Jul 2026· Current Alzheimer Research· Vol 23· 0 citations
Medicine
TL;DR
This study's Mendelian randomization approach revealed no causal relationship between depression and Alzheimer's disease, consistent with depression reflecting early disease manifestations rather than a direct causal factor, and hinting at possible shared pathological processes in both conditions.
Abstract
INTRODUCTION/
Background
Recent studies show that depression often occurs years before Alzheimer's disease onset in many older adults. However, it is unclear whether this link reflects a causal relationship.
Materials And Methods
Summary statistics from Genome-Wide Association Studies (GWAS) of depression and Alzheimer's disease were utilized. Data associated with broad depression included up to 407,746 Europeans, and data associated with major depression disorder included up to 480,359 Europeans; the corresponding Alzheimer's disease associations from consortia included up to 488,285 European participants in the UK Biobank. Two-sample Mendelian randomization analyses served as our primary approach, with additional three-sample analyses performed to validate the findings.
Results
In the sample of 407,746 participants, genetically predicted levels of broad depression showed no significant association with Alzheimer's disease risk (odds ratio, 1.00007; p = 0.908). As for the sample of 480,359 participants associated with major depressive disorder, the result was consistent (odds ratio, 0.99918, p = 0.138) with findings from broad depression. Secondary analyses present consistent results with primary findings. Statistically significant bias from pleiotropy or genetic confounding was not detected in sensitivity analyses.
Discussion
The study's findings do not support a causal role of depression in AD and are more consistent with depression reflecting early disease processes or shared mechanisms.
Conclusion
This study's Mendelian randomization approach revealed no causal relationship between depression and Alzheimer's disease, consistent with depression reflecting early disease manifestations rather than a direct causal factor, and hinting at possible shared pathological processes in both conditions.
Genetic evidence supporting a causal role for depression in the etiology of late-onset AD is provided, a link not observed for other major psychiatric disorders tested and highlighted the specific importance of managing depression as a potential strategy for mitigating AD risk.
INTRODUCTION
Alzheimer's disease stands as the most prevalent form of dementia, characterized by a progressive decline in cognitive function and memory. Numerous risk factors have been linked to its development, creating a complex interplay of influences. In this study, we aim to delve into the relationship between cardiovascular disease and Alzheimer's disease, exploring how conditions affecting heart health may impact the onset and progression of this debilitating neurological disorder. Through this research, we could find potential connections that inform prevention strategies and therapeutic approaches.
MATERIALS AND METHODS
We adopted the PRISMA guidelines and defined the PECOS framework as follows: Population (P) = individuals; exposure (E) = cardiovascular disease; comparison (C) = without cardiovascular disease; outcome (O) = Alzheimer's disease; and study design(S) = all kinds of studies with an association between cardiovascular disease and Alzheimer's disease without time limits. A meta-analysis was conducted using case-control, cohort, and genetic studies to estimate Odds Ratios (ORs) or Hazard Ratios (HRs).
RESULTS
The pooling of data in meta-analysis demonstrated that a person with any Cardiovascular Disease (CVD), Heart Failure (HF), Coronary Artery Disease (CAD), Atrial Fibrillation (AF), Hypertension (HTN), and Myocardial Infarction (MI) had more risk of developing Alzheimer's disease [CVD: HR = 1.30 (CI: 1.27-1.33) / HF: HR = 1.63 (CI: 1.37-1.94) / CAD: HR = 1.43 (CI: 1.40-1.46) / AF: HR = 1.38 (CI: 1.34-1.42) / HTN: HR = 1.22 (CI: 1,10-1.35) / MI: HR = 1.07 (CI: 1,01-1.13)]. Cross-sectional studies demonstrated an association between cardiovascular diseases and Alzheimer's disease [OR = 1.29 (CI: 1.23-1.35)]. Mendelian randomization meta-analysis did not demonstrate a causal relation between cardiovascular disease and Alzheimer's disease [AF: OR = 1.03 (CI: 1.00-1.01) / HF: OR = 1.00 (CI: 0,79-1.36)]. A Mendelian randomization meta-analysis demonstrated that a person with AD had a higher risk of developing myocardial infarction [OR = 1.07 (CI: 1.03-1.10)].
DISCUSSION
This review examines the connection between AD and CVD, noting that HF increases the risk of developing AD with a hazard ratio of 1.63. It suggests that altered brain perfusion and hypoxia appear to be one important neurodegenerative factor. Some genetic changes in individuals with CVD made them more vulnerable to AD. Effective prevention and treatment of CVD can help reduce the risk of AD.
CONCLUSION
HF, AF, and CAD were the CVDs with the highest risk of developing AD. The results suggest that changes in cerebral blood perfusion are a principal neuropathological event that leads to genetic alterations that end in AD.
Juliano Flávio Rubatino Rodrigues, Lívia Peregrino Rodrigues, Franciany Cunha Peregrino Rodrigues et al.· Current Alzheimer Research· 0 citations
Introduction Alzheimer's disease is a progressive neurodegenerative disorder that is the leading cause of dementia worldwide. Genetic factors, particularly Apolipoprotein E (APOE) polymorphisms, are known to play a significant role in increasing susceptibility to Alzheimer's disease. The increasing number of publications related to APOE and Alzheimer's disease has prompted the need for bibliometric analysis and systematic reviews to comprehensively understand research developments and their genetic relationships. This study aims to analyze the global development of research on APOE polymorphisms in Alzheimer's disease through a bibliometric study and systematic review approach. Methods The study used a combined bibliometric and systematic review design. Data were obtained from the Scopus database for the period 2000–2025 using keywords Title-Abs-Key ((“APOE” Or “APOE E4” Or “Apolipoprotein E4”) And (“Alzheimer's disease”And (“Genetic Susceptibility”Or”Risk Factor”)) And (Limit-To (Doctype,”Ar”)) And (Limit-To(Language,”English”)) And Pubyear > 1999 And Pubyear < 2026. Bibliometric analysis was performed using VOSviewer and Microsoft Excel to evaluate publication trends, countries, institutions, journals, author collaborations, and co-occurrence keywords . A systematic review was conducted on 26 articles that met the inclusion criteria to evaluate the association of APOE polymorphisms with Alzheimer's risk. Results A total of 3824 articles from 718 publication sources were identified with an average citation of 51.51 per document. The United States was the country with the highest publication contribution. Keyword co-occurrence analysis showed that APOE4, genetics, and biomarkers were the main research themes. The results of the systematic review showed that APOE polymorphisms, especially rs429358 and rs7412, had a significant association with an increased risk of Alzheimer's disease in various ethnic populations with a very low p-value of up to 1E-320. Conclusion APOE polymorphisms play an important role in the genetic susceptibility of Alzheimer's disease and have the potential to be key biomarkers in early detection and the development of precision medicine in neurodegenerative diseases.
D. Amukti, Nurul Kusumawardani, Ria Indah Pratami et al.· Journal of Genetic Engineeri...· 0 citations
INTRODUCTION
Alzheimer's Disease (AD) is a neurological condition that increases in severity from a gradual start. Previous studies have found an association between long sleep (LS) and AD. To slow its progression, it is important to recognize biomarkers associated with the early stages of both AD and LS.
METHODS
This study aimed to use two-sample Mendelian Randomization (MR) to identify blood and urine biomarkers associated with AD and LS. Thirty-five biomarkers from blood and urine were included as exposures in the MR analysis, while AD and LS were considered the outcomes. The AD dataset included 39,106 patients and 46,828 controls from Europe. Data on sleep duration were obtained from a GWAS in 34,184 cases and 305,742 controls of European ancestry. This study included 35 blood and urine biomarkers across 355,891 participants, including 318,953 white British, 23,582 non-white British, 6,019 African, and 7,338 South Asian participants from the UK Biobank.
RESULTS
Cystatin C, CRP, and Non-Albumin protein showed genetic association with AD and LS. The genetic association results after Bonferroni's correction are significant for Non-Albumin Protein in AD and LS.
DISCUSSION
This study provides further insight into the genetic associations and relationships among AD, LS, and other biomarkers; it also presents several potential candidates for AD and LS diagnosis and treatment. The opposing roles of C-reactive Protein, Cystatin C, and Non-Albumin protein in AD and LS warrant a greater exploration of their differential functions at various ages and in specific brain microenvironments in future studies.
CONCLUSION
This study provides a theoretical basis for the diagnosis and treatment of AD and LS. More experiments are needed in the future to verify this prediction.
Jian-Ran Ma, Zhen Wei, Chunshu Rong et al.· Current Alzheimer Research· 0 citations
Depression, hypertension, hypertension, and alcohol consumption were identified as significant mediators of the relationship between higher neuroticism and increased AD risk, suggesting that the neuroticism-AD relationship is unlikely to be causal.
N. Akbarian, M. Ebrahimi, F. D. Dos Santos et al.· medRxiv· 0 citations
Background Alzheimer's disease (AD) is the primary cause of dementia and represents a significant public health concern in aging populations. Existing evidence indicates geographic and sex-related differences in AD prevalence; however, comparability across time periods and diagnostic criteria is limited, and data from lower-resource regions remain scarce. This study synthesized evidence on reported AD prevalence from 1980 to 2024 and examined temporal, geographic, demographic, and methodological variation. Methods PubMed, Web of Science, and Embase were systematically searched from inception to December 31, 2024, for observational studies reporting AD prevalence in general or community-based populations. Eligible studies reported prevalence estimates with 95% confidence intervals or provided sufficient data for calculation. Studies with sample sizes below 100 and non-original reports were excluded. Two reviewers independently screened studies and extracted data; disagreements were resolved by a third reviewer. Pooled reported prevalence was estimated using a random-effects model. The review was prospectively registered in PROSPERO (CRD420251111597). Results Fifty-two studies from 19 countries met the inclusion criteria. The pooled reported prevalence of AD was 4.43 per 100 population (95% CI 3.47–5.50). Prevalence was higher among females (4.65 per 100, 95% CI 3.37–6.13) than males (2.30 per 100, 95% CI 1.71–2.97). By survey period, reported prevalence was 3.52 per 100 for 1980–1989, 4.21 for 1990–1999, 4.12 for 2000–2009, and 6.78 for 2010–2024. Adjusted meta-regression did not identify a significant association between survey year and reported prevalence. Estimates also varied by WHO region, Human Development Index (HDI) level, sample size, and study design. Conclusions Reported AD prevalence was substantial and varied by demographic, geographic, and methodological factors. Although prevalence was highest in the most recent survey period, meta-regression did not indicate a consistent global increase over time. Given the extremely high between-study heterogeneity, these findings should be interpreted with caution. More standardized, age-comparable, and geographically representative studies are needed, particularly in underrepresented and lower-resource settings. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251111597, identifier CRD420251111597.
Meng-Qi Hu, Zhiyuan Sun, Dewei Mao et al.· Frontiers in Public Health· 0 citations
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