Jpad-Journal of Prevention of Alzheimers Disease最新文献

{"title":"Lifestyle and Socioeconomic Transition and Health Consequences of Alzheimer's Disease and Other Dementias in Global, from 1990 to 2019.","authors":"Y Cui, W Yang, J Shuai, Y Ma, Y Yan","doi":"10.14283/jpad.2023.63","DOIUrl":"10.14283/jpad.2023.63","url":null,"abstract":"<p><strong>Background: </strong>Previous studies only focused on changes in the global age-specific incidence and mortality for Alzheimer's disease and other dementias, failed to distinguish between cohort and period effects, and did not discuss risk factors separately.</p><p><strong>Methods: </strong>In this study, Alzheimer's disease disability-adjusted life years (DALYs) data to estimate the burden by gender, age, locations, and social-demographic status for 21 regions from 1990 to 2019. Additionally, trend analysis was performed using the age-period-cohort (APC) model and Join-point model.</p><p><strong>Results: </strong>In most regions, indicators (incidence, mortality, and DALYs) increased steadily with socio-demographic index(SDI) increased. The age effects for Alzheimer's disease and other dementias showed a significant increase from 40 to 95 years. The cohort effects rate ratios (RRs) had a rapid reduction attributed to smoking, high fasting plasma glucose, and high body mass index (BMI).</p><p><strong>Conclusions: </strong>Countries in middle-low and low SDI regions have higher levels of risk factor exposure. As a result, rapid and effective government responses are necessary to control dementia risk factors and reduce the disease burden in these countries.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alzheimer's Disease and Aging Association: Identification and Validation of Related Genes.","authors":"T Liu, K Hou, J Li, T Han, S Liu, J Wei","doi":"10.14283/jpad.2023.101","DOIUrl":"10.14283/jpad.2023.101","url":null,"abstract":"<p><strong>Background: </strong>Aging is considered a key risk factor for Alzheimer's disease (AD). This study aimed to identify and validate potential aging-related genes associated with AD using bioinformatics analysis.</p><p><strong>Methods: </strong>Datasets GSE36980 and GSE5281 were selected to screen differentially expressed genes (DEGs), and the immune cell correlation analysis and GSEA analysis of DEGs were performed. The intersection with senescence genes was taken as differentially expressed senescence-related genes (DESRGs), and the GSE44770 dataset was used for further validation. The potential biological functions and signaling pathways were determined by GO and KEGG, and the hub genes were identified by 12 algorithms in Cytohubba. The expression of 10 hub genes in different brain regions was determined and single-cell sequencing analysis was performed, and diagnostic genes were further screened by gene expression and receiver operating characteristic (ROC) curve. Finally, a miRNA-gene network of diagnostic genes was constructed and targeted drug prediction was performed.</p><p><strong>Results: </strong>A total of 2137 DEGs were screened from the GSE36980 and GSE5281 datasets, and 278 SRGs were identified from the CellAge database. The overlapping DEGs and SRGs constituted 29 DESRGs, including 14 senescence suppressor genes and 15 senescence inducible genes. The top 10 hub genes, including MDH1, CKB, PSMD14, SMARCA4, PEBP1, DDB2, ITPKB, ATF7IP, YAP1, and EWSR1 were screened. Furthermore, four diagnostic genes were identified: PMSD14, PEBP1, ITPKB, and ATF7IP. The ROC analysis showed that the respective area under the curves (AUCs) of PMSD14, PEBP1, ITPKB, and ATF7IP were 0.732, 0.701, 0.747, and 0.703 in the GSE36980 dataset and 0.870, 0.817, 0.902, and 0.834 in the GSE5281 dataset. In the GSE44770 dataset, PMSD14 (AUC, 0.838) and ITPKB (AUC, 0.952) had very high diagnostic values in the early stage of AD. Finally, based on these diagnostic genes, we found that the drug Abemaciclib is a targeted drug for the treatment of age-related AD. Flutamide can aggravate aging-related AD.</p><p><strong>Conclusion: </strong>The results of this study suggest that cellular SRGs might play an important role in AD. PMSD14, PEBP1, ITPKB, and ATF7IP have the potential as specific biomarkers for the early diagnosis of AD.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Factor Structure of the Preclinical Alzheimer Cognitive Composite and Cognitive Function Index across Racial/Ethnic, Sex, and Aβ Status Groups in the A4 Study.","authors":"M Ruthirakuhan, M Wood Alexander, H Cogo-Moreira, T Robinson, R Amariglio, R F Buckley, R A Sperling, W Swardfager, S E Black, J S Rabin","doi":"10.14283/jpad.2023.98","DOIUrl":"10.14283/jpad.2023.98","url":null,"abstract":"<p><strong>Background: </strong>Disparities in Alzheimer's disease (AD) are well-documented among different racial/ethnic groups and between sex/genders. Neuropsychological assessment provides important information about cognitive changes and can offer valuable insights into disparities. However, neuropsychological measures must be comparable across racial/ethnic and sex/gender groups to accurately interpret disparities.</p><p><strong>Objectives: </strong>To evaluate measurement invariance (equivalence) of the Preclinical Alzheimer Cognitive Composite (PACC) and the Cognitive Function Index across racial/ethnic, sex/gender, and β-amyloid (Aβ) status groups.</p><p><strong>Design, setting, participants: </strong>Cross-sectional analysis of screening data from the Anti-Amyloid in Asymptomatic AD (A4) Study. The study enrolled participants aged 65-85 from sites across the United States, Canada, Australia, and Japan.</p><p><strong>Measurements: </strong>Participants completed the PACC and the Cognitive Function Index. Participants classified as cognitively normal also underwent a Positron Emission Tomography (PET) scan to determine Aβ status.</p><p><strong>Results: </strong>Participants self-identified as non-Hispanic White (n=5241), non-Hispanic Black (n=267), Asian (n=228), or Hispanic White (n=225) as well as male (n=2885) or female (n=3076). Among those who underwent a PET scan, 3115 were classified as Aβ- and 1309 were classified as Aβ+. We found support for a one-factor model for both the PACC and Cognitive Function Index across the full sample and in samples stratified by race/ethnicity, sex/gender, and Aβ status. The one-factor model of the PACC and Cognitive Function Index demonstrated scalar measurement invariance across racial/ethnic, sex/gender, and Aβ status groups.</p><p><strong>Conclusions: </strong>Our findings suggest that performance on the PACC and Cognitive Function Index can be compared across the racial/ethnic, sex/gender, and Aβ status groups examined in this study.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66895215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consistency between Treatment Effects on Clinical and Brain Atrophy Outcomes in Alzheimer's Disease Trials.","authors":"M Ten Kate, F Barkhof, A J Schwarz","doi":"10.14283/jpad.2023.92","DOIUrl":"10.14283/jpad.2023.92","url":null,"abstract":"<p><strong>Background: </strong>Longitudinal changes in volumetric MRI outcome measures have been shown to correlate well with longitudinal changes in clinical instruments and have been widely used as biomarker outcomes in clinical trials for Alzheimer's disease (AD). While instances of discordant findings have been noted in some trials, especially the recent amyloid-removing therapies, the overall relationship between treatment effects on brain atrophy and clinical outcomes, and how it might depend on treatment target or mechanism, clinical instrument or imaging variable is not yet clear.</p><p><strong>Objective: </strong>To systematically assess the consistency and therapeutic class-dependence of treatment effects on clinical outcomes and on brain atrophy in published reports of clinical trials conducted in mild cognitive impairment (MCI) and/or AD.</p><p><strong>Design: </strong>Quantitative review of the published literature. The consistency of treatment effects on clinical and brain atrophy outcomes was assessed in terms of statistical agreement with hypothesized equal magnitude effects (e.g., 30% slowing of both) and nominal directional concordance, as a function of therapeutic class.</p><p><strong>Setting: </strong>Interventional randomized clinical trials.</p><p><strong>Participants: </strong>MCI or AD trial participants.</p><p><strong>Intervention: </strong>Treatments included were those that involved ingestion or injection of a putatively active substance into the body, encompassing both pharmacological and controlled dietary interventions.</p><p><strong>Measurements: </strong>Each trial included in the analysis reported at least one of the required clinical outcomes (ADAS-Cog, CDR-SB or MMSE) and at least one of the required imaging outcomes (whole brain, ventricular or hippocampal volume).</p><p><strong>Results: </strong>Data from 35 trials, comprising 185 pairwise comparisons, were included. Overall, the 95% confidence bounds overlapped with the line of identity for 150/185 (81%) of the imaging-clinical variable pairs. The greatest proportion of outliers was found in trials of anti-amyloid antibodies that have been shown to dramatically reduce the level of PET-detectable amyloid plaques, for which only 13/33 (39%) of observations overlapped the identity line. A Deming regression calculated using all data points yielded a slope of 0.54, whereas if data points from the amyloid remover class were excluded, the Deming regression line had a slope of 0.92. Directional discordance of treatment effects was also most pronounced for the amyloid-removing class, and for comparisons involving ventricular volume.</p><p><strong>Conclusion: </strong>Our results provide a frame of reference for the interpretation of clinical and brain atrophy results from future clinical trials and highlight the importance of mechanism of action in the interpretation of imaging results.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10994869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66895156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Testosterone on Alzheimer's Disease Are Mediated by Lipid Metabolism and Obesity: A Mendelian Randomization Study.","authors":"L Zhang, F Yang, J Ma, Y Hu, M Li, C Wang, X Chang, L Yang","doi":"10.14283/jpad.2023.116","DOIUrl":"10.14283/jpad.2023.116","url":null,"abstract":"<p><strong>Background: </strong>To investigate the causal relationship between testosterone (BT) levels and Alzheimer's disease (AD) risk and to quantify the role of obesity and lipid metabolism as potential mediators.</p><p><strong>Methods: </strong>We used a two-sample, two-step MR to determine:1) the causal effect of BT levels on AD; 2) the causal effect of two lipid metabolites, obesity and LDLc on AD; and 3) the mediating effects of these metabolites. Pooled data for BT levels and lipid metabolism were obtained from the UK Biobank. AD data were obtained from the Alzheimer's Disease Project International Genomics Consortium, FinnGen Consortium, and UK Biobank study. Effect estimates from external genome-wide association study (GWAS) pooled statistics were obtained using inverse variance-weighted (IVW) MR analysis.</p><p><strong>Results: </strong>Higher levels of BT were associated with a reduced risk of AD (odds ratio [OR] 0.9992, 95% CI 0.9985-0.9998, P = 0.019), and there was a negative correlation with LDLc (OR 0.9208, 95% CI 0.8569-0.9895, P = 0.024) and obesity class 2 (OC2) (OR 0.7445, 95% CI 0.5873-0.9437, P = 0.014). Conversely, there was a positive correlation between LDLc (OR 1.0014, 95% CI 1.0000-1.0029, P = 0.043) and OC2 (OR 1.0005, 95% CI 1.0001-1.0009, P = 0.003) and AD. Mediation analysis showed that the indirect effect of BT levels on AD was achieved through LDLc and OC2, which accounted for 17% and 17% of the total effect, respectively.</p><p><strong>Conclusion: </strong>Our study identified a causal role of BT levels in LDLc and OC2. BT levels may affect AD through LDLc and OC2 metabolic processes.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral Health as a Risk Factor for Alzheimer Disease.","authors":"S M Pruntel, B C van Munster, J J de Vries, A Vissink, A Visser","doi":"10.14283/jpad.2023.82","DOIUrl":"10.14283/jpad.2023.82","url":null,"abstract":"<p><p>In patients with Alzheimer's disease pathophysiological changes of the brain that initiate the onset of Alzheimer's disease include accumulation of amyloid-β plaques and phosphorylation of tau-tangles. A rather recently considered risk factor for the onset of Alzheimer's disease is poor oral health. The aim of this systematic review of the literature was to assess the potential association(s) of oral health as a risk factor for the onset of Alzheimer's disease. After a systematic search of Pubmed, Embase and Web of Science. A total of 1962 studies were assessed, of which 17 studies demonstrated possible associations between oral health diseases and Alzheimer's disease. 4 theories could be distinguished that describe the possible links between oral health and the development or onset of Alzheimer's disease; 1) role of pathogens, 2) role of inflammatory mediators, 3) role of APOE alleles and 4) role of Aβ peptide. The main common denominator of all the theories is the neuroinflammation due to poor oral health. Yet, there is insufficient evidence to prove a link due to the diversity of the designs used and the quality of the study design of the included studies. Therefore, further research is needed to find causal links between oral health and neuroinflammation that possibly can lead to the onset of Alzheimer's disease with the future intention to prevent cognitive decline by better dental care.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10994994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66894851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data-Driven Thresholding Statistically Biases ATN Profiling across Cohort Datasets.","authors":"Y Salimi, D Domingo-Fernández, M Hofmann-Apitius, C Birkenbihl","doi":"10.14283/jpad.2023.100","DOIUrl":"10.14283/jpad.2023.100","url":null,"abstract":"<p><strong>Background: </strong>While the amyloid/tau/neurodegeneration (ATN) framework has found wide application in Alzheimer's disease research, it is unclear if thresholds obtained using distinct thresholding methods are concordant within the same dataset and interchangeable across cohorts.</p><p><strong>Objectives: </strong>To investigate the robustness of data-driven thresholding methods and ATN profiling across cohort datasets.</p><p><strong>Design and setting: </strong>We evaluated the impact of thresholding methods on ATN profiles by applying five commonly-used methodologies across cohort datasets. We assessed the generalizability of disease patterns discovered within ATN profiles by clustering individuals from different cohorts who were assigned to the same ATN profile.</p><p><strong>Participants and measurements: </strong>Participants with available CSF amyloid-β 1-42, phosphorylated tau, and total tau measurements were included from eleven AD cohort studies.</p><p><strong>Results: </strong>We observed high variability among obtained ATN thresholds, both across methods and datasets that impacted the resulting profile assignments of participants significantly. Clustering participants from different cohorts within the same ATN category indicated that identified disease patterns were comparable across most cohorts and biases introduced through distinct thresholding and data representations remained insignificant in most ATN profiles.</p><p><strong>Conlusion: </strong>Thresholding method selection is a decision of statistical relevance that will inevitably bias the resulting profiling and affect its sensitivity and specificity. Thresholds are likely not directly interchangeable between independent cohorts. To apply the ATN framework as an actionable and robust profiling scheme, a comprehensive understanding of the impact of used thresholding methods, their statistical implications, and a validation of results is crucial.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10995057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Balance Impairment with Risk of Incident Dementia among Older Adults.","authors":"H J Kim, S Jeong, Y H Oh, M J Suh","doi":"10.14283/jpad.2023.79","DOIUrl":"10.14283/jpad.2023.79","url":null,"abstract":"<p><strong>Background: </strong>A growing body of data suggests that balance impairment may be linked to the onset of dementia.</p><p><strong>Objectives: </strong>However, a large-scale epidemiologic investigation is needed to clarify its association in older adults.</p><p><strong>Design: </strong>A retrospective-prospective hybrid database.</p><p><strong>Setting: </strong>Cox proportional hazards regression model was used to assess the relationship between balance impairment and the risk of incident dementia, and the results were provided as adjusted hazard ratios (aHR) with 95% confidence intervals (CI). All participants were tracked until the date of incident dementia, death, or 31 December 2019 whichever came first.</p><p><strong>Participants: </strong>We analyzed 143,788 older adults who had at least one health screening between 2009 and 2019 from the Korea National Health Insurance Service-Senior Cohort.</p><p><strong>Measurements: </strong>A total of 3,774 cases of dementia were discovered throughout 850,425 person-years of follow-up investigation. Balance impairment was associated with a risk of dementia compared to those without balance impairment (adjusted hazard ratio [aHR] 1.83; 95% CI, 1.69-2.00; P value <0.001).</p><p><strong>Results: </strong>Risks of the Alzheimer's disease (aHR, 1.80; 95% CI, 1.65-1.96; P for trend <0.001) and the vascular dementia (aHR, 2.94; 95% CI, 1.89-4.58; P for trend <0.001) showed comparable trends and findings.</p><p><strong>Conclusions: </strong>Balance impairment was found to be independently associated with an increased risk of dementia in older adults.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66894420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digital Clock Drawing as an Alzheimer's Disease Susceptibility Biomarker: Associations with Genetic Risk Score and APOE in Older Adults.","authors":"L I Thompson, M Cummings, S Emrani, D J Libon, A Ang, C Karjadi, R Au, C Liu","doi":"10.14283/jpad.2023.48","DOIUrl":"10.14283/jpad.2023.48","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is the leading cause of dementia in older adults, but most people are not diagnosed until significant neuronal loss has likely occurred along with a decline in cognition. Non-invasive and cost-effective digital biomarkers for AD have the potential to improve early detection.</p><p><strong>Objective: </strong>We examined the validity of DCTclockTM (a digitized clock drawing task) as an AD susceptibility biomarker.</p><p><strong>Design: </strong>We used two primary independent variables, Apolipoprotein E (APOE) ε4 allele carrier status and polygenic risk score (PRS). We examined APOE and PRS associations with DCTclockTM composite scores as dependent measures.</p><p><strong>Setting: </strong>We used existing data from the Framingham Heart Study (FHS), a community-based study with the largest dataset of digital clock drawing data to date.</p><p><strong>Participants: </strong>The sample consisted of 2,398 older adults ages 60-94 with DCTclockTM data (mean age of 72.3, 55% female and 92% White).</p><p><strong>Measurements: </strong>PRS was calculated using 38 variants identified in a recent large genome-wide association study (GWAS) and meta-analysis of late-onset AD (LOAD).</p><p><strong>Results: </strong>Results showed that DCTclockTM performance decreased with advancing age, lower education, and the presence of one or more copies of APOE ε4. Lower DCTclockTM Total Score as well as lower composite scores for Information Processing Speed (both command and copy conditions) and Drawing Efficiency (command condition) were significantly associated with higher PRS levels and more copies of APOE ε4. APOE and PRS associations displayed similar effect sizes in both men and women.</p><p><strong>Conclusions: </strong>Our results indicate that higher AD genetic risk is associated with poorer DCTclockTM performance in older adults without dementia. This is the first study to demonstrate significant differences in clock drawing performance on the basis of APOE status or PRS.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10794851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66893913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationships of Hypnotics with Incident Dementia and Alzheimer's Disease: A Longitudinal Study and Meta-Analysis.","authors":"J-H Hou, S-L Sun, C-C Tan, Y-M Huang, L Tan, W Xu","doi":"10.14283/jpad.2023.78","DOIUrl":"10.14283/jpad.2023.78","url":null,"abstract":"<p><strong>Background: </strong>Evidence describing the association between hypnotics use and dementia risk is conflicting. It is unknown if the controversy is related to the type or dose of hypnotics or if hypnotics affect different populations.</p><p><strong>Objectives: </strong>We sought to derive lessons learned and future projections based on evidence from longitudinal studies.</p><p><strong>Measurements: </strong>In the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, 1,543 older adults without dementia (mean age = 73.3 years, female = 45%) were followed for four years. The association between hypnotics and the risk of Alzheimer's disease (AD) was investigated using Cox proportional hazards regressions. Next, electronic databases were searched until March 2022 to conduct the evidence synthesis of the associations of hypnotics with incident risk of dementia.</p><p><strong>Results: </strong>In the ADNI cohort, ever use of hypnotics was associated with an increased risk of AD (hazard ratio = 1.96, 95% confidence intervals = 1.23-3.11, p < 0.01). This association was significant for benzodiazepines and Z-drugs but not for melatonin. The association was stronger in long-term (more than one year) users and those with high cumulative doses. A meta-analysis of 26 longitudinal studies with 3,942,018 participants revealed a correlation between the use of hypnotics and the risk of dementia (relative risk = 1.23, 95% confidence intervals = 1.13-1.33, p < 0.001, median risk difference = 4%). It is a linear dose-response relationship, if a person takes the daily recommended dose for 100 days, their risk of developing dementia increases by 5% relative to non-users. According to subgroup analyses, neither association was significant among patients with a history of insomnia.</p><p><strong>Conclusions: </strong>Individuals who use hypnotics, especially high-dose or long-term users, are at a higher risk of dementia and AD. The main issue with conclusion credibility is heterogeneity.</p>","PeriodicalId":48606,"journal":{"name":"Jpad-Journal of Prevention of Alzheimers Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66894362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}