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Table 1 Major longitudinal studies about the association of chronic kidney disease and cognitive decline (modified after [34])

From: Kidney disease as a determinant of cognitive decline and dementia

Study Participants Mean age (years) Follow-up (years) Cognitive test Assessment (1) and classification (2) of renal function Adjustment for confounders Result (risk for cognitive decline depending on renal function/proteinuria/albuminuria)
Osteoporotic Fractures in Men Study [30] 5,929 men 74 5 3MS, Trails B (1) MDRD Age, education, race, health status, ADL impairment, alcohol, diabetes, hypertension, CHD, stroke, BMI, PAD Not significant for both tests in both CKD groups
      (2) Mild CKD = eGFR 45 to 59, moderate CKD = eGFR <45   
Rancho Bernardo Study [31] 1,345 75 6.6 MMSE, Trails B, Category Fluency Test (1) MDRD Age, hypertension, HbA1c, dyslipidemia, education, exercise, alcohol, estrogen, depression Not significant for eGFR
      (2) Moderate-to-severe CKD = eGFR <60   Significant only for men and baseline albuminuria
Three C Study [32] 7,839 74 7 MMSE (1) CKD-EPI Age, sex, education, ApoE, hypertension, CHD, dyslipidemia, diabetes, smoking, BMI, stroke Not significant except for eGFR decline over first 4 years and vascular dementia
      (2) CKD = eGFR <60   Borderline risk for proteinuria
Reasons for Geographic and Racial Differences in Stroke [33] 19,399 64 3.8 6-Item Screener (1) CKD-EPI Age, sex, race, education, region, hypertension, diabetes, stroke, CHD, alcohol, smoking Not significant for eGFR <60
      (2) CKD = eGFR <60   OR 1.30 (95% CI 1.02 to 1.66) for UACR <10 mg/g in eGFR <60
Cardiovascular Health Cognition Study [22] 3,349 77 6 Cognitive battery testing for dementia similar to DSM-IV criteria (1) Inverse of creatinine Age, sex, race, body weight, education, CHD, stroke, hypertension, diabetes, smoking, apoE genotype 37% increased risk of dementia (95% CI 1.06 to 1.78)
      (2) Moderate CKD = SCr ≥1.3 mg/dl for women and ≥1.5 for men   
Health, Aging, and Body Composition Study [23] 3,034 74 2, 4 3MS (1) MDRD at baseline Age, sex, race, education, diabetes, medication, hypertension, hyperlipidemia, CRP, interleukin-6, hematocrit, CHD, stroke OR 1.32 (95% CI 1.03 to 1.69) for eGFR 45 to 59
      (2) CKD = eGFR <60 with two subgroups (eGFR 45 to 59 and <45)   OR 2.43 (95% CI 1.38 to 4.29) for eGFR <45
INVADE study [24] 3,697 68 2 6-Item Cognitive Impairment Test (1) CG at baseline Age, sex, smoking, CHD, stroke, hypertension, diabetes, BMI, hyperlipidemia, alcohol, physical activity, depression Moderate-to severe CKD: OR 2.14 (95% CI 1.18 to 3.87)
      (2) Mild CKD = eGFR 45 to 59, moderate-to-severe CKD = eGFR <45   
Rush and Memory Aging Project [26] 886 81 3.4 Battery of 19 tests with five cognitive systems (1) MDRD at baseline Age, sex, education, BMI, hemoglobin, physical activity, social activity, hypertension, diabetes, smoking, CHD, stroke, PAD, depression Each GFR reduction of 15 = increased rate of global cognitive decline of being 3 years older
      (2) CKD = eGFR <60   
Northern Manhattan Study [25] 2,172 72 2.9 TICS (1) CG + MDRD at baseline Age, sex, race, education, insurance, hypertension, diabetes, alcohol, smoking, CHD, stroke homocysteine, hematocrit, psychoactive medication Decline by 0.3 TICS points/year for eGFR <60
      (2) Mildly reduced renal function = eGFR 60 to 90, eGFR <60   Decline by 0.2 TICS points/year for eGFR = 60 to 90
Osaka-Tajiri Project [27] 497 74 5 Clinical Dementia Rating (1) Not described Age, sex, education, hypertension, diabetes, dyslipidemia, CHD, anemia Conversion to dementia OR 5.3 (95% CI 1.7 to 16.2)
      (2) CKD = eGFR <60 or albuminuria   
Maine-Syracuse Longitudinal Study [28] 590 62 5 Composite scores of VM, VSOM, ST and WM (1) MDRD Age, sex, education, race, diabetes, BMI, smoking, HDL cholesterol, hypertension Global cognitive ability: b = 0.21 SD decline/unit ln(eGFR) (95% CI 0.04 to 0.38)
      (2) CKD = eGFR <60   Verbal episodic memory: b = 0.28 SD decline per unit ln(eGFR) (95% CI 0.02 to 0.54)
        Abstract reasoning: b = 0.36 SD decline per unit ln(eGFR) (95% CI 0.04 to 0.67)
Cardiovascular Health Study [29] 3,907 75 5.3 3MS, DSST (1) Cystatin C-based eGFR Age, sex, race, education, smoking, BMI, diabetes, hypertension, CRP, ApoE, depression Points/year faster decline:
      (2) CKD = eGFR <60   OR 0.64 (95% CI 0.51 to 0.77) in 3MS
        OR 0.42 (95% CI 0.28 to 0.56) in DSST
Osaka Follow-up Study for Carotid Atherosclerosis, Part 2 [8] 600 68 7.5 MMSE (1) MDRD Age, sex, ApoE, education, hypertension, diabetes, cerebrovascular events HR 1.96 (95% CI 1.08 to 3.58)
      (2) CKD = eGFR <60 brain atrophy, SVD  
  1. ADL, activities of daily living; ApoE, apolipoprotein E genotype; BMI, body mass index; CG, Cockcroft–Gault equation; CHD, coronary heart disease; CI, confidence interval; CKD, chronic kidney disease; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration equation; CRP, C-reactive protein; DSST, Digit Symbol Substitution Test; eGFR, estimated glomerular filtration rate (ml/minute/1.73 m2); HDL, high-density lipoprotein; HR, hazard ratio; INVADE, Intervention Project on Cerebrovascular Diseases and Dementia in the Community of Ebersberg; 3MS, Modified Mini-Mental State Examination; MDRD, Modification of Diet in Renal Disease; MMSE, Mini-Mental State Examination; OR, odds ratio; PAD, peripheral artery disease; SCr, serum creatinine; SD, standard deviation; ST, scanning and tracking; SVD, small-vessel disease; TICS, telephone interview for cognitive status; UACR, urine albumin–creatinine ratio; VM, verbal episodic memory; VSOM, visual–spatial organization and memory; WM, working memory.