2025/05/01 by Masud Husain · 1 voice
Medicine · #Blood Pressure and Hypertension Studies #Cardiovascular Health and Disease Prevention #Cardiovascular Health and Risk Factors
paper · pdf · doi:10.1093/brain/awaf126
openalex publication_date 2025/05/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
Mounting evidence points to the likelihood that optimizing vascular health may have beneficial effects for brain health and cognitive function. Hypertension has long been associated with increased risk of dementia but individual trial data that demonstrate a clear benefit of antihypertensives has been difficult to obtain (although data from the China Rural Hypertension Control Project Phase-3 are to be published imminently). The SPRINT-MIND trial did show a significant reduction in mild cognitive impairment (MCI) and combined rate of MCI and probable dementia.1 However, its early termination (because of unequivocal benefits in cardiovascular end-points) probably meant that its duration was not sufficiently long to establish effects on development of dementia alone.2 Nevertheless, meta-analyses, including individual participant data analyses, show that untreated hypertension is associated with significantly increased risk of dementia and that antihypertensive treatment can reduced this substantially.3,4 In this context it is interesting to note that in otherwise healthy people in middle age, systolic blood pressure (SBP) > 140 mmHg is associated with measurably worse cognitive function which continues to worsen monotonically as SBP increases.5 New findings point also to the beneficial effects on dementia risk mediated by vascular factors that affect lipid metabolism, glycaemic control and perhaps even beyond. First, a large retrospective study from South Korea reports that individuals with low-density lipoprotein (LDL) cholesterol levels below 1.8 mmol/l have a 26% reduction in dementia risk and 28% reduction for Alzheimer’s disease (AD) dementia.6 In their analysis, the investigators also found that people who were taking statins had additional benefits in risk which might not be attributable simply to effects on LDL cholesterol levels. These findings are consistent with a recent meta-analysis which includes more than 7.7 million participants.7 That study reported overall reductions on risk of developing all-cause dementia, AD dementia and vascular dementia in individuals taking statins. The second new finding is in type 2 diabetes mellitus (T2DM). Treatment with either glucagon-like peptide-1 (GLP-1) receptor agonists or sodium-glucose cotransporter-2 inhibitors (SGLT2is or ‘flozins’) was found to be associated with reduced incidence of AD dementia (33% and 43%, respectively, for the two classes of drug).8 Intriguingly, although there was no significant difference between the effects of these two classes at the group level, individuals on semaglutide (but not exenatide, dulaglutide or liraglutide) had a significantly decreased risk of AD dementia compared with people on SGLT2is (canagliflozin, dapagliflozin or empagliflozin). The data are from a large consortium database with the ‘baseline’ group being people on second-line glucose lowering therapies (e.g. sulfonylurea, thiazolidinedione, dipeptidyl peptidase4 inhibitor, α-glucosidase inhibitor or ormeglitinide). Finally, a new meta-analysis reports on the impact of glucose lowering drugs on dementia risk across a wide range individuals, including those with T2DM, heart failure, stroke, transient ischaemic attack, renal failure and even Parkinson’s disease.9 The authors conclude that although overall glucose lowering therapies were not associated with significantly reduced dementia risk, treatment with GLP-1 receptor agonists was linked to reduced all-cause dementia (odds ratio 0.55). However, it is unclear whether this effect of GLP-1 receptor agonists is attributable to effects beyond simply glycaemic control. Together these findings suggest that targeting vascular risk factors—blood pressure, LDL cholesterol and blood glucose—might be important, and relatively cheap, ways to reduce dementia risk at a population level (particularly important for low and middle-income countries). They also suggest that the mechanisms underlying some of the benefits of interventions may not be simply vascular. For example, some analyses9 reveal that in T2DM, GLP-1 receptor agonists might have benefits that are not offered by other glucose lowering drugs. There is now intense interest in establishing what these mechanisms (e.g. reduction in neuroinflammation, amyloid aggregation, tau phosphorylation or even effects on synapses) might be. Recent data published in Brain demonstrate that a group of people who go onto develop T2DM are particularly at risk of developing neurodegenerative diseases such as AD.10 Targeting these individuals at preclinical stages of T2DM with therapies that have an impact on dementia risk would be a natural way forward for future clinical investigations. Overall, this research demonstrates that targeting vascular health has the potential to improve brain health significantly, cheaply and at scale.