Project Summary
Large-scale changes in brain structure occur in aging and Alzheimer's Disease (AD) that demonstrate sulcal
vulnerability to age-related atrophy and AD-related amyloid-β (Aβ) deposition. Recent work has shown that the
morphology of tertiary sulci (the shallowest and latest-developing cortical indentations) is associated with
individual differences in cognitive development and symptoms of various disorders, but these sulci have not
been investigated in aging or AD. This project will investigate individual differences in gyrification in multiple
brain regions in cognitively normal older adults and adults with AD, and will combine positron emission
tomography (PET) and MRI imaging methods in investigating relationships between tertiary sulci, pathology,
and metabolism. All sulci in medial parietal cortex (MPC) and lateral prefrontal cortex (LPFC) will be manually
labeled on individual structural MRI scans of younger adults, cognitively normal older adults, and older adults
with AD. Morphological metrics (such as sulcal cortical thickness) will be extracted from these labels in order to
investigate their relationship to cognitive decline, AD pathology (Aβ and tau, measured with PET), and glucose
metabolism (measured with PET). Aim 1 will investigate changes in sulcal morphology in MPC and LPFC in
aging and AD. Aim 2 will identify how these changes in tertiary sulci relate to cognitive impairment and AD
pathology. Aim 3 will determine whether sulcal morphology relates to metabolism in early adulthood and
subsequent Aβ deposition in aging, as a putative explanation of how these sulci confer vulnerability to
pathology and neurodegeneration. Overall, this study will investigate whether tertiary sulci can serve as
structural markers of early degenerative and pathological changes relating to cognitive decline and AD. This
project will provide training in (1) multimodal neuroimaging acquisition and analysis techniques, (2) statistics
and data analysis methods, (3) pathophysiology of AD, (4) scientific communication, (5) teaching and
mentorship skills, and (6) career development. The UC Berkeley Helen Wills Neuroscience Institute is an ideal
environment for this research, ensuring access to cutting-edge PET and MRI neuroimaging facilities as well as
world-class neuroimaging, biostatistics, and cognitive neuroscience experts to support the project and training
goals. Ongoing collaboration with the UCSF Memory and Aging Center will provide additional training in AD
pathophysiology and research. The project’s co-sponsors are exceptionally suited to support its successful
completion: Dr. William Jagust is an expert in PET imaging and in applying multimodal neuroimaging
techniques to understand underlying mechanisms of aging and AD, and Dr. Kevin Weiner is an expert in
tertiary sulci and in linking individual differences in neuroanatomy to cognition. The proposed research and
training plans will provide the applicant with the skills and support necessary to ensure successful completion
of the project and a strong foundation to pursue a competitive post-doctoral fellowship and research career
investigating factors underlying cognitive decline in aging and dementia.