Small vessel disease and beta-amyloid deposition in mildly impaired cognition

轻度认知障碍中的小血管疾病和 β-淀粉样蛋白沉积

• 批准号: 8223287
• 负责人: Deborah L. BLACKER
• 金额: $ 34.99万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8223287
• 关键词: Address; Affect; Aging; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Amyloid deposition; Area; Autopsy; Binding; Blood Vessels; Brain; Brain Diseases; Brain Pathology; Brain region; Cerebrovascular Disorders; Cerebrum; Clinical Trials; Clinical Trials Design; Cognition; Cognitive; Cohort Studies; Communities; Complement; Data; Dementia; Development; Diffusion Magnetic Resonance Imaging; Diffusion weighted imaging; Disease; Elderly; Episodic memory; Future; High Prevalence; Image; Impaired cognition; Impairment; Individual; Infarction; Inferior; Investigation; Ischemia; Knowledge; Lacunar Infarctions; Left; Lesion; Life; Ligand Binding; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Modality; Neurofibrillary Tangles; Neuropsychological Tests; Pathology; Performance; Perfusion; Phenotype; Pittsburgh Compound-B; Population; Population Study; Positron-Emission Tomography; Prevention; Procedures; Process; Recruitment Activity; Relative (related person); Research; Risk; Senile Plaques; Spin Labels; Staging; Stroke; Testing; Vascular Diseases; age related; base; burden of illness; cognitive function; cohort; design; disability; falls; follow-up; in vivo; meetings; molecular imaging; neuroimaging; prevent; therapeutic target; therapy design; white matter; white matter damage; white matter injury

DESCRIPTION (provided by applicant): We propose to study the association between MRI markers of cerebral small vessel disease and cognitive decline in a population with mild impairment, both in individuals who meet research criteria for MCI and in individuals who fall short of these criteria but have some evidence of cognitive decline. Because evidence shows that pathological brain changes associated with Alzheimer's disease (including neurofibrillary tangles and senile plaques) modify the relationship between small vessel disease and cognition, there is a critical need to incorporate in vivo markers of Alzheimer's pathology into longitudinal studies of the effect of cerebral small vessel disease. The current proposal therefore represents an important advance by measuring a hallmark feature of Alzheimer's pathology, fibrillar beta-amyloid deposition by evidence of Pittsburgh Compound B (PIB) retention on PET, in addition to MRI markers of small vessel disease. The proposed study will complement current ongoing large neuroimaging studies by specifically addressing the relationship between advanced MRI markers of small vessel disease and perfusion, a PET marker of fibrillar beta-amyloid deposition, and cognitive decline. The following hypotheses will be tested: 1) white matter damage from small vessel disease is associated with cognitive decline, independent of the amount of cerebral beta-amyloid deposition, 2) white matter damage from small vessel disease causes cognitive impairment by damaging specific brain regions, and 3) progression of white matter damage from small-vessel disease is caused by ischemia in areas of relative hypoperfusion. Mildly impaired non-demented subjects will be recruited from the community and followed annually for cognitive decline. This is an population for study because it is an ideal target for therapies designed to reduce the burden of cognitive decline caused by vascular disease. Study procedures will include PET and MRI at baseline, with a second MRI during follow-up. This longitudinal study will 1) provide estimates of the rate of decline associated with MRI markers of small vessel disease that may be used in the design of future clinical trials in mildly impaired subjects, 2) identify a neuroanatomic phenotype of damage from small vessel disease that will more accurately predict cognitive decline than current global disease measures, and 3) identify cerebral perfusion as a potential target for therapies to prevent progression of white matter damage. Age-related small-vessel disease of the brain is common and causes silent stroke and damage to the white matter, visible on MRI, resulting in cognitive decline. It is not known how often these MRI abnormalities coexist with Alzheimer's disease, another common pathology of aging, and whether the relationship between these MRI abnormalities and cognitive decline is influenced by the presence or absence of Alzheimer-type pathology. We plan to study the relationship between MRI markers of small vessel disease, a PET marker of Alzheimer-type pathology, brain perfusion and cognition in subjects with mild impairments. Our results will aid the design of clinical trials to prevent dementia by defining imaging markers of small vessel disease and Alzheimer-type pathology and their effects on cognitive decline.

描述（由申请人提供）：我们建议研究脑部小血管疾病的MRI标记与符合MCI研究标准的个体以及符合这些标准但遇到这些标准但遇到这些标准但遇到这些标准但遇到这些标准但遇到这些标准但遇到这些标准但遇到这些标准但遇到这些标准但遇到这些标准但遇到这些标准但遇到这些标准但遇到这些标准但遇到这些标准的人的MRI标记和认知下降有一些认知能力下降的证据。因为有证据表明，与阿尔茨海默氏病有关的病理大脑变化（包括神经纤维缠结和老年斑块）会修改小血管疾病与认知之间的关系，因此，至关重要的需要将阿尔茨海默氏病的体内标记物纳入脑纵向研究的体内标记。小血管疾病。因此，当前的提案通过测量阿尔茨海默氏病理学的标志性特征，匹兹堡化合物B（PIB）保留对PET的证据，除了小血管疾病的MRI标记外，它是一个重要的进步。拟议的研究将通过专门解决小血管疾病和灌注的高级MRI标记，原纤维β-淀粉样蛋白沉积的宠物标记和认知能力下降之间的关系，以补充目前正在进行的大型神经影像学研究。将测试以下假设：1）小血管疾病造成的白质损害与认知能力下降有关，与脑β-淀粉样蛋白沉积的量无关，2）小血管疾病造成的白质损害通过损害特定的大脑区域造成认知障碍，和3）小血管疾病造成的白质损害进展是由相对灌注相对灌注方面的缺血引起的。轻度损害的非痴呆受试者将从社区招募，并每年跟随认知能力下降。这是研究人群，因为它是旨在减轻血管疾病引起的认知下降负担的疗法的理想靶标。研究程序将包括基线时的PET和MRI，随访期间第二次MRI。这项纵向研究将为1）提供与小血管疾病的MRI标记相关的下降率的估计值，该疾病可用于在轻度受试者中的未来临床试验设计中使用，2）确定小血管疾病损害的神经解剖表型，该表型被小血管疾病造成的损害将比当前的全球疾病措施更准确地预测认知能力下降，3）将脑灌注视为预防白质损害进展的疗法的潜在靶标。 与年龄相关的大脑小血管疾病很常见，在MRI上可见，对白质造成无声的中风和损害，导致认知能力下降。这些MRI异常与阿尔茨海默氏病，衰老的另一种常见病理以及这些MRI异常和认知能力下降之间的关系是否受阿尔茨海默氏症型病理学影响或不存在。我们计划研究小血管疾病的MRI标志物，小血管疾病，阿尔茨海默氏型病理学，脑灌注和认知受试者的宠物标记。我们的结果将有助于设计临床试验，以防止小血管疾病和阿尔茨海默氏症型病理学的成像标记及其对认知能力下降的影响。

项目成果

Leukoaraiosis and stroke.

• DOI: 10.1161/strokeaha.110.596056
• 发表时间: 2010-10
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Smith EE

Patterns and predictors of discharge statin prescription among hospitalized patients with intracerebral hemorrhage.

脑出血住院患者出院他汀类药物处方的模式和预测因素。

• DOI: 10.1161/strokeaha.110.593228
• 发表时间: 2010
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Ovbiagele,Bruce;Schwamm,LeeH;Smith,EricE;Hernandez,AdrianF;Olson,DaiWaiM;Pan,Wenqin;Fonarow,GreggC;Saver,JeffreyL
• 通讯作者: Saver,JeffreyL

Improvement in use of anticoagulation therapy in patients with ischemic stroke: results from Get With The Guidelines-Stroke.

• DOI: 10.1016/j.ahj.2011.07.019
• 发表时间: 2011-10
• 期刊: American heart journal
• 影响因子: 4.8
• 作者: W. Lewis;G. Fonarow;Maria V. Grau‐Sepulveda;Eric E. Smith;Deepak L. Bhatt;Adrian F. Hernandez;Daiwai M. Olson;E. Peterson;L. Schwamm