Gray Matter Imaging Biomarker Associated with Cognitive Function and Dementia Risk

According to results published in Alzheimer’s & Dementia, cortical thickness (assessed from brain MRI examination) is associated with an individual’s risk of developing Alzheimer disease (AD) and related dementias (ADRD). Cortical thickness also was associated with cognitive function in the 2 separate cohorts included in this study.

Researchers analyzed MRI samples of participants from the Framingham Heart Study (FHS), an ongoing population-based, longitudinal cohort study to investigate cardiovascular disease risk factors (N=1146). Since all FHS participants are non-Hispanic White, this study included a replication sample from the University of California Davis Alzheimer’s Disease Research Center (UCD-ADRC) cohort, consisting of participants aged ≥60 years with diverse racial and ethnic backgrounds (23% Black, 22.8% Hispanic) who received a brain MRI examination during their initial visit, with an average time between visit and MRI of 0.09 ± 0.11 years (n=513).

Researchers developed an ADRD signature by generating an “unbiased” statistical region of interest (ROI) using non-parametric t value cluster significance computations. Researchers then evaluated the association between thickness in the cortical ADRD signature and the incidence of ADRD using Cox proportional hazard-models. The ADRD signature was modeled as both a continuous measure and in quartile categories based on cortical thickness. 

• For each one-tenth of a point increase in thickness in the AD dementia ROI signature, there was a 20% reduced risk of all cause dementia (hazard ratio [HR] = 0.80; 95% CI, 0.75 to 0.85; P<.001), and a 21% reduced risk of AD dementia (HR = 0.80; 95% CI, 0.73 to 0.85; P<.001) in the FHS cohorts. These results were replicated in the UCD-ADRC cohort (all-cause dementia HR = 0.74; 95% CI, 0.70 to 0.78, P<.001; AD dementia HR = 0.73; 95% CI, 0.68 to 0.77], P<.001).
• In FHS participants in the lowest ADRD signature quartile, there was a >3-fold increased risk of all-cause dementia (HR = 3.38; 95% CI, 2.21 to 5.16; P<.001) and AD dementia (HR = 3.35; 95% CI, 2.04 to 5.50; P<.001) compared to those in the upper 3 quartiles.
• In UCD-ADRC participants in the lowest ADRD signature quartile, there was a > 5-fold increased risk of all-cause dementia (HR = 5.09; 95% CI, 3.52 to 7.37; P<.001) and AD dementia (HR = 5.89; 95% CI, 3.92 to 8.85; P<.001) compared to those in the upper 3 quartiles.
• There was a significant association between the ADRD signature and cognitive function.

Additional studies are needed to validate these findings and to determine risk factors that may be associated with cortical thinning. Researchers from this study are affiliated with The University of Texas Health Science Center at San Antonio, Boston University, and The University of California, Davis.