Wu, Aozhou

Background: Dementia is increasingly appreciated to have important vascular disease contributions. Albuminuria and decreased estimated glomerular filtration rate (eGFR) define chronic kidney disease (CKD) and are related to the risk of its consequences as well as microvascular disease and endothelial damage across multiple vascular beds. We extend previous studies by examining albuminuria and eGFR measured at both mid-life and older age as risk factors for dementia. Methods: We studied 10,876 adult participants in the Atherosclerosis Risk in Communities (ARIC) Study excluding participants with end-stage renal disease, stroke and incident dementia at baseline. We analyzed the adjusted relative hazard of incident dementia as a function of eGFR (linear spine with a knot at 60 ml/min per 1.73m 2 ) and log urinary albumin-creatinine-ratio (UACR) adjusting for age, sex, race, education level, Apolipoprotein E4 level, smoking, alcohol consumption, body mass index, diabetes and hypertension. We used two different baseline visits: (1) Starting in 1996-1999 (Visit 4, age 54-74 years); (2) Starting 2011-2013 (Visit 5, age 70-90 years) with follow-up to 2017. Results: We observed 2,001 dementia cases over 16 years of follow-up (446 after Visit 5). Risk of dementia increased with higher levels of albuminuria with a stronger magnitude at older-age than in midlife ( see table ). Estimated GFR was more weakly associated with dementia (p>0.05 at both baselines). The albuminuria association was consistent across sex and race (p-interaction>0.05). Conclusion: Albuminuria, a marker of kidney disease and endothelial damage, is strongly related to dementia incidence. Albuminuria’s association with dementia is stronger in late-life unlike other vascular risk factors, where the association is weaker at older age.

Objectives To examine the association between hospitalization, critical illness, and infection occurring during middle‐ and late‐life and structural brain abnormalities in older adults. Design Prospective cohort study. Setting Atherosclerosis Risk in Communities (ARIC) Study. Participants A community sample of adults who were 44 to 66 years of age at study baseline. Measurements Active surveillance of local hospitals and annual participant contact were used to gather hospitalization information (including International Classification of Diseases, Ninth Revision , codes) on all participants over a 24‐year surveillance period. Subsequently, a subset of participants underwent 3‐Tesla brain magnetic resonance imaging (MRI) to quantify total and regional brain volumes, white matter hyperintensity (WMH) volume, and white matter microstructural integrity (fractional anisotropy (FA) and mean diffusivity (MD) as measured using diffusion tensor imaging (DTI)). Results Of the 1,689 participants included (mean age at MRI 76±5), 72% were hospitalized, 14% had a major infection, and 4% had a critical illness during the surveillance period. Using covariate‐adjusted regression, hospitalization was associated with 0.12–standard deviation (SD) greater WMH volume (95% confidence interval (CI)=0.00–0.24) and poorer white matter microstructural integrity (0.17‐SD lower FA, 95% CI=–0.27 to –0.06; 0.16‐SD greater MD, 95% CI=0.07–0.25) than no hospitalization. There was a dose‐dependent relationship between number of hospitalizations, smaller brain volumes, and lower white matter integrity ( p ‐trends ≤.048). In hospitalized participants, critical illness was associated with smaller Alzheimer's disease (AD) signature region (–1.64 cm 3 , 95% CI=–3.16 to –0.12); major infection was associated with smaller AD signature region (–1.28 cm 3 , 95% CI=–2.21 to –0.35) and larger ventricular volume (3.79 cm 3 , 95% CI= 0.81–6.77). Conclusions Whereas all‐cause hospitalization was primarily associated with lower white matter integrity, critical illness and major infection were associated with smaller brain volume, particularly within regions implicated in AD.