A desnutrição protéica em estágios iniciais da vida produz alterações estruturais, neuroquímicas e funcionais no sistema nervoso central, podendo causar prejuízos no desenvolvimento cognitivo e comportamental. Assim, o objetivo do presente estudo foi o de investigar os efeitos da desnutrição protéica pós-natal em tarefas que avaliam a aprendizagem e memória. Estas investigações foram feitas comparando o desempenho de ratos Wistar, submetidos à desnutrição protéica (6% de proteína) durante a lactação e pós-lactação com animais controle (16% de proteína), nas tarefas de memória operacional no Labirinto Aquático de Morris (LAM), memória de reconhecimento de objetos no campo aberto e memória operacional no Labirinto em T Aquático (LTA). No experimento I a tarefa foi localizar uma plataforma oculta que mudou de posição a cada sessão diária com quatro tentativas no LAM. A memória a longo prazo foi avaliada após seis meses utilizando-se o mesmo procedimento. No experimento II os animais foram submetidos à tarefa de reconhecimento de objetos no campo aberto, em duas tentativas com diferentes intervalos intertentativas (3 e 24h). Na 1a tentativa o animal foi habituado a um objeto A e na 2a, discriminava o objeto A de um novo objeto B. No experimento III foi testado o desempenho dos animais no LTA, sendo inicialmente forçados a alternar os braços de entrada e, após esta fase, escolher em qual braço deveria entrar para encontrar a plataforma fixada em uns dos braços. Os resultados mostraram déficits na aprendizagem e memória dos animais desnutridos no experimento I. Porém, na fase 2 a diferença entre os grupos nutricionais desapareceu. No experimento II, o índice de reconhecimento dos animais desnutridos foi significativamente maior que dos controle nos intervalos de 3 e 24h. No experimento III, houve diferença apenas do tipo de intervalo, sendo que no intervalo de 30s todos os animais demoraram mais para atingirem o critério proposto. Com estes resultados se pode concluir que a desnutrição protéica pós-natal causou prejuízos na memória operacional no LAM; porém, este déficit diminuiu seis meses depois, sugerindo que a recuperação nutricional foi eficiente para reverter as alterações causadas pela desnutrição. A tarefa de memória operacional no LTA não foi afetada por este modelo de desnutrição, independente do intervalo. Entretanto, a tarefa de memória de reconhecimento foi prejudicada pela desnutrição pós-natal, independente do intervalo, e a atividade exploratória somente no intervalo de 24h. / Early protein malnutrition induces structural, neurochemical and functional changes in the Central Nervous System leading to alterations in cognitive and behavioral development of rats such as spatial learning and memory. The aim of this work was to investigate the effects of postnatal protein malnutrition on learning and memory tasks. This evaluation was done by comparing the performance of previously malnourished male Wistar rats (6% protein) from birth to 49 days of age with well-nourished control animals (16% protein) in three experiments: working memory tasks in the Morris water maze (Experiment I) at 70 days of age (phase 1) and six months later (phase 2), recognition memory of objects in the open field (Experiment II) with two types of intervals (3 and 24) between the trials, and working memory in the water T-maze (Experiment III) with two types of intervals between trials (10 and 30 s). The results showed that the escape latency in malnourished animals in experiment I was significantly higher than escape latency in controls. On phase 2, this difference disappeared. In Experiment II, recognition indexes of malnourished groups were significantly higher in both 3-h and 24-h intervals. In Experiment III, there was a difference only in the type of interval, as the animals took longer to achieve the criteria in the 30-s interval. These results suggest that protein malnutrition caused impairments on the working memory in the Morris water maze, but these deficits disappeared after nutritional recovery. Recognition memory was impaired by postnatal malnutrition independently of the type of interval. Working memory in the water T-maze was not affected by postnatal protein malnutrition.

A short wakeful rest immediately after new learning boosts verbal memory retention over several minutes. This memory boost is observed both in healthy people and in patients with amnesia, including patients with amnestic mild cognitive impairment (aMCI) and mild Alzheimer’s Disease (AD). Wakeful resting is hypothesized to boost memory by protecting the memory consolidation (strengthening) process from interfering sensory stimulation. The effect of a short wakeful rest immediately after new learning has, to this stage, been tested only over standard retention intervals (≤1 hour). The objectives of this PhD project were to: 1.) examine whether a short wakeful rest immediately after learning boosts memory over a longer retention interval (7 days) in healthy older adults (Experiment 1, Experiment 2) and aMCI/mild AD patients (Experiment 3) 2.) investigate whether intentional rehearsal is necessary and sufficient to boost memory during wakeful rest, over both short-term (15-minute) and long-term (7-day) delays (Experiment 4, 5 and 6) 3.) compare the effect of a short post-learning rest on retention as assessed via cued recall, free recall and recognition, both over short delays (15 minutes) and long delays (7 days and 4 weeks) (Experiments 4,5 and 7) 4.) examine whether a short wakeful rest immediately after learning boosts retention of real-life-like stimuli (face/name paired associates) in healthy older adults and aMCI/mild AD patients (Experiment 8, Experiment 9) In order to accomplish these aims, several samples of healthy adults and amnesic patients were tested, utilising a range of experimental designs. In all experiments, the learning of new material was followed immediately (i) by a brief wakeful rest, or (ii) by a cognitively demanding task. A delayed memory test took place after a range of intervals. The results demonstrate a pronounced memory enhancement over 15-30 minutes and 7 days in aMCI/mild AD patients via a short post-learning wakeful rest. A similar, albeit less pronounced 7-day memory benefit via post-learning wakeful rest was found in healthy older adults. Moreover, it was found that post-learning wakeful resting boosted 7-day recognition memory in healthy older adults, even when the learned material could not be rehearsed intentionally. Although intentional rehearsal did provide a 7-day memory improvement in healthy older adults, the present results indicate that it is not necessary in order to enhance long-term recognition memory via wakeful resting. The long-lived memory benefit gained via post-learning wakeful rest was shown to last at least 4 weeks in healthy adults, and free recall tests were more sensitive to the post-learning delay manipulation than cued recall tests. Finally, healthy controls and aMCI/mild AD patients who were able to learn face/name pairs showed enhanced 30-minute retention of these stimuli following wakeful rest conditions. The present findings demonstrate that both clinical and non-clinical populations are able to retain more new information over long periods, if the time interval immediately after new learning is devoid of further sensory stimulation. These results contribute to a growing body of literature stipulating that minimizing sensory stimulation frees early memory consolidation resources, allowing for superior offline consolidation of verbal material over a standard (≤1 hour) interval. The findings of this thesis extend this hypothesis over (i) a longer interval and (ii) to real-life-like stimuli, and these results are examined in light of memory consolidation theory. Implications of the premise of retroactive interference as a mechanism of longer-term forgetting are discussed.

A desnutrição protéica em estágios iniciais da vida produz alterações estruturais, neuroquímicas e funcionais no sistema nervoso central, podendo causar prejuízos no desenvolvimento cognitivo e comportamental. Assim, o objetivo do presente estudo foi o de investigar os efeitos da desnutrição protéica pós-natal em tarefas que avaliam a aprendizagem e memória. Estas investigações foram feitas comparando o desempenho de ratos Wistar, submetidos à desnutrição protéica (6% de proteína) durante a lactação e pós-lactação com animais controle (16% de proteína), nas tarefas de memória operacional no Labirinto Aquático de Morris (LAM), memória de reconhecimento de objetos no campo aberto e memória operacional no Labirinto em T Aquático (LTA). No experimento I a tarefa foi localizar uma plataforma oculta que mudou de posição a cada sessão diária com quatro tentativas no LAM. A memória a longo prazo foi avaliada após seis meses utilizando-se o mesmo procedimento. No experimento II os animais foram submetidos à tarefa de reconhecimento de objetos no campo aberto, em duas tentativas com diferentes intervalos intertentativas (3 e 24h). Na 1a tentativa o animal foi habituado a um objeto A e na 2a, discriminava o objeto A de um novo objeto B. No experimento III foi testado o desempenho dos animais no LTA, sendo inicialmente forçados a alternar os braços de entrada e, após esta fase, escolher em qual braço deveria entrar para encontrar a plataforma fixada em uns dos braços. Os resultados mostraram déficits na aprendizagem e memória dos animais desnutridos no experimento I. Porém, na fase 2 a diferença entre os grupos nutricionais desapareceu. No experimento II, o índice de reconhecimento dos animais desnutridos foi significativamente maior que dos controle nos intervalos de 3 e 24h. No experimento III, houve diferença apenas do tipo de intervalo, sendo que no intervalo de 30s todos os animais demoraram mais para atingirem o critério proposto. Com estes resultados se pode concluir que a desnutrição protéica pós-natal causou prejuízos na memória operacional no LAM; porém, este déficit diminuiu seis meses depois, sugerindo que a recuperação nutricional foi eficiente para reverter as alterações causadas pela desnutrição. A tarefa de memória operacional no LTA não foi afetada por este modelo de desnutrição, independente do intervalo. Entretanto, a tarefa de memória de reconhecimento foi prejudicada pela desnutrição pós-natal, independente do intervalo, e a atividade exploratória somente no intervalo de 24h. / Early protein malnutrition induces structural, neurochemical and functional changes in the Central Nervous System leading to alterations in cognitive and behavioral development of rats such as spatial learning and memory. The aim of this work was to investigate the effects of postnatal protein malnutrition on learning and memory tasks. This evaluation was done by comparing the performance of previously malnourished male Wistar rats (6% protein) from birth to 49 days of age with well-nourished control animals (16% protein) in three experiments: working memory tasks in the Morris water maze (Experiment I) at 70 days of age (phase 1) and six months later (phase 2), recognition memory of objects in the open field (Experiment II) with two types of intervals (3 and 24) between the trials, and working memory in the water T-maze (Experiment III) with two types of intervals between trials (10 and 30 s). The results showed that the escape latency in malnourished animals in experiment I was significantly higher than escape latency in controls. On phase 2, this difference disappeared. In Experiment II, recognition indexes of malnourished groups were significantly higher in both 3-h and 24-h intervals. In Experiment III, there was a difference only in the type of interval, as the animals took longer to achieve the criteria in the 30-s interval. These results suggest that protein malnutrition caused impairments on the working memory in the Morris water maze, but these deficits disappeared after nutritional recovery. Recognition memory was impaired by postnatal malnutrition independently of the type of interval. Working memory in the water T-maze was not affected by postnatal protein malnutrition.

Auditory recognition memory in non-human primates is not well understood. Monkeys have difficulty acquiring auditory memory tasks, and limited capability maintaining auditory information over memory delays, relative to studies of visual memory. Neural substrates of auditory discrimination and recognition memory depend on superior temporal gyrus (STG), instead of rhinal cortex necessary for visual memory (Fritz et al., 2005). The current project assessed behavioral and neural correlates of auditory processing and memory function in monkeys, particularly focusing on the dorsal temporal pole (dTP), the rostral portion of STG. Chapter 2 examined recognition memory of monkeys under influences of various sound types. In a delayed matching-to-sample (DMTS) task, rhesus monkeys were trained to determine if two sounds, separated by a 5-second delay, were same (match trials) or different (nonmatch trials). Results demonstrated monkey vocalizations served as better cues than other sound types for auditory memory performance. Memory improvements may be due to familiarity and biological significance of con-specific sounds, analogous to using facial stimuli during visual tasks. Chapter 3 examined neuronal activity of dTP, when two monkeys performed an auditory DTMS task and listened to sound stimuli. Population encoding of sample stimuli in dTP was closely associated with memory accuracy. Moreover, a suppression effect on identical sounds was present, similar to processing in the ventral visual processing stream, inferior temporal cortex (ITC) and ventral temporal pole (vTP). Delay-related activity of dTP was weak, limited and short-lived, in contrast to visual studies reporting sustained activity over memory delays in ITC, vTP and prefrontal cortex. The findings provide preliminary evidence on why monkeys show limited memory capability, compared to visual memory, for auditory information. Neurons of dTP were sound-selective, and mainly evoked by one to four discrete stimuli only. Sound types and simple acoustic properties of sound stimuli cannot completely account for response profiles of dTP neurons. The findings suggest dTP is a higher order auditory area, and receives information from various auditory areas along STG. Dorsal temporal pole fits into proposals of neural networks for auditory processing, in which a hierarchical organization of information flow exists within the primate auditory nervous system.

Disruptions in memory are a hallmark feature of several psychiatric diseases. These illnesses are often marred by an inability to recognize that a stimulus or event as been previously experienced, a phenomenon known as recognition memory. Previous study has demonstrated that cognitive disruptions reflect aberrant signaling, including disruptions in synaptic plasticity, in key regions of the brain, such as prefrontal cortex (PFC), hippocampus, and perirhinal cortex (PRh). However, in the case of recognition memory, how these disruptions arise and what specific plasticity mechanisms are involved is less clear. An understanding of the etiological factors underlying disruption and the synaptic processes involved in recognition will greatly advance the treatment and prevention of psychiatric disorders. As a result, the present thesis examined recognition memory in rodents in two experiments. In the first experiment, we blocked the endocytosis of AMPA receptors during the encoding, consolidation, or retrieval phase of object recognition memory using local PRh infusions of the cell membrane permeable Tat-GluA23Y interference peptide. Tat-GluA23Y infusion before the encoding and consolidation phases did not alter memory. In contrast, Tat-GluA23Y infusion prior to the retrieval phase significantly disrupted memory. These results indicate a distinct role for AMPA receptor endocytosis during a specific phase (retrieval) of visual recognition memory. In the second experiment, pregnant dams were treated with PolyI:C (4mg/kg, i.v.) on gestational day (GD) 15, and both the male and female offspring of these rats were tested as young adults in three different recognition memory tests: spontaneous novel object recognition, novel object location recognition, and object-in-place recognition. Male, but not female, rats were impaired in an object-in-place memory test that depends on processing between medial temporal lobe and PFC. However, neither male nor female rats were impaired on tests of simpler discriminations dependent on the medial temporal lobe. These findings support clinical studies demonstrating impaired object location binding in clinical populations and further demonstrate the plausibility of prenatal immune activation as an etiological factor in neurodevelopmental disease. Taken together, these results highlight the importance of a specific form of synaptic plasticity during the recognition of familiar stimuli and demonstrate that early life adversity can disrupt recognition memory processes.

Emotional information is commonly assumed to be recognized more accurately than neutral information. While emotionality enhances recognition accuracy, it also induces a more liberal response bias. In this study, the effects of arousal and valence axes of emotion on recognition memory accuracy and liberal bias were examined in young and older adults, for emotional words. For this purpose, memory was assessed with a surprise old/new recognition task, based on Signal Detection Theory. There are also some factors regarding words that influence visual word recognition. One is the dissociation between consonants and vowels / consonants and vowels are processed differently. In the study session, the participants were instructed to count vowels within a word under incidental encoding. Since vowels constrain lexical selection less tightly than consonants, deciding how many vowels each word contained is compatible with the idea that the vowels should be processed faster. The results of the recognition session showed that young adults recognized more accurately as compared to older adults, replicating the age effect. Valence differences of words also showed a significant effect on memory performance, that is positive words were recognized better in both groups. On the other hand, it was observed that there was a significant bias to respond as &lsquo / old&rsquo / only to positive words in older group / whereas young adults showed a liberal bias to negative words. This age-related difference suggested that older adults regulated their emotion in favour of maintaining well-being, even incidentally. Considering individual differences and mood state in emotional word processing is essential so personality traits and current mood states were assessed by commonly used Five Factor Personality Inventory and Positive and Negative Affect Schedule respectively. Except &lsquo / openness to experience&rsquo / , other personality dimensions did not predict recognition memory performance for emotional words.

Disruptions in memory are a hallmark feature of several psychiatric diseases. These illnesses are often marred by an inability to recognize that a stimulus or event as been previously experienced, a phenomenon known as recognition memory. Previous study has demonstrated that cognitive disruptions reflect aberrant signaling, including disruptions in synaptic plasticity, in key regions of the brain, such as prefrontal cortex (PFC), hippocampus, and perirhinal cortex (PRh). However, in the case of recognition memory, how these disruptions arise and what specific plasticity mechanisms are involved is less clear. An understanding of the etiological factors underlying disruption and the synaptic processes involved in recognition will greatly advance the treatment and prevention of psychiatric disorders. As a result, the present thesis examined recognition memory in rodents in two experiments. In the first experiment, we blocked the endocytosis of AMPA receptors during the encoding, consolidation, or retrieval phase of object recognition memory using local PRh infusions of the cell membrane permeable Tat-GluA23Y interference peptide. Tat-GluA23Y infusion before the encoding and consolidation phases did not alter memory. In contrast, Tat-GluA23Y infusion prior to the retrieval phase significantly disrupted memory. These results indicate a distinct role for AMPA receptor endocytosis during a specific phase (retrieval) of visual recognition memory. In the second experiment, pregnant dams were treated with PolyI:C (4mg/kg, i.v.) on gestational day (GD) 15, and both the male and female offspring of these rats were tested as young adults in three different recognition memory tests: spontaneous novel object recognition, novel object location recognition, and object-in-place recognition. Male, but not female, rats were impaired in an object-in-place memory test that depends on processing between medial temporal lobe and PFC. However, neither male nor female rats were impaired on tests of simpler discriminations dependent on the medial temporal lobe. These findings support clinical studies demonstrating impaired object location binding in clinical populations and further demonstrate the plausibility of prenatal immune activation as an etiological factor in neurodevelopmental disease. Taken together, these results highlight the importance of a specific form of synaptic plasticity during the recognition of familiar stimuli and demonstrate that early life adversity can disrupt recognition memory processes.

Positive sequential dependencies occur when the response on the current trial n is positively correlated with the response on trial n-1. This was recently observed in a Judgment of Frequency (JOF) task (Malmberg and Annis, 2011). A model of positive sequential dependencies was developed in the REM framework (Shiffrin & Steyvers, 1997) by assuming that features that represent the current test item in a retrieval cue carry over from the previous retrieval cue. To assess the model, we sought a set of data that allows us to distinguish between frequency similarity and item similarity. Therefore, we chose to use a JOF task in which we manipulated the item similarity of the stimuli by presenting either landscape photos (high similarity), or photos of everyday objects such as shoes, cars, etc (low similarity). Similarity was modeled by assuming either that the item representations share a proportion of features or by assuming that the exemplars from different stimulus classes vary in the distinctiveness or diagnosticity. The model fits indicated that the best way to model similarity was to assume that items share a proportions of features.

Recognition is the cognitive process by which we judge whether a given object, person, place, or event has occurred in our previous experience or is new to us. According to signal detection theory, old/new recognition decisions are based on how much evidence one finds in memory that an item has appeared previously (e.g., its familiarity) but can be affected substantially by response bias, a general proclivity to respond “old” or “new.” When experimental conditions evoke a “conservative” response bias, participants will require a relatively high amount of memory evidence before calling an item “old” and will give a high proportion of “new” responses to both old and new items; when conditions promote a “liberal” bias, participants will relax their required level of memory evidence and will call a high proportion of both old and new items “old.” Response bias is usually analyzed at a group level, but substantial individual differences in bias can underlie group means. These differences suggest that, independent of any experimental manipulation, some people require more memory evidence than others before they are willing to call an item “old.” The central motivation for the present work is the possibility that these individual differences are meaningful and reflect bias levels that inhere within individuals. Seven experiments were designed to test the hypothesis that response bias can be characterized as an intra-individually stable cognitive “trait” with an influence extending beyond recognition memory. The present experiments are based on the expectation that if response bias is a cognitive trait, it should a) be consistent within an individual across time, to-be-recognized materials, and situations; b) generalize beyond recognition memory to other tasks involving binary decisions based on accumulated evidence; c) be associated with personality traits that represent one’s willingness to take action based on limited information; and d) carry consequences for recognition in applied settings. The results indicated substantial within-individual bias consistency in two recognition tests separated by 10 minutes (Experiment 1) and a similar level of consistency when the two tests were separated by one week (Experiment 2). Bias was strongly correlated across the stimulus domains of words and paintings (Experiment 3) and words and faces (Experiment 7). Correlations remained significant across two ostensibly independent experiments differing markedly in context and materials and separated by an average of 2.5 weeks (Experiments 6 and 7). Recognition bias predicted frequency of false recall in the Deese-Roediger-McDermott (DRM) paradigm (Experiment 4) and false alarms in an eyewitness identification task (Experiment 7). No relationship was detected between bias and grain size in estimation from general knowledge (Experiment 2), risk avoidance through the use of report option on a trivia task (Experiments 4 and 5), or speed and accuracy on a go-no go task (Experiment 6). Personality measures suggested relationships between response bias and need for cognition, maximizing versus satisficing tendencies, and regret proneness. Collectively, these findings support the idea that response bias as measured in recognition memory tasks is a partial function of stable individual differences that have broad significance for cognition. / Graduate

Amnestic mild cognitive impairment (aMCI) has been established as a significant risk factor for Alzheimer‟s disease (AD) and in many cases this state appears to represent an early or incipient stage of AD. Due to difficulties with the diagnosis and prognosis of aMCI and AD, as well as with the projected significant socioeconomic ramifications of AD, there is a need to establish sensitive and reliable biomarkers. The application of event related potentials (ERPs) has been recommended in this context due to their reliability, non-invasive nature, inexpense and relatively widespread availability. This thesis aims to further assess the potential efficacy of ERP markers for such applications. These aims are pursued via investigations of ERPs in healthy ageing, MCI and AD utilising an explicit recognition task that requires the use of key cognitive/memory processes which are often impaired in aMCI and AD. Two ERP effects were analysed: the N400effect which is assumed to index familiarity or trace strength, and the Late Positive Complex (LPC) which appears to index recollection or decision-related factors such as accuracy. Chapter 3 reports ERP and recognition accuracy comparisons between samples of 15 young (mean age = 21.73 years) and 15 older, cognitively healthy adults (mean age = 66.67 years). ERP data were acquired during performance of a word recognition task with high and low memory load conditions (long and short encoding lists, respectively). At test, participants were required to make old/new judgements to visually presented words. There was a trend for young participants to perform more accurately than the older sample, especially on the long list; although these differences only approached significance. However, the N400 old/new effect was found to be significantly reduced in the old compared with the young participants across memory load conditions. LPC old/new effects were generally not observed and this is likely due to the nature of the task which generally places minimal demands on controlled retrieval processes. These results indicate that the N400 effect may be more sensitive to the deleterious effects of ageing on recognition memory-related process(s) than behavioural measures of memory accuracy. Consistent with the view that the N400 indexes familiarity, these results are in accordance with other evidence that familiarity is affected in healthy ageing. The same methodology was used to compare ERPs between aMCI (n = 11) and healthy older adults (n = 11) in Chapter 4. The aMCI participants performed significantly worse than vi healthy elderly participants in discriminating „old‟ from „new‟ words. In the corresponding ERP data, healthy control sample demonstrated significant N400 old/new effects at parietal electrode locations, whereas aMCI participants failed to demonstrate significant N400 old/new effects at any electrode location. Again, LPC effects were not observed in either sample. The absence of significant N400 effects in aMCI participants may reflect a disruption of familiarity-based recognition in aMCI. These results converge with other evidence that the N400 effect may be a sensitive ERP marker useful for detecting, monitoring and/or predicting amnestic related cognitive decline. There are reported variations in underlying causes and sequelae of aMCI (e.g., not all progress to AD). Chapter 5 reports an exploratory investigation aimed at determining whether baseline ERPs differentiate between aMCI participants on the basis of their clinical diagnosis at follow-up. Baseline ERP data were compared in a small sample (n = 7) of aMCI participant who remained cognitively stable at 12-month follow-up (SMCI) with two aMCI participants who progressed to meet an AD diagnosis (PMCI) at the latter time-point. There was a trend for PMCI participants to display smaller old/new effects. However, only one participant displayed significantly smaller N400 old/new effects under low memory load conditions. Interestingly, this participant was also more impaired in baseline cognitive functioning. Chapter 6 examines the relationship between baseline ERPs and performance on neuropsychological assessment at 12-month follow-up in a sample of aMCI and AD participants (n =13) in order to investigate whether ERPs may prove informative for prognoses regarding general trajectories of cognitive decline, irrespective of diagnostic status. Smaller N400 old/new effects (at Fz and CPz) were associated with poorer performance on tasks assessing global cognitive functioning and auditory attention span. Reduced LPC old/new differences were related to poorer performance on tasks assessing global cognitive functioning, verbal learning and memory and better performance on a task assessing working memory at follow-up. In contrast to these results, no relationships were observed between ERP effects and concurrent performance on neuropsychological assessment in this sample, or in 42 elderly participants (including healthy, aMCI and AD), as described in Chapter 7. Taken together these results suggest that ERPs may be more sensitive in predicting future rather than concurrent cognitive functioning and may provide a more objective measure/classification of cognitive impairment vii irrespective of diagnosis. These outcomes are particularly novel as the relationship between baseline ERP data and follow-up neuropsychological measures does not appear to have been systematically reported in the literature to date. Collectively these findings indicate that ERP measure(s), particularly the N400 old/new effect, are sensitive to neurocognitive changes associated with ageing and aMCI, and may prove a useful biomarker for the early detection of AD. This is interesting as the effects of healthy ageing and pathological decline on the N400 from explicit recognition tasks have not been thoroughly explored. Moreover, the N400 (and perhaps, to a lesser degree, LPC) effect(s) appear to have substantial value for informing future prognoses of subsequent cognitive trajectories, at least for persons with amnestic impairment. These results may have significant clinical implications pertaining to the selection and application of efficacious therapeutic interventions in aMCI and AD.