Combining structural brain changes improves the prediction of Alzheimer's disease and mild cognitive impairment

Abstract

Background: Several structural brain changes have been associated with Alzheimer's disease (AD). This study investigated the prediction of AD by combining multiple brain changes with the hallmark medial temporal lobe atrophy (MTA).

Methods: High-resolution magnetic resonance imaging (MRI) data of people with mild AD (n = 39), mild cognitive impairment (MCI; n = 82), and of healthy controls (HC; n = 58) were obtained at baseline. Among these people, 26 AD, 53 MCI, and 46 HC subjects had 24-month follow-up MRI scans. Bilateral MTA was evaluated using a medial temporal lobe atrophy scale (MTAS). Common changes in the aging brain were summarized using a brain atrophy and lesion index (BALI). The performance of the MTAS, BALI, and a score combining both, using a logistic regression model, were assessed.

Results: The MTAS and BALI scores were closely correlated (r(2) > 0.56); each differed between the diagnostic groups. Having an unfavorable MTAS score was associated with an increased risk of MCI-AD conversion (OR = 3.71, p = 0.039), adjusted for age, sex, and education; having an unfavorable BALI score marginally contributed to such risks (OR = 4.08, p = 0.080). Combining MTAS and BALI components resulted in a greater OR (8.99, p = 0.007) and an improved predictive accuracy (75.9%, p = 0.002).

Conclusion: Multiple structural changes have an additive effect on AD. The data support potential future roles of combining multiple coexisting structural changes to benefit AD diagnosis, progression monitoring, and/or treatment effect evaluation.

Figure 1

Example images showing the rating of the medial temporal lobe atrophy scale (MTAS) and the brain atrophy and lesion index (BALI). Left panel (A) shows a healthy control subject (HC; 76 years old, male); right panel (B) shows a subject diagnosed with Alzheimer’s disease (AD; 83 years old, female). Locations of specific deficits under evaluation are indicated by white arrows.

Figure 2

Relationships between the brain atrophy and lesions index (BALI) and the medial temporal lobe atrophy scales (MTAS). Symbols represent the observational data (circles: Alzheimer’s disease; diamond: mild cognitive impairment; squares: healthy control) and lines describe the linear fitting (MTAS=a+b·BALI). At baseline: a=−0.542, b=0.361, n=179, r²=0.555, p<0.001; open symbols; dashed line. At follow-up: a=−1.865, b=0.480, n=125, r²=0.565, p<0.001; filled symbols; solid line.

Figure 3

Receiver operating characteristic analysis (ROC) for the two-year prediction of individuals with mild cognitive impairment (MCI; n=53) who converted to AD versus those who remained MCI. Dashed line: brain atrophy and lesion index (BALI); dot-dashed line: medial temporal lobe atrophy scale (MTAS); solid line: combined BALI-MTAS. Diagonal lines indicate accuracy=0.50.