Tracing brain amyloid-β in asymptomatic older adults relying on a memory marker for Alzheimer's disease

Recent approaches to the early diagnosis of Alzheimer’s disease (AD) are aimed at detecting neuropathological signatures of this type of dementia in still healthy older adults. Should these efforts prove fruitful, strategies then focus on identifying the cognitive and functional decline that ensue. These approaches have proved both little effective and costly. In the present study, we investigated the hypothesis that effective cognitive markers for AD could help detect among still healthy older adults who would have likely started to accumulate the neuropathological changes pursued by costly neuroimaging procedures. A sample of 39 healthy older adults was recruited and assessed with an extensive neuropsychological and neuroimaging protocol. As the memory marker, we used the Visual Short-Term Memory Binding Task. Using existing data, participants were divided in two groups depending on whether or not they displayed the typical binding profile seen in AD subjects (i.e., strong binders – SB and weak binders - WB). The results show that in addition to the increased binding cost seen in WB, SB and WB could only be differentiated by the amount of Amyloid- accumulated in brain regions known to be involved in this cognitive function. No other neuropsychological tests proved informative, and neither volumetric nor cortical thickness metrics provided meaningful neuropathological signals. Our findings have significant implications for our understanding of the transition from normal ageing to preclinical AD and methodological approaches currently used to ascertain it. These are discussed at length.