Dataset Information

Antihypertensive Use and the Risk of Alzheimer's Disease and Related Dementias among Older Adults in the USA.

ABSTRACT:

Background

Epidemiological evidence on different classes of antihypertensives and risks of Alzheimer's disease and related dementias (ADRD) is inconclusive and limited. This study examined the association between antihypertensive use (including therapy type and antihypertensive class) and ADRD diagnoses among older adults with hypertension.

Methods

A retrospective, cross-sectional study was conducted, involving 539 individuals aged ≥ 65 years who used antihypertensives and had ADRD diagnosis selected from 2013 to 2018 Medical Expenditure Panel Survey (MEPS) data. The predictors were therapy type (monotherapy or polytherapy) and class of antihypertensives defined using Multum Lexicon therapeutic classification (with calcium channel blockers [CCBs] as the reference group). Weighted logistic regression was used to assess the relationships of therapy type and class of antihypertensives use with ADRD diagnosis, adjusting for sociodemographic characteristics and health status.

Results

We found no significant difference between monotherapy and polytherapy on the odds of ADRD diagnosis. As to monotherapy, those who used angiotensin-converting enzyme inhibitors (ACEIs) had significantly lower odds of developing AD compared to those who used CCBs (OR 0.36, 95 % CI 0.13-0.99).

Conclusions

Findings of the study suggest the need for evidence-based drug therapy to manage hypertension in later adulthood and warrant further investigation into the mechanism underlying the protective effect of antihypertensives, particularly ACEIs, against the development of AD among older adults with hypertension.

SUBMITTER: Pan X

PROVIDER: S-EPMC9851394 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Antihypertensive Use and the Risk of Alzheimer's Disease and Related Dementias among Older Adults in the USA.

Pan Xi X Zhang Donglan D Heo Ji Haeng JH Park Chanhyun C Li Gang G Dengler-Crish Christine M CM Li Yan Y Gu Yian Y Young Henry N HN Lavender Devin L DL Shi Lu L

Drugs & aging 20221017 11

<h4>Background</h4>Epidemiological evidence on different classes of antihypertensives and risks of Alzheimer's disease and related dementias (ADRD) is inconclusive and limited. This study examined the association between antihypertensive use (including therapy type and antihypertensive class) and ADRD diagnoses among older adults with hypertension.<h4>Methods</h4>A retrospective, cross-sectional study was conducted, involving 539 individuals aged ≥ 65 years who used antihypertensives and had ADR ...[more]

PMID: 36251143

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Project description:IntroductionThe aim of the study was to assess factors associated with the perceived risk of developing Alzheimer's disease and related dementias (ADRD) and how the perceived risk of ADRD was related to cognitive function.MethodsWe conducted a retrospective cohort study using 5 waves of data from the Health and Retirement Study (2012-2022) that included adults aged 65 years or older with no previous diagnosis of ADRD at baseline. Cognitive function was measured at baseline and over time using a summary score that included immediate/delayed word recall, serial 7's test, objective naming test, backwards counting, recall of the current date, and naming the president/vice-president (range = 0-35). Perceived risk of developing ADRD was categorized at baseline as "definitely not" (0% probability), "unlikely" (1-49%), "uncertain" (50%), and "more than likely" (>50-100%). Additional baseline measures included participants' sociodemographic background, psychosocial resources, health behaviors, physiological status, and healthcare utilization.ResultsOf 1457 respondents (median age 74 [IQR = 69-80] and 59.8% women), individuals who perceived that they were "more than likely" to develop ADRD had more depressive symptoms and were more likely to be hospitalized in the past two years than individuals who indicated that it was "unlikely" they would develop ADRD. Alternatively, respondnets who perceived that they would "definitely not" develop ADRD were more likely to be non-Hispanic Black, less educated, and have lower income than individuals who indicated it was "unlikely" they would develop ADRD. Respondents who reported their risks of developing ADRD as "more than likely" (β = -2.10, P < 0.001) and "definitely not" (β = -1.50, P < 0.001) had the lowest levels of cognitive function; and the associations were explained in part by their socioeconomic, psychosocial, and health status.ConclusionsPerceived risk of developing ADRD is associated with cognitive function. The (dis)concordance between individuals' perceived risk of ADRD and their cognitive function has important implications for increasing public awareness and developing interventions to prevent ADRD.

Project description:Currently, more than 55 million people around the world suffer from dementia, and Alzheimer's disease-related dementia (ADRD) accounts for nearly 60-70% of all those cases. The spread of AD pathology and progressive neurodegeneration in the hippocampus and cerebral cortex is strongly correlated with cognitive decline in AD patients; however, the molecular underpinning of the ADRD causality is still unclear. Studies of postmortem AD brains and animal models of AD suggest that elevated endoplasmic reticulum (ER) stress may have a role in ADRD pathology through altered neurocellular homeostasis in brain regions associated with learning and memory. To study the ER stress-associated neurocellular response and its effects on neurocellular homeostasis and neurogenesis, we modeled an ER stress challenge using Thapsigargin (TG), a specific inhibitor of sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), in induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) of two individuals from our Mexican American Family Study (MAFS). High-content screening and transcriptomic analysis of the control and ER stress-challenged NSCs showed that NSC’s ER stress response resulted in a significant decline in NSC self-renewal and an increase in apoptosis and cellular oxidative stress. A total of 2300 genes were significantly (moderated t statistics FDR corrected p-value ≤ 0.05 and Fold Change absolute ≥ 2.0) differentially expressed (DE). Pathway enrichment and gene network analysis of DE genes suggests that all three unfolded protein response (UPR) pathways (PERK, IRE1, and ATF6) were significantly activated and cooperatively regulated the NSC’s transcriptional response to ER stress. Our results show that IRE1/XBP1 mediated transcriptional regulation of E2F1 and its downstream targets have a dominant role in inducing G1/S-phase cell cycle arrest in the ER stress-challenged NSCs. The ER stress-challenged NSCs also showed activation of CHOP-mediated apoptosis and dysregulation of synaptic plasticity and neurotransmitter homeostasis-associated genes. Overall, our results suggest that ER stress-associated attenuation of NSC self-renewal, increased apoptosis, and dysregulated synaptic plasticity and neurotransmitter homeostasis plausibly play a role in the causation of ADRD.

Project description:IntroductionPlasma biomarkers-cost effective, non-invasive indicators of Alzheimer's disease (AD) and related disorders (ADRD)-have largely been studied in clinical research settings. Here, we examined plasma biomarker profiles and their associated factors in a population-based cohort to determine whether they could identify an at-risk group, independently of brain and cerebrospinal fluid biomarkers.MethodsWe measured plasma phosphorylated tau181 (p-tau181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid beta (Aβ)42/40 ratio in 847 participants from a population-based cohort in southwestern Pennsylvania.ResultsK-medoids clustering identified two distinct plasma Aβ42/40 modes, further categorizable into three biomarker profile groups: normal, uncertain, and abnormal. In different groups, plasma p-tau181, NfL, and GFAP were inversely correlated with Aβ42/40, Clinical Dementia Rating, and memory composite score, with the strongest associations in the abnormal group.DiscussionAbnormal plasma Aβ42/40 ratio identified older adult groups with lower memory scores, higher dementia risks, and higher ADRD biomarker levels, with potential implications for population screening.HighlightsPopulation-based plasma biomarker studies are lacking, particularly in cohorts without cerebrospinal fluid or neuroimaging data. In the Monongahela-Youghiogheny Healthy Aging Team study (n = 847), plasma biomarkers associated with worse memory and Clinical Dementia Rating (CDR), apolipoprotein E ε4, and greater age. Plasma amyloid beta (Aβ)42/40 ratio levels allowed clustering participants into abnormal, uncertain, and normal groups. Plasma Aβ42/40 correlated differently with neurofilament light chain, glial fibrillary acidic protein, phosphorylated tau181, memory composite, and CDR in each group. Plasma biomarkers can enable relatively affordable and non-invasive community screening for evidence of Alzheimer's disease and related disorders pathophysiology.

Project description:Objective: The prevalence of Alzheimer's disease and related dementias (ADRD) in women is higher than men. However, the knowledge of gender disparity in ADRD treatment is limited. Therefore, this study aimed to determine the gender disparities in the receipt of anti-dementia medications among Medicare beneficiaries with ADRD in the U.S. Methods: We used data from the Medicare Current Beneficiary Survey 2016. Anti-dementia medications included cholinesterase inhibitors (ChEIs; including rivastigmine, donepezil, and galantamine) and N-methyl-D-aspartate (NMDA) receptor antagonists (including memantine). Descriptive analysis and multivariate logistic regression models were implemented to determine the possible gender disparities in the receipt of anti-dementia medications. Subgroup analyses were conducted to identify gender disparities among beneficiaries with Alzheimer's disease (AD) and those with only AD-related dementias. Results: Descriptive analyses showed there were statistically significant differences in age, marital status, and Charlson comorbidities index (CCI) between Medicare beneficiaries who received and who did not receive anti-dementia medications. After controlling for covariates, we found that female Medicare beneficiaries with ADRD were 1.7 times more likely to receive anti-dementia medications compared to their male counterparts (odds ratio [OR]: 1.71; 95% confidence interval [CI]: 1.19-2.45). Specifically, among Medicare beneficiaries with AD, females were 1.2 times more likely to receive anti-dementia medications (Odds Radio: 1.20; 95% confidence interval: 0.58-2.47), and among the Medicare beneficiaries with only AD-related dementias, females were 1.9 times more likely to receive anti-dementia medications (OR: 1.90; 95% CI: 1.23-2.95). Conclusion: Healthcare providers should be aware of gender disparities in receiving anti-dementia medications among patients with ADRD, and the need to plan programs of care to support both women and men. Future approaches to finding barriers of prescribing, receiving and, adhering to anti-dementia medications by gender should include differences in longevity, biology, cognition, social roles, and environment.

Project description:BackgroundInjuries are a leading cause of emergency department (ED) visits among older adults, and individuals with Alzheimer's disease and related dementias (ADRD) may be at particular risk. We compared injury-related ED use among assisted living (AL) residents with and without ADRD and assessed differences in the risk of injury-related ED visits among individuals with ADRD residing in ALs with memory care designation versus general AL.MethodsUsing Medicare claims, we identified a cohort of fee-for-service beneficiaries who lived in AL in 2018 and resided in one of 20 states with site-specific information on memory care designation (n = 116,754). Outcomes included all injury-related ED visits and injury-related ED visits resulting in hospitalization in the calendar year 2018. We fit multilevel models of the association between ADRD and outcomes, adjusting for resident demographic characteristics and chronic conditions, license type characteristics, and AL characteristics, with random intercepts at the AL and license type levels. Among residents with ADRD, we examined whether memory care licensure was associated with injury-related ED visits.ResultsThe adjusted risk of injury-related ED use during the year was 20.1% (95% CI: 19.6%, 20.6%) for residents with ADRD compared to 16.1% for residents without ADRD (95% CI: 15.7%, 16.5%; p < 0.001). The adjusted risk of injury-related ED use ending in hospitalization was 4.9% (95% CI: 4.6%, 5.1%) for AL residents with ADRD and 3.9% for residents without ADRD (95% CI: 3.8%, 4.1%; p < 0.001). There were no significant differences in injury-related ED visits between residents with ADRD in ALs with memory care designation and residents in general AL.ConclusionsInjury-related ED visits are common among AL residents with ADRD and residents in memory care, but residents in memory care AL experienced similar risks of injury as those in general AL. Further research should identify modifiable factors that can prevent injury among AL residents with ADRD.

Dataset Information

Antihypertensive Use and the Risk of Alzheimer's Disease and Related Dementias among Older Adults in the USA.

Background

Methods

Results

Conclusions

Publications

Antihypertensive Use and the Risk of Alzheimer's Disease and Related Dementias among Older Adults in the USA.

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