Challenges Remain in Understanding Role of Hypertension in Cognition

Hypertension is associated with cognitive impairment, but there is not enough data to support evidence-based clinical recommendations, according to a scientific statement from the American Heart Association (AHA).¹

Cerebrovascular factors, including chronic arterial hypertension, have been pinpointed as significant risk factors for dementia^2,3; however the data, much of which is observational, has failed to elucidate the link between treatment of hypertension and cognitive health.

In an effort to better understand this link, several representatives from a multidisciplinary group of specialists in cardiology and neurology conducted a literature review to evaluate what is known about the connection between hypertension and cognitive impairment, what is not known, and what, if any, guidance can be provided for health care professionals.

In reviewing research pertaining to the impact of hypertension on cerebrovascular structure and function, the committee concluded that evidence suggests an interaction between hypertension and Alzheimer’s disease pathology in which hypertension exacerbates the accumulation of beta-amyloid plaques in the brain and may disrupt regulatory processes.

”Although it remains to be established whether the deleterious effects of hypertension on cognition are reversible or lessened by treatment, experimental evidence suggests that some vascular changes induced by hypertension may be reversible with appropriate treatments,” they wrote.

Evidence regarding the effect of late-life hypertension on cognitive health is inconclusive; however several studies suggest that treatment of hypertension from midlife to late life may help to decrease the risk of late-life cognitive impairment.^4,5 The authors noted that research in this area is particularly plagued by methodological issues, as cognitive function assessment is not standardized and consideration of confounding factors, including age, sex, and cardiovascular risk factors is not consistent.

Data on the impact of demographic and genetic factors is limited and not well understood; however factors including menopausal status, insulin resistance, inflammation, and APOE ε4 status have all been linked to cognitive decline in people with hypertension.

Research focused specifically on the pathological and epidemiological link between hypertension and Alzheimer’s disease has been limited due to the lag time between onset of hypertension and pathological diagnosis of Alzheimer’s. The authors noted that advances in PET and structural MRI will allow for more complete analysis of brain pathology in vivo, and that larger population-based and longitudinal studies will be needed to assess the impact of structural changes on risk over time.

Results from clinical trials have shown a benefit for lowering blood pressure, but many trials have been plagued by possible bias and errors in quality control protocols. “Direct evidence from randomized, clinical trials does not allow conclusive recommendations about treating hypertension throughout the life span to protect cognition,” the authors wrote. One ongoing trial, SPRINT-MIND (Systolic Blood Pressure Intervention Trial – Memory and Cognition in Decreased Hypertension), should make available extensive data on brain health and its link to blood pressure and cardiovascular events.⁶

“The evidence to date points strongly to a deleterious influence of midlife hypertension on cognitive function in midlife and late life,” the authors concluded. “Executive function and processing speed seem to be the cognitive domains most affected, but memory can also be impaired.”

As certain data have suggested that higher blood pressure in late-life is linked to better cognition, the authors noted that a recommendation for a uniform level of blood pressure across the life span is challenging, and future recommendations may need to be more fluid and personalized.

Ultimately, hypertension may be one of the strongest modifiable risk factors for cognitive impairment, given its prevalence and availability of effective treatments. Yet, there are many questions that remain regarding the risk-benefit of early, late, and long-term treatment of hypertension across the life span.

“Despite numerous outstanding questions and caveats, personalized treatment of hypertension, taking into account age, sex, APOE genotype, metabolic traits, comorbidities, etc, remains a most promising and eminently feasible approach to safeguard vascular health and, as a consequence, brain heath,” the authors concluded.

Disclosures: Dr Knopman reports grant support from Lilly, TauRx, and Biogen, and has served as a consultant or advisory board member for Lundbeck Pharmaceuticals and DIAN TU.

References

1. Iadecola C, Yaffe K, Biller J, et al; on behalf of the American Heart Association Council on Hypertension; Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young, Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; Stroke Council. Impact of hypertension on cognitive function: A scientific statement from the American Heart Association. Hypertension. 2016; doi: 10.1161/HYP.0000000000000053.

2. Gorelick PB, Scuteri A, Black SE, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42:2672-2713.

3. Gąsecki D, Kwarciany M, Nyka W, Narkiewicz K. Hypertension, brain damage and cognitive decline. Curr Hypertens Rep. 2013;15:547-558.

4. Gottesman RF, Schneider AL, Albert M, et al. Midlife hypertension and 20-year cognitive change: the Atherosclerosis Risk in Communities neurocognitive study. JAMA Neurol. 2014;71:1218-1227.

5. Köhler S, Baars MA, Spauwen P, Schievink S, Verhey FR, van Boxtel MJ. Temporal evolution of cognitive changes in incident hypertension: prospective cohort study across the adult age span. Hypertension. 2014;63:245-251.

6. ClinicalTrials.gov. Systolic Blood Pressure Intervention Trial (SPRINT). NCT01206062. https://clinicaltrials.gov/ct/show/NCT01206062. Accessed October 13, 2016.