Florbetapir PET may predict cognitive decline, Alzheimer’s conversion

Individuals at risk for progressive cognitive decline who had amyloid-positive florbetapir PET results performed worse on cognitive assessments and were more likely to convert to Alzheimer’s disease (AD) within 18 months than those with amyloid-negative results, according to a study published Oct. 16 in Neurology.

Although 10 to 15 percent of adults with mild cognitive impairment (MCI) progress annually to dementia, there is considerable variability in conversion, according to P. Murali Doraiswamy, MD, from Duke University Medical Center in Durham, N.C., and colleagues.

The researchers conducted a prospective study to determine the prognostic utility of florbetapir PET in older at-risk adults. The researchers focused on 151 subjects who had participated in a multicenter florbetapir PET study; the cohort included 51 subjects with MCI, 69 cognitively normal controls, and 31 with clinically diagnosed AD.  

Subjects underwent a baseline florbetapir PET study, which was independently rated as amyloid positive (AB+) or amyloid negative (AB-) by three nuclear medicine physicians. At baseline, 37 percent of subjects with MCI, 14 percent of normal control subjects and 68 percent of those with AD were rated as AB+. Researchers used PET data to determine cerebral to cerebrellar standard uptake value radios (SUVr). All subjects also underwent a baseline cognitive assessment, consisting of a series of tests, including the Alzheimer’s Disease Assessment Scale-Cognitive subscale and assessments of verbal fluency, recall, and executive function.

Cognitive assessments were repeated 18 months after the initial exams. MCI subjects rated AB+ tended to perform worse than MCI subjects rated AB- on almost all cognitive assessments. Normal control and AD subjects rated AB+ performed worse on several cognitive assessments at 18 months.

Higher SUVr in patients with MCI correlated with greater decline in the Alzheimer’s Disease Assessment Scale-Cognitive subscale, and other assessments of memory and executive function, reported Doraiswamy et al.

The researchers reported subjects with MCI rated AB+ were more likely to convert to AD than those rated AB-. Finally, 23.5 percent of AB+ MCI subjects and 30 percent of normal control subjects worsened their Clinical Dementia Rating score by at least 0.5 points. The corresponding rates  for AB- subjects were 6.7 percent for those with MCI and 5.5 percent among normal control subjects.

“This multicenter, longitudinal study of florbetapir F 18 amyloid imaging confirms and extends results from prior, mostly single site, studies with 11C-PiB showing that both cognitively normal subjects and subjects with MCI with higher levels of cortical AB on PET are at higher risk for future cognitive progression than individuals with lower levels of amyloid after controlling for age and baseline cognitive performance,” wrote Doraiswamy et al.

Thus, florbetapir PET may provide a predictive biomarker of cognitive decline in at-risk patients and dementia conversion among those with MCI.