Prediction of cognitive decline in healthy older adults using fMRI

Abstract

Few studies have examined the extent to which structural and functional MRI, alone and in combination with genetic biomarkers, can predict future cognitive decline in asymptomatic elders. This prospective study evaluated individual and combined contributions of demographic information, genetic risk, hippocampal volume, and fMRI activation for predicting cognitive decline after an 18-month retest interval. Standardized neuropsychological testing, an fMRI semantic memory task (famous name discrimination), and structural MRI (sMRI) were performed on 78 healthy elders (73% female; mean age = 73 years, range = 65 to 88 years). Positive family history of dementia and presence of one or both apolipoprotein E (APOE) ε4 alleles occurred in 51.3% and 33.3% of the sample, respectively. Hippocampal volumes were traced from sMRI scans. At follow-up, all participants underwent a repeat neuropsychological examination. At 18 months, 27 participants (34.6%) declined by at least 1 SD on one of three neuropsychological measures. Using logistic regression, demographic variables (age, years of education, gender) and family history of dementia did not predict future cognitive decline. Greater fMRI activity, absence of an APOE ε4 allele, and larger hippocampal volume were associated with reduced likelihood of cognitive decline. The most effective combination of predictors involved fMRI brain activity and APOE ε4 status. Brain activity measured from task-activated fMRI, in combination with APOE ε4 status, was successful in identifying cognitively intact individuals at greatest risk for developing cognitive decline over a relatively brief time period. These results have implications for enriching prevention clinical trials designed to slow AD progression.

Fig. 1

Mean baseline and follow-up performance (with standard errors) on principal neuropsychological outcome measures for cognitively stable and declining participants. There were no significant (p < 0.05) group differences at baseline. The 18-month follow-up shows expected group differences in cognitive functioning, validating the group selection criteria.

Fig. 2

Group differences in activation derived from the comparison of the famous versus unfamiliar names condition: Famous > Unfamiliar represented in red; Unfamiliar > Famous in blue. Note the greater spatial extent of activation in the Famous > Unfamiliar names comparison in the stable group. (Colours are visible in the electronic version of the article at www.iospress.nl.)

Fig. 3

A) Regions comprising the Cortical (green) and Hippocampal (purple) fMRI activation principal components for the Famous > Unfamiliar names comparison. B) Cortical and Hippocampal fMRI signals (areas under the curve) contrasting famous name recognition versus fixation and unfamiliar name identification versus fixation for cognitively stable and declining participants. (Colours are visible in the electronic version of the article at www.iospress.nl.)

Fig. 4

Odds ratios and 95% confidence intervals for seven logistic regression models. Odds ratios whose 95% confidence intervals overlap with 1.0 (represented by vertical dashed line) are not statistically significant. Odds ratios > 1 indicate greater probability of decline with increasing value of predictor; odds ratios < 1 indicate reduced probability with increasing predictor values.

Fig. 5

Percent MR signal intensity (± SEM) for stable and declining APOE ε4 carriers (ε4+) and non-carriers (ε4−). Positive values reflect greater BOLD response aggregated across activated cortical regions in response to famous relative to unfamiliar names; negative values reflect greater BOLD response to unfamiliar relative to familiar names.