*5.5. Drugs for Cardiovascular Disease and Adiponectin*

A recent study has suggested that medications aimed at cardiovascular diseases may also decrease the risk of dementia caused by AD [168]. Several neuroprotective pleiotropic agents have been shown to increase plasma adiponectin levels [169]. In studies with animal models, angiotensin II receptor blockers have shown beneficial effects on cognitive function related to AD [170–172]. Improvements in AD progress and cognitive function have also been observed in human clinical trials [173–175]. Moreover, angiotensin II receptor blockers can reduce neuroinflammation directly or by regulating the infiltration of inflammatory cytokines because of their ability to restore the blood-brain barrier [176–178]. Altogether, angiotensin II receptor blockers may be beneficial in AD therapy because it upregulates adiponectin [179–181].

Angiotensin-converting enzyme inhibitors (ACEIs) regulate the renin–angiotensin system and angiotensin II receptor blockers. Upregulation of blood adiponectin has been observed after treatment with ACEIs [182,183]. Some clinical and meta-analysis studies have also shown that ACEIs reduce the progression and risk of AD [184–187]. This result has also been observed in several animal model studies [188–190]. However, in one meta-analysis study, ACEIs had no effect on cognitive decline [191], and some studies have shown a negative effect of ACEIs in in-vivo AD models [192–194]. Thus, ACEI treatment is controversial for its effect on AD.

Another cardiovascular medication, fibrate, a PPARα agonist, has been shown to increase adiponectin levels [195,196]. Since ligand-activated PPARα decreases tau phosphorylation, Aβ pathology, and neuroinflammation, fibrate might be a good candidate for AD treatment [197].

Statins (such as simvastatin, paravastatin, and atorvastatin) have been reported to increase blood adiponectin levels [198–200]. Statins are well known for their anti-inflammatory properties in diabetic patients [201,202]. According to the above studies, statins might also be useful in the treatment of AD by increasing blood adiponectin levels and reducing neuroinflammation.
