The importance of the ventromedial prefrontal cortex for associative memory in older adults: A latent structural equation analysis.

Older adults show relatively minor age-related decline in memory for single items, while their memory for associations is markedly reduced. Inter-individual differences in memory function in older adults are substantial but the neurobiological underpinnings of such differences are not well understood. In particular, the relative importance of inter-individual differences in the medio-temporal lobe (MTL) and the lateral prefrontal cortex (PFC) for associative and item recognition in older adults is still ambiguous. We therefore aimed to first establish the distinction between inter-individual differences in associative memory (recollection-based) performance and item memory (familiarity-based) performance in older adults and subsequently link these two constructs to differences in cortical thickness in the MTL and lateral PFC regions, in a latent structural equation modelling framework. To this end, a sample of 160 older adults (65-75 years old) performed three intentional item-associative memory tasks, of which a subsample (n â€‹= â€‹72) additionally had cortical thickness measures in MTL and PFC regions of interest available. The results provided support for a distinction between familiarity-based item memory and recollection-based associative memory performance in older adults. Cortical thickness in the ventro-medial prefrontal cortex was positively correlated with associative recognition performance, above and beyond any relationship between item recognition performance and cortical thickness in the same region and between associative recognition performance and brain structure in the MTL (parahippocampus). The findings highlight the relative importance of the ventromedial prefrontal cortex in allowing for intentional recollection-based associative memory functioning in older adults.

Structure-function associations of successful associative encoding.

Functional magnetic resonance imaging (MRI) studies have demonstrated a critical role of hippocampus and inferior frontal gyrus (IFG) in associative memory. Similarly, evidence from structural MRI studies suggests a relationship between gray-matter volume in these regions and associative memory. However, how brain volume and activity relate to each other during associative-memory formation remains unclear. Here, we used joint independent component analysis (jICA) to examine how gray-matter volume and brain activity would be associated during associative encoding, especially in medial-temporal lobe (MTL) and IFG. T1-weighted images were collected from 27 young adults, and functional MRI was employed during intentional encoding of object pairs. A subsequent recognition task tested participants' memory performance. Unimodal analyses using voxel-based morphometry revealed that participants with better associative memory showed larger gray-matter volume in left anterior hippocampus. Results from the jICA revealed one component that comprised a covariance pattern between gray-matter volume in anterior and posterior MTL and encoding-related activity in IFG. Our findings suggest that gray matter within the MTL modulates distally distinct parts of the associative encoding circuit, and extend previous studies that demonstrated MTL-IFG functional connectivity during associative memory tasks.

Differential Effects of Encoding Instructions on Brain Activity Patterns of Item and Associative Memory.

Evidence from neuroimaging studies suggests a critical role of hippocampus and inferior frontal gyrus (IFG) in associative relative to item encoding. Here, we investigated similarities and differences in functional brain correlates for associative and item memory as a function of encoding instruction. Participants received either incidental (animacy judgments) or intentional encoding instructions while fMRI was employed during the encoding of associations and items. In a subsequent recognition task, memory performance of participants receiving intentional encoding instructions was higher compared with those receiving incidental encoding instructions. Furthermore, participants remembered more items than associations, regardless of encoding instruction. Greater brain activation in the left anterior hippocampus was observed for intentionally compared with incidentally encoded associations, although activity in this region was not modulated by the type of instruction for encoded items. Furthermore, greater activity in the left anterior hippocampus and left IFG was observed during intentional associative compared with item encoding. The same regions were related to subsequent memory of intentionally encoded associations and were thus task relevant. Similarly, connectivity of the anterior hippocampus to the right superior temporal lobe and IFG was uniquely linked to subsequent memory of intentionally encoded associations. Our study demonstrates the differential involvement of anterior hippocampus in intentional relative to incidental associative encoding. This finding likely reflects that the intent to remember triggers a specific binding process accomplished by this region.

Dopamine Receptor Genes Modulate Associative Memory in Old Age.

Previous research shows that associative memory declines more than item memory in aging. Although the underlying mechanisms of this selective impairment remain poorly understood, animal and human data suggest that dopaminergic modulation may be particularly relevant for associative binding. We investigated the influence of dopamine (DA) receptor genes on item and associative memory in a population-based sample of older adults (n = 525, aged 60 years), assessed with a face-scene item associative memory task. The effects of single-nucleotide polymorphisms of DA D1 (DRD1; rs4532), D2 (DRD2/ANKK1/Taq1A; rs1800497), and D3 (DRD3/Ser9Gly; rs6280) receptor genes were examined and combined into a single genetic score. Individuals carrying more beneficial alleles, presumably associated with higher DA receptor efficacy (DRD1 C allele; DRD2 A2 allele; DRD3 T allele), performed better on associative memory than persons with less beneficial genotypes. There were no effects of these genes on item memory or other cognitive measures, such as working memory, executive functioning, fluency, and perceptual speed, indicating a selective association between DA genes and associative memory. By contrast, genetic risk for Alzheimer disease (AD) was associated with worse item and associative memory, indicating adverse effects of APOE ε4 and a genetic risk score for AD (PICALM, BIN1, CLU) on episodic memory in general. Taken together, our results suggest that DA may be particularly important for associative memory, whereas AD-related genetic variations may influence overall episodic memory in older adults without dementia.

Training-induced changes in subsequent-memory effects: No major differences among children, younger adults, and older adults.

The neural correlates of encoding mode, or the state of forming new memory episodes, have been found to change with age and mnemonic training. However, it is unclear whether neural correlates of encoding success, termed subsequent-memory (SM) effects, also differ by age and mnemonic skill. In a multi-session training study, we investigated whether SM effects are altered by instruction and training in a mnemonic skill, and whether such alterations differ among children, younger adults, and older adults. Before and after strategy training, fMRI data were collected while participants were memorizing word pairs. In all age groups, participants receiving training showed greater performance gains than control group participants. Analysis of task-relevant regions showed training-induced reductions in SM effects in left frontal regions. Reductions in SM effects largely generalized across age and primarily reflected greater training-induced activation increases for omissions than for remembered items, indicating that training resulted in more consistent use of the mnemonic strategy. The present results reveal no major age differences in SM effects in children, younger adults, and older adults.

Behavioral correlates of changes in hippocampal gray matter structure during acquisition of foreign vocabulary.

Experience can affect human gray matter volume. The behavioral correlates of individual differences in such brain changes are not well understood. In a group of Swedish individuals studying Italian as a foreign language, we investigated associations among time spent studying, acquired vocabulary, baseline performance on memory tasks, and gray matter changes. As a way of studying episodic memory training, the language learning focused on acquiring foreign vocabulary and lasted for 10weeks. T1-weighted structural magnetic resonance imaging and cognitive testing were performed before and after the studies. Learning behavior was monitored via participants' use of a smartphone application dedicated to the study of vocabulary. A whole-brain analysis showed larger changes in gray matter structure of the right hippocampus in the experimental group (N=33) compared to an active control group (N=23). A first path analyses revealed that time spent studying rather than acquired knowledge significantly predicted change in gray matter structure. However, this association was not significant when adding performance on baseline memory measures into the model, instead only the participants' performance on a short-term memory task with highly similar distractors predicted the change. This measure may tap similar individual difference factors as those involved in gray matter plasticity of the hippocampus.

Structural brain correlates of associative memory in older adults.

Associative memory involves binding two or more items into a coherent memory episode. Relative to memory for single items, associative memory declines greatly in aging. However, older individuals vary substantially in their ability to memorize associative information. Although functional studies link associative memory to the medial temporal lobe (MTL) and prefrontal cortex (PFC), little is known about how volumetric differences in MTL and PFC might contribute to individual differences in associative memory. We investigated regional gray-matter volumes related to individual differences in associative memory in a sample of healthy older adults (n=54; age=60years). To differentiate item from associative memory, participants intentionally learned face-scene picture pairs before performing a recognition task that included single faces, scenes, and face-scene pairs. Gray-matter volumes were analyzed using voxel-based morphometry region-of-interest (ROI) analyses. To examine volumetric differences specifically for associative memory, item memory was controlled for in the analyses. Behavioral results revealed large variability in associative memory that mainly originated from differences in false-alarm rates. Moreover, associative memory was independent of individuals' ability to remember single items. Older adults with better associative memory showed larger gray-matter volumes primarily in regions of the left and right lateral PFC. These findings provide evidence for the importance of PFC in intentional learning of associations, likely because of its involvement in organizational and strategic processes that distinguish older adults with good from those with poor associative memory.

Plasticity of brain and cognition in older adults.

Aging is typically related to changes in brain and cognition, but the aging process is heterogeneous and differs between individuals. Recent research has started investigating the influence of cognitive and physical training on cognitive performance, functional brain activity, and brain structure in old age. The functional relevance of neural changes and the interactions among these changes following interventions is still a matter of debate. Here we selectively review research on structural and functional brain correlates of training-induced performance changes in healthy older adults and present exemplary longitudinal intervention studies sorted by the type of training applied (i.e., strategy-based training, process-specific training, and physical exercise). Although many training studies have been conducted recently, within each task domain, the number of studies that used comparable methods and techniques to assess behavioral and neural changes is limited. We suggest that future studies should include a multimodal approach to enhance the understanding of the relation between different levels of brain changes in aging and those changes that result from training. Investigating inter-individual differences in intervention-induced behavioral and neuronal changes would provide more information about who would benefit from a specific intervention and why. In addition, a more systematic examination of the time course of training-related structural and functional changes would improve the current level of knowledge about how learning is implemented in the brain and facilitate our understanding of contradictory results.

Association between personality traits, leisure activities, and cognitive levels and decline across 12 years in older adults.

The engagement in cognitively stimulating activities has been found to be associated with slower rates of cognitive decline in old age. In which type of activities people engage in may depend on their personality traits, which thus might have an impact on later cognitive fitness. To study these potential links, we examined the associations between Neuroticism, Extraversion, and Openness; different types of leisure activities (e.g., social, mental, physical); and cognitive ability levels and decline in older adults. Analyses were based on a sample of young-old (60-72 years old; n = 1,609) and old-old (78 years or older; n = 1,085) adults from the Swedish National Study on Aging and Care in Kungsholmen, who participated in up to five repeated measurements of cognitive abilities spanning 12 years. We used latent growth curve models to estimate cognitive levels and decline, as well as the correlations with initial personality trait levels and leisure activity engagement. In both groups, lower Neuroticism, higher Extraversion, and higher Openness levels were moderately associated with stronger engagement in all types of activities. Lower Neuroticism, higher Extraversion, and a more activity lifestyle were weakly to moderately associated with slower cognitive decline in the old-old age group. There, personality traits and activities explained 9.3% of the variance in cognitive decline after controlling for age, sex, education, and chronic diseases (which explained 9.0%). Taken together, this study provides further evidence for the connection between personality traits, activity engagement, and later cognitive decline in old age. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Stimulus material selection for the Dutch famous faces test for older adults.

Worldwide, approximately 22% of all individuals aged 50 years and older are currently estimated to fall somewhere on the Alzheimer's disease (AD) continuum, which can be roughly divided into preclinical AD, mild cognitive impairment (MCI), and AD dementia. While episodic memory loss (among other aspects) is typically required for a diagnosis of AD dementia, MCI is said to have occurred when cognitive impairment (including memory loss) is worse than expected for the person's age but not enough to be classified as dementia. On the other hand, preclinical AD can currently only be detected using biomarkers; clinical symptoms are not apparent using traditional neuropsychological tests. The main aim of the current paper was to explore the possibility of a test which could distinguish preclinical AD from normal aging. Recent scientific evidence suggests that the Famous Faces Test (FFT) could differentiate preclinical AD from normal aging up to 5 years before a clinical AD diagnosis. Problematic with existing FFTs is the selection of stimulus material. Faces famous in a specific country and a specific decade might not be equally famous for individuals in another country or indeed for people of different ages. The current article describes how famous faces were systematically selected and chosen for the Dutch older (60+) population using five steps. The goal was to design and develop short versions of the FFT for Dutch older adults of equivalent mean difficulty. In future work, these nine parallel versions will be necessary for (a) cross-sectional comparison as well as subsequent longitudinal assessment of cognitively normal and clinical groups and (b) creating personalized norms for the normal aged controls that could be used to compare performance within individuals with clinical diagnoses. The field needs a simple, cognitive test which can distinguish the earliest stages of the dementia continuum from normal aging.

Dopamine D1 receptor associations within and between dopaminergic pathways in younger and elderly adults: links to cognitive performance.

Age-related dopamine (DA) losses have been extensively demonstrated for the D2 receptor subtype. Comparatively little is known about adult age changes regarding D1 receptors. In this study, we demonstrate marked age-related D1 receptor losses in striatal, limbic, and cortical areas using positron emission tomography and the radioligand [(11)C]SCH23390 in humans. Interregional correlations of binding potential (BP) values were high for areas within DA pathways in younger and elderly adults alike. Furthermore, interregional correlations in D1 BP between DA pathways were uniformly high in younger adults, indicating that D1 receptor densities in striatal, limbic, and cortical areas are not regulated independently, despite dopaminergic innervation from different midbrain areas. For elderly adults, between-pathway correlations of D1 receptor densities were preserved only between mesolimbic and mesocortical areas, whereas striatal BPs were weakly related to those in limbic and neocortical regions. Importantly, weak between-pathway correlations in elderly adults were found only for the slower half of the sample when BP was estimated during a cognitive interference task. These results suggest that D1 receptor densities in different pathways are not regulated independently in younger adults, but segregate in older age, and that this segregation of D1 receptor systems may be related to age-related cognitive slowing.

Preclinical Alzheimer's dementia: a useful concept or another dead end?

The term, preclinical dementia, was introduced in 2011 when new guidelines for the diagnosis of Alzheimer's dementia (AD) were published. In the intervening 11 years, many studies have appeared in the literature focusing on this early stage. A search conducted in English on Google Scholar on 06.23.2022 using the term "preclinical (Alzheimer's) dementia" produced 121, 000 results. However, the label is arguably more relevant for research purposes, and it is possible that the knowledge gained may lead to a cure for AD. The term has not been widely adopted by clinical practitioners. Furthermore, it is still not possible to predict who, after a diagnosis of preclinical dementia, will go on to develop AD, and if so, what the risk factors (modifiable and non-modifiable) might be. This Review/Theoretical article will focus on preclinical Alzheimer's dementia (hereafter called preclinical AD). We outline how preclinical AD is currently defined, explain how it is diagnosed and explore why this is problematic at a number of different levels. We also ask the question: Is the concept 'preclinical AD' useful in clinical practice or is it just another dead end in the Holy Grail to find a treatment for AD? Specific recommendations for research and clinical practice are provided.

Neural correlates of training-related working-memory gains in old age.

Working memory (WM) functioning declines in old age. Due to its impact on many higher-order cognitive functions, investigating whether training can modify WM performance has recently been of great interest. We examined the relationship between behavioral performance and neural activity following five weeks of intensive WM training in 23 healthy older adults (M=63.7 years). 12 participants received adaptive training (i.e. individually adjusted task difficulty to bring individuals to their performance maximum), whereas the others served as active controls (i.e. fixed low-level practice). Brain activity was measured before and after training, using fMRI, while subjects performed a WM task under two difficulty conditions. Although there were no training-related changes in WM during scanning, neocortical brain activity decreased post training and these decreases were larger in the adaptive training group than in the controls under high WM load. This pattern suggests intervention-related increases in neural efficiency. Further, there were disproportionate gains in the adaptive training group in trained as well as in non-trained (i.e. attention, episodic memory) tasks assessed outside the scanner, indicating the efficacy of the training regimen. Critically, the degree of training-related changes in brain activity (i.e. neocortical decreases and subcortical increases) was related to the maximum gain score achieved during the intervention period. This relationship suggests that the decreased activity, but also specific activity increases, observed were functionally relevant.

Helping out or helping yourself? Volunteering and life satisfaction across the retirement transition.

It has been suggested that volunteering leads to increases in well-being, particularly in older and retiring adults, and that volunteering could be used as a public health intervention to increase well-being. However, the causal relationship has been questioned. We investigated the association between voluntary work and life satisfaction in a bivariate dual-change score model, using 4 years of longitudinal data from 1,123 participants from the Health, Aging and Retirement Transitions in Sweden (HEARTS) study. Both the frequency of volunteering and the level of life satisfaction increased across the retirement transition. However, baseline life satisfaction and volunteering were only marginally associated. Further, the coupling parameters suggest that higher levels of volunteering were followed by decreases in life satisfaction and that higher levels of life satisfaction were followed by increases in volunteering. These findings suggest that increasing levels of volunteering might not be a fruitful strategy for improving life satisfaction for all older adults-if people engage too much in voluntary work, it might even be detrimental for their life satisfaction. More research is needed to better understand when and for whom increased levels of volunteering might have positive effects on life satisfaction. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Foreign language learning in older age does not improve memory or intelligence: Evidence from a randomized controlled study.

Foreign language learning in older age has been proposed as a promising avenue for combatting age-related cognitive decline. We tested this hypothesis in a randomized controlled study in a sample of 160 healthy older participants (aged 65-75 years) who were randomized to 11 weeks of either language learning or relaxation training. Participants in the language learning condition obtained some basic knowledge in the new language (Italian), but between-groups differences in improvements on latent factors of verbal intelligence, spatial intelligence, working memory, item memory, or associative memory were negligible. We argue that this is not due to either poor measurement, low course intensity, or low statistical power, but that basic studies in foreign languages in older age are likely to have no or trivially small effects on cognitive abilities. We place this in the context of the cognitive training and engagement literature and conclude that while foreign language learning may expand the behavioral repertoire, it does little to improve cognitive processing abilities. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Modulation of striatal dopamine D1 binding by cognitive processing.

There is strong evidence that dopamine (DA) is implicated in higher-order cognitive functioning, but it remains controversial whether D1 receptor binding can be modified by cognitive activity. We examined striatal D1 binding potential (BP) in 20 younger (22-30 years) and 20 older (65-75 years) persons who underwent two [(11)C] SCH 23390 PET measurements, one while resting and one while performing a cognitive task taxing inhibitory functioning. The younger persons showed significant task-related BP reductions in sensorimotor, limbic, and associative striatum during cognitive activity compared to rest. Older persons showed no reliable BP reductions in any striatal subregion. These findings demonstrate that D1 receptor binding can be modified by cognitive activity in younger persons, but also provide novel evidence for the notion that human aging is associated not only with lower DA receptor density but also with altered modifiability of the DA system.

Electrophysiological correlates of selective attention: a lifespan comparison.

BACKGROUND: To study how event-related brain potentials (ERPs) and underlying cortical mechanisms of selective attention change from childhood to old age, we investigated lifespan age differences in ERPs during an auditory oddball task in four age groups including 24 younger children (9-10 years), 28 older children (11-12 years), 31 younger adults (18-25), and 28 older adults (63-74 years). In the Unattend condition, participants were asked to simply listen to the tones. In the Attend condition, participants were asked to count the deviant stimuli. Five primary ERP components (N1, P2, N2, P3 and N3) were extracted for deviant stimuli under Attend conditions for lifespan comparison. Furthermore, Mismatch Negativity (MMN) and Late Discriminative Negativity (LDN) were computed as difference waves between deviant and standard tones, whereas Early and Late Processing Negativity (EPN and LPN) were calculated as difference waves between tones processed under Attend and Unattend conditions. These four secondary ERP-derived measures were taken as indicators for change detection (MMN and LDN) and selective attention (EPN and LPN), respectively. To examine lifespan age differences, the derived difference-wave components for attended (MMN and LDN) and deviant (EPN and LPN) stimuli were specifically compared across the four age groups. RESULTS: Both primary and secondary ERP components showed age-related differences in peak amplitude, peak latency, and topological distribution. The P2 amplitude was higher in adults compared to children, whereas N2 showed the opposite effect. P3 peak amplitude was higher in older children and younger adults than in older adults. The amplitudes of N3, LDN, and LPN were higher in older children compared with both of the adult groups. In addition, both P3 and N3 peak latencies were significantly longer in older than in younger adults. Interestingly, in the young adult sample P3 peak amplitude correlated positively and P3 peak latency correlated negatively with performance in the Identical Picture test, a marker measure of fluid intelligence. CONCLUSION: The present findings suggest that patterns of event-related brain potentials are highly malleable within individuals and undergo profound reorganization from childhood to adulthood and old age.

Comparing memory skill maintenance across the life span: preservation in adults, increase in children.

The authors examined life-span differences in the maintenance of skilled episodic memory performance by assessing 100 individuals (10 -11, 12-13, 21-26, and 66-79 years old) 11 months after termination of an intensive multisession mnemonic training program (Y. Brehmer, S.-C. Li, V. Müller, T. von Oertzen, & U. Lindenberger, 2007). Skill maintenance was tested in 2 follow-up sessions, the first without and the second with mnemonic reinstruction. Younger and older adults' average performance levels were stable across time. In contrast, both younger and older children's memory performance improved beyond originally attained levels. Older adults' performance improved from the first to the second follow-up session, presumably profiting from instruction-induced skill reactivation. Results suggest that (a) skill maintenance is largely intact in healthy older adults, (b) older adults need environmental support to fully reactivate their former skill levels (cf. F. I. M. Craik, 1983), and (c) children adapt a skill learned 11 months ago to their increasing cognitive capabilities.

Memory plasticity across the life span: uncovering children's latent potential.

Memory plasticity, or the ability to improve one's memory performance through instruction and training, is known to decline during adulthood. However, direct comparisons among middle childhood, adulthood, and old age are lacking. The authors examined memory plasticity in an age-comparative multisession training study. One hundred and eight participants ages 9-10, 11-12, 20-25, and 65-78 years learned and practiced an imagery-based mnemonic technique to encode and retrieve words by location cues. Individuals of all ages were able to acquire and optimize use of the technique. Older adults and children showed similar baseline performance and improvement through mnemonic instruction. However, in line with tenets from life-span psychology (P. B. Baltes, 1987), children profited more from mnemonic practice and reached higher levels of final performance than did older adults.

Neuromodulation of associative and organizational plasticity across the life span: empirical evidence and neurocomputational modeling.

Developmental plasticity is the key mechanism that allows humans and other organisms to modify and adapt to contextual and experiential influences. Thus, reciprocal co-constructive interactions between behavioral and neuronal plasticity play important roles in regulating neurobehavioral development across the life span. This review focuses on behavioral and neuronal evidence of lifespan differences in associative memory plasticity and plasticity of the functional organization of cognitive and cortical processes, as well as the role of the dopaminergic system in modulating such plasticity. Special attention is given to neurocomputational models that help exploring lifespan differences in neuromodulation of neuronal and behavioral plasticity. Simulation results from these models suggest that lifespan changes in the efficacy of neuromodulatory mechanisms may shape associative memory plasticity and the functional organization of neurocognitive processes by affecting the fidelity of neuronal signal transmission, which has consequences for the distinctiveness of neurocognitive representations and the efficacy of distributed neural coding.