Association of combination statin and antihypertensive therapy with reduced Alzheimer’s disease and related dementia risk

Abstract

BackgroundHyperlipidemia and hypertension are modifiable risk factors for Alzheimer's disease and related dementias (ADRD). Approximately 25% of adults over age 65 use both antihypertensives (AHTs) and statins for these conditions. While a growing body of evidence found statins and AHTs are independently associated with lower ADRD risk, no evidence exists on simultaneous use for different drug class combinations and ADRD risk. Our primary objective was to compare ADRD risk associated with concurrent use of different combinations of statins and antihypertensives. MethodsIn a retrospective cohort study (2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014), we analyzed 694,672 Medicare beneficiaries in the United States (2,017,786 person-years) who concurrently used both statins and AHTs. Using logistic regression adjusting for age, socioeconomic status and comorbidities, we quantified incident ADRD diagnosis associated with concurrent use of different statin molecules (atorvastatin, pravastatin, rosuvastatin, and simvastatin) and AHT drug classes (two renin-angiotensin system (RAS)-acting AHTs, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin-II receptor blockers (ARBs), vs non-RAS-acting AHTs).

Brain Renin–Angiotensin System at the Intersect of Physical and Cognitive Frailty

“…AD (Zhuang et al, 2016). A more recent retrospective cohort study found that ARBs combined with statins reduced AD more than statins combined with non-RAS-acting antihypertensives (Barthold et al, 2020). Consistent with previous studies, ARBs were found to be more effective than ACEIs in reducing dementia risk.…”

“…Furthermore, a meta-analysis of studies on AD and aging showed that ARBs have a protective role in the risk of cognitive impairment of aging and AD, while both ACEIs and ARBs have benefits on prevention of AD ( Zhuang et al, 2016 ). A more recent retrospective cohort study found that ARBs combined with statins reduced AD more than statins combined with non-RAS-acting antihypertensives ( Barthold et al, 2020 ). Consistent with previous studies, ARBs were found to be more effective than ACEIs in reducing dementia risk.…”

Paraoxonase Role in Human Neurodegenerative Diseases

“…The association between the PON1 enzyme and the development of AD was described in the late 1990s [ 188 , 189 ]. In addition, treatment with statins have shown to improve the cognitive function in patients with AD [ 190 , 191 , 192 , 193 ]. Paraoxonases-1 and -2 are expressed in the human frontal cortex [ 194 ].…”

Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons

“…Interestingly, disruption of cholesterol homeostasis has been associated with AD pathogenesis [ 22 , 23 , 24 ]. Early epidemiological studies reported a lower risk of dementia in patients under statin treatment [ 25 , 26 ] and, more recently, a combination of statins and antihypertensive drugs was shown to be more effective in reducing the risk of AD and related dementias [ 22 ]. Statins reduce cholesterol by inhibiting its biosynthesis at a critical rate-limiting step in the mevalonate pathway, i.e., by blocking the activity of HMG-CoA (5-hydroxy-3-methylglutaryl coenzyme A) reductase in the liver.…”