Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI

Abstract

The Functional Activities Questionnaire (FAQ) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) are frequently used indices of cognitive decline in Alzheimer's disease (AD). The goal of this study was to compare FDG-PET and clinical measurements in a large sample of elderly subjects with memory disturbance. We examined relationships between glucose metabolism in FDG-PET regions of interest (FDG-ROIs), and ADAS-cog and FAQ scores in AD and mild cognitive impairment (MCI) patients enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Low glucose metabolism at baseline predicted subsequent ADAS-cog and FAQ decline. In addition, longitudinal glucose metabolism decline was associated with concurrent ADAS-cog and FAQ decline. Finally, a power analysis revealed that FDG-ROI values have greater statistical power than ADAS-cog to detect attenuation of cognitive decline in AD and MCI patients. Glucose metabolism is a sensitive measure of change in cognition and functional ability in AD and MCI, and has value in predicting future cognitive decline.

Figure 1

Histograms of FDG-ROIs baseline status (A) and longitudinal change (B) are shown for AD, MCI, and cognitively normal groups. Error bars represent standard error. Individual FDG regions of interest (FDG-ROIs) are defined based on a meta-analysis (see Methods). The Composite FDG-ROI is the average of the five individual FDG-ROIs and was used for all subsequent analyses. FDG-ROI means are listed in Table 1.

Figure 2

Fitted regression lines are shown in order to visualize results of mixed effects models shown in Table 2A. As in the mixed effects models, we adjusted each variable for age, education, sex, number of ApoE4 allleles (and baseline FDG-ROI for the FDG-ROI change model), and plotted the standardized residuals. For the AD (solid line) and MCI (dashed line) groups, adjusted baseline FDG-ROI values (x-axis) are plotted against adjusted ADAS-cog change (12 month – baseline) (Figure 2A). Similarly, adjusted FDG-PET change (12 month – baseline) is plotted against adjusted ADAS-cog change for both groups (Figure 2B). The adjusted values can be interpreted as follows: a value of 1 on either axis indicates that the subject is 1 standard deviation higher for that measure than would be expected for an individual with that age, education, sex, and ApoE4 status.

Figure 3

Histograms show sample sizes per group (treatment, placebo) that would be required to detect a 25% (black bars) or 33% (white bars) attenuation in annual decline of each outcome measure during a clinical trial of a candidate therapeutic treatment. Analyses were carried out for AD subjects with all available up to 24 months post-baseline (Figure 3A) and using only data up to 12 months post-baseline (Figure 3B), and similarly for MCI subjects with all available data (Figure 3C) and using data up to 12 months (Figure 3D). Power calculations assume linear rate of decline, equal treatment and placebo group sizes, and were carried out at power = 0.80, α = 0.05, 2-tailed.