The Journal of Prevention of Alzheimer's Disease最新文献

{"title":"Informing Alzheimer’s Biomarker Communication: Concerns and Understanding of Cognitively Unimpaired Adults During Amyloid Results Disclosure","authors":"Fred B. Ketchum, C. M. Erickson, K. E. Basche, N. A. Chin, M. L. Eveler, C. E. Conway, D. M. Coughlin, L. R. Clark","doi":"10.14283/jpad.2024.151","DOIUrl":"https://doi.org/10.14283/jpad.2024.151","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Biomarker results are increasingly disclosed in research and clinical settings, but less is known about how individuals interpret their results or concerns raised during the disclosure visit that may need to be addressed by clinicians to ensure appropriate disclosure.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Fifty-two cognitively unimpaired older adults aged 65 to 89 years old from the Wisconsin Registry for Alzheimer’s Prevention, who had undergone an amyloid PET scan in the previous 18 months, were enrolled in the disclosure substudy. After ensuring psychological readiness, trained study clinicians disclosed amyloid PET results using a structured protocol. We assessed participants’ level of understanding, concerns, and the perceived personal significance of their biomarker results during the disclosure visit through a series of question prompts in real-time.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Thirty-four received a non-elevated amyloid result and 18 received an elevated result. The average age was 72.2 years (range 65–81); most were women (64%) and non-Hispanic White (92%). Participants understood their results (98%), and both non-elevated and elevated groups provided similar responses around topics of sharing with others, privacy, accuracy of testing, and risk. Participants with elevated results were significantly more likely than those with non-elevated results to want to change their lifestyle (78% vs 12%, p=&lt;0.01) and have questions about their results (61% vs 30%, p=0.05). Participants interpreted the personal significance of results in terms of several themes relating to individual risk status, emotional impact, whether the result was expected, and prevention/planning.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Results show that participants understand their biomarker results, and have a number of concerns during the disclosure process that clinical and research protocols could address. en These findings could be important considerations as effective processes are developed for widespread biomarker disclosure in clinical and research settings.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"45 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141929871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Causal Effect of Type 2 Diabetes on Alzheimer’s Disease Using Large-Scale Genetic Data","authors":"D. Liu, A. Baranova, Fuquan Zhang","doi":"10.14283/jpad.2024.148","DOIUrl":"https://doi.org/10.14283/jpad.2024.148","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Alzheimer’s disease (AD) has a high comorbidity with type 2 diabetes (T2D). However, there is still some controversy over whether T2D has a causal impact on AD at present.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>We aimed to reveal whether T2D has a causal effect on AD using large-scale genetic data.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Firstly, we performed a primary two-sample Mendelian randomization (MR) analysis to assess the potential causal effects of T2D on AD. For this analysis, we used the largest available genome-wide association studies (GWAS) T2D (T2D1, including 80,154 cases and 853,816 controls) and AD (AD1, including 111,326 cases and 677,663 controls) datasets. Additionally, we performed a validation MR analysis using two largely overlapping-sample datasets from FinnGen, including T2D (T2D2, including 57,698 cases and 308,252 controls) and AD (AD2, including 13,393 cases and 363,884 controls). In all MR analyses, the inverse variance-weighted method was used as the primary analysis method, supplemented by the weighted-median and MR-Egger techniques.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In the primary analysis, we found that T2D was not associated with the risk of AD (OR: 0.98, CI: 0.95–1.01, P=0.241). Similarly, no significant association was detected in the validation MR analysis (OR: 0.97, CI: 0.64–1.47, P=0.884).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Our findings provide robust evidence that T2D does not have a causal impact on AD. Future studies need to further explore the effect of T2D on the non-AD components of the dementia phenotype.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"63 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141783223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Japanese Subgroup Analyses from EMERGE and ENGAGE, Phase 3 Clinical Trials of Aducanumab in Patients with Early Alzheimer’s Disease","authors":"Yasuo Toda, T. Iwatsubo, Y. Nakamura, N. Matsuda, M. Miyata, M. Jin, T. Chen, K. Kuribayashi, Y. Tian, R. Hughes, J. Yamamoto, K. K. Muralidharan, C. Rubel, R. M. Hutchison, S. Budd Haeberlein","doi":"10.14283/jpad.2024.106","DOIUrl":"https://doi.org/10.14283/jpad.2024.106","url":null,"abstract":"&lt;h3 data-test=\"abstract-sub-heading\"&gt;Background&lt;/h3&gt;&lt;p&gt;Global prevalence and incidence of dementia continue to rise at a rapid rate. There is a need for new Alzheimer’s disease (AD) treatments globally. Aducanumab is a human monoclonal antibody that selectively targets aggregated soluble amyloid beta oligomers and insoluble amyloid beta fibrils. In June 2021, aducanumab was approved by the US Food and Drug Administration for the treatment of AD under the accelerated approval pathway.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Objectives&lt;/h3&gt;&lt;p&gt;We evaluated the efficacy, safety, biomarker and pharmacokinetics (PK) of aducanumab in Japanese subgroups in EMERGE and ENGAGE studies.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Design&lt;/h3&gt;&lt;p&gt;EMERGE and ENGAGE were two randomized, double-blind, placebo-controlled, global, phase 3 studies of aducanumab in patients with early AD (mild cognitive impairment due to AD or mild AD dementia).&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Setting&lt;/h3&gt;&lt;p&gt;These studies involved 348 sites in 20 countries. PARTICIPANTS: Participants enrolled in Japan included 121 (7.4% of total 1638 in EMERGE) and 100 (6.1% of total 1647 in ENGAGE) patients (aged 50–85 years with confirmed amyloid pathology) who met clinical criteria for mild cognitive impairment due to AD or mild AD dementia.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Intervention&lt;/h3&gt;&lt;p&gt;Participants were randomly assigned 1:1:1 to receive aducanumab low dose (3 or 6 mg/kg target dose), high dose (6 or 10 mg/kg target dose) or placebo via IV infusion once every 4 weeks over 76 weeks.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Measurements&lt;/h3&gt;&lt;p&gt;The primary outcome measure was change from baseline to Week 78 on the Clinical Dementia Rating Sum of Boxes (CDR-SB), an integrated scale that assesses both function and cognition. Other measures included safety assessments; secondary and tertiary clinical outcomes that assessed cognition, function, and behavior; biomarker endpoints (amyloid PET and plasma p-tau181); serum PK profiles and immunogenicity.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Results&lt;/h3&gt;&lt;p&gt;Results from the Japanese subgroup analyses were generally consistent with those of the overall study population across endpoints, while a lower mean body weight (kg) and a smaller proportion of ApoE ε4 carriers were observed in the Japanese subgroup population. A treatment effect was observed in favor of aducanumab on the primary and secondary efficacy endpoints at Week 78 in EMERGE, but not ENGAGE. The incidence and type of adverse events in the Japanese subgroups were generally comparable to those observed in the overall study population; amyloid related imaging abnormalities (ARIA) were common treatment-related adverse events that appeared to be related to the aducanumab dose. ARIA incidence was generally lower in the Japanese subgroup compared with the overall population. Consistent with the overall data set, a robust dose-dependent decrease in amyloid beta levels as assessed with am","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"83 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141783224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Daytime Sleepiness, Apnea, Neuroimaging Correlates and Cortisol Dysregulation in a Memory Clinic Cohort","authors":"Charlotte Sørensen, I. Kåreholt, G. Kalpouzos, C. T. Udeh-Momoh, J. Holleman, M. Aspö, G. Hagman, G. Spulber, M. Kivipelto, A. Solomon, S. Sindi","doi":"10.14283/jpad.2024.145","DOIUrl":"https://doi.org/10.14283/jpad.2024.145","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Sleep disturbances as well as cortisol hypersecretion are increasingly acknowledged as risk factors for Alzheimer’s disease (AD). However, the mechanisms underlying the association, and the interplay with cortisol abnormalities, remain unclear.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>This study aims to identify how self-reported sleep disturbances are associated with structural brain measures and diurnal cortisol dysregulation among memory clinic patients.</p><h3 data-test=\"abstract-sub-heading\">Design</h3><p>A cross-sectional study performed at Karolinska University Hospital Memory Clinic, Sweden.</p><h3 data-test=\"abstract-sub-heading\">Participants</h3><p>The study was based on 146 memory clinic patients diagnosed with either subjective cognitive impairment or mild cognitive impairment.</p><h3 data-test=\"abstract-sub-heading\">Measurements</h3><p>Self-reported sleep was measured using the Karolinska Sleep Questionnaire. MRI or CT was used to quantify structural brain measures using four visual rating scales (Scheltens, Pasquier, Koedam, and Fazekas scales), and salivary cortisol was sampled to measure diurnal cortisol patterns through measures of cortisol immediately after awakening, cortisol awakening response, bedtime cortisol, total cortisol from awakening to bedtime, and the AM/PM cortisol ratio.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Increased sleep apnea index (OR=1.20, 95% CI=1.04:1.39, p=0.015) was associated with greater odds of posterior brain atrophy, measured by the Koedam visual rating scale, and reduced awakening Cortisol (β=−0.03, 95% CI=− 0.07:0.00, p=0.045). Increased daytime sleepiness was associated with both reduced awakening cortisol (β=−0.03, 95% CI=−0.06:0.00, p=0.025) and a reduced AM/PM cortisol ratio (β=−0.04, CI=−0.08:−0.01, p= 0.021).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>In a memory clinic cohort self-reported sleep disturbances are associated with both worse structural brain tissue integrity and altered diurnal cortisol profiles. These findings may add insights into possible mechanisms behind sleep disturbances in aging with subjective and cognitive impairment.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"30 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141745597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semorinemab Pharmacokinetics and The Effect on Plasma Total Tau Pharmacodynamics in Clinical Studies","authors":"Vidya Ramakrishnan, B. Bender, J. Langenhorst, M. O. Magnusson, M. Dolton, J. Shim, R. N. Fuji, C. Monteiro, E. Teng, N. Kassir, J. Jin","doi":"10.14283/jpad.2024.146","DOIUrl":"https://doi.org/10.14283/jpad.2024.146","url":null,"abstract":"&lt;h3 data-test=\"abstract-sub-heading\"&gt;Background&lt;/h3&gt;&lt;p&gt;Semorinemab is a monoclonal antibody that targets the N-terminal domain of the tau protein that is in clinical development for the treatment of Alzheimer’s disease.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Objectives&lt;/h3&gt;&lt;p&gt;To perform model-based evaluations of the observed pharmacokinetics in serum and the total plasma tau target-engagement dynamics from clinical studies evaluating semorinemab.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Design&lt;/h3&gt;&lt;p&gt;The observed semorinemab pharmacokinetics and plasma tau target engagement from phase 1 and 2 clinical studies were modeled using a non-linear mixed effect targetmediated drug disposition model. The model was simulated to understand target engagement at clinical dose levels.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Settings and Participants&lt;/h3&gt;&lt;p&gt;The clinical studies testing semorinemab were evaluated in healthy volunteers, subjects with prodromal-to-mild Alzheimer’s disease, and subjects with mild-to-moderate Alzheimer’s disease. The data included a total of 8430 semorinemab serum concentrations and 4772 total tau protein plasma concentrations from 463 subjects treated with a range of single and multiple doses of semorinemab.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Measurements&lt;/h3&gt;&lt;p&gt;Serum concentrations of semorinemab and the total plasma tau concentrations were measured after administration of a range of doses of semorinemab to subjects with Alzheimer’s disease. A sensitivity analysis was performed wherein key target-mediated drug disposition model parameters were estimated separately between healthy volunteers, subjects with prodromal-to-mild Alzheimer’s disease, and subjects with mild-to-moderate Alzheimer’s disease.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Results&lt;/h3&gt;&lt;p&gt;Serum concentrations of semorinemab were consistent across studies and showed a dose-proportional increase across the evaluated dose range. The pharmacokinetic profile was comparable between healthy volunteers and subjects with Alzheimer’s disease. Total plasma tau concentrations increased in a dose-dependent non-linear manner upon semorinemab administration. The target-mediated drug disposition model adequately described the serum pharmacokinetics and protein dynamics with an estimated antibody-ligand binding strength, K&lt;sub&gt;ss&lt;/sub&gt;, of 42.7 nM. The estimated values of clearance and central volume of distribution were 0.109 L/day/70 kg and 2.95 L/70 kg, respectively, and were consistent with typical values for IgG mAbs. In the sensitivity analysis, K&lt;sub&gt;ss&lt;/sub&gt; (32 nM) and baseline tau protein (0.30 &lt;i&gt;µ&lt;/i&gt;M) were estimated to be lower for healthy volunteers compared to subjects with Alzheimer’s disease but were comparable between subjects with Alzheimer’s disease of different severities (K&lt;sub&gt;ss&lt;/sub&gt;: 52–57 nM, baseline tau: 0.44–0.47 &lt;i&gt;µ&lt;/i&gt;M). The models suggested that peripheral target engagement was over 90% at the clinical doses in each of the diagnostic subgroup","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"33 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141722465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Biomarkers of Alzheimer’s Disease and Neurodegeneration According to Sociodemographic Characteristics and Chronic Health Conditions","authors":"H. T. Zheng, Z. Wu, M. M. Mielke, A. M. Murray, Joanne Ryan","doi":"10.14283/jpad.2024.142","DOIUrl":"https://doi.org/10.14283/jpad.2024.142","url":null,"abstract":"<p>Ultrasensitive assays have been developed which enable biomarkers of Alzheimer’s disease pathology and neurodegeneration to be measured in blood. These biomarkers can aid in diagnosis, and have been used to predict risk of cognitive decline and Alzheimer’s disease. The ease and cost-effectiveness of blood collections means that these biomarkers could be applied more broadly in population-based screening, however it is critical to first understand what other factors could affect blood biomarker levels. The aim of this review was to determine the extent that sociodemographic, lifestyle and health factors have been associated with blood biomarkers of Alzheimer’s disease and neuropathology. Of the 32 studies included in this review, all but one measured biomarker levels in plasma, and age and sex were the most commonly investigated factors. The most consistent significant findings were a positive association between age and neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), and females had higher GFAP than men. Apolipoprotein ε4 allele carriers had lower Aβ42 and Aβ42/40 ratio. Body mass index was negatively associated with GFAP and NfL, and chronic kidney disease with higher levels of all biomarkers. Too few studies have investigated other chronic health conditions and this requires further investigation. Given the potential for plasma biomarkers to enhance Alzheimer’s disease diagnosis in primary care, it is important to understand how to interpret the biomarkers in light of factors that physiologically impact blood biomarker levels. This information will be critical for the establishment of reference ranges and thus the correct interpretation of these biomarkers in clinical screening.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"1 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141571045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Universal Prevention of Dementia in Italy: A Document Analysis of the 21 Italian Regional Prevention Plans","authors":"S. Salemme, D. Marconi, S. M. Pani, G. Zamboni, C. Sardu, G. Lazzeri, M. Corbo, E. Lacorte, N. Locuratolo, A. Ancidoni, N. Vanacore, Guido Bellomo","doi":"10.14283/jpad.2024.144","DOIUrl":"https://doi.org/10.14283/jpad.2024.144","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Up to 40% of dementia cases are theoretically avoidable and population-level interventions (i.e., universal prevention) are a key component in facing the global public health challenge of dementia. However, information on the agenda for the universal prevention of dementia at the national and sub-national levels is still lacking.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>We aim to provide a comprehensive description of the universal prevention strategies specific to dementia in Italian regions and autonomous provinces (APs).</p><h3 data-test=\"abstract-sub-heading\">Design</h3><p>We conducted a document analysis of the 21 Italian Regional Prevention Plans (RPPs), with a focus on interventions that target potentially modifiable risk factors for dementia. We analysed the final version of the documents, which were previously downloaded from the dedicated section of the Italian Ministry of Health website in January 2023. We classified the interventions as direct, indirect, or absent. Additionally, we created a quality checklist to outline the essential programmatic elements and applied it to summarise the key findings of the RPPs.</p><h3 data-test=\"abstract-sub-heading\">Measurements</h3><p>We reported the number of populationlevel interventions specific for dementia with sub-national detail. We reported information on the risk factor targeted by the interventions, the age groups and populations they were designed for. We summarized the presence or absence of 63 programmatic items using a four-domain checklist.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>We identified 248 interventions for dementia prevention among the assessed RPPs: 100% of the plans addressed physical inactivity; 30–35% addressed smoking, alcohol, obesity, and social isolation; 25% addressed hypertension, diabetes, and air pollution; only 5–10% addressed education, depression, and hearing loss. Most interventions targeted the general population. Quality checklist scores significantly varied among regions, with demographics and prevention strategies domains scoring higher than disease burden and intervention feasibility ones.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The population-level interventions in the Italian Regional Prevention Programs dedicated to dementia prevention primarily focus on vascular risk factors, with limited coverage of dementia-specific factors such as traumatic brain injury and hearing loss. This data should be considered when planning future interventions for dementia prevention.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"17 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141571047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No Association Found: Adverse Childhood Experiences and Cognitive Impairment in Older Australian Adults","authors":"James Lian, K. M. Kiely, B. L. Callaghan, R. Eramudugolla, M. Mortby, K. J. Anstey","doi":"10.14283/jpad.2024.133","DOIUrl":"https://doi.org/10.14283/jpad.2024.133","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Objective</h3><p>This study aimed to investigate the relationship between childhood adversity and cognitive impairment in older adults.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We analysed data from 1568 participants aged 72–79 (M = 75.1, SD = 1.5, % male = 52.6%) from Wave 4 of the Personality and Total Health (PATH) Through Life Project. The outcome variable was the presence of mild cognitive impairment (MCI) or dementia, determined through a clinically validated algorithmic diagnostic criteria. Childhood adversity was assessed using a 17-item scale covering various domestic adversities such as poverty, neglect, physical abuse, and verbal abuse. Adversity was operationalised using cumulative analysis, dichotomisation (&lt;3 adversities; 3+ adversities), and latent class analysis. Multiple logistic regressions were employed to estimate the association between childhood adversity and cognitive impairment, while controlling for covariates including education, gender, ethnicity, and APOE ε4 status.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Our analyses revealed no significant association between childhood adversity and the presence of MCI or dementia across all tested models. Sensitivity analyses, exploring alternative scenarios, consistently failed to yield statistically significant findings.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>In contrast to prevailing research findings, this study does not support a link between childhood domestic adversity and late-life cognitive outcomes. These results underscore the mixed results on adversity and cognition, highlighting the need for further research. Future investigations should consider the roles of potential mediating and protective factors within this complex relationship.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"40 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141570988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lower Incidence of Dementia Following Cancer Diagnoses: Evidence from a Large Cohort and Mendelian Randomization Study","authors":"D. T. Bassil, B. Zheng, B. Su, D. Kafetsouli, C. Udeh-Momoh, I. Tzoulaki, S. Ahmadi-Abhari, D. C. Muller, Elio Riboli, L. T. Middleton","doi":"10.14283/jpad.2024.135","DOIUrl":"https://doi.org/10.14283/jpad.2024.135","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>The reported inverse association between cancer and subsequent Alzheimer’s disease and related dementias (ADRD) remains uncertain.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>To investigate the association between these common conditions of old age and explore possible causal factors.</p><h3 data-test=\"abstract-sub-heading\">Design, Setting, Participants and Measurements</h3><p>We conducted a large population-based cohort analysis using data from 3,021,508 individuals aged 60 and over in the UK Clinical Practice Research Datalink (CPRD), over a period up to 30 years (1988–2018). Cox proportional hazards models were fitted to estimate hazard ratios (HR) for risk of dementia associated with previous cancer diagnosis. Competing risk models were employed to account for competing risk of death. Two-sample Mendelian Randomization analysis based on meta-analysis data from large-scale GWAS studies was also conducted.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In the CPRD cohort, 412,903 participants had cancer diagnosis and 230,558 were subsequently diagnosed with dementia over a median follow-up period of 7.9 years. Cancer survivors had a 25% lower risk of developing dementia (HR=0.75, 95% CI:0.74–0.76) after adjustment for potential confounders. Accounting for competing risk of death provided a sub-distribution HR of 0.56 (95% CI:0.55–0.56). Results were consistent for prevalent and incident cancer and different common cancer types. Two-sample Mendelian Randomization analysis, using 357 cancer-related instrumental single-nucleotide polymorphisms (SNPs) revealed evidence of vertical pleiotropy between genetically predicted cancer and reduced risk of Alzheimer’s disease (OR=0.97,95% CI:0.95–0.99).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Our results provide strong epidemiological evidence of the inverse association between cancer and risk of ADRD and support the potential causal nature of this association via genetic instruments. Further investigations into the precise underlying biological mechanisms may reveal valuable information for new therapeutic approaches.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"32 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141571046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypothetical Interventions on Cardiovascular Health Metrics for Abnormal Cognitive Aging: An Application of the Parametric g-formula in the CLHLS Cohort Study with 12 Years Follow-Up","authors":"S. Huang, Z. Zhao, S. Wang, Y. Xu, Z. Wang, J. Wang, H. Wang, X. Yu, Xiaozhen Lv","doi":"10.14283/jpad.2024.143","DOIUrl":"https://doi.org/10.14283/jpad.2024.143","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Abnormal cognitive aging is closely related to dementia.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>This study aimed to estimate the effect of cardiovascular health (CVH) metrics on abnormal cognitive aging.</p><h3 data-test=\"abstract-sub-heading\">Design</h3><p>A longitudinal cohort study.</p><h3 data-test=\"abstract-sub-heading\">Setting</h3><p>Participants were recruited from the Chinese Longitudinal Health Longevity Survey.</p><h3 data-test=\"abstract-sub-heading\">Participants</h3><p>A total of 3298 participants aged ≥65 years with normal cognitive performance at baseline were included.</p><h3 data-test=\"abstract-sub-heading\">Measurements</h3><p>Cognitive performance was measured by the Chinese version of the Mini-Mental State Examination (MMSE). CVH was assessed with six metrics, including hypertension, diabetes, exercise, body mass index (BMI), diet, and smoking. Group-based trajectory model was used to identify the trajectory groups of cognitive aging over 12 years (2002–2014 and 2005–2018). The parametric g-formula was applied to estimate the effect of each single six CVH metrics and their combinations on the 12-year cognitive aging trajectory.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Four trajectory groups of cognitive aging were identified: Stable-high (77.4%), Unstable (4.9%), Slow decline (11.1%), and Rapid decline (6.6%). Unstable, Slow decline, and Rapid decline trajectory groups were considered as abnormal cognitive aging (22.6%). Single interventions on hypertension, exercise, BMI, and diet could reduce the risk of abnormal cognitive aging. Moreover, the risk ratios of joint intervention on exercise, BMI, and diet for Unstable, Slow decline, and Rapid decline trajectory groups were 0.38 (95% CI: 0.30–0.48), 0.45 (95% CI: 0.37–0.54), and 0.3 (95% CI: 0.23–0.41), respectively.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>A considerable proportion of the participants experienced abnormal cognitive aging during their aging process. Interventions on these CVH metrics (i.e., exercise, BMI, and diet), which are fairly practical and feasible for older adults, may be effective strategies for preventing abnormal cognitive aging.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"25 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141571048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}