Quantifying Brain Aging in Diabetes Type 2 Patients – The BIOCARD Study

Researchers from Johns Hopkins University have recently discovered several prominent biomarkers that allow for the early diagnosis of dementia and/or mild cognitive impairment (MCI). In a recently published article, evidence has been presented that patients with diabetes type 2 exhibited more changes to their brains than healthy controls, including the shrinking of certain brain areas. These changes occurred earlier in life, and some of the patients developed MCI sooner than others.

The Older Controls at Risk for Dementia (BIOCARD) study is a long-term trial which has been conducted for the past 27 years with the goal of determining how medical conditions and other factors might be impacting cognitive function and perhaps even affecting the biological age of the brain as a whole. BIOCARD was originally a National Institutes of Health initiative, which began in 1995 and later continued at Johns Hopkins University from 2015 to 2023. The cohort consisted of 185 participants, with an average age of 55 years and normal cognitive function.

The trial subjects received routine brain scans and cerebrospinal fluid (CSF) tests for 20 years, in order to measure changes in brain structures and levels of proteins associated with Alzheimer’s disease. Scientists have been increasingly using CSF to attempt to uncover early signs of neurodegenerative disease, since it is a minimally-invasive procedure which is inexpensive and widely available.

The researchers claim to have found specific proteins in CSF which are linked to faster brain shrinkage and quicker progression of neurodegenerative disease. The main culprits are amyloid beta (Aβ) peptides, protein fragments naturally produced by the cells, which form the famous plaque deposits that have been found to characterize the brains of Alzheimer’s Disease patients more than 100 years ago.

Aβ peptides come in two main types, Aβ42 and Aβ40, with different individuals exhibiting different ratios of the two types, correlated with different levels of cognitive function and different symptomatology. The study results suggest that a low ratio of Aβ42 to Aβ40 in CSF was associated with a 48% higher risk of developing MCI.

The findings further showed that white matter shrinkage and enlargement of the brain’s ventricles (fluid-filled spaces) allowed the researchers to predict earlier onset of MCI, with an 86% and 71% higher risk, respectively.

Diabetes type 2 patients showed an average 41% higher risk of progressing from normal cognitive function to MCI compared to individuals without pathology.

When test subjects had both diabetes type 2 and a low Aβ42 to Aβ40 ratio, the risk of MCI increased by 55%, elucidating the link between these biomarkers and the symptoms exhibited by the trial subjects later in life. The unique scope of the study’s timetable, the novel detection methods employed and the compliance of the trial subjects allowed for observations which have not been possible earlier in history.

Source: Indicators of an aging brain: A 20-year study
https://medicalxpress.com/news/2024-11-indicators-aging-brain-year.html

Paper: Acceleration of Brain Atrophy and Progression From Normal Cognition to Mild Cognitive Impairment
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2825474