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

{"title":"The effect of sleep disturbances on the incidence of dementia for varying lag times.","authors":"Peter Alders, Almar Kok, Elisabeth M van Zutphen, Jurgen A H R Claassen, Dorly J H Deeg","doi":"10.1016/j.tjpad.2024.100024","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100024","url":null,"abstract":"<p><strong>Background: </strong>Few studies have addressed the association of sleep disturbances with incident dementia with long lag times. We add to this literature by investigating how lag times varying from 2.2 to 23.8 years affect the relationship between sleep disturbance and incident dementia in a Dutch cohort study on aging.</p><p><strong>Methods: </strong>Using eight waves of data from the Longitudinal Aging Study Amsterdam, we investigated the association of hours of sleep, difficulty falling asleep, interrupted sleep, and waking up early with incident dementia. For dementia an algorithm was used based on repeated measurements of cognitive tests and other data sources that provide strong indications of dementia. Sleep disturbances were assessed with a self-report questionnaire.</p><p><strong>Results: </strong>Of 2,218 participants, 237 (11%) developed dementia in the period 1992/3 to 2015/6. Participants ≥70 years more often reported sleep disturbances compared to those <70. Only for a short lag time (3 years), sleeping ≥9 h was associated with incident dementia. Sleeping ≤6 h, interrupted sleep and waking up early were associated with incident dementia, particularly for lag times ≥15 years.</p><p><strong>Discussion: </strong>We found that the association of sleep disturbances with incident dementia becomes stronger with longer lag times (particularly ≥15 years). Studies with lag times <15 years may suffer from reverse causation due to the changes in sleep patterns caused by the prodromal phase of neurodegenerative disease. The association of sleeping ≥9 h and the incidence of dementia in analyses with a short lag time seem to be the result of reverse causation.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 2","pages":"100024"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042046","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":"High definition transcranial direct current stimulation as an intervention for cognitive deficits in Alzheimer's dementia: A randomized controlled trial.","authors":"Christian LoBue, Hsueh-Sheng Chiang, Amber Salter, Shawn McClintock, Trung P Nguyen, Rebecca Logan, Eric Smernoff, Seema Pandya, John Hart","doi":"10.1016/j.tjpad.2024.100023","DOIUrl":"10.1016/j.tjpad.2024.100023","url":null,"abstract":"<p><strong>Background: </strong>Recent disease-modifying treatments for Alzheimer's disease show promise to slow cognitive decline, but show no efficacy towards reducing symptoms already manifested.</p><p><strong>Objectives: </strong>To investigate the efficacy of a novel noninvasive brain stimulation technique in modulating cognitive functioning in Alzheimer's dementia (AD).</p><p><strong>Design: </strong>Pilot, randomized, double-blind, parallel, sham-controlled study SETTING: Clinical research site at UT Southwestern Medical Center PARTICIPANTS: Twenty-five participants with clinical diagnoses of AD were enrolled from cognition specialty clinics.</p><p><strong>Intervention: </strong>Treatment consisted of high definition transcranial direct current stimulation (HD-tDCS) delivered for 20 min over the medial prefrontal cortex. Ten sessions of sham, 1 mA, or 2 mA stimulation were received.</p><p><strong>Measurements: </strong>Cognitive outcomes were measured at baseline, after the last HD-tDCS session, and 8-weeks post-treatment. The primary outcome was change in total learning and delayed recall on the Rey Auditory Verbal Learning Test (RAVLT) immediately post-treatment and at 8-weeks. Secondary outcomes included measures of language, processing speed, and executive functioning. A multi-stage approach was used to examine cognitive outcomes, which included evaluation of effect sizes, statistical effects, and rate of clinically meaningful responses.</p><p><strong>Results: </strong>In this pilot trial, no statistically significant differences on cognitive outcomes were found between sham and active HD-tDCS immediately post-treatment (p's > 0.05). However, moderate-to-large effect sizes were identified for enhanced RAVLT total learning (Cohen's d = 0.69-0.93) and phonemic fluency (d = 1.08-1.49) for both active HD-tDCS conditions compared to sham, with rates of clinically relevant improvement between 25 and 33%. Meaningful enhancement persisted to 8 weeks only for the 1 mA condition.</p><p><strong>Conclusions: </strong>Multiple sessions of HD-tDCS over the medial prefrontal cortex appears to have potential to produce meaningful cognitive enhancements in a proportion of patients having AD with improvements maintained for at least 8 weeks in some.</p><p><strong>Trial registration information: </strong>ClinicalTrials.gov (NCT05270408). Registered December 30, 2021.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 2","pages":"100023"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042009","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":"Basal forebrain global functional connectivity is preserved in asymptomatic presenilin-1 E280A mutation carriers: Results from the Colombia cohort.","authors":"Alice Grazia, Martin Dyrba, Nunzio Pomara, Anna G Temp, Michel J Grothe, Stefan J Teipel","doi":"10.1016/j.tjpad.2024.100030","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100030","url":null,"abstract":"<p><strong>Background: </strong>Imaging studies showed early atrophy of the cholinergic basal forebrain in prodromal sporadic Alzheimer's disease and reduced posterior basal forebrain functional connectivity in amyloid positive individuals with subjective cognitive decline. Similar investigations in familial cases of Alzheimer's disease are still lacking.</p><p><strong>Objectives: </strong>To test whether presenilin-1 E280A mutation carriers have reduced basal forebrain functional connectivity and whether this is linked to amyloid pathology.</p><p><strong>Design: </strong>This is a cross-sectional study that analyzes baseline functional imaging data.</p><p><strong>Setting: </strong>We obtained data from the Colombia cohort Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease Trial.</p><p><strong>Participants: </strong>We analyzed data from 215 asymptomatic subjects carrying the presenilin-1 E280A mutation [64% female; 147 carriers (M = 35 years), 68 noncarriers (M = 40 years)].</p><p><strong>Measurements: </strong>We extracted functional magnetic resonance imaging data using seed-based connectivity analysis to examine the anterior and posterior subdivisions of the basal forebrain. Subsequently, we performed a Bayesian Analysis of Covariance to assess the impact of carrier status on functional connectivity in relation to amyloid positivity. For comparison, we also investigated hippocampus connectivity.</p><p><strong>Results: </strong>We found no effect of carrier status on anterior (Bayesian Factor₁₀ = 1.167) and posterior basal forebrain connectivity (Bayesian Factor₁₀ = 0.033). In carriers, we found no association of amyloid positivity with basal forebrain connectivity.</p><p><strong>Conclusions: </strong>We falsified the hypothesis of basal forebrain connectivity reduction in preclinical mutation carriers with amyloid pathology. If replicated, these findings may not only confirm a discrepancy between familial and sporadic Alzheimer's disease, but also suggest new potential targets for future treatments.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 2","pages":"100030"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041990","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":"Microstructural white matter injury contributes to cognitive decline: Besides amyloid and tau.","authors":"He-Ying Hu, Hong-Qi Li, Wei-Kang Gong, Shu-Yi Huang, Yan Fu, Hao Hu, Qiang Dong, Wei Cheng, Lan Tan, Mei Cui, Jin-Tai Yu","doi":"10.1016/j.tjpad.2024.100037","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100037","url":null,"abstract":"<p><strong>Background: </strong>Cognitive decline and the progression to Alzheimer's disease (AD) are traditionally associated with amyloid-beta (Aβ) and tau pathologies. This study aims to evaluate the relationships between microstructural white matter injury, cognitive decline and AD core biomarkers.</p><p><strong>Methods: </strong>We conducted a longitudinal study of 566 participants using peak width of skeletonized mean diffusivity (PSMD) to quantify microstructural white matter injury. The associations of PSMD with changes in cognitive functions, AD pathologies (Aβ, tau, and neurodegeneration), and volumes of AD-signature regions of interest (ROI) or hippocampus were estimated. The associations between PSMD and the incidences of clinical progression were also tested. Covariates included age, sex, education, apolipoprotein E4 status, smoking, and hypertension.</p><p><strong>Results: </strong>Higher PSMD was associated with greater cognitive decline (β=-0.012, P < 0.001 for Mini-Mental State Examination score; β<0, P < 0.05 for four cognitive domains) and a higher risk of clinical progression from normal cognition to mild cognitive impairment (MCI) or AD (Hazard ratio=2.11 [1.38-3.23], P < 0.001). These associations persisted independently of amyloid status. PSMD did not predict changes in Aβ or tau levels, but predicted changes in volumes of AD-signature ROI (β=-0.003, P < 0.001) or hippocampus (β=-0.002, P = 0.010). Besides, the whole-brain PSMD could predict cognitive decline better than regional PSMDs.</p><p><strong>Conclusions: </strong>PSMD may be a valuable biomarker for predicting cognitive decline and clinical progression to MCI and AD, providing insights besides traditional Aβ and tau pathways. Further research could elucidate its role in clinical assessments and therapeutic strategies.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 2","pages":"100037"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042033","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":"Corrigendum to \"Multiomics Blood-Based Biomarkers Predict Alzheimer's Predementia with High Specificity in a Multicentric Cohort Study\" [The Journal of Prevention of Alzheimer's Disease 2024;11(3):567-581].","authors":"B Souchet, A Michaïl, M Heuillet, A Dupuy-Gayral, E Haudebourg, C Pech, A Berthemy, F Autelitano, B Billoir, K Domoto-Reilly, C Fowler, T Rabowski, S Jayadev, C L Masters, J Braudeau","doi":"10.1016/j.tjpad.2024.100026","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100026","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 2","pages":"100026"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041960","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":"Cerebral perfusion correlates with amyloid deposition in patients with mild cognitive impairment due to Alzheimer's disease.","authors":"Caixia Wang, Deli Ji, Xiao Su, Fang Liu, Yanxin Zhang, Qingzheng Lu, Li Cai, Ying Wang, Wen Qin, Gebeili Xing, Peng Liu, Xin Liu, Meili Liu, Nan Zhang","doi":"10.1016/j.tjpad.2024.100031","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100031","url":null,"abstract":"<p><strong>Background: </strong>Changes in cerebral blood flow (CBF) may contribute to the initial stages of the pathophysiological process in patients with Alzheimer's disease (AD). Hypoperfusion has been observed in several brain regions in patients with mild cognitive impairment (MCI). However, the clinical significance of CBF changes in the early stages of AD is currently unclear.</p><p><strong>Objectives: </strong>The aim of this study was to investigate the characteristics, diagnostic value and cognitive correlation of cerebral perfusion measured with arterial spin labeling (ASL) magnetic resonance imaging (MRI) in patients with MCI due to AD.</p><p><strong>Design, setting and participants: </strong>A total of fifty-nine MCI patients and 49 cognitively unimpaired controls (CUCs) were recruited and underwent multimodal MRI scans, including pseudocontinuous ASL, and neurocognitive testing. MCI patients were dichotomously classified according to the presence of amyloid deposition on ¹¹C-labelled Pittsburgh compound B (PiB) positron emission tomography (PET).</p><p><strong>Measurements: </strong>The differences in CBF and expression of the AD-related perfusion pattern (ADRP), established by spatial covariance analysis in our previous study, were compared between the PiB+ MCI group and the CUC group and between the PiB+ and PiB- MCI groups. The diagnostic accuracy and correlations with cognitive function scores for CBF and ADRP expression were further analyzed.</p><p><strong>Results: </strong>Hypoperfusion in the precuneus and posterior cingulate cortex (PCC) was more characteristic of patients with MCI due to AD than of those with non-AD-related MCI. The relative regional CBF value of the left precuneus best distinguished patients with MCI due to AD from CUCs and patients with MCI due to non-AD conditions. Cerebral perfusion, as indicated by either the relative regional CBF or the expression score of the ADRP, was strongly correlated with certain cognitive function scores.</p><p><strong>Conclusions: </strong>Here, we show that changes in CBF in the precuneus/PCC are promising MRI biomarkers for the identification of an AD etiology in patients with MCI. ASL, a noninvasive and cost-effective tool, has broad application prospects in the screening and early diagnosis of AD.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 2","pages":"100031"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041993","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":"Ultra-processed food consumption and risk of dementia and Alzheimer's disease: The Framingham Heart Study.","authors":"Galit Weinstein, Daniel Kojis, Ayantika Banerjee, Sudha Seshadri, Maura Walker, Alexa S Beiser","doi":"10.1016/j.tjpad.2024.100042","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100042","url":null,"abstract":"<p><strong>Background: </strong>Ultra-processed food consumption is emerging as a risk factor for various cardiometabolic diseases, however its association with dementia and Alzheimer's disease has rarely been explored.</p><p><strong>Objectives: </strong>We sought to examine whether ultra-processed food consumption is associated with risk of all-cause dementia and Alzheimer's disease among middle-age and older adults.</p><p><strong>Design: </strong>A prospective cohort study.</p><p><strong>Setting: </strong>The Framingham Heart Study, a single-site, community-based cohort study.</p><p><strong>Participants: </strong>Offspring cohort participants who attended examination cycles 5 (1991-1995) and 7 (1998-2001) at age ≥60 years and who were dementia-free at baseline.</p><p><strong>Measurements: </strong>Nutritional information was retrieved from food frequency questionnaires, and ultra-processed food was categorized based on the NOVA system. Participants were followed-up for all-cause dementia and Alzheimer's disease. Cox regression models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) adjusting for potential confounders.</p><p><strong>Results: </strong>The study sample included 1,375 participants free of dementia and stroke at baseline (mean age 68 ± 6y, 54 % females). During a mean follow-up of 12.7 ± 6.0 years, 224 and 172 individuals were diagnosed with all-cause dementia and Alzheimer's disease, respectively. An interaction of ultra-processed food consumption with age was observed with regard to dementia and Alzheimer's disease (p for interaction = 0.02 and 0.007, respectively). Therefore, all analyses were stratified by the median age of 68 years. Among participants who were <68 years of age at baseline, each serving per day of ultra-processed food was associated with 13 % increased risk for Alzheimer's disease (HR = 1.13, 95 % CI:1.03-1.25), and consumption of ≥10 servings/day vs. <10 servings/day of ultra-processed food was associated with a 2.7-fold increase in Alzheimer's disease risk (HR = 2.71, 95 % CI:1.18-6.24), after adjustment for age, sex, education, total energy, metabolic factors and diet quality. The associations with all-cause dementia were less robust, and no significant findings were observed when age at baseline was 68 years or above.</p><p><strong>Conclusions: </strong>Our findings suggest that consumption of ultra-processed food in middle-age may be linked with an increased risk for Alzheimer's disease. Future clinical studies are warranted to assess whether reduction of ultra-processed food consumption improves brain health.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 2","pages":"100042"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042047","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":"Determinants of dementia diagnosis in U.S. primary care in the past decade: A scoping review.","authors":"Chelsea G Cox, Barbara L Brush, Lindsay C Kobayashi, J Scott Roberts","doi":"10.1016/j.tjpad.2024.100035","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100035","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease and related dementias (ADRD) are chronically underdiagnosed in the U.S., particularly among minoritized racial and ethnic groups. Primary care providers are at the forefront of diagnosis given the increasing prevalence of cases and shortage of dementia specialists. Advances in policy, detection, and treatment in the past decade necessitate an updated review of the current state of determinants of ADRD diagnosis in U.S. primary care settings.</p><p><strong>Methods: </strong>Following Joanna Briggs Institute guidelines, we conducted a scoping literature review on ADRD diagnosis among older adults in U.S. primary care settings. Studies published in English from January 2010 to January 2024 were retrieved from PubMed, PsycINFO, and CINAHL. We extracted primary data on study characteristics and synthesized key findings according to facilitators, barriers, and rates of diagnosis in primary care.</p><p><strong>Results: </strong>Of 563 articles retrieved, 12 met eligibility criteria. Three studies reported rates of diagnosis, and all but one reported facilitators and/or barriers to diagnosis. ADRD remains underdiagnosed in primary care settings, especially in the earliest symptomatic stage (i.e., mild cognitive impairment). Multi-level barriers and facilitators were identified including individual beliefs about ADRD (e.g., value of early diagnosis), interpersonal relationships between patients and their family members and providers (e.g., importance of an established clinical relationship), and healthcare system limitations (e.g., insufficient resources and training).</p><p><strong>Conclusion: </strong>Despite national policy efforts to improve timely diagnosis of ADRD, underdiagnosis remains a clinical and public health challenge. Increased attention to social and community contexts will be important for future research and intervention.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 2","pages":"100035"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041961","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":"Blood-brain barrier integrity disruption is associated with both chronic vascular risk factors and white matter hyperintensities.","authors":"James Xiao Yuan Chen, Ashwati Vipin, Gurveen Kaur Sandhu, Yi Jin Leow, Fatin Zahra Zailan, Pricilia Tanoto, Ee Soo Lee, Khang Leng Lee, Christine Cheung, Nagaendran Kandiah","doi":"10.1016/j.tjpad.2024.100029","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100029","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular risk factors (CRFs) like hypertension, high cholesterol, and diabetes mellitus are increasingly linked to cognitive decline and dementia, especially in cerebral small vessel disease (cSVD). White matter hyperintensities (WMH) are closely associated with cognitive impairment, but the mechanisms behind their development remain unclear. Blood-brain barrier (BBB) dysfunction may be a key factor, particularly in cSVD.</p><p><strong>Objective: </strong>This study explores the relationship between CRFs, BBB integrity, and WMH burden.</p><p><strong>Design, setting, and participants: </strong>The study included 155 participants from the Biomarkers and Cognition Study, Singapore (BIOCIS). CRFs were assessed through blood tests for glucose and lipid profiles, and blood pressure measurements. WMH volumes were quantified using MRI.</p><p><strong>Measurements: </strong>BBB integrity was evaluated using a Transendothelial Electrical Resistance (TEER) assay with human brain microvascular endothelial cells (hBMEC) exposed to participant plasma.</p><p><strong>Results: </strong>Plasma from individuals with a higher WMH burden was associated with increased BBB disruption in hBMEC. Higher systolic and diastolic blood pressure, as well as body mass index, were correlated with greater BBB disruption. Regression analyses revealed that elevated blood glucose and lipid levels were linked to increased BBB disruption. Both periventricular and subcortical WMH burdens were associated with increased BBB disruption.</p><p><strong>Conclusion: </strong>This study highlights a relationship between CRFs, BBB disruption, and WMH burden, suggesting that CRFs may impair BBB integrity and contribute to WMH and cognitive decline in cSVD.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 2","pages":"100029"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041991","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":"Distinct CSF α-synuclein aggregation profiles associated with Alzheimer's disease phenotypes and MCI-to-AD conversion.","authors":"Yanfei Ding, Lingbing Wang, Jun Liu, Yulei Deng, Yang Jiao, Aonan Zhao","doi":"10.1016/j.tjpad.2024.100040","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100040","url":null,"abstract":"<p><strong>Background: </strong>α-Synuclein (α-Syn) pathology is present in 30-50 % of Alzheimer's disease (AD) patients, and its interactions with tau proteins may further exacerbate pathological changes in AD. However, the specific role of different aggregation forms of α-Syn in the progression of AD remains unclear.</p><p><strong>Objectives: </strong>To explore the relationship between various aggregation types of CSF α-Syn and Alzheimer's disease progression.</p><p><strong>Design: </strong>We conducted a retrospective analysis of data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to examine the association between different α-Syn aggregation forms-Syn0 (no detectable α-Syn aggregates) and Syn1 (α-Syn aggregates detected, resembling those found in Parkinson's disease)-with the pathological and clinical features of AD. Additionally, we evaluated their potential as predictors of conversion from mild cognitive impairment (MCI) to AD.</p><p><strong>Setting: </strong>The ADNI database.</p><p><strong>Participants: </strong>A total of 250 participants, including 70 cognitively normal controls, 119 patients diagnosed with MCI, and 61 patients diagnosed with AD.</p><p><strong>Measurements: </strong>Pearson correlation was employed to assess the relationship between α-Syn levels and cerebrospinal fluid (CSF) biomarkers, including total tau (T-tau), phosphorylated tau (p-tau), and amyloid-β₄₂ (Aβ₄₂). Multivariate Cox proportional hazards models were applied, adjusting for APOE4 status, age, and sex, to determine the association between α-Syn forms and AD-related pathological and clinical outcomes. Kaplan-Meier curves were used to evaluate the prognostic value of different α-Syn aggregation states in predicting the conversion from MCI to AD.</p><p><strong>Results: </strong>Compared with controls, overall MCI and AD patients had elevated α-Syn levels. Notably, in the α-Syn0 group, α-Syn levels were increased in the MCI patients and further increased in AD patients, whereas in the α-Syn1 group, α-Syn levels did not significantly differ across diagnostic groups. Both in the α-Syn0 and α-Syn1 groups, α-Syn levels were found to correlate more strongly with CSF tau levels than with Aβ₄₂, indicating a possible role for α-Syn in tau-related pathology in AD. Importantly, α-Syn0-AD patients exhibited more rapid cognitive decline and greater hippocampal atrophy than α-Syn1-AD patients. However, MCI patients with CSF α-Syn1 aggregation status had an increased risk of conversion to AD.</p><p><strong>Conclusions: </strong>CSF α-Syn is associated with tau pathology and neurodegeneration in Alzheimer's disease. The distinct aggregation profiles of α-Syn serve as valuable biomarkers, offering insights into differing prognoses in AD and aiding in the prediction of early disease progression.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 2","pages":"100040"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042006","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}