Functional Impairment In Older Adults Research Articles

Age-related increase in the excitability of mouse layer V pyramidal neurons in the primary motor cortex is accompanied by an increased persistent inward current.

Sarcopenia, or pathological age-related loss of muscle strength and mass, contributes to physical function impairment in older adults. While current understanding of sarcopenia is centered mostly on neuromuscular mechanisms, mounting evidence supports that deficits at the level of the primary motor cortex (PMC) play a significant role. Despite the importance of the PMC to initiate movement, understanding of how age affects the excitability of layer V pyramidal neurons (LVPNs) of the PMC is limited. To address this, we used the whole-cell patch clamp technique to measure the excitability of LVPNs of the PMC in young, late adulthood, and old mice. Old LVPNs had increased firing frequency and membrane input resistance, but no differences in action potential kinetics versus young and late adulthood mice. Since changes in the persistent inward current (PIC) are known to contribute to changes in motor neuron excitability, we measured LVPN PICs as a putative contributor to LVPN excitability. The PIC amplitude was increased in old LVPN via increases in Na+ and Ca2+ PICs, in addition to being active across a wider voltage range. Given that LVPN function is integral to initiation of voluntary muscle contraction, altered LVPN excitability likely contributes to age-related impairment of physical function.

PFIMPA: A Multimodal Approach to Predict Physical Function Impairment in Older Adults Using Physical Activity From Wrist-Worn Accelerometer

PFIMPA: A Multimodal Approach to Predict Physical Function Impairment in Older Adults Using Physical Activity From Wrist-Worn Accelerometer

Sarcopenic Obesity Burden, Determinants, and Association With Risk of Frailty, Falls, and Functional Impairment in Older Adults With Diabetes: A Propensity Score Matching Analysis.

Sarcopenic obesity (SO) is a medical and functional state characterized by the coexistence of excessive adipose tissue and sarcopenia inside an individual. Recent epidemiological studies suggest a rising prevalence of SO in patients with diabetes mellitus (DM) probably due to the conducive environment resulting from adipose tissue dysfunction and muscle wasting accelerated by insulin resistance, chronic inflammation, and altered protein metabolism. Individuals with SO may have higher risk of experiencing falls, frailty, and disabilities due to compromised musculoskeletal integrity, gait abnormalities, and reduced functional capacity.The primary study objective was to determine the prevalence and predictors of SOamong older adults with a history of DM. The secondary objective was to assess the association of falls, frailty, and functional disabilitywith SO in patients with DM. This cross-sectional study analyzed data from the nationally representative Longitudinal Aging Study in India (LASI) Wave 1, focusing on individuals aged 60 and above, with an emphasis on diabetes. SOwas assessed using the Asian Working Group for Sarcopenia criteria. Propensity score matching (PSM), logistic regression, and mediation analysis were used to explore relationships between diabetes, SO, and health outcomes (falls, frailty, and disabilities). Among 31,902 participants aged 60 and above, 14.26% had diabetes, and 17.67% of those with diabetes exhibited SO. Female gender (aOR = 2.63) and urban residence (aOR = 1.40) were significantly associated with higher odds of SO in individuals with diabetes. PSM analysis revealed a 9.0% higher likelihood of SO in older adults with DM than those without DM. SO was further linked to increased risk of falls, frailty, and various levels of activities of daily living (ADL) and instrumental activities of daily living (IADL) disabilities, with significant mediation effects ranging from 3.67% to 45.81%. Diabetes substantially increases the risk ofSO and associated functional disability with the risk of falls in older adults.Standard diabetes care should integrate health promotion especially nutritionto mitigate the risk of SO-linked functional disability and falls.

67 Cognitive Reserve, Depressive Symptoms, and Functional Ability in Older Adults

Objective:Cognitive reserve has been linked to functional ability, and depression has been shown to be associated with more functional impairment in older adults. While cognitive reserve and depression are associated and have each been shown to impact functional impairment, the independent impact of cognitive reserve on functional ability after accounting for depressive symptoms has not been explored. For the purpose of this study, years of education served as a proxy for cognitive reserve, which is consistent with the literature. It was predicted that higher levels of education would be associated with better functional ability regardless of age and severity of depressive symptoms.Participants and Methods:Participants (ages 55 to 90) were drawn from the Alzheimer’s Disease Neuroimaging Initiative (N=3407); participants with major depression were not included. Subsyndromal depressive symptoms were measured using the Geriatric Depression Scale (GDS < 6) and functional impairment was assessed using the Functional Activities questionnaire. A three-stage hierarchical regression was conducted with functional ability as the dependent variable.Results:Age, entered at stage one of the regression model, was a significant predictor (F(1,1427) =49.75, p<.001) and accounted for 3.4% of the variance in functional ability. Adding depressive symptoms to the regression model led to a significant increase in variance explained (F(1,1426) = 64.57, p<.001), accounting for an additional 4.2% of the variance in functional ability. Adding years of education to the regression model explained an additional 1.4% of variance in functional ability and this increase in variance explained was significant (F(1,1425) = 22.53, p<.001).Conclusions:Cognitive reserve (operationalized as higher levels of education) was associated with higher functional ability even after accounting for age and depressive symptoms.

Chinese expert consensus on prevention and control interventions for older adults with physical functional impairment (2022).

Older adults are at high risk for functional impairment, which is closely related to sarcopenia, falls, and frailty. This seriously affects their quality of life and health, and places a heavy burden on society and families. Although domestic and foreign sports recommendations and prevention and control guidelines/expert consensus have been issued for healthy older adults and functional impairment-related diseases, there is no guidance on prevention and control interventions for older adults with physical functional impairment. In China, there is insufficient understanding of the importance of prevention and control interventions for functional impairment in older adults, and there are many drawbacks, such as unstandardized diagnosis and treatment, and relatively simple intervention methods. Therefore, the consensus expert group formulated a consensus based on domestic and foreign guidelines related to functional impairment in older adults to provide guidance for Chinese medical professionals working in the field of geriatrics.

Long-term exposure to ambient particulate matter and kidney function in older adults

BackgroundAccumulating studies have linked ambient particulate matter (PM) pollution to impaired kidney function, but the results are still inconsistent and the effect of particulate matter with an aerodynamic diameter ≤1 μm (PM1) on the kidney remains less clear. ObjectiveThis study aimed to investigate the association of long-term exposure to ambient PM1, particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5), and particulate matter with an aerodynamic diameter ≤10 μm (PM10) with kidney function in older adults. MethodsIn this cross-sectional study, we investigated 199,635 adults who were ≥65 years and underwent physical examinations in 695 community health service centers in Shenzhen, China from 2018 to 2019. An estimated glomerular filtration rate (eGFR) of each subject was derived by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Chronic kidney disease (CKD) was defined as eGFR <60 ml/min/1.73 m2. Proteinuria was assessed by a urine dipstick test on freshly voided urine. A validated 10 km × 10 km grid dataset was used to assess long-term residential exposure to PM1, PM2.5, and PM10 for each subject. Linear regression models and logistic regression models were implemented to quantify the association of exposure to PM with eGFR level, CKD, and proteinuria. ResultsEach 10 μg/m3 increase of exposure to PM1, PM2.5, and PM10 was associated with a 0.9%, 2.7%, and 1.0% decrease in eGFR level, an 18%, 36%, and 17% increase in odds of CKD, and a 15%, 11%, and 10% increase in odds of proteinuria, respectively (all p < 0.05). The associations of exposure to PM with the eGFR level and CKD were stronger among women and subjects who were aged <75 years, never smoked, and never drank alcohol. ConclusionsLong-term exposure to ambient PM1, PM2.5, and PM10 was significantly associated with kidney function impairment in older adults.

Aging alters antiviral signaling pathways resulting in functional impairment in innate immunity in response to pattern recognition receptor agonists

The progressive impairment of immunity to pathogens and vaccines with aging is a significant public health problem as the world population shifts to an increased percentage of older adults (> 65). We have previously demonstrated that cells obtained from older volunteers have delayed and defective induction of type I interferons and T cell and B cell helper cytokines in response to TLR ligands when compared to those from adult subjects. However, the underlying intracellular mechanisms are not well described. Herein, we studied two critical pathways important in the production of type I interferon (IFN), the interferon response factor 7 (pIRF7), and TANK-binding kinase (pTBK-1). We show a decrease in pIRF7 and pTBK-1 in cross-priming dendritic cells (cDC1s), CD4+ T cell priming DCs (cDC2s), and CD14dimCD16+ vascular patrolling monocytes from older adults (n = 11) following stimulation with pathway-specific agonists in comparison with young individuals (n = 11). The decrease in these key antiviral pathway proteins correlates with decreased phagocytosis, suggesting impaired function in Overall, our findings describe molecular mechanisms which explain the innate functional impairment in older adults and thus could inform us of novel approaches to restore these defects.Graphical abstract

The relationship between multimorbidity, obesity and functional impairment in older adults.

Declining mortality rates and an aging population have contributed to increasing rates of multimorbidity (MM) in the United States. MM is strongly associated with a decline in physical function. Obesity is an important risk factor for the development of MM, and its prevalence continues to rise. Our study aimed to evaluate the associations between obesity, MM, and rates of functional limitations in older adults. We analyzed body mass index (BMI) and self-reported comorbidity data from 7261 individuals aged ≥60 years from the National Health and Nutrition Examination Surveys 2005-2014. Weight status was defined based on standard BMI categories. MM was defined as 2 or more comorbidities, while functional limitations were self-reported. Adjusted logistic regression quantified the association between standard BMI categories and MM. We also examined the difference in the prevalence of limitations between those with and without MM. The overall proportion of individuals with concomitant MM and obesity was 27.0%. Compared to a normal BMI, older adults with obesity had higher odds of MM (Prevalence odds ratio 1.79, 95% CI 1.49, 2.12). Overall, 67.5% of patients with MM also reported a functional limitation, with rates of functional limitation increasing with increasing BMI. When evaluating functional limitations in those with MM by BMI class, 90% of patients classified as severely obese (BMI ≥40 kg/m2 ) with MM also had a concomitant functional limitation. Compared to normal weight status, obesity is associated with an increased burden of MM and functional limitation among older adults. Our results underscore the importance of identifying and addressing obesity, MM, and functional limitation patterns and the need for evidence-based interventions that address all three conditions in this population.

Reliability and Validity of the Function Impairment Screening Tool in Chinese Older Adults.

Background: Physical function gradually decreases with age in older adults, affecting their independence and quality of life and leaving them prone to adverse outcomes. Despite the importance of assessing function for older adults, most studies have focused on disability and paid less attention to functional impairment. Thus, given the lack of valid and practical methods for evaluating functional impairment for older adults, we developed the function impairment screening tool (FIST) using the Delphi method.Objective: This study aimed to evaluate the reliability and validity of the FIST in Chinese older adults.Methods: A total of 489 participants aged 60 years or older, and who had completed the FIST were included. A subgroup of 50 participants completed the FIST a second time, 1 week after the first round, and the test–retest reliability was evaluated using the intraclass correlation coefficient (ICC). Reliability was tested using Cronbach's alpha. Validity was examined using exploratory factor analysis. Criterion-related validity was assessed using correlations between the FIST and the Barthel Index activities of daily living (ADL), Lawton, and Brody instrumental activities of daily living (LB-IADL).Results: The Cronbach's alpha coefficient for the FIST was 0.930 (P < 0.001). The test–retest reliability was good, with an ICC of 0.928 (95% confidence interval [0.874, 0.960]). Exploratory factor analyses revealed one factor accounting for 60.14% of the scale's variance and the load values of every item were >0.4 (0.489–0.872). The correlation coefficient was 0.572 (P < 0.001) between the FIST score and ADL, and was 0.793 (P < 0.001) between the FIST score and IADL. The FIST score was positively correlated with walking speed (r = 0.475, P < 0.001) and grip strength (r = 0.307, P < 0.001), and negatively correlated with age (r = −0.588, P < 0.001) and Fried frailty phenotype (r = −0.594, P < 0.001).Conclusion: The FIST is a reliable and valid instrument for assessing physical function impairment in older adults.

Changes in the Hierarchy of Functional Impairment From Middle Age to Older Age

Understanding the hierarchy of functional impairment in older adults has helped illuminate mechanisms of impairment and inform interventions, but little is known about whether hierarchies vary by age. We compared the pattern of new-onset impairments in activities of daily living (ADLs) and instrumental ADLs (IADLs) from middle age through older age. We conducted a cohort study using nationally representative data from 32 486 individuals enrolled in the Health and Retirement Study. The outcomes were new-onset impairment in each ADL and IADL, defined as self-reported difficulty performing each task, assessed yearly for 9 years. We used multistate models and competing risks survival analysis to estimate the cumulative incidence of impairment in each task by age group (ages 50-64, 65-74, 75-84, and 85 or older). The pattern of incident ADL impairments differed by age group. Among individuals ages 50-64 and 65-74 who were independent at baseline, over 9 years' follow-up, difficulties dressing and transferring were the most common impairments to develop. In individuals ages 75-84 and 85 or older who were independent at baseline, difficulties bathing, dressing, and walking were most common. For IADLs, the pattern of impairments was similar across age groups; difficulty shopping was most common followed by difficulty managing money and preparing meals. Complementary analyses demonstrated a similar pattern. These findings suggest that the hierarchy of ADL impairment differs by age. These findings have implications for the development of age-specific interventions to prevent or delay functional impairment.

Low Dietary Intakes of Vitamin K and Leafy Green Vegetables Are Individually Associated With Low Cognitive Functioning in A National Sample of U.S. Older Adults

ObjectivesThis study aimed to examine the individual associations between dietary intake of vitamin K and leafy green vegetables with cognitive functioning in the US population of adults aged 60 years or older. MethodsCross-sectional data of older adults (≥60years; n = 2,342) from the 2011–2014 NHANES were analyzed. Dietary data were assessed by two 24-hour dietary recalls. ‘Low intake of vitamin K’ was defined as below the recommended daily intake (RDI) (i.e.,< 90mcg for women, < 120mcg for men). ‘Low intake of leafy green vegetables’ was defined as consuming below 90gr a day of green vegetables (e.g., broccoli, asparagus, green pees and beans) and below 30gr a day of leafy greens (e.g., kale, spinach, celery, and lettuce). The cognitive functioning assessment included four separate tests and their ‘overall score’: (1) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) word learning test; (2) Delayed Word Recall (DWR); (3) the Animal Fluency Test (AFT); (4) the Digit Symbol Substitution Test (DSST). Low cognitive functioning was defined as receiving the lowest 20th percentile on each test score. Weighted logistic regressions examined the study aims by tests while controlling for associated covariates: age, sex, race/ethnicity, socioeconomics, body mass index, lifestyle factors, energy intake, chronic diseases, and antithrombotic medication. ResultsMore than half of the sample (55%) did not consume sufficient intake of vitamin K a day, and about two thirds (66%) were defined as having low intake of leafy green vegetables. The multivariable model showed that participants with low intake of vitamin K are more likely, by 45–111%, to have low cognitive functioning than those with sufficient intake of vitamin K (overall score: Odds Ratio (OR) = 1.75, 95% CI: 1.36–2.26). Participants with low intake of leafy green vegetables had higher odds of having low cognitive functioning in three tests (i.e., CERAD, DWR, AFT) (ORs = 1.40–1.57) and in the overall test score (OR = 1.46, 95% CI: 1.14–1.87) than those who consumed ≥90 gr of green vegetables or ≥30 gr of leafy greens a day. ConclusionsLow intakes of dietary vitamin K and leafy green vegetables might be linked with cognitive function impairment in older adults. The causality of such associations needs to be examined using prospective study design or interventions. Funding SourcesN/A.

Plasma acylcarnitines and risk of lower-extremity functional impairment in older adults: a nested case\u2013control study

Elevated concentrations of acylcarnitines have been associated with higher risk of obesity, type 2 diabetes and cardiovascular disease. The aim of the present study was to assess the association between L-carnitine and acylcarnitine profiles, and 2-year risk of incident lower-extremity functional impairment (LEFI). This case–control study is nested in the Seniors-ENRICA cohort of community-dwelling older adults, which included 43 incident cases of LEFI and 86 age- and sex- matched controls. LEFI was assessed with the Short Physical Performance Battery. Plasma L-carnitine and 28 acylcarnitine species were measured. After adjusting for potential confounders, medium-chain acylcarnitines levels were associated with 2-year incidence of LEFI [odds ratio per 1-SD increase: 1.69; 95% confidence interval: 1.08, 2.64; p = 0.02]. Similar results were observed for long-chain acylcarnitines [odds ratio per 1-SD increase: 1.70; 95% confidence interval: 1.03, 2.80; p = 0.04]. Stratified analyses showed a stronger association between medium- and long-chain acylcarnitines and incidence of LEFI among those with body mass index and energy intake below the median value. In conclusion, higher plasma concentrations of medium- and long-chain acylcarnitines were associated with higher risk of LEFI. Given the role of these molecules on mitochondrial transport of fatty acids, our results suggest that bioenergetics dysbalance contributes to LEFI.

Glucose Levels as a Mediator of the Detrimental Effect of Abdominal Obesity on Relative Handgrip Strength in Older Adults.

Excess central adiposity accelerates the decline of muscle strength in older people. Additionally, hyperglycemia, independent of associated comorbidities, is related to the loss of muscle mass and strength, and contributes to functional impairment in older adults. We studied the mediation effect of glucose levels, in the relationship between abdominal obesity and relative handgrip strength (HGS). A total of 1571 participants (60.0% women, mean age 69.1 ± 7.0 years) from 86 municipalities were selected following a multistage area probability sampling design. Measurements included demographic and anthropometric/adiposity markers (weight, height, body mass index, and waist circumference). HGS was measured using a digital dynamometer for three sets and the mean value was recorded. The values were normalized to body weight (relative HGS). Fasting glucose was analyzed by enzymatic colorimetric methods. Mediation analyses were performed to identify associations between the independent variable (abdominal obesity) and outcomes (relative HGS), as well as to determine whether fasting glucose levels mediated the relationship between excess adiposity and relative HGS. A total of 1239 (78.8%) had abdominal obesity. Abdominal obesity had a negative effect on fasting glucose (β = 9.04, 95%CI = 5.87 to 12.21); while fasting glucose to relative HGS was inversely related (β = −0.003, 95%CI = −0.005 to −0.001), p < 0.001. The direct effect of abdominal obesity on relative HGS was statistically significant (β = −0.069, 95%CI = −0.082 to −0.057), p < 0.001. Lastly, fasting glucose levels mediates the detrimental effect of abdominal obesity on relative HGS (indirect effect β = −0.002, 95%CI = −0.004 to −0.001), p < 0.001. Our results suggest that the glucose level could worsen the association between abdominal obesity status and lower HGS. Thus, it is plausible to consider fasting glucose levels when assessing older adults with excess adiposity and/or suspected loss of muscle mass.

Habitual dietary fat intake and risk of muscle weakness and lower-extremity functional impairment in older adults: A prospective cohort study.

Fatty acid supplementation increases muscle mass and function in older adults, but the effect of habitual dietary intake is uncertain. Therefore, the objective of this study was to examine the association between habitual dietary fat intake and risk of muscle weakness and lower-extremity functional impairment (LEFI) in older adults. Prospective study with 1873 individuals aged ≥60 years from the Seniors-ENRICA cohort. In 2008-10 and 2012, a validated face-to-face diet history was used to record the one-year consumption of up to 880 foods. Then, fatty acids, other nutrients and energy intake were estimated using standard food composition tables. Means of intake between these years were calculated to represent cumulative consumption over the follow-up. Study participants were followed up through 2015 to assess incident muscle weakness (lowest quintile of grip strength) and incident LEFI (Short Physical Performance Battery score ≤6). Analyses were performed with Cox regression and adjusted for the main confounders, including other types of fatty acids. Over a median follow-up of 5.2 years, 331 participants developed muscle weakness and 397 LEFI. Intake of saturated fatty acids (SFA) did not show an association with muscle weakness but was associated with higher risk of LEFI (multivariable hazard ratio (HR) for tertile 3 vs. tertile 1: 1.15; 95% confidence interval: 1.05-2.01; p-trend=0.02). This association was mostly due to consumption of Spanish cold cuts and pastry and, to a lesser extent, dairy. Monounsaturated fatty acids (MUFA) intake was associated with lower risk of muscle weakness (HR t3 vs. t1: 0.73; 0.54-0.99; p trend=0.04), and intake of n-3 polyunsaturated fatty acids (PUFA) was associated with reduced risk of both muscle weakness (0.70; 0.52-0.95; p-trend=0.02) and LEFI (0.49; 0.35-0.68; p-trend <0.001). Olive oil and blue fish, the main sources of MUFA and PUFA, were also associated with lower risk of muscle weakness and LEFI. Habitual intake of SFA was associated with increased risk of LEFI. By contrast, habitual intake of MUFA and PUFA were associated with lower risk of physical performance impairment.

GENOME-WIDE ANALYSIS OF LOW STRENGTH IN OLDER PEOPLE: META-ANALYSIS OF &amp;gt;250,000 VOLUNTEERS IN 16 COHORTS

Dynapenia or muscle weakness is a core feature of sarcopenia and frailty, and leads to significant functional impairment in older adults. We aimed to identify genetic variants associated with dynapenia in older adults, to shed light on the underlying mechanisms. A large-scale meta-analysis of >250,000 volunteers of European descent from 16 cohorts in the CHARGE and GEFOS consortia aged 60+ years at assessment is underway, using maximum hand grip strength to define dynapenia. Preliminary analysis in UK Biobank found that dynapenia is associated with nine genomic loci at genome wide significance (p<5x10-8), with differences between men and women, suggesting sex-specific routes to dynapenia. These results suggest that there are specific genetic determinants of low strength in older adults, and these differ from the determinants of normal-range strength differences. The full meta-analysis of all cohorts will extend these findings. Understanding the biological mechanisms may lead to geroscience interventions.

Is skeletal muscle radiodensity able to indicate physical function impairment in older adults with gastrointestinal cancer?

Worsening nutritional status in older adult cancer patients can lead to sarcopenia, a condition that occurs with low quantity or quality of muscle mass associated with low physical function. However, most of the studies with cancer patients have only analyzed the quantity of muscle mass for diagnostic of sarcopenia, without exploring muscle characteristics and physical function. The purpose of the present study is to explore the associations between muscle mass characteristics and physical function in older adult patients with cancer. Gastric older cancer patients were enrolled in a cross-sectional study. Computed tomography images of the abdominal region evaluated skeletal muscle mass using the Slice-O-Matic version 5.0 Software program (Tomovision, Montreal, Canada) to determine the parameters of skeletal muscle index (SMI, muscle quantity) and skeletal muscle radiodensity (SMD). The physical function was evaluated through handgrip strength and gait speed test. Four musculature phenotypes were identified: normal SMI and SMD, only low SMI, only low SMD, and low SMI and SMD. Linear regression analyses adjusted by age and tumor stage verified the associations between SMI, SMD and physical function. A One-Way Covariance Analysis with Bonferroni post hoc test was used to compare the physical function variables among the four different phenotypes. In total, 167 patients were evaluated (58.1% males; mean age 69.17 ± 7.97 years). The results showed that muscle mass characteristics explains, at least partially, the variability in handgrip strength and gait speed in a direct relationship. The phenotypes with low muscular SMI and/or SMD presented worse performances in handgrip strength and gait speed tests. When stratified for sexes, the significant difference occurs only in males. Low SMD has negatively impacted physical function in older adults with gastrointestinal cancer, especially in males.

Functional Impairment in Older Adults With Bipolar Disorder: Erratum.

Functional Impairment in Older Adults With Bipolar Disorder: Erratum.

Social Relationships and Functional Impairment in Aging Cancer Survivors: A Longitudinal Social Network Study.

The intersection of cancer, treatment, and aging accelerates functional decline. Social networks, through the provision of social support and resources, may slow the progression of functional deterioration. Socioemotional selectivity theory posits that aging and major life events, like cancer, cause an intentional social network pruning to procure and maintain emotionally fulfilling bonds, while shedding weaker, less supportive relationships. However, it is relatively unknown if such network changes impact functional impairment in cancer survivors. This study examined the relationships between changes in the egocentric social network and functional impairment in older adult cancer survivors and a similarly aged group without cancer (older adults). Data were analyzed from 1,481 community dwelling older adults (n = 201 cancer survivors) aged 57-85 years, from Waves 1 and 2 (2005-2006 and 2010-2011) of the National Social Life, Health and Aging Project. Associations were analyzed with multiple logistic regression. Cancer survivors and older adults reported similar levels of functional impairment and social network change. Adding 2 new relationships exhibited protective effects against functional impairment, irrespective of cancer status (odds ratio [OR]: 0.64, 95% confidence interval [CI]: 0.41-0.99). Declines in frequent contact were associated with higher odds of functional impairment among cancer survivors (OR: 1.92, 95% CI: 1.15-3.20). Social network components were not significantly associated with functional impairment in older adults. Adding new relationships may reduce disability in older adults and increasing network contact may help cancer survivors remain independent. Social network interventions may improve quality of life for older adults.

Association Between Symptom Burden and Physical Function in Older Patients with Cancer.

To evaluate the independent association between symptom burden and physical function impairment in older adults with cancer. Cross-sectional. Two university-based geriatric oncology clinics. Patients with cancer aged 65 years or older who underwent evaluation with geriatric assessment (GA). Symptom burden was measured as a summary score of severity ratings (range = 0-10) of 10 commonly reported symptoms using a Clinical Symptom Inventory (CSI). Functional impairment was defined as the presence of one or more impairments of instrumental activities of daily living (IADLs), any significant physical activity limitation on the Medical Outcomes Survey (MOS), one or more recent falls in the previous 6 months, or a Short Physical Performance Battery (SPPB) score of 9 or less. Multivariate analysis evaluated the association between symptom burden and physical function impairment, adjusting for other clinical and sociodemographic variables. From 2011 to 2015, 359 patients with cancer and a median age of 81 years (range = 65-95 y) consented. The mean CSI score was 23.2 ± 20.5 with an observed range of 0 to 90. Patients in the highest quartile of symptom burden (N = 91; CSI score 52 ± 13) had a higher prevalence of IADL impairment (91% vs 51%), physical activity limitation (93% vs 65%), falls (55% vs 21%), and SPPB score of 9 or less (92% vs 69%) (all P values <.01) when compared with those in the bottom quartile (N = 81; CSI score: 2 ± 2). With each unit increase in CSI score, the odds of having IADL impairment, physical activity limitations, falls, and SPPB scores of 9 or less increased by 4.8%, 4.4%, 2.9%, and 2.5%, respectively (P < .05 for all results). In older patients with cancer, higher symptom burden is associated with functional impairment. Future studies are warranted to evaluate if improved symptom management can improve function in older cancer patients. J Am Geriatr Soc 67:998-1004, 2019.

3551 Intermittent Theta Burst Stimulation to Relieve Depression and Executive Function impairment in older adults

OBJECTIVES/SPECIFIC AIMS: The objective of the study is to examine the ability of iTBS to improve depression and executive impairment in depressed older adults. If effective, this treatment will have the potential to improve the quality of life in LLD. METHODS/STUDY POPULATION: From 12- 2016 to date older adults (60 – 85 y/o) in a major depressive episode, with evidence of executive dysfunction (on the NIH Tool Box battery) were enrolled. iTBS protocol: This brief paradigm (3 min 9 seconds duration) was administered on weekdays for four weeks (20 sessions total). Stimulation intensity was set up to 120% of the observed motor threshold. Depression primary outcome: Change in the Montgomery Asberg Depression Rating Scale (MADRS) from baseline to the end of iTBS course. Executive function primary outcome: Change in executive measures from the electronic NIH Tool Box cognitive domain battery8. Executive secondary outcome: Change in scores from baseline to the end of iTBS on the Frontal Systems Behavior Scale (FrSBe), this self reported instrument measures dys-executive behavior. Statistical Analysis: paired t-test examined changes in depression and executive variables from baseline to post iTBS. Pearson correlation examined the association between degree of mood improvement and degree of improvement in executive function. SPSS v 24 was used for all analyses. RESULTS/ANTICIPATED RESULTS: We examined 11 subjects. Primary outcomes: Patients showed a significant decrease in scores on the Montgomery Asberg Depression Rating Scale (MADRS) from baseline Mean (M) = 27.73, Standard Deviation (SD) 8.2 to the end of 4 weeks of iTBS: M = 15.91, SD = 10.05, t = 7.4, p &lt; .001. The Flanker Inhibitory Control and attention test significantly improved from baseline M = 91.0, SD = 7 to the end of iTBS M = 98.7, SD = 12.8, t = −2.9, p = .014 (higher scores at week 4 denote improvement). The List Sorting Working Memory test and the Dimensional Change Card sort a measure of cognitive flexibility improved but did not reach statistical significance. The self reported executive measure improved from baseline M = 48.6, SD = 9.4 to post iTBS M = 39.4, SD = 8.5, t = 3.8, p = .003 (lower scores at week 4 denote improvement). We also examined whether the degree of improvement in depression related to the degree of improvement in executive function. We found positive correlations between change in mood scores with iTBS with change in executive scores with iTBS, with a strong relationship with working memory r = 0.34. Tolerability and Side effects: Common side effects were twitching in facial muscles during the stimulation (n =11), headaches (n =10) and pain or discomfort at the stimulation site and face (n =4). One participant withdrew due to intolerance to the stimulation. DISCUSSION/SIGNIFICANCE OF IMPACT: The iTBS paradigm was effective in improving mood and executive function in older adults. Both the psychometric measure and the self reported executive function measure (indicative of dysexecutive behavior) reflected improvements post iTBS. Improvement in executive function was correlated with depression improvement. We targeted the Dorso Lateral Prefrontal cortex, which exhibits decreased connectivity with the dorsal anterior cingulate in depressed elderly and is a key in orchestration of executive function. Our findings are consistent with the conceptualization of depression as a circuit level disorder affecting interconnected networks involving mood and cognition. Although we demonstrated potential therapeutic effects, the mechanism of action of iTBS remains unknown. We are presently conducting a randomized controlled trial to examine the effects of iTBS on brain connectivity using functional MRI. Results of this study underway will hopefully demonstrate engagement of the TMS target and contribute to a neurocircuitry based approach treatment of geriatric depression.