Abstract:
OBJECTIVE:To model the temporal trajectory of β-amyloid accumulation using serial amyloid PET imaging. METHODS:Participants, aged 70-92 years, were enrolled in either the Mayo Clinic Study of Aging (n = 246) or the Mayo Alzheimer's Disease Research Center (n = 14). All underwent 2 or more serial amyloid PET examinations. There were 205 participants classified as cognitively normal and 55 as cognitively impaired (47 mild cognitive impairment and 8 Alzheimer dementia). We measured baseline amyloid PET-relative standardized uptake values (SUVR) and, for each participant, estimated a slope representing their annual amyloid accumulation rate. We then fit regression models to predict the rate of amyloid accumulation given baseline amyloid SUVR, and evaluated age, sex, clinical group, and APOE as covariates. Finally, we integrated the amyloid accumulation rate vs baseline amyloid PET SUVR association to an amyloid PET SUVR vs time association. RESULTS:Rates of amyloid accumulation were low at low baseline SUVR. Rates increased to a maximum at baseline SUVR around 2.0, above which rates declined-reaching zero at baseline SUVR above 2.7. The rate of amyloid accumulation as a function of baseline SUVR had an inverted U shape. Integration produced a sigmoid curve relating amyloid PET SUVR to time. The average estimated time required to travel from an SUVR of 1.5-2.5 is approximately 15 years. CONCLUSION:This roughly 15-year interval where the slope of the amyloid SUVR vs time curve is greatest and roughly linear represents a large therapeutic window for secondary preventive interventions.
journal_name
Neurologyjournal_title
Neurologyauthors
Jack CR Jr,Wiste HJ,Lesnick TG,Weigand SD,Knopman DS,Vemuri P,Pankratz VS,Senjem ML,Gunter JL,Mielke MM,Lowe VJ,Boeve BF,Petersen RCdoi
10.1212/WNL.0b013e3182840bbesubject
Has Abstractpub_date
2013-03-05 00:00:00pages
890-6issue
10eissn
0028-3878issn
1526-632Xpii
WNL.0b013e3182840bbejournal_volume
80pub_type
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