Long term use of statins & BP meds do NOT reduce risk for dementia

[Julie G]

I haven't had time to read the full text, but the HOPE-3 press release seems to conclude that pharma (to reduce cholesterol and BP) doesn't appear to protect cognition. We know that heart disease and hypertension are strongly correlated with AD, but medications failed to provide neuroprotection. From a cursory glance, the moral of the story appears to be: You can't fool mother nature. Perhaps it's best to reduce heart disease risk with lifestyle and dietary changes to protect cognition? I'd appreciate hearing from anyone who has time to take a deep dive.

[JudyH]

Julie, this is a very interesting study and of significant interest to me. Thank you for finding and posting it. With heart disease being my biggest mortality risk (both mom and grandmother died at 42 of CAD) and me showing signs that I inherited that heart at 14 years old, I have been on BP medication since age 29 and a statin since age 40. I am a classic long term user of both. My new knowledge of my e3/e4 status has me looking at everything I take and do and questioning its role in each disease, CAD and AD. I am not questioning my use of BP medication, that is a must have for my health but I am studying the debate on statins.

From the detail in your link, this supports what multiple studies have shown for BP medication and statins -
"In two 2016 New England Journal of Medicine papers, and a presentation at the 2016 American College of Cardiology annual meeting in Chicago, HOPE-3 results showed that rosuvastatin reduced vascular events by 25% in all participants, and that lowering blood pressure (BP) reduced events by 24% for those with the highest baseline BP levels."

I found these points interesting -
"Lipid- or BP-lowering with cardiovascular medications did not reduce or increase the rate of cognitive or functional decline among 1,626 study participants (ages ≥70) over a median follow-up of 5.7 years.
However, exploratory analysis showed that the combination of BP lowering and rosuvastatin compared with placebo reduced the rate of cognitive decline among study participants who had the highest systolic BP and LDL-C at baseline (mean SBP 156.3 mm Hg; mean LDL-C 164.7 mg/dL)."

Their findings on statins with a warning -
""Statin use has previously been associated with cognitive impairment, but this study demonstrated that there was none, which is an important finding for those taking statins," Bosch added.
But the treatment duration of 5.7 years may have been too short to see effects of an intervention on cognitive decline, according to the authors."

I didn't take this study to imply anything negative about the use of BP medications or statins. From my family experience, which is probably very unique to me, e4 genetic risk is two fold and I need to balance the risks of both diseases. I was a health, athletic 29 years old, 120 lbs when I started on BP medication and was still only 130 lbs when I started a statin. At the time my doctor said for most people she would wait until their cholesterol numbers were a little worse but not with my family history. I think genetics trumps lifestyle for some people in these diseases and lifestyle trumps genetics for others. They certainly seem to go hand in hand in both diseases.

Right now, as I learn more, I am making lifestyle changes to help protect me from AD and I probably need to add some of the right medical interventions in the form of supplements and hormones to help me on this road. Still reading and studying and trying to plot my course.

[mike]

I haven't had time to read the full text...I'd appreciate hearing from anyone who has time to take a deep dive.

There were many reservations about the findings from the authors themselves - subjects possibly self-selecting, subjects were maybe too healthy, or too old, test too short... Interesting, but needs more follow-up research.

[Julie G]

Thanks for your insights, guys. Here's another press release on the study. I certainly hope this doesn't dissuade anyone from using diet/lifestyle to reduce BP and cardiovascular risk factors. From this press release:

Bosch stressed that the current results should not detract in any way from previous observations that a healthy diet and regular exercise can help to stave off cognitive decline. "These benefits could be mediated through many different mechanisms — not just via lipid or blood pressure reduction. The whole package of living well in midlife for benefits in later life is definitely a sound approach," she said.

[aphorist]

Seems to indicate a possible benefit in a subset of the highest risk patients.

However, exploratory analysis showed that the combination of BP lowering and rosuvastatin compared with placebo reduced the rate of cognitive decline among study participants who had the highest systolic BP and LDL-C at baseline (mean SBP 156.3 mm Hg; mean LDL-C 164.7 mg/dL).

Think HOPE-3 primary endpoint was cardiovascular outcomes based on lipid/hypertension interventions. If I was aiming for an anti-hypertensive, cognitive endpoint, I would look to telmisartan. Telmisartan actually activates AMPK upregulates BDNF [4], improves insulin sensitivity [3], inhibits GSK-3B [2], reduces amyloid plaque [1] and ultimately mimics exercise.

I think low dose telmisartan is a legitimate life extending medication [5], but I don't know the trade-offs in terms of increased lung cancer risk.

It's widely abused in tour de france, as a legal prescription drug.


1. Kurata, T., Lukic, V., Kozuki, M., Wada, D., Miyazaki, K., Morimoto, N., ... & Matsuzono, K. (2015). Long-term effect of telmisartan on Alzheimer’s amyloid genesis in SHR-SR after tMCAO. Translational stroke research, 6(2), 107-115.

2. Pang, T., Sun, L. X., Wang, T., Jiang, Z. Z., Liao, H., & Zhang, L. Y. (2014). Telmisartan protects central neurons against nutrient deprivation-induced apoptosis in vitro through activation of PPARγ and the Akt/GSK-3β pathway. Acta Pharmacologica Sinica, 35(6), 727.

3. Shiota, A., Shimabukuro, M., Fukuda, D., Soeki, T., Sato, H., Uematsu, E., ... & Masuzaki, H. (2012). Telmisartan ameliorates insulin sensitivity by activating the AMPK/SIRT1 pathway in skeletal muscle of obese db/db mice. Cardiovascular diabetology, 11(1), 139.

4. Wincewicz, D., Juchniewicz, A., Waszkiewicz, N., & Braszko, J. J. (2016). Angiotensin II type 1 receptor blockade by telmisartan prevents stress-induced impairment of memory via HPA axis deactivation and up-regulation of brain-derived neurotrophic factor gene expression. Pharmacology Biochemistry and Behavior, 148, 108-118.


5. Mattson MP, Maudsley S. Live longer sans the AT1A receptor. Cell Metab. 2009;9(5):403-5.

[Fiver]

This one doesn't surprise me. After reading everything I could about statins and AD it seemed that there is either no benefit or a very small benefit to statin use in terms of protection from cognitive decline. In terms of CVD risks, however, the benefits are clear. I've learned that many doctors, researchers, and patients are of the opinion that some, but not all, patients can manage dyslipidemia via diet of lifestyle changes. Either way, statins certainly aren't going to cure AD.

[Michae_M]

For anyone wanting a deep dive into the renin angiotensin system in the brain and its relations to various anti-hypertensive medications, I would recommend this review:

Within the Brain: The Renin Angiotensin System

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877737/


This recent paper would suggest that ACE inhibitors are to be avoided as they inhibit the conversion of amyloid β-protein 42 (Aβ42) to Aβ40 which promotes toxicity and loss of cognitive function in humans and mice.

https://www.ncbi.nlm.nih.gov/pubmed/31072831

Inhibition of angiotensin-converting enzyme (ACE) is a strategy used worldwide for managing hypertension. In addition to converting angiotensin I to angiotensin II, ACE also converts neurotoxic amyloid β-protein 42 (Aβ42) to Aβ40. Because of its neurotoxicity, Aβ42 is believed to play a causative role in the development of Alzheimer's disease (AD), whereas Aβ40 has neuroprotective effects against Aβ42 aggregation and also against metal-induced oxidative damage.

Clearly, every effort should be taken to manage cardiovascular health with diet, lifestyle,and strategic nutraceuticals. Pharmacologic interventions complicate things significantly-the choice of optimal anti-hypertensive medications needs to be done carefully and on a personalized basis.

In general, based on the Liu paper, I would not be taking or recommending ACE inhibitors.