Role of light walking pace on cognition: Findings from the Maine-Syracuse Longitudinal Study.

Moderate- to vigorous intensities of physical activity are recommended for health promotion, including brain health. Regular physical activity is considered a modifiable factor to delay -perhaps prevent- onset of dementias such as Alzheimer's disease. Little is known about the benefits of light physical activity. We analyzed data from a 998 community-dwelling, cognitively unimpaired participants from the Maine-Syracuse Longitudinal Study (MSLS) and investigated the role of light physical activity, defined by walking pace, across two time points. Results revealed light levels of walking pace were associated with higher performance at the first timepoint and less decline by time 2 in the domains of verbal abstract reasoning and visual scanning and tracking, which includes both processing speed and executive function skills. When examining change over time (N = 583), increasing walking pace was associated with less decline at time two for the domains of visual scanning and tracking, working memory, visual spatial ability, and working memory, but not verbal abstract reasoning. These findings highlight the relevance of light physical activity and the need to investigate its contribution to cognitive function. From a public health perspective, this may encourage more adults to adopt a light level of exercise and still reap health benefits.

Optimizing Graft Extraction From the Femoral Condyle for Fresh Osteochondral Allograft Transplantation in Treating Osteochondritis Dissecans of the Capitellum: Best Fit Based on Radius of Curvature.

BACKGROUND: Osteochondritis dissecans (OCD) of the capitellum is a common cause of pain and dysfunction in adolescents that engage in repetitive elbow loading. For large, unstable lesions fresh osteochondral allograft transplantation (FOCAT) from the femoral condyle has been described as an effective treatment. Current practice involves significant guesswork in obtaining an appropriately sized graft, with anatomic variations resulting in poor graft fit. No studies currently exist that analyze and identify the best distal femur FOCAT graft site to repair OCD lesions of the capitellum based on the radius of curvature (ROC) and simulated matching. METHODS: Computed tomography scans of the elbow were used to estimate the subchondral bone ROC of capitella in adolescents aged 11 to 21 years. The capitellar location used corresponds to the most commonly reported site of OCD lesions in the elbow. Computed tomography scans of the lower extremity were used to estimate the subchondral bone ROC of 4 potential donor femoral condyle grafts. ROC from distinct regions at the posterior section of both the medial and lateral femoral condyles were measured: 2 areas representing 10 mm grafts from the center (MC1 and LC1), and 2 areas estimating 10 mm grafts posterior and adjacent to the physeal scar (MC2 and LC2). Intraobserver and interobserver reliability measurements were preformed to corroborate precision and validate the method. RESULTS: The mean ROC of healthy subchondral bone at the region of the capitellum were OCD lesions most commonly occur was 9.79±1.39 mm. The mean ROC of MC1 was 18.61±2.26 mm. The average ROC of the MC2 was 15.23±1.43 mm. The average ROC of LC1 was 16.47±1.34 mm. The average ROC of LC2 was 18.19±3.09 mm. After 15,000 simulated condyle-to-capitellar site matchings based on these measurements, a good fit graft was achieved at a frequency of 15%. DISCUSSION: No site measured from the femoral condyle demonstrated a subchondral ROC that exactly matched the subchondral ROC of the capitellum at the center location where OCD lesions most commonly occur; of the locations measured, a 10 mm section from MC2 demonstrated the closest match. On the basis of this analysis, extracting a graft from MC2 has the potential to further optimize FOCAT fit to the capitellum. LEVEL OF EVIDENCE: Level III.

Depressive symptoms prospectively predict cardiovascular disease among older adults: Findings from the Maine-Syracuse Longitudinal Study.

A recent meta-analysis identified a prospective association between depression and cardiovascular disease; however, there was no association for studies with long-term follow-up periods. The literature has primarily focused on baseline depression status or symptoms, which may not capture the chronic nature of depression. This study examined the prospective relationship between depressive symptoms and cardiovascular disease up to 15 years later in 274 cardiovascular disease-free older adults. Depressive and anxiety symptoms, mean arterial pressure, and cardiovascular disease status were assessed. Baseline and chronic depressive symptoms predicted increased risk of cardiovascular disease, underscoring the importance of assessing and treating depression in older adults.

Acute Changes in NADPH Oxidase 4 in Early Post-Traumatic Osteoarthritis.

Knee injuries cause structural damage and acute inflammation that initiates the development of post-traumatic osteoarthritis (PTOA). NADPH oxidase 4 (Nox4), a member of a family of enzymes that generates reactive oxygen species (ROS), plays a pivotal role in normal development of the musculoskeletal system, but may increase ROS production to harmful levels after joint injury. The role of ROS in both normal joint homeostasis and injury is poorly understood, but inhibition of excessive ROS production by Nox4 after joint injury could be protective to the joint, decreasing oxidative stress, and initiation of PTOA. Knee injuries were simulated using inflammatory cytokines in cultured primary human chondrocytes and a non-invasive mouse model of PTOA in C57BL/6N and Nox4 knockout mice. There is an acute decrease in Nox4 activity within 24 h after injury in both systems, followed by a subsequent sustained low-level increase, a novel finding not seen in any other system. Inhibition of Nox4 activity by GKT137831 was protective against early structural changes after non-invasive knee injury in a mouse model. Nox4 knockout mice had significant differences in structural and mechanical properties of bone, providing further evidence for the role of Nox4 in development of joint tissues and biochemical response after joint injury. Nox4 plays a significant role in the acute phase after joint injury, and targeted inhibition of inflammation caused by Nox4 may be protective against early joint changes in the pathogenesis of PTOA. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2429-2436, 2019.

Headless Compression Screw Fixation of Vertical Medial Malleolus Fractures is Superior to Unicortical Screw Fixation.

This study is the first biomechanical research of headless compression screws for fixation of vertical shear fractures of the medial malleolus, a promising alternative that potentially offers several advantages for fixation. Vertical shear fractures were simulated by osteotomies in 20 synthetic distal tibiae. Models were randomly assigned to fixation with either 2 parallel cancellous screws or 2 parallel Acutrak 2 headless compression screws (Acumed). Specimens were subjected to offset axial loading to simulate supination-adduction loading and tracked using high-resolution video. The headless compression screw construct was significantly stiffer (P < .0001) (360 ± 131 N/mm) than the partially threaded cancellous screws (180 ± 48 N/mm) and demonstrated a significantly increased (P < .0001) mean load to clinical failure (719 ± 91 N vs 343 ± 83 N). When specimens were displaced to 6 mm and allowed to relax, the headless compression screw constructs demonstrated an elastic recoil and were reduced to the pretesting fragment alignment, whereas the parallel cancellous screw constructs remained displaced. Along with the headless design that may decrease soft tissue irritation, the increased stiffness and elastic recoil of the headless compression screw construct offers improved fixation of medial malleolus vertical shear fractures over the traditional methods.

Poorer Visual Acuity Is Associated with Declines in Cognitive Performance Across Multiple Cognitive Domains: The Maine-Syracuse Longitudinal Study.

OBJECTIVES: Prior studies have found associations between visual acuity (VA) and cognitive function. However, these studies used a limited range of cognitive measures and did not control for cardiovascular disease risk factors (CVD-RFs) and baseline function. The primary objective of this study was to analyze the associations of VA and cognitive performance using a thorough neuropsychological test battery. METHODS: This study used community-dwelling sample data across the sixth (2001-2006) and seventh (2006-2010) waves of the Maine-Syracuse Longitudinal Study (n=655). Wave 6 VA as measured by the Snellen Eye Test was the primary predictor of wave 6 and wave 7 Global cognitive performance, Visual-Spatial Organization and Memory, Verbal Episodic Memory, Working Memory, Scanning and Tracking, and Executive Function. Additionally, VA was used to predict longitudinal changes in wave 7 cognitive performance (wave 6 performance adjusted). We analyzed these relationships with multiple linear and logistic regression models adjusted for age, sex, education, ethnicity, depressive symptoms, physical function deficits in addition to CVD-RFs, chronic kidney disease, homocysteine, continuous systolic blood pressure, and hypertension status. RESULTS: Adjusted for demographic covariates and CVD-RFs, poorer VA was associated with concurrent and approximate 5-year declines in Global cognitive function, Visual-Spatial Organization and Memory, and Verbal Episodic Memory. DISCUSSION: VA may be used in combination with other screening measures to determine risk for cognitive decline. (JINS, 2018, 24, 746-754).

Associations between Type 2 Diabetes Mellitus and Arterial Stiffness: A Prospective Analysis Based on the Maine-Syracuse Study.

BACKGROUND: The aim of this study was to investigate prospective associations between type 2 diabetes mellitus status and the gold standard non-invasive method for ascertaining arterial stiffness, carotid femoral pulse wave velocity. METHODS: The prospective analysis employed 508 community-dwelling participants (mean age 61 years, 60% women) from the Maine-Syracuse Longitudinal Study. Pulse wave velocity at wave 7 (2006-2010) was compared between those with type 2 diabetes mellitus at wave 6 (2001-2006) (n = 52) and non-diabetics at wave 6 (n = 456), with adjustment for demographic factors, cardiovascular risk factors and lifestyle- and pulse wave velocity-related factors. RESULTS: Type 2 diabetes mellitus status was associated with a significantly higher pulse wave velocity (12.5 ± 0.36 vs. 10.4 ± 0.12 m/s). Multivariate adjustment for other cardiovascular risk factors and lifestyle- and pulse wave velocity-related variables did not attenuate the findings. The risk of an elevated pulse wave velocity (≥12 m/s) was over 9 times higher for those with uncontrolled type 2 diabetes mellitus than for those without diabetes (OR 9.14, 95% CI 3.23-25.9, p < 0.001). CONCLUSIONS: Type 2 diabetes mellitus, particularly if uncontrolled, is significantly associated with risk of arterial stiffness later in life. Effective management of diabetes mellitus is an important element of protection from arterial stiffness.

Mini-Fragment Fixation Is Equivalent to Bicortical Screw Fixation for Horizontal Medial Malleolus Fractures.

Horizontal fractures of the medial malleolus occur through application of valgus or abduction force through the ankle that creates a tension failure of the medial malleolus. The authors hypothesize that mini-fragment T-plates may offer improved fixation, but the optimal fixation construct for these fractures remains unclear. Forty synthetic distal tibiae with identical osteotomies were randomized into 4 fixation constructs: (1) two parallel unicortical cancellous screws; (2) two parallel bicortical cortical screws; (3) a contoured mini-fragment T-plate with 2 unicortical screws in the fragment and 2 bicortical screws in the shaft; and (4) a contoured mini-fragment T-plate with 2 bicortical screws in the fragment and 2 unicortical screws in the shaft. Specimens were subjected to offset axial tension loading on a servohydraulic testing system and tracked using high-resolution video. Failure was defined as 2 mm of articular displacement. Analysis of variance followed by a Tukey-Kramer post hoc test was used to assess for differences between groups, with significance defined as P<.05. The mean stiffness (±SD) values of both mini-fragment T-plate constructs (239±83 N/mm and 190±37 N/mm) and the bicortical screw construct (240±17 N/mm) were not statistically different. The mean stiffness values of both mini-fragment T-plate constructs and the bicortical screw construct were higher than that of a parallel unicortical screw construct (102±20 N/mm). Contoured T-plate constructs provide stiffer initial fixation than a unicortical cancellous screw construct. The T-plate is biomechanically equivalent to a bicortical screw construct, but may be superior in capturing small fragments of bone. [Orthopedics. 2018; 41(3):e395-e399.].

Challenging the "jolly fat" hypothesis among older adults: High body mass index predicts increases in depressive symptoms over a 5-year period.

Several investigators have observed lowered risk of depression among obese older adults, coining the "jolly fat" hypothesis. We examined this hypothesis using baseline and a 5-year follow-up body mass index, depressive symptoms, and covariates from 638 community-based older adults. High objectively measured body mass index and functional limitations predicted increased future depressive symptoms. However, symptoms did not predict future body mass index. Self-reported body mass index showed similar associations despite underestimating obesity prevalence. Results did not differ on the basis of gender. Results for this study, the first longitudinal reciprocal risk analysis between objectively measured body mass index and depressive symptoms among older adults, do not support the "jolly fat" hypothesis.

Age modifies the relation between intraindividual measurement-to-measurement variation in blood pressure and cognitive function: the Maine-Syracuse Study.

BACKGROUND: There is evidence to suggest that intraindividual variability in blood pressure (BP IIV) may be superior to mean BP for predicting cognitive function, taken from both within a single visit and between-visits. BP IIV increases with age in studies of persons middle-aged and older. The aim was therefore to investigate age by BP IIV (SBP and DBP) interactions with regard to cognitive functioning while considering medication class and polypharmacy, which may also affect BP IIV with advancing age. METHOD AND RESULTS: Cross-sectional analyses were performed on 980 community-dwelling individuals from the Maine-Syracuse Longitudinal Study. Automated BP measures were taken 15 times (five times each in sitting, reclining, and standing positions). Cognitive function was assessed using a thorough neuropsychological test battery following the BP assessment. A significant age by BP IIV interaction was observed. For individuals aged over age 60 years, IIV in SBP and DBP was inversely associated with Global Composite, Scanning and Tracking, and the Similarities test. IIV in SBP was additionally associated with Verbal Memory and the Mini-Mental State Examination. DBP IIV was additionally related to the Visual-Spatial Memory and Organization composite. There were no significant associations between BP IIV and cognitive function in those aged less than 60 years. CONCLUSION: BP IIV is an important predictor of cognition with advancing age.

Stem Cells in Spinal Fusion.

STUDY DESIGN: Review of literature. OBJECTIVES: This review of literature investigates the application of mesenchymal stem cells (MSCs) in spinal fusion, highlights potential uses in the development of bone grafts, and discusses limitations based on both preclinical and clinical models. METHODS: A review of literature was conducted looking at current studies using stem cells for augmentation of spinal fusion in both animal and human models. RESULTS: Eleven preclinical studies were found that used various animal models. Average fusion rates across studies were 59.8% for autograft and 73.7% for stem cell-based grafts. Outcomes included manual palpation and stressing of the fusion, radiography, micro-computed tomography (µCT), and histological analysis. Fifteen clinical studies, 7 prospective and 8 retrospective, were found. Fusion rates ranged from 60% to 100%, averaging 87.1% in experimental groups and 87.2% in autograft control groups. CONCLUSIONS: It appears that there is minimal clinical difference between commercially available stem cells and bone marrow aspirates indicating that MSCs may be a good choice in a patient with poor marrow quality. Overcoming morbidity and limitations of autograft for spinal fusion, remains a significant problem for spinal surgeons and further studies are needed to determine the efficacy of stem cells in augmenting spinal fusion.

Risk for cognitive impairment across 22 measures of cognitive ability in early-stage chronic kidney disease.

Background: Chronic kidney disease (CKD) is a significant risk factor for cognitive impairment. Previous studies have examined differences in cognitive impairment between persons with and without CKD using multiple cognitive outcomes, but few have done this for an extensive battery of cognitive tests. We relate early-stage CKD to two indices of impairment for 22 measures of cognitive ability. Methods: The study was community-based and cross-sectional with 898 individuals free from dementia and end-stage renal disease. Estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration equation and classified as <60 or ≥60 mL/min/1.73 m2, based on consensus definitions of Stage 3 or greater CKD. The eGFR classifications were related to modest [≥1 standard deviation (SD) below the mean] and severe (≥1.5 SD below the mean) impairment on each measure using logistic regression analyses adjusting for potential risk factors. Results: A total of 146 individuals (16.3%) had eGFR <60 mL/min/1.73 m2 (mean 51.6 ± 10.1 mL/min/1.73 m2). These participants had significantly greater risk for modestly impaired abilities in the scanning and tracking and visual-spatial organization/memory (VSOM) domains after accounting for comorbidity-related risk factors [odds ratios (ORs) between 1.68 and 2.16], as well as greater risk for severely impaired functioning in the language domain (OR = 2.65). Conclusions: Participants with eGFR <60 mL/min/1.73 m2 were at higher risk for cognitive impairment than those with eGFR ≥60 mL/min/1.73 m2 on the majority of cognitive abilities, specifically those within the VSOM, Language, and scanning and tracking domains. Targeted screening for cognitive deficits in kidney disease patients early in their disease course may be warranted.

Sled fixation for horizontal medial malleolus fractures.

BACKGROUND: Horizontal fractures of the medial malleolus occur through exertion of various rotational forces on the ankle, including supination--external rotation, pronation--external rotation, and pronation-abduction. Many methods of fixation are employed for these fractures, but the optimal fixation construct remains unclear. METHODS: Horizontal medial malleolus osteotomies were performed in synthetic distal tibiae and randomized into two fixation groups: 1) two parallel unicortical cancellous screws or 2) medial malleolar sled fixation. Specimens were subjected to offset axial tension loading and tracked using high-resolution video. Clinical failure was defined as 2mm of articular displacement. FINDINGS: There were statistically significant increases in mean stiffness (127% higher, P=0.0007) and mean force to clinical failure (52% higher, P=0.0002) with the medial malleolar sled. The mean stiffness in offset tension loading was 232 (SD 83) N/mm for medial malleolar sled and 102 (SD 20) N/mm for parallel unicortical cancellous screws. The mean force to clinical failure was 595 (SD 112) N for medial malleolar sled and 392 (SD 34) N for unicortical screws. In addition, the medial malleolar sled demonstrated elastic recoil to pre-testing alignment while the unicortical screws did not. INTERPRETATION: Medial malleolar sled fixation was significantly stiffer and required more force to clinical failure than parallel unicortical cancellous screws. A medial malleolar sled requires more dissection to apply surgically, but provides significantly more initial fixation strength. Additionally, a medial malleolar sled acts like a tension band in its ability to capture comminuted fragments while being low profile enough to minimize soft tissue irritation.

Association between depressive symptoms, use of antidepressant medication and the metabolic syndrome: the Maine-Syracuse Study.

BACKGROUND: Both depression and the metabolic syndrome (MetS) are two major public health issues. The aim of this study was to examine associations between depressive symptoms, the use of antidepressant medications, and the prevalence of MetS. METHODS: Cross-sectional analyses were undertaken on 970 participants from the Maine-Syracuse Study. Depressive symptoms were measured using two self-reported depression scales, the Center for Epidemiological Studies Depression Scale (CES-D), and the Zung self-rating depression scale. Antidepressant medication use was also self-reported. MetS was defined according to the recent harmonized criteria. RESULTS: The risk of MetS were approximately 79 and 86 % higher for those in the highest quartile for the CESD and the Zung (CES-D: OR = 1.79, p = 0.003; Zung: OR = 1.71, p = 0.006), compared to those in the lowest quartile. With adjustment for socio-demographic variables, lifestyle factors and C-reactive protein (CRP), risk was attenuated, but remained statistically significant for the CES-D. In those who reported using antidepressant medication, the odds of having MetS were over 2-fold higher (OR = 2.22, p < 0.001, fully adjusted model), compared to those who did not use antidepressants. Both measures of depressed mood were also associated with low high density-lipoprotein (HDL) cholesterol levels. Antidepressant use was associated with elevated fasting plasma glucose concentrations, hypertension, and low HDL-cholesterol. CONCLUSION: Depressive symptoms and the use of antidepressant medications are associated with the prevalence of MetS, and with some of the individual components of the syndrome.

Antiglide plating of vertical medial malleolus fractures provides stiffer initial fixation than bicortical or unicortical screw fixation.

BACKGROUND: Vertical shear fractures of the medial malleolus (44-A2 ankle fractures) occur through a supination-adduction mechanism. There are numerous methods of internal fixation for this fracture pattern. METHODS: Vertical medial malleolus osteotomies were created in synthetic distal tibiae. The models were divided into four fixation groups: two parallel unicortical cancellous screws, two divergent unicortical cancellous screws, two parallel bicortical cortical screws, or an antiglide plate construct. Specimens were subjected to offset axial loading and tracked using high-resolution video. FINDINGS: The antiglide plate construct was stiffer (P<0.05) than each of the other three constructs, and the bicortical screw construct was stiffer (P<0.05) than both unicortical screw constructs. The mean stiffness (standard deviation) was 111 (SD 35) N/mm for the parallel unicortical screw construct, 173 (SD 57) N/mm for the divergent unicortical screw construct, 279 (SD 30) N/mm for the bicortical screw construct, and 463 (SD 91) N/mm for the antiglide plate construct. The antiglide plate construct resisted displacement better (P<0.05) than each of the other three constructs. The mean force for 2mm of articular displacement was 284 (SD 51) N for the parallel unicortical screw construct, 339 (SD 46) N for the divergent unicortical screw construct, 429 (SD 112) N for the bicortical construct, and 922 (SD 297) N for the antiglide plate construct. INTERPRETATION: An antiglide plate construct provides the stiffest initial fixation while withstanding higher load to failure for vertical medial malleolus fractures when compared to unicortical and bicortical screw fixation.

Higher HDL cholesterol is associated with better cognitive function: the Maine-Syracuse study.

Few studies have examined associations between different subcategories of cholesterol and cognitive function. We examined relationships between total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglyceride levels and cognitive performance in the Maine-Syracuse Longitudinal Study, a community-based study of cardiovascular risk factors. Cross-sectional analyses were undertaken on data from 540 participants, aged 60 to 98 years, free of dementia and stroke. TC, HDL, LDL, and triglyceride levels were obtained. Cognitive function was assessed using a thorough neuropsychological test battery, including domains of cognitive function indexed by multiple cognitive tests. The cognitive outcomes studied were as follows: Visual-Spatial Memory and Organization, Verbal and Working Memory, Scanning and Tracking, Abstract Reasoning, a Global Composite score, and the Mini-Mental State Examination (MMSE). Significant positive associations were observed between HDL-cholesterol and the Global Composite score, Working Memory, and the MMSE after adjustment for demographic and cardiovascular risk factors. Participants with desirable levels of HDL (≥60 mg/dL) had the highest scores on all cognitive outcomes. There were no significant associations observed between TC, LDL, or triglyceride concentrations and cognition. In older individuals, HDL-cholesterol was related to a composite of Working Memory tests and for general measures of cognitive ability when adjusted for cardiovascular variables. We speculate that persons over 60 are survivors and thus less likely to show cognitive deficit in relation to TC, LDL-cholesterol, and triglycerides. Longitudinal studies are needed to examine relations between specific cognitive abilities and the different subcategories of cholesterol.

Measurement-to-measurement blood pressure variability is related to cognitive performance: the Maine Syracuse study.

The objective was to investigate the association between variability in blood pressure (BP) and cognitive function for sitting, standing, and reclining BP values and variability derived from all 15 measures. In previous studies, only sitting BP values have been examined, and only a few cognitive measures have been used. A secondary objective was to examine associations between BP variability and cognitive performance in hypertensive individuals stratified by treatment success. Cross-sectional analyses were performed on 972 participants of the Maine Syracuse Study for whom 15 serial BP clinic measures (5 sitting, 5 recumbent, and 5 standing) were obtained before testing of cognitive performance. Using all 15 measures, higher variability in systolic and diastolic BP was associated with poorer performance on multiple measures of cognitive performance, independent of demographic factors, cardiovascular risk factors, and pulse pressure. When sitting, reclining, and standing systolic BP values were compared, only variability in standing BP was related to measures of cognitive performance. However, for diastolic BP, variability in all 3 positions was related to cognitive performance. Mean BP values were weaker predictors of cognition. Furthermore, higher overall variability in both systolic and diastolic BP was associated with poorer cognitive performance in unsuccessfully treated hypertensive individuals (with BP ≥140/90 mm Hg), but these associations were not evident in those with controlled hypertension.

Deterioration in renal function is associated with increased arterial stiffness.

BACKGROUND: Higher levels of baseline pulse wave velocity (PWV) have been associated with longitudinal decline in renal function in patients with kidney disease. We examined longitudinal decline in renal function in relation to levels of PWV. We hypothesized that longitudinal decline in renal function in a community-based, nonclinic sample would be associated with higher levels of PWV. METHODS: We conducted a 4-5 year longitudinal study with 482 community-living individuals free from acute stroke, dementia, and end-stage renal disease (mean age = 60.9 years; 59% women; 93.2% white; 10% with diabetes mellitus; mean estimated glomerular filtration rate (eGFR) = 79.2 ml/min/1.73 m2). Multiple linear regression analyses were used to examine the association between changes in renal function (eGFR and serum creatinine) from baseline to follow-up and PWV levels at follow-up, the outcome measure. Regression coefficients were adjusted for age, sex, education, race/ethnicity, weight, activity level, mean arterial pressure, treatment of hypertension, and cardiovascular risk factors. RESULTS: With adjustment for covariables, decline in renal function was associated with higher levels of PWV over a mean follow-up of 4.68 years. CONCLUSIONS: Decline in renal functioning from baseline levels measured 4-5 years before measurement of PWV is related to higher levels of PWV in a community sample.

Decline in renal functioning is associated with longitudinal decline in global cognitive functioning, abstract reasoning and verbal memory.

BACKGROUND: Decreased estimated glomerular filtration rate (eGFR) and higher serum creatinine (sCR) levels have been associated with longitudinal decline in global mental status measures. Longitudinal data describing change in multiple domains of cognitive functioning are needed in order to determine which specific abilities are most affected in individuals with impaired renal function. METHODS: We conducted a 5-year longitudinal study with 590 community-living individuals (mean age 62.1 years, 60.2% female, 93.2% white, 11.4% with diabetes mellitus, mean eGFR 78.4 mL/min/1.73 m²) free from dementia, acute stroke and end-stage renal disease. To measure longitudinal change-over-time, cognitive performance measures were regressed on eGFR adjusting for baseline eGFR and cognitive performance, comorbidity and vascular risk factors. Outcome measures were scores from 17 separate tests of cognitive abilities that were used to index 5 theoretically relevant domains: verbal episodic memory, visual-spatial organization and memory, scanning and tracking, working memory and similarities (abstract reasoning). RESULTS: Declines in eGFR values were associated with cognitive declines, when adjusted for eGFR and cognitive function scores at baseline. Change in renal functioning over time was related to change observed in global cognitive ability [b=0.21SD decline per unit ln(eGFR), 95% CI: 0.04-0.38, P=.018], verbal episodic memory [b=0.28 SD decline per unit ln(eGFR), 95% CI: 0.02-0.54, P=0.038] and abstract reasoning [b=0.36 SD decline per unit ln(eGFR), 95% CI: 0.04-0.67, P=0.025]. Decline in cognitive functioning in association with declining renal functioning was observed despite statistical adjustment for demographic variables and CVD risk factors and the exclusion of persons with dementia or a history of acute stroke. CONCLUSIONS: Early detection of mild to moderate kidney disease is an important public health concern with regard to cognitive decline.