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Amyloid-Related Memory Decline in Preclinical Alzheimer's Disease Is Dependent on APOE ε4 and Is Detectable over 18-Months.

Thai C, Lim YY, Villemagne VL, Laws SM, Ames D, Ellis KA, Rainey-Smith SR, Martins RN, Masters CL, Rowe CC, Maruff P, Australian Imaging, Biomarkers and Lifestyle (AIBL) Research Gro - PLoS ONE (2015)

Bottom Line: Planned comparisons indicated that CN older adults with high Aβ who were also APOE ε4 carriers demonstrated the most pronounced decline in learning and working memory.Carriage of APOE ε4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months.These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer's disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, Royal Melbourne Institute of Technology, Melbourne, Australia.

ABSTRACT
High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. However, the relationship between these two biomarkers and cognitive decline is unclear. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 months, in 317 cognitively healthy (CN) older adults (47.6% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SD = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults with high Aβ who were also APOE ε4 carriers demonstrated the most pronounced decline in learning and working memory. In CN older adults who were APOE ε4 non-carriers, high Aβ was unrelated to cognitive decline in learning and working memory. Carriage of APOE ε4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months. These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer's disease.

No MeSH data available.


Related in: MedlinePlus

Magnitude of difference for cognitive decline over 18 months, relative to the Aβ- ε4 non-carrier group.0 line represents the Aβ- ε4 non-carrier group; error bars represent 95% confidence intervals. *p<.05.
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pone.0139082.g001: Magnitude of difference for cognitive decline over 18 months, relative to the Aβ- ε4 non-carrier group.0 line represents the Aβ- ε4 non-carrier group; error bars represent 95% confidence intervals. *p<.05.

Mentions: Baseline- and covariate-adjusted means for the 18-month assessment are shown in Table 2, and the magnitude of difference between groups is shown in Fig 1. In the Aβ- groups, no differences between ε4 carriers and non-carriers were observed for any of the cognitive measures. Compared to Aβ- ε4 non-carriers, Aβ- ε4 carriers showed a slight improvement on the CVLT-II immediate total recall at 18 months, and no decline on any other cognitive measure. In contrast, compared to Aβ- ε4 non-carriers, Aβ+ ε4 carriers performed significantly worse at 18 months on the OCL, OBK and the OCLOBK composite scores, with each of these differences between groups moderate in magnitude (Table 2).


Amyloid-Related Memory Decline in Preclinical Alzheimer's Disease Is Dependent on APOE ε4 and Is Detectable over 18-Months.

Thai C, Lim YY, Villemagne VL, Laws SM, Ames D, Ellis KA, Rainey-Smith SR, Martins RN, Masters CL, Rowe CC, Maruff P, Australian Imaging, Biomarkers and Lifestyle (AIBL) Research Gro - PLoS ONE (2015)

Magnitude of difference for cognitive decline over 18 months, relative to the Aβ- ε4 non-carrier group.0 line represents the Aβ- ε4 non-carrier group; error bars represent 95% confidence intervals. *p<.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4592244&req=5

pone.0139082.g001: Magnitude of difference for cognitive decline over 18 months, relative to the Aβ- ε4 non-carrier group.0 line represents the Aβ- ε4 non-carrier group; error bars represent 95% confidence intervals. *p<.05.
Mentions: Baseline- and covariate-adjusted means for the 18-month assessment are shown in Table 2, and the magnitude of difference between groups is shown in Fig 1. In the Aβ- groups, no differences between ε4 carriers and non-carriers were observed for any of the cognitive measures. Compared to Aβ- ε4 non-carriers, Aβ- ε4 carriers showed a slight improvement on the CVLT-II immediate total recall at 18 months, and no decline on any other cognitive measure. In contrast, compared to Aβ- ε4 non-carriers, Aβ+ ε4 carriers performed significantly worse at 18 months on the OCL, OBK and the OCLOBK composite scores, with each of these differences between groups moderate in magnitude (Table 2).

Bottom Line: Planned comparisons indicated that CN older adults with high Aβ who were also APOE ε4 carriers demonstrated the most pronounced decline in learning and working memory.Carriage of APOE ε4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months.These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer's disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, Royal Melbourne Institute of Technology, Melbourne, Australia.

ABSTRACT
High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. However, the relationship between these two biomarkers and cognitive decline is unclear. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 months, in 317 cognitively healthy (CN) older adults (47.6% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SD = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults with high Aβ who were also APOE ε4 carriers demonstrated the most pronounced decline in learning and working memory. In CN older adults who were APOE ε4 non-carriers, high Aβ was unrelated to cognitive decline in learning and working memory. Carriage of APOE ε4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months. These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer's disease.

No MeSH data available.


Related in: MedlinePlus