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Time Delay: Searching for a Meaningful Outcome of Disease Modification in Alzheimer Disease: A Report of the Educational Symposium Held at ISPOR Europe 2023.
IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1097/WAD.0000000000000654
Anja Schiel, Niels Juul Brogaard, Julie Hahn-Pedersen, Max Schlueter, Linus Jönsson
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引用次数: 0
Long-term Cognitive Trajectories in Older Adults After Surgery: A Population-based Cohort Study.
IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2025-01-09 DOI: 10.1097/WAD.0000000000000655
Parthasarathy D Thirumala, Beth E Snitz, Erin Jacobsen, Chung-Chou H Chang, Yue-Fang Chang, Mary Ganguli

Introduction: Postoperative cognitive decline (POCD) is a common, but often unrecognized condition after surgery. We evaluate postsurgical cognitive changes in a longitudinal population-based study.

Methods: The study cohort comprises an age-stratified population-based random sample of individuals aged 65+ years from a small-town region of the United States. We identified as cases those participants who, during annual assessments, self-reported having undergone surgery under general anesthesia during the preceding year. We identified as controls those who reported no surgery for at least 6 consecutive years. The outcome variable changed over time (4 y) in annual cognitive test composite scores encompassing the domains of attention/processing speed, executive function, memory, language, and visuospatial functions, which were modeled using Generalized Estimating Equations.

Results: A total of 436 participants had the required cognitive data; 179 participants (cases) had undergone surgery, while 257 participants (controls) had not undergone surgery. After adjusting for age, years of education, gender, race, heart failure, irregular heartbeat, and stroke, participants who underwent surgery had a greater decline in executive function, memory, and attention over a 2-year period.

Discussion: Participants who underwent surgery had a significant subsequent decline in cognitive function over the long term.

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引用次数: 0
Clinical Utility and Safety of an Ultrasonic Head Stimulator in Dementia With Lewy Bodies. 超声波头部刺激器在路易体痴呆症中的临床实用性和安全性
IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-11-26 DOI: 10.1097/WAD.0000000000000652
Yuta Manabe

Background: The potential of Ultra-Ma, an ultrasonic head stimulator, for the supplementary treatment of dementia with Lewy bodies (DLB) was evaluated in patients with various symptoms under poor control by drug therapy.

Methods: Patients with DLB treated with choline esterase inhibitor or L-DOPA, either alone or in combination, and who met inclusion criteria were enrolled. Four weeks of placebo stimulation was followed by 8 weeks of active ultrasonic stimulation and a 4-week follow-up. Primary endpoints were the effects of ultrasonic head stimulation on both cognitive dysfunction and behavioral and psychological symptoms of dementia (BPSD). Cognitive dysfunction was evaluated using the Japanese versions of the Mini-Mental State Examination and Montreal Cognitive Assessment, and BPSD was assessed using the Neuropsychiatric Inventory Brief Questionnaire Form. For cognitive fluctuations, the Cognitive Fluctuation Inventory served as an index. Improvements in parkinsonism, activities of daily living, and caregiver burden were examined as secondary endpoints.

Results: Twelve patients were enrolled. The primary endpoint was significantly improved during the active stimulation period, as were secondary endpoint ratings for parkinsonism and caregiver burden. No notable adverse events occurred.

Conclusions: The findings suggest that ultrasonic head stimulation has supplementary potential when combined with drug treatment in DLB.

背景:在药物治疗控制不佳的各种症状患者中评估了超声波头部刺激器 Ultra-Ma 辅助治疗路易体痴呆症(DLB)的潜力:方法:研究人员招募了接受胆碱酯酶抑制剂或左旋多巴单独或联合治疗的路易体痴呆患者,这些患者均符合纳入标准。在进行为期四周的安慰剂刺激后,再进行为期八周的主动超声波刺激和为期四周的随访。主要终点是头部超声波刺激对认知功能障碍以及痴呆症的行为和心理症状(BPSD)的影响。认知功能障碍采用日语版的迷你精神状态检查和蒙特利尔认知评估进行评估,BPSD则采用神经精神量表简明问卷表进行评估。认知波动量表作为认知波动的指标。帕金森病、日常生活活动和护理负担的改善情况作为次要终点进行研究:结果:共招募了 12 名患者。主要终点在主动刺激期间有明显改善,次要终点帕金森症和护理负担的评分也有明显改善。无明显不良事件发生:结论:研究结果表明,超声波头部刺激与药物治疗相结合,对 DLB 有辅助治疗的潜力。
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引用次数: 0
The Difference in Cognitive Profiles Between Patients With Alzheimer Dementia With and Without Psychosis: A Rapid Review. 有无精神病的阿尔茨海默氏症痴呆患者在认知方面的差异:快速回顾
IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-10-01 Epub Date: 2024-09-25 DOI: 10.1097/WAD.0000000000000644
Jean-François Carmel, Doris Clerc, Vincent Couture, Isabelle Reid, Ali Filali, Juan Manuel Villalpando

Background: Psychosis in Alzheimer disease (AD) is a major burden for patients and their family. Identifying the characteristics of delusions and hallucinations in the AD population is key to understanding the interconnection between the psychiatric and cognitive symptoms in neurocognitive disorders. The aim of this study is to compare the cognitive profiles of AD patients with and without psychosis.

Methods: We conducted a rapid review to explore the relationship between psychotic symptoms and cognitive performances in patients with AD. We used MEDLINE, Embase, and PsychINFO literature databases between January 2015 and January 2023. This rapid review was guided by the Cochrane Rapid Reviews Methods Group.

Results: We identified 2909 records from the initial searches. After reviewing the titles, abstracts, and full texts, we selected 8 cross-sectional and 5 cohort studies for the qualitative analysis. Among them, 6 studies were included in the final quantitative analysis. Most studies suggested a correlation between general cognitive decline and the risk of presenting psychotic symptoms. Three studies found an association between hallucinations and deficits in the visuocognitive domains (visuospatial, visuoperceptual, and visuoconstructive skills). Two studies found a relationship between psychotic symptoms and executive dysfunction. Two studies also found a correlation between psychotic symptoms and language. Our results are in line with previous data in the literature, especially regarding the outcome of psychosis on executive function and visuocognitive abilities.

Conclusions: There appears to be an association between cognitive deficits and psychotic symptoms in AD, but the direction of causality is still unclear, and further studies using longitudinal designs would give more insight into the pathophysiological process of psychosis in AD.

背景:阿尔茨海默病(AD)中的精神病是患者及其家人的主要负担。确定阿尔茨海默病患者妄想和幻觉的特征是了解神经认知障碍中精神症状和认知症状之间相互联系的关键。本研究旨在比较患有和未患有精神病的 AD 患者的认知特征:我们进行了一项快速综述,以探讨精神病症状与 AD 患者认知表现之间的关系。我们使用了 2015 年 1 月至 2023 年 1 月期间的 MEDLINE、Embase 和 PsychINFO 文献数据库。本次快速综述由 Cochrane 快速综述方法小组指导:我们从初步检索中确定了 2909 条记录。在审阅了标题、摘要和全文后,我们选择了 8 项横断面研究和 5 项队列研究进行定性分析。其中,6 项研究被纳入最终的定量分析。大多数研究表明,一般认知能力下降与出现精神病性症状的风险之间存在相关性。三项研究发现,幻觉与视觉认知领域(视觉空间、视觉感知和视觉建构能力)的缺陷之间存在关联。两项研究发现精神病症状与执行功能障碍之间存在关系。两项研究还发现精神病症状与语言之间存在相关性。我们的研究结果与之前的文献数据一致,尤其是关于精神病对执行功能和视觉认知能力的影响:结论:AD患者的认知缺陷与精神病性症状之间似乎存在关联,但因果关系的方向尚不明确,采用纵向设计的进一步研究将有助于深入了解AD患者精神病的病理生理过程。
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引用次数: 0
Dementia and Its Profound Impact on Family Members and Partners: A Large UK Cross-Sectional Study. 痴呆症及其对家庭成员和伴侣的深远影响:英国一项大型横断面研究
IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-10-01 Epub Date: 2024-11-07 DOI: 10.1097/WAD.0000000000000647
R Shah, M S Salek, F M Ali, S J Nixon, K Otwombe, J R Ingram, A Y Finlay

Introduction: Dementia can adversely affect the quality of life (QoL) of family members/partners of those affected. Measuring this often-neglected burden is critical to planning and providing appropriate support services. This study measures this impact using the Family-Reported Outcome Measure (FROM-16).

Methods: A large UK cross-sectional online study through patient research platforms, recruited family members/partners of people with dementia, to complete the FROM-16.

Results: Totally, 711 family members/partners (mean age=58.7 y, SD=12.5; females=81.3%) of patients (mean age=81.6, SD=9.6; females=66.9) with dementia completed the FROM-16. The FROM-16 mean total score was 17.5 (SD=6.8), meaning "a very large effect" on QoL of family members, with females being more adversely impacted.

Conclusions: Dementia profoundly impacts the QoL of family members/partners of patients. Routine use of FROM-16 could signpost provision of care support, reducing family members' burnout. Such routine data could be used in economic analysis of the burden of dementia as well as in predicting institutionalization.

引言痴呆症会对患者家庭成员/伴侣的生活质量(QoL)产生不利影响。衡量这种经常被忽视的负担对于规划和提供适当的支持服务至关重要。本研究采用 "家庭报告结果测量法"(FROM-16)来衡量这种影响:方法:英国通过患者研究平台开展了一项大型横断面在线研究,招募痴呆症患者的家庭成员/伴侣填写 FROM-16:共有 711 名痴呆症患者(平均年龄为 58.7 岁,SD=12.5;女性=81.3%)的家庭成员/伴侣(平均年龄为 81.6 岁,SD=9.6;女性=66.9)完成了 FROM-16。FROM-16 的平均总分为 17.5(SD=6.8),这意味着对家庭成员的 QoL 有 "非常大的影响",女性受到的负面影响更大:痴呆症对患者家庭成员/伴侣的 QoL 影响深远。常规使用 FROM-16 可以提供护理支持,减少家庭成员的倦怠感。这些常规数据可用于痴呆症负担的经济分析,以及预测入院治疗的情况。
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引用次数: 0
Mapping the Landscape of Those Left Behind When a Person With Dementia Dies: Roles of Race and Ethnicity. 绘制痴呆症患者去世后留守人员的分布图:种族和民族的作用。
IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-10-01 Epub Date: 2024-09-23 DOI: 10.1097/WAD.0000000000000645
Zachary G Baker, SeungYong Han, Justine S Sefcik, Darina V Petrovsky, Kris Pui Kwan Ma, Matthew Lee Smith, Juanita-Dawne R Bacsu, Zahra Rahemi, Joseph Saenz

Introduction: People with dementia can have many family and friends who might be affected by their deaths. Pursuing the long-term aim of understanding how dementia deaths affect close family and friends, this project lays groundwork through estimates of who those close family and friends are, with special attention to race and ethnicity.

Method: Regression models estimated associations between dementia, race/ethnicity, and close family and friend network size, controlling for age, sex, education, marital status, and household wealth for 1386 deceased people with dementia from the Health and Retirement Study (2004 to 2018).

Results: Persons with dementia had an average of 9.4 close family and friends at death. But patterns of close family and friends were different among non-Latino Black (10.8), Latino (9.9), and non-Latino White (9.2) people with dementia at death. Notably, non-Latino White persons with dementia had the fewest close family (3.7), followed by non-Latino Black (5.1), and Latino (7.7) persons with dementia.

Discussion: Knowing who might be affected by dementia deaths is the first step to explore how dementia-related deaths impact close family and friends. Future work can now sample bereaved family and friends of people with dementia to explore their experiences and develop culturally appropriate supports.

导言:痴呆症患者可能有很多家人和朋友,他们的死亡可能会影响到这些人。本项目的长期目标是了解痴呆症患者的死亡对近亲属和朋友的影响,通过估算这些近亲属和朋友的身份奠定基础,并特别关注种族和民族:回归模型估算了《健康与退休研究》(Health and Retirement Study,2004-2018 年)中 1386 名痴呆症患者的痴呆症、种族/民族、近亲属和朋友网络规模之间的关联,同时控制了年龄、性别、教育程度、婚姻状况和家庭财富:痴呆症患者去世时平均有 9.4 个亲密的家人和朋友。但非拉丁裔黑人(10.8 人)、拉丁裔(9.9 人)和非拉丁裔白人(9.2 人)痴呆症患者死亡时的亲密亲友模式有所不同。值得注意的是,非拉丁裔白人痴呆症患者的近亲(3.7)最少,其次是非拉丁裔黑人(5.1)和拉丁裔(7.7)痴呆症患者:讨论:了解哪些人可能会受到痴呆症死亡的影响是探索痴呆症相关死亡如何影响近亲属和朋友的第一步。今后的工作可以对痴呆症患者的遗属和朋友进行抽样调查,以探索他们的经历并开发适合其文化的支持。
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引用次数: 0
G2019S Mutation of Leucine-Rich Repeat Kinase 2 Is a Cause of Lewy Body Dementia in Patients With North African Ancestors. 富亮氨酸重复激酶 2 的 G2019S 突变是北非祖先路易体痴呆症的病因之一。
IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-07 DOI: 10.1097/WAD.0000000000000643
Kurt Segers, Florence Benoit, Sophie Levy, Valérie Martinet, Joachim G Schulz, Frédéric Bertrand, Gabrielle De Bourgoing, Chiara Tatillo, Jean-Philippe Praet, Isabelle Vandernoot, Laurence Desmyter, Xavier Peyrassol, Pashalina Kehagias, Guillaume Smits, Baptiste Dumoulin, Tatiana Besse-Hammer, Bernard Dachy, Murielle Surquin

Background: Mutations in the LRRK2 gene are the most common genetic cause of Parkinson disease but are believed to play no significant role in Lewy body disease (LBD).

Objectives: As the frequency of G2019S LRRK2 mutation is extremely high in North African patients with Parkinson disease, we postulate that the high prevalence of LBD in North Africa might be due to the same mutation because LBD and Parkinson disease share many clinical, pathological, and genetic features.

Methods: We screened patients with LBD or prodromal LBD for the G2019S mutation of LRRK2.

Results: A total of 162 patients were tested for the mutation, which was present in 5 of the 47 patients with North African ancestors. This is a much higher prevalence (10.6%) than in healthy North African subjects (1.45%) but lower than in North African patients with Parkinson disease (36% to 39%). Carriers tended to develop more often orthostatic hypotension and swallowing problems.

Conclusions: Where previous studies in European and North American patients found no link between LRRK2 mutations and LBD, we found an LRRK2 mutation associated with Lewy body disease, namely the G2019S mutation that might be restricted to patients with North African ancestors. Our study illustrates the need to introduce ethnic diversity as stratifying factor in the analysis of genetic causes of neurodegenerative disorders. The current development of disease-modifying drugs modulating LRRK2 kinase activity could justify to screen North African patients with LBD for the G2019S LRRK2 mutation.

背景:LRRK2基因突变是帕金森病最常见的遗传病因,但据信在路易体病(LBD)中并未发挥重要作用:由于 G2019S LRRK2 基因突变在北非帕金森病患者中出现的频率极高,我们推测北非路易体病的高发病率可能是由于该基因突变所致,因为路易体病和帕金森病在临床、病理和遗传学方面有许多共同特征:我们对枸杞多糖症或前驱枸杞多糖症患者进行了 LRRK2 G2019S 突变筛查:结果:共对 162 名患者进行了突变检测,在 47 名祖先为北非人的患者中,有 5 人存在这种突变。这一发病率(10.6%)远高于健康的北非人(1.45%),但低于北非帕金森病患者(36% 至 39%)。携带者往往更容易出现正性低血压和吞咽困难:我们发现了一种与路易体病相关的 LRRK2 基因突变,即 G2019S 基因突变,这种突变可能仅限于有北非祖先的患者。我们的研究表明,在分析神经退行性疾病的遗传原因时,有必要引入种族多样性作为分层因素。目前正在开发改变 LRRK2 激酶活性的药物,这为筛查 LBD 北非患者的 G2019S LRRK2 突变提供了依据。
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引用次数: 0
Examining the Measurement Equivalence of Alzheimer Disease Research Centers' Neuropsychological Test Battery (Version 3) Between Singapore and US Samples. 研究阿尔茨海默病研究中心神经心理测试库(第 3 版)在新加坡和美国样本之间的测量等效性。
IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-28 DOI: 10.1097/WAD.0000000000000649
Sze Yan Tay, Way Inn Koay, Simon Kang Seng Ting, Tau Ming Liew

Purpose: Standardization of neuropsychological tests is crucial for consistency in cognitive assessment, as well as for validity and comparability of results across different populations. We examined the applicability and measurement equivalence of the Alzheimer Disease Research Centers' Neuropsychological Test Battery (version 3) (ADRC-NTB3) in Singapore.

Methods: The ADRC-NTB3 was administered to 978 older persons with normal cognition in Singapore. To provide comparison between Singapore and US samples, a US sample with similar profile was retrieved from the National Alzheimer Coordinating Center (NACC) database.

Patients: Scores were compared with 1853 participants with similar profile from the United States. Score-difference between the populations was computed using multiple linear regression (adjusted for covariates), with equivalent score considered present when 90% CI of the score-difference fell within the predefined margin of equivalence.

Results: Tasks assessing for memory, processing speed, and executive functioning showed equivalence in scores between US and Singapore samples (adjusted-score difference=-0.94 to 0.09). Singapore sample performed marginally better on the visuospatial task (adjusted-score difference=0.50), but poorer on the language task (adjusted-score difference=-3.22).

Discussion: Nonequivalence of visuospatial and language tasks, which may increase potential misinterpretation of cognitive profiles and misdiagnosis, are related to educational and cultural differences. This highlights the need for different normative data for more accurate diagnostic accuracy as well as research priorities.

目的:神经心理测试的标准化对于认知评估的一致性以及不同人群结果的有效性和可比性至关重要。我们研究了阿尔茨海默病研究中心神经心理测试库(第 3 版)(ADRC-NTB3)在新加坡的适用性和测量等效性:对新加坡 978 名认知能力正常的老年人进行了 ADRC-NTB3 测试。为了对新加坡和美国的样本进行比较,我们从美国国家阿尔茨海默氏症协调中心(NACC)的数据库中提取了具有相似特征的美国样本:患者:与来自美国的 1853 名具有相似特征的参与者进行了评分比较。使用多元线性回归法计算人群间的得分差异(根据协变量进行调整),当得分差异的 90% CI 在预定的等效范围内时,则认为存在等效得分:结果:在评估记忆力、处理速度和执行功能的任务中,美国和新加坡样本的得分相等(调整后的分数差异=-0.94 到 0.09)。新加坡样本在视觉空间任务上的表现略胜一筹(调整后分数差异=0.50),但在语言任务上的表现较差(调整后分数差异=-3.22):讨论:视觉空间任务和语言任务的非等效性可能会增加对认知概况的潜在误读和误诊,这与教育和文化差异有关。这凸显了需要不同的常模数据来提高诊断准确性以及研究重点。
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引用次数: 0
Discontinuation of Alzheimer Disease Medications in Patients Receiving Home Care Medicine. 接受家庭护理药物治疗的阿尔茨海默病患者停药问题。
IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-28 DOI: 10.1097/WAD.0000000000000650
Kiwami Kidana, Ryonosuke Yamaga, Hiroko Fujii, Masahiro Akishita, Takashi Yamanaka

There is no consensus on how long antidementia medications should be administered to patients with Alzheimer disease (AD). To clarify this issue, we investigated the discontinuation of antidementia medications in Japanese home care settings, including community-dwelling and institutionalized patients. Using medical records from April 2017 to March 2022 at 3 clinics in Tokyo and Chiba prefectures, we selected patients with AD who started receiving home care medicine. Forty-nine patients discontinued antidementia medications during the observation period, there was no apparent deterioration in cognitive function or new occurrence of behavioral and psychological symptoms of dementia caused by the discontinuation of medications. More aggressive discontinuation of AD medications probably is recommended for patients with activities of daily living dysfunction, such as those receiving home care medicine.

关于阿尔茨海默病(AD)患者应服用多长时间的抗痴呆药物,目前还没有达成共识。为了澄清这一问题,我们调查了日本家庭护理环境中抗痴呆药物的停药情况,包括社区居住和机构护理的患者。我们利用东京都和千叶县 3 家诊所 2017 年 4 月至 2022 年 3 月的医疗记录,选取了开始接受家庭护理药物治疗的 AD 患者。有49名患者在观察期间停用了抗痴呆药物,但停药并未导致认知功能明显恶化,也未出现新的痴呆行为和心理症状。对于有日常生活功能障碍的患者,如接受家庭护理药物治疗的患者,可能建议更积极地停用抗痴呆药物。
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引用次数: 0
DXA-Measured Abdominal Adipose Depots and Structural Brain Integrity in Postmenopausal Women. 通过 DXA 测量的绝经后妇女腹部脂肪沉积和大脑结构完整性。
IF 1.8 4区 医学 Q3 CLINICAL NEUROLOGY Pub Date : 2024-10-01 Epub Date: 2024-08-12 DOI: 10.1097/WAD.0000000000000642
Zeinah Al-Darsani, Hailey R Banack, Mallory N Ziegler, Stephen R Rapp, Maria M Corrada, Andrew O Odegaard

Background: This study extends prior research from the MRI substudy of the Women's Health Initiative Memory Study (WHIMS-MRI) linking BMI to reduced brain atrophy and ischemic lesion load by examining DXA-based measurements of total body fat, total abdominal adipose tissue (TAT), abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue, gynoid fat, and overall leg fat.

Methods: The analytic sample consisted of 61 postmenopausal women (baseline mean age 69.5 [3.6]) enrolled in WHIMS-MRI who had undergone DXA scans. DXA scans were completed at years 0, 3, and 6, and MRI scans were conducted ~8 years after baseline. Adjusted linear regression models were used to analyze the association between adiposity averaged across the 3-time points and volumes of brain regions previously linked to dementia.

Results: Higher levels of total body fat, TAT, VAT, SAT, gynoid, and overall leg fat were associated with larger hippocampal volume (β 0.02 [95% CI, 0.004-0.04]; 0.11 [0.02-0.21]; 0.26 [0.04-0.47]; 0.18 [0.03-0.33]; 0.18 [0.05-0.30]; 0.07 [0.009-0.12], respectively). No other significant associations were observed.

Conclusion: Higher levels of adiposity were positively associated with hippocampal volume. Additional research with larger sample sizes is needed to ascertain the significance of this association.

研究背景这项研究通过检查基于 DXA 的总体脂、总腹部脂肪组织(TAT)、腹部内脏脂肪组织(VAT)和皮下脂肪组织(SAT)、妇科脂肪和腿部总脂肪的测量值,对妇女健康倡议记忆研究(WHIMS-MRI)磁共振成像子研究中有关 BMI 与脑萎缩和缺血性病变负荷减少之间联系的先前研究进行了扩展:分析样本包括61名绝经后妇女(基线平均年龄为69.5 [3.6]),她们都参加了WHIMS-MRI并接受了DXA扫描。DXA扫描在第0、3和6年完成,MRI扫描在基线后约8年进行。采用调整线性回归模型分析了3个时间点的平均脂肪含量与先前与痴呆症相关的脑区体积之间的关系:结果:身体总脂肪、TAT、VAT、SAT、雌激素和腿部总脂肪水平越高,海马体积越大(分别为β 0.02 [95% CI, 0.004-0.04]; 0.11 [0.02-0.21]; 0.26 [0.04-0.47]; 0.18 [0.03-0.33]; 0.18 [0.05-0.30]; 0.07 [0.009-0.12])。没有观察到其他重大关联:结论:较高的肥胖水平与海马体积呈正相关。结论:较高的脂肪水平与海马体积呈正相关,需要进行更多的样本研究,以确定这种关联的重要性。
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引用次数: 0
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Alzheimer Disease & Associated Disorders
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