Investigation of visual long-term potentiation and visual recognition memory in older adults: Developing a protocol to identify an early marker of Alzheimer's disease

Abstract

This research aimed to investigate recognition memory and electrophysiological functioning of healthy older adults in order to establish a procedure that could potentially be developed and tested in the future for utility as an early AD marker. This project was comprised of two parts: a recognition memory study and an electrophysiological study that used electroencephalography. The rationale underlying the recognition memory study was guided by two bodies of research. The first relates to findings that AD neuropathology develops first in perirhinal and entorhinal cortices, prior to the hippocampus. The second body of research relates to a model of recognition memory, which implicates a key role of the hippocampus in recollection and the involvement of perirhinal cortex in familiarity-based recognition. Together these two bodies of research suggest that assessing familiarity and recollection recognition, which are reliant on distinct medial temporal lobe regions that are differentially impacted early in the course of AD, may provide a sensitive memory test able to detect the earlier changes associated with AD. Research examining recognition memory in AD and MCI has produced conflicting findings. This study aimed to test and further develop the learning parameters for two recognition memory tasks. Participants were tested on two versions of recognition memory tasks: a replication of the task used by Westerberg et al.’s (2006) and an experimental task, in which the learning procedure was modified with the aim of reducing recollection learning. Both included a yes-no task (recollection) and a forced choice task (familiarity). The results indicated that the performance of healthy older adults on the tasks of recognition memory was reduced on the experimental procedure relative to the replication task. This suggests that opportunities for learning material were reduced by conditions of the experimental task as hypothesised. This study also found that older adults performed equally on the tests of the experimental procedure, suggesting that the tests show an equal level of difficulty. These tests may, thus, be useful for further research with patient groups as interpreting a difference in performance on the yes-no and forced-choice tasks will not be confounded by differential difficulty of the two tasks. The EEG study measured induction of long-term potentiation (LTP), a molecular mechanism thought to underlie memory formation in older adults. This study used a protocol that has successfully induced an LTP-like effect in young adults through the repeated brief presentation of a simple visual stimulus (tetanic stimulation). The results suggest that LTP may be induced and maintained over 30 minutes in healthy older adults. When examining possible relationship between visual LTP activity and memory performance, a significant correlation was found between the magnitudes of late LTP and forced-choice recognition memory scores (familiarity) on the experimental test procedure. The findings of this research, thus, provide a foundation to guide further research in explicating the potential role of LTP in older adults as a marker of subtle neuropathological change related to early AD or MCI. The study findings indicate that the recognition protocol, on which the experimental task is based, may offer greater sensitivity in detecting early or transitional changes in individuals with AD and MCI. The current study, hence, provides a platform for further longitudinal research which can clarify the contribution of LTP as a biomarker of early cognitive change and provide opportunities for convergence with existing biomarkers from neuroimaging and biochemical paradigms.