In healthcare, managing hypertension in the elderly relies on antihypertensive medication therapy to mitigate cardiovascular risks.

However, recent studies suggest a potential link between this disease, it’s medications and dementia risk, prompting a reevaluation of their use.

This highlights the importance of balancing blood pressure management benefits with cognitive function risks, urging further exploration into this intricate relationship.

Actually, the majority of cross-sectional research conducted on elderly individuals indicate that either low blood pressure or high dementia prevalence are connected to hypertension.

Introduction

A gradual deterioration in cognitive abilities that impacts memory, language, problem-solving, and decision-making is known as dementia.

Dementia is primarily brought on by high blood pressure, especially in middle age.

The development of dementia and hypertension are both influenced by a number of circumstances, making the relationship between the two disorders complicated.

With the possible hazards and advantages of antihypertensive medication therapy, managing hypertension in the aged population presents special issues.

As important as blood pressure management is in lowering cardiovascular morbidity and death, there is growing worry over a potential link between antihypertensive medication use and dementia risk.

Epidemiological Evidence

The connection between midlife blood pressure elevation and subsequent cognitive decline is well-established and widely accepted.

However, the impact of blood pressure on cognitive function varies with age.

Some studies in the elderly population indicate that episodes of hypotension or excessive blood pressure reduction may contribute to or exacerbate cognitive decline.

The relationship between older persons' risk of dementia and antihypertensive medication has been the subject of numerous epidemiological research, with varying degrees of success.

While some research indicates that antihypertensive drugs may protect against dementia, other studies point to a higher risk being connected to specific drug types.

Chronic hypertension associates with higher dementia risk. Anti-hypertensive therapy may mitigate this risk, as shown in some studies.

All age groups, including the extremely old (≥85 years), showed an inverse risk for dementia or Alzheimer's disease when taking antihypertensive medications; however, the reduction in dementia risk was less evident in patients ≥85 years old than in those 65-74 years old.

A nested case-control study was conducted in Lombardy, Italy, involving a cohort of 215,547 patients aged ≥65 years who initiated antihypertensive medication between 2009 and 2012.

The cases comprised 13,812 patients who developed dementia or Alzheimer’s disease during follow-up until 2019.

The relationship between hypertension and cognitive function is complex. While hypertension is linked to cognitive decline and dementia, its impact varies across age groups.

High blood pressure in midlife increases the risk of cognitive impairment later on, but the association is less clear in older adults. Executive function, attention, and motor speed are most affected, particularly by subcortical diseases.

During the study period, researchers recorded 99,384 cases of all-cause dementia.

When comparing the incidence rate ratio (IRR) of dementia in individuals using Proton Pump Inhibitors versus those who never used them.

IRRs were 1.36 for ages 60–69, 1.12 for ages 70–79, 1.06 for ages 80–89, and 1.03 for ages 90 and older.

These findings suggest that in patients with cerebrovascular illness, perindopril either prevented or slowed the development of white matter hyperintensities.

Chronic infusion of angiotensin II at hypertensive levels in mice led to cognitive deficits and increased anxiety compared to controls.

These effects were observed after 3 weeks of infusion, highlighting a link between angiotensin II, cognitive dysfunction, and sustained high blood pressure.

Low serum potassium levels in midlife, but not in late life, are linked to reduced cerebrospinal fluid Abeta42 levels in late life.

It is plausible that potassium correlates with another factor associated with cerebrospinal fluid Abeta42.

Longer treatment durations were associated with higher IRRs. Notably, individuals under 90 years old showed increased dementia rates, regardless of treatment initiation, up to >15 years before diagnosis.

854 men developed cognitive impairment during a 5.8-year follow-up. β-Blocker use alone at baseline was consistently associated with a lower risk of cognitive impairment, compared to non-users, after adjusting for multiple factors.

Other antihypertensive medications showed no significant association. Results remained consistent after excluding those with cardiovascular disease or <1 year follow-up, and adjusting for additional factors.

When comparing the usage of angiotensin II receptor blockers to other antihypertensive medicines, a meta-analysis of comparator trials revealed evidence of a lower incidence of Alzheimer's disease and dementia.

The results of a study revealed that a significant blood pressure fluctuation over several years was linked to a heightened long-term risk of dementia.

This association was particularly notable when the variation occurred well before the dementia diagnosis. Both substantial increases and decreases in blood pressure were associated with an elevated long-term risk of dementia.

Potential Mechanisms

There are a number of plausible explanations for the link between hypertension antihypertensive medication, and dementia risk.

These include disturbance of cerebral autoregulation, neurovascular dysfunction, and hypotension-induced cerebral hypoperfusion.

Furthermore, antihypertensive drugs' effects on amyloid-beta metabolism, cerebral blood flow, and neuroinflammation may influence an older person's risk of dementia.

Brain artery rupture, or hemorrhagic stroke, can lead to brain cell death and subsequent vascular dementia, while small vessel disease may result in subcortical vascular dementia.

These conditions, often asymptomatic initially, can cause cognitive decline over time due to microbleed accumulation and brain changes.

High or low blood pressure can contribute to brain atrophy, impacting cognitive function, although further research is needed to fully understand this relationship.

Symptoms of brain shrinkage include reasoning difficulties, memory loss, and communication challenges, often associated with dementia such as frontotemporal dementia.

Clinical Implications

Both early cerebrovascular brain aging and cognitive decline are influenced by hypertension. A higher chance of cognitive impairment is associated with hypertension, according to subclinical brain injury.

The association between dementia and hypertension is well-established; nevertheless, it is unclear how managing other risk factors and using antihypertensive medication would affect cognitive function.

Controlling blood pressure will advance our understanding of both hypertension-related dementia and cerebrovascular illness.

For healthcare professionals who treat hypertension in older persons, knowing the link between antihypertensive medication and dementia risk has important therapeutic ramifications.

Careful assessment of each patient's unique characteristics, comorbidities, and drug regimens is necessary to strike a balance between the potential hazards to cognitive function and the benefits of blood pressure control.

For older persons at risk of dementia, clinicians must use the information from observational data, clinical trials, and epidemiological research when deciding which antihypertensive therapy techniques to use.

Further research is necessary to clarify the intricate relationship between antihypertensive drug therapy and dementia risk in older adults.

Prospective cohort studies, randomized controlled trials, and mechanistic investigations are crucial for understanding underlying mechanisms, identifying potential risk factors, and developing targeted interventions to alleviate cognitive decline associated with hypertension treatment.

In Summary

The link between antihypertensive therapy and dementia risk in older adults is complex and evolving.

While controlling blood pressure is vital for cardiovascular health, concerns exist about cognitive effects of these medications.

This review emphasizes understanding this association to inform geriatric care decisions.