Albuminuria in Association with Cognitive Function and Dementia: A Systematic Review and Meta-Analysis.
OBJECTIVE
Cerebral microvascular disease is considered to contribute to cognitive dysfunction. We opted to explore whether albuminuria, a marker of systemic microangiopathy, is associated with cognitive impairment, dementia, and cognitive function.


METHODS
Systematic review; independent reviewers screened 2359 articles, derived through the search strategy, for identification of observational studies quantifying an association of albuminuria with the outcomes of interest, abstracted data on study characteristics and results and evaluated studies on quality using the Newcastle-Ottawa scale.


METHODS
Community.


METHODS
Adults.


METHODS
Cognitive impairment and dementia, defined by validated neuropsychological tests or clinical guidelines, respectively, and cognitive function, assessed by validated instruments.


RESULTS
Thirty-two eligible studies were identified. Albuminuria was associated with cognitive impairment (Odds Ratio (OR): 1.35, 95% Confidence Interval (CI): 1.19-1.53; 7,852 cases), dementia (OR: 1.35, 95% CI: 1.10-1.65; 5,758 cases), clinical Alzheimer's disease (OR: 1.37, 95% CI: 1.11-1.69; 629 cases) and vascular dementia (OR: 1.96, 95% CI: 1.16-3.31; 186 cases); the effect remained significant among longitudinal, population-based and high quality studies. Time-to-event analysis on prospective studies of non-demented at baseline individuals also showed a significant association with incident dementia (Risk Ratio: 1.52, 95% CI: 1.16-1.99; 971 cases). Worse global cognitive performance (Hedge's g: -0.13, 95% CI: -0.18, -0.09; 68,348 subjects) and accelerated cognitive decline (g: -0.20, 95% CI: -0.34, -0.07; 31,792 subjects) were noted among subjects with albuminuria, who also scored lower in executive function, processing speed, verbal fluency, and verbal memory.


CONCLUSIONS
Albuminuria was independently associated with cognitive impairment, dementia and cognitive decline. The stronger effects for vascular dementia and cognitive performance in domains primarily affected by microvascular disease support that the association could be mediated by shared microvascular pathology in the kidney and the brain.
Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Marios K
MK
Georgakis
Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Nikolaos G
NG
Dimitriou
Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Maria A
MA
Karalexi
Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.|Internal Medicine Department, General Hospital of Kimi, Kimi, Greece.
Constantinos
C
Mihas
Hypertension Unit and Cardiovascular Research Laboratory, First Department of Propaedeutic Internal Medicine, Laiko Hospital, Athens, Greece.
Efthimia G
EG
Nasothimiou
First Department of Cardiology, School of Medicine, Hippokrateion Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Dimitrios
D
Tousoulis
Second Department of Neurology, Attikon University General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.|Department of Neurology, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA.|International Clinical Research Center, St. Anne's University Hospital in Brno, Brno, Czech Republic.
Georgios
G
Tsivgoulis
Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Eleni Th
ET
Petridou
D000419:Albuminuria / Q000150:complications* / Q000453:epidemiology / Q000652:urine; D003071:Cognition / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000209:etiology; D003704:Dementia / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D009483:Neuropsychological Tests; D014652:Vascular Diseases
albuminuria; cognitive impairment; dementia; kidney disease; microvascular disease