Uric Acid and High-Density Lipoprotein Cholesterol Are Differently Associated with Alzheimer’s Disease and Vascular Dementia

Abstract

Uric acid (UA) is a major contributor to naturally-occurring antioxidant activity and is thought to have protective effects against neurodegenerative processes. However, UA is also implicated as a risk factor in vascular, including cerebrovascular, disease. Its association with, and role in, dementia and its component diseases including Alzheimer's disease (AD) and vascular dementia (VaD) remains unclear and inconsistently studied. Changes in blood lipids, particularly cholesterol measures, have also been implicated in dementias although the relationship or interactions with UA have been little studied.We have measured plasma UA and lipids taken from 187 subjects first attending a general hospital neurology department for symptoms associated with dementia, and from a series of 79 healthy control subjects. Diagnoses of AD and VaD were made following neuroimaging; laboratory measures were compared between dementia and control groups and between AD and VaD subgroups. No overall change in UA was seen in dementia, although a substantial and highly significant reduction was found in the AD patients. Reduced values in total cholesterol, HDL, and LDL were found in dementia, independent of statin treatment. Further investigation found a significant reduction of HDL only in the VaD group, while total cholesterol was significantly reduced in both AD and VaD subjects.These findings indicate that in our Chinese sample, UA deficits are specifically associated with AD, while deficits in HDL cholesterol found in dementia tend to be greater in VaD.

Agricultural work and reduced circulating uric acid are both associated with initial hospital admission for Parkinson’s disease

“…There were a smaller proportion of current smokers in the agricultural workers with PD which did not reach statistical significance. UA was found to be reduced in the PD group (286 ± 83 µmol/L) in comparison with both the VD sample (361 ± 113 µmol/L; F = 19.92, p < 0.001) and a previously studied (Liu et al 2020) and approximately agematched (62.5 ± 10.3 years; n = 79) healthy control sample (348 ± 86 µmol/L; F = 31.12, p < 0.001), controlling for age and sex. UA concentrations were lower in agricultural workers in both PD and VD samples (Table 1).…”

“…Data from a previously studied sample (Liu et al 2020) of 124 patients meeting diagnostic criteria for VD, including mixed dementia, were used for comparison of UA results and their relationship with agricultural work. Details of recent admissions to the hospital neurology department were used for comparison with the proportion of agricultural workers in the study.…”

“…We aimed to investigate whether there is evidence that this group has an increased risk of PD and/ or an earlier disease onset. We also aimed to determine the association of circulating UA with PD in agricultural and non-agricultural workers, using a sample of patients with vascular dementia (VD) for comparison, in whom we previously found no significant abnormality in UA (Liu et al 2020).…”

Risk of dementia in gout and hyperuricaemia: a meta-analysis of cohort studies

“…36 In a recent study, Liu et al came to the same conclusion that a lower level of uric acid is associated with AD in Chinese. 37 In our study, we analysed the AD subgroup of dementia and found that gout can reduce the risk of AD. This may also confirm the neuroprotective role of uric acid.…”

Association of cardiovascular risk burden with risk of dementia and brain pathologies: A population‐based cohort study

“…Many studies have investigated the impact of individual cardiovascular risk factors, including old age, diabetes, hypertension, smoking, and hypercholesterolemia on dementia risk, and have shown inconsistent results 3–8 . Given that these cardiovascular risk factors tend to cluster and interact in an individual, 9 a multivariate risk prediction algorithm incorporating these risk factors is preferable to examine the overall impact of cardiovascular risk burden on dementia.…”