Albuminuria and decline in cognitive function: The ONTARGET/TRANSCEND studies.
BACKGROUND
Microvascular disease of the kidney (manifesting as albuminuria) and of the brain (manifesting as cognitive decline) may share a common pathogenesis. Gaining an understanding of the concomitant history of these 2 conditions may inform clinical practice and lead to novel prevention and treatment approaches.


METHODS
A total of 28 384 participants with vascular disease or diabetes mellitus were examined. At baseline and year 5, participants underwent a Mini-Mental State Examination (MMSE) and urine testing for albumin excretion. Multivariable logistic regression was used to determine the association between albumin excretion and MMSE score, cross-sectionally and prospectively, and whether angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker use modified the association.


RESULTS
Compared with participants with normoalbuminuria, those with microalbuminuria (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.11-1.44]) and macroalbuminuria (1.49; 1.20-1.85) were more likely to have a reduced MMSE score (<24). On follow-up, participants with baseline albuminuria had increased odds of cognitive decline (decrease in MMSE score ≥3 points) compared with those with normoalbuminuria (microalbuminuria: OR, 1.22; 95% CI, 1.07-1.38; macroalbuminuria: 1.21; 0.94-1.55). Participants who developed new albuminuria had increased odds of cognitive decline during follow-up compared with those who remained normoalbuminuric (new microalbuminuria: OR, 1.30; 95% CI, 1.12-1.52; new macroalbuminuria: 1.77; 1.24-2.54). Participants with baseline macroalbuminuria treated with an angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker had lower odds of MMSE decline than participants treated with placebo.


CONCLUSIONS
Factors that contribute to albuminuria may contribute to cognitive decline, supporting the notion that both conditions share a common microvascular pathogenesis. Trial Registration clinicaltrials.gov Identifier: NCT00153101.
Kaiser Permanente of Georgia, Emory University School of Medicine, Atlanta, USA. Joshua.barzilay@kp.org
Joshua I
JI
Barzilay
Peggy
P
Gao
Martin
M
O'Donnell
Johannes F E
JF
Mann
Craig
C
Anderson
Robert
R
Fagard
Jeffrey
J
Probstfield
Gilles R
GR
Dagenais
Koon
K
Teo
Salim
S
Yusuf
D000368:Aged; D000419:Albuminuria / Q000150:complications* / Q000188:drug therapy*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000209:etiology* / Q000517:prevention & control*; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000453:epidemiology; D003928:Diabetic Nephropathies / Q000150:complications; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors