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Delayed Decline of Cognitive Function by Antihypertensive Agents: A Cohort Study Linked with Genotype Data

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The Journal of Prevention of Alzheimer's Disease Aims and scope Submit manuscript

Abstract

Background

Arterial hypertension is among factors with the potential for increasing the risk of cognitive impairment in elderly subjects. However, studies investigating the effects of antihypertensives on cognitive function have reported mixed results.

Methods

We have used the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) to investigate the effect of each class of antihypertensives, both as single and combined, in reducing the rate of conversion from normal to mild cognitive impairment (MCI).

Results

The use of antihypertensive drugs was associated with 21% (Hazard ratio: 0.79, p<01001) delay in the rate of conversion to MCI. This effect was modulated by age, gender, and genotypic APOE4 allele. Among different antihypertensive subclasses, calcium channel blockers (CCBs) (24%, HR: 0.76, P=0.004), diuretics (21%, HR: 0.79, P=0.006), and α1-adrenergic blockers (α1-ABs) (23%, HR: 0.77, P=0.034) significantly delayed the rate of MCI conversion. A significant effect was observed with the selective L-type voltage-gated CCBs, dihydropyridines, amlodipine (47%, HR=0.53, P<0.001) and nifedipine (49%, HR=0.51, P=0.012), whereas non-DHPs showed insignificant effect. Loop diuretics, potassium sparing diuretics, and thiazides all significantly reduced the rate of MCI conversion. Combination of α1-AB and diuretics led to synergistic effects; combination of vasodilators plus β-blockers (βBs), and α1-AB plus βBs led to additive effect in delaying the rate of MCI conversion, when compared to a single drug.

Conclusion

Our results could have implications for the more effective treatment of hypertensive elderly adults who are likely to be at high risk of cognitive decline and dementia. The choice of combination of antihypertensive therapy should also consider the combination which would lead to an optimum benefit on cognitive function.

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Abbreviations

α1-AB :

α1-adrenergic blockers

AD :

Alzheimer disease

ADRC :

Alzheimer’s Disease Research Centers

ACEI :

Angiotensin-Converting Enzyme Inhibitors

ARB :

Angiotensin Receptor Blockers

βB :

β-blockers

Aβ :

β-amyloid

CCB:

Calcium Channel Blockers

CDR®:

Dementia Staging Instrument

CDR-SOB :

Clinical Dementia Rating Scale Sum of Boxes

MCI :

Mild Cognitive Impairment

MMSE :

Mini-Mental State Examination

MoCA :

Montreal Cognitive Assessment

NACC :

National Alzheimer’s Coordinating Center

NIA :

National Institute on Aging

NFT :

Neurofibrillary Tangles

UDS :

Uniform Data Set.

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Acknowledgement

The authors thank the National Alzheimer’s Coordinating Center (NACC) for provision of the Uniform Data Set, and Ms. Merilee Taylan and Mr. Zachary Miller for guidance and clarifications related to the data set. We are indebted to the study members and their families for their ongoing commitment and support of NACC research philosophy. The NACC database is funded by NIA/NIH Grant U01 AG016976. NACC data are contributed by the NIA-funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG005131 (PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD,PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD).

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Authors and Affiliations

  1. Jacobs School of Medicine and Biomedical Sciences, Stroke Center, Buffalo Medical Center, Buffalo, NY, 14203, USA

    Zohara Sternberg, R. Podolsky & D. Hojnacki

  2. Department of Biostatistics, University at Buffalo, Buffalo, NY, USA

    J. Yu & M. Tian

  3. Institute of Physiopathology, Department of Pathology, University of Buenos Aires, Buenos Aires, Argentina

    B. Schaller

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  1. Zohara Sternberg
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  2. R. Podolsky
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  4. M. Tian
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Correspondence to Zohara Sternberg.

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Conflict of interest: ZS, RP, JY, MT, DH, BS have no conflict of interest to report.

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Sternberg, Z., Podolsky, R., Yu, J. et al. Delayed Decline of Cognitive Function by Antihypertensive Agents: A Cohort Study Linked with Genotype Data. J Prev Alzheimers Dis 9, 679–691 (2022). https://doi.org/10.14283/jpad.2022.73

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