Biomarkers.

Background: Estimating the time course of locus coeruleus integrity changes is important for a better understanding of the pathophysiological cascade and for identifying the optimal window of opportunity for prevention trials. We used samples iterative local approximation (SILA) to determine the individual estimated time of onset of low LC integrity and related this to early cortical tau deposition and cognitive decline.

Methods: 101 individuals from the Harvard Aging Brain Study+ with longitudinal 3T MRI-LC imaging, 18F-Flortaucipir (FTP)-PET imaging (n=92 with longitudinal data), longitudinal cognitive assessments and baseline PiB-PET imaging were included (mean age: 69.

Biomarkers.

Background: Higher cerebrospinal fluid noradrenergic metabolic turnover has been associated with higher levels of Alzheimer's disease pathology in cognitively impaired individuals. It remains unclear whether there is a specific anatomic vulnerability to metabolic alterations within the locus coeruleus (LC) and whether this hypermetabolism relates to steeper rates of pathology accumulation. Here, we overcome a spatial limitation of Positron Emission Tomography (PET) imaging in small nuclei with a dedicated Magnetic Resonance Imaging (MRI)-guided framework to recover PET resolution.

Public Health.

Background: Social restrictions during the COVID-19 pandemic raised acute concerns about the impacts of loneliness on older adults' well-being, particularly for those who live alone. Loneliness is a perceived state of isolation from others that is only partly determined by quantities of social ties and interactions. Drawing a subsample from the Harvard Aging Brain Study, we measured self-reported loneliness in older adults living alone and those living with others during the pandemic.

Developing Topics.

Background: The locus coeruleus (LC)-norepinephrine (NE) system is one of the first systems affected in Alzheimer's Disease (AD), prior to cortical involvement. LC-NE system dysregulation has also been associated with neuropsychiatric and stress-related symptoms, early non-cognitive signals of AD. This study investigates whether structural and functional LC-NE system metrics are associated with affective and stress-related reports among predominantly cognitively healthy adults, and whether these associations are exacerbated by AD fluid biomarkers of tau, neurodegeneration and astrocyte reactivity.

Developing Topics.

Background: The locus coeruleus (LC) is one of the earliest regions accumulating tau pathology in Alzheimer's Disease (AD). As the disease progresses, tau in the LC has been linked to increasing cortical tau and amyloid-beta (Aβ) pathologies and cognitive decline. Previous animal research suggested that novelty-like phasic LC activity protects against AD-related cognitive decline.