A feasibility randomized controlled trial of a community-level physical activity strategy for older adults with motoric cognitive risk syndrome.

The motoric cognitive risk syndrome (MCR) is a syndrome characterized by subjective memory complaints and slow walking speeds that can identify older adults at increased risk for developing Alzheimer's disease or a related dementia (ADRD). To date, the feasibility of community-based physical activity (PA) programs for improving outcomes in MCR have yet to be examined. To address this knowledge gap, we conducted a translational randomized controlled trial (RCT) comparing 24-weeks of PA to a healthy aging education (HE) control intervention delivered within the infrastructure of an urban senior center in Greater Boston (clincaltrials.gov identifier: NCT03750682). An existing senior center employee was trained to administer the multimodal group-based PA program that included moderate-intensity aerobic walking, strength, flexibility and balance training. A total of 79 older adults attended the senior center for a screening visit, of whom 29 met the MCR criteria and 25 were randomized to PA or HE (mean age: 74.4 ± 7 years; BMI: 32.4 ± 7 kg/m2; 85% female; 3MSE score: 92.4 ± 7; gait speed: 0.52 ± 0.1 m/s; SPPB score 4.8 ± 1.9). Due to the Covid-19 pandemic the study was stopped prematurely. Participants could successfully adhere to the study interventions (overall attendance rate: PA: 69% vs. HE:70% at study termination). Participants also successfully completed baseline and follow-up study assessments that included a computerized cognitive testing battery and objective tests of physical performance and functional exercise capacity. No study-related adverse events occurred. Notable trends for improved cognitive performance, gait speed and 6-min walk distance were exhibited in PA compared to HE. Our study provides important preliminary information to aid the design of larger-scale RCTs of PA that may help to preserve the independence of vulnerable older adults at high risk for ADRD in community-based settings.

Distinct Patterns of Brain Atrophy in Amnestic Mild Cognitive Impairment and Motoric Cognitive Risk Syndromes.

INTRODUCTION: Motoric cognitive risk (MCR) and amnestic mild cognitive impairment (aMCI) syndromes are each reliable predictors of incident Alzheimer's disease (AD), but MCR may be a stronger predictor of vascular dementia than AD. This study contrasted cortical and hippocampal atrophy patterns in MCR and aMCI. METHODS: Cross-sectional data from 733 older adults without dementia or disability (M age = 73.6; 45% women) in the multicountry MCR consortium were examined. MCR was defined as presence of slow gait and cognitive concerns. Amnestic MCI was defined as poor episodic memory performance and cognitive concerns. Cortical thickness and hippocampal volumes were quantified from structural MRIs. Multivariate and univariate general linear models were used to examine associations between cortical thickness and hippocampal volume in MCR and aMCI, adjusting for age, sex, education, total intracranial volume, white matter lesions, and study site. RESULTS: The prevalence of MCR and aMCI was 7.64% and 12.96%, respectively. MCR was associated with widespread cortical atrophy, including prefrontal, insular, cingulate, motor, parietal, and temporal atrophy. aMCI was associated with hippocampal atrophy. CONCLUSION: Distinct patterns of atrophy were associated with MCR and aMCI. A distributed pattern of cortical atrophy - that is more consistent with VaD or mixed dementia- was observed in MCR. A more restricted pattern of atrophy - that is more consistent with AD - was observed in aMCI. The biological underpinnings of MCR and aMCI likely differ and may require tailored interventions.

Prefrontal Cortex Oxygenation During Exercise in Older Adults with Motoric Cognitive Risk Syndrome.

Motoric cognitive risk syndrome (MCR) is a pre-dementia syndrome characterized by subjective memory complaints and gait impairments that may be related to lower prefrontal cortex (PFC) function. Acute bouts of aerobic exercise are shown to improve PFC function, however, the acute effects of exercise on PFC oxygenation have not yet been examined in MCR. This study aims to characterize the PFC oxygenation responses during acute exercise in older adults with MCR. Nineteen older adults with MCR performed a submaximal cycling exercise protocol. Functional near-infrared spectroscopy (fNIRS) is used to measure concentrations of oxygenated (OxyHb) and deoxygenated (DeoxyHb) hemoglobin from the PFC. There is a trend for increased OxyHb concentrations and decreased DeooxyHb concentrations during exercise. Exercise also induced significant increases in ratings of perceived exertion (RPEs) and heart rate. A significant, positive correlation between PFC OxyHb and RPEs during the cycling exercise are also observed. The findings reveal that PFC oxygenation increases during exercise in an intensity-dependent manner and the subjective perception of exertion is associated with the magnitude of PFC oxygenation. These results suggest that moderate-intensity cycling exercise may have beneficial effects on increasing cerebral blood flow in the PFC of older adults with MCR.

White Matter Hyperintensities Are Associated with Slower Gait Speed in Older Adults without Dementia.

INTRODUCTION: Slow gait speed is associated with poor health outcomes in aging, but the relationship between cerebral small vessel disease (CSVD) pathologies and gait speed in aging is not well understood. We investigated the relationships between CSVD imaging markers and gait speed during simple (normal pace walking [NPW]) and complex (walking while talking [WWT]) as both measures are associated with shared health outcomes such as falls, frailty, disability, mortality, and dementia. METHODS: A total of 113 Ashkenazi Jewish adults over 65 (M age = 78.6 ± 6.3 years, 45.8% women) and without dementia were examined. Established rating systems were used to quantify white matter hyperintensities (WMHs) and lacunes of presumed vascular origin from fluid-attenuated inversion recovery (FLAIR) images. Linear regression models adjusted for age, sex, global health, and total intracranial volume were used to examine associations between CSVD markers and gait speed during NPW and WWT. Student t tests were used to contrast gait speed in those with "confluent-diffuse" WMH and those with "mild or no" WMH. RESULTS: The number of WMH in the basal ganglia (ß = -3.274 cm/s p = 0.047) and temporal lobes (ß = -3.113 cm/s p = 0.048) were associated with slower NPW speed in adjusted models. Participants with higher CSVD burden (confluent-diffuse pattern) in the frontal lobe (94.65 cm/s vs. 105.21 cm/s, p = 0.018) and globally (98.98 cm/s vs. 107.24 cm/s, p = 0.028) also had lower NPW speed. WMHs were not associated with WWT speeds. Lacunes were not associated with NPW or WWT speed. CONCLUSION: Adjusted models found higher CSVD burden as measured by the presence of WMH in the basal ganglia and temporal lobes were associated with slower normal pace gait speed in older adults, but not with complex walking speeds. Participants with confluent-diffuse WMHs in the frontal lobes were found to have slower average normal gait speed. Further studies are needed to establish the temporality of WMH and gait speed decline as well as mechanistic links between the two.

Non-literacy biased, culturally fair cognitive detection tool in primary care patients with cognitive concerns: a randomized controlled trial.

Dementia is often undiagnosed in primary care, and even when diagnosed, untreated. The 5-Cog paradigm, a brief, culturally adept, cognitive detection tool paired with a clinical decision support may reduce barriers to improving dementia diagnosis and care. We performed a randomized controlled trial in primary care patients experiencing health disparities (racial/ethnic minorities and socioeconomically disadvantaged). Older adults with cognitive concerns were assigned in a 1:1 ratio to the 5-Cog paradigm or control. Primary outcome was improved dementia care actions defined as any of the following endpoints within 90 days: new mild cognitive impairment syndrome or dementia diagnoses as well as investigations, medications or specialist referrals ordered for cognitive indications. Groups were compared using intention-to-treat principles with multivariable logistic regression. Overall, 1,201 patients (mean age 72.8 years, 72% women and 94% Black, Hispanic or Latino) were enrolled and 599 were assigned to 5-Cog and 602 to the control. The 5-Cog paradigm demonstrated threefold odds of improvement in dementia care actions over control (odds ratio 3.43, 95% confidence interval 2.32-5.07). No serious intervention-related adverse events were reported. The 5-Cog paradigm improved diagnosis and management in patients with cognitive concerns and provides evidence to promote practice change to improve dementia care actions in primary care.ClinicalTrials.gov: NCT03816644 .

Linking Dementia Pathology and Alteration in Brain Activation to Complex Daily Functional Decline During the Preclinical Dementia Stages: Protocol for a Prospective Observational Cohort Study.

BACKGROUND: Progressive difficulty in performing everyday functional activities is a key diagnostic feature of dementia syndromes. However, not much is known about the neural signature of functional decline, particularly during the very early stages of dementia. Early intervention before overt impairment is observed offers the best hope of reducing the burdens of Alzheimer disease (AD) and other dementias. However, to justify early intervention, those at risk need to be detected earlier and more accurately. The decline in complex daily function (CdF) such as managing medications has been reported to precede impairment in basic activities of daily living (eg, eating and dressing). OBJECTIVE: Our goal is to establish the neural signature of decline in CdF during the preclinical dementia period. METHODS: Gait is central to many CdF and community-based activities. Hence, to elucidate the neural signature of CdF, we validated a novel electroencephalographic approach to measuring gait-related brain activation while participants perform complex gait-based functional tasks. We hypothesize that dementia-related pathology during the preclinical period activates a unique gait-related electroencephalographic (grEEG) pattern that predicts a subsequent decline in CdF. RESULTS: We provide preliminary findings showing that older adults reporting CdF limitations can be characterized by a unique gait-related neural signature: weaker sensorimotor and stronger motor control activation. This subsample also had smaller brain volume and white matter hyperintensities in regions affected early by dementia and engaged in less physical exercise. We propose a prospective observational cohort study in cognitively unimpaired older adults with and without subclinical AD (plasma amyloid-ß) and vascular (white matter hyperintensities) pathologies. We aim to (1) establish the unique grEEG activation as the neural signature and predictor of decline in CdF during the preclinical dementia period; (2) determine associations between dementia-related pathologies and incidence of the neural signature of CdF; and (3) establish associations between a dementia risk factor, physical inactivity, and the neural signature of CdF. CONCLUSIONS: By establishing the clinical relevance and biological basis of the neural signature of CdF decline, we aim to improve prediction during the preclinical stages of ADs and other dementias. Our approach has important research and translational implications because grEEG protocols are relatively inexpensive and portable, and predicting CdF decline may have real-world benefits. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56726.

Loneliness predicts decreased physical activity in widowed but not married or unmarried individuals.

Background: Physical activity is associated with improved health and function in older adults, yet most older adults are sedentary. Loneliness is associated with decreased physical activity at the cross-section, but longitudinal studies are scarce. We examined longitudinal associations between loneliness and physical activity-and whether they were modified by marital status and network size (the number of children, relatives, and friends a person interacts with at least once a month). Methods: We analyzed data from 1,931 older adults without dementia at baseline from the Rush Memory and Aging Project with a mean follow-up of 4.8 years (mean age 79.6 ± 7.7, 74.9% women). Loneliness was assessed using the de Jong Gierveld Loneliness Scale. Physical activity was assessed as the frequency with which participants engaged in five categories of activities (e.g., walking, gardening, calisthenics, bicycling, and swimming). Linear mixed effects models examined associations between baseline loneliness and change in physical activity over time after adjusting for demographics, depressive symptoms, global cognition, disability, network size, marital status, social support, and social and cognitive activities. We assessed for effect modification by marital status and network size. Results: Associations between loneliness and physical activity differed by marital status. In widowed individuals, baseline loneliness was associated with a 0.06 h/week greater decrease in physical activity per year compared to those who were not lonely (p = 0.005, CI -0.1, 0.02)-which equaled a 150% decrease in physical activity per year. Loneliness did not predict a statistically significant decrease in physical activity in married or unmarried individuals. Discussion: Loneliness is associated with decreased physical activity in widowed older adults and should be considered in the design of interventions to prevent or slow the decline in physical activity and promote healthy aging.

Cognitive reserve proxies are associated with age-related cognitive decline - Not age-related gait speed decline.

Cognition and gait share brain substrates in aging and dementia. Cognitive reserve (CR) allows individuals to cope with brain pathology and delay cognitive impairment and dementia. Yet, evidence for that CR is associated with age-related cognitive decline is mixed, and evidence for that CR is associated with age-related gait decline is limited. In 1,079 older (M Age = 75.4 years; 56.0% women) LonGenity study participants without dementia at baseline and up to 12 years of annual follow-up (M follow-up = 3.9 years, SD = 2.5 years), high CR inferred from cognitive (education years), physical (number of blocks walked per day; weekly physical activity days), and social (volunteering/working; living with someone) proxies were associated with slower rates of age-related decline in global cognition - not gait speed decline. Thus, cognitive, physical, and social CR proxies are associated with cognitive decline in older adults without dementia. The multifactorial etiology and earlier decline in gait than cognition may render it less modifiable by CR proxies later in life.

Elevated Blood Homocysteine Increases the Risk of Incident Motoric Cognitive Risk Syndrome: A Two-Cohort Study.

BACKGROUND: Motoric Cognitive Risk (MCR) syndrome, a predementia syndrome characterized by cognitive complaints and slow gait, may have an underlying vascular etiology. Elevated blood levels of homocysteine, a known vascular risk factor, have been linked to physical and cognitive decline in older adults, though the relationship with MCR is unknown. We aimed to identify the association between homocysteine and MCR risk. METHODS: We examined the association between baseline homocysteine levels and incident MCR using Cox proportional hazard models in 1826 community-dwelling older adults (55% women) from 2 cohorts (Einstein Aging Study [EAS] and Quebec Longitudinal Study on Nutrition and Successful Aging [NuAge]). We calculated hazard ratios (HR) with 95% confidence intervals (CI), for each cohort as well as stratified by sex and vascular disease/risk factors. RESULTS: Median follow-up time was 2.2 years in EAS and 3.0 years in NuAge. Individuals with elevated baseline homocysteine levels (>14 µmol/L) had a significantly higher risk of incident MCR compared to those with normal levels in NuAge (HR 1.41, 95% CI: 1.01-1.97, p = .04), after adjusting for covariates. Our exploratory stratified analyses found that these associations were significant only in men with vascular disease/risk factors. CONCLUSIONS: Higher blood homocysteine levels are associated with an increased risk of developing MCR in older adults, particularly in men with vascular disease or vascular risk factors.

Plasma proteomic profile of abdominal obesity in older adults.

OBJECTIVE: This study examines the plasma proteomic profile of abdominal obesity in older adults. METHODS: The association of abdominal obesity (waist circumference [WC]) with 4265 plasma proteins identified using the SomaScan Assay was examined in 969 Ashkenazi Jewish participants (LonGenity cohort), aged 65 years and older (mean [SD] age 75.7 [6.7] years, 55.4% women), using regression models. Pathway analysis, as well as weighted correlation network analysis, was performed. WC was determined from the proteome using elastic net regression. RESULTS: A total of 480 out of 4265 proteins were associated with WC in the linear regression model. Leptin (ß [SE] = 12.363 [0.490]), inhibin ß C chain (INHBC; ß [SE] = 24.324 [1.448]), insulin-like growth factor-binding protein 2 (IGFBP-2; ß [SE] = -12.782 [0.841]), heparan-sulfate 6-O-sulfotransferase 3 (H6ST3; ß [SE] = -39.995 [2.729]), and matrix-remodeling-associated protein 8 (MXRA8; ß [SE] = -27.101 [1.850]) were the top proteins associated with WC. Cell adhesion, extracellular matrix remodeling, and IGF transport pathways were the top enriched pathways associated with WC. WC signature determined from plasma proteins was highly correlated with measured WC (r = 0.80) and was associated with various metabolic and physical traits. CONCLUSIONS: The study unveiled a multifaceted plasma proteomic profile of abdominal obesity in older adults, offering insights into its wide-ranging impact on the proteome. It also elucidated novel proteins, clusters of correlated proteins, and pathways that are intricately associated with abdominal obesity.

"Cognitive" Criteria in Older Adults With Slow Gait Speed: Implications for Motoric Cognitive Risk Syndrome.

BACKGROUND: Motoric cognitive risk syndrome (MCR) is a predementia condition that combines slow gait speed and subjective cognitive concerns (SCC). The SCC criterion is presently unstandardized, possibly limiting risk detection. We sought to (a) characterize SCC practices through MCR literature review; (b) investigate the ability of SCC in slow gait individuals in predicting the likelihood of cognitive impairment in a demographically diverse sample of community-dwelling, nondemented older adults. METHODS: First, we comprehensively reviewed the MCR literature, extracting information regarding SCC measures, items, sources, and cognitive domain. Next, Einstein Aging Study (EAS) participants (N = 278, Mage = 77.22 ±â€…4.74, %female = 67, Meducation = 15 ±â€…3.61, %non-Hispanic White = 46.3) completed gait, Clinical Dementia Rating Scale (CDR), and SCC assessment at baseline and annual follow-up (Mfollow-up = 3.5). Forty-two participants met slow gait criteria at baseline. Generalized linear mixed-effects models examined baseline SCC to predict cognitive impairment on CDR over follow-up. RESULTS: We reviewed all published MCR studies (N = 106) and documented ambiguity in SCC criteria, with a prevalent approach being use of a single self-reported memory item. In EAS, high SCC endorsement on a comprehensive, validated screen significantly affected the rate of cognitive impairment (CDR; ßinteraction = 0.039, p = .018) in slow gait individuals. CONCLUSIONS: An assessment approach that queries across numerous SCC domains was found to predict future decline in clinical dementia status in slow gait older adults. Current SCC practices in MCR, which tend to utilize a single-memory item, may not be the optimal approach. We discuss the implications of SCC criteria validation and standardization to enhance early dementia detection in MCR.

Is the Montreal cognitive assessment culturally valid in a diverse geriatric primary care setting? Lessons from the Bronx.

BACKGROUND: Efficacy and validity of the MoCA for cognitive screening in ethnoculturally and linguistically diverse settings is unclear. We sought to examine the utility and discriminative validity of the Spanish and English MoCA versions to identify cognitive impairment among diverse community-dwelling older adults. METHODS: Participants aged ≥65 with cognitive concerns attending outpatient primary care in Bronx, NY, were recruited. MoCA and neuropsychological measures were administered in Spanish or English, and a neuropsychologist determined cognitive status (normal with subjective cognitive concerns [SCC], mild cognitive impairment [MCI], and dementia). One-way ANOVA compared cognitive statuses. ROC analyses identified optimal MoCA cutpoints for discriminating possible cognitive impairment. RESULTS: There were 231 participants, with mean age 73, 72% women, 43% Hispanic; 39% Black/African American; 113 (49%) completed testing in English and 118 (51%) in Spanish. Overall MoCA mean was 17.7 (SD = 4.3). Neuropsychological assessment identified 90 as cognitively normal/SCC, average MoCA 19.9 (SD = 4.1), 133 with MCI, average MoCA 16.6 (SD = 3.7), and 8 with dementia, average MoCA 10.6 (SD = 3.1). Mean English MoCA average was 18.6 (SD = 4.1) versus Spanish 16.7 (SD = 4.3). The published cutpoint ≤23 for MCI yielded a high false-positive rate (79%). ROC analyses identified ≤18.5 as the score to identify MCI or dementia using the English MoCA (65% sensitivity; 77% specificity) and ≤16.5 for the Spanish MoCA (64% sensitivity;73% specificity) in this sample of older adults with cognitive concerns. CONCLUSIONS: Current MoCA cutpoints were inappropriately high in a culturally/linguistically diverse urban setting, leading to a high false-positive rate. Lower Spanish and English MoCA cutpoints may improve diagnostic accuracy for identifying cognitive impairment in this group, highlighting the need for the creation and validation of accurate cognitive screeners for ethnoculturally and linguistically diverse older adults.

Longitudinal Associations of Social Support and Gait Speed Decline in Aging.

BACKGROUND: Social support predicts functional and cognitive decline in aging. Yet, the associations between social support and gait speed decline-a functional vital sign-are not well understood. This study examined associations between social support and gait speed decline in aging. METHODS: Social support and gait data from 542 older adults without dementia were examined (mean age 76.1 ±â€…6.5 years). Baseline emotional support, tangible support, affectionate support, positive social interactions, and overall support from the Medical Outcomes Study Social Support Survey were the predictors of interest. Annual change in simple (normal pace walking) and complex (walking while reciting alternate letters of the alphabet) gait speed (cm/s) were the outcomes of interest. Linear mixed effects models examined associations between social support and gait speed decline, after adjusting for gender, race, depressive symptoms, overall cognition, and comorbidities. RESULTS: The mean annual change in gait speed was 1.8 cm/s during simple walking and 1.13 cm/s during complex walking. Tangible support was the only category of social support that predicted decline in simple and complex gait speed over a median follow-up of 3 years. The annual decline in gait speed was 0.51 cm/s (p = .008, 95% confidence intervals [CI] 0.13, 0.89) and 0.58 cm/s (p = .007, CI 0.16, 1.0) greater among those with low tangible support than in those with high tangible support during simple and complex walking, respectively. CONCLUSIONS: Tangible support is a potentially modifiable risk factor for gait speed decline. Further study is needed to examine mechanisms behind the observed associations and the potential for intervention.

Difference-Making Pathways to Frailty Through Social Factors: A Configurational Analysis.

BACKGROUND AND OBJECTIVES: Social disconnection is highly prevalent in older adults and is associated with frailty. It is unclear which aspects of social disconnection are most associated with frailty, which ones are difference-making, and which combination of social factors are directly linked to frailty. RESEARCH DESIGN AND METHODS: We conducted a secondary coincidence analysis (CNA) of 1,071 older adults from the Rush Memory and Aging Project (mean age 79.3 ± 7.1; 75.8% female) to identify combinations of social factors that are difference-making for frailty. We included 7 demographic (e.g., age, sex, socioeconomic status) and structural (e.g., social network), functional (e.g., social support, social activity), and quality (e.g., loneliness) aspects of social connection. An established cut score of 0.2 on a frailty index was used to define frailty as the outcome. RESULTS: CNA produced 46 solution models for the presence of frailty in the data set. The top-scoring model was underfit, leaving a final complex solution path for frailty with the highest fit-robustness score that met the fit parameter cutoffs. We found that the combination of loneliness, low social activity, and older age was present 82% of the time when frailty was present. DISCUSSION AND IMPLICATIONS: The combination of loneliness, social activity, and old age is difference-making for frailty, and supports the inclusion of social factors in frailty prevention and intervention. Further research is needed in diverse data sets to better understand the interrelationships between the 3 aspects of social connection and frailty.

Prodromal Motoric Cognitive Risk Syndrome and Everyday Function.

BACKGROUND: Motoric cognitive risk syndrome (MCR), a pre-dementia syndrome characterized by subjective cognitive complaints and slow gait, is associated with disability in instrumental activities of daily living. It is unknown whether these functional limitations occur even before this pre-dementia syndrome is diagnosed. OBJECTIVE: To assess profiles of complex and instrumental activities of daily living in the prodromal stages of MCR. METHODS: We examined functional profiles in 46 older adults (mean age 79 years, 59% women) living in the community with normal cognition at baseline who developed MCR over follow-up ('pre-MCR') with 264 older adults (mean age 75 years, 57% women) who remained cognitively intact over the follow-up period. RESULTS: Pre-MCR individuals had more limitations on complex everyday function at baseline compared to normal controls in multivariable logistic regression models (odds ratio 1.21). Pre-MCR cases at baseline had limitations in handling finances (odds ratio 3.0) and performing hobbies (odds ratio 5.5) as compared to normal controls. Pre-MCR cases had a greater difference in the number of complex functional limitations from baseline to MCR compared to the difference from baseline to final visit for the controls (1.2±3.0 versus 0.5±2.2, p < 0.001). CONCLUSIONS: Limitations in complex everyday tasks arise in the prodromal stages of MCR and can assist in risk prognostication.

Epidemiology of Motoric Cognitive Risk Syndrome in the Kerala Einstein Study: Protocol for a Prospective Cohort Study.

BACKGROUND: The southern India state of Kerala has among the highest proportion of older adults in its population in the country. An increase in chronic age-related diseases such as dementia is expected in the older Kerala population. Identifying older individuals early in the course of cognitive decline offers the best hope of introducing preventive measures early and planning management. However, the epidemiology and pathogenesis of predementia syndromes at the early stages of cognitive decline in older adults are not well established in India. OBJECTIVE: The Kerala Einstein Study (KES) is a community-based cohort study that was established in 2008 and is based in the Kozhikode district in Kerala state. KES aims to establish risk factors and brain substrates of motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by the presence of slow gait and subjective cognitive concerns in individuals without dementia or disability. This protocol describes the study design and procedures for this KES project. METHODS: KES is proposing to enroll a sample of 1000 adults ≥60 years old from urban and rural areas in the Kozhikode district of Kerala state: 200 recruited in the previous phase of KES and 800 new participants to be recruited in this project. MCR is the cognitive phenotype of primary interest. The associations between previously established risk factors for dementia as well as novel risk factors (apathy and traumatic brain injury) and MCR will be examined in KES. Risk factor profiles for MCR will be compared between urban and rural residents as well as with individuals who meet the criteria for mild cognitive impairment (MCI). Cognitive and physical function, medical history and medications, sociodemographic characteristics, lifestyle patterns, and activities of daily living will be evaluated. Participants will also undergo magnetic resonance imaging and electrocardiogram investigations. Longitudinal follow-up is planned in a subset of participants as a prelude to future longitudinal studies. RESULTS: KES (2R01AG039330-07) was funded by the US National Institutes of Health in September 2019 and received approval from the Indian Medical Council of Research to start the study in June 2021. We had recruited 433 new participants from urban and rural sites in Kozhikode as of May 2023: 41.1% (178/433) women, 67.7% (293/433) rural residents, and 13.4% (58/433) MCR cases. Enrollment is actively ongoing at all the KES recruitment sites. CONCLUSIONS: KES will provide new insights into risk factors and brain substrates associated with MCR in India and will help guide future development of regionally specific preventive interventions for dementia. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49933.

Frailty, Acute Brain Dysfunction, and Posthospitalization Disability Outcomes in Critically Ill Older Adults.

BACKGROUND: Identifying potentially modifiable factors that mediate adverse outcomes in frail adults with critical illness may facilitate development of interventions to improve intensive care unit (ICU) survivorship. OBJECTIVES: To estimate the relationship between frailty, acute brain dysfunction (as reflected by delirium or persistent coma), and 6-month disability outcomes. METHODS: Older adults (aged ≥50 years) admitted to the ICU were enrolled prospectively. Frailty was identified with the Clinical Frailty Scale. Delirium and coma were assessed daily with the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale, respectively. Disability outcomes (death and severe physical disability [defined as new dependence in 5 or more activities of daily living]) were assessed by telephone within 6 months after discharge. RESULTS: In 302 older adults (mean [SD] age, 67.2 [10.8] y), both frail and vulnerable patients had a higher risk for acute brain dysfunction (adjusted odds ratio [AOR], 2.9 [95% CI, 1.5-5.6], and 2.0 [95% CI, 1.0-4.1], respectively) compared with fit patients. Both frailty and acute brain dysfunction were independently associated with death or severe disability at 6 months (AOR, 3.3 [95% CI, 1.6-6.5] and 2.4 [95% CI, 1.4 -4.0], respectively). The average proportion of the frailty effect mediated by acute brain dysfunction was estimated to be 12.6% (95% CI, 2.1%-23.1%; P = .02). CONCLUSION: Frailty and acute brain dysfunction were important independent predictors of disability outcomes in older adults with critical illness. Acute brain dysfunction may be an important mediator of increased risk for physical disability outcomes after critical illness.

Frailty Resilience Score: A Novel Measure of Frailty Resilience Associated With Protection From Frailty and Survival.

Frailty is characterized by increased vulnerability to disability and high risk for mortality in older adults. Identification of factors that contribute to frailty resilience is an important step in the development of effective therapies that protect against frailty. First, a reliable quantification of frailty resilience is needed. We developed a novel measure of frailty resilience, the Frailty Resilience Score (FRS), that integrates frailty genetic risk, age, and sex. Application of FRS to the LonGenity cohort (n = 467, mean age 74.4) demonstrated its validity compared to phenotypic frailty and its utility as a reliable predictor of overall survival. In a multivariable-adjusted analysis, 1-standard deviation increase in FRS predicted a 38% reduction in the hazard of mortality, independent of baseline frailty (p < .001). Additionally, FRS was used to identify a proteomic profile of frailty resilience. FRS was shown to be a reliable measure of frailty resilience that can be applied to biological studies of resilience.

Loneliness and Functional Decline in Aging: A Systematic Review.

Loneliness is prevalent in adults aged ≥65 years in the United States and is associated with functional decline. The purpose of the current review was to synthesize evidence on the relationship between loneliness and functional decline using Roy's Adaptation Model as a theoretical framework. A comprehensive review of PubMed, Medline, and Embase databases was performed. Inclusion criteria were samples including adults primarily aged >60 years, peer-reviewed, published in the English language, and included a measure for loneliness and function. A total of 47 studies were analyzed. Most studies examined correlates, risk factors, and predictors of loneliness, rather than the relationship between loneliness and function. Evidence suggests there is bidirectionality in the relationship between loneliness and functional decline. Loneliness is associated with functional decline in aging via multiple possible pathways. Further studies are needed to determine causality and biological mechanisms underlying the relationship. [Research in Gerontological Nursing, 16(4), 202-212.].