Cross-Sectional and Longitudinal Association Between Antihypertensive Medications and Cognitive Impairment in an Elderly Population

Hajjar, Ihab; Catoe, Heath W.; Sixta, Sherry; Boland, Rebecca; Johnson, Dale A.; Hirth, Victor; Wieland, Darryl; Eleazer, Paul D.

doi:10.1093/gerona/60.1.67

Cited by 81 publications

(59 citation statements)

References 36 publications

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“…This is consistent with clinical findings of lower dementia risk in subjects with persistent elevated BP, despite antihypertensive treatments. 19,29 Furthermore, these results, consistent with the Honolulu Asia Aging Study (HAAS) and Rotterdam findings, 13,14 provide a neuropathologic basis to support the clinical 18,20 and population studies 4,[15][16][17]19 that found significant reductions in dementia and AD risk in persons treated with antihypertensive medications. Antiamyloidogenic and neuroprotective effects of the antihypertensive drug valsartan were reported in the Tg2576 AD mouse model, even at a dose corresponding to half the lowest recommended dose for HTN treatment in humans, 33 providing evidence that at least some antihypertensive medications can directly affect biologic processes involved in AD.…”

Section: Resultssupporting

confidence: 58%

“…Antihypertensive treatments have been associated with lower incidence of clinically diagnosed AD and better cognitive function [15][16][17] ; similarly, treatment of hypertensive subjects was associated with lower dementia risk. [18][19][20] However, the specific classes of anti-HTN medication Editorial,…”

Section: Discussionmentioning

confidence: 99%

“…4,[10][11][12] Elevated midlife SBP was associated with lower brain weight and increased neuritic plaque (NP) densities in neocortex and hippocampus (Hipp), and elevated DBP was associated with increased NFT densities in Hipp. 13 Additionally, elevated midlife SBP and DBP 14 were correlated with late-life hippocampal atrophy on MRI in untreated patients clinically diagnosed with AD.Antihypertensive treatments have been associated with lower incidence of clinically diagnosed AD and better cognitive function [15][16][17] ; similarly, treatment of hypertensive subjects was associated with lower dementia risk. [18][19][20] However, the specific classes of anti-HTN medication Editorial,…”

mentioning

confidence: 96%

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Less Alzheimer disease neuropathology in medicated hypertensive than nonhypertensive persons

Hoffman

Schmeidler²,

Lesser³

et al. 2009

Neurology

138

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Objective:To test the hypothesis that use of antihypertensive medication is associated with lower Alzheimer disease (AD) neuropathology. Methods:This was a postmortem study of 291 brains limited to those with normal neuropathology or with uncomplicated AD neuropathology (i.e., without other dementia-associated neuropathology) in persons with or without hypertension (HTN) who were and were not treated with antihypertensive medications. Neuritic plaque (NP) and neurofibrillary tangle (NFT) densities, quantified in selected brain regions according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropathologic criteria, with additional cortical NP counts, yielded 24 neuropathologic regional measures or summaries. Medicated hypertension (HTN-med; n ϭ 77), nonmedicated HTN (HTN-nomed; n ϭ 42), and non-HTN (no-HTN; n ϭ 172) groups were compared by analyses of variance. Results:The HTN-med group had significantly less neuropathology than the no-HTN group. The no-HTN group averaged over 50% higher mean NP and NFT ratings, and double the mean NP count, of the HTN-med group. The HTN-nomed group had significantly more neuropathology than the HTN-med group, but not significantly less than the no-HTN group. Conclusions:There was substantially less Alzheimer disease (AD) neuropathology in the medicated hypertension group than the nonhypertensive group, which may reflect a salutary effect of antihypertensive medication against AD-associated neuropathology. Neurology ® 2009;72:1720-1726 GLOSSARY AD ϭ Alzheimer disease; ANCOVA ϭ analysis of covariance; ANOVA ϭ analysis of variance; BB ϭ ␤-blockers; BMI ϭ body mass index; CCB ϭ calcium channel blockers; CDR ϭ Clinical Dementia Rating scale; CERAD ϭ Consortium to Establish a Registry for Alzheimer's Disease; DBP ϭ diastolic blood pressure; EC ϭ entorhinal cortex; HAAS ϭ Honolulu Asia Aging Study; Hipp ϭ hippocampus; HTN ϭ hypertension; IPL ϭ inferior parietal lobule; JHH ϭ Jewish Home and Hospital; MFG ϭ midfrontal gyrus; MSSM ϭ Mount Sinai School of Medicine; NFT ϭ neurofibrillary tangle; NH ϭ nursing homes; NP ϭ neuritic plaque; OC ϭ occipital calcarine cortex; OFG ϭ orbital frontal cortex; SBP ϭ systolic blood pressure; STG ϭ superior temporal gyrus.Hypertension has been associated with cognitive decline, dementia, vascular dementia, and Alzheimer disease (AD) in some studies 1-5 but not others. 6-9 Elevated systolic blood pressure (SBP) or diastolic blood pressure (DBP) levels, or both, have been reported decades before onset of AD symptoms. 4,[10][11][12] Elevated midlife SBP was associated with lower brain weight and increased neuritic plaque (NP) densities in neocortex and hippocampus (Hipp), and elevated DBP was associated with increased NFT densities in Hipp. 13 Additionally, elevated midlife SBP and DBP 14 were correlated with late-life hippocampal atrophy on MRI in untreated patients clinically diagnosed with AD.Antihypertensive treatments have been associated with lower incidence of clinically diagnosed AD and better cognitive functio...

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Section: Resultssupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 96%

See 1 more Smart Citation

Less Alzheimer disease neuropathology in medicated hypertensive than nonhypertensive persons

Hoffman

Schmeidler²,

Lesser³

et al. 2009

Neurology

138

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“…18 In a retrospective analysis, lower rates of cognitive decline were observed with diuretic, ACE inhibitor, and BB use in the elderly, and improved cognition was seen with angiotensin receptor blockers (ARB). 17 Another retrospective, casecontrol study showed decreased odds of dementia with BB use during the preceding 3 years. 19 However, a small, 6-year follow-up study suggested worse cognitive decline among those with BB and ACE inhibitor use, and improved cognition with calcium channel blocker use in the elderly.…”

Section: Resultsmentioning

confidence: 99%

“…Limited data from observational studies suggest that BB use may slow cognitive decline 17,18 and possibly prevent dementia, 19 while others have found divergent results. 20 The current study examines the association between antihypertensive drug class and the risk of cognitive impairment in a large prospective cohort of elderly Japanese American men.…”

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confidence: 99%

Antihypertensive medication use and risk of cognitive impairment

et al. 2013

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Objective: To determine the associations between classes of antihypertensive medication use and the risk of cognitive impairment among elderly hypertensive men. Methods:The Honolulu-Asia Aging Study is a prospective, community-based cohort study of Japanese American men conducted in Honolulu, Hawaii. We examined 2,197 participants (mean age 77 years at cohort entry, 1991-1993, followed through September 2010) with hypertension and without dementia or cognitive impairment at baseline, who provided information on medication use. Cognitive function was assessed at 7 standardized examinations using the Cognitive Abilities Screening Instrument (CASI). Cognitive impairment was defined as a CASI score ,74.Results: A total of 854 men developed cognitive impairment (median follow-up, 5.8 years).b-Blocker use as the sole antihypertensive drug at baseline was consistently associated with a lower risk of cognitive impairment (incidence rate ratio [IRR] 0.69; 95% confidence interval [CI] 0.50-0.94), as compared with men not taking any antihypertensive medications, adjusting for multiple potential confounders. The use of diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors, or vasodilators alone was not significantly associated with cognitive impairment. Results were similar excluding those with cardiovascular disease or ,1 year of follow-up, and additionally adjusting for pulse pressure, heart rate, baseline and midlife systolic blood pressure, and midlife antihypertensive treatment (IRR 0.65; 95% CI 0.45-0.94). The association between b-blocker use and cognitive impairment was stronger among men with diabetes, men aged .75 years, and those with pulse pressure $70 mm Hg.Conclusions: b-blocker use is associated with a lower risk of developing cognitive impairment in elderly Japanese American men. Neurology â 2013;81:888-895 GLOSSARY ACE 5 angiotensin-converting enzyme; ARB 5 angiotensin receptor blocker; BB 5 b-blockers; BMI 5 body mass index; CASI 5 Cognitive Abilities Screening Instrument; CI 5 confidence interval; CVD 5 cardiovascular disease; DBP 5 diastolic blood pressure; HAAS 5 Honolulu-Asia Aging Study; HHP 5 Honolulu Heart Program; HR 5 heart rate; IRR 5 incidence rate ratio; LRT 5 likelihood ratio test; PP 5 pulse pressure; SBP 5 systolic blood pressure.Current treatments for dementia provide limited clinical benefit, 1 highlighting the need for preventive approaches to stem the epidemic estimated to affect more than 115 million people worldwide by 2050. 2 Hypertension, particularly elevated systolic blood pressure (SBP), has been associated with the development of cognitive impairment and dementia in late life, 3-8 as well as the neuropathologic lesions of dementia at autopsy. 6,9,10 Previous analyses from the HonoluluAsia Aging Study (HAAS) have estimated that 27% of dementia cases may be attributed to midlife SBP $120 mm Hg among inadequately treated men. 11 The effects of antihypertensive drug class in late life to prevent cognitive impairment, however, remain unclear. Data from ...

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Current awareness in geriatric psychiatry

2005

Int. J. Geriat. Psychiatry

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Cross-Sectional and Longitudinal Association Between Antihypertensive Medications and Cognitive Impairment in an Elderly Population

Cited by 81 publications

References 36 publications

Less Alzheimer disease neuropathology in medicated hypertensive than nonhypertensive persons

Less Alzheimer disease neuropathology in medicated hypertensive than nonhypertensive persons

Antihypertensive medication use and risk of cognitive impairment

Current awareness in geriatric psychiatry

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