Physical Activity Over the Life Course and Its Association with Cognitive Performance and Impairment in Old Age

OBJECTIVE: To determine how physical activity at various ages over the life course is associated with cognitive impairment in late life. DESIGN: Cross‐sectional study. SETTING: Four U.S. sites. PARTICIPANTS: Nine thousand three hundred forty‐four women aged 65 and older (mean 71.6) who self‐reported teenage, age 30, age 50, and late‐life physical activity. MEASUREMENTS: Logistic regression was used to determine the association between physical activity status at each age and likelihood of cognitive impairment (modified Mini‐Mental State Examination (mMMSE) score >1.5 standard deviations below the mean, mMMSE score≤22). Models were adjusted for age, education, marital status, diabetes mellitus, hypertension, depressive symptoms, smoking, and body mass index. RESULTS: Women who reported being physically active had a lower prevalence of cognitive impairment in late life than women who were inactive at each time (teenage: 8.5% vs 16.7%, adjusted odds ratio (AOR)=0.65, 95% confidence interval (CI)=0.53–0.80; age 30: 8.9% vs 12.0%, AOR=0.80, 95% CI=0.67–0.96); age 50: 8.5% vs 13.1%, AOR=0.71, 95% CI=0.59–0.85; old age: 8.2% vs 15.9%, AOR=0.74, 95% CI=0.61–0.91). When the four times were analyzed together, teenage physical activity was most strongly associated with lower odds of late‐life cognitive impairment (OR=0.73, 95% CI=0.58–0.92). However, women who were physically inactive as teenagers and became active in later life had lower risk than those who remained inactive. CONCLUSIONS: Women who reported being physically active at any point over the life course, especially as teenagers, had a lower likelihood of cognitive impairment in late life. Interventions should promote physical activity early in life and throughout the life course.     

Renal Dysfunction in Heart Failure With Preserved Ejection Fraction: Insights From the RELAX Trial

BackgroundPatients with heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD) represent a high-risk phenotype. The Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial enrolled a high proportion of CKD participants, allowing investigation into differences in HFpEF by CKD status.Methods and ResultsAmong 212 participants, we investigated the associations of CKD with biomarkers, cardiac structure, and exercise capacity, and identified predictors of change in estimated glomerular filtration rate (eGFR) over trial follow-up. CKD participants (eGFR ≤60 mL/min/1.73m²) were older, had more comorbidities, and had worse diastolic function. Lower eGFR was associated with higher levels of endothelin-1, N-terminal pro–B-type natriuretic peptide, aldosterone, uric acid, and biomarkers of fibrosis (P < .05 for all). Whereas lower eGFR was associated with worse peak oxygen consumption (VO₂) after adjustment for demographics, clinical comorbidities, exercise modality, ejection fraction, and chronotropic index (β coefficient per 1 SD decrease in eGFR: −0.61, 95% CI: −1.01, −0.22, P = .002), this association was attenuated after further adjustment for hemoglobin (β coefficient: −0.26, 95% CI: −0.68, 0.16, P = .22). Hemoglobin mediated 35% of the association between eGFR and peak VO₂. Sildenafil therapy was independently associated with worsening eGFR over the trial (β coefficient: −2.79, 95% CI: −5.34, −0.24, P = .03).ConclusionRenal dysfunction in HFpEF is characterized by echocardiographic and biomarker profiles indicative of more advanced disease, and reduced hemoglobin is a strong mediator of the association between renal dysfunction and low exercise capacity. Sildenafil therapy was associated with worsening of renal function in RELAX.     

Health Literacy and Cognitive Performance in Older Adults

OBJECTIVES: To study the relationship between health literacy and memory and verbal fluency in older adults.
DESIGN: Cross-sectional cohort.
SETTING: Twenty senior centers and apartment buildings in New York, New York.
PARTICIPANTS: Independently living, English- and Spanish-speaking adults aged 60 and older (N=414).
MEASUREMENTS: Health literacy was measured using the Short Test of Functional Health Literacy in Adults (S-TOFHLA). The associations between S-TOFHLA scores and immediate and delayed recall (Wechsler Memory Scale II), verbal fluency (Animal Naming), and global cognitive function (Mini-Mental State Examination, MMSE) were modeled using multivariable logistic and linear regression.
RESULTS: Health literacy was inadequate in 24.3% of participants. Impairment of immediate recall occurred in 20.4%; delayed recall, 15.0%; verbal fluency, 9.9%; and MMSE, 17.4%. Abnormal cognitive function was strongly associated with inadequate health literacy: immediate recall (adjusted odds ratio (AOR)=3.44, 95% confidence interval (CI)=1.71–6.94, P <.001), delayed recall (AOR=3.48, 95% CI=1.58–7.67, P =.002), and verbal fluency (AOR=3.47, 95% CI=1.44–8.38, P =.006). These associations persisted in subgroups that excluded individuals with normal age-adjusted MMSE scores.
CONCLUSION: Memory and verbal fluency are strongly associated with health literacy, independently of education and health status, even in those with subtle cognitive dysfunction. Reducing the cognitive burden of health information might mitigate the detrimental effects of limited health literacy in older adults. Research that examines the effect of materials modified to older adults' cognitive limitations on health literacy and health outcomes is needed.     

Cognitive impairment,depressive symptoms,and functional decline in older people

OBJECTIVES: Although cognitive impairment and depressive symptoms are associated with functional decline, it is not understood how these risk factors act together to affect the risk of functional decline. The purpose of this study is to determine the relative contributions of cognitive impairment and depressive symptoms on decline in activity of daily living (ADL) function over 2 years in an older cohort. DESIGN: Prospective cohort study. SETTING: A U.S. national prospective cohort study of older people, Asset and Health Dynamics in the Oldest Old. PARTICIPANTS: Five thousand six hundred ninety-seven participants (mean age 77, 64% women, 86% white) followed from 1993 to 1995. MEASUREMENTS: Cognitive impairment and depressive symptoms were defined as the poorest scores: 1.5 standard deviations below the mean on a cognitive scale or 1.5 standard deviations above the mean on validated depression scales. Risk of functional decline in participants with depressive symptoms, cognitive impairment, and both, compared with neither risk factor, were calculated and stratified by baseline dependence. Analyses were adjusted for demographics and comorbidity. RESULTS: Eight percent (n = 450) of subjects declined in ADL function. In participants who were independent in all ADLs at baseline, the relative risk (RR) of 2-year functional decline was 2.3 (95% confidence interval (CI) = 1.7-3.1) for participants with cognitive impairment, 1.9 (95% CI = 1.3-2.6) for participants with depressive symptoms, and 2.4 (95% CI = 1.4-3.7) for participants with cognitive impairment and depressive symptoms. In participants who were dependent in one or more ADLs at baseline, RR of 2-year functional decline was 1.9 (95% CI = 1.2-2.8) for participants with cognitive impairment, 0.6 (95% CI = 0.3-1.3) for participants with depressive symptoms, and 1.5 (95% CI = 0.8-2.6) for participants with cognitive impairment and depressive symptoms. CONCLUSIONS: In participants with no ADL dependence at baseline, cognitive impairment and depressive symptoms are risk factors for decline, but that, in participants with dependence in ADL at baseline, cognitive impairment, but not depressive symptoms, is a risk factor for additional decline.     

Does concealed chronic kidney disease predict survival of older patients discharged from acute care hospitals?

We aimed at verifying whether unrecognized chronic kidney disease (CKD) (i.e., reduced estimated glomerular filtration rate in spite of normal serum creatinine) has prognostic significance in an unselected population of older patients discharged from 11 acute care hospitals located throughout Italy. Our series consisted of 396 participants aged 70 and older. Estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease (MDRD) study equation. We compared three groups: Normal renal function (normal serum creatinine levels and normal eGFR), concealed (normal serum creatinine levels and reduced eGFR), or overt (increased creatinine levels and reduced eGFR) renal failure. The relationship between renal function and 1-year mortality was evaluated using Kaplan-Meier curves and Cox regression analysis including potential confounders. Overall, 56 patients died over a cumulative follow-up time of 335 months, with an estimated incidence rate of 16.7/100 person-year (PY). The corresponding figures in patients with normal renal function, concealed CKD, and overt CKD were 9.8/100 PY (95% CI, 5.7-15.7), 28.3/100 PY (95% CI, 13.6-52.1), and 23.0 (95% CI, 15.4-33.0), respectively (log rank test p = 0.006). According to the fully adjusted model, both concealed (hazard ratio [HR], 2.35; 95% CI, 1.09-6.01) and overt CKD (HR, 2.09; 95% CI, 1.05-5.34) were significantly associated with the outcome. Concealed CKD contributes to profile the elderly patient at greater risk of death after being discharged from acute care medical wards. If confirmed in broader populations, this finding might have both clinical and epidemiological implications.     

Depressive symptoms, chronic diseases, and physical disabilities as predictors of cognitive functioning trajectories in older Americans

OBJECTIVES: To determine the concurrent influence of depressive symptoms, medical conditions, and disabilities in activities of daily living (ADLs) on rates of decline in cognitive function of older Americans. DESIGN: Prospective cohort. SETTING: National population based. PARTICIPANTS: A national sample of 6,476 adults born before 1924. MEASUREMENTS: Differences in cognitive function trajectories were determined according to prevalence and incidence of depressive symptoms, chronic diseases, and ADL disabilities. Cognitive performance was tested five times between 1993 and 2002 using a multifaceted inventory examined as a global measure (range 0–35, standard deviation (SD) 6.0) and word recall (range 0–20, SD 3.8) analyzed separately. RESULTS: Baseline prevalence of depressive symptoms, stroke, and ADL limitations were independently and strongly associated with lower baseline cognition scores but did not predict future cognitive decline. Each incident depressive symptom was independently associated with a 0.06‐point lower (95% confidence interval (CI)=0.02–0.10) recall score, incident stroke with a 0.59‐point lower total score (95% CI=0.20–0.98), each new basic ADL limitation with a 0.07‐point lower recall score (95% CI=0.01–0.14) and a 0.16‐point lower total score (95% CI=0.07–0.25), and each incident instrumental ADL limitation with a 0.20‐point lower recall score (95% CI=0.10–0.30) and a 0.52‐point lower total score (95% CI=0.37–0.67). CONCLUSION: Prevalent and incident depressive symptoms, stroke, and ADL disabilities contribute independently to poorer cognitive functioning in older Americans but do not appear to influence rates of future cognitive decline. Prevention, early identification, and aggressive treatment of these conditions may ameliorate the burdens of cognitive impairment.     

Incorporating Geriatric Assessment into a Nephrology Clinic: Preliminary Data from Two Models of Care

Older adults with advanced chronic kidney disease (CKD) experience functional impairment that can complicate CKD management. Failure to recognize functional impairment may put these individuals at risk of further functional decline, nursing home placement, and missed opportunities for timely goals‐of‐care conversations. Routine geriatric assessment could be a useful tool for identifying older adults with CKD who are at risk of functional decline and provide contextual information to guide clinical decision‐making. Two innovative programs were implemented in the Veterans Health Administration that incorporate geriatric assessment into a nephrology visit. In one program, a geriatrician embedded in a nephrology clinic used standardized geriatric assessment tools with individuals with CKD aged 70 and older (Comprehensive Geriatric Assessment for CKD) (CGA‐4‐CKD). In the second program, a nephrology clinic used comprehensive appointments for individuals aged 75 and older to conduct geriatric assessments and CKD care (Renal Silver). Data on 68 veterans who had geriatric assessments through these programs between November 2013 and May 2015 are reported. In CGA‐4‐CKD, difficulty with one or more activities of daily living (ADLs), history of falls, and cognitive impairment were each found in 27.3% of participants. ADL difficulty was found in 65.7%, falls in 28.6%, and cognitive impairment in 51.6% of participants in Renal Silver. Geriatric assessment guided care processes in 45.4% (n = 15) of veterans in the CGA‐4‐CKD program and 37.1% (n = 13) of those in Renal Silver. Findings suggest there is a significant burden of functional impairment in older adults with CKD. Knowledge of this impairment is applicable to CKD management.     

Uric acid, hypertension, and chronic kidney disease among Alaska Eskimos: the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study

J Clin Hypertens (Greenwich).****;**:**–**. ©2011 Wiley Periodicals, Inc. It is unknown what role uric acid (UA) may play in the increasing rates of cardiovascular disease (CVD) among Alaska Eskimos. UA is associated with both hypertension (HTN) and chronic kidney disease (CKD). The authors analyzed 1078 Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) participants. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine measures using the Modification of Diet in Renal Disease equation. CKD was defined by an eGFR of <60 mL/min/1.73 m². The authors adjusted for age, sex, education, diabetes, hypertension (or eGFR), obesity, lipids, and smoking status; 7% (n=75) had prevalent CKD. eGFR decreased with increasing tertiles of serum UA (P<.001). UA was independently associated with prevalent CKD (adjusted odds ratio [OR] and 95% confidence interval [CI] of 2.04 (1.62–2.56), respectively). Twenty‐one percent (n=230) had prevalent HTN and UA was independently associated with prevalent HTN (adjusted OR, 1.2; 95% CI, 1.1–1.5). UA is independently associated with prevalent CKD and HTN in this population.     

Chronic kidney disease as a predictor of cardiovascular disease (from the Framingham Heart Study)

Chronic kidney disease (CKD) is a risk factor for cardiovascular disease (CVD), although shared risk factors may mediate much of the association. CKD and CVD were related in the setting of specific CVD risk factors, and whether more advanced CKD was a CVD risk equivalent was determined. The Framingham Heart Study original cohort (n = 2,471, mean age 68 years, 58.9% women) was studied. Glomerular filtration rate was estimated (eGFR) using the simplified Modification of Diet in Renal Disease Study equation. CKD was defined as eGFR <59 (women) and <64 ml/min/1.73 m(2) (men), and stage 3b CKD was defined as eGFR of 30 to 44 (women) and 30 to 50 ml/min/1.73 m(2) (men). Cox proportional hazard models adjusting for CVD risk factors were used to relate CKD to CVD. Effect modification by CVD risk factors was tested for. Overall, 23.2% of the study sample had CKD (n = 574, mean eGFR 50 ml/min/1.73 m(2)) and 5.3% had stage 3b CKD (n = 131, mean eGFR 42 ml/min/1.73 m(2)). In multivariable models (mean follow-up 16 years), stage 3 CKD was marginally associated with CVD (hazard ratio [HR] 1.17, 95% confidence interval [CI] 0.99 to 1.38, p = 0.06), whereas stage 3b CKD was associated with CVD (HR 1.41, 95% CI 1.05 to 1.91, p = 0.02). Testing CVD risk equivalency, the risk of CVD for stage 3b CKD in subjects with previous CVD was significantly lower compared with subjects with previous CVD and no stage 3b CKD (age- and sex-adjusted HR for CVD 0.66, 95% CI 0.47 to 0.91, p = 0.01). Low high-density lipoprotein cholesterol modified the association between CKD and CVD (p = 0.004 for interaction). Stage 3b CKD was associated with CVD, but was not a CVD risk equivalent. In conclusion, CVD risk in the setting of CKD is higher in the setting of low high-density lipoprotein cholesterol.     

Development rate of chronic kidney disease in hepatitis C virus patients with advanced fibrosis after interferon therapy

Aim: The aim of this retrospective cohort study is to assess the development incidence and predictive factors for chronic kidney disease (CKD) after the termination of interferon therapy in hepatitis C virus (HCV) positive Japanese patients with liver cirrhosis. Methods: A total of 650 HCV positive, liver cirrhotic patients who were treated with interferon and showed an estimated glomerular filtration rate (eGFR) of ≥60 mL/min per 1.73 m² after the termination of interferon therapy were enrolled. CKD was defined as an eGFR of <60 mL/min per 1.73 m². End‐stage‐CKD was defined as an eGFR of <15 mL/min/1.73 m². The primary goal is the new development of CKD and end‐stage‐CKD. Results: Eighty‐five patients developed CKD, and six patients progressed to end‐stage‐CKD. The development rate of CKD was 5.2% at the 5th year, 14.5% at the 10th year and 30.6% at the 15th year. Multivariate Cox proportional hazards analysis showed that CKD occurred when patients had age increments of 10 years (hazard ratio: 2.32; 95% confidence interval [CI] 1.61–3.35; P < 0.001), eGFR decrements of 10 mL/min per 1.73 m² (hazard ratio: 1.66; 95% CI 1.27–2.16; P < 0.001), hypertension (hazard ratio: 2.00; 95% CI 1.13–3.53; P = 0.017), diabetes (hazard ratio: 1.79; 95% CI 1.02–3.14; P = 0.042), and non‐clearance of HCV (hazard ratio: 2.67; 95% CI 1.34–5.32; P = 0.005). The development rate of end‐stage‐CKD was 0.4% at the 5th year, 1.6% at the 10th year and 2.8% at the 15th year. Conclusions: The annual incidence for CKD among cirrhotic patients with HCV was determined to be about 1.0–1.5%. In addition, the annual incidence for end‐stage‐CKD is one order of magnitude lower than that of CKD.     

Anticholinergic medication use and cognitive impairment in the older population: the medical research council cognitive function and ageing study

OBJECTIVES: To determine whether the use of medications with possible and definite anticholinergic activity increases the risk of cognitive impairment and mortality in older people and whether risk is cumulative. DESIGN: A 2‐year longitudinal study of participants enrolled in the Medical Research Council Cognitive Function and Ageing Study between 1991 and 1993. SETTING: Community‐dwelling and institutionalized participants. PARTICIPANTS: Thirteen thousand four participants aged 65 and older. MEASUREMENTS: Baseline use of possible or definite anticholinergics determined according to the Anticholinergic Cognitive Burden Scale and cognition determined using the Mini‐Mental State Examination (MMSE). The main outcome measure was decline in the MMSE score at 2 years. RESULTS: At baseline, 47% of the population used a medication with possible anticholinergic properties, and 4% used a drug with definite anticholinergic properties. After adjusting for age, sex, educational level, social class, number of nonanticholinergic medications, number of comorbid health conditions, and cognitive performance at baseline, use of medication with definite anticholinergic effects was associated with a 0.33‐point greater decline in MMSE score (95% confidence interval (CI)=0.03–0.64, P=.03) than not taking anticholinergics, whereas the use of possible anticholinergics at baseline was not associated with further decline (0.02, 95% CI=?0.14–0.11, P=.79). Two‐year mortality was greater for those taking definite (OR=1.68; 95% CI=1.30–2.16; P<.001) and possible (OR=1.56; 95% CI=1.36–1.79; P<.001) anticholinergics. CONCLUSION: The use of medications with anticholinergic activity increases the cumulative risk of cognitive impairment and mortality.     

Cognitive impairment in chronic kidney disease

Objectives: To assess the prevalence of cognitive impairment in persons with chronic kidney disease (CKD) and its relation to the severity of CKD.
Design: Cross-sectional study.
Setting: University-affiliated ambulatory nephrology and dialysis practices.
Participants: Eighty subjects with CKD Stages III and IV not requiring dialysis (CKD) and 80 subjects with CKD Stage V on hemodialysis (end-stage renal disease (ESRD)) with a mean age±standard deviation of 62.5±14.3.
Measurements: Three standardized cognitive tests, the Modified Mini-Mental State Examination (3MS), Trailmaking Test B (Trails B), and California Verbal Learning Trial (CVLT). Glomerular filtration rate was estimated in subjects with CKD using the six-variable Modification of Diet in Renal Disease equation.
Results: There was a graded relation between cognitive function and severity of CKD. Mean scores on the 3MS, Trails B, and CVLT immediate and delayed recall were significantly worse for subjects with ESRD than for subjects with CKD or published norms ( P<. 001 for all comparisons). Scores on the Trails B ( P<. 001) and CVLT immediate ( P=. 01) and delayed ( P<. 001) recall were significantly worse for subjects with CKD not requiring dialysis than for published norms. In addition, the fraction of subjects with impairment on the 3MS and Trails B increased with decreasing kidney function.
Conclusion: Cognitive impairment is associated with the severity of kidney disease. Further studies are needed to determine the reasons for cognitive impairment in subjects with CKD and ESRD.     

Cardiac and kidney benefits of empagliflozin in heart failure across the spectrum of kidney function: Insights from the EMPEROR-Preserved trial

Aim

In the EMPEROR-Preserved trial, empagliflozin improved clinical outcomes of patients with heart failure (HF) with preserved ejection fraction. In this pre-specified analysis, we aim to study the effect of empagliflozin on cardiovascular and kidney outcomes across the spectrum of kidney function.

Methods and results

Patients were categorized by the presence or absence of chronic kidney disease (CKD) at baseline (CKD defined by an estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m² or urine albumin to creatinine ratio >300 mg/g). The primary and key secondary outcomes were (i) a composite of cardiovascular death or first HF hospitalization (primary outcome); (ii) total number of HF hospitalization, (iii) eGFR slope; and a pre-specified exploratory composite kidney outcome including a sustained ≥40% decline in eGFR, chronic dialysis or renal transplant. The median follow-up was 26.2 months. A total of 5988 patients were randomized to empagliflozin or placebo, of whom 3198 (53.5%) had CKD. Irrespective of CKD status, empagliflozin reduced the primary outcome (with CKD: hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.69–0.94; without CKD: HR 0.75, 95% CI 0.60–0.95; interaction p = 0.67) and total (first and recurrent) hospitalizations for HF (with CKD: HR 0.68, 95% CI 0.54–0.86; without CKD: HR 0.89, 95% CI 0.66–1.21; interaction p = 0.17). Empagliflozin slowed the slope of eGFR decline by 1.43 (1.01–1.85) ml/min/1.73 m²/year in patients with CKD and 1.31 (0.88–1.74) ml/min/1.73 m²/year in patients without CKD (interaction p = 0.70). Empagliflozin did not reduce the pre-specified kidney outcome in patients with or without CKD (with CKD: HR 0.97, 95% CI 0.71–1.34; without CKD: HR 0.92, 95% CI 0.58–1.48; interaction p = 0.86) but slowed progression to macroalbuminuria and reduced the risk of acute kidney injury. The effect of empagliflozin on the primary composite outcome and the key secondary outcomes was consistent across five baseline eGFR categories (all interaction p >0.05). Empagliflozin was well tolerated independent of CKD status.

Conclusions

In EMPEROR-Preserved, empagliflozin had a beneficial effect on the key efficacy outcomes in patients with and without CKD. Overall, the benefit and safety of empagliflozin was consistent across a wide range of kidney function spectrum, down to a baseline eGFR of 20 ml/min/1.73 m².     

Relation of uric acid level to rapid kidney function decline and development of kidney disease: The Jackson Heart Study

Whether elevated uric acid (UA) is an independent risk factor for chronic kidney disease (CKD) is not well established. The authors evaluated the relationship of UA with rapid kidney function decline (RKFD) and incident CKD among 3702 African Americans (AAs) in the Jackson Heart Study with serum UA levels measured at baseline exam (2000‐2004). RKFD was defined as ≥ 30% eGFR loss and incident CKD as development of eGFR < 60 mL/min/1.73 m² with a ≥ 25% decline in eGFR between baseline and exam 3 (2009‐2013). RKFD and CKD were found in 11.4% and 7.5% of the participants, respectively. In a fully adjusted model, the odds of RKFD (OR, 1.8; 95% CI, 1.25‐2.49) and incident CKD (OR, 2.00; 95% CI, 1.31‐3.06) were significantly higher among participants in the top UA quartile vs bottom quartile. In the JHS, elevated UA was significantly associated with RKFD and incident CKD.     

Association of chronic kidney disease with atrial fibrillation among adults in the United States: REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

BACKGROUND: Atrial fibrillation (AF) is common among patients with end-stage renal disease, but few data are available on its prevalence among adults with chronic kidney disease (CKD) of lesser severity. methods and results: We evaluated the association of CKD with ECG-detected AF among 26 917 participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a population-based cohort of African-American and white US adults ≥45 years of age. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease study equation and albuminuria was defined as a urinary albumin to creatinine ratio ≥30 mg/g. Participants were categorized by renal function: no CKD (eGFR ≥60 mL/min/1.73 m(2) without albuminuria, n=21 081), stage 1 to 2 CKD (eGFR ≥60 mL/min/1.73 m(2) with albuminuria n=2938), stage 3 CKD (eGFR 30 to 59 mL/min/1.73 m(2), n=2683) and stage 4 to 5 CKD (eGFR <30 mL/min/1.73 m(2), n=215). The prevalence of AF among participants without CKD, and with stage 1 to 2, stage 3, and stage 4 to 5 CKD was 1.0%, 2.8%, 2.7% and 4.2%, respectively. Compared with participants without CKD, the age-, race-, and sex-adjusted odds ratios for prevalent AF were 2.67 (95% confidence interval, 2.04 to 3.48), 1.68 (95% confidence interval, 1.26 to 2.24) and 3.52 (95% confidence interval, 1.73 to 7.15) among those with stage 1 to 2, stage 3, and stage 4 to 5 CKD. The association between CKD and prevalent AF remained statistically significant after further multivariable adjustment and was consistent across numerous subgroups. CONCLUSIONS: Regardless of severity, CKD is associated with an increased prevalence of AF among US adults.     

Trajectories of Quality of Life in Older Persons with Advanced Illness

OBJECTIVES: To examine subjective ratings of quality of life (QoL) in older adults with advanced illness. DESIGN: Observational cohort study with interviews at least every 4 months for up to 2 years conducted between December 1999 and December 2002. SETTING: Participants' homes. PARTICIPANTS: One hundred eighty‐five community‐dwelling individuals aged 60 and older with advanced cancer, heart failure, or chronic obstructive pulmonary disease. MEASUREMENTS: Participants were asked how they would rate their overall QoL. RESULTS: Of participants who died, 46% reported good or best possible QoL at their final interview, 21% reported improvement in QoL from their penultimate to final interview, and 39% reported no change. Forty‐nine percent of participants reported two or more changes in the direction of their QoL trajectories (e.g., QoL improved then declined). As measured over time in a multivariable longitudinal regression analysis, greater activity of daily living disability (adjusted odds ratio (AOR)=0.85, 95% confidence interval (CI)=0.75–0.95) and depressed mood (AOR=0.42, 95%CI=0.27–0.66) were associated with poorer QoL, whereas better self‐rated health (AOR=4.79, 95% CI=2.99–7.69) and having grown closer to one's church (AOR=1.99, 95% CI=1.17–3.39) were associated with better QoL. CONCLUSION: Although declining QoL is not an inevitable consequence of advancing illness, individuals' ratings of QoL are highly variable over time, suggesting that temporary factors may influence subjective QoL. Functional status, depression, and connection to one's religious community are shared determinants of QoL.     

Predicting cognitive impairment in high-functioning community-dwelling older persons: MacArthur Studies of Successful Aging

OBJECTIVES: To examine whether simple cognitive tests, when applied to cognitively intact older persons, are useful predictors of cognitive impairment 7 years later. DESIGN: Cohort study. SETTING: Durham, North Carolina; East Boston, Massachusetts; and New Haven, Connecticut, areas that are part of the National Institute on Aging Established Populations for Epidemiological Studies of the Elderly. PARTICIPANTS: Participants, aged 70 to 79, from three community-based studies, who were in the top third of this age group, based on physical and cognitive functional status. MEASUREMENTS: New onset of cognitive impairment as defined by a score of less than 7 on the Short Portable Mental Status Questionnaire (SPMSQ) in 1995. RESULTS: At 7 years, 21.8% (149 of 684 subjects) scored lower than 7 on the SPMSQ. Using multivariate logistic regression, three baseline (1988) cognitive tests predicted impairment in 1995. These included two simple tests of delayed recall-the ability to remember up to six items from a short story and up to 18 words from recall of Boston Naming Test items. For each story item missed, the adjusted odds ratio (AOR) for cognitive impairment was 1.44 (95% confidence interval (CI) = 1.16-1.78, P <.001). For each missed item from the word list, the AOR was 1.20 (95% CI = 1.09-1.31, P <.001). The Delayed Recognition Span, which assesses nonverbal memory, also predicted cognitive impairment, albeit less strongly (odds ratio = 1.06 per each missed answer, 95% CI = 1.003-1.13, P =.04). CONCLUSIONS: This study identifies measures of delayed recall and recognition as significant early predictors of subsequent cognitive decline in high-functioning older persons. Future efforts to identify those at greatest risk of cognitive impairment may benefit by including these measures.     

Cognitive training decreases motor vehicle collision involvement of older drivers

OBJECTIVES: To test the effects of cognitive training on subsequent motor vehicle collision (MVC) involvement of older drivers. DESIGN: Randomized, controlled, multisite, single‐blind clinical trial. SETTING: Community‐dwelling seniors at four U.S. sites: Birmingham, Alabama; Baltimore, Maryland; Indianapolis, Indiana; and State College, Pennsylvania. PARTICIPANTS: Nine hundred eight older drivers (mean age 73.1; 18.6% African American) who were randomized to one of three cognitive interventions or a control condition. INTERVENTIONS: Up to 10 sessions of cognitive training for memory, reasoning, or speed of processing. MEASUREMENTS: State‐recorded MVC involvement up to 6 years after study enrollment. RESULTS: Speed‐of‐processing and reasoning training resulted in lower rates of at‐fault collision involvement over the subsequent approximately 6‐year period than controls. After adjusting for age, sex, race, education, mental status, health, vision, depressive symptoms, and testing site, participants randomized to the speed‐of‐processing and reasoning interventions had an approximately 50% lower rate (per person‐mile) of at‐fault MVCs than the control group (rate ratio (RR)=0.57, 95% confidence interval (CI)=0.34–0.96 for speed of processing), and (RR=0.50, 95% CI=0.27–0.92 for reasoning). There was no significant difference observed for the memory group. CONCLUSION: Cognitive speed‐of‐processing and reasoning training resulted in a lower at‐fault MVC rate in older drivers than in controls. Considering the importance of driving mobility, the costs of crashes, and the benefits of cognitive training, these interventions have great potential to sustain independence and quality of life of older adults. More research is needed to understand the effects of different types and quantities of training.     

Hyponatremia and Cognitive Impairment in Patients Treated with Peritoneal Dialysis

Background and objectives

Hyponatremia has been identified as a relevant factor for cognitive impairment but has not been investigated in patients receiving peritoneal dialysis (PD). This study investigated the relationship between hyponatremia and cognitive functions in PD patients.

Design, setting, participants, & measurements

A total of 476 clinically stable patients from five PD units who were older than 18 years of age and had undergone PD for at least 3 months between March 2013 and March 2014 were enrolled in this multicenter cross-sectional study. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS); executive function, by trail making tests A (trails A) and B (trails B); and immediate memory, delayed memory, and language ability, by subtests of Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Hyponatremia was defined as serum sodium level ≤135 mmol/L, which was calculated as the mean of measurements taken over the preceding 3 months.

Results

Fifty patients (10.5%) had hyponatremia; these patients tended to be older and less educated, to have less inflammation, and to have the higher prevalence of cognitive impairment. They also had lower scores on RBANS subtests. After adjustment for demographic and clinical confounders, hyponatremia was independently associated with lower 3MS score (coefficient, −5.28; 95% confidence interval [CI], −8.44 to –2.13) and longer completion time of trials A (coefficient, 22.68; 95% CI, 3.44 to 41.92) and B (coefficient, 45.56; 95% CI, 1.30 to 89.81). After additional adjustment for laboratory measures, hyponatremia was still associated with 3MS score and completion time of trails A. Hyponatremia was independently associated with CI (odds ratio, 2.17; 95% CI, 1.02 to 4.94) and executive dysfunction (odds ratio, 2.43; 95% CI, 1.01 to 5.87) using multivariate logistic regression analysis. Sensitivity analyses with multivariable models that included propensity score still supported the association between hyponatremia and cognitive impairment.

Conclusions

Hyponatremia was associated with global and specific cognitive impairment in PD patients.     

Chronic kidney disease and functional limitation in older people: health, aging and body composition study

OBJECTIVES: To assess whether chronic kidney disease (CKD) is independently associated with incident physical-function limitation. DESIGN: Prospective cohort study. SETTING: Two sites: Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Two thousand one hundred thirty-five men and women aged 70 to 79 without functional limitation at baseline from the Health, Aging and Body Composition Study. MEASUREMENTS: Functional limitation was defined as difficulty in walking one-quarter of a mile or climbing 10 steps on two consecutive reports 6 months apart (in the same function). Kidney function was measured using serum cystatin C. Estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease formula (<60 versus > or =60 mL/min per 1.73 m(2)), was a secondary predictor. Muscle strength, lean body mass according to dual energy x-ray absorptiometry, comorbidity, medication use, and inflammatory markers were evaluated as covariates. RESULTS: Persons in the highest (> or =1.13 mg/L) quartile of cystatin C experienced a significantly higher risk of developing functional limitation than those in the lowest (<0.86 mg/L) quartile (hazard ratio (HR)=1.70, 95% confidence interval (CI)=1.40-2.07). The association between the fourth cystatin C quartile and functional limitation remained after adjustment for demographics, lean body mass, comorbidity, muscle strength, and gait speed (HR=1.41, 95% CI=1.13-1.75), although the association was attenuated after adjustment for markers of inflammation (HR=1.15, 95% CI=0.90-1.46). Similar results were found for eGFR less than 60 mL/min per 1.73 m(2), although the association with functional limitation remained after adjustment for inflammatory markers (HR=1.30, 95% CI=1.08-1.56). CONCLUSION: CKD is associated with the development of functional impairment independent of comorbidity, body composition, and tests of strength and physical performance. The mechanism may be related to a heightened inflammatory state in CKD.