{"title":"Sentiment analysis of social media responses to the approval of lecanemab for the treatment of Alzheimer's disease in Japan.","authors":"Kenichiro Sato, Yoshiki Niimi, Ryoko Ihara, Atsushi Iwata, Kiyotaka Nemoto, Tetsuaki Arai, Shinji Higashi, Ataru Igarashi, Kensaku Kasuga, Takeshi Iwatsubo","doi":"10.1177/25424823241307639","DOIUrl":"10.1177/25424823241307639","url":null,"abstract":"<p><p>Lecanemab, an anti-amyloid therapy for early Alzheimer's disease, received approval by the FDA and Japan in 2023. Public response on social media was scrutinized, aiming to obtain insights into communication and treatment development. For 478 posts from X and Facebook, their sentiments on efficacy, safety, societal significance, and overall lecanemab impression were assessed by GPT-4 and the authors. Results indicated impressions were 43.7% negative, 26.6% neutral, and 29.7% positive. Social significance concerns dominated negative views. Specific attitude patterns were observed in the overall impression to lecanemab's approval. These insights highlight the need for targeted communication and research on anti-amyloid therapies.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241307639"},"PeriodicalIF":2.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anum Saeed, Yuefang Chang, Justin Swanson, Michael Vu, Mark Mapstone, Victor L Villemagne, Beth E Snitz, Sarah K Royse, Hongtian Wang, Brian Lopresti, Howard J Aizenstein, Minjie Wu, Kevin Kip, Steven E Reis, Oscar Lopez, Ann Cohen
{"title":"Association of mid-life cardiovascular risk with biomarkers of Alzheimer's disease, neurodegeneration, and white matter hyperintensities: Heart SCORE brain study.","authors":"Anum Saeed, Yuefang Chang, Justin Swanson, Michael Vu, Mark Mapstone, Victor L Villemagne, Beth E Snitz, Sarah K Royse, Hongtian Wang, Brian Lopresti, Howard J Aizenstein, Minjie Wu, Kevin Kip, Steven E Reis, Oscar Lopez, Ann Cohen","doi":"10.1177/25424823241299297","DOIUrl":"10.1177/25424823241299297","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerotic cardiovascular disease (ASCVD) risk factors in mid-life are associated with cognitive decline and late-life dementia. However, the role of these risk factors in Alzheimer's disease (AD) pathology remains elusive.</p><p><strong>Objective: </strong>We investigated the association of mid-life 10-year ASCVD risk with late-life amyloid, tau, neurodegeneration [AT(N)] measures and white matter hyperintensities (WMHs).</p><p><strong>Methods: </strong>Participants enrolled in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study between 2003-2005 (mid-life) and underwent brain MRI and PET scans in 2018-2022 (age >65 years, late-life) to detect and quantify amyloid (A, PiB-PET) and tau (T, Flortaucipir (FTP) PET) deposition, cortical thickness (N) and WMHs. Mid-life ASCVD risk was categorized as; borderline (5%-7.4%), intermediate (7.5%-<15%), or high (≥15%). Association of mid-life ASCVD risk HR (95% CI) was assessed using logistic and linear regressions with A, T, or N and chi square beta coefficients for WMH in late life.</p><p><strong>Results: </strong>Over a ∼16 years follow up, in 135 participants (mean age 73 years), mid-life ASCVD risk categories had a graded association with neurodegeneration (OR<sub>ASCVD high vs low risk%</sub> 6.98 [2.44-19.95]; p < 0.05) driven primarily by self-identified Black race and age, while none with A and T. ASCVD risk score was also associated with WMHs ((β=0.42 ± 0.22; p = 0.05).</p><p><strong>Conclusions: </strong>In this asymptomatic, diverse cohort, 10-year ASCVD risk was predictive of late-life neurodegeneration and WMHs but not amyloid or tau. Further mechanistic studies can elucidate whether midlife ASCVD risk factors associated neurodegeneration initiates brain vulnerability leading to AD in late life.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241299297"},"PeriodicalIF":2.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A 52-week, open-label, observational study evaluating tolerability, efficacy and physicians satisfaction of rivastigmine oral solution in Alzheimer's disease in Taiwan.","authors":"Chuo-Yu Lee, Wen-Fu Wang, Jung-Lung Hsu, Yuan-Han Yang, Kai-Ming Jhang","doi":"10.1177/25424823241311860","DOIUrl":"10.1177/25424823241311860","url":null,"abstract":"<p><strong>Background: </strong>There is limited data on the use of rivastigmine oral solution in patients with Alzheimer's disease (AD).</p><p><strong>Objective: </strong>To evaluate the tolerability, efficacy and physicians' satisfaction of Rivast<sup>®</sup> (rivastigmine oral solution 2 mg/ml) in Taiwanese patients with mild to moderate AD over a 52-week period.</p><p><strong>Methods: </strong>An open-label, non-comparative, observational study was conducted across four hospitals in Taiwan. 142 Patients with mild to moderate AD were enrolled. Adverse events and adherence rates were monitored throughout the 52-week study period, while cognitive (Mini-Mental State Examination (MMSE)) and global functional outcomes (Clinical Dementia Rating (CDR)-Sum of Boxes) were recorded at baseline and at week 52. Factors associated with discontinuation, adverse events, and declines in cognitive and global function were determined.</p><p><strong>Results: </strong>The study achieved a 92.3% adherence rate, with 19% experiencing adverse events. The optimal dose was 3.8 ml, reached within 8.3 weeks. 43.7% of the patients reached an optimal dose of 4 ml and 59.8% achieved optimal dose within 4 weeks. Age and clinically significant electrocardiogram (EKG) abnormalities were associated with a higher risk of discontinuation, while female patients exhibited a lower risk. Additionally, both a higher initial dose and a higher optimal dose were associated with a reduced risk of adverse effects. Abnormal EKG findings were significantly associated with cognitive decline. More time to optimal dose was significantly associated with worse global function. All physicians regarded the medication is ease of use and the administration schedule is simple.</p><p><strong>Conclusions: </strong>This study provides valuable insights into the tolerability and efficacy of rivastigmine oral solution in Taiwanese patients with mild to moderate AD.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241311860"},"PeriodicalIF":2.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sudhir Kshirsagar, Md Ariful Islam, Arubala P Reddy, P Hemachandra Reddy
{"title":"Cell culture research in aging and Alzheimer's disease: The strategic use/reuse of untreated controls and savings people's tax dollars.","authors":"Sudhir Kshirsagar, Md Ariful Islam, Arubala P Reddy, P Hemachandra Reddy","doi":"10.1177/25424823241310716","DOIUrl":"10.1177/25424823241310716","url":null,"abstract":"<p><p>Cell culture is an essential tool in both fundamental and translational research, particularly for understanding complex diseases like Alzheimer's disease (AD). The use of cell lines provides the advantage of genetic homogeneity, ensuring reproducible and consistent results. This article explores the application of mammalian cell cultures to model AD, focusing on the transfection of cells with key genes associated with the disease to replicate the cellular environment of AD. It explains various transfection methods and challenges related to the process. These models offer a robust platform for investigating cellular biology, molecular pathways, physiological processes, and drug discovery efforts. A range of assays, including RT-PCR, western blotting, ELISA, mitochondrial respiration, and reactive oxygen species analysis, are employed to assess the impact of genetic modifications on cellular functions and to screen potential AD therapies. Researchers often design experiments with multiple variables such as genetic modifications, chemical treatments, or time points, paired with positive and negative controls. By using a consistent control group across all conditions and under identical experimental conditions, researchers can minimize variability and enhance data reproducibility. This approach is particularly valuable in AD research, where small experimental differences can significantly influence outcomes. Using a shared control group ensures data comparability across experiments, saving time and resources by eliminating redundant control tests. This strategy not only streamlines the research process but also improves the reliability of results, making it a sensible, resource-efficient method that ultimately conserves public funding in the pursuit of AD treatments.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241310716"},"PeriodicalIF":2.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A historic case of relapsing-remitting Alzheimer's disease in an adolescent attributed to scarlet fever.","authors":"Richard Lathe, Brian Balin","doi":"10.1177/25424823241298530","DOIUrl":"10.1177/25424823241298530","url":null,"abstract":"<p><p>We draw attention to a historic case of a boy who suffered from scarlet fever (typically caused by the bacterium <i>Streptococcus pyogenes</i>) at age 7 years and went on to develop the symptoms of Alzheimer's disease (AD). His physicians believed that the subsequent dementia was related to the infection. After death at 24 years of age, postmortem brain examination revealed abundant AD-type senile plaques and fibrils, formally confirming AD. Other potential causes of early-onset dementia are discussed, but these are distinct from patient E.H. This case is pertinent regarding the current debate about the potential role of infection in AD.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241298530"},"PeriodicalIF":2.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pivotal trial of low-intensity pulsed ultrasound therapy for early Alzheimer's disease: Rationale and design.","authors":"Hiroaki Shimokawa, Masahiro Akishita, Masafumi Ihara, Satoshi Teramukai, Aiko Ishiki, Yoji Nagai, Masanori Fukushima","doi":"10.1177/25424823241312108","DOIUrl":"10.1177/25424823241312108","url":null,"abstract":"<p><strong>Background: </strong>There are lines of evidence suggesting that cerebral microcirculatory dysfunction is involved in the pathogenesis of Alzheimer's disease (AD). We have developed a low-intensity pulsed ultrasound (LIPUS) therapy that upregulates endothelial NO synthase with therapeutic angiogenesis. We demonstrated that the LIPUS therapy ameliorates cognitive declines in mouse models of AD and tended to do so in patients with early AD (mild AD and mild cognitive impairment due to AD) in the pilot trial. Thus, the Japanese government has designated our LIPUS device as the first breakthrough medical device in Japan.</p><p><strong>Objective: </strong>We are performing a pivotal clinical trial (LIPUS-AD) to finally address the efficacy and safety of our LIPUS therapy in patients with early AD in Japan.</p><p><strong>Methods: </strong>LIPUS-AD is a randomized, double-blind, placebo-controlled trial, in which a total of 220 patients with early AD, who are positive for amyloid-β (Aβ) PET, will be randomized in a 1:1 fashion. The LIPUS therapy is performed for the whole brain for one hour 3 times a week as one session under the special conditions (32 cycles, 0.5 MHz, 0.25 W/cm<sup>2</sup>). It is performed for 6 sessions with 3-month intervals in the LIPUS group for 72 weeks, while the placebo group receives placebo therapy. Before and at 72 weeks of the trial, all subjects undergo brain Aβ PET and MRI and 9 cognitive functions tests. The primary efficacy endpoint is the changes in ADAS-J-cog-14 scores from baseline to 72 weeks.</p><p><strong>Conclusions: </strong>LIPUS-AD addresses efficacy and safety of the LIPUS therapy in patients with early AD.Clinical Trial Gov. No.: NCT05983575.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241312108"},"PeriodicalIF":2.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gut microbiota may affect Alzheimer's disease through synaptic function mediated by CAMs pathway: A study combining Mendelian randomization and bioinformatics.","authors":"Ji-Yun Liu, Cong-Yan Tan, Li Luo, Xuan Yin","doi":"10.1177/25424823241310719","DOIUrl":"10.1177/25424823241310719","url":null,"abstract":"<p><strong>Background: </strong>The association between gut microbes and Alzheimer's disease (AD) has not been entirely elucidated.</p><p><strong>Objective: </strong>We aimed to demonstrate the association between gut microbes and AD and to further investigate the pathogenesis of microbes with a causal relationship to AD.</p><p><strong>Methods: </strong>Mendelian randomization analyses were used to determine the significant causal relationship between gut microbes and AD. Protein-protein interaction (PPI) network was used to identify the hub genes. Functional enrichment analysis was used to reveal the pathogenesis theoretically between gut microbes and AD.</p><p><strong>Results: </strong>In the present study, a total of 32 microbes were identified that were significantly associated with AD. Subsequently, DLGAP2, NRXN3, NEGR1, NTNAP2, MYH9, and SCN3A were identified as hub genes. The genes NRXN3, NEGR1, and NTNAP2 were enriched in the cell adhesion molecules (CAMs) signaling, and the taxons of gut microbes that corresponded to these were <i>Bifidobacterium adolescentis, Actinomycetales,</i> and <i>Intestinimonas massiliensis</i>.</p><p><strong>Conclusions: </strong><i>Bifidobacterium adolescentis, Actinomycetales</i>, and <i>Intestinimonas massiliensis</i> may promote the progression of AD through the regulation of the CAMs signaling pathway-mediated synaptic function. Hence, the in-depth study of gut microbes may increase the efficiency of screening and diagnosis of AD.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241310719"},"PeriodicalIF":2.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Single-session gamma sensory stimulation entrains real-time electroencephalography but does not enhance perception, attention, short-term memory, or long-term memory.","authors":"Cai-Syuan Wu, Ting-Xuan Lin, Yu-Hui Lo, Shih-Chiang Ke, Prangya Parimita Sahu, Philip Tseng","doi":"10.1177/25424823241311927","DOIUrl":"10.1177/25424823241311927","url":null,"abstract":"<p><strong>Background: </strong>Studies have shown that gamma (40 Hz) audiovisual stimulation can enhance gamma oscillations and improve cognitive functioning in patients with Alzheimer's disease. However, despite promising long-term results, the efficacy of short-duration or single-session 40 Hz entrainment in humans has been questioned by behavioral studies that fail to find observable cognitive aftereffects, for two possible reasons: 1) lack of validated gamma entrainment, as most studies lacked concurrent electroencephalography (EEG) data to verify that gamma neural entrainment did take place, and 2) lack of diverse cognitive tests, as most studies did not test a wide range of cognitive factors.</p><p><strong>Objective: </strong>This study aimed to increase sensitivity for detecting single-session gamma entrainment. We employed 1) mid- and post-stimulation EEG monitoring to ensure entrainment worked, and 2) a comprehensive cognitive battery that probes perception, attention, working memory, and long-term memory.</p><p><strong>Methods: </strong>Participants received 30 min of synchronized 40 Hz light and sound stimulation, followed by a visual perceptual task, attentional network task, change detection working memory task, and long-term picture memory task, with concurrent EEG.</p><p><strong>Results: </strong>We observed robust 40 Hz EEG entrainment during stimulation but no significant 40 Hz oscillation after stimulation, and no significant cognitive improvements.</p><p><strong>Conclusions: </strong>Despite robust 40 Hz online entrainment, gamma sensory entrainment requires consistent long-term exposure to induce cognitive and neurological changes. Future research should determine the optimal duration and frequency of 40 Hz stimulation to maximize its therapeutic potential.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241311927"},"PeriodicalIF":2.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Linyang Cui, Yahui Wan, Yunyao Lu, Meng Meng, Nan Zhang
{"title":"Sleep disturbances and their correlation with memory impairment in patients with Alzheimer's disease and amnestic mild cognitive impairment.","authors":"Linyang Cui, Yahui Wan, Yunyao Lu, Meng Meng, Nan Zhang","doi":"10.1177/25424823241309063","DOIUrl":"10.1177/25424823241309063","url":null,"abstract":"<p><strong>Background: </strong>Episodic memory impairment is the core clinical feature of patients with typical Alzheimer's disease (AD) at an early stage. Since sleep plays a very important role in memory consolidation, the relationship between memory impairment and sleep disorders in AD patients is worthy of investigation.</p><p><strong>Objective: </strong>To investigate sleep disturbances and their correlations with memory impairment in patients with AD and amnestic mild cognitive impairment (aMCI).</p><p><strong>Methods: </strong>Forty-three patients with AD, 43 patients with aMCI, and 43 cognitively unimpaired controls (CUCs) were recruited and subjected to memory assessment via the Hopkins Verbal Learning Test-Revised and objective sleep evaluation via polysomnography (PSG).</p><p><strong>Results: </strong>The total sleep time and the percentages of nonrapid eye movement (NREM) sleep stage 3 (N3) and the rapid eye movement (REM) were lower, while the percentages of NREM sleep stage 2 (N2) were greater in the AD and aMCI groups than in the CUC group (all p < 0.01). Compared with the CUC group, the AD group also presented a longer sleep latency and higher NREM sleep stage 1 (N1) percentage, apnea-hypopnea index (AHI), periodic limb movements during sleep index (PLMSI), and arousal index (AI). Both total learning scores and delayed recall scores were positively correlated with the N3 sleep percentage and negatively correlated with the AHI and PLMSI (all p < 0.01). Recognition scores were positively correlated with the N3 sleep percentage and negatively correlated with the AI (all p < 0.01).</p><p><strong>Conclusions: </strong>Our results suggest that sleep disturbance is correlated with learning and memory disability in AD and aMCI patients. PSG is useful for screening and monitoring AD.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241309063"},"PeriodicalIF":2.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The causal role of lipids in dementia: A Mendelian randomization study.","authors":"Boyang Su, Zhengqing He, Li Mao, Xusheng Huang","doi":"10.1177/25424823241312106","DOIUrl":"10.1177/25424823241312106","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence suggests that abnormal lipid metabolism is one of the pathogeneses of dementia. It is necessary to reveal the relationship between lipids and dementia.</p><p><strong>Objective: </strong>This study used bidirectional two-sample Mendelian randomization to explore the causal relationship between 179 lipid species and the risk of dementia.</p><p><strong>Methods: </strong>We assessed the causal effects of 179 lipid species and four subtypes of dementia including Alzheimer's disease (AD), vascular dementia (VaD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). Inverse variance weighting, MR-Egger method, weighted median, simple mode, and weighted mode were used to analyze the relationship between lipids and dementia. Cochran's Q, MR-Egger intercept test, and MR-PRESSO test were used to test the heterogeneity and pleiotropy of the results. In addition, we performed an inverse MR analysis testing the causal effects of dementia on lipids.</p><p><strong>Results: </strong>Our study revealed causal effects of glycerophospholipid, glycerolipid, and sterol on the risk of dementia. Phosphatidylcholine, phosphatidylinositol, and triglycerides play significant roles in AD. Notably, phosphatidylcholine played a protective role in both FTD and DLB. However, this study did not observe a significant effect of phosphatidylinositol on FTD. In the case of VaD, not only glycerophospholipid, but also glycerolipid, exerted an influence, but sterol was also a risk factor.</p><p><strong>Conclusions: </strong>Our study provided new evidence supporting the causal role of genetically predicted lipid species in dementia. Future clinical trials are necessary to evaluate the potential role of lipid levels in dementia prevention.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823241312106"},"PeriodicalIF":2.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}