Strategies for Recruiting Older Black Men into Aging and Alzheimer's Research.

BACKGROUND: Despite their high risks for Alzheimer's disease, older Black men are minimally represented in Alzheimer's research and clinical trials. The absence of older Black men in Alzheimer's research limits our ability to characterize the changes associated with cognitive impairments in older Black men-a key health disparity concern. METHODS: Drawing on lessons we learned from years of community-based participatory research in Newark, NJ, we highlight recruitment strategies developed alongside community partners to guide our enrollment and retention efforts for Black men. RESULTS: We identified seven recruitment strategies: provide indirect health education through social programming, target older men through the younger men in their lives, go beyond Black churches, use older Black men as trained community ambassadors, enlist the women in Black men's lives, frame research participation as a legacy to leave their sons, and use past and current Black men participants as role models. CONCLUSIONS: These recruitment strategies help us address many barriers to recruiting older Black men. They can be easily implemented by researchers conducting aging and brain health research or interested in working with older Black men and under-represented populations.

Reward and Punishment Learning as Predictors of Cognitive Behavioral Therapy Response in Parkinson's Disease Comorbid with Clinical Depression.

Depression is highly comorbid among individuals with Parkinson's Disease (PD), who often experience unique challenges to accessing and benefitting from empirically supported interventions like Cognitive Behavioral Therapy (CBT). Given the role of reward processing in both depression and PD, this study analyzed a subset (N = 25) of participants who participated in a pilot telemedicine intervention of PD-informed CBT, and also completed a Reward- and Punishment-Learning Task (RPLT) at baseline. At the conclusion of CBT, participants were categorized into treatment responders (n = 14) and non-responders (n = 11). Responders learned more optimally from negative rather than positive feedback on the RPLT, while this pattern was reversed in non-responders. Computational modeling suggested group differences in learning rate to negative feedback may drive the observed differences. Overall, the results suggest that a within-subject bias for punishment-based learning might help to predict response to CBT intervention for depression in those with PD.Plain Language Summary Performance on a Computerized Task may predict which Parkinson's Disease Patients benefit from Cognitive Behavioral Treatment of Clinical DepressionWhy was the study done? Clinical depression regularly arises in individuals with Parkinson's Disease (PD) due to the neurobiological changes with the onset and progression of the disease as well as the unique psychosocial difficulties associated with living with a chronic condition. Nonetheless, psychiatric disorders among individuals with PD are often underdiagnosed and likewise undertreated for a variety of reasons. The results of our study have implications about how to improve the accuracy and specificity of mental health treatment recommendations in the future to maximize benefits for individuals with PD, who often face additional barriers to accessing quality mental health treatment.What did the researchers do? We explored whether performance on a computerized task called the Reward- and Punishment-Learning Task (RPLT) helped to predict response to Cognitive Behavioral Therapy (CBT) for depression better than other predictors identified in previous studies. Twenty-five individuals with PD and clinical depression that completed a 10-week telehealth CBT program were assessed for: Demographics (Age, gender, etc.); Clinical information (PD duration, mental health diagnoses, levels of anxiety/depression, etc.); Neurocognitive performance (Memory, processing speed, impulse control, etc.); and RPLT performance.What did the researchers find? A total of 14 participants significantly benefitted from CBT treatment while 11 did not significantly benefit from treatment.There were no differences before treatment in the demographics, clinical information, and neurocognitive performance of those participants who ended up benefitting from the treatment versus those who did not.There were, however, differences before treatment in RPLT performance so that those individuals that benefitted from CBT seemed to learn better from negative feedback.What do the findings mean? Our results suggest that the CBT program benefitted those PD patients with clinical depression that seemed to overall learn best from avoiding punishment rather than obtaining reward which was targeted in CBT by focusing on increasing engagement in rewarding activities. The Reward- and Punishment-Learning Task hence may be a useful tool to help predict treatment response and provide more individualized recommendations on how to best maximize the benefits of psychotherapy for individuals with PD that may struggle to connect to mental health care. Caution is recommended about interpretating these results beyond this study as the overall number of participants was small and the data for this study were collected as part of a previous study so there was no opportunity to include additional measurements of interest.

Examining the efficacy of a cardio-dance intervention on brain health and the moderating role of ABCA7 in older African Americans: a protocol for a randomized controlled trial.

Introduction: African Americans are two to three times more likely to be diagnosed with Alzheimer's disease (AD) compared to White Americans. Exercise is a lifestyle behavior associated with neuroprotection and decreased AD risk, although most African Americans, especially older adults, perform less than the recommended 150 min/week of moderate-to-vigorous intensity exercise. This article describes the protocol for a Phase III randomized controlled trial that will examine the effects of cardio-dance aerobic exercise on novel AD cognitive and neural markers of hippocampal-dependent function (Aims #1 and #2) and whether exercise-induced neuroprotective benefits may be modulated by an AD genetic risk factor, ABCA7 rs3764650 (Aim #3). We will also explore the effects of exercise on blood-based biomarkers for AD. Methods and analysis: This 6-month trial will include 280 African Americans (≥ 60 years), who will be randomly assigned to 3 days/week of either: (1) a moderate-to-vigorous cardio-dance fitness condition or (2) a low-intensity strength, flexibility, and balance condition for 60 min/session. Participants will complete health and behavioral surveys, neuropsychological testing, saliva and venipuncture, aerobic fitness, anthropometrics and resting-state structural and functional neuroimaging at study entry and 6 months. Discussion: Results from this investigation will inform future exercise trials and the development of prescribed interventions that aim to reduce the risk of AD in African Americans.

Obesity reduces hippocampal structure and function in older African Americans with the APOE-ε4 Alzheimer's disease risk allele.

Introduction: Excess body weight and Alzheimer's disease (AD) disproportionately affect older African Americans. While mid-life obesity increases risk for AD, few data exist on the relationship between late-life obesity and AD, or how obesity-based and genetic risk for AD interact. Although the APOE-ε4 allele confers a strong genetic risk for AD, it is unclear if late-life obesity poses a greater risk for APOE-ε4 carriers compared to non-carriers. Here we assessed: (1) the influence of body mass index (BMI) (normal; overweight; class 1 obese; ≥ class 2 obese) on cognitive and structural MRI measures of AD risk; and (2) the interaction between BMI and APOE-ε4 in older African Americans. Methods: Seventy cognitively normal older African American participants (Mage = 69.50 years; MBMI = 31.01 kg/m2; 39% APOE-ε4 allele carriers; 86% female) completed anthropometric measurements, physical assessments, saliva collection for APOE-ε4 genotyping, cognitive testing, health and lifestyle questionnaires, and structural neuroimaging [volume/surface area (SA) for medial temporal lobe subregions and hippocampal subfields]. Covariates included age, sex, education, literacy, depressive symptomology, and estimated aerobic fitness. Results: Using ANCOVAs, we observed that individuals who were overweight demonstrated better hippocampal cognitive function (generalization of learning: a sensitive marker of preclinical AD) than individuals with normal BMI, p = 0.016, ηp2 = 0.18. However, individuals in the obese categories who were APOE-ε4 non-carriers had larger hippocampal subfield cornu Ammonis region 1 (CA1) volumes, while those who were APOE-ε4 carriers had smaller CA1 volumes, p = 0.003, ηp2 = 0.23. Discussion: Thus, being overweight by BMI standards may preserve hippocampal function, but obesity reduces hippocampal structure and function in older African Americans with the APOE-ε4 Alzheimer's disease risk allele.

Altered learning and transfer abilities in Korsakoff's syndrome depending on task complexity.

Korsakoff's syndrome (KS) is characterized by episodic memory impairment due to damage to the medial diencephalic structures. Although commonly associated with chronic alcoholism, starvation due to the hunger strike is one of its nonalcoholic causes. Learning the stimulus-response associations and transferring the just-learned associations to novel combinations were previously tested by specific tasks in memory-impaired patients with hippocampal, basal forebrain, and basal ganglia damage. To add to this previous research, we aimed to use the same tasks in a group of patients with hunger strike-related KS presenting a stable isolated amnestic profile. Twelve patients with hunger strike-related KS and matched healthy controls were tested in two tasks varying in task complexity. Each task included two phases: the initial phase is feedback-based learning of (simple vs. complex) stimulus-response associations, and the following phase is transfer generalization (in the presence vs. absence of feedback). On a task involving simple associations, five patients with KS failed to learn the associations, while the other seven patients showed intact learning and transfer. On the other task involving more complex associations, seven patients showed slower learning and failed at transfer generalization, whereas the other five patients failed even at the acquisition phase. These findings of a task-complexity-related impairment on associative learning and transfer represent a distinct pattern from the spared learning but impaired transfer previously observed on these tasks in patients with medial temporal lobe amnesia.

High-Quality Sleep Mitigates ABCA7-Related Generalization Deficits in Healthy Older African Americans.

BACKGROUND: Both sleep deficiencies and Alzheimer's disease (AD) disproportionately affect older African Americans. Genetic susceptibility to AD further compounds risk for cognitive decline in this population. Aside from APOE ɛ4, ABCA7 rs115550680 is the strongest genetic locus associated with late-onset AD in African Americans. While sleep and ABCA7 rs115550680 independently influence late-life cognitive outcomes, we know too little about the interplay between these two factors on cognitive function. OBJECTIVE: We investigated the interaction between sleep and ABCA7 rs115550680 on hippocampal-dependent cognitive function in older African Americans. METHODS: One-hundred fourteen cognitively healthy older African Americans were genotyped for ABCA7 risk (n = 57 carriers of risk "G" allele; n = 57 non-carriers), responded to lifestyle questionnaires, and completed a cognitive battery. Sleep was assessed via a self-reported rating of sleep quality (poor, average, good). Covariates included age and years of education. RESULTS: Using ANCOVA, we found that carriers of the risk genotype who reported poor or average sleep quality demonstrated significantly poorer generalization of prior learning-a cognitive marker of AD-compared to their non-risk counterparts. Conversely, there was no genotype-related difference in generalization performance in individuals who reported good sleep quality. CONCLUSION: These results indicate that sleep quality may be neuroprotective against genetic risk for AD. Future studies employing more rigorous methodology should investigate the mechanistic role of sleep neurophysiology in the pathogenesis and progression of AD associated with ABCA7. There is also need for the continued development of non-invasive sleep interventions tailored to racial groups with specific AD genetic risk profiles.

A Mini-Review of Strategies for Recruiting Older African Americans to Alzheimer's Disease Research.

African Americans experience higher incidence and prevalence of Alzheimer's disease (AD). Yet, they continue to be underrepresented in AD research, limiting the ability to generalize findings to the increasingly diverse US population. To reduce AD disparities, targeted efforts are needed to increase the representation of African Americans in AD research. This mini review identified evidence-based strategies that increased research participation among older African Americans. Four recruitment strategies emerged from eight published peer-reviewed studies that directly evaluated the effectiveness of strategies aimed at increasing the number of African American participants in Alzheimer's research. The strategies include community outreach and education, face-to-face discussions, remote access, and referral and partnership with local organizations. Across different locations, these strategies increased the number of African Americans enrolled into AD research, the number of people that signed up to donate their brains for AD research upon death, and the knowledge and perception of AD in the communities. Targeted efforts are effective in increasing AD research participation among older African Americans, especially when combined with approaches that emphasize transparency and mutual trust and involve the community as stakeholders in the research process.

Sleep Facilitates Extraction of Temporal Regularities With Varying Timescales.

Evidence suggests that memory consolidation is facilitated by sleep, both through the strengthening of existing memories and by extracting regularities embedded in those memories. We previously observed that one sleep stage, Slow-Wave sleep (SWS), is particularly involved in the extraction of temporal regularities. We suggested that this attribute can naturally stem from the time-compressed memory replay known to occur in the hippocampus during SWS. A prediction coming out of this "temporal scaffolding" hypothesis is that sleep would be especially influential on extraction of temporal regularities when the time gap between the events constituting the regularities is shortish. In this study, we tested this prediction. Eighty-three participants performed a cognitive task in which hidden temporal regularities of varying time gaps were embedded. Detecting these regularities could significantly improve performance. Participants performed the task in two sessions with an interval filled with either wake or sleep in between. We found that sleep improved performance across all time gaps and that the longer the gap had been, the smaller was the improvement across both sleep and wake. No interaction between sleep and gap size was observed; however, unlike sleeping participants, awake participants did not exhibit any further performance improvement for the long gaps following the interval. In addition, across all participants, performance for the long gaps was associated with the development of conscious awareness to the regularities. We discuss these results in light of the temporal scaffolding hypothesis and suggest future directions to further elucidate the mechanisms involved.

Low body mass and high-quality sleep maximize the ability of aerobic fitness to promote improved cognitive function in older African Americans.

ABSTRACTObjectives: Because African Americans are at elevated risk for cognitive decline and Alzheimer's disease, it is important to understand which health and lifestyle factors are most important for reducing this risk. Obesity and poor sleep quality are common in lower-income, urban African Americans and have been linked to cognitive decline in older age. Fortunately, increasing aerobic fitness via regular exercise can improve cognitive function. This study sought to (1) examine the cross-sectional relationship between aerobic fitness and cognitive function in older African Americans, and (2) determine whether body mass index and sleep quality moderated the relationship between aerobic fitness and cognition.Design: 402 older African Americans, ages 60-90 (84% female, mean education level = 14 years) completed neuropsychological testing, computerized behavioral tasks, physical performance measures, and health and lifestyle questionnaires. Hierarchical linear regressions were performed to determine associations between aerobic fitness and cognition and whether body mass index and sleep quality moderate the fitness-cognition relationship while controlling for age, sex, education, depressive symptoms, and literacy.Results: Higher aerobic fitness levels were significantly associated with better executive function. The relationships between fitness and hippocampal-dependent cognitive functions (learning and memory, generalization) were attenuated in those who are obese (body mass index ≥ 30 kg/m2) or rated their sleep quality as poor, ps < .05.Conclusion: Our results suggest that while exercise and associated improvements in aerobic fitness are key for improved cognition, these benefits are maximized in those who maintain low body weight and get sufficient, high quality sleep. Exercise programs for older African Americans will be most effective if they are integrated with education programs that emphasize healthy eating, weight control, and sleep hygiene and conceptualize individuals as part of their broader social and environmental context.

Cardio-Dance Exercise to Improve Cognition and Mood in Older African Americans: A Propensity-Matched Cohort Study.

The current study sought to determine the influence of initial sleep quality and body mass index on the cognitive and mood outcomes of a community-based cardio-dance exercise program. Thirty-two older African Americans who participated in a 5-month cardio-dance exercise program were propensity-matched to 32 no-contact controls. Participants completed neuropsychological tests of attention, executive function, and memory and a self-reported depression measure at baseline and post-test. Among exercise participants, we observed significant improvements in depression (baseline = 6.16 ± 5.54, post-test = 4.66 ± 4.89, ηp2=.12, p = .009) and attention (baseline = 40.53 ± 14.01, post-test = 36.63 ± 13.29, ηp2=.12, p = .009) relative to controls. Improvements in executive function and attention were most pronounced among exercise participants with poor sleep quality (baseline = 7.71 ± 1.25, post-test = 8.29 ± 2.06, ηp2=.41, p = .04) and with obesity (baseline = 38.05 ± 12.78, post-test = 35.67 ± 13.82, ηp2=.30, p = .001), respectively. This study provides novel evidence that exercise has the potential to improve depression in older African Americans. For those with poor sleep quality or obesity, exercise can also improve some cognitive outcomes.

Effects of Ketamine Versus Midazolam on Neurocognition at 24 Hours in Depressed Patients With Suicidal Ideation.

Objective: Subanesthetic ketamine rapidly reduces depressive symptoms and suicidal ideation in some depressed patients. Its effects on neurocognitive functioning in such individuals with significant suicidal ideation is not well understood, even though certain neurocognitive deficits are associated with suicide behavior beyond clinical symptoms.Methods: In this study, depressed patients with clinically significant suicidal ideation (n = 78) underwent neuropsychological testing before and 1 day after double-blind treatment with intravenous ketamine (n = 39) or midazolam (n = 39). A subgroup randomized to midazolam whose ideation did not remit after initial infusion received open ketamine and additional neurocognitive testing a day after this treatment. The primary outcome was change in performance on this neurocognitive battery. The study was conducted between November 2012 and January 2017.Results: Blinded ketamine produced rapid improvement in suicidal ideation and mood in comparison to midazolam, as we had reported previously. Ketamine, relative to midazolam, was also associated with specific improvement in reaction time (Choice RT) and interference processing/cognitive control (computerized Stroop task)-the latter a measure that has been associated with past suicide attempt in depression. In midazolam nonremitters later treated with open ketamine and retested, reaction time and interference processing/cognitive control also improved relative to both of their prior assessments. Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood.Conclusions: Overall, ketamine was found to have a positive therapeutic effect on neurocognition 1 day after treatment on at least 1 measure associated with suicidal behavior in the context of depression. Results suggest additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior.Trial Registration: ClinicalTrials.gov identifier: NCT01700829.

Sleep to remember, sleep to forget: Rapid eye movement sleep can have inverse effects on recall and generalization of fear memories.

Rapid Eye Movement (REM) sleep has been shown to modulate the consolidation of fear memories, a process that may contribute to the development of Post-Traumatic Stress Disorder (PTSD). However, contradictory findings have been reported regarding the direction of this modulation and its differential effects on recall versus generalization. In two complementary experiments, we addressed this by employing sleep deprivation protocols together with a novel fear-conditioning paradigm that required the discrimination between coexisting threat and safety signals. Using skin conductance responses and functional imaging (fMRI), we found two opposing effects of REM sleep: While REM impaired recall of the original threat memories, it improved the ability to generalize these memories to novel situations that emphasized the discrimination between threat and safety signals. These results, as well as previous findings in healthy participants and patients diagnosed with PTSD, could be explained by the degree to which the balance between threat and safety signals for a given stimulus was predictive of threat. We suggest that this account can be integrated with contemporary theories of sleep and fear learning, such as the REM recalibration hypothesis.

Increased dynamic flexibility in the medial temporal lobe network following an exercise intervention mediates generalization of prior learning.

Recent work has conceptualized the brain as a network comprised of groups of sub-networks or modules. "Flexibility" of brain network(s) indexes the dynamic reconfiguration of comprising modules. Using novel techniques from dynamic network neuroscience applied to high-resolution resting-state functional magnetic resonance imaging (fMRI), the present study investigated the effects of an aerobic exercise intervention on the dynamic rearrangement of modular community structure-a measure of neural flexibility-within the medial temporal lobe (MTL) network. The MTL is one of the earliest brain regions impacted by Alzheimer's disease. It is also a major site of neuroplasticity that is sensitive to the effects of exercise. In a two-group non-randomized, repeated measures and matched control design with 34 healthy older adults, we observed an exercise-related increase in flexibility within the MTL network. Furthermore, MTL network flexibility mediated the beneficial effect aerobic exercise had on mnemonic flexibility, as measured by the ability to generalize past learning to novel task demands. Our results suggest that exercise exerts a rehabilitative and protective effect on MTL function, resulting in dynamically evolving networks of regions that interact in complex communication patterns. These reconfigurations may underlie exercise-induced improvements on cognitive measures of generalization, which are sensitive to subtle changes in the MTL.

Gordon H. Bower (1932-2020).

Memorializes Gordon H. Bower (1932-2020). One of the founders and leaders of cognitive science, Gordon was widely recognized for his contributions to science. He was elected to the National Academy of Sciences, the American Academy of Arts and Sciences, the Society of Experimental Psychologists, and the American Philosophical Society. Among his many awards were the Distinguished Scientific Contributions Award from the American Psychological Association in 1979 and the National Medal of Science in 2005 "for his unparalleled contributions to cognitive and mathematical psychology, for his lucid analysis of memory and learning, and for his important service to psychology and American science." Gordon was active both at Stanford University, serving as department chair and associate dean of humanities and sciences, and on the national stage, where he served as chief scientific adviser to the National Institute of Mental Health and was president of the Cognitive Science Society, the Psychonomic Society, and the Association for Psychological Science. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

ABCA7 Genotype Moderates the Effect of Aerobic Exercise Intervention on Generalization of Prior Learning in Healthy Older African Americans.

African Americans are at elevated risk for age-related cognitive decline, with double the prevalence of Alzheimer's disease (AD) compared to Caucasians Americans. Various behavioral, biological, and lifestyle factors may underlie this health disparity, but little is known about the relative importance and interactions among these different risk factors in African Americans. While the neuroprotective effects of aerobic exercise on biomarkers are well established, few studies have examined the differential benefits of exercise based on genetic risk for AD. Furthermore, evidence is limited regarding the potential moderating effects of ABCA7, a gene known to confer significantly greater AD risk in African Americans. In a case-control matched sample of 56 healthy older African Americans, we investigated the effect of an aerobic exercise intervention on a hippocampus-related assessment of generalization following rule learning, in individuals who were carriers of the ABCA7 rs3764650 non-risk (TT) or high-risk (GG) genotype. Following the exercise-intervention, the non-risk group made significantly fewer generalization errors, while there was no improvement in generalization for the high-risk group. For the controls, no changes in generalization scores were observed regardless of genotype status. Our results indicate that the ongoing adverse effects of ABCA7 high-risk genotype may diminish the benefits associated with aerobic exercise. As such, the potential disease-modifying effects of aerobic exercise on AD-related neuropathology may be limited to carriers of the ABCA7 rs3764650 non-risk genotype.

Age-Related Decline in Learning Deterministic Judgment-Based Sequences.

OBJECTIVES: Because sequence learning is integral to cognitive functions across the life span, the present study examined the effect of healthy aging on deterministic judgment-based sequence learning. METHODS: College-aged, younger-old (YO), and older-old (OO) adults completed a judgment-based sequence learning task which required them to learn a full sequence by chaining together single stimulus-response associations in a step-by-step fashion. RESULTS: Results showed that younger adults outperformed YO and OO adults; older adults were less able to acquire the full sequence and committed significantly more errors during learning. Additionally, higher sequence learning errors were associated with advancing age among older adults, even when controlling for other factors known to contribute to sequence learning abilities. Such impairments were selective to learning sequential information, because adults of all ages performed equivalently on postlearning probe trials, as well as on learning simple stimulus-response associations. DISCUSSION: This pattern of age deficits during deterministic sequence learning challenges past reports of age preservation. Though the neural processes underlying learning cannot be determined here, our patterns of age deficits and preservation may reflect different brain regions that are involved in the task phases, adding behavioral evidence to the emerging hypothesis of frontostriatal declines despite spared hippocampal function with age.

The Effects of APOE and ABCA7 on Cognitive Function and Alzheimer's Disease Risk in African Americans: A Focused Mini Review.

African Americans have double the prevalence of Alzheimer's disease (AD), as compared to European Americans. However, the underlying causes of this health disparity are due to a multitude of environmental, lifestyle, and genetic factors that are not yet fully understood. Here, we review the effects of the two largest genetic risk factors for AD in African Americans: Apolipoprotein E (APOE) and ABCA7. We will describe the direct effects of genetic variation on neural correlates of cognitive function and report the indirect modulating effects of genetic variation on modifiable AD risk factors, such as aerobic fitness. As a means of integrating previous findings, we present a novel schematic diagram to illustrate the many factors that contribute to AD risk and impaired cognitive function in older African Americans. Finally, we discuss areas that require further inquiry, and stress the importance of racially diverse and representative study populations.

Learning functions in short-term cocaine users.

OBJECTIVE: This study examined learning functions in short-term cocaine users and control participants. METHOD: Seventeen active cocaine users (reporting 3.5 mean years of cocaine use) and seventeen non-cocaine-using controls (with similar reported levels of alcohol and marijuana use) were compared on tasks measuring different aspects of learning. RESULTS: The cocaine users performed more poorly on the Weather Prediction and List-Learning tasks, as well as supplementary executive and psychomotor function tasks, than controls. CONCLUSIONS: Individuals with a relatively short duration of cocaine use exhibited moderate weaknesses in probabilistic category learning, verbal learning and psychomotor functions, relative to controls. These weaknesses may underpin difficulty in learning from the probabilistic consequences of behavior and hinder the ability to respond to cognitive-behavioral treatments.

Sleep and the extraction of hidden regularities: A systematic review and the importance of temporal rules.

As part of its role in memory consolidation, sleep has been repeatedly identified as critical for the extraction of regularities from wake experiences. However, many null results have been published as well, with no clear consensus emerging regarding the conditions that yield this sleep effect. Here, we systematically review the role of sleep in the extraction of hidden regularities, specifically those involving associative relations embedded in newly learned information. We found that the specific behavioral task used in a study had far more impact on whether a sleep effect was discovered than either the category of the cognitive processes targeted, or the particular experimental design employed. One emerging pattern, however, was that the explicit detection of hidden rules is more likely to happen when the rules are of a temporal nature (i.e., event A at time t predicts a later event B) than when they are non-temporal. We discuss this temporal rule sensitivity in reference to the compressed memory replay occurring in the hippocampus during slow-wave-sleep, and compare this effect to what happens when the extraction of regularities depends on prior knowledge and relies on structures other than the hippocampus.

ABCA7 Risk Genotype Diminishes the Neuroprotective Value of Aerobic Fitness in Healthy Older African Americans.

Although the association of ABCA7 risk variants with Alzheimer's disease (AD) has been established worldwide, its effect size on the relative odds of being diagnosed with AD is significantly higher in African Americans. Across ethnicities, two common ABCA7 loci (rs115550680 and rs3764650) have been confirmed to increase the risk of AD. While ABCA7 rs115550680 has been linked to the development of late-onset AD in African Americans, no association between ABCA7 variant rs3764650 and AD has been found in this population. In order to elucidate the influence of ABCA7 rs3764650 on AD risk in African Americans, we sought to investigate the relationship between this variant, aerobic fitness, and cognition. The present study tested the hypothesis that in African Americans, ABCA7 rs3764650 confers an indirect risk for AD via its interaction with aerobic fitness, a modifiable lifestyle factor known to attenuate AD-related neuropathology. In a case-control sample of 100 healthy African Americans, we observed that ABCA7 rs3764650 genotype modulates the association between aerobic fitness and a cognitive assessment of generalization following rule learning. For carriers of the non-risk genotype, higher levels of aerobic fitness were significantly associated with fewer generalization errors, while carriers of the risk genotype did not show any relationship between aerobic fitness and generalization. Our findings imply that ABCA7 rs3764650 risk genotype may diminish the neuroprotective effects of aerobic fitness, and, they suggest differing risk patterns between cognitive decline and fitness by ABCA7 genotype. Thus, in African Americans the interactive effects of ABCA7 rs3764650 and aerobic fitness likely compound overall ABCA7-related AD risk, and may contribute to health disparities whereby African Americans are at a higher risk for dementia, with double the prevalence of AD.