chapters of the Alzheimer's Association and lifestyle specialists to assist with intervention delivery. The primary outcome is 2‐year change in cognitive function measured with a composite score that permits harmonization with FINGER. Results: Recruitment began in 2019 at the vanguard site in North Carolina. Study progress at all 5 participating sites will be presented. Progress toward harmonization with FINGER and other international study teams in the WW‐FINGERS network will also be discussed. Conclusion: As a member of the WW‐FINGERS network of trials, U.S. POINTER provides an unprecedented opportunity to leverage lessons learned in FINGER and expand this work to test the generalizability of the findings to a heterogeneous American cohort with different cultural needs and practices. The results, in combination with those from other WW‐FINGERS studies, have the potential to identify a strategy to slow cognitive decline on a global scale. [ABSTRACT FROM AUTHOR]

Background: Non‐pharmacological approaches that target modifiable risks through lifestyle interventions provide the most promising evidence to delay disease. In older adults, chronic sleep disturbances marked by sleep‐disordered breathing (SDB) and sleep fragmentation are associated with impaired hippocampal functioning, increased beta‐amyloid burden, and greater Alzheimer's risk. These and other sleep abnormalities are associated with reduced vascular health. Although some evidence suggests that diet, exercise, and cardiovascular risk reduction can improve sleep and improved sleep benefits cognition in older adults, these effects have not been confirmed in a rigorous clinical trial. Methods: The U.S. study to PrOtect brain health through lifestyle INTErvention to Reduce risk (U.S. POINTER), funded by the Alzheimer's Association, was launched in the Fall of 2018. It is investigating whether lifestyle interventions ‐ Self‐Guided (SG) versus a Structured (STR) lifestyle intervention ‐ influence cognitive trajectories over 2 years in 2000 older cognitively normal adults (aged 60‐79 yrs) who are at increased risk for cognitive decline, Alzheimer's disease and other dementias. The NIH‐funded POINTER‐zzz ancillary study adds in‐home objective sleep assessments for 700 participants to examine the effects of lifestyle modification and cardiovascular risk management on sleep disturbances that are linked to cognitive decline and Alzheimer's disease and that may improve with U.S. POINTER interventions. Results: POINTER‐zzz methods and study design will be presented, which will permit over 2000 objective sleep assessments to be completed over 2 years. These assessments will provide extensive oximetry and actigraphy data for analysis by lifestyle intervention group assignment. Sleep data will be examined relative to intervention effects on cognition and other parent trial and ancillary study outcomes, including MRI and amyloid/tau PET brain imaging. POINTER‐zzz leverages resources provided by the parent trial and other funded ancillary studies, and by well‐established collaborations with sleep experts. Conclusions: POINTER‐zzz provides an unparalleled opportunity to test the effects of a multi‐domain lifestyle intervention on sleep abnormalities that are linked to cognitive decline and Alzheimer's in a well‐characterized, diverse cohort of at‐risk older adults. The study may identify an effective strategy for improving sleep that could have important consequences for reduced risk of Alzheimer's disease and related dementias. [ABSTRACT FROM AUTHOR]

Background: Clonal Hematopoiesis of Indeterminate Potential (CHIP) occurs when hematopoietic stem cells in bone marrow undergo somatic mutations and yield genetically distinct leukocyte subpopulations with increased expression of inflammatory genes in innate immune cells. Genes commonly mutated in CHIP are associated with DNA methylation, inflammation, generation of reactive oxygen species, and DNA damage response. Factors associated with CHIP, including inflammation, cardiovascular disease (CVD), metabolic disorders, and stroke are risks for Alzheimer's disease and other dementias, however the association between CHIP and dementia is unknown. We examined the association between CHIP and the incidence of MCI or probable dementia over 22 years of follow‐up in the Women's Health Initiative Memory Study (WHIMS). We also examined these associations by common driver mutations for CHIP. Method: Women without a baseline (1993‐1998) history of stroke, who participated in WHIMS and had baseline blood sample, were followed with annual cognitive assessments, adjudication of MCI or probable dementia, and provided self‐report of dementia diagnoses for up to 22 years. CHIP was defined by whole genome sequencing through TOPMed. Proportional hazards models were used to examine survival to onset of cognitive impairment (mild cognitive impairment (MCI), probable dementia, or self‐reported dementia). Result: We classified 934 women into two groups, CHIP (11%) and no CHIP (89%). A total of 300 women developed cognitive impairment by Year 22. Survival analyses for time to cognitive impairment was adjusted for baseline age, education, 3MS score, hypertension, diabetes, and BMI. There was no difference in risk of cognitive impairment between the women with and without CHIP (p = 0.63). When CHIP was categorized by gene‐specific driver mutations, survival free of impairment among women with DNMT3A mutations was not different from those without CHIP. Risk for impairment was higher among women with TET2 (HR 1.75, p=0.19). Overall results were not statistically significant, however power was limited by low numbers of women with CHIP (see Figure). Conclusion: CHIP was not associated with cognitive outcomes overall but when stratified by the primary CHIP mutations (DNMT3A or TET2), different trends emerged. Future work in WHIMS will explore the cognitive performance over time by different CHIP mutations. [ABSTRACT FROM AUTHOR]

Background: Sleep disturbances are common in individuals with Mild Cognitive Impairment (MCI); and sleep disturbances increase the risk of Alzheimer's disease (AD). Lower ratings of quality of life (QoL) are also found in MCI. We examined the association between sleep disturbances and QoL ratings among participants with MCI. Methods: Baseline in‐home sleep assessments using the WatchPAT (Itamar Medical) and the QoL in AD questionnaire were collected from amnestic MCI (aMCI) participants from the diet intervention trial, Brain Energy for Amyloid Transformation in Alzheimer's Disease (BEAT‐AD) at the Wake Forest ADRC. The WatchPAT assessed sleep time, efficiency, and sleep‐related hypoxemia measures including the apnea‐hypopnea index (AHI), oxygen desaturation index (ODI) and respiratory disturbance index (RDI), where higher values indicate greater disturbances in sleep. The QoL in AD scale ranged from 13–52 with lower scores indicating poorer QoL ratings. We assessed the association between total sleep time and sleep efficiency with QoL. Pearson correlations and regression models measured the association of sleep metrics with QoL scores. Results: Forty‐two aMCI participants (mean age =69.0 ± 7.4 years; N=23 female; mean BMI =27.6) were studied. Disturbed sleep indicated by the average number of apneas and hypopneas (AHI, mean = 18.6 ± 14.6) and respiratory events or related arousals (RDI, mean = 20.7 ± 14.2) was negatively associated with lower subjective measures of QoL. Higher AHI and RDI scores, indicating greater intermittent hypoxia and respiratory burden, were associated with lower QoL (AHI: r= ‐0.359, p=0.027; RDI: r= ‐0.340, p=0.037). There was a trend toward a negative association of ODI and QoL scores (r= ‐0.309, p=0.059). Regression models including age, sex, and BMI did not significantly predict QoL scores with AHI (F(4,35)=1.95, p>.1) or RDI (F(4,34)=1.76, p>.15), however, AHI and RDI individually added significantly to the prediction of QoL scores (AHI: B=‐.136, t=‐2.4,P<.05; RDI: B=‐.162, t=‐2.4, p<.05). Conclusions: Greater sleep disturbances related to hypoxic and respiratory events were associated with lower self‐ratings of QoL in MCI participants. Further research will increase the sample, investigate the impact of hypoxic and respiratory events on brain function, and whether longitudinal changes in diet influence the relationship of sleep‐related hypoxemia and QoL. [ABSTRACT FROM AUTHOR]

Background: Data on cardiovascular diseases (CVD) and cognitive decline are conflicting. Our objective was to investigate if CVD is associated with an increased risk for cognitive decline and to examine whether hypertension, diabetes, or adiposity modify the effect of CVD on cognitive functioning., Methods and Results: Prospective follow-up of 6455 cognitively intact, postmenopausal women aged 65 to 79 years old enrolled in the Women's Health Initiative Memory Study (WHIMS). CVD was determined by self-report. For cognitive decline, we assessed the incidence of mild cognitive impairment (MCI) or probable dementia (PD) via modified mini-mental state examination (3 MS) score, neurocognitive, and neuropsychiatric examinations. The median follow-up was 8.4 years. Women with CVD tended to be at increased risk for cognitive decline compared with those free of CVD (hazard ratio [HR], 1.29; 95% CI: 1.00, 1.67). Women with myocardial infarction or other vascular disease were at highest risk (HR, 2.10; 95% CI: 1.40, 3.15 or HR, 1.97; 95% CI: 1.34, 2.87). Angina pectoris was moderately associated with cognitive decline (HR 1.45; 95% CI: 1.05, 2.01) whereas no significant relationships were found for atrial fibrillation or heart failure. Hypertension and diabetes increased the risk for cognitive decline in women without CVD. Diabetes tended to elevate the risk for MCI/PD in women with CVD. No significant trend was seen for adiposity., Conclusions: CVD is associated with cognitive decline in elderly postmenopausal women. Hypertension and diabetes, but not adiposity, are associated with a higher risk for cognitive decline. More research is warranted on the potential of CVD prevention for preserving cognitive functioning.

Objectives/hypothesis: Although flexible endoscopic evaluation of swallowing (FEES) is an established diagnostic tool, little data exist on the effects of varying liquid types on the swallowing outcomes in healthy older adults., Study Design: Prospective., Methods: Seventy-six healthy older adult volunteers participated (i.e., 18, 28, and 30 volunteers in the 7th, 8th, and 9th decades of life, respectively). The effects of age, sex, liquid type (i.e., water, skim, 2% milk, or whole milk), delivery method (i.e., cup or straw), and volume (i.e., 5, 10, 15, or 20 mL) on Penetration Aspiration Scale (PAS) scores were assessed during FEES., Results: Penetration and silent aspiration were observed in 83% and 28% of the participants, respectively. This represented 19% and 3% of participants' 2,432 swallows, respectively. Liquid type (P = .0001), bolus volume (P = .02), and delivery method (P = .04) significantly affected PAS scores. PAS scores were significantly (P < .05) greater for milk versus water swallows, whole- versus skim-milk swallows, 10- and 20-mL versus 5-mL volumes, and straw versus cup delivery. The risk for aspiration increased by approximately two-, three-, and seven-fold with maximal increases in bolus volume, fat content of liquids, and age, respectively., Conclusions: Occasional aspiration may be an underappreciated phenomenon during FEES in healthy older adults. In addition, milk yielded a higher likelihood of aspiration than water. Accordingly, different liquid types, bolus volumes, and delivery methods should be used to ensure an accurate assessment of aspiration status in healthy older adults.