Investigating Associative Learning Effects in Patients with Prodromal Alzheimer’s Disease Using the Temporal Context Model

Abstract

Objective: The purpose of this study was to investigate associative learning effects in patients with prodromal Alzheimer's disease (prAD) by referring to the Temporal Context Model (TCM; Howard, Jing, Rao, Provyn, & Datey, 2009), in an attempt to enhance the understanding of their associative memory impairment. TCM explains fundamental effects described in classical free-recall tasks and cued-recall tasks involving overlapping word pairs (e.g., A-B, B-C), namely (1) the contiguity effect, which is the tendency to successively recall nearby items in a list, and (2) the observation of backward (i.e., B-A) and transitive associations (i.e., A-C) between items. In TCM, these effects are hypothesized to rely on contextual representation, binding and retrieval processes, which supposedly depend on hippocampal and parahippocampal regions. As these regions are affected in prAD, the current study investigated whether prAD patients would show reduced proportions of backward and transitive associations in free and cued-recall, coupled to a reduced contiguity effect in freerecall.Method: Seventeen older controls and 17 prAD patients performed a cued-recall task implying overlapping word pairs and a final free-recall task.Results: Proportions of backward and transitive intrusions in cued-recall did not significantly differ between groups. However, in free-recall, prAD patients demonstrated a reduced contiguity effect as well as reduced proportions of backward and transitive associations compared to older controls.Conclusions: These findings are discussed within the hypothesis that the contextual representation, binding and/or retrieval processes are affected in prAD patients compared to healthy older individiuals.

MicroRNA‐134‐5p inhibition rescues long‐term plasticity and synaptic tagging/capture in an Aβ(1–42)‐induced model of Alzheimer’s disease

“…Aβ (1–42) treatment to hippocampal rat slices have been known to affect long‐term plasticity (late LTP) and associativity such as synaptic tagging and capture (STC) (Jiang et al, ; Krishna et al, ; Lei et al, ; Ma et al, ; Quenon, de Xivry, Hanseeuw, & Ivanoiu, ; Sharma et al, ). Since the impaired synaptic plasticity was associated with the upregulation of miR‐134‐5p expression in rat hippocampal slices, we investigated if inhibition of miR‐134‐5p expression using miR‐134i could rescue late LTP in Aβ (1–42)‐treated hippocampal slices.…”

“…Synaptic associativity such as synaptic tagging and capture (STC), a unique feature of healthy neurons, enables weak memory engram to transform to relatively stable memory engram and thus helps with the formation of long‐term memory (Frey & Morris, ; Redondo & Morris, ; Sajikumar & Frey, ). Various studies have reported the dysregulation of synaptic associativity in AD pathology (Bastin et al, ; Jiang et al, ; Quenon et al, ). It has been reported earlier that STC is highly impaired during aging and in Aβ‐induced AD conditions (Sharma et al, , ; Shetty & Sajikumar, ).…”

Epigenetic regulation by G9a/GLP complex ameliorates amyloid‐beta 1‐42 induced deficits in long‐term plasticity and synaptic tagging/capture in hippocampal pyramidal neurons

“…The conversion of short‐term plasticity to long‐term plasticity widely relies on associative properties of a neural network. One characteristic feature of progressive dementia and AD is the deficit in associative plasticity or memory (Bastin et al ., ; Jiang et al ., ; Quenon et al ., ). Our data provide the evidence that Aβ leads to deficits in synaptic tagging/capture (STC), which is considered as one of the major contributors of associative plasticity (Frey & Morris, ; Redondo & Morris, ).…”

“…Exogenous application of Aβ 1–42 impairs synaptic plasticity in vitro as well as in vivo , which underlies the process of memory formation (Ma et al ., ; Lei et al ., ). Deficits in associative learning have also been reported in the preclinical form of AD (Jiang et al ., ; Quenon et al ., ). STC model explains the formation of memories in an associative and time‐dependent manner (Frey & Morris, ; Redondo & Morris, ).…”

The First Word Recalled Measure – A Potential Addition to Clinical Exams

“…To compute this measure, the number of actual lag was calculated and normalized by the number of transition this participant performed in this trial. The normalization system used by Quenon et al (34) was employed since it yields a temporal contiguity measure that deals well with the minimal data available per condition/participant and is relatively insensitive to potential group-differences in overall recall level. The recall temporal contiguity measures were constructed only for the delayed recall trial, since these measure are known to change along the retrieval process in immediate recall and accordingly, different lag-CRP patterns are expected for each output position (i.e., for the 1st, 2nd, 3rd etc.…”