Having high blood pressure has consistently predicted an increased risk of developing cognitive decline and dementia.[i] Several plausible mechanisms support the potential for raised BP driving impairment in brain structure and function.[ii] But does lowering it with medication help reduce risk? Several randomised controlled and double-blind trials of anti-hypertensives have assessed cognition or dementia outcomes. However, their results have largely been inconclusive.[iii]

The latest such study is a case in point and shows how one has to not only consider the potential benefit, but also the potential for harm of medication. It was a study[iv] of almost ten thousand over 50 year olds with high blood pressure, using either standard hypertensive medication to reduce high ‘systolic’ blood pressure to the usual level of below 140 versus intensive medication to get blood pressure below 120 found a modest, non-significant difference in the number who developed dementia (149 vs 176).

In other words, 27 people with high blood pressure given drugs to bring it below 140 may not have developed mild cognitive impairment (MCI) as a result, compared to 31 in the intensive drug treatment group. So that’s four fewer people on the intensive drug treatment getting MCI. But there were almost 5,000 people in each group. That means that you’d have to treat 1,000 people with intensive blood pressure lowering drugs to potentially save one from MCI. This study was not significant yet reported a non-significant 20% ‘relative’ reduced risk with intensive medication versus standard treatment. This is rather misleading. In addition, there was no placebo group so we don’t even know if this apparent reduction was better or worse than doing nothing.

Intensive drug treatment sounds a bit scary. Just how many people in a thousand given intensive blood pressure lowering medication would be expected to have a serious adverse effect? Studies report between 10%[v] and 30%[vi] develop adverse drug reactions, with tiredness, muscle pain and poor sleep being the most common adverse reactions[vii] . The higher figure is perhaps more realistic with intensive blood pressure lowering treatment. That would mean that 300 people would be expected to have adverse drug reactions for one to potentially not be diagnosed three years later with MCI.

Although this study did not report adverse reactions another study using the same trial participants, looking at cardiovascular outcomes, did.[viii] You have to hunt to find this kind of information. What it shows is that serious adverse events occurred in 1793 participants in the intensive treatment group (38.3%). A serious adverse reaction was defined as ‘events that were fatal or life-threatening, that resulted in clinically significant or persistent disability, that required, or prolonged, a hospitalisation, or that were judged by the investigator to represent a clinically significant hazard or harm to the participant that might require medical or surgical intervention to prevent one of the other events listed above.’

So, if one thousand people were treated – that’s the number needed to potentially save one person from an MCI diagnosis – 380 would have a potentially life-threatening adverse effect and either die or require prolonged hospitalisation. I think we can conclude, at this point in time, lowering blood pressure with medication is not the way to go for dementia prevention.

But that doesn’t mean that lowering blood pressure by other means isn’t worth investigating. It is entirely probable that the very things that raise blood pressure in the first place – a high sugar diet, lack of omega-3, high homocysteine levels, lack of antioxidants including magnesium, lack of exercise, stress and insomnia – might be the real underlying contributors to high blood pressure in the first place. A study targeting these factors in order to reduce high blood pressure would be well worth doing.

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References

[i] Qiu C, Winblad B, Fratiglioni L. The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol. 2005;4(8):487-499.

[ii] Iadecola C, Yaffe K, Biller J, et al. Impact of Hypertension on Cognitive Function: a Scientific Statement From the American Heart Association. Hypertension. 2016;68(6):e67-e69

[iii] Peters R, Warwick J, Anstey KJ, Anderson CS. Blood pressure and dementia: what the SPRINT-MIND trial adds and what we still need to know. Neurology. 2019;92(21):1017-1018; see also. Elias MF, Torres RV, Davey A. Clinical Trials of Blood Pressure Low- ering and Antihypertensive Medication: is Cognitive Measurement State-of-the-Art?. Am J Hypertens. 2018;31(6):631-642.

[iv] SPRINT MIND Investigators for the SPRINT Research Group, Williamson JD, Pajewski NM, Auchus AP, Bryan RN, Chelune G, Cheung AK, Cleveland ML, Coker LH, Crowe MG, Cushman WC, Cutler JA, Davatzikos C, Desiderio L, Erus G, Fine LJ, Gaussoin SA, Harris D, Hsieh MK, Johnson KC, Kimmel PL, Tamura MK, Launer LJ, Lerner AJ, Lewis CE, Martindale-Adams J, Moy CS, Nasrallah IM, Nichols LO, Oparil S, Ogrocki PK, Rahman M, Rapp SR, Reboussin DM, Rocco MV, Sachs BC, Sink KM, Still CH, Supiano MA, Snyder JK, Wadley VG, Walker J, Weiner DE, Whelton PK, Wilson VM, Woolard N, Wright JT Jr, Wright CB. Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial. JAMA. 2019 Feb 12;321(6):553-561. doi: 10.1001/jama.2018.21442. PMID: 30688979; PMCID: PMC6439590.

[v] Khurshid, F., Aqil, M., Alam, M.S. et al. Monitoring of adverse drug reactions associated with antihypertensive medicines at a university teaching hospital in New Delhi. DARU J Pharm Sci 20, 34 (2012). https://doi.org/10.1186/2008-2231-20-34

[vi] ROY, Bikash et al. The study of adverse drug reactions of antihypertensive medicines in essential hypertension patients in Hi-Tech Medical College and Hospital, Bhubaneswar, Odisha, India. International Journal of Basic & Clinical Pharmacology, [S.l.], v. 8, n. 5, p. 886-891, apr. 2019. ISSN 2279-0780. https://www.ijbcp.com/index.php/ijbcp/article/view/3168

[vii] Gebreyohannes, E.A., Bhagavathula, A.S., Abebe, T.B. et al. Adverse effects and non-adherence to antihypertensive medications in University of Gondar Comprehensive Specialized Hospital. Clin Hypertens 25, 1 (2019). https://doi.org/10.1186/s40885-018-0104-6

[viii] SPRINT Research Group, Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, Reboussin DM, Rahman M, Oparil S, Lewis CE, Kimmel PL, Johnson KC, Goff DC Jr, Fine LJ, Cutler JA, Cushman WC, Cheung AK, Ambrosius WT. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 2015 Nov 26;373(22):2103-16. doi: 10.1056/NEJMoa1511939. Epub 2015 Nov 9. Erratum in: N Engl J Med. 2017 Dec 21;377(25):2506. PMID: 26551272; PMCID: PMC4689591.