Predicting Cognitive Decline in Alzheimer's Disease

The FreeSurfer suite of software tools has helped advance countless studies over the years. Not least: a 2018 paper published in the journal Neurology in which a team of investigators led by the Center’s David Salat explored the contributions of white matter damage in Alzheimer’s disease. Such damage could serve as a biomarker to aid in clinical diagnoses of the disease as well as in predicting changes in cognition over time.

“There is a good deal of evidence linking white matter damage to Alzheimer’s,” says Emily Lindemer, lead author of the Neurology study. Lindemer was a graduate student working in the Martinos Center’s Brain Aging and Dementia (BAnD) Lab with senior author Salat when the study was conducted. “White matter signal abnormalities seen on MRI, which reflect white matter damage, have been tied to cognitive decline and dementia. Until this study, though, we still didn’t know how prominent a role they played. Nor did we fully understand the relationship between white matter signal abnormalities and the biomarkers amyloid and tau—two proteins in the brain. We set out to study this relationship and the combined impact of the three on cognitive decline.”

To this end, the researchers examined data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, a University of Southern California-based initiative established to provide researchers with access to imaging findings from the ongoing, large-scale ADNI study. They included data from 236 individuals from the database: 61 with an Alzheimer’s diagnosis, 56 cognitively healthy age-matched controls, and 119 with a diagnosis of mild cognitive impairment.

With help from FreeSurfer, the study compared brain imaging measures from two groups of patients with clinical diagnoses of Alzheimer’s. The groups differed in the extent to which the biomarkers amyloid and tau were present: one had levels of the biomarkers typical for Alzheimer’s disease and the other had lower-than-usual levels. The researchers observed a greater amount of white matter damage in the patients with lower-than-usual biomarker levels and found that the damage was a stronger predictor of a patient’s future clinical status. The damage itself was presumed to be the result of deterioration of blood flow to the brain, likely due to vascular disease.

The white matter findings have important implications for clinical care. For example, because they point toward a possible vascular origin in at least some individuals with a clinical diagnosis of Alzheimer’s disease, researchers may want to explore the white matter damage presumed to be caused by vascular disease as a potential target for future therapies.

The researchers hope to follow up the findings in future work. “The white matter damage examined here has been described in several prior studies of Alzheimer’s disease, yet is not considered a primary feature of the disease,” Lindemer says. “It is most often considered a simple independent comorbidity. We are interested in better understanding the etiology of this tissue damage in Alzheimer’s disease and specifically how this damage fits in with the classical understanding of the disease.”

In the photo above: The Brain Aging and Dementia (BAnD) Lab with principal investigator David Salat, right.