Early Markers of Alzheimer Disease

阿尔茨海默病的早期标志

• 批准号: 10688754
• 负责人: Susan Resnick
• 金额: $ 60.32万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10688754
• 关键词: Adult; Affect; Age; Age-Years; Aging; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Anterior; Autopsy; Baltimore; Brain; Brain region; COVID-19 pandemic; Cerebrospinal Fluid; Characteristics; Clinical; Cognition; Cognitive; Cognitive aging; Collaborations; Complex; Data; Dementia; Diagnosis; Diagnostics Research; Disease; Disease Marker; Elderly; Enrollment; Extramural Activities; Family; Gait; Genetic; Genetic study; Goals; Health; Hearing; Home; Hormonal; Image Analysis; Impaired cognition; Impairment; Individual; Investigation; Learning; Letters; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Metabolic; Mission; Modality; Motor; National Institute on Aging; Neurodegenerative Disorders; Neurologic; Neuropsychology; Odors; Participant; Pennsylvania; Performance; Persons; Phase; Physical activity; Play; Positron-Emission Tomography; Prevalence; Process; Prospective Studies; Public Health Schools; Publications; Reporting; Research; Research Personnel; Research Project Grants; Risk Factors; Role; Sample Size; Scanning; Schedule; Sensory; Site; Sleep; Sleep disturbances; Smell Perception; Structure of middle temporal gyrus; Testing; Universities; Vision; Visit; Visual impairment; Walking; aged; aging brain; cerebral atrophy; cognitive change; cognitive load; cognitive testing; dementia risk; depressive symptoms; early detection biomarkers; genome sequencing; hearing impairment; high risk; imaging genetics; interest; lipidomics; mild cognitive impairment; multisensory; neuroimaging; neuroimaging marker; neuropathology; pre-clinical; prevent; programs; prospective; protective factors; psychologic; resilience; symposium; tau Proteins; whole genome; β-amyloid burden

The Baltimore Longitudinal Study of Aging (BLSA) was established in 1958 and is one the oldest prospective studies of aging in the USA and the world. The mission of the BLSA is to learn what happens to people as they age and how to distinguish changes due to aging from those due to disease or other causes. Technological advances increasingly allow us to examine subclinical disease markers in the brain and body more generally, blurring distinctions between aging-related and disease-related changes. Thus, longitudinal studies have assumed increasing importance in elucidating the earliest changes that may be associated with later symptomatic cognitive impairment. The Early Markers of Alzheimer's Disease program continues to perform cognitive assessments and establish research diagnoses of Mild Cognitive Impairment and Alzheimer's Disease and related dementias for BLSA participants. This information is also used in multiple collaborative research projects conducted by intramural and extramural investigators, including our LBN studies of brain aging and neuroimaging biomarkers of cognitive decline and AD (reported separately). Due to the COVID-19 pandemic, the full BLSA participant schedule of visits was suspended in mid-March 2020. Participant studies subsequently resumed in summer 2020 but at less than 20% of the usual participant flow, which has increased over the last 6 months to about 75% of the prior level. Nevertheless, we have continued performing research diagnostic case conferences in collaboration with Dr. Moghekar of the Johns Hopkins ADRC to establish research diagnoses of cognitive impairment and have continued analyses to define age-associated cognitive changes. We also continued our studies of possible modifiers of cognitive aging, risk for dementia, and the presence of Alzheimer's pathology at autopsy. BLSA cognitive, imaging, and genetic (including whole genome sequencing) data continue to bbe used in numerous studies of hearing loss, visual impairment, vestibular function, motor function sleep, as well as genetic studies of a variety of neurodegenerative diseases. Several publications are highlighted in the following sections. Recent studies have used BLSA data to investigate the prevalence of multisensory impairment (Armstrong et al., 2021) and shown that multisensory impairments are common in older adults. The most common co-occurring impairments were in hearing and vision (17.4%). Further, in a collaborative study with investigators at Columbia University (Irace et al., 2022), we found that even subclinical hearing loss was associated with cognitive decline on a measure of letter fluency. In collaboration with investigators at Johns Hopkins School of Public Health, we also investigated whether performance on cognitive tests was biased by hearing and visual impairments (Nichols et al., 2022). We hypothesized that scores on tests dependent on hearing or vision would differ across specific tests among participants with hearing or visual impairments, controlling for underlying cognition. Surprisingly, we found differences between sensory impaired and unimpaired individuals that did not depend on test administration characteristics, which could indicate that elevated cognitive load among persons with sensory impairment plays is more important than the specific modality of test presentation. Over the last year, we have begun analysis and publication of measures of olfactory function that were implemented in BLSA prior to the COVID19 pandemic. In an initial publication (Tian et al., 2022) we investigated the relation between olfactory function and cognitive impairment and AD biomarkers measured with PET scanning of amyloid and tau burden. We first investigated the relation between baseline olfaction data and incident MCI in 364 initially cognitively normal participants during an average 2.4-year. 17 (5%) participants developed MCI. Each unit lower odor identification score was associated with 22% higher risk of developing MCI (p=0.04). A subset of 129 participants had PET-PiB (ABeta) (n=72 repeated) and 105 had 18F-flortaucipir (FTP)-PET (tau) (n=44 repeated) scans. Lower olfaction scores were associated with higher amyloid burden in orbitofrontal cortex (OFC), precuneus, and middle temporal gyrus (p0.04), and this association was limited to the group of individuals with amyloid positive scans. In addition with found that greater longitudinal decline in the odor identification score was associated with greater increase in anterior OFC amyloid burden and entorhinal tau. These findings showed that poorer olfaction predicts incident MCI and is associated with greater overall and regional amyloid, and that greater declines in olfaction are associated with greater increases in AD neuropathology measured by PET scanning. Ongoing studies are investigations whether olfaction predicts MRI volume losses in AD-affected brain regions. We continue to collaborate extensively with both intramural and extramural investigators, including ongoing studies of motor function and energy utilization. Publications over the last year include studies of combined slow gait and low activity fragmentation with later cognitive impairment (Tian et al., 2022), daily physical activity and cognitive impairment (Wanigatunga et al., 2022), and associations between walking energetics and brain atrophy (Dougherty et al., 2021) and amyloid burden (Dougherty et al. 2021). We also continue a very active collaboration with a 5-study consortium of longitudinal studies focused on preclinical AD. Participants at the study sites are included in the consortium if they are cognitively normal at baseline, have either PET-PiB or cerebral spinal fluid measures of amyloid-beta and serial cognitive assessments. The collaboration and larger sample sizes provided by the 5 studies and the University of Pennsylvania image analysis core will allow tests of more complex interactions influencing risk and protective factors for Alzheimer's disease during the preclinical asymptomatic stage. Data from the preclinical AD consortium have been included in a number of publications from the iSTAGING consortium (described in separate reports).

巴尔的摩老龄化纵向研究（BLSA）成立于1958年，是美国和世界上最古老的老龄化前瞻性研究之一。BLSA的使命是了解人们随着年龄的增长会发生什么，以及如何区分由于衰老和疾病或其他原因引起的变化。技术进步越来越多地使我们能够更广泛地检查大脑和身体中的亚临床疾病标志物，模糊了与衰老相关的变化和与疾病相关的变化之间的区别。因此，纵向研究在阐明可能与后来的症状性认知障碍相关的早期变化方面越来越重要。阿尔茨海默病早期标记项目继续对BLSA参与者进行认知评估，并建立轻度认知障碍和阿尔茨海默病及相关痴呆的研究诊断。这些信息也被用于校内和校外研究者开展的多个合作研究项目，包括我们的LBN研究脑衰老和认知能力下降和AD的神经成像生物标志物（单独报道）。