title: Cognition and beta-amyloid in preclinical Alzheimer's disease: data from the AIBL study.
abstract: The 'preclinical' phase of Alzheimer's disease is a future target for treatment, but additional research is essential to understand the relationship between β-amyloid burden and cognition during this time. We investigated this relationship using a large sample of apparently healthy older adults (N=177), which also enabled examination of whether the relationship differed according to age, gender, years of education, apolipoprotein E status, and the presence of subjective memory complaints. In addition to episodic memory, a range of cognitive measures (global cognition, semantic memory, visuospatial performance, and executive function) were examined. Participants were aged over 60 years with no objective cognitive impairment and came from the imaging arm of the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study of ageing. (11)C-PiB PET was used to measure β-amyloid burden and a PiB 'cut-off' level of 1.5 was used to separate participants with low PiB retention from those with high PiB retention. Thirty-three percent of participants had a PiB positive scan. PiB positive participants were 5 years older, twice as likely to carry an apolipoprotein E ɛ4 allele, and their composite episodic memory was 0.26 SD worse than PiB negative volunteers. Linear regressions with β-amyloid burden as a dichotomous predictor, revealed an interaction between β-amyloid burden and gender, as well as age and education effects, in predicting episodic memory and visuospatial performance. In females, but not in males, increased β-amyloid was related to worse episodic memory and visuospatial performance. Furthermore, an interaction between β-amyloid burden and APOE status was found in predicting visuospatial performance, whereby there was a trend for increased β-amyloid to relate to worse visuospatial performance for those without an APOE ɛ4 allele. There were no other main or interaction effects of β-amyloid on any of the other composite cognitive measures. These cross-sectional findings suggest that β-amyloid burden does not have a large effect on cognition in this subset of apparently healthy older people. The finding of gender differences deserves further research to answer definitively the important question of gender susceptibility to adverse cognitive effects from β-amyloid.
authors.affiliation: Department of Nuclear Medicine, Centre for PET, Austin Health, Heidelberg, VIC, Australia. k.pike@latrobe.edu.au
authors.forename: Kerryn E
authors.initials: KE
authors.lastname: Pike
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Ellis
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.forename: Norm
authors.initials: N
authors.lastname: Good
authors.forename: Gael
authors.initials: G
authors.lastname: Chételat
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.forename: Cassandra
authors.initials: C
authors.lastname: Szoeke
authors.forename: Simon M
authors.initials: SM
authors.lastname: Laws
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Verdile
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000009:adverse effects / Q000378:metabolism*; D000814:Aniline Compounds; D052160:Benzothiazoles; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D003072:Cognition Disorders / Q000150:complications / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011877:Radionuclide Imaging; D012016:Reference Values; D012737:Sex Factors; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D002250:Carbon Radioisotopes; D013844:Thiazoles