Impaired Kidney Function, Cerebral Small Vessel Disease and Cognitive Disorders: The Framingham Heart Study

Dearbhla M Kelly; Adlin A Pinheiro; Marisa Koini; Christopher D Anderson; Hugo Aparicio; Edith Hofer; Daniela Kern; Deborah Blacker; Charles DeCarli; Shih-Jen Hwang; Anand Viswanathan; Mitzi M Gonzales; Alexa S Beiser; Sudha Seshadri; Reinhold Schmidt; Serkalem Demissie; Jose R Romero

doi:10.1093/ndt/gfae079

Impaired Kidney Function, Cerebral Small Vessel Disease and Cognitive Disorders: The Framingham Heart Study

Nephrol Dial Transplant. 2024 Apr 2:gfae079. doi: 10.1093/ndt/gfae079. Online ahead of print.

Authors

Dearbhla M Kelly¹, Adlin A Pinheiro^{2

3}, Marisa Koini⁴, Christopher D Anderson^{5

6

7}, Hugo Aparicio^{3

8}, Edith Hofer^{4

9}, Daniela Kern⁴, Deborah Blacker¹⁰, Charles DeCarli¹¹, Shih-Jen Hwang³, Anand Viswanathan¹, Mitzi M Gonzales¹², Alexa S Beiser^{2

3}, Sudha Seshadri^{3

12}, Reinhold Schmidt⁴, Serkalem Demissie^{2

3}, Jose R Romero^{3

8}

Affiliations

¹ J Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
² Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
³ NHLBI's Framingham Heart Study, Framingham, MA, USA.
⁴ Department of Neurology, Medical University of Graz, Graz, Austria.
⁵ McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA.
⁶ Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
⁷ Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
⁸ Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
⁹ Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Austria.
¹⁰ Department of Epidemiology, Harvard T. H. Chan School of Public Health and Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹¹ Department of Neurology, University of California, Davis School of Medicine, Sacramento, CA, USA.
¹² The Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX, USA.

PMID: 38565317
DOI: 10.1093/ndt/gfae079

Abstract

Background and hypothesis: It remains unclear if the relation of chronic kidney disease (CKD) with cognitive dysfunction is independent of blood pressure (BP). We evaluated kidney function in relation to premorbid BP measurements, cerebral small vessel disease (CSVD) and incident mild cognitive impairment (MCI) and dementia in Framingham Offspring Cohort participants.

Methods: We included Framingham Offspring participants free of dementia, attending an examination during midlife (exam cycle 6, baseline) for ascertainment of kidney function status, with brain MRI late in life (exam cycles 7-9), cognitive outcome data and available interim hypertension and blood pressure assessments. We related CKD (estimated glomerular filtration rate < 60 ml/min/1.73m2) and albuminuria (urine albumin-to-creatinine ratio ≥ 30 mg/g) to CSVD markers and cognitive outcomes using multivariable regression analyses.

Results: Among 2604 participants (mean age 67.4 ± 9.2, 64% women, 7% had CKD and 9% albuminuria), albuminuria was independently associated with covert infarcts (adjusted OR, 1.55 [1.00-2.38]; P = 0.049) and incident MCI and dementia (adjusted HR, 1.68 [1.18-2.41]; P = 0.005 and 1.71, [1.11-2.64]; P = 0.015, respectively). CKD was not associated with CSVD markers but was associated with higher risk of incident dementia (HR, 1.53 [1.02-2.29]; P = 0.041), While albuminuria was predictive of the Alzheimer's disease subtype (Adjusted HR = 1.68, [1.03-2.74]; P = 0.04), CKD was predictive of vascular dementia (Adjusted HR, 2.78, [1.16-6.68]; P = 0.023).

Conclusions: Kidney disease was associated with CSVD and cognitive disorders in asymptomatic community dwelling participants. The relation was independent of premorbid BP, suggesting that the link between kidney and brain disease may involve additional mechanisms beyond blood pressure related injury.

Keywords: CKD; albuminuria; cerebral small vessel disease; cognitive impairment; dementia; hypertension.