Associations of Blood Pressure with Functional and Cognitive Changes in Patients with Alzheimer's Disease

Abstract

Background: Midlife hypertension followed by late life hypotension resulting from neurodegeneration increases amyloidogenesis and tauopathy. Methods: Consecutive outpatients with late-onset Alzheimer's disease (AD) at various stages and their respective caregivers were assessed for score variations in 1 year of tests assessing caregiver burden, functionality and cognition according to blood pressure (BP) variations and APOE haplotypes, while also taking into account differential effects of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, calcium channel blockers, diuretics, or no antihypertensive medication on score changes. The diagnosis and treatment of arterial hypertension followed the JNC 7 report. Results: Variations in systolic BP (-11.76 ± 17.1 mm Hg), diastolic BP (-4.92 ± 10.3 mm Hg) and pulse pressure (-6.84 ± 12.6 mm Hg) were significant after 1 year (n = 191; ρ < 0.01). For APOE4+ carriers, rises in systolic or diastolic BP improved Clinical Dementia Rating Scale Sum of Boxes scores (ρ < 0.04), with marginally significant improvements in Mini-Mental State Examination scores resulting from risen systolic (ρ = 0.069) or diastolic BP (ρ = 0.079), and in basic independence only regarding risen diastolic BP (ρ = 0.055). APOE4- carriers resisted any functional or cognitive effects of BP variations. No differences were found regarding any antihypertensive class for variations in BP or any test scores, regardless of APOE haplotypes. Conclusions: Targeting mild BP elevations brings better functional and cognitive results for APOE4+ carriers with AD.

The association of multiple anti-hypertensive medication classes with Alzheimer’s disease incidence across sex, race, and ethnicity

“…Why RAS AHTs may provide benefit in AD, compared to other AHTs, is potentially driven by a combination of genetic, pre-clinical, epidemiological, and a limited number of directly relevant clinical factors [ 18 , 42 , 43 ]. Multiple components of the RAS are associated with changes to amyloid-beta (Aβ) and tau levels in both pre-clinical models as well as human post-mortem studies [ 18 , 24 , 44 – 46 ].…”

Associations of Pulse and Blood Pressure with Hippocampal Volume by APOE and Cognitive Phenotype: The Alzheimer’s Disease Neuroimaging Initiative (ADNI)

“…Interestingly, age-related arterial stiffening measured by brachial artery pulse pressure (PPR) has been linked to cerebral atrophy and cognitive deterioration [17]. While both systolic (SBP) and diastolic (DBP) blood pressure increase with age up to around the 6th decade in life [18], subsequent decreases in DBP alone result in widening of PPR [8]. Because increasing PPR can further endorse widespread atherosclerosis and increased arterial stiffness implicated in neurodegeneration, it may also influence brain volume in regions of interest.…”

Synergism of antihypertensives and cholinesterase inhibitors in Alzheimer's disease

“…Second, we did not measure the blood pressure levels, which might have been an intermediate factor for the effect of aHTN drugs on cognitive decline. Although some studies reported that high blood pressure is a contributing factor to cognitive decline [98] , [99] , other studies also reported a U-shaped relationship between blood pressure and cognitive impairment [100] , [101] , suggesting that mildly elevated blood pressure may be beneficial in patients with AD, particularly in APOE ε4 carriers [35] . Without blood pressure measurements, our study does not reveal the role of blood pressure in the therapeutic effect of aHTN medications on cognitive decline.…”

“…Moreover, our study is the first to discover an optimal combination of different aHTN drug classes on the cognitive decline in AD patients with hypertension. According to a recent review article on the protective effect of aHTN medications against AD and cognitive decline [30], most studies have supported a preference for RAAS inhibitors [31–33] and CCBs [15,34] in protecting against cognitive decline, whereas some studies also reported no difference among the aHTN classes [35]. It is worth noting that although many studies also involved patients under combinations of aHTN drug classes, most of them tested the effect of different drug classes separately [16,17].…”