Certain factors are linked to faster brain shrinkage and quicker progression from normal thinking abilities to mild cognitive impairment (MCI), as Johns Hopkins University-led researchers found in a study involving a large cohort of 600 seniors known as the Biomarkers for Older Controls at Risk for Dementia (BIOCARD). People with type 2 diabetes who had lower levels of specific cerebrospinal fluid (CSF) proteins had faster brain changes and developed MCI sooner than those with higher amounts of the CSF proteins.
Tracking brain changes over many years in people is rare, but invaluable. Other research has mostly given us snapshots in time that can’t tell us about how our individual brains change with experience over decades. This study involving participants of up to 27 years of age (20-year median) provides new insights into how health conditions might accelerate brain aging.
A study published in JAMA Network Open, based on the BIOCARD cohort, identified risk factors associated with accelerated brain atrophy with progression from normal cognition to MCI. An Invited Commentary is also provided.
The National Institutes of Health began BIOCARD in 1995, and Johns Hopkins University brought it home in 2015 and ran it until 2023. All 185 participants were 55 years old during the start of the study and were cognitively normal. All were given a brain scan to scan the cerebral fluid for a span of 20 years. They observed structural changes in the brain along with protein levels which are critical for Alzheimer’s condition.
Significant predictors of earlier onset of MCI included high rates of shrinkage and enlargement of white matter and the fluid-filled spaces within the brain, the ventricles. 1316 subjects affected by MCl, were studied using structural biomarkers of white matter atrophy and enlarged ventricles, which resulted in 86% higher risk of progressing MCl and 71% higher risk of CBT.
Progression from normal cognition to MCI was 41% more likely in individuals with diabetes compared to those without, with diabetes being associated with progression to MCI (HR, 1.41 [95% CI, 1.06-1.76]; P=.04). Additionally, a low Aβ42 to Aβ40 ratio, a condition found in cerebrospinal fluid, was predictive of an extra 48% higher risk of progressing from normal cognition to MCI (HR, 1.48 [95% CI, 1.09-1.88]; P=.04). This biomarker ratio indicates an imbalance between the two forms of amyloid beta proteins associated with harmful plaques forming on the brain.
The risk of becoming MCI was 55 percent higher for those with both diabetes and a low Aβ42 to Aβ40 ratio, showing that together these two conditions increase significantly the odds of cognitive decline.
These results suggest that early identification of individuals with accelerated brain atrophy and selected unfavorable biomarkers is important. Optimization of the effectiveness of preventive intervention strategies to delay or hopefully even prevent the onset of MCI is possible by recognizing when a higher risk is present. To understand how these factors interact, however, we do need long-term longitudinal studies like the one we currently have.
Reference: Uchida Y, Nishimaki K, Soldan A, Moghekar A, Albert M, Oishi K. Acceleration of Brain Atrophy and Progression From Normal Cognition to Mild Cognitive Impairment. JAMA Network Open. 2024;7(10):e2441505. doi:10.1001/jamanetworkopen.2024.41505
