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Perspectives From Black and White Participants and Care Partners on Return of Amyloid and Tau PET Imaging and Other Research Results. 黑人和白人参与者以及护理伙伴对淀粉样蛋白和Tau PET成像和其他研究结果的回报的看法。
IF 2.1 4区 医学 Pub Date : 2023-10-01 Epub Date: 2023-10-30 DOI: 10.1097/WAD.0000000000000591
Annalise Rahman-Filipiak, Mary Lesniak, Shima Sadaghiyani, Scott Roberts, Peter Lichtenberg, Benjamin M Hampstead

Purpose: Alzheimer disease (AD) biomarker testing is now common in research and approaching clinical translation. Disclosure protocols must be informed by diverse participants' perspectives on if/how the information would be useful.

Methods: This study utilized semistructured interviews assessing interest in receiving positron emission tomography (PET) amyloid and tau results, as well as perceived risks and benefits of hypothetical PET disclosure as a function of race and participant diagnosis.

Participants: Participants [39% Black; 61% White; Mage =74.28 (5.98)] included 57 adults diagnosed as either cognitively healthy (58%) or with mild cognitive impairment (42%) and their respective care partners [33% Black; 67% White; Mage =66.93 (10.92)].

Results: Most dyads endorsed strong interest in PET results (82.5% of both participants and partners) regardless of race or diagnosis. Black care partners were less interested in receiving the participant's results than White care partners ( χ2(4) =8.31, P =0.047). Reasons for disclosure were diverse and highly personalized, including access to treatments or clinical trials (23.2% participants; 29.8% partners), advance planning (14.3% participants; 17.5% partners), and improved health knowledge (12.5% participants; 15.8% partners). In contrast, over 80% of respondents denied any risks of disclosure.

Discussion: Results suggest that predisclosure education, decisional capacity assessment, and a flexible disclosure approach are needed.

目的:阿尔茨海默病(AD)生物标志物检测现在在研究和临床翻译中很常见。披露协议必须根据不同参与者对信息是否有用/如何有用的看法。方法:本研究利用半结构访谈评估对接受正电子发射断层扫描(PET)淀粉样蛋白和tau结果的兴趣,以及假设PET披露作为种族和参与者诊断的函数的感知风险和益处。参与者:参与者[39%黑人;61%白人;Mage=74.28(5.98)]包括57名被诊断为认知健康(58%)或轻度认知障碍(42%)的成年人及其各自的护理伙伴[33%黑人;67%白人;Mage=66.93(10.92)]。与白人护理伙伴相比,黑人护理伙伴对接受参与者的结果不太感兴趣(χ2(4)=8.31,P=0.047)。披露的原因多种多样且高度个性化,包括获得治疗或临床试验(23.2%的参与者;29.8%的伙伴)、提前计划(14.3%的参与者,17.5%的伙伴),提高了健康知识(12.5%的参与者;15.8%的合作伙伴)。相比之下,超过80%的受访者否认存在任何披露风险。讨论:结果表明,披露前教育、决策能力评估和灵活的披露方法是必要的。
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引用次数: 0
Alzheimer Disease: A New Beginning in Therapeutics. 阿尔茨海默病:治疗学的新开端。
IF 2.1 4区 医学 Pub Date : 2023-10-01 Epub Date: 2023-11-28 DOI: 10.1097/WAD.0000000000000592
Lawrence S Honig
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引用次数: 0
Virtual Assessment as a Way to Reduce Help-seeking Barriers in Older Adults With Subjective Cognitive Decline. 虚拟评估是减少老年人主观认知能力下降求助障碍的一种方法。
IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-10-01 Epub Date: 2023-09-19 DOI: 10.1097/WAD.0000000000000582
Michael R Kann, Peter J Zeiger, Sandra J Rizer, Stephanie Cosentino, Martina Azar

Subjective cognitive decline (SCD), a potential early marker for neurodegenerative disease such as Alzheimer's disease, is common among older adults. Although it is often regarded as a personal health concern, most individuals with SCD do not seek help from a health care professional. Help-seeking (HS) is a complex, individualized process with significant life-course implications, and older adults often face several barriers to HS across personal, socioeconomic, and cultural domains. The pandemic exacerbated these barriers by imposing additional limitations on in-person care. In response, virtual assessment became a popular method to conduct remote care. We provide a narrative review of the challenges and triumphs that came with the transition from in-person, pen-paper cognitive assessments to virtual cognitive assessments. In addition, we address the impact virtual assessment had in tackling barriers that previously limited individuals with SCD from formal HS. We argue that virtual cognitive assessment helps alleviate health access barriers to HS (e.g., cost, transportation, and physician availability) and allows individuals with different coping styles to undergo assessment within more convenient environments. We hope the findings presented in this review inform health care practice, public education, and future research targeted towards the use of virtual assessment to facilitate HS in older adults with SCD.

主观认知能力下降(SCD)是阿尔茨海默病等神经退行性疾病的潜在早期标志,在老年人中很常见。尽管SCD通常被视为个人健康问题,但大多数SCD患者不会向医疗保健专业人员寻求帮助。寻求帮助(HS)是一个复杂的、个性化的过程,具有重大的人生历程意义,老年人在个人、社会经济和文化领域往往面临着HS的几个障碍。新冠疫情对面对面的护理施加了额外的限制,从而加剧了这些障碍。作为回应,虚拟评估成为进行远程护理的一种流行方法。我们对从面对面、纸笔认知评估到虚拟认知评估的转变所带来的挑战和成功进行了叙述性回顾。此外,我们还讨论了虚拟评估在解决以前限制SCD患者进入正式HS的障碍方面所产生的影响。我们认为,虚拟认知评估有助于缓解HS的健康获取障碍(如成本、交通和医生可用性),并允许具有不同应对方式的个人在更方便的环境中接受评估。我们希望这篇综述中的研究结果能为医疗保健实践、公共教育和未来的研究提供信息,这些研究旨在使用虚拟评估来促进患有SCD的老年人的HS。
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引用次数: 0
Gender, Pain, and Function Associated With Physical Activity After Hospitalization in Persons Living With Dementia. 痴呆症患者住院后与身体活动相关的性别、疼痛和功能。
IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2023-10-01 Epub Date: 2023-09-20 DOI: 10.1097/WAD.0000000000000583
Ashley Kuzmik, Marie Boltz, Barbara Resnick, Brittany F Drazich, James E Galvin

Background: The purpose of this study was to identify factors that are associated with physical activity after hospitalization in persons living with dementia.

Methods: Multiple linear regressions were conducted to test factors associated with objective activity levels (sedentary, low, moderate, and vigorous) among 244 patients living with dementia from a randomized controlled trial.

Results: Within 48 hours of hospital discharge, time in sedentary behavior was associated with increased pain (β=0.164, P =0.015). Time in low activity was associated with less pain (β=-0.130, P =0.049) and higher physical function (β=0.300, P =<0.001). Time in moderate activity was associated with increased physical function (β=0.190, P =0.008) and male gender (β=0.155, P =0.016). No significant associations of potential factors were found with time in vigorous activity.

Conclusions: Our findings suggest that managing or reducing pain, encouraging individual functional level, and gender could influence time spent in physical activity after acute hospitalization in persons living with dementia.

背景:本研究的目的是确定与痴呆症患者住院后体育活动相关的因素。方法:在一项随机对照试验中,对244名痴呆症患者进行多元线性回归,以检验与客观活动水平(久坐、低、中等和剧烈)相关的因素。结果:出院48小时内,久坐时间与疼痛增加有关(β=0.164,P=0.015)。低活动时间与疼痛减轻有关(β=-0.130,P=0.049)和身体功能增强有关(β=0.300,P=结论:我们的研究结果表明,管理或减轻疼痛、提高个体功能水平和性别可能会影响痴呆症患者急性住院后的体育活动时间。
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引用次数: 0
A Randomized Double-blind Study to Assess the Skin Irritation and Sensitization Potential of a Once-weekly Donepezil Transdermal Delivery System in Healthy Volunteers. 一项随机双盲研究评估健康志愿者每周一次的多奈哌齐透皮给药系统的皮肤刺激和致敏潜力。
IF 2.1 4区 医学 Pub Date : 2023-10-01 Epub Date: 2023-09-11 DOI: 10.1097/WAD.0000000000000578
Marwan N Sabbagh, Philip Mathew, Alan Blau
Background: A once-weekly donepezil transdermal delivery system (TDS; Adlarity; Corium, LLC) is indicated for the treatment of mild, moderate, and severe dementia of the Alzheimer type. Methods: In this placebo-controlled, randomized, double-blind phase 1 trial, healthy volunteers aged 40 years or older were randomized to receive a placebo and donepezil TDS and were evaluated for the primary endpoints of skin irritation and sensitization potential. Skin irritation was scored. Results: Two hundred fifty-six participants were randomized and received ≥1 dose of any treatment. After the first weekly TDS application, no skin irritation or minimal irritation was evident between donepezil and placebo TDSs. At the third weekly TDS application, for donepezil TDS, the average of the mean combined skin irritation score was 0.55 of a possible maximum of 7, indicating none to minimal skin irritation, and for placebo, the score was 0.19, indicating no skin irritation. Of 198 participants, 4 (2.0%) were considered potentially sensitized to donepezil TDS, and 0 were potentially sensitized to placebo TDS. Conclusion: Once-weekly 5-mg/d donepezil TDS demonstrated minimal skin irritation under conditions of use of 3 consecutive weekly patch applications to the same skin site and minimal sensitization potential.
研究背景:每周一次的多奈哌齐透皮给药系统(TDS;Adlarity;Corium, LLC)适用于治疗轻度、中度和重度阿尔茨海默型痴呆。方法:在这项安慰剂对照、随机、双盲的1期试验中,年龄在40岁或以上的健康志愿者随机接受安慰剂和多奈哌齐TDS,并评估皮肤刺激和致敏潜力的主要终点。对皮肤刺激进行评分。结果:256名参与者随机接受≥1剂量的任何治疗。在第一周TDS应用后,多奈哌齐和安慰剂TDS之间没有明显的皮肤刺激或最小刺激。在第三周TDS应用时,对于多奈哌齐TDS,平均联合皮肤刺激评分的平均值为0.55(可能的最大值为7),表明没有到最小的皮肤刺激,对于安慰剂,得分为0.19,表明没有皮肤刺激。198名参与者中,4人(2.0%)被认为对多奈哌齐TDS潜在致敏,0人对安慰剂TDS潜在致敏。结论:每周一次5mg /d多奈哌齐TDS在使用连续3周的贴片应用于同一皮肤部位的情况下表现出最小的皮肤刺激和最小的致敏潜力。
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引用次数: 0
High-Frequency rTMS Could Improve Impaired Memory in Mild Cognitive Impairment Patients in China: A Randomized Controlled Study. 高频rTMS可以改善中国轻度认知障碍患者的记忆受损:一项随机对照研究。
IF 2.1 4区 医学 Pub Date : 2023-10-01 Epub Date: 2023-08-25 DOI: 10.1097/WAD.0000000000000577
Tao Wang, Zhiwei Guo, Hongxia Wu, Yi Jiang, Qiwen Mu

Objective: The purpose of this study was to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on improving memory deficits in mild cognitive impairment (MCI), as well as to provide visualized evidence for neuronal specificity by using resting-state functional magnetic resonance imaging.

Materials and methods: Forty MCI patients were enrolled to receive 10-session and sham-controlled 10Hz-rTMS over the left dorsolateral prefrontal cortex. The resting-state functional magnetic resonance imaging combined with memory scales assessment were performed before and after the intervention. To elucidate the therapeutic mechanism of rTMS, amplitude of low-frequency fluctuations (ALFF) and functional connectivity were calculated. The Pearson correlation was used to measure the relationship between ALFF and memory performance.

Results: Compared with the sham group, ALFF significantly increased in the right insula, right inferior frontal gyrus-opercular part, and decreased in the left middle occipital gyrus, left angular gyrus, and left lingual gyrus after rTMS. The change in Auditory Verbal Learning Test scores were negatively correlated with ALFF decreases in the left lingual gyrus. Functional connectivity significantly increased between the posterior cingulate cortex and right supramarginal gyrus, and decreased between the right frontoinsular cortex and right supramarginal gyrus after intervention.

Conclusion: High-frequency rTMS over the left dorsolateral prefrontal cortex could facilitate improvement on impaired memory in patients with MCI via modulating the neuronal activity and brain network.

目的:探讨重复经颅磁刺激(rTMS)对轻度认知障碍(MCI)患者记忆缺陷的改善作用,并利用静息状态功能磁共振成像技术为神经元特异性提供可视化证据。材料与方法:选取40例轻度认知障碍患者,在左前额叶背外侧皮质区接受10期假对照10Hz-rTMS。干预前后分别进行静息状态功能磁共振成像及记忆量表评估。为了阐明rTMS的治疗机制,我们计算了低频波动幅度(ALFF)和功能连通性。使用Pearson相关来衡量ALFF与记忆性能之间的关系。结果:与假手术组比较,rTMS后右侧脑岛、右侧额下回-眼部ALFF明显升高,左侧枕中回、左侧角回、左侧舌回ALFF明显降低。听觉语言学习测试成绩的变化与左舌回ALFF的减少呈负相关。干预后,后扣带皮层与右侧边缘上回之间的功能连通性显著增加,右侧额岛皮层与右侧边缘上回之间的功能连通性显著降低。结论:左背外侧前额叶皮层高频rTMS可通过调节神经元活动和脑网络促进MCI患者记忆受损的改善。
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引用次数: 0
A Longitudinal Evaluation of the Pattern of Social Cognition Impairment in Brazilians With Alzheimer's Disease. 巴西阿尔茨海默病患者社会认知障碍模式的纵向评估。
IF 2.1 4区 医学 Pub Date : 2023-10-01 Epub Date: 2023-11-02 DOI: 10.1097/WAD.0000000000000588
Tatiana Teresa Belfort Almeida Dos Santos, Marcela Moreira Lima Nogueira, Isabel Barbeito Lacerda, Michelle Brandt, Aline Tavares de Lucena, Rogeria Rangel, Julia Gaigher, Felipe Oliveira, Marcia Cristina Nascimento Dourado

Background: Social cognition (SC) impairments contribute to the dependence of people with Alzheimer disease (AD), influencing their functional disability and the burden on family members and caregivers. Our objective was to longitudinally investigate the relationship between SC and cognitive and clinical variables in persons with AD and their caregivers. We also evaluated the different SC predictors from 3 perspectives: people with AD, caregivers of people with AD, and discrepancy analysis.

Methods: In all, 137 dyads (people with AD and their caregivers) underwent 2 assessments: at baseline (M1) and after 1 year (M2). During follow-up, 58 dyads were excluded, and the study was thus concluded with 79.

Results: Longitudinal analysis of the people with AD showed that while some cognitive functions declined (which is consistent with disease progression), SC impairments showed a more stable pattern. Another interesting result was related to SC predictors. For people with AD, SC was associated with cognition at both time points. For caregivers, besides cognition, other predictors included reduced functional abilities and quality of life in people with AD. These results are consistent with the discrepancy predictors.

Conclusion: The stable pattern in SC functioning over 12 months in AD suggests that this neurocognitive domain may be influenced more by emotional processing than by cognitive impairment. In addition, the SC predictors showed that the investigation of different points of view enables a more global understanding, contributing to better and more targeted treatment for the patient.

背景:社会认知(SC)障碍导致阿尔茨海默病(AD)患者的依赖性,影响他们的功能残疾以及家庭成员和照顾者的负担。我们的目的是纵向调查AD患者及其照顾者的SC与认知和临床变量之间的关系。我们还从3个角度评估了不同的SC预测因素:AD患者、AD患者的照顾者和差异分析。方法:总共有137对二人组(AD患者及其照顾者)接受了2次评估:基线时(M1)和1年后(M2)。在随访期间,排除了58对二人组,因此研究得出79对。结果:对AD患者的纵向分析表明,虽然一些认知功能下降(这与疾病进展一致),但SC损伤表现出更稳定的模式。另一个有趣的结果与SC预测因子有关。对于AD患者,SC在两个时间点都与认知有关。对于照顾者,除了认知,其他预测因素包括AD患者的功能能力和生活质量下降。这些结果与差异预测因素一致。结论:AD患者SC功能在12个月内的稳定模式表明,这一神经认知领域可能更多地受到情绪处理的影响,而不是认知障碍的影响。此外,SC预测因子表明,对不同观点的调查能够更全面地理解,有助于更好、更有针对性地治疗患者。
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引用次数: 0
Novel APOE Mutation in a Moroccan Subject Suffering from Alzheimer Disease: A Case Study and Exploration of Pathogenic Implication. 摩洛哥阿尔茨海默病患者的新型APOE突变:一个病例研究和致病意义的探索。
IF 2.1 4区 医学 Pub Date : 2023-10-01 Epub Date: 2023-11-28 DOI: 10.1097/WAD.0000000000000590
Youssef Razouqi, Ihssane El Bouchikhi, Hassan El-Abid, Soukayna Baammi, Ayoub Nedbour, Ahmed Omar Touhami Ahami, Achraf El Allali, Laila Bouguenouch

Alzheimer disease (AD) is a major public health concern worldwide. It is a severe neurodegenerative disease that primarily affects the elderly and causes significant brain cell death. According to the most complete scientific research, the APOE gene, which encodes the APOE protein, maybe the key to identifying the likely cause of delayed AD. The development of plaques and tangles, as well as increased amyloid (amyloid-β) levels and deposition, have been linked to APOE4. Pathogenic mutations in this gene can impact how beta-amyloid deposits and how they are cleared from the body. In this study, we report a novel pathogenic mutation, Arg160Leu, in APOE that was identified in a Moroccan patient. The magnetic resonance imaging of this 67-year-old woman revealed hippocampal shrinkage, and the results of her cognition testing revealed that she is suffering from severe AD. The current study may increase awareness of the genetic risk factors for AD caused by APOE4 mutations.

阿尔茨海默病(AD)是全球主要的公共卫生问题。这是一种严重的神经退行性疾病,主要影响老年人,并导致严重的脑细胞死亡。根据最完整的科学研究,编码APOE蛋白的APOE基因可能是识别延迟性AD可能病因的关键。斑块和缠结的形成,以及淀粉样蛋白(β淀粉样蛋白)水平的增加和沉积,都与APOE4有关。该基因的致病性突变会影响β -淀粉样蛋白沉积的方式以及它们如何从体内清除。在这项研究中,我们报告了一种新的致病突变Arg160Leu,在APOE中被发现在一个摩洛哥病人。这位67岁女性的磁共振成像显示海马萎缩,认知测试结果显示她患有严重的阿尔茨海默病。本研究可能会增加人们对APOE4突变引起AD的遗传危险因素的认识。
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引用次数: 0
Proteomic Analysis Reveals Potential Exosomal Biomarkers in Patients With Sporadic Alzheimer Disease. 蛋白质组学分析揭示散发性阿尔茨海默病患者潜在的外泌体生物标志物
IF 2.1 4区 医学 Pub Date : 2023-10-01 Epub Date: 2023-11-28 DOI: 10.1097/WAD.0000000000000589
Konstanze Plaschke, Jürgen Kopitz, Johannes Gebert, Nadine D Wolf, Robert Christian Wolf

Background: Despite substantial progress made in the past decades, the pathogenesis of sporadic Alzheimer disease (sAD) and related biological markers of the disease are still controversially discussed. Cerebrospinal fluid and functional brain imaging markers have been established to support the clinical diagnosis of sAD. Yet, due to the invasiveness of such diagnostics, less burdensome markers have been increasingly investigated in the past years. Among such markers, extracellular vesicles may yield promise in (early) diagnostics and treatment monitoring in sAD.

Materials and methods: In this pilot study, we collected the blood plasma of 18 patients with sAD and compared the proteome of extracted extracellular vesicles with the proteome of 11 age-matched healthy controls. The resulting proteomes were characterized by Gene Ontology terms and between-group statistics.

Results: Ten distinct proteins were found to significantly differ between sAD patients and controls (P<0.05, False Discovery Rate, corrected). These proteins included distinct immunoglobulins, fibronectin, and apolipoproteins.

Conclusions: These findings lend further support for exosomal changes in neurodegenerative disorders, and particularly in sAD. Further proteomic research could decisively advance our knowledge of sAD pathophysiology as much as it could foster the development of clinically meaningful biomarkers.

背景:尽管在过去的几十年里,散发性阿尔茨海默病(sAD)的发病机制和相关的生物学标志物仍存在争议。脑脊液和功能性脑成像标志物已经建立,以支持sAD的临床诊断。然而,由于这种诊断的侵入性,在过去的几年里,越来越多地研究了负担较轻的标记物。在这些标志物中,细胞外囊泡可能在sAD的(早期)诊断和治疗监测中产生希望。材料与方法:在本初步研究中,我们收集了18例sAD患者的血浆,并将提取的细胞外囊泡蛋白质组与11名年龄匹配的健康对照进行了比较。所得到的蛋白质组通过基因本体术语和组间统计进行表征。结果:10种不同的蛋白在sAD患者和对照组之间存在显著差异(p结论:这些发现进一步支持神经退行性疾病,特别是sAD的外泌体改变。进一步的蛋白质组学研究可以决定性地推进我们对sAD病理生理学的认识,也可以促进临床有意义的生物标志物的发展。
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引用次数: 0
Regional White Matter Hyperintensities Relate to Specific Cognitive Abilities in Older Adults Without Dementia. 区域白质高强度与无痴呆老年人的特定认知能力有关。
IF 2.1 4区 医学 Pub Date : 2023-10-01 Epub Date: 2023-11-28 DOI: 10.1097/WAD.0000000000000585
Rachel Membreno, Kelsey R Thomas, Amanda T Calcetas, Lauren Edwards, Maria Bordyug, Maya Showell, Morgan Stanfill, Einat K Brenner, Kayla S Walker, Lindsay J Rotblatt, Adam M Brickman, Emily C Edmonds, Katherine J Bangen

Introduction: White matter hyperintensities (WMHs) are magnetic resonance imaging markers of small vessel cerebrovascular disease that are associated with cognitive decline and clinical Alzheimer disease. Previous studies have often focused on global or total WMH; less is known about associations of regional WMHs and cognitive abilities among older adults without dementia.

Methods: A total of 610 older adults with normal cognition (n=302) or mild cognitive impairment (n=308) from the Alzheimer's Disease Neuroimaging Initiative underwent neuropsychological testing and magnetic resonance imaging. Linear regression models examined associations between regional WMH volumes and cognition, adjusting for age, sex, education, apolipoprotein E ε4 allele frequency, and pulse pressure.

Results: Among all participants, greater regional WMH volume in all lobes was associated with poorer performance on memory and speed/executive functioning. Among participants with normal cognition, greater temporal and occipital WMH volumes were associated with poorer memory, whereas no regional WMH volumes were associated with speed/executive function.

Discussion: Results show that greater regional WMH volume relates to poorer cognitive functioning-even among those with normal cognition. Together with results from previous studies, our findings raise the possibility that WMH may be a useful therapeutic target and/or important effect modifier in treatment or prevention dementia trials.

简介:白质高强度(WMHs)是小血管脑血管疾病的磁共振成像标志物,与认知能力下降和临床阿尔茨海默病有关。以前的研究往往集中在全球或全部的WMH上;对于区域性脑卒中与无痴呆老年人认知能力之间的关系,我们所知较少。方法:来自阿尔茨海默病神经影像学倡议的610名认知正常(n=302)或轻度认知障碍(n=308)的老年人接受了神经心理测试和磁共振成像。线性回归模型检验了区域WMH量与认知之间的关系,调整了年龄、性别、教育程度、载脂蛋白ε4等位基因频率和脉压。结果:在所有参与者中,所有脑叶的地区性脑mh体积越大,记忆力和速度/执行功能的表现就越差。在认知正常的参与者中,颞部和枕部脑前皮层体积较大与较差的记忆力有关,而脑后皮层区域体积与速度/执行功能无关。讨论:研究结果表明,地区性脑mh体积越大,认知功能越差——即使在认知正常的人群中也是如此。结合以往的研究结果,我们的发现提出了一种可能性,即WMH可能是治疗或预防痴呆试验中有用的治疗靶点和/或重要的效果调节剂。
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引用次数: 0
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Alzheimer Disease & Associated Disorders
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