Journal of Alzheimer's disease reports最新文献

{"title":"Synergistic activity of nootropic herbs as potent therapeutics for Alzheimer's disease: A cheminformatics, pharmacokinetics, and system pharmacology approach.","authors":"Reiya Bosco Don Bosco, Johnson Retnaraj Samuel Selvan Christyraj, Beryl Vedha Yesudhason","doi":"10.1177/25424823241307019","DOIUrl":"10.1177/25424823241307019","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder, which subdues over 55 million people and finding a cure, still remains disenchanting. Indian medicinal herbs notably, <i>Withania somnifera</i>, <i>Bacopa monnieri</i>, <i>Curcuma longa</i>, and <i>Clitoria ternatea</i> are traditionally utilized for their memory-enhancing properties.</p><p><strong>Objective: </strong>We computationally investigated the therapeutic potential of four nootropic herbs by uncovering the molecular mechanisms underlying their treatment for AD.</p><p><strong>Methods: </strong>Cheminformatics, pharmacokinetics, and system pharmacology studies were carried out to predict the phytocompounds drug-like properties, protein targets, targets functional association and enrichment analysis. A comparative study was performed with phytocompounds and FDA-approved drugs. Investigation on the expression of protein targets in the hippocampus and entorhinal cortex of the AD brain was performed. Network was constructed to depict the interaction between phytocompounds, drugs, and molecular targets.</p><p><strong>Results: </strong>Through comparative analysis, we found that the phytocompounds shared common targets with both FDA drugs and drugs under clinical trials. We identified potential active compounds notably, Withaferin A, Withanolide-D, Withanolide-E, Withanolide-G, and Humulene epoxide II, that can combat AD. Interestingly, the enzyme inhibition scores of the identified drugs were much higher than FDA-approved drugs. In addition, regulatory proteins such as AβPP, acetylcholinesterase, BACE1, and PTPN1 were the targets of 8, 16, 9, and 22 phytocompounds, respectively. Nonetheless, AR and CYP19A, were the primary targets of most phytocompounds.</p><p><strong>Conclusions: </strong>Herbal medicines can synergistically stimulate multiple protein targets, rendering a holistic and integrative treatment, encouraging a promising avenue to treat AD.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1745-1762"},"PeriodicalIF":2.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544887","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":"Exploring causal relationship of traumatic brain injury and comorbidities: A Mendelian randomization study.","authors":"Xiaohang Zhang, Wenze Wu, Yaqing Mao, Jiaxin Cheng, Zixuan Zhou, Yaqi Tang, Qiulong Zhao, Hui Yan","doi":"10.1177/25424823241304393","DOIUrl":"10.1177/25424823241304393","url":null,"abstract":"<p><strong>Background: </strong>Previous observational studies demonstrated a link existed between traumatic brain injury (TBI) and cerebral disease and multisystem complications, such as dementia, pneumonia, and gastrointestinal disease, but they could be confused by confounding and reverse causality.</p><p><strong>Objective: </strong>We aimed to figure out the causal correlation between TBI and the following complications.</p><p><strong>Methods: </strong>Database concerning TBI and complications from genome-wide association study (GWAS) and two-sample Mendelian randomization (MR) analysis was employed to examine whether TBI was causally associated with the risk of some complications. All the analysis was carried out through R, version 4.3.3.</p><p><strong>Results: </strong>MR analyses indicated that any dementia has a promotional effect on TBI (OR = 1.067, 95% CI, 1.011-1.123, p = 0.017). However, there was no causal genetically association between TBI and Alzheimer's disease (AD), Parkinson's disease (PD), pneumonia, or gastrointestinal disease.</p><p><strong>Conclusions: </strong>Contrary to observational studies, our results uncovered little causal association between TBI and PD, AD, depression, pneumonia, and gastrointestinal diseases. Interestingly, we found any dementia might be the risk of TBI, which was a new discovery.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1670-1676"},"PeriodicalIF":2.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544871","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 microbiome synthesizes important core metabolites to prevent cognitive decline and mitigate onset and progression of Alzheimer's disease.","authors":"Nouf S Al-Abbas, Nehad A Shaer","doi":"10.1177/25424823241309024","DOIUrl":"10.1177/25424823241309024","url":null,"abstract":"<p><strong>Background: </strong>This study explores how gut metabolites, produced through bacterial metabolism in the gut, influence neurological conditions like Alzheimer's disease (AD). Key metabolites such as succinate and short-chain fatty acids signal through the autonomic nervous system and can cross the blood-brain barrier, impacting central nervous system functions.</p><p><strong>Objective: </strong>The aim is to examine the role of the gut microbiota in compensating for metabolic deficiencies in AD. By analyzing wild-type (WT) and APP/PS1 mice, the study investigates how the microbiome affects key metabolic processes and whether it can slow AD progression.</p><p><strong>Methods: </strong>High-throughput sequencing data from the gut microbiomes of APP/PS1 transgenic AD model mice and age-matched WT C57BL/6 male mice were analyzed for microbial and metabolite profiles.</p><p><strong>Results: </strong>Alpha and beta diversity analyses showed differences in microbial composition between groups. Partial least squares discriminant analysis and Anosim confirmed distinct microbiome profiles in WT and APP/PS1 mice. At the genus level, <i>Vescimonas</i> was more abundant in WT mice, while <i>Odoribacter</i>, <i>Lacrimispora</i>, <i>Helicobacter</i>, <i>Bacteroides</i>, and <i>Alloprevotella</i> were more prevalent in APP/PS1 mice.</p><p><strong>Conclusions: </strong>While taxonomic differences did not directly link specific microorganisms to AD, functional analysis identified key metabolites-acetyl-CoA, glucose, succinate, lipids, choline, and acetylcholine-that may alleviate energy deficits and synaptic dysfunction. This study suggests that the microbiome may help compensate for AD-related impairments, opening avenues for microbiome-based therapies.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1705-1721"},"PeriodicalIF":2.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544872","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 progranulin gene deletion in frontotemporal lobar degeneration with corticobasal syndrome in a TREDEM case report.","authors":"Maurizio Gallucci, Chiara Da Ronch, Matteo Bendini, Vittorio Fiore, Licia Turolla, Moreno Ferrarini, Gian Maria Fabrizi, Pietro Tiraboschi","doi":"10.1177/25424823241302743","DOIUrl":"10.1177/25424823241302743","url":null,"abstract":"<p><strong>Background: </strong>Behavioral variant frontotemporal dementia usually presents with behavioral and personality changes, social disinhibition, apathy, and lack of empathy, and is characterized by atrophy of the frontal and temporal lobes. Corticobasal syndrome is characterized by asymmetrical involuntary movements, rigidity, apraxia, tremor, dystonia, and cortical sensory deficits.</p><p><strong>Objective: </strong>We present the case of a 59-year-old patient with a frontotemporal presentation and parkinsonism linked to progranulin gene deletion. We also report the clinical workup needed to reach the diagnosis.</p><p><strong>Methods: </strong>Clinical, neuropsychological, computed tomography, magnetic resonance imaging, ¹⁸F-fluorodeoxyglucose and ¹⁸F-Flutemetamol positron emission tomography (PET), dopamine-transporter-single-photon emission computed tomography imaging, electroencephalography, and genetic evaluations were conducted.</p><p><strong>Results: </strong>Our patient presented initially with executive and mnesic deficits along with the presence of apathy and loss of autonomy. Subsequently the cognitive deficits became associated with parkinsonian-like movement disorders and apraxia. Structural images showed right onset temporal and insular atrophy, and the PET images demonstrated right frontotemporal hypometabolism and the absence of amyloid in the cortex. The molecular analysis revealed a heterozygous deletion c.813_816delCACT on the <i>GRN</i> gene. This variant has been reported in the literature as pathogenic and associated with autosomal dominant frontotemporal dementia and corticobasal degeneration. Our patient presented different clinical features than those of the members of the families already described. In these families, some patients either presented immediately with motor syndrome with extrapyramidal features, or never developed extrapyramidal signs. Some subjects presented prevalent language dysfunction while others never presented memory disorders.</p><p><strong>Conclusions: </strong>The clinical case highlights the phenotypic variability of this entity.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1649-1660"},"PeriodicalIF":2.8,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543927","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":"How to assess cognitive decline when test administration changes across study waves? Harmonizing cognitive scores across waves in the China Health and Retirement Longitudinal Study.","authors":"Yingyan Wu, Yuan S Zhang, Lindsay C Kobayashi, Elizabeth Rose Mayeda, Alden L Gross","doi":"10.1177/25424823241302759","DOIUrl":"10.1177/25424823241302759","url":null,"abstract":"<p><strong>Background: </strong>Conducting longitudinal cognitive analyses is an essential part of understanding the underlying mechanism of Alzheimer's disease, especially for social and health behavior determinants. However, the cognitive test administration is highly likely to change across time and thus complicate the longitudinal analyses. The China Health and Retirement Longitudinal Study assessed memory through word recall tests across five study waves from 2011 to 2020. Since 2018, changes in the test stimuli and administration posed challenges for longitudinal cognitive analyses.</p><p><strong>Objective: </strong>To address differences in administration and to preserve differences attributed to characteristics such as age and education and to derive equated scores for use in longitudinal analyses in CHARLS.</p><p><strong>Methods: </strong>To ensure consistent underlying test ability across waves in the full sample (N = 19,364), we derived a calibration sample (N = 11,148) balancing age, gender, and education. Within this sample, we used weighted equipercentile equating to crosswalk percentile ranks between 2015 and 2018/2020 scores, then applied the algorithm to the full sample.</p><p><strong>Results: </strong>Mean original delayed word recall was higher in 2018 (4.3 words) and 2020 (5.1 words) versus 2015 (3.2 words). Following equating, scores in 2018 and 2020 aligned better with previous waves (2015, 2018, 2020 immediate means: 4.1, 3.6, 4.0; delayed: 3.2, 2.4, 2.9 words).</p><p><strong>Conclusions: </strong>Equipercentile equating enables the derivation of comparable scores, facilitating longitudinal analysis when cognitive test administration procedures change over time. We recommended the use of equated scores for longitudinal analyses using CHARLS cognitive data.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1661-1669"},"PeriodicalIF":2.8,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544873","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":"Retinal vascular changes are associated with PET-based biomarkers of Alzheimer's disease: A pilot study.","authors":"Kristie Hing Chi Leung, Victor T T Chan, Bonnie Yin Ka Lam, Vincent Ct Mok, Carol Y Cheung","doi":"10.1177/25424823241300416","DOIUrl":"10.1177/25424823241300416","url":null,"abstract":"<p><strong>Background: </strong>Retina is a non-invasive channel for assessing changes in brain microvasculature, which has been implicated in the pathophysiology of Alzheimer's disease (AD). Previous studies revealed significant relationship between clinically diagnosed AD and retinal vasculature. However, clinical diagnosis has limited sensitivity and specificity, and those investigations were conducted from traditional retinal fundus photographs which only captured a narrow section of the fundus.</p><p><strong>Objective: </strong>Determining changes in retinal vasculature from larger area of retina between subjects with positron emission tomography (PET) biomarker-confirmed AD compared to controls.</p><p><strong>Methods: </strong>Participants were recruited from the community and cognitive disorder clinics. Diagnosis of AD was confirmed by significant amyloid-β (Aβ) and tau uptake on PET scan. Retinal vasculature was imaged with ultra-widefield (UWF) scanning laser ophthalmoscopy and a series of vessel parameters were quantified using the semi-automated Singapore I Vessel Assessment (SIVA) software. Statistical analyses were adjusted for age, gender and systolic blood pressure. In addition, arteriole parameters were adjusted against the same measurements in venules, and vice versa.</p><p><strong>Results: </strong>Out of the 39 patients, 18 had radiologically confirmed AD. These individuals with AD showed significantly smaller arteriolar fractal dimension (<i>p </i>= 0.032) in UWF images and greater venular tortuosity (<i>p</i> = 0.011) in standard fundus images compared with controls. Presence of significant Aβ and tau burden was associated with lower arteriolar caliber (OR 3.857; 95% CI 1.014-14.67; <i>p </i>= 0.048).</p><p><strong>Conclusions: </strong>Reduction of fractal dimension in retinal arterioles observed in UWF imaging is associated with cerebral Aβ and tau burden in people with biomarker-confirmed AD. Wide field retinal imaging provides an alternative perspective in demonstrating microvascular alterations related to AD in this pilot study.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1639-1648"},"PeriodicalIF":2.8,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544878","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":"<i>Centella asiatica</i> improves cognitive function and alters the hippocampal metabolome of aged Tg2576 and wild-type mice.","authors":"Donald G Matthews, Mona Khorani, Gerd Bobe, Maya Caruso, Armando Alcazar Magana, Nora E Gray, Joseph F Quinn, Jan F Stevens, Claudia S Maier, Amala Soumyanath","doi":"10.1177/25424823241296740","DOIUrl":"10.1177/25424823241296740","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a growing public health problem in the aging population, with limited treatment options. We previously reported that <i>Centella asiatica</i> herb water extract (CAW) attenuates cognitive decline in murine models of AD and aging.</p><p><strong>Objective: </strong>To explore changes in the hippocampal metabolome associated with CAW's modulation of cognitive function and amyloid-β (Aβ) plaque load in aged Tg2576 and wild-type (WT) mice.</p><p><strong>Methods: </strong>We compared cognitive function, hippocampal Aβ plaque burden, and hippocampal metabolite profile in 20-month-old Tg2576 female mice and their WT littermates following 3-5 weeks treatment with CAW (0, 200, or 1000 mg/kg/d p.o.). Cognitive testing included contextual fear response (CFR) and novel object recognition task (NORT). Aβ plaque burden was measured via immunohistochemistry. Metabolomic profiles of mouse hippocampi were obtained using liquid chromatography coupled with high resolution tandem mass spectrometry.</p><p><strong>Results: </strong>CAW treatment resulted in dose-related improvements in CFR and NORT performance of Tg2576 and WT mice. However, while CFR correlated with neurosignaling and glycosylated ceramide levels, NORT performance correlated with lysophosphatidylcholines and oxidized metabolites, and Aβ accumulation was linked to elevated excitatory and suppressed inhibitory neurotransmission. Only a subset of the metabolite changes induced by CAW in Tg2576 mice represented a reversal of metabolite differences between Tg2576 and WT mice, suggesting the involvement of other pathways in CAW's cognitive effects.</p><p><strong>Conclusions: </strong>Mechanisms underlying CAW's cognitive effects extend beyond reversing metabolic effects of Aβ accumulation. The data support the potential use of CAW to manage memory challenges in aged individuals with or without AD.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1611-1638"},"PeriodicalIF":2.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544864","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":"Association between dementia, Alzheimer's disease, and liver cancer: A Mendelian randomization analysis.","authors":"Tianze Li, Jianwei Yi, Xuliang Hu, Huajun Wu, Kai Wang, Binghai Zhou","doi":"10.1177/25424823241299661","DOIUrl":"10.1177/25424823241299661","url":null,"abstract":"<p><strong>Background: </strong>Epidemiological studies have indicated an inverse association between neurodegenerative diseases and cancer. However, the relationship between liver cancer and dementia, particularly Alzheimer's disease (AD), remains underexplored.</p><p><strong>Objective: </strong>This study aimed to determine the association between dementia, specifically AD, and liver cancer using Mendelian randomization (MR) analysis.</p><p><strong>Methods: </strong>We conducted a bidirectional, two-sample MR analysis using publicly available genome-wide association studies data. The inverse-variance weighted method was employed as the primary analytical approach. To detect and correct for the effects of horizontal pleiotropy, we applied three complementary methods: MR Egger, weighted median, and Maximum likelihood.</p><p><strong>Results: </strong>The analysis indicated significant associations between dementia and a reduced risk of hepatocellular carcinoma (HCC) (OR: 0.87; 95%CI: 0.81-0.95; p < 0.001) and intrahepatic cholangiocarcinoma (ICC) (OR: 0.81; 95%CI: 0.72-0.92; p < 0.001). AD was significantly associated with a decreased risk of HCC (OR: 0.94; 95%CI: 0.88-0.99; p = 0.033), ICC (OR: 0.85; 95%CI: 0.78-0.93; p < 0.001), and combined hepatocellular-cholangiocarcinoma (CHC) (OR: 0.64; 95%CI: 0.43-0.93; p = 0.020). Conversely, inverse MR analyses indicated that ICC was associated with increased dementia risk (OR: 1.05; 95%CI: 1.01-1.09; p = 0.019) and CHC with increased AD risk (OR: 1.03; 95%CI: 1.00-1.04; p = 0.014).</p><p><strong>Conclusions: </strong>This study suggests that dementia, particularly AD, is associated with a reduced risk of liver cancer. Conversely, liver cancer may be associated with a slightly increased risk of developing dementia and AD, although some observational studies have reported a lower risk of these conditions among cancer survivors.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1587-1595"},"PeriodicalIF":2.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544638","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":"Cardio and cerebrovascular diseases risk among Alzheimer's disease patients and racial/ethnic disparities, based on Hawaii Medicare data.","authors":"Chathura Siriwardhana, Enrique Carrazana, Kore Liow, John J Chen","doi":"10.1177/25424823241289038","DOIUrl":"10.1177/25424823241289038","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) and cardiovascular and cerebrovascular diseases (CVD) are significant concerns among the elderly, sharing overlapping risk factors. Hawaii's unique demographic profile, characterized by its strong ethnic diversity, shows marked racial health disparities. For instance, the Native Hawaiian/Pacific Islander (NHPI) population is identified as a high-risk group for multiple health conditions, including CVD.</p><p><strong>Objective: </strong>This study investigates the impact of AD on the risk of developing CVD, with a focus on racial influences, utilizing Hawaii Medicare data.</p><p><strong>Methods: </strong>Employing nine years of longitudinal Hawaii Medicare data, this study identified elderly patients diagnosed with AD who subsequently developed heart failure (HF), ischemic heart disease (IHD), atrial fibrillation (AF), acute myocardial infarction (AMI), or stroke. To assess the risk of CVD, we utilized multistate models and employed propensity score-matched controls. Additionally, we evaluated racial and ethnic differences in the risk of these diseases, while accounting for other relevant risk factors.</p><p><strong>Results: </strong>Our findings revealed an elevated risk of AMI, HF, and IHD among individuals diagnosed with AD. Additionally, socioeconomic status (SE) was identified as a crucial factor in the risk of cardio and cerebrovascular diseases. Within the low SE group, NHPIs exhibited increased risks of HF and IHD compared to their white counterparts. Interestingly, NHPIs demonstrated reduced risks of HF in the higher SE group.</p><p><strong>Conclusions: </strong>The presence of AD increases the likelihood of developing AMI, HF, and IHD. Moreover, the risk of CVD appears to be influenced by race/ethnicity in Hawaii, as well as socioeconomic status.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1529-1540"},"PeriodicalIF":2.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544789","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":"Therapeutic drug monitoring for dose optimization in Alzheimer's disease and in dementia with Lewy bodies: A randomized single-blinded clinical trial.","authors":"Michael Hén Forbord Fischer, Ivan Chrilles Zibrandtsen, Peter Johannsen, Volkert Siersma, Jan Borg Rasmussen, Jens Borggaard Larsen, Peter Høgh","doi":"10.1177/25424823241289373","DOIUrl":"10.1177/25424823241289373","url":null,"abstract":"<p><strong>Background: </strong>Previous evidence suggests serum concentrations of donepezil varies in clinical populations and that a dose higher than standard may have additional positive effect on cognition. Therapeutic drug monitoring (TDM) is a tool for dose optimization (DO) whereby treatment is adjusted based on previous quantification of the prescribed drug.</p><p><strong>Objective: </strong>Investigate whether TDM-based DO of donepezil or memantine improves clinical outcomes and/or reduce the frequency of adverse reactions (ARs) in neurodegenerative conditions commonly treated with these two study drugs.</p><p><strong>Methods: </strong>Single-blinded 1:1 randomized controlled study in an outpatient memory clinic. Eligible participants either newly diagnosed with Alzheimer's disease dementia (AD), dementia with Lewy bodies (DLB), or Parkinson's disease dementia (PDD) scheduled for treatment with donepezil or memantine. The intervention group received TDM based DO. The control group received DO solely based on clinical assessment. Clinical outcomes were change in Mini-Mental State Examination, Addenbrooke's Cognitive Examination, Neuropsychiatric Inventory, and Disability Assessment in Dementia from baseline to 12 months. Additionally, data on incidence and severity of ARs and proportion of participants with a serum concentration within the therapeutic reference range were collected.</p><p><strong>Results: </strong>132 participants recruited (125 AD, 7 DLB, none with PDD) of whom 107 completed the study (101 AD and 6 DLB), fewer in the control group than planned. Statistical analysis did not reveal significant differences between groups neither for clinical outcomes nor for frequency of ARs.</p><p><strong>Conclusions: </strong>TDM based DO did not significantly improve clinical outcomes nor reduce the frequency of ARs albeit important caveats to the results apply.</p><p><strong>Clincialtrialsgov identifier: </strong>NCT04117178 (first posted October 7, 2019).</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1516-1528"},"PeriodicalIF":2.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544890","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}