title: Episodic memory decline predicts cortical amyloid status in community-dwelling older adults.
abstract: Intra-individual decline in memory and cognition is characteristic of prodromal Alzheimer's disease (AD) and may allow detection of very early AD pathology. Episodic memory task scores on a brief computerized cognitive battery (CogState) were prospectively evaluated at baseline, and 3-, 6-, 9-, 12-, and 24-months post-baseline. Linear mixed models were conducted to compute age-adjusted slopes. Subjects with slopes declining ≥90th percentile ("memory decliners") and age- and gender-matched subjects without such decline ("non-decliners") were studied with clinical, neuropsychological, and neuroimaging evaluations. Of 195 who completed 24-month evaluation (age 51 to 80 years), 15 memory decliners (mean age 62.7 years, SD 7.6) were identified, and matched with 33 non-decliners (mean age 63.3 years, SD 8.2). Amyloid-PET imaging was qualitatively abnormal with excess cortical amyloid accumulation in 7 memory decliners (46.7%) and 4 (12.1%) non-decliners (odds ratio 6.34), and quantitatively abnormal with standardized uptake value ratios >1.4 in 5 memory decliners (33.3%) and 2 (6.1%) non-decliners (odds ratio 8.3). One of the memory decliners and none of the non-decliners fulfilled criteria for mild cognitive impairment, but the groups did not differ with respect to subjective memory impairment, neuropsychological evidence of episodic memory impairment, or MRI imaging abnormalities. Intra-individual decline in episodic memory can be detected using a brief computerized cognitive performance test optimized to detect change in community-dwelling non-demented older persons and appears predictive of the presence of cerebral amyloid in about half of these persons. This approach may help detect early prodromal AD pathology in wider-scale community screening programs.
authors.affiliation: CogState Ltd, Melbourne, Australia. ddarby@cogstate.com
authors.forename: David G
authors.initials: DG
authors.lastname: Darby
authors.forename: Amy
authors.initials: A
authors.lastname: Brodtmann
authors.forename: Robert H
authors.initials: RH
authors.lastname: Pietrzak
authors.forename: Julia
authors.initials: J
authors.lastname: Fredrickson
authors.forename: Michael
authors.initials: M
authors.lastname: Woodward
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.forename: Amy
authors.initials: A
authors.lastname: Fredrickson
authors.forename: Paul
authors.initials: P
authors.lastname: Maruff
authors.forename: Christopher
authors.initials: C
authors.lastname: Rowe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002540:Cerebral Cortex / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis* / Q000523:psychology; D061212:Memory, Episodic; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000175:diagnosis* / Q000523:psychology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012111:Residence Characteristics