Not a cure, but a start

USC study shows that some combinations of cardiovascular drugs may reduce Alzheimer's risk

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LOS ANGELES—Drug repurposing is nothing new, whether the drug fails for one purpose and ends up being good for another or whether it just tackles multiple maladies. And the cardiovascular R&D segment is no exception to this—after all, Pfizer originally discovered sildenafil (most famously known under the brand name Viagra) not for erectile dysfunction but with heart-related chest pain in mind.
Now, the cardiovascular drug segment might bring relief for Alzheimer’s disease (AD) patients, according to published research by University of Southern California (USC) scientists.
As detailed in a study titled “Association of combination statin and antihypertensive therapy with reduced Alzheimer’s disease and related dementia risk,” recently published in PLOS ONE, certain combinations of cardiovascular drugs may reduce risk for Alzheimer’s disease. This study looked at nearly 700,000 Medicare beneficiaries.
Specifically, the research indicated that drugs already in use for blood pressure and cholesterol control could reduce the number of people with Alzheimer’s disease and related dementias (ADRD).
“Our research found dementia risk may be reduced with a specific combinations of drug treatments for vascular health,” said lead author Julie Zissimopoulos, director of the Aging and Cognition program at the USC Leonard D. Schaeffer Center for Health Policy & Economics. “This is the first study to investigate the association of different combinations of these frequently used drugs and dementia risk in a large and broadly representative sample of older Americans and to illuminate the differences in effect for women compared to men, and for whites, Hispanics and African Americans.”
Given that there is as yet no cure for Alzheimer’s disease, one area of focus has been on prevention and risk reduction of dementia, including maintenance of a healthy lifestyle and management of risk factors such as high blood pressure and high cholesterol.
“We know that managing hyperlipidemia and hypertension is important, and this study tells us there might be certain combinations of drugs that have additional benefits for Alzheimer’s and other dementias beyond the management of those targeted conditions,” commented co-author Douglas Barthold, research assistant professor with the Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute at the Department of Pharmacy at the University of Washington, Seattle.
The study examined the medical and pharmacy claims of a random 20-percent sample of Medicare beneficiaries, aged 67 and higher. To be included in the analysis, individuals had to have used both an antihypertensive and a statin for the two previous years and have no prior dementia diagnoses and no prior use of medications specific to Alzheimer’s disease.
The study found the use of cholesterol-lowering drugs pravastatin and rosuvastatin, combined with ACE inhibitors or angiotensin II receptor blockers (ARBs) for high blood pressure, was associated with reduced risk for dementia as compared to other combinations of drugs.
The risk was especially lower for people using pravastatin and rosuvastatin in combination with ARBs, and more so for men than women.
As the authors wrote, “The magnitudes of estimated risk reductions were meaningful; for example, using ARBs combined with pravastatin was associated with 21% lower odds of ADRD, as compared to individuals using other statins and non-RAS acting AHTs in combination.”
“We don’t currently have drugs that are proven to treat dementia, but even small delays in onset can dramatically reduce the burden on patients, caregivers and the health system as a whole,” Zissimopoulos noted.
There remains much left to study in terms of the potential utility of these cardiovascular medications for ADRD, particularly figuring out why this is happening.
“n this study we cannot test what mechanisms are driving the differential associations that were observed between the four statins investigated, all of which work to reduce low-density lipoprotein (LDL) cholesterol levels, and combinations of ARBs or ACEIs. A potential mechanism, and one that may explain some of the ethnic differences observed, are differences in drug metabolism and transport. Rosuvastatin, for example, is metabolized by CYP2C9 and CYP2C19 cytochrome P-450 enzymes,” the authors noted. “These CYP enzymes could be related to differential associations with ADRD in two ways. First, if there are pharmacokinetic interactions between certain statins and certain AHTs, the metabolism of one or both drugs could be altered in a way that confers differential benefit regarding ADRD. CYP2C9, for example, metabolizes Rosuvastatin, and is a substrate for several ARBs (e.g., losartan and irbesartan), potentially leading to interactions. Second, statins and/or AHTs may affect the activity of CYP enzymes that have a direct impact on ADRD risk factors. For example, some genetic variants in CYP2C19 confer protection against amyloid-beta burden in persons with AD. Additionally, CYP2C9 is encoded for by a gene previously linked to familial AD.”

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