Brain Atrophy Is a Risk Factor for Progression to Mild Cognitive Impairment

Accelerated brain atrophy significantly increases the risk of transitioning from normal cognition to mild cognitive impairment, according to study findings published in JAMA Network Open.

Researchers conducted a cohort study to determine which risk factors are associated with the acceleration of brain atrophy and progression to mild cognitive impairment from normal cognition. Data were sourced from the Biomarkers for Older Controls at Risk for Dementia (BIOCARD) study, which was conducted between January 1995 and October 2023. Participants with normal cognition at baseline who had at least 10 years of brain magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) data were eligible for inclusion.

The primary outcome was annual change rates of segmental brain volumes. Kaplan-Meier survival curves and multivariable Cox proportional hazards regression models were used in statistical analyses.

A total of 185 participants (mean age, 55.4; women, 63%) were included in the study, of whom 60 experienced progression to mild cognitive impairment during the follow-up period (mean, 20.2 years). A total of 951 MRI scans were obtained (median per participant, 5).

Cortical gray and white matter volumes decreased annually by 0.0053% and 0.0229%, respectively. The relative volumes of the ventricles and sulci demonstrated increased annually by a mean 0.0089% and 0.0144%, respectively.

According to the multivariable Cox proportional hazards regression analysis, high rates of volume change in the white matter (hazard ratio [HR], 1.86; 95% CI, 1.24-2.49; P =.001) and ventricles (HR, 1.71; 95% CI, 1.19-2.24; P =.009) were associated with progression from normal cognition to the onset of mild cognitive impairment symptoms.

Additional factors that were found to be associated with the progression to mild cognitive impairment included:

• Age (HR, 1.06; 95% CI, 1.03-1.10; P <.001);
• Type 2 diabetes (HR, 1.41; 95% CI, 1.06-1.76; P =.04); and,
• Low CSF ratio of amyloid β peptide 42 (Aβ₄₂) to Aβ₄₀ (HR, 1.48; 95% CI, 1.09-1.88; P =.04).

A synergistic association between diabetes and amyloid pathology was observed. Compared with participants who only had one risk factor, participants with both diabetes and low CSF Aβ₄₂:Aβ₄₀ ratio had a 55% increased risk for mild cognitive impairment (HR, 1.55; 95% CI, 1.13-1.98; P =.03).

Study limitations include the small sample, potential underestimation of intracranial volumes, and reduced generalizability of results to more diverse populations.

“These results support the importance of identifying individuals who have accelerated brain atrophy to optimize preventive strategies for progression to MCI [mild cognitive impairment],” the researchers concluded.