MRI PREDICTORS OF COGNITIVE DECLINE IN CKD: THE BRINK STUDY

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Poster Presentations: Sunday, July 24, 2016

association of change in volume and change in cognitive performance was investigated in stable and declined participants. Methods: Participants (n¼123, 70.366.0 years, 61% men, out of the Heinz Nixdorf Recall study) performed neuropsychological and MR-tomographic tests twice within 2.560.2 years. Participants were classified as “cognitively healthy”, “mildly cognitively impaired” (MCI) or “demented” at both time points. Participants who did not change over time were classified as “stable”, those who changed from “cognitively healthy” to “MCI” or from “MCI” to “demented” were classified as “declined”. Annualized percentage volume changes of HC, TL, and the whole brain were determined by atlas-based MRI volumetry, an investigator-independent method using SPM algorithms. All volumetric data were adjusted for intracranial volume. Group comparisons were performed using covariance analysis adjusted for age, gender and education. The association of percentage volume changes and change in cognitive performance were examined using linear regression models adjusted for age, gender and education in both groups. Results: Cognitively declined participants showed more volume loss in the HC (stable: 0.12% 6 1.82 SD; declined: -2.31% 6 1.87 SD), TL (stable: -0.75% 6 0.90 SD; declined: -1.75% 6 0.93 SD) and in the whole brain (stable: -0.78% 6 0.74 SD; declined: -1.40% 6 0.76 SD). Furthermore, change in cognitive performance was strongly associated with change in hippocampal volume in the declined group (R2¼ 42.6%, b¼ 0.659, B¼2.487; 95% confidence interval (0.77;4.20), p¼0.008) but not in the stable group (R2¼ 1.8%, b¼ -0.093, B¼-0.142; 95% confidence interval (-0.44;-0.16), p¼0.35). Conclusions: This study shows that volume changes of HC, TL and the whole brain are potential biomarkers for cognitive deficits. Our results support previous studies regarding the predictive value of HC volume for cognitive performance in a population-based setting.

P1-390

LOWER GAIT SPEED IS INDEPENDENTLY ASSOCIATED WITH INCREASED MORTALITY RISK AMONG PEOPLE WITH DEMENTIA IN LOWAND MIDDLE-INCOME COUNTRIES: RESULTS FROM THE 10/66 DEMENTIA RESEARCH GROUP POPULATION-BASED COHORT STUDY

Ronaldo D. Piovezan1, Daysi Acosta2, Mariella Guerra3, Y. Huang4, Juan J. Llibre Rodriguez5, Aquiles Salas6, Ana Luisa Sosa-Ortiz7, Ivonne Z. Jimenez-Velazquez8, Martin J. Prince9, Cleusa Ferri10, 10/66 Dementia Research Group, 1Universidade Federal de Sao Paulo, Sao Paulo, Brazil; 2Universidad Nacional Pedro Henriquez Ure~na (UNPHU), Santo Domingo, Dominican Republic; 3Universidad Peruana Cayetano Heredia, Lima, Peru; 4Peking University, Beijing, China; 5Alzheimer Research Center, Medical University of Havana, Havana, Cuba; 6Caracas University Hospital, Caracas, Venezuela (Republic of Bolivarian); 7Dementia Laboratory National Institute of Neurology And Neurosurgery, Mexico City, Mexico; 8University of Puerto Rico School of Medicine, San Juan, PR, USA; 9 King’s College London, London, United Kingdom; 10Universidade Federal de Sao Paulo, Sao Paulo, Brazil. Contact e-mail: [email protected] Background: In the general older population, gait speed has been re-

ported to predict mortality. A population-based study including people with dementia (PWD) found that gait speed predicted mortality in very old people. Little is known about this association restrict to older PWD. We investigated if lower gait speed independently increases mortality risk among older PWD in 8 Low and Middle-Income Countries (LMIC). Methods: The sample comprise 958 PWD aged > 65 who complete a gait speed test (seconds taken

to walk 10 meters, which was categorized in quartiles). Vital status was ascertained 3-4 years later. Cox proportional hazards regression models were adjusted for socio-demographic characteristics, physical impairments, cardiovascular risk factors, nutritional status, depression, dementia severity and dementia subtypes, to estimate the association between gait speed and mortality. The final model was also stratified by dementia severity (CDR). Results: Gait speed (per quartile) was associated to an increased mortality risk (HR¼1.13, 95%CI 1.01-1.25). Stratification by dementia severity showed that this association decreases with dementia severity (from HR¼1.25, 95%CI 1.01 – 1.54 for CDR¼0.5 to HR¼0.95 95%CI 0.64-1.40 for CDR¼3). Conclusions: Among older people with dementia in LMIC, lower gait speed was independently associated to higher mortality risk, after controlling for major potential confounders. Gait speed is a potential clinical indicator of health status in PWD.

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MRI PREDICTORS OF COGNITIVE DECLINE IN CKD: THE BRINK STUDY

Anne Murray1, Cynthia Davey2, Prashanthi Vemuri3, David Tupper1, Elizabeth Amiot4, Emily S. Lundt3, Samantha M. Zuk3, Kaely Steinert3, Clifford R. Jack Jr.3, 1Hennepin County Medical Center, Minneapolis, MN, USA; 2University of Minnesota, Minneapolis, MN, USA; 3Mayo Clinic, Rochester, MN, USA; 4Minneapolis Medical Research Foundation, Minneapolis, MN, USA. Contact e-mail: [email protected] Background: The BRain IN Kidney disease (BRINK) study is a lon-

gitudinal study of cognitive impairment (CI) and brain MRI in moderate to severe chronic kidney disease (CKD). We report baseline MRI predictors of cognitive decline over 2 years in CKD participants. Methods: Participants  45 years old with moderate/ severe (non- dialysis) CKD (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2; Stage 3a-5) in Minneapolis/St. Paul. Composite memory scores were calculated using the Hopkins Verbal Memory Test- R and the Brief Visual Memory Test- R; composite executive function with the Color Trails B, SDMT and Digit Span. T scores adjusted for age and education for each test component. Brain images were obtained on a 1.5 T Phillips Ingenia machine. We computed cortical thickness and hippocampal volumes using Freesurfer v5.3 on structural MRIs and computed FA, WMH, brain lesion, and microhemorrhage assessments using inhouse tools. Logistic regression models measured the association between baseline MRI measures and change in composite score from baseline to 2 years, adjusted for baseline composite scores, gender, race, education (years), prior stroke, baseline eGFR, TNFa, PTH, SBP avg, and diabetes (not for age due to adjustment by T-scores). Results: Characteristics of the 256 MRI participants are described in Table 1. The associations of MRI measures with change in executive function and memory composite scores over 2 years in the CKD cohort are described in Table 2. MD temporal and frontal lobes (P < 0.003) and WMH (P< 0.009) were negatively associated with baseline to 2 year change in comprehensive executive function domain score, whereas frontal and temporal FA and global, frontal and temporal cortical thickness were positively associated (P¼ 0.020 for all). MD temporal and WMH volume were negatively associated with baseline to 2 year change in comprehensive memory domain score; temporal thickness marginally positively associated. Conclusions: These results suggest strong roles for disrupted white matter integrity, small vessel ischemic disease (SVID) and atrophy consistent with white and grey matter

Poster Presentations: Sunday, July 24, 2016

Lincoln, NE, USA; 3University Hospitals of Cleveland, Cleveland, OH, USA. Contact e-mail: [email protected]

Table 1 Demographics CKD n ¼ 155 Age, years Median (IQR) Range Gender, n (%) Female Male Race, n (%) African-American White American Indian or Alaska Native Asian Hispanic Native Hawaiian or Other Pacific Islander More than one race Education, years, n (%) 12 or less 12-16 16 or more Diabetes, n (%) Yes, current Yes, former

Background: Despite the high prevalence of multimorbidity (MM)

Mild CKD n¼ 15

Control n ¼ 75

P 0.31a

69 (63,77) 45 to 92

71 (64,73) 58 to 94

67 (64,73) 47 to 88

4 (27) 11 (73)

41 (55) 34 (45)

0.12b 70 (45) 85 (55)

0.79c 14 (9) 131 (85) 1 (1)

0 (0) 14 (93) 0 (0)

6 (8) 65 (87) 0 (0)

1 (1) 3 (2) 1 (1)

0 (0) 0 (0) 0 (0)

3 (4) 0 (0) 0 (0)

3 (2)

1 (7)

1 (1) <0.001d

64 (41) 65 (42) 26 (17)

3 (20) 9 (60) 3 (20)

8 (11) 42 (56) 25 (33)

72 (46) 1 (1)

8 (53) 0 (0)

25 (33) 2 (3)

0.21e

Table 2 Multiple regression models for association of MRI measures with baseline to 2 year changes in executive function composite scores MRI predictor (all MRI Measures are baseline)

N

Slope (SE) estimate

p-value for slope

WMH Volume (per 1000 units) MD frontal MD temporal FA frontal (x 1000) FA temporal (x 1000) Overall Thickness Frontal thickness Temporal thickness Number of large infarcts Number of subcortical infarcts Sum frontal vascular (per 1000) Sum global GM (per 1000)

94 93 93 93 93 96 96 96 94 94 96 96

-0.06 (0.02) -0.04 (0.01) -0.05 (0.01) 0.05 (0.02) 0.04 (0.02) 8.55 (3.65) 0.69 (0.30) 0.69 (0.29) -0.09 (1.63) -0.51 (1.20) 0.08 (0.05) 0.02 (0.01)

0.009 0.003 0.003 0.011 0.031 0.022 0.022 0.020 0.958 0.672 0.101 0.070

neurodegenerative and vascular processes in executive function decline in CKD, and disrupted white matter integrity and SVID in memory decline.

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MULTIMORBIDITY AND LEADING CAUSES OF DEATH IN OLDER ADULTS ACROSS GRADIENTS OF COGNITIVE IMPAIRMENT

Siran M. Koroukian1, Nicholas K. Schiltz1, David F. Warner2, Jiayang Sun1, Kathleen Smyth1, Stefan Gravenstein3, Kurt Stange1, 1Case Western Reserve University, Cleveland, OH, USA; 2University of Nebraska,

among older adults with cognitive impairment (CI), little is known about how the specific combinations of conditions constituting MM relate to the leading causes of death by level of CI. This study analyzes leading causes of death across CI levels, and in relation to specific combinations of MM conditions. Methods: We used linked data from the 1992–2010 Health and Retirement Study and National Death Index. The HRS is a longitudinal study of a U.S. representative sample of older adults, and includes a rich array of data on chronic conditions, functional limitations, and geriatric syndromes, including cognitive status. Compiled from death certificates from all 50 states, the NDI includes the underlying cause of death, which we grouped in the broad categories defined by the National Center for Health Statistics (NCHS). Using the 35-point Telephone Interview Cognitive Survey (TICS) or proxy report, we grouped respondents in three categories: a) Normal Cognition or No-CI (TICS  11; proxy report: Excellent); Mild-CI (TICS 8-10; proxy report: Very Good/Good); and Moderate/Severe-CI (TICS:  7; proxy report: Fair/Poor). In addition to descriptive analysis, we conducted Classification and Regression Tree (CART) analysis, stratified by cognitive gradient. We used CART to identify empirically emerging combinations of conditions associated with specific causes of death. Results: Our study population included 9,691 decedents; of whom 6.6% and 14.8% were identified with Mild-CI and Moderate/Severe-CI, respectively. Using pre-defined NCHS categories, the top two causes of death in respondents with No-CI or Mild-CI were heart disease and malignant neoplasm. In decedents with Mild-CI, heart disease accounted for 20-40% of deaths in the presence of severe hypertension alone or when co-occurring with severe diabetes or lung disease. In decedents with Moderate/Severe-CI, however, the second leading cause of death was Alzheimer’s disease (AD). Indeed, in this group, among those not previously diagnosed with cancer or lung disease, nearly 20% of deaths were attributed to AD. Conclusions: Except among respondents with Moderate/Severe-CI, the leading causes of death are similar between those with No-CI or Mild-CI, highlighting the importance of chronic disease management in individuals with Mild-CI.

P1-393

PHYSICAL ACTIVITY ACROSS ADULTHOOD AND SUBJECTIVE COGNITIVE DECLINE IN OLDER MEN

Elinor Fondell1,2, Leslie D. Unger1, Olivia I. Okereke1,2, Mary K. Townsend2, Francine Grodstein1,2, Alberto Ascherio1,2, Walter Willett1,2, 1Harvard T. H. Chan School of Public Health, Boston, MA, USA; 2Brigham and Women’s Hospital / Harvard Medical School, Boston, MA, USA. Contact e-mail: [email protected] Background: Subjective cognitive decline (SCD) can be a preclinical indicator of dementia. We examined if physical activity during early adulthood or mid-to-late life is associated with late-life SCD. Methods: The Health Professionals Follow-up Study is a longitudinal study of U.S. male health professionals with a mean age of 51.3 (SD 8.3) years at enrollment in 1986. We included in analyses 28,768 men who reported their SCD in 2008-2012 at an average age of 75 years. Participants reported the average time per week spent on eight different activities on biennial questionnaires starting in 1986. Using metabolic equivalents (MET) for each activity level,