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Study Indicates Rate of Beta Amyloid Accumulation Associated With Rate of Decline in Memory

June 23, 2015

Archives of Clinical NeuropsychologyAs researchers gain greater understanding of the many processes that give rise to the dementia Alzheimer’s disease, they begin to appreciate relationships and linkages between changes in brain chemistry and brain biology and how such changes manifest in behavior. Combining an understanding of the physiological changes with behavioral changes helps establish the order of causality in the disease. This provides a foundation for strategies designed to slow or even halt physiological changes and thereby allow individuals to retain their normal cognitive abilities into older age.

Three central and related indicators of Alzheimer’s disease are the presence of beta amyloid, loss of neurons, in particular in the hippocampus and a decline in a person’s cognitive function. While cross-sectional studies have shown these factors to be associated, and disease models shown their inter-relatedness, there have been few studies to actually measure the nature and strength of relationships between increasing amyloid, neuronal loss and cognitive decline in humans.

The physiological changes that ultimately give rise to dementia in AD can begin up to 30 years before patients gain a clinical diagnosis. In this preclinical stage there is an accumulation of beta amyloid (Aβ) which can be detected using positron emission tomography (PET) brain scans. This begins a process of neuronal loss, in particular in those areas of the brain responsible for memory such as the hippocampus. Neuronal loss is most often determined by using magnetic resonance imaging (MRI) and measuring the extent to which the volume of the hippocampus (i.e. hippocampal volume; HV is reduced over time. Because memory function depends on the function of the hippocampus, a loss of neurons is most likely to be associated with of loss of memory efficiency.

Monitoring a person’s cognitive function through neuropsychological testing provides a more accessible and cost efficient tracking tool than scanning for changes in Aβ or HV, provided the chosen test can measure subtle changes in brain functioning, particularly memory. Recently, Australian and American researchers used the Cogstate Brief Battery (CBB), MRI and amyloid PET to describe the relationships between accumulation of Aβ, HV loss and memory decline in individuals who did not have dementia.

Dr. Yen Ying Lim of Brown University and Dr. Paul Maruff, Chief Science Officer at Cogstate, along with colleagues from the University of Melbourne, Yale University and Edith Cowan University set out to evaluate the relationship between decline in cognition and rates of change in HV and Aβ accumulation over a 36-month period in cognitively normal older adults and adults who had been classified clinically with mild cognitive impairment (MCI). In addition, they sought to understand how these changes evolve over the preclinical and prodromal phases of Alzheimer’s disease.

They hypothesized that adults who already had Aβ plaques present in their brain would show greater decline in memory and loss in HV than those adults that showed no sign of Aβ accumulation. Second, the team hypothesized accumulation of Aβ would be linked with HV loss which would lead to more memory loss.

Research participants were recruited from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study who were either cognitively normal (n=178) or had mild cognitive impairment (MCI) (n=49). To determine the presence of Aβ and to measure their HV at baseline, all volunteers underwent positron emission tomography (PET) imaging as well as magnetic resonance imaging.

To establish their cognitive performance levels, they completed the CBB, which included four tests; psychomotor function (Detection; DET), attention (Identification; IDN), visual learning (One Card Learning; OCL), and working memory (One Back; OBK)

Each series of tests was repeated after 18 months and 36 months to detect changes over time.

As the researchers expected, those adults who already had Aβ present showed greater rates of cognitive decline and hippocampal volume than those that had no Aβ at baseline. Their second hypothesis was also correct showing that the rate of Aβ accumulation was associated with the rate of HV loss, which was related to the rate of episodic and working memory decline. Beta amyloid plaques may represent a precursor to other signs and symptoms, often resulting in an eventual and unfortunate diagnosis of Alzheimer’s disease or dementia.

The research has been published in the Archives of Clinical Neuropsychology.

Understanding the relationship between these three indicators can help guide future research by relying on periodic cognitive testing results.

“This is one of the first studies to actually compare rates of change over time in AB accumulation, HV loss and memory decline over 36 months and also one of the first to provide statistically reliable estimates of the relationships between changes in these different factors,” said Dr. Maruff, who led the study. “Our results do support the amyloid cascade hypothesis of AD and also provide a basis for understanding how to measure the effects of treatments designed to slow or even halt amyloid related disease before these evolve into dementia.”

Questions or comments?  Please contact Dan Peterson