Table 2.

Landmark randomized controlled trials looking at the benefits of clinical management of modifiable risk factors in diabetes and cognitive dysfunction

Intervention/ treatment	Study characteristics & benefit(s) of treatment/intervention group	Ref.
Treatment with antihypertensives acting on renin angiotensin axis	Better executive function, processing speed, verbal memory and composite score compared to those treated with other antihypertensives	Wharton et al[105], 2022
Intensive BP and lipid control compared to standard treatment (ACCORD trial)	Intense BP control and lipid reduction had no effects on cognitive decline. Moreover, total brain volume was found to be less with intense BP control (systolic BP < 120 mm Hg) than standard treatment after 40 mo	Williamson et al[107], 2014
Liraglutide therapy for T2DM	Activation of different cerebral areas with improved memory, attention, and better scores in all cognitive function tests	Li et al[112], 2021
Intense vs standard BP control (SPRINT trial)	Intense BP control was not associated with improvements in memory or processing speed compared to standard BP reduction	Rapp et al[113], 2020
10 yr of ILI vs standard care (Look AHEAD trial)	ILI resulted in better odds for emergence of: Decision-making inability (OR = 0.851) and problem solving inability (OR = 0.694) in those without these baseline complaints	Espeland et al[114], 2018
Finnish diabetes prevention study	Middle-aged overweight participants with impaired glucose tolerance showed better cognitive performance with low total fat & saturated fat intake, and frequent physical activities compared to standard lifestyle	Lehtisalo et al[115], 2016

BP: Blood pressure; T2DM: Type 2 diabetes mellitus; ILI: Intense lifestyle intervention; OR: Odds ratio.