Trials and Treatments for Vascular Brain Health: Risk Factor Modification and Cognitive Outcomes

Abstract

There is robust evidence linking vascular health to brain health, cognition, and dementia. In this article, we present evidence from trials of vascular risk factor treatment on cognitive outcomes. We summarize findings from randomized controlled trials of antihypertensives, lipid-lowering medications, diabetes treatments (including antidiabetic drugs versus placebo, and intensive versus standard glycemic control), and multidomain interventions (that target several domains simultaneously such as control of vascular and metabolic factors, nutrition, physical activity, and cognitive stimulation etc). We report that evidence on the efficacy of vascular risk reduction interventions is promising, but not yet conclusive, and several methodological limitations hamper interpretation. Evidence mainly comes from high-income countries and, as cognition and dementia have not been the primary outcomes of many trials, evaluation of cognitive changes have often been limited. As the cognitive aging process occurs over decades, it is unclear whether treatment during the late-life window is optimal for dementia prevention, yet older individuals have been the target of most trials thus far. Further, many trials have not been powered to explore interactions with modifiers such as age, race, and apolipoprotein E, even though sub-analyses from some trials indicate that the success of interventions differs depending on patient characteristics. Due to the complex multifactorial etiology of dementia, and variations in risk factors between individuals, multidomain interventions targeting several risk factors and mechanisms are likely to be needed and the long-term sustainability of preventive interventions will require personalized approaches that could be facilitated by digital health tools. This is especially relevant during the coronavirus disease 2019 (COVID-19) pandemic, where intervention strategies will need to be adapted to the new normal, when face-to-face engagement with participants is limited and public health measures may create changes in lifestyle that affect individuals’ vascular risk profiles and subsequent risk of cognitive decline.

White matter abnormalities mediate the association between masticatory dysfunction and cognition among older adults

“…Modifiable vascular risk factors have been associated with damage to white matter integrity among increased inflammation and cerebrovascular injury. 44 As mentioned, masticatory function has been proposed to be an unrecognised modifiable risk factor 4 although the evidence of this association is limited. Thus, our findings contribute to further hypothesising.…”

“…There is strong evidence in the literature of the link between vascular disease and cognitive decline. Modifiable vascular risk factors have been associated with damage to white matter integrity among increased inflammation and cerebrovascular injury 44 . As mentioned, masticatory function has been proposed to be an unrecognised modifiable risk factor 4 although the evidence of this association is limited.…”

Vascular risk, gait, behavioral, and plasma indicators of VCID

“…To screen large populations for VCID, obtaining high‐quality MRI for surrogate measures like DTI and quantitative WMH is challenging, as this information is not routinely available during annual physician visits. Current efforts, such as MarkVCID 64 and lifestyle intervention studies, 65 focus on screening high‐risk individuals based on VRFs, but there is significant heterogeneity in WM damage, even among those at high risk. As suggested by Hulleck et al., 66 quantitative gait analysis remains largely associated with research institutions and not well leveraged in clinical settings.…”

Optimal anti-amyloid-beta therapy for Alzheimer’s disease via a personalized mathematical model

“…This uncertainty, combined with the 99% failure rate of trials of other classes of AD treatments, is rooted in an incomplete understanding of the complex mechanisms resulting in AD, and how disease trajectory and response to treatment may vary individual-to-individual. It is likely, therefore, that personalized treatment will need to play a central role in the future management and counseling of patients with AD [ 3 , 4 ]. Tailored approaches to treatment will be facilitated by the growing availability of electronic data in AD subjects and those at risk.…”