Amyloid-β assessed by florbetapir F 18 PET and 18-month cognitive decline: a multicenter study.
OBJECTIVE
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.
Duke University Medical Center, Durham, NC, USA. murali.doraiswamy@duke.edu
P Murali
PM
Doraiswamy
Reisa A
RA
Sperling
R Edward
RE
Coleman
Keith A
KA
Johnson
Eric M
EM
Reiman
Mat D
MD
Davis
Michael
M
Grundman
Marwan N
MN
Sabbagh
Carl H
CH
Sadowsky
Adam S
AS
Fleisher
Alan
A
Carpenter
Christopher M
CM
Clark
Abhinay D
AD
Joshi
Mark A
MA
Mintun
Daniel M
DM
Skovronsky
Michael J
MJ
Pontecorvo
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001921:Brain / Q000000981:diagnostic imaging; D003072:Cognition Disorders / Q000000981:diagnostic imaging* / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000523:psychology; D003704:Dementia / Q000175:diagnosis / Q000523:psychology; D005026:Ethylene Glycols; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods*; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance / Q000502:physiology; D019275:Radiopharmaceuticals; D012306:Risk
D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D005026:Ethylene Glycols; D019275:Radiopharmaceuticals; C545186:florbetapir