In older cognitively healthy adults, the amount of β-amyloid (Aβ) in the brain is a more important factor in determining risk for future memory decline than is the APOE ε4 allele, a study from Australia shows.

"Amyloid-related deterioration in memory occurs in cognitively normal healthy older adults with high Aβ and who carry the APOE ε4 allele," lead author Yen Ying Lim, MPsych, and PhD candidate, Florey Institute of Neuroscience and Mental Health, in Parkville, Victoria, Australia, told Medscape Medical News. "[Our] data suggest that Aβ amyloid is the most important factor in predicting this decline."

Moderate Effect Sizes

The study involved 141 adults with an average age of 76 years enrolled in the Australian Imaging Biomarkers and Lifestyle (AIBL) study, a prospective longitudinal study of aging in Australia. All participants underwent positron emission tomography (PET) neuroimaging for cerebral Aβ, APOE genotyping, and cognitive assessment at baseline. Cognitive function was reassessed 18 months later.

Compared with the cognitive performance of healthy older adults with normal baseline cerebral Aβ load (PET standardized uptake value ratio [SUVR] < 1.5), those with an SUVR of 1.5 or higher showed significantly greater decline at 18 months on all measures of episodic memory assessed, the researchers report.

The magnitudes of these declines were moderate (Cohen d = 0.40 - 0.60), they say. A decline of similar magnitude was also seen for visual working memory in patients with high baseline Aβ load.

In contrast to memory, no effect of cerebral Aβ load was seen for psychomotor function or visual attention. Therefore, the decline in episodic memory observed could not have been due to changes in arousal or attention, the researchers say.

Compared with noncarriers, APOE ε carriers also showed a greater decline in visual memory at the 18-month assessment, but the effect was less than that observed for cerebral Aβ load. There was no interaction between APOE ε4 and cerebral Aβ load for any measure of cognitive function.

Confirmatory Data

Dr. Lim said the findings were not unexpected. Prior data from the AIBL study, reported at that time by Medscape Medical News, showed that healthy older adults who show a decline in memory "also have higher risk of having high Aβ amyloid levels." This latest analysis, she said, "provides confirmation that high Aβ amyloid is the causal factor for the memory decline."

Identifying the effects of amyloid in healthy older adults, Dr. Lim added, "could provide a platform for us to begin to investigate whether pharmaceutical therapies designed to alter or halt amyloid accumulation can prevent the disease from progressing to the more severe stages."

Reached for comment, Rahul S. Desikan, MD, PhD, from the University of California, San Diego, School of Medicine, told Medscape Medical News, "though interesting, I think these findings are not surprising," given that several research groups have already shown this effect.

Dr. Desikan, who was not involved in the study, also felt the study was "incomplete" because it didn't examine the role of tau.

"Based on our work and findings from [others], I think it has become clear that simply examining the role of amyloid in preclinical AD is insufficient; you also need to look at tau as a lot of these amyloid positive older folks who show 'cognitive decline' are likely also p-tau positive," Dr. Desikan said.

The study was supported by the Australian Commonwealth Scientific Industrial and Research Organization, Edith Cowan University, Mental Health Research Institute, Alzheimer's Australia, National Aging Research Institute, Austin Health, CogState Ltd., Hollywood Private Hospital, Sir Charles Gardner Hospital, the Australian National Health and Medical Research Council, the Dementia Collaborative Research Centers Program, and the Science and Industry Endowment Fund. Dr. Lim has disclosed no relevant financial relationships. A complete list of disclosures for the AIBL study investigators is listed with the original article.

The study was published October 16 in Neurology. 2012;79:1645-1652.