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2020 Alzheimer's Association Research Fellowship (AARF)

Longitudinal changes in connectivity profiles across the AD spectrum

Can long-term changes in the brain’s ability to promote cell-to-cell communication help predict the onset and progression of Alzheimer’s?

Kylie Alm, Ph.D.
Johns Hopkins University
Baltimore, MD - United States


For a brain to function properly, nerve cells from various brain regions need to communicate rapidly with each other. Such communication requires proper “connectivity” between the different brain regions. Scientists can measure connectivity in several ways. For example, they can assess “structural” connectivity by examining the “wiring system” that facilitates cell-to-cell communication across the brain. Scientists can determine “functional” connectivity by assessing which brain regions tend to be active at the same time. 

Recent studies suggest impairment in connectivity may be one of the earliest brain changes in Alzheimer’s, years before memory loss and other cognitive problems are evident. In preliminary studies, Dr. Kylie Alm and colleagues, observed that changes in structural connectivity may be an indicator for older adults who are more likely to develop dementia-related memory problems.  Dr. Alm believes that both structural and functional connectivity may be an important measure of biological factors (or biomarkers) to identify Alzheimer’s at its earliest stages.

Research Plan

Dr. Alm and colleagues will explore how changes in both structural connectivity and functional connectivity may impact Alzheimer’s risk and the rate of Alzheimer’s progression. The researchers will use pre-existing brain scan (Magnetic Resonance Imaging MRI) datasets belonging to the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) and Alzheimer’s Disease Neuroimaging Initiative (ADNI). Dr. Alm and colleagues will compare three groups of individuals those with Alzheimer’s, mild cognitive impairment (a state of subtle memory loss that may precede Alzheimer’s) or no cognitive impairment. 

Dr. Alm and her team will analyze the MRI data to determine the state of each person’s structural and functional connectivity (or connectivity “profile”). Subsequently, the researchers will use sophisticated statistical techniques to determine how each individual’s connectivity profile may be associated with memory changes during aging and identify how these interactions may alter in the brain over time. Finally, the researchers will also study how the association between the connectivity profiles and memory may change during the course of the disease progression.


The study results could shed new light on how  changes in nerve cell connectivity impact the aging brain over time. If successful, the brain connectivity profiles may be used as biomarkers for early detection of Alzheimer’s. Families facing Alzheimer’s now and in future will benefit greatly from early detection, allowing for important care and planning. Furthermore, when we have new therapies, we will be in a better position to know who needs treatment at the earliest time point.  

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