Amyloid

The main purpose of this study is to evaluate whether treatment with donanemab slows the progression of cognitive (how we think, learn, remember, pay attention, and make decisions) and functional (how we are able to perform daily activities) decline. For each participant, the study will last one and a half years.

Dementia caused by Alzheimer's disease affects approximately 5.6 million adults over age 65, with costs expected to rise from $307 billion to $1.5 trillion over the next 30 years. Behavioral interventions have shown promise for mitigating neurodegeneration and cognitive impairments. Sleep is a modifiable health behavior that is critical for cognition and deteriorates with advancing age and Alzheimer's disease. Thus, it is a priority to examine whether improving sleep modifies Alzheimer's disease pathophysiology and cognitive function. Extant research suggests that deeper, more consolidated sleep is positively associated with memory and executive functions and networks that underlie these processes. Preliminary studies confirm that time-in-bed restriction interventions increase sleep efficiency and non-rapid eye movement slow-wave activity (SWA) and suggest that increases in SWA are associated with improved cognitive function. SWA reflects synaptic downscaling predominantly among prefrontal connections. Downscaling of prefrontal connections with the hippocampus during sleep may help to preserve the long-range connections that support memory and cognitive function. In pre-clinical Alzheimer's disease, hyperactivation of the hippocampus is thought to be excitotoxic and is shown to leave neurons vulnerable to further amyloid deposition. Synaptic downscaling through SWA may mitigate the progression of Alzheimer's disease through these pathways. The proposed study will behaviorally increase sleep depth (SWA) through four weeks of time-in-bed restriction in older adults characterized on amyloid deposition and multiple factors associated with Alzheimer's disease risk. This study will examine whether behaviorally enhanced SWA reduces hippocampal hyperactivation, leading to improved task-related prefrontal-hippocampal connectivity, plasma amyloid levels, and cognitive function. This research addresses whether a simple, feasible, and scalable behavioral sleep intervention improves functional neuroimaging indices of excitotoxicity, Alzheimer's pathophysiology, and cognitive performance.

\[18F\]FT8, a derivative of 1-(4-pyridyl)-4-piperazinyl arene (\[18F\]TPZA), exhibits high affinity for AL amyloid in myocardial tissue sections and shows no significant binding to transthyretin amyloid. By comparing its diagnostic performance against established clinical methods, including echocardiography, contrast-enhanced MRI, and relevant laboratory tests, this study aims to establish \[18F\]FT8 as the basis for a robust PET protocol for the direct visualization and differential diagnosis of AL amyloidosis . The study preimarily evaluates the safety and diagnostic efficacy of \[18F\]FT8 PET imaging in human subjects.

To evaluate the potential usefulness of 18F-92/AV45/TPZA/FT8, 11C-PIB positron emission tomography/computed tomography (PET/CT) for the diagnosis of primary and metastatic lesions in various Pan-Amyloid-related disease patients.

To evaluate the potential usefulness of 18F-92/AV45, 11C-PIB positron emission tomography/computed tomography (PET/CT) for the diagnosis of primary and metastatic lesions in various Tau-related disease patients.