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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]

Introduction: This study presents a rare case of multiple evanescent white dot syndrome (MEWDS) with atypical electrooculogram (EOG) findings, as well as abnormal en-face images of minimum intensity projection (Min-IP) and the en-face inner segment/outer segment-ellipsoid complex. Methods: A 25-year-old female patient presented with painless visual impairment and photopsia in her right eye for a duration of two days. Multimodal imaging was employed including color fundus photography (CFP), fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT), and optical coherence tomography angiography (OCTA), and en-face images of Min-IP and the en-face inner segment/outer segment-ellipsoid complex were performed. Results: In the right eye, multifocal small white spots were observed surrounding the posterior pole and optic disc of retina with the granular appearance of the fovea. FAF displayed of hyperfluorescence. SD-OCT appearance of MEWDS demonstrated primarily disrupted ellipsoid zone (EZ), photoreceptor outer segments, and interdigitation zone (IZ) complex within the fovea. The en-face images of the inner segment/outer segment-ellipsoid complex and Min-IP exhibited hyperreflective spots in the right eye. In the left eye, interestingly, hyperreflective spots were also observed on the en-face image of the inner segment/outer segment-ellipsoid complex. EOG revealed an Arden ratio of 2.5 for the right eye, while the left eye exhibited an Arden ratio of 1.7. Conclusion: The en-face image of the inner segment/outer segment-ellipsoid complex in MEWDS exhibits aberrant features and it is noteworthy that a similar alteration may occur in the fellow eye. Further investigation is required to explore the relationship between MEWDS and EOG. The en-face images of the inner segment/outer segment-ellipsoid complex and Min-IP may help to elucidate the pathogenesis of MEWDS. [ABSTRACT FROM AUTHOR]

Cellular senescence is a biological aging process that is exacerbated by obesity and leads to inflammation and age- and obesogenic-driven chronic diseases including type 2 diabetes. Caloric restriction (CR) may improve metabolic function in part by reducing cellular senescence and the pro-inflammatory senescence-associated phenotype (SASP). We conducted an ancillary investigation of an 18-week randomized controlled trial (RCT) of CR (n  = 31) or Control (n  = 27) in 58 middle-aged/older adults (57.6 ± 5.8 years; 75% Women) with obesity and prediabetes. We measured mRNA expression of select senescence and apoptosis genes in blood CD3 + T cells (qRT-PCR) and a panel of 25 plasma SASP proteins (Luminex/multiplex; ELISA). Participants randomized to CR lost −10.8 ± 0.9 kg (−11.3% ± 5.4%) over 18 weeks compared with +0.5 ± 0.9 kg (+0.03% ± 3.5%) in Control group. T-cell expression of senescence biomarkers, p16INK4a and p21CIP1/WAF1, and apoptosis markers, BCL2L1 and BAK1, was not different between CR and Control groups in age, race, and sex-adjusted mixed models (p  > .05, all). Iterative principal axis factor analysis was used to develop composite SASP Factors, and the Factors comprising TNFRI, TNFRII, uPAR, MMP1, GDF15, OPN, Fas, and MPO were significantly altered with CR intervention (age, sex, race-adjusted mixed model time × treatment F  = 4.17, p  ≤ .05) and associated with the degree of weight loss (R 2 = 0.12, p  ≤ .05). Our study provides evidence from an RCT that specific circulating biomarkers of senescent cell burden are changed by CR in middle-aged and older adults with obesity and prediabetes. Future studies compare tissue and circulating levels of p16INK4a and pro-inflammatory SASP biomarkers in other populations, and interventions. [ABSTRACT FROM AUTHOR]

Purpose: Dietary variation is important for health maintenance and disease prevention among older adults. However, oral health deficits impair ability to bite and chew foods. This study examines the association between oral health and foods avoided or modified in a multiethnic rural population of older adults. It considers implications for nutrition and medical service provision to this population. Design and Methods: In-home interviews and oral examinations were conducted with 635 adults in rural North Carolina counties with substantial African American and American Indian populations. Avoidance and modification data were obtained for foods representing different dental challenges and dietary contributions. Data were weighted to census data for ethnicity and sex. Bivariate analyses of oral health measures and foods avoided used chi-square and logistic regression tests. Multivariable analyses used proportional odds or nominal regression models. Results: Whole fruits and raw vegetables were the most commonly avoided foods; substantial proportions of older adults also avoided meats, cooked vegetables, and other foods. Food avoidance was significantly associated with self-rated oral health, periodontal disease, bleeding gums, dry mouth, having dentures, and having fewer anterior and posterior occlusal contacts. Associations persisted when controlling for demographic and socioeconomic status indicators. From 24% to 68% of participants reported modifying specific fruits, vegetables, and meats. Modifying harder foods was related to location of teeth and periodontal disease and softer foods to oral pain and dry mouth. Implications: Food services for older adults should consider their oral health status. Policy changes are needed to provide oral health care in benefits for older adults.

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]

Background. Chronic subclinical inflammation may contribute to impaired physical function in older adults; however, more data are needed to determine whether inflammation is a common mechanism for functional decline, independent of disease or health status. Methods. We examined associations between physical function and inflammatory biomarkers in 542 older men and women enrolled in four clinical studies at Wake Forest University between 2001 and 2006. All participants were at least 55 years and had chronic obstructive pulmonary disease, congestive heart failure, high cardiovascular risk, or self-reported physical disability. Uniform clinical assessments were used across studies, including grip strength; a Short Physical Performance Battery (SPPB; includes balance, 4-m walk, and repeated chair stands): inflammatory biomarker assays for interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-[alpha]), and C-reactive protein (CRP); and anthropometric Measures. Results. Higher levels of CRP and IL-6, but not TNF-[alpha]. were associated with lower grip strength and SPPB scores and longer times to complete the 4-m walk and repeated chair stands tests, independent of age, gender, and race. More importantly, these relationships were generally independent of disease status. Further adjustment for fat mass, lean mass, or percent body fat altered some of these relationships but did not significantly change the overall results. Conclusions. Elevated CRF and IL-6 levels are associated with poorer physical function in older adults with various comorbidities, as assessed by a common battery of clinical assessments. Chronic subclinical inflammation may be a marker of functional limitations in older persons across several diseases/health conditions. Key Words: Inflammation--Physical function--Aging--Comorbidities.

We investigated whether caloric restriction (CR) improves physical performance in a rodent model of aging, and whether this effect is accompanied with a decrease in visceral adipose tissue production of proinflammatory cytokines. Body composition, standardized physical performance measures, as well as in vitro visceral adipose tissue cytokine secretion and circulating levels of an inflammatory marker were cross-sectionally assessed in ad libitum (AL)-fed and lifelong CR Fischer 344 x Brown Norway male rats aged 18, 24, and 29 months. Fat to lean mass ratio increased and physical performance declined with age in the AL rats. Compared to AL rats, CR rats had lower fat mass, fat to lean ratio, adipose tissue secretion of interleukin-6, and circulating levels of C-reactive protein, and higher physical performance scores. Therefore, CR may be an effective intervention for improving functional status into advanced age and is perhaps mediated via a reduction in adipose tissue-generated proinflammatory cytokine production.

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]

Abstract Background Dendritic cells (DC) play a central role in primary immune responses and become potent stimulators of the adaptive immune response after undergoing the critical process of maturation. Understanding the dynamics of DC maturation would provide key insights into this important process. Time course microarray experiments can provide unique insights into DC maturation dynamics. Replicate experiments are necessary to address the issues of experimental and biological variability. Statistical methods and averaging are often used to identify significant signals. Here a novel strategy for filtering of replicate time course microarray data, which identifies consistent signals between the replicates, is presented and applied to a DC time course microarray experiment. Results The temporal dynamics of DC maturation were studied by stimulating DC with poly(I:C) and following gene expression at 5 time points from 1 to 24 hours. The novel filtering strategy uses standard statistical and fold change techniques, along with the consistency of replicate temporal profiles, to identify those differentially expressed genes that were consistent in two biological replicate experiments. To address the issue of cluster reproducibility a consensus clustering method, which identifies clusters of genes whose expression varies consistently between replicates, was also developed and applied. Analysis of the resulting clusters revealed many known and novel characteristics of DC maturation, such as the up-regulation of specific immune response pathways. Intriguingly, more genes were down-regulated than up-regulated. Results identify a more comprehensive program of down-regulation, including many genes involved in protein synthesis, metabolism, and housekeeping needed for maintenance of cellular integrity and metabolism. Conclusions The new filtering strategy emphasizes the importance of consistent and reproducible results when analyzing microarray data and utilizes consistency between replicate experiments as a criterion in both feature selection and clustering, without averaging or otherwise combining replicate data. Observation of a significant down-regulation program during DC maturation indicates that DC are preparing for cell death and provides a path to better understand the process. This new filtering strategy can be adapted for use in analyzing other large-scale time course data sets with replicates.

Abstract Background Older heart failure (HF) patients exhibit exercise intolerance during activities of daily living. We hypothesized that reduced lower extremity blood flow (LBF) due to reduced forward cardiac output would contribute to submaximal exercise intolerance in older HF patients. Methods and Results Twelve HF patients both with preserved and reduced left ventricular ejection fraction (LVEF) (aged 68 ± 10 years) without large (aorta) or medium sized (iliac or femoral artery) vessel atherosclerosis, and 13 age and gender matched healthy volunteers underwent a sophisticated battery of assessments including a) peak exercise oxygen consumption (peak VO2), b) physical function, c) cardiovascular magnetic resonance (CMR) submaximal exercise measures of aortic and femoral arterial blood flow, and d) determination of thigh muscle area. Peak VO2 was reduced in HF subjects (14 ± 3 ml/kg/min) compared to healthy elderly subjects (20 ± 6 ml/kg/min) (p = 0.01). Four-meter walk speed was 1.35 ± 0.24 m/sec in healthy elderly verses 0.98 ± 0.15 m/sec in HF subjects (p < 0.001). After submaximal exercise, the change in superficial femoral LBF was reduced in HF participants (79 ± 92 ml/min) compared to healthy elderly (222 ± 108 ml/min; p = 0.002). This occurred even though submaximal stress-induced measures of the flow in the descending aorta (5.0 ± 1.2 vs. 5.1 ± 1.3 L/min; p = 0.87), and the stress-resting baseline difference in aortic flow (1.6 ± 0.8 vs. 1.7 ± 0.8 L/min; p = 0.75) were similar between the 2 groups. Importantly, the difference in submaximal exercise induced superficial femoral LBF between the 2 groups persisted after accounting for age, gender, body surface area, LVEF, and thigh muscle area (p ≤ 0.03). Conclusion During CMR submaximal bike exercise in the elderly with heart failure, mechanisms other than low cardiac output are responsible for reduced lower extremity blood flow.

Abstract Background Temporal gene expression profiles characterize the time-dynamics of expression of specific genes and are increasingly collected in current gene expression experiments. In the analysis of experiments where gene expression is obtained over the life cycle, it is of interest to relate temporal patterns of gene expression associated with different developmental stages to each other to study patterns of long-term developmental gene regulation. We use tools from functional data analysis to study dynamic changes by relating temporal gene expression profiles of different developmental stages to each other. Results We demonstrate that functional regression methodology can pinpoint relationships that exist between temporary gene expression profiles for different life cycle phases and incorporates dimension reduction as needed for these high-dimensional data. By applying these tools, gene expression profiles for pupa and adult phases are found to be strongly related to the profiles of the same genes obtained during the embryo phase. Moreover, one can distinguish between gene groups that exhibit relationships with positive and others with negative associations between later life and embryonal expression profiles. Specifically, we find a positive relationship in expression for muscle development related genes, and a negative relationship for strictly maternal genes for Drosophila, using temporal gene expression profiles. Conclusion Our findings point to specific reactivation patterns of gene expression during the Drosophila life cycle which differ in characteristic ways between various gene groups. Functional regression emerges as a useful tool for relating gene expression patterns from different developmental stages, and avoids the problems with large numbers of parameters and multiple testing that affect alternative approaches.

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]

Background and Objectives While several studies have examined the association between cognitive and physical function, the consistency of these associations across functional contexts is unclear. The consistency of the association between cognitive and physical function performance was examined at baseline across 17 clinical studies with diverse and heterogeneous conditions such as overweight/obese, sedentary, at risk for a mobility disability, osteoarthritis, low vitamin D, or had signs of cognitive impairment. Research Design and Methods Data are from 1,388 adults 50 years and older who completed a cognitive and physical function assessment as part of a research study at the Wake Forest Alzheimer's Disease Research Center or the Wake Forest Older Americans Independence Center. Linear regression models were used to relate cognitive measures (Mini-Mental Status Examination, Montreal Cognitive Assessment, and the Digit Symbol Substitution Task) and physical measures (the Short Physical Performance Battery and hand grip strength) for the whole sample and treat each study as a fixed effect. All models controlled for age, sex, race, and body mass index. Results Overall, there was a significant association between higher scores on the Mini-Mental Status Examination (per standard deviation) and better physical function performance (Short Physical Performance Battery score b = 0.24, p <.001) and its components (gait speed, chair rise, and standing balance; p s <.05). Higher scores on the Montreal Cognitive Assessment produced similar results (Short Physical Performance Battery score b = 0.31, p ≤.001), and higher scores on the Digit Symbol Substitution Task were also significantly associated with a better Short Physical Performance Battery score (b = 0.75, p <.001). The relationship between Digit Symbol Substitution Task and physical function performance demonstrated a stronger magnitude of association compared to the Mini-Mental Status Examination or Montreal Cognitive Assessment. Discussion and Implications Older adults with heterogeneous health conditions showed a consistent pattern between better cognitive function and better physical function performance with the strongest association among Digit Symbol Substitution Task scores. [ABSTRACT FROM AUTHOR]

We examine Internet use and eHealth literacy among older adults (aged 55+ years) who were patients at clinics serving low-income populations. Participants included 200 minority and White adults who completed interviews based on a technology acceptance conceptual model. A total of 106 participants (53.0%) used the Internet; utilization was associated with personal characteristics (age, ethnicity, education, poverty), computer characteristics (number of e-devices, computer stress), social support (marital status), and health knowledge and attitudes (health literacy, medical decision making, health information sources), but not health status. Of the 106 participants who used the Internet, 52 (49.1%) had high eHealth literacy; eHealth literacy was associated with computer characteristics (number of e-devices, computer stress), and health knowledge and attitudes (medical decision making, health information sources). In multivariate analysis, computer stress maintained a significant inverse association with eHealth literacy. Educational interventions to help older adults successfully use technology and improve eHealth literacy must be identified. [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: Obesity compounds aging-related declines in cardiorespiratory fitness, with accompanying fatigue and disability. This study determined the effects of two different levels of caloric restriction (CR) during aerobic training on cardiorespiratory fitness, fatigue, physical function, and cardiometabolic risk.Methods: The INFINITE study was a 20-week randomized trial in 180 older (65-79 years) men and women with obesity (body mass index = 30-45 kg/m2). Participants were randomly assigned to (i) aerobic training (EX; treadmill 4 days/wk for 30 minutes at 65%-70% of heart rate reserve), (ii) EX with moderate (-250 kcal/d) CR (EX + Mod-CR), or (iii) EX with more intensive (-600 kcal/d) CR (EX + High-CR). Cardiorespiratory fitness (peak aerobic capacity, VO2 peak, primary outcome) was determined during a graded exercise test.Results: One hundred and fifty-five participants returned for 20-week data collection (87% retention). VO2 peak increased by 7.7% with EX, by 13.8% with EX + Mod-CR, and by 16.0% with EX + High-CR, and there was a significant treatment effect (EX + High-CR = 21.5 mL/kg/min, 95% confidence interval = 19.8-23.2; EX + Mod-CR = 21.2 mL/kg/min, 95% confidence interval = 19.4-23.0; EX = 20.1 mL/kg/min, 95% confidence interval = 18.4-21.9). Both CR groups exhibited significantly greater improvement in self-reported fatigue and disability and in glucose control, compared with EX.Conclusion: Combining aerobic exercise with even moderate CR is more efficacious for improving cardiorespiratory fitness, fatigue and disability, and glucose control than exercise alone and is as effective as higher-dose CR. [ABSTRACT FROM AUTHOR]

Background: Previous studies support beneficial effects of both resistance exercise training (RT) and caloric restriction (CR) on skeletal muscle strength and physical performance. The goal of this study was to determine the effects of adding CR to RT on single-muscle fiber contractility responses to RT in older overweight and obese adults.Methods: We analyzed contractile properties in 1,253 single myofiber from muscle biopsies of the vastus lateralis, as well as physical performance and thigh muscle volume, in 31 older (65-80 years), overweight or obese (body mass index = 27-35 kg/m2) men (n = 19) and women (n = 12) who were randomly assigned to a standardized, progressive RT intervention with CR (RT+CR; n = 15) or without CR (RT; n = 16) for 5 months.Results: Both interventions evoked an increase in force normalized to cross-sectional area (CSA), in type-I and type-II fibers and knee extensor quality. However, these improvements were not different between intervention groups. In the RT group, changes in total thigh fat volume inversely correlated with changes in type-II fiber force (r = -.691; p = .019). Within the RT+CR group, changes in gait speed correlated positively with changes in type-I fiber CSA (r = .561; p = .030). In addition, increases in type-I normalized fiber force were related to decreases in thigh intermuscular fat volume (r = -0.539; p = .038).Conclusion: Single muscle fiber force and knee extensor quality improve with RT and RT+CR; however, CR does not enhance improvements in single muscle fiber contractility or whole muscle in response to RT in older overweight and obese men and women. [ABSTRACT FROM AUTHOR]