Study Finds Albuminuria Associated With Cognitive Decline, Increased Risk of Dementia

A longitudinal cohort study found that mild albuminuria was associated with cognitive decline, worse baseline cognitive function, and increased risk of incident cognitive impairment and dementia.

Worse baseline cognitive function, cognitive decline, and increased risk of incident cognitive impairment without dementia (CIND) and dementia demonstrated an association with mild albuminuria, according to a study published in Kidney360.

A longitudinal cohort study was conducted with the ASPREE trial population in Australia and the United States, which was a randomized, placebo-controlled trial of low-dose aspirin in health older individuals with a mean of 4.7 years of follow-up. Patients who were free from cardiovascular disease (CVD), physical disability, dementia, and being expected to survive for at least 5 years were included. Patients with a self-report or physician diagnosis of dementia at recruitment were ineligible.

Cognitive assessments were administered by trained staff at baseline and year 1 and then biennially. The cognitive assessments included the Modified Mini-Mental State Examination (3MS), a 100-point measure of global cognition; the Delayed Recall component for episodic memory of the Hopkins Verbal Learning Test-Revised (HVLT-R); the Controlled Oral Word Association Test (COWAT); and the Symbol Digit Modalities Test (SDMT).

There were 18,560 and 18,131 of the 19,114 ASPREE participants who had baseline measures of eGFR and UACR respectively. The median age of the participants was 74 years, 56% were female, 74% had hypertension, and 11% had diabetes. The median (IQR) estimated glomerular filtration rate (eGFR) was 74 (63-84) mL/min per 1.73 m2; median urine albumin-creatinine ratio (UACR) was 0.8 (0.5-1.5) mg/mmol (7.1 [IQR, 4.4-13.3] mg/g).

In adjusted analyses, baseline eGFR was not associated with scores on any of the 4 cognitive tests. UACR greater than or equal to 3 mg/mmol (greater than or equal to 26.6 mg/g) was significantly associated with baseline scores for 3 of the 4 tests in adjusted models, with the association with SDMT clinically significant (b, –1.24; 95% CI, –1.66 TO –0.81) as it was more than double the size of the mean change in SDMT in all participants.

A mean of 3.2 annual cognitive assignments per participant was performed during the follow-up. eGFR at baseline was statistically associated with decline of 3MS and SDMT scores but the associations were clinically negligible. Baseline albuminuria was associated with cognitive decline on all cognitive tests except the COWAT, and most strongly associated with the SDMT (b, –0.76; 95% CI, ­–1.18 to –0.33).

There were 2777 cases of CIND and 563 cases of incident dementia with eGFR or UACR measures in the median 4.7 years follow up. There was no statistic significant association between baseline eGFR and time to CIND or dementia. Both binary and continuous measures of UACR were associated with increased risk of incident CIND and dementia. Baseline albuminuria demonstrated a 19% increased risk of CIND (HR, 1.19; 95% CI, 1.07-1.33) and 32% increased risk of incident dementia (HR, 1.32; 95% CI, 1.06-1.66).

This study had some limitations. There was a minor decline in cognitive function during the follow-up overall which could have decreased the ability to detect associations between kidney function and cognitive decline. Fewer participants had cognitive assessments as the study went on as some were recruited later in the study and others were not willing to participate in cognitive testing as they were aware of their own cognitive decline.

The results are likely not generalizable to older populations with a higher risk of CVD and advanced CKD. Urine samples were also harder to obtain in the older population.

The researchers concluded that mild albuminuria was associated with lower baseline performance, decline on tests of global cognitive function, and increased risk of incident CIND and dementia.

“Our findings suggest that screening global cognitive tests could be considered for those greater than or equal to 70 years with a UACR of greater than or equal to 3 mg/mmol and without an eGFR of less than 45 ml/min per 1.73 m2 to identify those at highest risk of cognitive decline and dementia,” the authors wrote.


Murray AM, Thao LTP, Ryan J, et al. CKD biomarkers, cognitive impairment, and incident dementia in an older healthy cohort. Kidney360. 2022;3:435-445. doi:10.34067/KID.0005672021