Dopamine and memory dedifferentiation in aging.

The dedifferentiation theory of aging proposes that a reduction in the specificity of neural representations causes declines in complex cognition as people get older, and may reflect a reduction in dopaminergic signaling. The present pharmacological fMRI study investigated episodic memory-related dedifferentiation in young and older adults, and its relation to dopaminergic function, using a randomized placebo-controlled double-blind crossover design with the agonist Bromocriptine (1.25mg) and the antagonist Sulpiride (400mg). We used multi-voxel pattern analysis to measure memory specificity: the degree to which distributed patterns of activity distinguishing two different task contexts during an encoding phase are reinstated during memory retrieval. As predicted, memory specificity was reduced in older adults in prefrontal cortex and in hippocampus, consistent with an impact of neural dedifferentiation on episodic memory representations. There was also a linear age-dependent dopaminergic modulation of memory specificity in hippocampus reflecting a relative boost to memory specificity on Bromocriptine in older adults whose memory was poorer at baseline, and a relative boost on Sulpiride in older better performers, compared to the young. This differed from generalized effects of both agents on task specificity in the encoding phase. The results demonstrate a link between aging, dopaminergic function and dedifferentiation in the hippocampus.This research was funded mainly by a Fellowship to AMM from Research into Ageing, UK, and by an RCUK Academic Fellowship at the University of Edinburgh. Some of the research was conducted by Hunar Abdulrahman as part of a dissertation for the MSc in Neurosciences at the University of Edinburgh. The research was also supported by a Human Brain Project grant from the National Institute of Mental Health and the National Institute of Biomedical Imaging & Bioengineering. PCF was supported by a Wellcome Trust Senior Fellowship in Clinical Science, and by the Bernard Wolfe Health Neuroscience Fund. ETB is a part-time (50%) employee and shareholder of GSK. AMM is a member of the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative, Grant number G0700704/84698.This is the accepted manuscript. The final version is available at http://dx.doi.org/10.1016/j.neuroimage.2015.03.03

Working Memory Training in Amnestic and Non-amnestic Patients With Mild Cognitive Impairment: Preliminary Findings From Genotype Variants on Training Effects

Working memory training (WMT) effects may be modulated by mild cognitive impairment (MCI) subtypes, and variations in APOE-epsilon (APOE-ε) and LMX1A genotypes. Sixty-one individuals (41 men/20 women, mean age 66 years) diagnosed with MCI (31 amnestic/30 non-amnestic) and genotyped for APOE-ε and LMX1A completed 4 weeks/20–25 sessions of WMT. Cognitive functions were assessed before, 4 weeks and 16 weeks after WMT. Except for Processing Speed, the non-amnestic MCI group (naMCI) outperformed the amnestic MCI (aMCI) group in all cognitive domains across all time-points. At 4 weeks, working memory function improved in both groups (p < 0.0001), but at 16 weeks the effects only remained in the naMCI group. Better performance was found after training for the naMCI patients with LMX1A-AA genotype and for the APOE-ε4 carriers. Only the naMCI-APOE-ε4 group showed improved Executive Function at 16 weeks. WMT improved working memory and some non-trained cognitive functions in individuals with MCI. The naMCI group had greater training gain than aMCI group, especially in those with LMX1A-AA genotype and among APOE-ε4-carriers. Further research with larger sample sizes for the subgroups and longer follow-up evaluations is warranted.publishedVersio

Healthy ageing reduces the precision of episodic memory retrieval.

Episodic memory declines with older age, but it is unresolved whether this decline reflects reduced probability of successfully retrieving information from memory, or decreased precision of the retrieved information. Here, we used continuous measures of episodic memory retrieval in combination with computational mixture modeling of participants' retrieval errors to distinguish between these two potential accounts of age-related memory deficits. In three experiments, young and older participants encoded stimulus displays consisting of everyday objects varying along different perceptual features (e.g., location, color and orientation) in a circular space. At test, participants recreated the features of studied objects using a continuous response dial. Across all 3 experiments, we observed significant age-related declines in the precision of episodic memory retrieval, whereas significant age differences in retrieval success were limited to the most challenging task condition. Reductions in mnemonic precision were evident across different object features retained in long-term memory and persisted after controlling for age-related decreases in the fidelity of perception and working memory. The findings highlight impoverished precision of memory representations as one factor contributing to age-related episodic memory loss and suggest that the cognitive and neural changes associated with older age may differentially affect distinct aspects of episodic retrieval. (PsycINFO Database Record (c) 2020 APA, all rights reserved).This study was funded by BBSRC grant BB/L02263X/1 and James S. McDonnell Foundation Scholar Award #220020333 awarded to J.S.S., and was carried out within the University of Cambridge Behavioural and Clinical Neuroscience Institute, funded by a joint award from the Medical Research Council and the Wellcome Trust

Investigating the relationship between impulsivity and executive function in Parkinson’s disease, and healthy older and younger participants: A quantitative database and real-world study.

Executive function (EF) in this study will be explored in older healthy controls and Parkinson’s Disease patients, with regards to working memory (WM) in younger healthy controls. Past literature suggests a lack of understanding between EF, WM and impulsivity despite vast research that shows the relationship between these concepts are related to a multitude of negative behaviours such as substance abuse (Moeller et al., 2004), addiction (Zhou et al., 2014; 2016), and the development of impulsive-compulsive disorders (ICDs) in neurodegenerative diseases such as Parkinson’s (Foster et al., 2013).The present study intends to build on previous literature by investigating the relationship between the two variables in 102 younger healthy controls, 196 older healthy controls, and 498 PD patients. Correlation analyses supported literature that suggests impulsivity is higher in younger participants and that the relationship between impulsivity and EF is different across age groups; however, previous assumptions that PD patients who have not yet begun medication will be less impulsive than age-matched controls and therefore exhibit an altered relationship between their EF scores were not met. Future research should expand on data using unmedicated PD patients to better understand the relationship between impulsivity and EF, and the development of ICDs

Evidence for adult age-invariance in associative false recognition

Older people are more prone to memory distortions and errors than young people, but do not always show greater false recognition in the Deese-Roediger-McDermott (DRM) task. We report two preregistered experiments investigating whether recent findings of age-invariant false recognition extend to designs in which studied items are blocked. According to Tun, Wingfield, Rosen, & Blanchard (1998), age effects on false recognition in the DRM task are due to a greater reliance on gist processing which is enhanced under blocked study conditions. Experiment 1 assessed false recognition in an online variant of the DRM task where words were presented visually, with incidental encoding. The results showed Bayesian evidence against greater false recognition by older adults, whether lures were semantically associated with studied lists, or perceptually related (presented in the same distinctive font as studied lists) or both. Experiment 2 used a typical DRM procedure with auditory lists and intentional encoding, closely reproducing Tun et al.’s (1998) Experiment 2 but omitting an initial test of recall. The results showed evidence against an age-related increase in critical lure false recognition under these conditions. Together, the data suggest that older people do not make more associative memory errors in recognition tests than young people

Age differences in retrieval-related reinstatement reflect age-related dedifferentiation at encoding

Age-related reductions in neural selectivity have been linked to cognitive decline. We examined whether age differences in the strength of retrieval-related cortical reinstatement could be explained by analogous differences in neural selectivity at encoding, and whether reinstatement was associated with memory performance in an age-dependent or an age-independent manner. Young and older adults underwent fMRI as they encoded words paired with images of faces or scenes. During a subsequent scanned memory test participants judged whether test words were studied or unstudied and, for words judged studied, also made a source memory judgment about the associated image category. Using multi-voxel pattern similarity analyses, we identified robust evidence for reduced scene reinstatement in older relative to younger adults. This decline was however largely explained by age differences in neural differentiation at encoding; moreover, a similar relationship between neural selectivity at encoding and retrieval was evident in young participants. The results suggest that, regardless of age, the selectivity with which events are neurally processed at the time of encoding can determine the strength of retrieval-related cortical reinstatement

Avaliação da Atenção com recurso ao Teste da Galeria Virtual

Orientação: Jorge Oliveira ; co-orientação: Paulo LopesO presente estudo tem como objetivo específico avaliar o desempenho de participantes com idade superior a 60 anos, na realização da prova da Galeria Virtual de forma a poder ser feita uma comparação relativamente à prova Color Trail Test, d2, FAB (Frontal Assessment Battery) e MoCA (Montreal Cognitive Assessment) a fim de se comprovar se esta prova é um bom preditor da avaliação do constructo da Atenção e permitir aferir a sua validade convergente. A Galeria Virtual é uma prova em ambiente virtual que avalia o contructo da Atenção, originalmente integrada na bateria sistémica de Lisboa 2.0. Esta prova consiste na apresentação de três sequências de quadros distintos em que o participante inicialmente tem de encontrar as diferenças entre dois quadros apresentados lado a lado. Existem sete diferenças entre os dois quadros apresentados. O segundo conjunto de quadros consiste em um quadro central que é dividido em várias partes, em que o sujeito tem de clicar na figura de fora e na figura de dentro, de modo a esta desaparecer. No terceiro conjunto de quadros, os participantes têm de encontrar cinco figuras destacadas nos quadros que estão demonstrados em cima. A amostra é constituída por 27 participantes com idades compreendidas entre os 65 e os 92 anos, com uma média de 76. Através da análise dos resultados é possivel concluir que existe uma correlação entre as provas do Color Trail Test e as provas da Galeria Virtual, significando que esta tem uma avaliação mais executiva.The present study has the specific objective of evaluating the performance of participants over 60 years old, in the accomplishment of the Art Gallery Test in order to compare the Color Trail Test, d2, FAB (Frontal Assessment Battery) and MoCA (Montreal Cognitive Assessment) in order to verify if this test is a good predictor of the evaluation of the Attention construct and allow to verify its convergent validity. The Art Gallery is a proven virtual environment that evaluates the contruct of attention, originally built in the assessment battery of Lisbon 2.0. This test consists of the presentation of three sequences of distinct frames in which the participant initially has to find the differences between two frames presented side by side. There are seven differences between the two frames presented. The second set of frames consists of a central frame that is divided into several parts, in which the participant has to click on the outside figure and the figure inside so that it disappears. In the third set of paintings, participants have to find five figures highlighted on the set of paintings that are shown above. The sample consisted of 27 participants aged between 65 and 92 years, with a mean of 76. Through the analysis of the results it is possible to conclude that there is a correlation between the tests of the Color Tail Test and the tests of the Art Gallery meaning that it has a more executive evaluation

Healthy aging reduced the precision of episodic memory retrieval

Episodic memory declines with older age, but it is unresolved whether this decline reflects reduced probability of successfully retrieving information from memory, or decreased precision of the retrieved information. Here, we used continuous measures of episodic memory retrieval in combination with computational modelling of participants’ retrieval errors to distinguish between these two potential accounts of age-related memory deficits. In three experiments, young and older participants encoded stimulus displays consisting of everyday objects varying along different perceptual features (e.g., location, colour and orientation) in a circular space. At test, participants recreated the features of studied objects using a continuous response dial. Across all three experiments, we observed significant age-related declines in the precision of episodic memory retrieval, whereas significant age differences in retrieval success were limited to the most challenging task condition. Reductions in mnemonic precision were evident across different object features retained in long-term memory, and persisted after controlling for age-related decreases in the fidelity of perception and working memory. The findings highlight impoverished precision of memory representations as one factor contributing to age-related episodic memory loss, and suggest that the cognitive and neural changes associated with older age may differentially affect distinct aspects of episodic retrieval.Action Contro