Hypertensive and cognitive function: did we come to a dead end?

The relationship between arterial hypertension and a decline in cognitive function has been investigated for decades with very conflicting results. The main question about this relationship

has not yet been answered. The available data are incomparable, as populations included in these studies are heterogeneous in regard to demographic characteristics, blood pressure (BP)

levels, and antihypertensive treatment (the latter is neglected in many circumstances); furthermore, concomitant diseases are often not considered, and tests used for the evaluation of

cognitive function in published studies are not the same. These are the reasons for the controversial findings despite an obvious effort to answer this question. In the current issue of the

Journal, Moll et al. provided the results from the Wisconsin Longitudinal Study that followed 4314 participants who graduated high school from 1957 to 2011 [1]. The authors evaluated

cognitive, demographic, and health data from 2003 to 2005 and 2011 and reported that self-reported hypertension was related to minimal to no cognitive effects in older adults. Adjustment for

cardiovascular risk factors removed all associations between self-reported hypertension and cognition in the investigated population [1]. The authors separated patients with diabetes and

hypertension and reported that both groups of patients did not show deterioration during follow-up (2003–2005 vs. 2011), but cognitive function slightly improved in participants without

these conditions (diabetes and hypertension) [1]. The relationship between hypertension duration and cognitive performance and decline was not demonstrated in this study. There are several

important points that should be addressed to fully understand the reported findings. One of the most relevant topics is the assessment of cognitive function in the observed population. There

is a lack of a standard score for this kind of evaluation in patients with hypertension or diabetes. Most cardiologists are familiar with the Mini-Mental State Test, but it seems that it

cannot show small differences in cognitive function, as some other tests can [2]. The investigators in the Wisconsin Longitudinal Study evaluated cognitive function using Letter and Category

Fluency, Digit Ordering, Similarities, and Immediate and Delayed Recall, which is not used often in studies that research cognitive dysfunction in hypertensive patients. Some other studies

used similar scores but obtained different results [3]. In the ELSA, investigators reported that both younger and older age of hypertension, but not duration of hypertension, were related to

cognitive decline in different abilities, even though participants were significantly younger (58.9 ± 5.9 years) [3]. However, the ELSA study included a multiethnic population, and only

approximately half of participants were white, which is not the case with the Wisconsin Longitudinal Study, which included only a white population [1]. The large Women’s Health Initiative

Memory study that included 7207 women aged 65–79 years who were followed for at least 10 years used the Telephone Interview for Cognitive Status-modified and other tests of memory, language,

executive function, and working memory and reported a significant relationship between hypertension and elevated systolic (BP) and pulsed pressure and risk of mild cognitive impairment [4].

Elevated BP was significantly related to an elevated risk of mild cognitive impairment and cognitive loss, but hypertensive patients with strictly controlled BP (SBP < 120 mmHg) did not

have a significantly increased risk of mild cognitive impairment (HR 1.33, 95% CI: 0.98–1.82, _p_ = 0.071) or cognitive loss (1.09, (95% CI: 0.82–1.44, _p_ = 0.57) in comparison with

normotensive individuals [4]. The cumulative data from the ELSA and Health and Retirement Study that used the same tests for the evaluation of cognitive function included almost 17,000

participants with a median age of 62 and 65 years, respectively, during a median follow-up of 8 years and found that long-term cumulative BP was related to subsequent cognitive decline,

dementia risk, and all-cause mortality in cognitively healthy adults aged >50 years [5]. The authors adjusted the models for a large number of demographic and clinical characteristics,

including comorbidities and therapy. A recently published systematic review found that hypertensive patients had worse performance in processing speed, working memory in short-term memory

and learning and delayed recall [6]. The SPRINT trial provided many answers (and raised even more questions), and one post hoc analysis revealed that intensive BP control significantly

reduced the risk of mild cognitive impairment and the combined rate of mild cognitive impairment or probable dementia [7]. However, there was no significant reduction in the risk of probable

dementia between patients treated to a systolic BP goal of <120 mmHg and those with a goal of <140 mmHg. The authors of the current study claimed that while the relationship between

mid-life hypertension and late-life cognitive decline has been consistently demonstrated, associations between late-life hypertension and cognitive performance have been less consistent, and

clarifying this was the main aim of their study [1]. However, the mean age of patients in other studies is very similar to that in this study, and investigators showed a relationship

between hypertension and cognitive decline [2,3,4]. There are several potential reasons for this. First, self-reported hypertension is not an accurate method for the assessment of

hypertension. Second, the lack of BP values in the current study does not allow for an analysis of the relationship between BP levels and cognitive decline. It is not the same if a patient

has borderline or mild or severe hypertension. Third, lack of information about therapy and success of this therapy is a major limitation, as it is possible that hypertensive patients in

this study were well controlled with normal BP values, and this could explain the lack of association of hypertension with cognitive impairment in this setting. Finally, the investigators

also reported that the association between hypertension and cognitive decline vanished after adjustment for hypertension duration, diabetes, cardiovascular disease, hypercholesterolemia, and

smoking. However, other authors included even more covariables and still demonstrated a significant relationship [2,3,4]. The authors of the Wisconsin Longitudinal Study separated

hypertensive from diabetic patients and reported that cognitive decline was not found in these patients (either group separately) over follow-up, whereas patients without these conditions

showed improvement during follow-up [1]. However, it was not clarified by the authors how cognitive function in patients without hypertension and diabetes during follow-up improved in their

late life in the absence of some stimulating exercise for cognitive function. Some previous studies suggested that diabetes can be one of the main influencing factors of cognitive

dysfunction in hypertensive patients [8], but this was not reported in the current investigation. The Bayesian analytic approach used in the current study is challenging for clinicians who

are used to _p_ values or odds/hazard ratios. The authors claimed that this approach added further precision for detecting the obvious presence or absence of group differences and

quantifying the magnitudes of the associations between hypertension and cognition. However, this also significantly complicates the understanding of their results for average clinicians who

are the main readers of this kind of article. Despite its limitations, this study showed that there are still many questions that remain to be answered in the future. This showed that the

relationship between hypertension and cognitive decline is not straightforward, as we thought. However, before we even start answering these questions, we should agree about tools that will

be used for evaluation of cognitive function, as it seems to be the main obstacle. Other limitations, such as establishing a diagnosis of hypertension, BP level, important clinical

parameters (primarily comorbidities), concomitant therapy and other covariates, may be easily overcome with well-planned longitudinal studies. REFERENCES * Moll AC, Woodard JL. Hypertension

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FUNDING Open Access funding enabled and organized by Projekt DEAL. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Klinik für Innere Medizin II, Universitätsklinikum Ulm, Albert-Einstein Allee

23, 89081, Ulm, Germany Marijana Tadic * Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy Cesare Cuspidi Authors * Marijana Tadic View author publications You

can also search for this author inPubMed Google Scholar * Cesare Cuspidi View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR

Correspondence to Marijana Tadic. ETHICS DECLARATIONS CONFLICT OF INTEREST The authors declare no competing interests. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral

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http://creativecommons.org/licenses/by/4.0/. Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Tadic, M., Cuspidi, C. Hypertensive and cognitive function: did we come to a dead

end?. _Hypertens Res_ 45, 1667–1669 (2022). https://doi.org/10.1038/s41440-022-00983-4 Download citation * Received: 27 May 2022 * Accepted: 23 June 2022 * Published: 22 July 2022 * Issue

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function * late-life