Neurology最新文献

{"title":"Consensus Recommendations to Establish Reporting Standards in fMRI of Migraine: A Delphi Study.","authors":"Severin Schramm, Corinna Börner-Schröder, Miriam Reichert, Constanze Ramschütz, Xiao Michelle Androulakis, Messoud Ashina, Gianluca Coppola, Brett Cucchiara, Zhao Dong, Xiaoxia Du, Laura H Fischer-Schulte, Peter J Goadsby, Rune Häckert Christensen, Luke A Henderson, Anders Hougaard, Jian-Ren Liu, Gabriella Juhasz, Nazia Karsan, Jian Kong, Jeungchan Lee, Mi Ji Lee, Clas Linnman, Vani Mathur, Arne May, Jan Mehnert, Eric Moulton, David M Niddam, Jean Schoenen, David A Seminowicz, Anne Stankewitz, Yiheng Tu, Dániel Veréb, Tao Yin, Claus Zimmer, Florian Heinen, Thomas Baum, Michaela V Bonfert, Nico Sollmann","doi":"10.1212/WNL.0000000000210235","DOIUrl":"https://doi.org/10.1212/WNL.0000000000210235","url":null,"abstract":"<p><strong>Background and objectives: </strong>Migraine is a multifaceted primary headache disorder. In neuroimaging of migraine, fMRI has been used to elucidate pathophysiology or monitor treatment effects. The current literature, however, is highly heterogeneous regarding reported variables and methodologies. This begets a lack of comparability and complicates synthesis of results across studies. We developed a framework for standardized reporting of fMRI studies in migraine.</p><p><strong>Methods: </strong>Experts on fMRI in migraine were identified from the literature and subjected to structured questionnaires in 2 iterations of 3 rounds according to the DELPHI method. A total of 157 statements across 17 reporting domains were rated on 5-point Likert scales (strong support to strong opposition). The first iteration covered demographic data, migraine-specific factors, medication, scan timing, healthy controls (HCs), participant sampling/recruiting, standardized forms, study preregistration, region of interest (ROI) analyses, validation data sets, data sharing, preprocessing documentation, and analysis software. The second iteration of the questionnaire covered scanner-related factors, sequence-related factors, physiology monitoring, and stimulation-related factors. Items showing strong consensus/consensus (≥90%/≥75% of participants indicating scores 4 or 5) were included as standard reporting items.</p><p><strong>Results: </strong>All 3 rounds of the first/second iteration were completed by 29 and 26 researchers (age 46 ± 11 years; 38% female/age 46 ± 12 years; 44% female) from 23 and 21 institutions. Across both iterations, strong consensus and consensus was achieved for 34 (3 scanner-related factors, 9 sequence-related factors, 1 stimulation-related factor, 2 demographic factors, 7 migraine-specific factors, 2 medication-factors, 2 scan timing factors, 4 HC factors, 1 preregistration factor, 1 analysis software factor, and 2 ROI analyses factors) and 33 (1 scanner-related factors, 4 sequence related factors, 1 factor related to physiology monitoring, 1 stimulation-related factor, 3 demographic factors, 6 migraine-specific factors, 4 medication factors, 3 HC factors, 2 sampling factors, 1 standardized form, 1 preregistration factor, 1 data sharing factor, 2 analysis software factors, and 3 ROI analyses factors) items, respectively. From these, a checklist covering 63 items from 14 reporting domains was created.</p><p><strong>Discussion: </strong>We present an expert-based framework for reporting standards in fMRI studies of migraine, which can be used for future studies to homogenize cohort characterization, fMRI acquisitions, and analysis protocols.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 5","pages":"e210235"},"PeriodicalIF":7.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What Is the Function and Relevance of 14-3-3 Proteins in Neurologic Disease?","authors":"Eduardo Benarroch","doi":"10.1212/WNL.0000000000213418","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213418","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 5","pages":"e213418"},"PeriodicalIF":7.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unbiased CSF Proteomics in Patients With Idiopathic Normal Pressure Hydrocephalus to Identify Molecular Signatures and Candidate Biomarkers.","authors":"Matthijs B de Geus, Chao-Yi Wu, Hiroko Dodge, Shannon N Leslie, Weiwei Wang, TuKiet T Lam, Kristopher T Kahle, Diane Chan, Pia Kivisäkk, Angus C Nairn, Steven E Arnold, Becky C Carlyle","doi":"10.1212/WNL.0000000000213375","DOIUrl":"10.1212/WNL.0000000000213375","url":null,"abstract":"<p><strong>Background and objectives: </strong>Idiopathic normal pressure hydrocephalus (iNPH) is a reversible neurologic disorder that remains poorly understood. Accurate differential diagnosis of iNPH and Alzheimer disease (AD) is complicated by overlapping clinical manifestations. Beyond neuroimaging, there are currently no biomarkers available for iNPH leading to frequent misdiagnosis, and proteomic studies into iNPH have been limited by low sample sizes and inadequate analytical depth. In this study, we report the results of a large-scale proteomic analysis of CSF from patients with iNPH to elucidate pathogenesis and identify potential disease biomarkers.</p><p><strong>Methods: </strong>CSF samples were collected through lumbar puncture during diagnostic visits to the Mass General Brigham neurology clinic. Samples were analyzed using mass spectrometry. Differential expression of proteins was studied using linear regression models. Results were integrated with publicly available single-nucleus transcriptomic data to explore potential cellular origins. Biological process enrichment was analyzed using gene-set enrichment analyses. To identify potential diagnostic biomarkers, decision tree-based machine learning algorithms were applied.</p><p><strong>Results: </strong>Participants were classified as cognitively unimpaired (N = 53, mean age: 66.5 years, 58.5% female), AD (N = 124, mean age: 71.2 years, 46.0% female), or iNPH (N = 44, mean age: 74.6 years, 34.1% female) based on clinical diagnosis and AD biomarker status. Gene Ontology analyses indicated upregulation of the immune system and coagulation processes and downregulation of neuronal signaling processes in iNPH. Differential expression analysis showed a general downregulation of proteins in iNPH. Integration of differentially expressed proteins with transcriptomic data indicated that changes likely originated from neuronal, endothelial, and glial origins. Using machine learning algorithms, a panel of 12 markers with high diagnostic potential for iNPH were identified, which were not all detected using univariate linear regression models. These markers spanned the various molecular processes found to be affected in iNPH, such as LTBP2, neuronal pentraxin receptor (NPTXR), and coagulation factor 5.</p><p><strong>Discussion: </strong>Leveraging the etiologic insights from a typical neurologic clinical cohort, our results indicate that processes of immune response, coagulation, and neuronal signaling are affected in iNPH. We highlight specific markers of potential diagnostic interest. Together, our findings provide novel insights into the pathophysiology of iNPH and may facilitate improved diagnosis of this poorly understood disorder.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 5","pages":"e213375"},"PeriodicalIF":7.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Dynamics of CSF and Serum Neurofilament Light Chain in Adult Patients With 5q Spinal Muscular Atrophy Treated With Nusinersen.","authors":"Isabell Cordts, Cornelia Fuetterer, Annika Wachinger, Ricarda von Heynitz, Tobias Kessler, Maren Freigang, Anna Lisa Quinten, Bogdan Bjelica, Svenja Brakemeier, Elke Hobbiebrunken, Tim Hagenacker, Susanne Petri, Jan Christoph Koch, Andreas Hahn, Paul Lingor, Marcus Deschauer, Rene Günther, Markus Weiler, Bernhard Haller, Emily Feneberg","doi":"10.1212/WNL.0000000000213371","DOIUrl":"10.1212/WNL.0000000000213371","url":null,"abstract":"<p><strong>Background and objectives: </strong>The availability of disease-modifying therapies for 5q-associated spinal muscular atrophy (SMA) has heightened the need to identify suitable biomarkers. This study investigates neurofilament light chain (NfL) concentrations during long-term nusinersen treatment in adult SMA.</p><p><strong>Methods: </strong>In a retrospective study of prospectively collected data, NfL concentrations in the CSF (cNfL) and serum (sNfL) were measured in patients with SMA from 8 German centers and in neurologic controls using a single-molecule array (Simoa) assay. NfL concentrations and clinical characteristics, including the clinical scores Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), were analyzed for defined treatment intervals (T1-T4 [loading phase until 4 months], T5-T8 [until 23 months], T9-T12 [until 37 months], and T13-T19 [until 60 months]). Linear mixed models with a random intercept were used to assess the changes in NfL levels during treatment, considering time and covariates as fixed effects.</p><p><strong>Results: </strong>One hundred thirteen adult patients with SMA (median age 35, 46% female), with a treatment duration of maximum 60 months, and 52 controls were included. At baseline, NfL concentrations were significantly higher in SMA {cNfL median, 585 (interquartile range [IQR] 428-787) pg/mL; sNfL, 11 (IQR 8-14) pg/mL} than in controls (cNfL, 420 [IQR 323-662] pg/mL; sNfL, 8 [IQR 6-12] pg/mL) (cNfL, <i>p</i> = 0.021; sNfL, <i>p</i> = 0.030). Median differences for all clinical scores were the highest for T5-T8 compared with the loading phase (Δ HFMSE, 0.6 [IQR 0.1-1.4], <i>p</i> = 0.017; Δ RULM, 0.9 [IQR 0.4-1.3], <i>p</i> < 0.001; Δ ALSFRS-R, 0.7 [IQR 0.4-1.0], <i>p</i> < 0.001), but not for subsequent intervals. Longitudinal analysis revealed a significant decrease of NfL concentrations during each treatment interval compared with the loading phase (<i>p</i> < 0.05, respectively) except for sNfL in T13-T19. Even among patients with no measurable clinical improvement (Δ HFMSE ≤ 0), more than 50% showed declining cNfL and sNfL levels up to T13-T19.</p><p><strong>Discussion: </strong>NfL decreased during nusinersen treatment, suggesting its potential as a pharmacodynamic response marker in adult SMA. However, in patients without detectable clinical improvement, our study cannot determine whether they represent a more sensitive outcome measure or are not clinically meaningful.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 5","pages":"e213371"},"PeriodicalIF":7.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shedding Light on REM Sleep Behavior Disorder in Progressive Supranuclear Palsy: Window Into Neurodegeneration or Diagnostic Challenge?","authors":"Luca Baldelli, Giovanna Calandra-Buonaura","doi":"10.1212/WNL.0000000000213449","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213449","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 5","pages":"e213449"},"PeriodicalIF":7.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reader Response: Association of Cardiovascular Health With Brain Age Estimated Using Machine Learning Methods in Middle-Aged and Older Adults.","authors":"Qing Zhou","doi":"10.1212/WNL.0000000000209833","DOIUrl":"https://doi.org/10.1212/WNL.0000000000209833","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 5","pages":"e209833"},"PeriodicalIF":7.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do the Right Thing: Carefully Measuring Social Determinants of Health in Neurologic Research.","authors":"H E Hinson","doi":"10.1212/WNL.0000000000213390","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213390","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 5","pages":"e213390"},"PeriodicalIF":7.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidural Steroids for Cervical and Lumbar Radicular Pain and Spinal Stenosis Systematic Review Summary: Report of the AAN Guidelines Subcommittee.","authors":"Carmel Armon, Pushpa Narayanaswami, Sonja Potrebic, Gary Gronseth, Misha-Miroslav Bačkonja, Viet L Cai, James Dorman, Christopher Gilligan, Scott A Heller, Heather M Silsbee, Don B Smith","doi":"10.1212/WNL.0000000000213361","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213361","url":null,"abstract":"<p><strong>Background and objectives: </strong>This review systematically evaluates and incorporates evidence for the use of epidural steroid injections (ESIs) in cervical and lumbar spinal stenosis and radiculopathies, assessing short-term (≤3 months) and long-term (≥6 months) improvements in pain and disability.</p><p><strong>Methods: </strong>We searched databases for randomized controlled trials (RCTs) on the efficacy of ESIs published between January 2005 and January 2021. Data analysis was performed by American Academy of Neurology methodologists. A panel of ESI experts was engaged to interpret the evidence in a clinical context. Owing to the great variability in efficacy measures used in the articles, we report differences based on any measure of success: the success rate difference (SRD).</p><p><strong>Results: </strong>Ninety RCTs met inclusion criteria. In cervical and lumbar radiculopathies, ESIs probably reduce short-term pain (SRD -24.0%, 95% CI -34.9 to -12.6, number needed to treat [NNT] 4) and disability (SRD -16.0%, 95% CI -26.6 to -5, NNT 6) and possibly decrease long-term disability (SRD -11.1%, 95% CI -25.3 to 3.6, NNT 9). There is insufficient evidence to determine whether ESIs reduce long-term pain in radiculopathies (SRD -10.3%, 95% CI -27.8 to 7.6). In lumbar spinal stenosis, ESIs possibly reduce short-term (SRD -26.2%, 95% CI -52.4 to 3.6, NNT 4) and long-term (SRD -11.8%, 95% CI -26.9 to 3.8, NNT 8) disability, but not short-term pain (SRD -3.5%, 95% CI -12.6 to 5.6). In lumbar stenosis, there is insufficient evidence to determine whether ESIs reduce long-term pain (SRD -6.5%, 95% CI -22.5 to 9.8). For cervical spinal stenosis, evidence is insufficient to determine the effectiveness of ESIs.</p><p><strong>Discussion: </strong>The review affirms limited efficacy of ESIs in reducing pain and disability in cervical and lumbar radiculopathies and possibly in lumbar spinal stenosis, largely in the short term. The heterogeneity of outcome measures reported preclude presenting integrated data regarding effect size. There is controversy regarding the appropriate choice of inactive comparator treatments as a true placebo in clinical trials of ESIs. The panel recommends that future trials of ESIs use minimal meaningful clinical difference as the measure of efficacy and paraspinal muscle injection of saline as an inactive placebo.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 5","pages":"e213361"},"PeriodicalIF":7.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal Magnitude of Blood Pressure Reduction and Hematoma Growth and Functional Outcomes in Intracerebral Hemorrhage.","authors":"Qi Li, Xinni Lv, Andrea Morotti, Adnan I Qureshi, Dar Dowlatshahi, Guido J Falcone, Kevin Navin Sheth, Ashkan Shoamanesh, Santosh B Murthy, Anand Viswanathan, Joshua N Goldstein","doi":"10.1212/WNL.0000000000213412","DOIUrl":"10.1212/WNL.0000000000213412","url":null,"abstract":"<p><strong>Background and objectives: </strong>Early intensive systolic blood pressure (SBP) reduction is a promising strategy for intracerebral hemorrhage (ICH), but the optimal magnitude of reduction in the first 2 hours remains uncertain. This study aimed to determine the optimal SBP reduction magnitude to maximize benefit in patients enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial.</p><p><strong>Methods: </strong>We performed a post hoc analysis of the ATACH-2 trial. Participants with baseline SBP ≥180 mm Hg were randomized within 4.5 hours from onset and assigned to the intensive or standard group. The magnitude of SBP reduction was calculated as admission SBP minus minimum SBP at 2 hours. Eligible participants were divided into 5 groups by 15 mm Hg stratum: <40, 40-55, 55-70, 70-85, and ≥85 mm Hg. Poor functional outcome was defined as the modified Rankin Scale score at 3-6 and hematoma expansion (HE) as a relative increase of >33% from baseline to 24 hours. Multivariable logistic regression assessed associations between SBP reduction and outcomes.</p><p><strong>Results: </strong>Our study included 925 patients, of whom 360 (38.9%) were female. The median age was 62 years (IQR: 53-71). The median hematoma volume was 10.2 mL (IQR: 5.1-18.4), and the median magnitude of SBP reduction was 68 mm Hg (IQR: 48-88). Of those, 209 (22.6%) experienced HE, 122 (13.2%) experienced acute kidney injury (AKI), and 516 (55.8%) had poor outcome. Hematoma expansion decreased linearly as the magnitude of blood pressure reduction increased in 5 SBP reduction groups (<i>p</i> < 0.001). After multivariable adjustment, patients with a greater degree of SBP reduction (≥70 mm Hg) were less likely to experience HE and a SBP reduction ≥55 mm Hg was associated with a lower risk of poor outcomes (odds ratio [OR] 0.49, 95% CI 0.28-0.85). However, a SBP reduction ≥85 mm Hg increased AKI risk compared with <40 mm Hg (OR, 2.00; 95% CI 1.01-3.94).</p><p><strong>Discussion: </strong>Targeting a SBP reduction within the range of 55-85 mm Hg during the first 2 hours seems to be associated with optimal outcomes in patients with mild-to-moderate ICH, balancing the need to limit hematoma growth while avoiding adverse effect. Further study focusing on severe ICH is warranted.</p><p><strong>Trial registration information: </strong>Clinical trial registration number: NCT01176565.</p><p><strong>Classification of evidence: </strong>This post hoc analysis of the ATACH-2 trial provides Class III evidence that SBP reduction of 55-85 mm Hg during the initial 2 hours is associated with lower frequency of HE and better functional outcomes in patients with acute cerebral hemorrhage.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 5","pages":"e213412"},"PeriodicalIF":7.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Lifestyle at Different Life Periods and Brain Integrity in Older Adults.","authors":"Anne-Laure Turpin, Francesca Felisatti, Léa Chauveau, Sacha Haudry, Florence Mézenge, Brigitte Landeau, Denis Vivien, Vincent De La Sayette, Gaël Chételat, Julie Gonneaud","doi":"10.1212/WNL.0000000000213347","DOIUrl":"10.1212/WNL.0000000000213347","url":null,"abstract":"<p><strong>Background and objectives: </strong>Lifestyle behaviors, including engagement in complex mental activities, have been associated with dementia risk and neuroimaging markers of aging and Alzheimer disease. However, the life period(s) at which lifestyle factors have the greatest influence on brain health remains unclear. Our objective was to determine the relative influence of lifestyle (i.e., engagement in complex mental activities) at different life periods on older adults' brain health.</p><p><strong>Methods: </strong>This observational study included community-dwelling cognitively unimpaired seniors (older than 65 years) from the Age-Well randomized controlled trial (Caen, France). All participants completed at baseline the Lifetime of Experiences Questionnaire, assessing engagement in complex mental activities during young adulthood (13-30 years: LEQ-young), midlife (30-65 years: LEQ-midlife), and late-life (older than 65 years: LEQ-late). LEQ scores were divided into specific and non-specific activities. Multiple regressions were conducted including LEQ scores at the 3 life periods (same model) to predict gray matter volume (GMv; structural-MRI), glucose metabolism (fluorodeoxyglucose-PET), perfusion (early-Florbetapir-PET), or amyloid burden (late-Florbetapir-PET), both in AD-signature regions and voxel-wise (significance for voxel-wise analyses: <i>p</i> < 0.005_uncorrected, k > 100). Correlations between LEQ and neuroimaging outcomes were then compared between (1) life periods and (2) specific and non-specific activities. Analyses were controlled for age and sex.</p><p><strong>Results: </strong>In 135 older adults (mean age = 69.3 years; women = 61.5%), no associations were found within AD-signature regions (all <i>p</i> > 0.25). Voxel-wise analyses revealed no association between LEQ-young and neuroimaging. LEQ-midlife showed stronger voxel-wise associations than the other periods with GMv, notably in the anterior cingulate cortex, and with amyloid burden in the precuneus. These correlations were stronger for the LEQ-midlife specific (i.e., occupation) than the non-specific subscore (GMv: z = 3.25, <i>p</i> < 0.001, 95% CI [0.1292-0.5135]; amyloid: z = -1.88, <i>p</i> < 0.05, 95% CI [-0.3810 to -0.0113]). LEQ-late showed stronger voxel-wise associations than the other periods with perfusion and glucose metabolism in medial frontal regions. The correlation of perfusion with LEQ-late was stronger for non-specific than specific subscore (z = 2.88, <i>p</i> < 0.01, 95% CI [0.0894-0.4606]).</p><p><strong>Discussion: </strong>Lifestyle at different life periods may have complementary benefits on brain health in regions related to reserve/resilience in aging. While past (midlife) engagement could promote resistance against structural/pathologic alterations, current (late-life) engagement could enhance cognitive reserve. Future larger longitudinal studies should explore mechanisms by which lifestyle promotes reserve.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 5","pages":"e213347"},"PeriodicalIF":7.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}