Amyloid-β assessed by florbetapir F 18 PET and 18-month cognitive decline: a multicenter study

Abstract

Objectives: Florbetapir F 18 PET can image amyloid-β (Aβ) aggregates in the brains of living subjects. We prospectively evaluated the prognostic utility of detecting Aβ pathology using florbetapir PET in subjects at risk for progressive cognitive decline.

Methods: A total of 151 subjects who previously participated in a multicenter florbetapir PET imaging study were recruited for longitudinal assessment. Subjects included 51 with recently diagnosed mild cognitive impairment (MCI), 69 cognitively normal controls (CN), and 31 with clinically diagnosed Alzheimer disease dementia (AD). PET images were visually scored as positive (Aβ+) or negative (Aβ-) for pathologic levels of β-amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVr) were determined from the baseline PET images. Subjects were followed for 18 months to evaluate changes in cognition and diagnostic status. Analysis of covariance and correlation analyses were conducted to evaluate the association between baseline PET amyloid status and subsequent cognitive decline.

Results: In both MCI and CN, baseline Aβ+ scans were associated with greater clinical worsening on the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog (p < 0.01) and Clinical Dementia Rating-sum of boxes (CDR-SB) (p < 0.02). In MCI Aβ+ scans were also associated with greater decline in memory, Digit Symbol Substitution (DSS), and Mini-Mental State Examination (MMSE) (p < 0.05). In MCI, higher baseline SUVr similarly correlated with greater subsequent decline on the ADAS-Cog (p < 0.01), CDR-SB (p < 0.03), a memory measure, DSS, and MMSE (p < 0.05). Aβ+ MCI tended to convert to AD dementia at a higher rate than Aβ- subjects (p < 0.10).

Conclusions: Florbetapir PET may help identify individuals at increased risk for progressive cognitive decline.

Figure 1. Illustrative florbetapir PET scans in controls, patients with mild cognitive impairment (MCI), and patients with Alzheimer disease (AD)

Representative florbetapir PET images for an amyloid-negative (Aβ−) cognitively normal subject (A), an amyloid-positive (Aβ+) patient with AD (B), an Aβ− patient with MCI (C), and an Aβ+ patient with MCI who converted to dementia during the course of this study (D). Aβ+ was determined per the majority of 3 raters. Color scale is shown in SUVr units. Standardized uptake value ratio (SUVr) was calculated as described in the text.

Figure 2. Change from baseline on cognitive assessment measures in subjects with mild cognitive impairment (MCI)

Least squares mean change (SE) in test scores from baseline to month 18. Note that in this graph the direction of change on the Alzheimer's Disease Assessment Scale–Cognitive subscale (ADAS) and Clinical Dementia Rating–Sum of Boxes (CDR SB) are reversed to show worsening scores as a negative change consistent with other measures (graph based on MCI data from table 2). DSS = Digit Symbol Substitution; MMSE = Mini-Mental State Examination; WMS = Wechsler Memory Scale.

Figure 3. Correlation between baseline florbetapir standardized uptake value ratio (SUVr) (averaged across 6 brain regions) and change from baseline to 18 months on the Alzheimer's Disease Assessment Scale–Cognitive subscale (ADAS) and Digit Symbol Substitution (DSS) in subjects with mild cognitive impairment

The correlations are not adjusted for other variables. Correlations adjusted for age and baseline cognitive score remained significant (table 2). Correlations conducted separately within Aβ+ and Aβ− groups were not statistically significant, indicating that the presence of Aβ may be a more important predictor of cognitive decline than the exact amount of Aβ present.