Kidney Function And Cognitive Performance And Decline in Older Men

Contact: Audrey Hu Whatsapp/hp: 0086 13880143964 Email: audrey.hu@wecistanche.com

Yelena Slinin, et al

OBJECTIVES: To examine the association between kidney function and cognitive impairment and decline in elderly men.

DESIGN: Observational prospective cohort.

SETTING: Community-based.

PARTICIPANTS: Five thousand five hundred twenty-nine community-dwelling men aged 65 and older (mean age 73.6+- 5.9).

MEASUREMENTS: Estimated glomerular filtration rate (eGFR) calculated using the standardized Modification of Diet in Renal Disease (MDRD) equation; cognitive function assessed using the Modified Mini-Mental State Examination (3MS) and Trail Making Test B (Trails B).

RESULTS: At baseline, 148 (2.7%) and 494 (9.1%) men were classified as cognitively impaired and, in the 5-year prospective analysis, 931 (23%) and 432 (11.6%) met the criteria for cognitive decline at follow-up defined according to 3MS and Trails B performance, respectively. In unadjusted analysis, the odds of prevalent cognitive impairment and risk of cognitive decline were significantly higher in men with an eGFR less than 45 and 45 to 59 mL/min per 1.73 m2 than in men with an eGFR 60 mL/min per 1.73 m2 or greater. Differences in age, race and education between eGFR categories largely explained these associations, with the exception of the association between poorer renal function and higher odds of impairment based on Trails B test score, which persisted despite adjustment for multiple potential confounders.

CONCLUSION: This study found evidence of an independent association between mild to moderate reductions in kidney function and poor executive function at baseline but not with global cognitive impairment or risk of cognitive decline in older men. J Am Geriatr Soc 56:2082–2088, 2008.

Keywords: kidney function; cognition; elderly

Cistanche can improve kidney function

Kidney function declines with age;1 at least 35% of adults in the United States aged 70 and older have moderately to severely compromised kidney function.2Kidney disease has been associated with cognitive impairment and dementia in patients undergoing dialysis3–6 and patients with moderate chronic kidney disease (CKD).7–11 Individuals with CKD have a heavy burden of traditional coronary disease risk factors, such as older age, hypertension, diabetes mellitus, and hyperlipidemia, as well as nontraditional risk factors such as hyperhomocysteinemia, oxidative stress, and inflammation,12–14 associated with cognitive impairment in the general population.15–17 Kidney disease is also associated with a greater risk of stroke,18,19 which in turn increases the risk of cognitive impairment and dementia.20 Retention of uremic toxins has been implicated in poorer cognitive function, with improvement in cognitive performance as a result of more-intensive dialysis and after kidney transplantation.21,22 Of the studies that have reported the association between kidney function and cognitive function, only two published studies were prospective in design.10,11 In addition, prior studies examining the association between cognitive function and kidney disease have included only women or a few men.9 This study aimed to determine whether poorer kidney function, defined as lower glomerular filtration rate, was associated with greater odds of prevalent cognitive impairment and risk of cognitive decline in community-dwelling elderly men.

METHODS

Study Participants

The Osteoporotic Fractures in Men Study (MrOS) is a multicenter prospective study of risk factors for vertebral and nonvertebral fractures in older men. The design, measures, and recruitment methods have been described previously.23,24 Briefly, 5,995 men aged 65 and older were recruited from March 2000 to April 2002 from the populations of Birmingham, Alabama; Minneapolis, Minnesota; the Monongahela Valley near Pittsburgh, Pennsylvania; Palo Alto, California; Portland, Oregon; and San Diego, California. Approval was obtained from the institutional review boards of the participating institutions, and written informed consent was obtained from all study participants. Men were excluded from the study if they could not walk without assistance, had had bilateral hip replacements, did not live in or planned to move from the area surrounding the study site, or had a severe medical condition that would preclude participation in follow-up. Five thousand five hundred twenty-nine men (92% of the cohort) with measurement of serum creatinine (SCr) and cognitive testing with the Modified Mini-Mental State Examination (3MS) at baseline were included in this study. Of these, 5,403 (90% of the cohort) had Trail Making Test Part B (Trails B) testing at baseline. An average-standard deviation of 4.6 +- 0.4 years later, 4,833 men (97% of survivors) participated in a second visit, including 654 who completed a mailed questionnaire only and 4,179 who also attended a second clinical examination during which they underwent cognitive testing.

Cistanche can improve kidney function

Estimation of Kidney Function

SCr was measured on previously thawed specimens collected in the morning from MrOS participants at baseline examination and centrally stored at - 1201C using the Roche COBAS Integra 800 automated analyzer (Roche Diagnostics Corp., Indianapolis, IN) using a variation of the Jaffe enzymatic method. This assay was calibrated daily. Inter- and intraassay coefficients of variation were 5.3%.Kidney function was expressed as estimated glomerular filtration rate (eGFR) using standardized SCr based formula derived using the Modification of Diet in Renal Disease (MDRD) equation: GFR=175 x SCr^-1.154 - age^{- 0.203} x 1.212 ( if black) x 0.742 (if female).25

A modification of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative kidney disease classification guidelines was used to define categories of kidney disease according to eGFR categories.26 Given a large number of subjects with an eGFR between 30 and 59 mL/min per 1.73 m2 and few subjects with an eGFR less than 30 mL/min per 1.73 m2, the category of eGFR between 45 and 59 mL/min per 1.73 m2 was defined as mild CKD and eGFR less than 45 mL/min per 1.73 m2 as moderate CKD. This classification has been used in other studies.10 Dialysis status of participants at baseline was unknown, but during follow-up visits, it became apparent that six individuals were on dialysis. Excluding these individuals did not alter the overall results. Results presented herein include these individuals.

Cognitive Function

Testing A trained technician assessed cognitive function using the 3MS (primary outcome) and the Trails B (secondary outcome) at baseline and follow-up. The 3MS is a test of global cognitive function, with scores ranging from 0 to 100, with higher scores representing a better cognitive function. When a score of less than 80 is used to define cognitive impairment, it has 85% to 91% sensitivity and 84% to 97% specificity for dementia in elderly people;27 has been used in studies of cognitive impairment in kidney disease.8,10 Trails B is a test of executive function28 that assesses attention, concentration, psychomotor speed, cognitive shifting, and complex sequencing function by measuring the time required to connect a series of sequentially numbered and lettered circles. Shorter completion times indicate better performance; age, education, and general intelligence affect test scores. Better performance on Trials B is significantly associated with the ability to perform instrumental activities of daily living (IADLs) in community-dwelling elderly people.28

For cross-sectional analyses, prevalent cognitive impairment was defined as having a baseline 3MS score of less than 80 or a Trails B time greater than 1.5 standard deviations above the mean. For prospective analyses, incident cognitive impairment was defined as having a 3MS score of less than 80 or a decline of 5 points or more on the follow-up 3MS (approximately 1 standard deviation change) or having a change in Trails B completion time that was one standard deviation or more above the sample’s mean change in completion time between the baseline and follow-up examinations. Men with prevalent cognitive impairment at baseline as defined according to each of the cognitive tests were excluded from longitudinal analyses examining the association between kidney function and risk of cognitive decline as defined according to that test.

Cistanche can improve kidney function

Other Measurements

A trained technician interviewed participants at the baseline visit, and participants completed a self-administered questionnaire. Self-reported health status and Mental Component Summary (MCS) scale were obtained from the Medical Outcomes Study 12-Item Short-Form Health Survey (SF+-12).29 A self-reported medical history of conditions listed in Table 1 was obtained. Height and weight were used to calculate a standard body mass index (kg/m2). Ankle–arm blood pressure index was determined at the baseline visit and a score of 0.9 or less was used to define peripheral arterial disease (PAD).

Statistical Analysis

Differences in baseline characteristics according to the category of eGFR (o45, 45–59, 60 mL/min per 1.73 m2) were compared using analysis of variance for normally distributed continuous data, Kruskal-Wallis for skewed continuous data, and chi-square tests for categorical data.

The association between renal function and cognitive impairment or decline was analyzed using logistic regression, with a test for linear trend across categories of eGFR performed. Models presented include an unadjusted base model; age-adjusted model; base model adjusted for age, education, and race; and final multivariable model further adjusted for additional variables associated with baseline renal function at P=.10 in univariate analyses. All models were adjusted for the clinic site. Longitudinal analyses were additionally adjusted for baseline 3MS and Trails B score.

Additional analyses were performed expressing the predictor variable as four categories of eGFR (o30, 30–45, 45–59, and >=60 mL/min per 1.73 m2), eGFR as a continuous variable (per 10 mL/min per 1.73 m2), SCr as a continuous variable (per 1 mg/dL), and quartiles of SCr. Because the alternative definitions of the predictor variable did not substantially alter the results, only analyses using the three eGFR categories are presented in this article. All analyses were performed using SAS 9.1 (SAS Institute, Inc., Cary, NC).

Cistanche can improve kidney function

RESULTS

Baseline Characteristics

Of the 5,995 men in the cohort, 5,529 had baseline measurements of SCr and 3MS testing and were included in cross-sectional analysis. Four hundred sixty-six men without baseline SCr (n = 461), 3MS score (n=5), or both were older and less likely to be Caucasian and had fewer years of education and a higher prevalence of diabetes mellitus than men with complete baseline measures. Men with SCr measurements who did not have baseline Trails B scores (n =126) were older, less educated, less likely to be Caucasian, and more likely to report comorbidities, and had lower baseline 3MS scores (83.5 vs 93.6, Po.001) than men with baseline Trails B scores.

Characteristics of the 5,529 men in the cohort according to category of eGFR are presented in Table 1; 753 (13.6%) had baseline eGFR of 45 to 59 mL/min per 1.73 m2, 204 (3.7%) less than 45 mL/min per 1.73 m2, 28 (0.5%) less than 30 mL/min per 1.73 m2, six (0.1%) less than 20 mL/min per 1.73 m2, and only two (0.04%) less than 10 mL/min per 1.73 m2. Men with baseline eGFR less than 60 mL/min per 1.73 m2 were older and less likely to report their health as good or excellent, had a greater functional impairment, consumed fewer alcoholic drinks per week, had a higher prevalence of PAD, and were more likely to report medical conditions than men with higher eGFR.

eGFR and Baseline Cognitive Function

Unadjusted baseline 3MS mean scores were 93.6+-5.8, 92.5+-6.0, and 91.4+-6.5 (P for trend o.001), and unadjusted mean times in seconds to complete the Trails B were 131 +-57, 147+-62, and 157+-65 (P for trend 0.001) in participants with an eGFR of 60 and greater, 45 to 59, and less than 45 mL/min per 1.73 m2, respectively.

A total of 148 (2.7%) men were classified as cognitively impaired at baseline based on having a 3MS score of less than 80. Compared with men with an eGFR of 60 mL/min per 1.73 m2 or greater, the unadjusted odds ratios of cognitive impairment (3MS o80) were 1.89 (95% confidence interval (CI) = 1.26–2.83) in men with an eGFR of 45 to 59 mL/min per 1.73 m2 and 2.11 (95% CI = 1.08–4.11) in men with an eGFR less than 45 mL/min per 1.73 m2 (Table 2). Older age partially explained the association between poorer kidney function and cognitive impairment. Further attenuation was noted after adjustment for clinic site, education, and race.

Four hundred ninety-four (9.1%) men were classified as cognitively impaired based on Trails B. Compared with men with normal renal function, the unadjusted odds ratios of impairment were 1.74 (95% CI= 1.37–2.21) in men with an eGFR of 45 to 59 mL/min per 1.73 m2 and 2.37 (95% CI = 1.61–3.49) in men with an eGFR less than 45 mL/min per 1.73 m2 (Table 2). After adjustment for the potential confounders (Table 2), the odds ratios of cognitive impairment were 1.31 (95% CI = 1.00–1.72) in men with an eGFR of 45 to 59 mL/min per 1.73 m2 and 1.30 (95% CI = 0.83–2.06) in men with an eGFR less than 45 mL/min per 1.73 m2 (P for trend = .05).

eGFR and Cognitive Decline

Of the 5,529 men with 3MS scores and kidney function at baseline, 1,350 did not attend the follow-up visit (78 terminated, 524 died, 654 completed a self-administered questionnaire only, and 94 did not attend the follow-up visit). Participants who attended the follow-up visit tended to be younger, Caucasian, and more educated, have self-reported excellent or very good health, be less likely to report a history of a physician-diagnosed medical condition, and have better scores on baseline cognitive testing than those who did not (mean 3MS score 94.1 +- 5.0 and mean time to complete Trails B 126.7 +- 52.9 for men with follow-up vs 91.1 +- 7.6 and 158.5 +- 66.8, respectively, for men without follow-up; Po.001 for both).

Of the 4,179 men with baseline 3MS scores who attended the follow-up visit, 69 did not complete follow-up 3MS testing. Of the 4,107 men with baseline Trails B scores who attended the follow-up visit, 159 did not complete follow-up Trails B testing. Men without follow-up testing were older, less educated, less likely to report their health status as excellent or good, and more likely to report a history of cardiovascular disease or diabetes mellitus for the 3MS and Trails B tests alike. In addition, 64 men, who were defined as impaired based on their baseline 3MS performance were excluded from the prospective analysis, leaving 4,046 men in the prospective analysis of cognitive decline according to 3MS performance. Similarly, 226 men who were defined as impaired based on their baseline Trails B performance were excluded, leaving 3,722 participants for prospective analysis of cognitive decline according to Trails B performance.

At follow-up, 931 of 4,046 (23%) men met criteria for cognitive decline as defined according to a 3MS score less than 80 or a 5-point decline or more in their score, and 432 of 3,722 (11.6%) men met criteria for cognitive decline based on performance on the Trails B. One hundred sixty-one men (4.4%) met the criteria for cognitive decline on both tests.

Compared with men with an eGFR of 60 mL/min per 1.73 m2 or greater, the unadjusted odds ratios of cognitive decline as defined according to 3MS score were 1.25 (95% CI = 1.00–1.57) in men with an eGFR of 45 to 59 mL/min per 1.73 m2 and 1.65 (95% CI = 1.07–2.53) in men with an eGFR less than 45 mL/min per 1.73 m2 (P for trend 5 .004) (Table 3). Older age in men with poorer renal function largely explained this association. Similarly, after adjustment for age, there was no association between kidney function and odds of cognitive decline as defined according to Trails B performance (Table 3).

DISCUSSION

This study of older community-dwelling men found an independent association between low eGFR and poorer performance on Trails B scores at baseline, but older age largely or entirely explained the associations between low eGFR and baseline cognitive impairment as measured according to the 3MS or cognitive decline as measured according to the 3MS or the Trails B in those with poor renal function.

The finding of the association between mild to moderate kidney disease and poor performance on the Trails B but not 3MS is in agreement with prior findings. One study showed that patients undergoing dialysis scored worse than normal controls on the 3MS and Trails B but that subjects with CKD performed worse on the Trails B but had 3MS scores not different from those of normal controls.8 It has been suggested that mild CKD is associated with poorer executive function and attention, whereas severe CKD and end-stage kidney disease are associated with a global decrease in cognitive function.4,8

The findings of the current study regarding the lack of evidence for an independent association between mild to moderate CKD and risk of cognitive decline as measured according to the 3MS differ from those previously reported.10,11 One study found a graded independent association between estimated GFR according to the MDRD formula at baseline and incident cognitive impairment (similarly defined as 3MS score o80 or 5-point decline in 3MS score) in 3,075 community-dwelling elderly people in the Health, Aging, and Body Composition Study.10 The Health Aging, and Body Composition study participants were more likely than the MrOS cohort to have evidence of cognitive impairment at baseline (10%) and follow-up (36%), less educated, more racially diverse, and more likely to have diabetes mellitus.10 Another cross-sectional study found an association between kidney function and the likelihood of cognitive impairment (assessed according to 3MS, Trails B, and Boston Naming Test) in a cohort of 1,015 postmenopausal women with a history of atherosclerotic heart disease who participated in the Heart Estrogen/Progestin Replacement Study.9 Differences in findings between the MrOS and these two studies may be related to the lower prevalence of CKD and cognitive impairment in the MrOS cohort, use of the accepted cutoffs to define impairment in the highly educated cohort, effect of sex on the association between kidney dysfunction and cognitive impairment,30 or in the case of the Heart Estrogen/Progestin Replacement Study, the presence of residual confounding by atherosclerotic vascular disease.

The current study did not find an independent association between CKD and risk of cognitive decline. The Cardiovascular Health Cognition Study11 revealed that high creatinine ( >=1.3 mg/dL for women and >=1.5 mg/dL for men) was independently associated with a 37% increase in the risk of a new diagnosis of dementia, established according to extensive neuropsychiatric testing in 1,013 participants and detailed record review in 1,072 participants. It is possible that excluding participants with baseline cognitive impairment from the analyses and limiting the test battery to a few cognitive domains limited the ability to observe an association. In addition, using unequal thresholds for impairment limited the Trails B cohort to a less-impaired group of people and could have differentially affected the association between kidney function and cognitive decline as defined according to the two tests.

Although prior studies have reported a robust association between moderate to severe CKD or end-stage kidney disease and cognitive dysfunction,8 it is unknown whether a mild reduction in kidney function is an independent risk factor for global decrease in cognitive function. Few men in the MrOS study (28, 0.5%) had an eGFR less than 30 mL/ min per 1.73 m2. If cognitive dysfunction in kidney disease is the result of uremic toxin accumulation, more-advanced CKD might be required before an adverse global effect on cognition is observed.

The study had a number of strengths, including comprehensive measures of the cohort baseline characteristics, outcome assessment blinded to the status of renal function, and complete follow-up of survivors, but it also had several limitations. The participants were mostly healthy, white, elderly, community-dwelling men; therefore, the findings might not be generalizable to other populations. The study might have been underpowered to detect an association because of the healthy participant population. Serum creatinine may be a biased marker of kidney function in elderly people, because it depends on muscle mass and nutritional status, resulting in an overestimation of kidney function in participants with malnutrition and sarcopenia; using the MDRD formula, which adjusts for age, only partially corrects this limitation. In addition, the MDRD formula underestimates GFR particularly if the GFR is 60 mL/min per 1.73 m2 or greater. These misclassifications might have skewed the findings toward the null. In addition, serial measurements of kidney function that would allow the association between change in kidney function and cognitive decline or baseline dialysis status to be examined were not available. Finally, although widely accepted measures of cognition in older people were used, a more-comprehensive battery of neuropsychiatric testing might have increased the power to detect an association.

In conclusion, this study found an association between mild to moderate CKD and poorer executive performance at baseline but did not find evidence of an independent association between mild to moderate CKD and the likelihood of global cognitive impairment or risk of cognitive decline in older men. Further prospective studies should include participants of both sexes, a spectrum of CKD severity, serial kidney function testing, and a more comprehensive battery of neuropsychiatric testing.

Cistanche can improve kidney function

ACKNOWLEDGMENTS

Conflict of Interest: The editor-in-chief has reviewed the conflict of interest checklist provided by the author and has determined that the author has no financial or any other kind of personal conflicts with this manuscript.

Dr. Orwoll has received funding from a National Institutes of Health (NIH) grant. Drs. Cummings and Ensrud have received funding from NIH grants. Supported in part by Public Health Service research grants from the National Institutes of Health (AR45580, AR45614, AR45632, AR45647, AR45654, AR45583, AG18197, AG027810, and RR024140). The MrOS is supported by NIH funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute on Aging, the National Center for Research Resources, and NIH Roadmap for Medical Research under the following grants: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140.

Author Contributions: Yelena Slinin: interpretation of data, preparation of the manuscript. Misti L. Paudel: analysis and interpretation of data. Areef Ishani: interpretation of data, critical review of the manuscript. Brent C. Taylor: analysis and interpretation of data, critical review of the manuscript. Kristine Yaffe, Anne M. Murray, Howard A. Fink, and Simerjot Jassal: a critical review of the manuscript. Eric S. Orwoll and Kristine E. Ensrud: study concept and design, acquisition of subjects and data, interpretation of data, critical review of the manuscript. Steven R. Cummings: study concept and design, interpretation of data, critical review of the manuscript. Elizabeth Barrett-Connor: acquisition of subjects and data, critical review of the manuscript.

Sponsor's Role: The sponsors had no direct role in the conduct of the study; the collection, management, analyses, and interpretation of the data; or preparation or approval of the manuscript.

From: ' Kidney Function and Cognitive Performance and Decline in Older Men' by Yelena Slinin, et al

---NOVEMBER 2008–VOL. 56, NO. 11 JAGS

REFERENCE

1. Lindeman RD, Tobin J, Shock NW. Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 1985;33:278–285.

2. Coresh J, Selvin E, Stevens LA et al. Prevalence of chronic kidney disease in the United States. JAMA 2007;298:2038–2047.
3. Kurella M, Mapes DL, Port FK et al. Correlates and outcomes of dementia among dialysis patients: The Dialysis Outcomes and Practice Patterns Study. Nephrol Dial Transplant 2006;21:2543–2548.
4. Murray AM, Tupper DE, Knopman DS et al. Cognitive impairment in hemodialysis patients is common. Neurology 2006;67:216–223.
5. Pereira AA, Weiner DE, Scott T et al. Cognitive function in dialysis patients. Am J Kidney Dis 2005;45:448–462.
6. Sehgal AR, Grey SF, DeOreo PB et al. Prevalence, recognition, and implications of mental impairment among hemodialysis patients. Am J Kidney Dis 1997;30:41–49.
7. Hailpern SM, Melamed ML, Cohen HW et al. Moderate chronic kidney disease and cognitive function in adults 20 to 59 years of age: Third National Health and Nutrition Examination Survey (NHANES III). J Am Soc Nephrol 2007;18:2205–2213.
8. Kurella M, Chertow GM, Luan J et al. Cognitive impairment in chronic kidney disease. J Am Geriatr Soc 2004;52:1863–1869.
9. Kurella M, Yaffe K, Shlipak MG et al. Chronic kidney disease and cognitive impairment in menopausal women. Am J Kidney Dis 2005;45:66–76.
10. Kurella M, Chertow GM, Fried LF et al. Chronic kidney disease and cognitive impairment in the elderly: The Health, Aging, And Body Composition Study. J Am Soc Nephrol 2005;16:2127–2133.
11. Seliger SL, Siscovick DS, Stehman-Breen CO et al. Moderate renal impairment and risk of dementia among older adults: The Cardiovascular Health Cognition Study. J Am Soc Nephrol 2004;15:1904–1911.
12. Francis ME, Eggers PW, Hostetter TH et al. Association between serum homocysteine and markers of impaired kidney function in adults in the United States. Kidney Int 2004;66:303–312.
13. Muntner P, Hamm LL, Kusek JW et al. The prevalence of nontraditional risk factors for coronary heart disease in patients with chronic kidney disease. Ann Intern Med 2004;140:9–17.
14. Shlipak MG, Fried LF, Crump C et al. Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency. Circulation 2003;107:87–92.
15. Keller JN, Schmitt FA, Scheff SW et al. Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology 2005;64:1152–1156.
16. Seshadri S, Beiser A, Selhub J et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 2002;346:476–483.
17. Teunissen CE, van Boxtel MP, Bosma H et al. Inflammation markers in relation to cognition in a healthy aging population. J Neuroimmunol 2003;134: 142–150.
18. Koren-Morag N, Goldbourt U, Tanne D. Renal dysfunction and risk of ischemic stroke or TIA in patients with cardiovascular disease. Neurology 2006;67:224–228.
19. Seliger SL, Gillen DL, Longstreth WT Jr. et al. Elevated risk of stroke among patients with end-stage renal disease. Kidney Int 2003;64:603–609.
20. Desmond DW, Moroney JT, Sano M et al. Incidence of dementia after ischemic stroke: Results of a longitudinal study. Stroke 2002;33:2254–2260.
21. Griva K, Thompson D, Jayasena D et al. Cognitive functioning pre- to post kidney transplantation prospective study. Nephrol Dial Transplant 2006; 21:3275–3282.
22. Jassal SV, Devins GM, Chan CT et al. Improvements in cognition in patients converting from thrice weekly hemodialysis to nocturnal hemodialysis: A longitudinal pilot study. Kidney Int 2006;70:956–962.
23. Blank JB, Cawthon PM, Carrion-Petersen ML et al. Overview of recruitment for the osteoporotic fractures in men study (MrOS). Contemp Clin Trials 2005;26:557–568.
24. Orwoll E, Blank JB, Barrett-Connor E et al. Design and baseline characteristics of the Osteoporotic Fractures in Men (MrOS) StudyFa large observational study of the determinants of fracture in older men. Contemp Clin Trials 2005;26:569–585.
25. Levey AS, Coresh J, Greene T et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 2006;145:247–254.
26. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1–S266.
27. Teng EL, Chui HC. The modified mini-mental state (3MS) examination. J Clin Psychiatry 1987;48:314–318.
28. Cahn-Weiner DA, Boyle PA, Malloy PF. Tests of executive function predict instrumental activities of daily living in community-dwelling older individuals. Appl Neuropsychol 2002;9:187–191.
29. Ware JE, Kosinski M, Keller SD. SF-12: How to Score the SF-12 Physical and Mental Health Summary Scores, 3rd Ed. Lincoln, RI: QualityMetric, Inc., 1998.
30. Azad NA, Al BM, Loy-English I. Gender differences in dementia risk factors. Gend Med 2007;4:120–129.