Abell JG, Kivimäki M, Dugravot A, Tabak AG, Fayosse A, Shipley M, Sabia S, Singh-Manoux A. Association between systolic blood pressure and dementia in the Whitehall II cohort study: role of age, duration, and threshold used to define hypertension. Eur Heart J. 2018 Sep 1;39(33):3119-3125. PubMed.

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  1. This paper adds to the growing literature suggesting an important role of hypertension as a risk factor for dementia. This has been found in other studies, but this study confirms those other results. It also specifically addresses whether this is entirely through other cardiovascular end-organ injury (heart disease and stroke), and they do find that hypertension is still at least somewhat associated with later-life dementia risk even in people without other cardiovascular disease.

    The other important finding in this paper, which has also been supported by other studies, is that midlife or earlier life blood-pressure assessment is probably especially important in subsequent dementia risk. The size of the risk is similar to what’s been shown in other community-based studies. They find a risk with hypertension at age 50 but not ages 60 or 70. This finding, along with other studies similarly emphasizing the midlife period as a critical window during which hypertension may be especially harmful for brain outcomes, points out the importance of identifying and treating hypertension at a younger age, and not waiting for it to start causing symptoms or disease. This study doesn’t show that treatment of hypertension would reduce risk of dementia, but it supports the possible role of treating hypertension, at least in middle age if not earlier, as a possible preventive strategy.

    This paper is also very timely given the relatively new definitions of hypertension that were released last fall, which suggest that Stage 1 hypertension starts at a systolic blood pressure of 130 mm hg, due to the potential harm of having even this modestly elevated blood pressure. This matches the findings of this study, which found that elevated blood pressures of  >130 mm hg, at age 50, were associated with an increased risk of dementia.

    View all comments by Rebecca Gottesman

  2. Caution is warranted in interpreting the association between midlife hypertension and AD. Hypertension tends to exacerbate atherosclerosis and small vessel disease, and so increase the risk of vascular dementia. It may also lead to impaired clearance of Aβ. 

    However, we should bear in mind that cerebral blood flow tends to be reduced well before cognitive impairment is detectable in AD (including in familial AD, in which white-matter hypoperfusion has been demonstrated up to two decades before dementia). This early reduction in blood flow seems to be the result of increased vascular resistance rather than reduced metabolic demand.

    The findings of Warnert and colleagues suggest strongly that increased cerebral vascular resistance induces an increase in systemic blood pressure to ensure the maintenance of cerebral perfusion (Warnert et al., 2016). The process is analogous to the development of pulmonary hypertension in people with increased pulmonary vascular resistance. We have shown that cerebroventricular or cerebral infusion of Aβ induces hypertension (Tayler et al., 2017), as might be expected in response to an increase in cerebral vascular resistance.

    Midlife hypertension may, at least in some people, be a marker of the cerebral accumulation of Aβ in early AD rather than a risk factor for the disease. That is not to say that we should not treat the hypertension, as reduction in blood pressure slows the progression of vascular disease, and first-line therapies for hypertension may also address one of the mechanisms responsible for the increased cerebral vascular resistance in AD, namely elevated angiotensin II within the brain (Miners et al., 2009). 

    References:

    Miners S, Ashby E, Baig S, Harrison R, Tayler H, Speedy E, Prince JA, Love S, Kehoe PG. Angiotensin-converting enzyme levels and activity in Alzheimer's disease: differences in brain and CSF ACE and association with ACE1 genotypes. Am J Transl Res. 2009;1(2):163-77. PubMed.

    Tayler HM, Palmer JC, Thomas TL, Kehoe PG, Paton JF, Love S. Cerebral Aβ40 and systemic hypertension. J Cereb Blood Flow Metab. 2017 Jan 1;:271678X17724930. PubMed.

    Warnert EA, Rodrigues JC, Burchell AE, Neumann S, Ratcliffe LE, Manghat NE, Harris AD, Adams Z, Nightingale AK, Wise RG, Paton JF, Hart EC. Is High Blood Pressure Self-Protection for the Brain?. Circ Res. 2016 Dec 9;119(12):e140-e151. Epub 2016 Sep 26 PubMed.

    View all comments by Seth Love

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