Pittsburgh compound B imaging and prediction of progression from cognitive normality to symptomatic Alzheimer disease.
OBJECTIVE
To determine whether preclinical Alzheimer disease (AD), as detected by the amyloid-imaging agent Pittsburgh Compound B (PiB) in cognitively normal older adults, is associated with risk of symptomatic AD.


METHODS
A longitudinal cohort study of cognitively normal older adults assessed with positron emission tomography (PET) to determine the mean cortical binding potential for PiB and followed up with annual clinical and cognitive assessments for progression to very mild dementia of the Alzheimer type (DAT).


METHODS
The Alzheimer's Disease Research Center, Washington University, St Louis, Missouri.


METHODS
One hundred fifty-nine participants with a mean age of 71.5 years with a Clinical Dementia Rating (CDR) of 0 on a PET PiB scan at baseline.


METHODS
Progression from CDR 0 to CDR 0.5 status (very mild dementia).


RESULTS
Twenty-three participants progressed to CDR 0.5 at follow-up assessment (range, 1-5 assessments after PET PiB). Of these, 9 also were diagnosed with DAT. Higher mean cortical binding potential values for PiB (hazard ratio, 4.85; 95% confidence interval, 1.22-19.01; P = .02) and age (hazard ratio, 1.14; 95% confidence interval, 1.02-1.28; P = .03) predicted progression to CDR 0.5 DAT. The CDR 0.5 DAT group showed decline in 3 cognitive domains (episodic memory, semantic memory, and visuospatial performance) and had volume loss in the parahippocampal gyrus (includes entorhinal cortex) compared with individuals who remained at CDR 0.


CONCLUSIONS
Preclinical AD as detected by PET PiB is not benign, as it is associated with progression to symptomatic AD.
Morris
John C
JC
Alzheimer's Disease Research Center, St Louis, Missouri 63108, USA. morrisj@abraxas.wustl.edu
Roe
Catherine M
CM
Grant
Elizabeth A
EA
Head
Denise
D
Storandt
Martha
M
Goate
Alison M
AM
Fagan
Anne M
AM
Holtzman
David M
DM
Mintun
Mark A
MA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology / Q000523:psychology; D000814:Aniline Compounds; D002250:Carbon Radioisotopes; D003071:Cognition; D003072:Cognition Disorders / Q000000981:diagnostic imaging* / Q000523:psychology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D011237:Predictive Value of Tests; D013844:Thiazoles
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D002250:Carbon Radioisotopes; D013844:Thiazoles