Bias Effects in the Possible/Impossible Object Decision Test with Matching Objects

In the possible/impossible object decision test, priming has consistently been found for structurally possible, but not impossible, objects, leading Schacter, Cooper, and Delaney (1990) to suggest that priming relies on a system that represents the global 3-D structure of objects. Using a modified design with matching objects to control for the influence of episodic memory, Ratcliff and McKoon (1995) and Williams and Tarr (1997) found negative priming for impossible objects (i.e., lower performance for old than for new items). Both teams argued that priming derives from (1) episodic memory for object features and (2) bias to respond "possible" to encoded objects or their possible parts. The present study applied the matched-objects design to the original Schacter and Cooper stimuli-same possible objects and matching impossible figures-with minimal procedural variation. The data from Experiment 1 only partially supported the bias models and suggested that priming was mediated by both local and global structural descriptions. Experiment 2 showed that negative priming for impossible objects derived from the structural properties of these objects, not from the influence of episodic memory on task performance. Supplemental materials for this study may be downloaded from mc.psychonomic-journals.org/content/supplemental

Global Familiarity of Visual Stimuli Affects Repetition-Related Neural Plasticity but Not Repetition Priming

In this study, we tested the prediction of the component process model of priming [Henson, R.N. (2003). Neuroimaging studies of priming. Prog Neurobiol, 70 (1), 53-81] that repetition priming of familiar and unfamiliar objects produces qualitatively different neural repetition effects. In an fMRI study, subjects viewed four repetitions of familiar objects and globally unfamiliar objects with familiar components. Reliable behavioral priming occurred for both item types across the four presentations and was of a similar magnitude for both stimulus types. The imaging data were analyzed using multivariate linear modeling, which permits explicit testing of the hypothesis that the repetition effects for familiar and unfamiliar objects are qualitatively different (i.e., non-scaled versions of one another). The results showed the presence of two qualitatively different latent spatial patterns of repetition effects from presentation 1 to presentation 4 for familiar and unfamiliar objects, indicating that familiarity with an object's global structural, semantic, or lexical features is an important factor in priming-related neural plasticity. The first latent spatial pattern strongly weighted regions with a similar repetition effect for both item types. The second pattern strongly weighted regions contributing a repetition suppression effect for the familiar objects and repetition enhancement for the unfamiliar objects, particularly the posterior insula, superior temporal gyrus, precentral gyrus, and cingulate cortex. This differential repetition effect might reflect the formation of novel memory representations for the unfamiliar items, which already exist for the familiar objects, consistent with the component process model of priming

Aging Does Not Affect Brain Patterns of Repetition Effects Associated with Perceptual Priming of Novel Objects

This study examined how aging affects the spatial patterns of repetition effects associated with perceptual priming of unfamiliar visual objects. Healthy young (n = 14) and elderly adults (n = 13) viewed four repetitions of structurally possible and impossible figures while being scanned with blood oxygenation level-dependent functional magnetic resonance imaging. Although explicit recognition memory for the figures was reduced in the elder subjects, repetition priming did not differ across the two age groups. Using multivariate linear modeling, we found that the spatial networks of regions that demonstrated repetition-related increases and decreases in activity were identical in both age groups, although there was a trend for smaller magnitude repetition effects in these networks in the elder adults for objects that had been repeated thrice. Furthermore, repetition-related reductions in activity in the left inferior frontal cortex for possible objects correlated with repetition-related facilitation in reaction time across both young and elder subjects. Repetition-related increases of an initially negative response were observed for both object types in both age groups in parts of the default network, suggesting that less attention was required for processing repeated stimuli. These findings extend prior studies using verbal and semantic picture priming tasks and support the view that perceptual repetition priming remains intact in later adulthood because the same spatial networks of regions continue to show repetition-related neural plasticity across the adult life span

Priming of Familiar and Unfamiliar Visual Objects over Delays in Young and Older Adults

Although priming of familiar stimuli is usually age invariant, little is known about how aging affects priming of preexperimentally unfamiliar stimuli. Therefore, this study investigated the effects of aging and encoding-to-test delays (0 min, 20 min, 90 min, and 1 week) on priming of unfamiliar objects in block-based priming paradigms. During the encoding phase, participants viewed pictures of novel objects (Experiments 1 and 2) or novel and familiar objects (Experiment 3) and judged their left-right orientation. In the test block, priming was measured using the possible-impossible object-decision test (Experiment 1), symmetric-asymmetric object-decision test (Experiment 2), and real-nonreal object-decision test (Experiment 3). In Experiments 1 and 2, young adults showed priming for unfamiliar objects at all delays, whereas older adults whose baseline task performance was similar to that of young adults did not show any priming. Experiment 3 found no effects of age or delay on priming of familiar objects; however, priming of unfamiliar objects was only observed in the young participants. This suggests that when older adults cannot rely on preexisting memory representations, age-related deficits in priming can emerge

Identifying Changepoints in Biomarkers During the Preclinical Phase of Alzheimer’s Disease

Objective: Several models have been proposed for the evolution of Alzheimer’s disease (AD) biomarkers. The aim of this study was to identify changepoints in a range of biomarkers during the preclinical phase of AD.Methods: We examined nine measures based on cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) and cognitive testing, obtained from 306 cognitively normal individuals, a subset of whom subsequently progressed to the symptomatic phase of AD. A changepoint model was used to determine which of the measures had a significant change in slope in relation to clinical symptom onset.Results: All nine measures had significant changepoints, all of which preceded symptom onset, however, the timing of these changepoints varied considerably. A single measure, CSF t-tau, had an early changepoint (34 years prior to symptom onset). A group of measures, including the remaining CSF measures (CSF Abeta and phosphorylated tau) and all cognitive tests had changepoints 10–15 years prior to symptom onset. A second group is formed by medial temporal lobe shape composite measures, with a 6-year time difference between the right and left side (respectively nine and 3 years prior to symptom onset).Conclusion: These findings highlight the long period of time prior to symptom onset during which AD pathology is accumulating in the brain. There are several significant findings, including the early changes in cognition and the laterality of the MRI findings. Additional work is needed to clarify their significance

Alzheimer’s disease genetic risk and cognitive reserve in relationship to long-term cognitive trajectories among cognitively normal individuals

Background: Both Alzheimer’s disease (AD) genetic risk factors and indices of cognitive reserve (CR) influence risk of cognitive decline, but it remains unclear whether they interact. This study examined whether a CR index score modifies the relationship between AD genetic risk factors and long-term cognitive trajectories in a large sample of individuals with normal cognition. Methods: Analyses used data from the Preclinical AD Consortium, including harmonized data from 5 longitudinal cohort studies. Participants were cognitively normal at baseline (M baseline age = 64 years, 59% female) and underwent 10 years of follow-up, on average. AD genetic risk was measured by (i) apolipoprotein-E (APOE) genetic status (APOE-ε2 and APOE-ε4 vs. APOE-ε3; N = 1819) and (ii) AD polygenic risk scores (AD-PRS; N = 1175). A CR index was calculated by combining years of education and literacy scores. Longitudinal cognitive performance was measured by harmonized factor scores for global cognition, episodic memory, and executive function. Results: In mixed-effects models, higher CR index scores were associated with better baseline cognitive performance for all cognitive outcomes. APOE-ε4 genotype and AD-PRS that included the APOE region (AD-PRSAPOE) were associated with declines in all cognitive domains, whereas AD-PRS that excluded the APOE region (AD-PRSw/oAPOE) was associated with declines in executive function and global cognition, but not memory. There were significant 3-way CR index score × APOE-ε4 × time interactions for the global (p = 0.04, effect size = 0.16) and memory scores (p = 0.01, effect size = 0.22), indicating the negative effect of APOE-ε4 genotype on global and episodic memory score change was attenuated among individuals with higher CR index scores. In contrast, levels of CR did not attenuate APOE-ε4-related declines in executive function or declines associated with higher AD-PRS. APOE-ε2 genotype was unrelated to cognition. Conclusions: These results suggest that APOE-ε4 and non-APOE-ε4 AD polygenic risk are independently associated with global cognitive and executive function declines among individuals with normal cognition at baseline, but only APOE-ε4 is associated with declines in episodic memory. Importantly, higher levels of CR may mitigate APOE-ε4-related declines in some cognitive domains. Future research is needed to address study limitations, including generalizability due to cohort demographic characteristics

Whitepaper: Defining and investigating cognitive reserve, brain reserve, and brain maintenance

Several concepts, which in the aggregate get might be used to account for “resilience” against age‐ and disease‐related changes, have been the subject of much research. These include brain reserve, cognitive reserve, and brain maintenance. However, different investigators have use these terms in different ways, and there has never been an attempt to arrive at consensus on the definition of these concepts. Furthermore, there has been confusion regarding the measurement of these constructs and the appropriate ways to apply them to research. Therefore the reserve, resilience, and protective factors professional interest area, established under the auspices of the Alzheimer's Association, established a whitepaper workgroup to develop consensus definitions for cognitive reserve, brain reserve, and brain maintenance. The workgroup also evaluated measures that have been used to implement these concepts in research settings and developed guidelines for research that explores or utilizes these concepts. The workgroup hopes that this whitepaper will form a reference point for researchers in this area and facilitate research by supplying a common language

Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer's disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer's disease, 55 controls from the Dominantly Inherited Alzheimer's Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer's disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer's disease and cerebrospinal fluid tau levels in sporadic Alzheimer's disease cases. In both autosomal dominant and sporadic Alzheimer's disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer's disease, a significant left frontal cortex connectivity × estimated years of onset interaction was found, indicating slower decline of memory and global cognition at higher levels of connectivity. Similarly, in sporadic amyloid-positive elderly subjects, the effect of tau on cognition was attenuated at higher levels of left frontal cortex connectivity. Polynomial regression analysis showed that the trajectory of cognitive decline was shifted towards a later stage of Alzheimer's disease in patients with higher levels of left frontal cortex connectivity. Together, our findings suggest that higher resilience against the development of cognitive impairment throughout the early stages of Alzheimer's disease is at least partially attributable to higher left frontal cortex-hub connectivity