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2988Multi-omic derived cell-type specific Alzheimer disease polygenic risk scores 2988多组学衍生的细胞型特异性阿尔茨海默病多基因风险评分

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-07-16 DOI: 10.1016/j.neurobiolaging.2025.07.009

Nicholas O’Neill , Nuzulul Kurniansyah , Congcong Zhu , Oluwatosin A. Olayinka , Richard Mayeux , Jonathan L. Haines , Margaret A. Pericak-Vance , Li-San Wang , Gerard D. Schellenberg , Lindsay A. Farrer , Xiaoling Zhang

Alzheimer disease (AD) polygenic risk scores (ADPRS) built from cell-type (ct) specific genetic variants can be used to infer cell-type contributions to AD. We derived two ct-ADPRSs using variants near single-nuclei RNA-seq (snRNA) derived cell-type specific genes or on single-nuclei ATAC-seq (snATAC) derived cell-type specific accessible chromatin regions. We generated a multi-omic ct-ADPRS for eight neuron subtypes using both single-nuclei datasets. SnATAC-derived ct-ADPRSs demonstrated considerably lower correlations among cell types (average r = 0.071) than snRNA-derived ct-ADPRSs (average r = 0.19), indicating their heightened cell-type specificity. The association of these ct-ADPRSs with AD endophenotypes was evaluated using logistic and linear regression models. Tau tangle burden was associated with astrocyte (AST) ct-ADPRS derived from snATAC (β=0.82, FDR=0.0013) and snRNA (β=0.60, FDR=0.045) as well as microglia (MIC) ct-ADPRS from both (snATAC: β=0.75, FDR=0.0047) (snRNA: β=0.63, FDR=0.028). AST ct-ADPRS was significantly associated with Mini-Mental State Examination score only when derived from snATAC data (β=-0.82, FDR=0.011). SST expressing GABAergic neuron ADPRS was strongly associated ct-ADPRS with neuritic plaque burden (β=0.087, FDR=0.0014) and the only neuron subtype ct-ADPRS significantly associated with AD endophenotypes. We investigated 1954 SNPs contributing to this ct-ADPRS and found the strongest association with variants upstream of the neuropeptide Y gene, NPY, particularly rs3940268 (β=-0.13, P = 8.2x10⁻⁵). This association is significant even after adjusting for diffuse plaque (β=-0.12, P = 1.5x10⁻⁴) or neurofibrillary tangle burden (β=-0.08, P = 3.9x10⁻³). NPY was expressed in a small subset of neurons, and these findings suggest its strong impact on the association of SST+ GABAergic neurons with early AD pathology.

从细胞类型（ct）特异性遗传变异构建的阿尔茨海默病（AD）多基因风险评分（ADPRS）可用于推断细胞类型对AD的贡献。我们利用靠近单核RNA-seq （snRNA）衍生的细胞类型特异性基因或单核ATAC-seq （snATAC）衍生的细胞类型特异性可及染色质区域的变体获得了两个ct- adprs。我们使用两个单核数据集生成了8个神经元亚型的多组学ct-ADPRS。与snrna衍生的ct- adprs（平均r = 0.19）相比，snac衍生的ct- adprs在细胞类型之间的相关性明显较低（平均r = 0.071），表明它们具有更高的细胞类型特异性。使用逻辑和线性回归模型评估这些ct- adprs与AD内表型的关系。Tau缠结负担与来自snATAC （β=0.82， FDR=0.0013）和snRNA （β=0.60， FDR=0.045）的星形胶质细胞（AST） ct-ADPRS以及来自两者的小胶质细胞（MIC） ct-ADPRS相关（snATAC: β=0.75， FDR=0.0047）（snRNA: β=0.63， FDR=0.028）。AST ct-ADPRS仅在从snATAC数据中得出时与迷你精神状态检查评分显著相关（β=-0.82， FDR=0.011）。表达gaba能神经元ADPRS的SST与神经斑块负荷密切相关（β=0.087， FDR=0.0014），并且是唯一与AD内表型显著相关的神经元亚型ct-ADPRS。我们研究了1954个与此相关的单核苷酸多态性，发现与神经肽Y基因NPY上游变异的相关性最强，特别是rs3940268 （β=-0.13, P = 8.2x10−5）。即使在调整弥漫性斑块（β=-0.12, P = 1.5x10−4）或神经原纤维缠结负担（β=-0.08, P = 3.9x10−3）后，这种关联也是显著的。NPY在一小部分神经元中表达，这些发现表明它在SST+ gabaergy神经元与早期AD病理的关联中具有重要影响。

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引用次数: 0

Blood oxygenation level-dependent responses in neuromodulatory nuclei and their associations with attention and memory across age groups 各年龄组神经调节核的血氧水平依赖性反应及其与注意和记忆的关系

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-07-15 DOI: 10.1016/j.neurobiolaging.2025.07.010

Elizabeth Riley, Nicholas Cicero, Khena Swallow, Adam Anderson, Eve De Rosa

Using multi-echo blood oxygenation level-dependent (BOLD) neuroimaging, we examined lifespan differences in three subcortical nuclei important to the neuromodulation of cognition and target sites for early Alzheimer’s pathogenesis in the isodendritic core: the locus coeruleus (LC) the major source of noradrenaline, the nucleus basalis of Meynert (NBM) the major source of acetylcholine, and the ventral tegmental area (VTA) the major source of dopamine. Seventy-one participants, from 19 to 86 years old (young n = 29, middle-aged, n = 18, and older n = 24), were tasked with memorizing visual images while monitoring auditory tones for a predefined target to assess attentional modulation of subsequent memory for the images. Young adults demonstrated a memory advantage for images paired with a target tone relative to no tone, which was diminished in middle age, and absent in older adults. Elevated NBM and VTA BOLD responses to subsequently remembered target-paired images were present in all groups but were selectively absent in the LC of older adults. Moreover, only LC activity explained individual variation in subsequent memory performance. Even though activity in multiple modulatory nuclei contributed, age-related change in the attentional boosting of memory was specifically tied to altered LC activity.

利用多回声血氧水平依赖（BOLD）神经成像技术，研究了对认知神经调节和早期阿尔茨海默病发病机制至关重要的三个皮质下核的寿命差异：蓝斑核（LC）是去甲肾上腺素的主要来源，迈纳特基底核（NBM）是乙酰胆碱的主要来源，腹侧被皮层区（VTA）是多巴胺的主要来源。71名参与者，年龄从19岁到86岁（年轻人n = 29，中年人n = 18，老年人n = 24），被要求在记忆视觉图像的同时，监测预设目标的听觉音调，以评估对图像后续记忆的注意调节。相对于没有音调，年轻人对带有目标音调的图像表现出记忆优势，这种优势在中年时减弱，而在老年人中则不存在。所有组对随后记忆的目标配对图像的NBM和VTA BOLD反应均升高，但在老年人LC中选择性地不存在。此外，只有LC活动可以解释个体在后续记忆表现上的差异。尽管多个调节核的活动有所贡献，但与年龄相关的注意力增强记忆的变化与LC活动的改变特别相关。

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引用次数: 0

Longitudinal non-linear changes in the microstructure of the hippocampal subfields in older adults 老年人海马亚区结构的纵向非线性变化

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-07-12 DOI: 10.1016/j.neurobiolaging.2025.07.008

Ghina Zia , Syed Salman Shahid , Ho-Ching Yang , Sujuan Gao , Shannon L. Risacher , Andrew J. Saykin , Yu-Chien Wu

Human brains undergo considerable morphologic variation with age, a primary risk factor for neurodegenerative disorders. While aging often causes neurocognitive decline, its governing biological mechanisms remain unclear. These age-related brain microstructural changes may be quantified by advanced diffusion MRI (dMRI) with tissue-specific compartment modeling approach. This longitudinal study investigates age-related differences in hippocampal subfields vulnerable to early stages of Alzheimer’s disease (AD). Thirty-seven cognitively normal (CN) older adults (70.6 ± 6.7 years) from the Indiana Alzheimer's Disease Research Center (IADRC) underwent baseline and follow-up MRI scans, within 24 ± 11.7 months. Grey matter-specific multi-compartment diffusion model, cortical-neurite orientation dispersion, and density imaging (cortical-NODDI) was used to derive diffusion microstructural metrics, namely orientation dispersion index (ODI) and neurite density index (NDI) in hippocampal-subfields (CA1–3, CA4DG, and subiculum). We investigated rate of change in diffusion metrics and its associations with age and baseline diffusion metrics in hippocampal subfields using linear regression analysis, after adjusting for confounding factors (i.e., sex, education, Apolipoprotein E (APOE) ε4, and baseline subfield volumes). CA1–3 and subiculum volumes significantly decreased between baseline and follow-up scans. ODI rate of change was significantly higher than zero in CA4DG, while rate of change in NDI was significantly lower than zero in CA1–3 and CA4DG. ODI rate of change in CA1–3 was significantly associated with baseline age of participants and initial microstructural value of ODI in CA1–3. Results showed that Cornu Ammonis is most sensitive to age-related changes with increased microstructural dispersion and decreased neurite density with age- and initial state-dependent changes.

随着年龄的增长，人类大脑经历了相当大的形态变化，这是神经退行性疾病的主要危险因素。虽然衰老经常导致神经认知能力下降，但其控制生物学机制尚不清楚。这些与年龄相关的脑微结构变化可以通过高级弥散MRI （dMRI）与组织特异性室建模方法进行量化。这项纵向研究调查了早期阿尔茨海默病（AD）易感海马亚区与年龄相关的差异。来自印第安纳州阿尔茨海默病研究中心（IADRC）的37名认知正常（CN）老年人（70.6 ± 6.7岁）在24 ± 11.7个月内接受了基线和随访MRI扫描。采用灰质特异性多室扩散模型、皮质-神经突定向弥散和密度成像（皮质- noddi）得出扩散微结构指标，即海马亚区（CA1-3、CA4DG和耻骨下）的定向弥散指数（ODI）和神经突密度指数（NDI）。在调整混杂因素（即性别、教育程度、载脂蛋白E (APOE) ε4和基线子区体积）后，我们使用线性回归分析研究了扩散指标的变化率及其与年龄和基线海马子区扩散指标的关系。CA1-3和耻骨下体积在基线和随访扫描期间显著降低。CA4DG的ODI变化率显著高于零，而CA1-3和CA4DG的NDI变化率显著低于零。CA1-3 ODI变化率与受试者基线年龄和CA1-3 ODI初始微结构值显著相关。结果表明，山茱萸对年龄相关的变化最为敏感，微结构分散增加，神经突密度降低，并伴有年龄和初始状态相关的变化。

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引用次数: 0

Comparison of CSF neurofilament light chain and total tau as neurodegeneration markers: Associations with synaptic markers and cognitive outcomes 脑脊液神经丝轻链和总tau蛋白作为神经退行性变标志物的比较：与突触标志物和认知结果的关联

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-07-10 DOI: 10.1016/j.neurobiolaging.2025.07.005

Grit Richter , Bjørn-Eivind Kirsebom , Jonas Alexander Jarholm , Lene Pålhaugen , Berglind Gísladóttir , Dag Aarsland , Gøril Rolfseng Grøntvedt , Ragnhild Eide Skogseth , Knut Waterloo , Tormod Fladby , Kaja Nordengen

Clinically, Alzheimer's disease (AD) is characterized by progressive cognitive decline due to neuronal and synaptic degeneration. Neurofilament light chain (NfL) and total tau (T-tau) reflect neurodegeneration, NfL putatively more related to white and T-tau to grey matter. This study examines how cerebrospinal fluid (CSF) neurodegeneration markers (T-tau, NfL or both) are correlated with synaptic markers and clinical progression. We included 331 individuals with (n = 212) and without (n = 119) pathological CSF Aβ42/40 ratios. Associations between CSF NfL, T-tau, and the synaptic biomarkers neurogranin and BACE1 were assessed using Pearson’s correlation. Group differences in synaptic marker levels were evaluated using linear regression comparing individuals with isolated pathological T-tau, NfL, or both, versus biomarker-negative individuals. Clinical progression to MCI or dementia was assessed using a Cox proportional hazards model (n = 257; mean follow-up = 3.75 years). Linear regression and Cox proportional hazards models included age, sex, and dichotomized APOE-ε4 carriership as covariates. T-tau had a stronger correlation with neurogranin(r = 0.84) and BACE1(r = 0.73) than NfL(r = 0.51 and 0.48; p < 0.001). Group-wise comparisons confirmed this, showing that only individuals with pathological T-tau—alone or with NfL—had significantly higher synaptic marker levels (p < 0.001). Only the combination of pathological T-tau and NfL was associated with a significantly increased risk of clinical progression(HR=6.79; p < 0.001). These findings suggest that T-tau is more closely related to early synaptic dysfunction in AD than NfL. The combined elevation of both biomarkers, linked to greater clinical decline, supports a dual contribution of grey- and white matter degeneration to disease progression.

在临床上，阿尔茨海默病（AD）的特征是由于神经元和突触变性导致的进行性认知能力下降。神经丝轻链（NfL）和总tau （T-tau）反映神经退行性变，NfL被认为与白质有关，而T-tau与灰质有关。本研究探讨脑脊液（CSF）神经变性标志物（T-tau， NfL或两者）如何与突触标志物和临床进展相关。我们纳入了331例（n = 212）和（n = 119）脑脊液a β病理比值为42/40的个体。采用Pearson相关法评估CSF NfL、T-tau与突触生物标志物neurogranin和BACE1之间的相关性。使用线性回归比较分离的病理性T-tau、NfL或两者的个体与生物标志物阴性个体，评估突触标志物水平的组间差异。使用Cox比例风险模型评估MCI或痴呆的临床进展(n = 257；平均随访= 3.75年)。线性回归和Cox比例风险模型以年龄、性别和二分类APOE-ε4携带者为协变量。T-tau与神经颗粒蛋白（r = 0.84）和BACE1（r = 0.73）的相关性强于NfL(r = 0.51和0.48)；p & lt; 0.001)。组间比较证实了这一点，显示只有病理性t -tau单独或nfl个体的突触标记物水平显著较高（p <； 0.001）。只有病理性T-tau和NfL联合使用与临床进展风险显著增加相关(HR=6.79；p & lt; 0.001)。这些发现表明，与NfL相比，T-tau与AD早期突触功能障碍的关系更为密切。这两种生物标志物的联合升高与更大的临床衰退有关，支持灰质和白质变性对疾病进展的双重贡献。

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引用次数: 0

White matter hyperintensities contribute to early cortical thinning in addition to tau in aging 在衰老过程中，除了tau蛋白外，白质高信号还会导致早期皮层变薄

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-07-09 DOI: 10.1016/j.neurobiolaging.2025.07.007

Riccardo Leone , Xenia Kobeleva , for the Alzheimer's Disease Neuroimaging Initiative

White matter hyperintensities (WMH) are associated with cortical thinning in distant brain regions. However, it is currently unclear how WMH affect neurodegeneration in early Alzheimer’s disease (AD). Here, we investigated associations between WMH and cortical thickness in temporal regions involved in early AD (AD cortical signature), while correcting for regional amyloid and tau accumulation assessed by PET. We performed cross-sectional (n = 551), and longitudinal (n = 125) analyses in older adults without dementia, also stratified by amyloid positivity. We evaluated WMH volume - as a measure of the global burden of WMH-related cerebrovascular pathology (GB-WMH) - and investigated the role of deep versus periventricular WMH. We also tested whether a higher focal burden of WMH in specific tracts connected to AD signature regions (FB-WMH) would lead to greater cortical thinning than expected solely from GB-WMH. We performed exploratory analyses in other brain regions to check the specificity of our findings to the temporal AD signature. GB-WMH damage, especially involving periventricular WMH, was cross-sectionally (not longitudinally) associated with cortical thinning in the fusiform, inferior and middle temporal gyri. Stronger associations were found in amyloid-positive individuals, including for the entorhinal cortex. Effects were mostly confined to regions of the temporal AD signature. FB-WMH did not yield higher cortical thinning than expected solely by GB-WMH. Cerebrovascular disease is associated with cortical thinning of temporal regions involved in early AD. Interventions aimed at improving cerebrovascular health might help to mitigate neurodegeneration in these regions.

白质高信号（WMH）与大脑远端皮层变薄有关。然而，目前尚不清楚WMH如何影响早期阿尔茨海默病（AD）的神经变性。在这里，我们研究了WMH与阿尔茨海默病早期颞区皮层厚度之间的关系（阿尔茨海默病皮层特征），同时校正了PET评估的区域淀粉样蛋白和tau蛋白积累。我们对无痴呆的老年人进行了横断面（n = 551）和纵向（n = 125）分析，也按淀粉样蛋白阳性分层。我们评估了WMH体积——作为衡量WMH相关脑血管病理（GB-WMH）全球负担的指标——并研究了深部与心室周围WMH的作用。我们还测试了与AD特征区（FB-WMH）连接的特定神经束中较高的WMH局灶负担是否会比单独由GB-WMH引起的皮质变薄更严重。我们对其他大脑区域进行了探索性分析，以检查我们的发现对颞叶AD特征的特异性。GB-WMH损伤，特别是涉及脑室周围的WMH，在横截面上（而不是纵向上）与梭状回、下颞回和中颞回皮质变薄有关。在淀粉样蛋白阳性的个体中发现了更强的关联，包括内嗅皮层。影响主要局限于时间AD特征区域。FB-WMH并不比单独使用GB-WMH产生更高的皮质变薄。脑血管疾病与早期AD所涉及的颞区皮质变薄有关。旨在改善脑血管健康的干预措施可能有助于减轻这些区域的神经退行性变。

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引用次数: 0

Epigenetic age is associated with regional brain aging along the sensorimotor-to-association axis of cortical organization 表观遗传年龄与皮层组织的感觉-运动-关联轴上的区域大脑衰老有关

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-07-08 DOI: 10.1016/j.neurobiolaging.2025.07.006

Nicholas Riccardi , Carolyn Banister , Natalie Busby , Sarah Newman-Norlund , Roger Newman-Norlund , Ida Rangus , Alex Teghipco , Chris Roden , Julius Fridriksson , Leonardo Bonilha

Brain age and epigenetic age (DNAmAge) are ‘biological clocks’ independently linked to health outcomes. However, the relationship between brain and epigenetic age remains unclear. We used path analysis to investigate relationships between chronological age, DNAmAge, and brain age and explored whether advanced aging in specific brain regions relates to DNAmAge. BrainAge (global and regional) was estimated from brain MRI in 149 participants (ages 20–80). From whole blood, four DNAmAges were calculated: Pheno, Hannum, Horvath, and SkinBlood. Mediation was used to test the indirect effect of DNAmAge on global BrainAge, as well as the reverse, with chronological age as the independent variable. Correlations between accelerated region-specific BrainAge and DNAmAge were also examined. DNAmPhenoAge mediated the relationship between chronological age and global BrainAge. DNAmPhenoAge was related to advanced BrainAge of regions higher on the sensorimotor-to-association axis of cortical organization (F(1104) = 17.5, R² = .15, p < .001). DNAmPhenoAge age may uniquely capture cellular aging processes that are related to brain health across the adult lifespan. Region-based results suggest that biological aging in higher-order association cortices is related to epigenetic aging.

大脑年龄和表观遗传年龄（DNAmAge）是与健康结果独立相关的“生物钟”。然而，大脑和表观遗传年龄之间的关系仍不清楚。我们使用通径分析来研究实足年龄、DNAmAge和脑年龄之间的关系，并探讨特定脑区域的高龄是否与DNAmAge有关。通过对149名参与者（年龄在20-80岁之间）的脑MRI估计脑年龄（全球和区域）。从全血中，计算出四个dnamage: Pheno， Hannum， Horvath和SkinBlood。使用中介来测试DNAmAge对整体脑年龄的间接影响，以及以实足年龄为自变量的反向影响。加速区域特异性脑龄和DNAmAge之间的相关性也被检查。DNAmPhenoAge介导了实足年龄与脑龄之间的关系。DNAmPhenoAge与皮层组织感觉运动-关联轴上较高区域的脑龄相关（F(1104) = 17.5,R2 = ）。15日,p & lt; 措施)。DNAmPhenoAge年龄可能独特地捕捉到与成人一生中大脑健康相关的细胞衰老过程。基于区域的研究结果表明，高阶关联皮层的生物老化与表观遗传老化有关。

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引用次数: 0

Serum HDL-cholesterol is associated with the clinical-biological profile of early-stage Parkinson’s disease patients independently of APOE 血清高密度脂蛋白胆固醇与早期帕金森病患者的临床生物学特征相关，与APOE无关

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-07-05 DOI: 10.1016/j.neurobiolaging.2025.07.004

Davide Mascioli , Matteo Conti , Jacopo Bissacco , Roberta Bovenzi , Clara Simonetta , Veronica Buttarazzi , Maria Mancini , Silvio Bagetta , Giulia Maria Sancesario , Daniela Maftei , Federica Veltri , Enrica Marchionni , Alessandro Stefani , Nicola Biagio Mercuri , Massimo Pieri , Tommaso Schirinzi

Emerging evidence highlights a possible interplay between serum lipid profiles and Parkinson’s disease (PD), but the biological underpinnings remain largely unexplored. In this cross-sectional study, we investigated whether serum lipid levels (total cholesterol, high-density lipoprotein cholesterol (HDL), non-high-density lipoprotein cholesterol, and triglycerides) were associated with clinical severity and cerebrospinal fluid (CSF) biomarkers in early-stage PD patients. A cohort of 90 PD patients and 74 matched controls underwent serum lipid and CSF biomarker assessment and APOE genotyping. While serum lipid levels did not differ significantly between groups, PD patients showed reduced CSF α-synuclein. Notably, higher HDL levels correlated with higher CSF α-synuclein and amyloid-β42 (Aβ42) concentrations and milder motor impairment, independent of APOE ε4 status. APOE ε4 carriers displayed increased CSF phosphorylated tau and reduced Aβ42/Aβ40 ratio, but APOE genotype did not modify the observed HDL associations. These findings suggest that higher circulating HDL levels are associated with a milder clinical phenotype and a more favorable CSF biomarker profile in early-stage PD, potentially reflecting a protective role independent of APOE genotype. Further studies are warranted to validate these observations and to assess their therapeutic implications.

新出现的证据强调了血清脂质谱与帕金森病（PD）之间可能存在的相互作用，但其生物学基础在很大程度上仍未被探索。在这项横断面研究中，我们调查了早期PD患者的血脂水平（总胆固醇、高密度脂蛋白胆固醇（HDL）、非高密度脂蛋白胆固醇和甘油三酯）是否与临床严重程度和脑脊液（CSF）生物标志物相关。90名PD患者和74名匹配的对照组接受了血脂和脑脊液生物标志物评估和APOE基因分型。虽然两组间血脂水平无显著差异，但PD患者脑脊液α-突触核蛋白含量降低。值得注意的是，较高的HDL水平与脑脊液α-突触核蛋白和淀粉样蛋白-β42 （a -β42）浓度升高和较轻的运动损伤相关，与APOE ε4状态无关。APOE ε4携带者脑脊液磷酸化tau蛋白升高，a - β42/ a - β40比值降低，但APOE基因型未改变所观察到的HDL相关性。这些发现表明，在早期PD患者中，较高的循环HDL水平与较温和的临床表型和更有利的CSF生物标志物谱相关，可能反映了一种独立于APOE基因型的保护作用。需要进一步的研究来验证这些观察结果并评估其治疗意义。

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引用次数: 0

Evaluating the link between hearing loss and Alzheimer’s disease neuropathology: A systematic review and meta-analysis 评估听力损失与阿尔茨海默病神经病理学之间的联系：一项系统回顾和荟萃分析

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-07-03 DOI: 10.1016/j.neurobiolaging.2025.07.003

Avinash Chandra , Benjamin A. Levett , Sheena Waters , Petroula Proitsi , Yue Liu , Chris J.D. Hardy , Jason D. Warren , Charles R. Marshall

Hearing loss has been linked with cognitive decline and increased dementia risk. The neurobiological mechanisms underlying this relationship are not clear. In this systematic review and meta-analysis, we evaluated associations between hearing loss and Alzheimer’s disease (AD) neuropathology, specifically β-amyloid (Aβ) and tau burden. Databases including PubMed, MEDLINE via Ovid, Web of Science, and EMBASE were searched to identify cohort and cross-sectional studies that examined the relationship between hearing loss and Aβ and/or tau neuropathology in humans. Meta-analyses were conducted using random-effects models and examined associations between hearing loss, either peripheral, central, or subjective, and in vivo AD neuropathology measured through PET or CSF. Estimates were converted to correlation coefficients prior to quantitative analysis. 6224 records were screened, of which 22 studies were included in the review. Significant associations between hearing loss and both Aβ (r, 0.09; 95 % CI, 0.02–0.16) and tau burden (r,0.16; 95 % CI, 0.08–0.23), were found across cross-sectional in vivo studies. However, in subgroup analyses, associations between Aβ burden and hearing loss were only significant for studies using central hearing measures or PET. Findings from studies in the systematic review, including post-mortem and longitudinal ones, were mixed. This study provides evidence for an association between hearing loss and AD neuropathology. The pattern of stronger meta-analytic findings localised to central hearing, PET, and tau studies suggests that higher levels of neuropathological burden may be linked to dysfunction in central auditory processing. The causality underpinning this relationship should be investigated in future studies.

听力损失与认知能力下降和痴呆风险增加有关。这种关系背后的神经生物学机制尚不清楚。在这项系统综述和荟萃分析中，我们评估了听力损失与阿尔茨海默病（AD）神经病理学之间的关系，特别是β-淀粉样蛋白（Aβ）和tau负担。检索PubMed、MEDLINE via Ovid、Web of Science和EMBASE等数据库，以确定检测人类听力损失与Aβ和/或tau神经病理之间关系的队列和横断面研究。使用随机效应模型进行meta分析，并检查外周、中枢或主观听力损失与通过PET或CSF测量的体内AD神经病理学之间的关系。在定量分析之前，将估计值转换为相关系数。6224份记录被筛选，其中22项研究被纳入本综述。听力损失与Aβ均有显著相关性(r, 0.09；95 % CI, 0.02-0.16)和tau负荷(r,0.16；95 % CI, 0.08-0.23)，在横断面体内研究中发现。然而，在亚组分析中，β负荷与听力损失之间的关联仅在使用中枢性听力测量或PET的研究中具有显著性。系统综述的研究结果，包括死后研究和纵向研究，好坏参半。这项研究为听力损失和AD神经病理学之间的联系提供了证据。中枢听力、PET和tau研究的荟萃分析结果表明，较高水平的神经病理负担可能与中枢听觉处理功能障碍有关。这种关系的因果关系应该在未来的研究中进行调查。

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引用次数: 0

Identifying lifestyle risk factors that discriminate memory trajectories: Differential findings across racial and ethnic groups in older adults 识别区分记忆轨迹的生活方式风险因素：在老年人中不同种族和民族的差异发现

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-07-02 DOI: 10.1016/j.neurobiolaging.2025.07.002

Shraddha Sapkota , Pauline Maillard , Evan M. Fletcher , Danielle J. Harvey , John M. Olichney , Sarah Tomaszewski Farias , Paola Gilsanz , Dan Mungas , Rachel A. Whitmer , Charles DeCarli

Introduction

Differences in lifestyle factors contribute towards inequalities in dementia incidence and memory trajectories across racial and ethnic groups. We identifieded lifestyle risk factors that best discriminat memory trajectories in older adults without cognitive impairment.

Method

The study included 523 older adults from the University of California, Davis–Alzheimer’s disease Research Center and 1097 from the Kaiser Healthy-Aging and Diverse Life-Experiences Study. Age, sex, and 13 lifestyle risk factors were used to discriminate latent class memory trajectories in African Americans, Hispanics, and Whites. Structural equation modeling and machine learning methods were applied.

Results

In both cohorts, three patterns of memory trajectories were identified. While there was overlap between risk factors discriminating high and low memory patterns for everyone, we also identified key differences in the top predictors across groups in both cohorts.

Discussion

Identifying relative importance of lifestyle risk factors will promote early identification of adults with differential memory performance across and within racial and ethnic groups.

生活方式因素的差异导致痴呆发病率和记忆轨迹在种族和民族群体中的不平等。我们确定了生活方式的风险因素，这些因素在没有认知障碍的老年人中最能区分记忆轨迹。该研究包括来自加州大学戴维斯分校-阿尔茨海默病研究中心的523名老年人和来自凯撒健康-老龄化和多样化生活经历研究的1097名老年人。使用年龄、性别和13种生活方式风险因素来区分非裔美国人、西班牙裔美国人和白人的潜在阶级记忆轨迹。采用结构方程建模和机器学习方法。结果两组受试者的记忆轨迹均有三种模式。虽然区分每个人的高记忆模式和低记忆模式的风险因素之间存在重叠，但我们也确定了两个队列中各组之间最重要的预测因素的关键差异。确定生活方式风险因素的相对重要性将有助于早期识别不同种族和民族群体之间的不同记忆表现的成年人。

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引用次数: 0

Balance training improves postural control and performance-related prefrontal brain activation in healthy older adults: Results of a six-month randomized controlled training intervention 平衡训练改善健康老年人的姿势控制和与表现相关的前额叶脑激活：六个月随机对照训练干预的结果

IF 3.7 3区医学 Q2 GERIATRICS & GERONTOLOGY

Neurobiology of Aging

Pub Date : 2025-07-02 DOI: 10.1016/j.neurobiolaging.2025.07.001

Nico Lehmann , Yves-Alain Kuhn , Martin Keller , Norman Aye , Fabian Herold , Bogdan Draganski , Wolfgang Taube , Marco Taubert

Age-related deterioration in postural control is an important factor decreasing quality of life. Functional neuroimaging studies have shown that the activation of the prefrontal cortex (PFC) during balancing is typically higher in older (OA) compared to younger adults (YA), probably reflecting a mechanism contributing to worsened balance control with aging. Here, we hypothesized that balance training (BAL) shifts PFC activation towards a more efficient pattern, enabling improved balance performance. To test this hypothesis, we conducted a randomized controlled trial with healthy older (65–80 y) and young adults (18–35 y) of both sexes (n = 63) comparing the effects of a 6-month BAL intervention (1 h of BAL twice weekly) against age-matched, non-BAL controls (CON). In both age groups, we found that BAL led to a significant reduction in sway in trained and untrained balance tasks compared to CON, which could still be observed 6 months after the end of training (multivariate p’s < .003). In OA, we found a larger reduction in PFC activation assessed with functional near-infrared spectroscopy in BAL compared to CON after training (multivariate p < .02), and a similar yet not significant trend was observed in YA (p < .06). Importantly, in OA, both cross-sectional correlations and longitudinal correlated changes showed that reduced PFC activation was associated with better balance performance. Our results support the idea that BAL may reduce dysfunctional PFC activation in OA, resulting in activation patterns more similar to those of YA, with positive effects on postural control and possibly fall risk.

与年龄相关的姿势控制恶化是降低生活质量的重要因素。功能性神经影像学研究表明，在平衡过程中，老年人（OA）的前额叶皮层（PFC）的激活通常高于年轻人（YA），这可能反映了一种导致平衡控制随着年龄增长而恶化的机制。在这里，我们假设平衡训练（BAL）将PFC激活转向更有效的模式，从而提高平衡表现。为了验证这一假设，我们对男女健康老年人（65-80岁）和年轻人（18-35岁）进行了一项随机对照试验（n = 63），比较了6个月BAL干预（每周一次1 小时）与年龄匹配的非BAL对照组（CON）的效果。在两个年龄组中，我们发现与CON相比，BAL导致训练和未训练平衡任务的摇摆显著减少，这在训练结束6个月后仍然可以观察到（多变量p 's <； .003）。在OA中，我们发现，与训练后的CON相比，BAL中PFC激活的减少幅度更大（多变量p <； .02），而在YA中观察到类似但不显著的趋势（p <； .06）。重要的是，在OA中，横断面相关性和纵向相关性变化都表明，PFC激活减少与更好的平衡表现相关。我们的研究结果支持这样一种观点，即BAL可能会减少OA患者功能失调的PFC激活，导致激活模式更类似于YA，对姿势控制和可能的跌倒风险有积极影响。

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引用次数: 0