Umbrella review and Delphi study on modifiable factors for dementia risk reduction.

A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the "LIfestyle for BRAin health" (LIBRA) score. We systematically evaluated whether LIBRA requires revision based on new evidence. To identify modifiable risk and protective factors suitable for dementia risk reduction, we combined an umbrella review of systematic reviews and meta-analyses with a two-round Delphi consensus study. The review of 608 unique primary studies and opinions of 18 experts prioritized six modifiable factors: hearing impairment, social contact, sleep, life course inequalities, atrial fibrillation, and psychological stress. Based on expert ranking, hearing impairment, social contact, and sleep were considered the most suitable candidates for inclusion in updated dementia risk scores. As such, the current study shows that dementia risk scores need systematic updates based on emerging evidence. Future studies will validate the updated LIBRA score in different cohorts. HIGHLIGHTS: An umbrella review was combined with opinions of 18 dementia experts. Various candidate targets for dementia risk reduction were identified. Experts prioritized hearing impairment, social contact, and sleep. Re-assessment of dementia risk scores is encouraged. Future work should evaluate the predictive validity of updated risk scores.

COVID-19 Vaccine Confidence Mediates the Relationship between Health Literacy and Vaccination in a Diverse Sample of Urban Adults.

We sought to analyze the relationship between health literacy, confidence in COVID-19 vaccines, and self-reported vaccination. We hypothesized that the relationship between health literacy and vaccination would be mediated by vaccine confidence. We recruited (N = 271) English- and Spanish-speaking adults in Boston and Chicago from September 2018 to September 2021. We performed a probit mediation analysis to determine if confidence in COVID-19 vaccines and health literacy predicted self-reported vaccination. We hypothesized that the relationship between health literacy and vaccination would be mediated by vaccine confidence. Participants were on average 50 years old, 65% female, 40% non-Hispanic Black, 25% Hispanic, and 30% non-Hispanic White; 231 (85%) reported at least one COVID-19 vaccination. A higher mean vaccine confidence score (t = -7.9, p < 0.001) and higher health literacy (t = -2.2, p = 0.03) were associated with vaccination, but only vaccine confidence predicted vaccination in a multivariate model. Vaccine confidence mediated the relationship between health literacy and COVID-19 vaccination (mediated effects: 0.04; 95% CI [0.02, 0.08]). We found that using a simple tool to measure vaccine confidence identified people who declined or delayed COVID-19 vaccination in a diverse sample of adults with varying levels of health literacy. Simple short survey tools can be useful to identify people who may benefit from vaccine promotion efforts and evidence-based communication strategies.

Hormonal contraception and risk for cognitive impairment or Alzheimer's disease and related dementias in young women: a scoping review of the evidence.

Introduction: Women are significantly more likely to develop Alzheimer's disease and related dementias (ADRD) than men. Suggestions to explain the sex differences in dementia incidence have included the influence of sex hormones with little attention paid to date as to the effect of hormonal contraception on brain health. The aim of this scoping review is to evaluate the current evidence base for associations between hormonal contraceptive use by women and non-binary people in early adulthood and brain health outcomes. Methods: A literature search was conducted using EMBASE, Medline and Google Scholar, using the keywords "hormonal contraception" OR "contraception" OR "contraceptive" AND "Alzheimer*" OR "Brain Health" OR "Dementia". Results: Eleven papers were identified for inclusion in the narrative synthesis. Studies recruited participants from the UK, USA, China, South Korea and Indonesia. Studies included data from women who were post-menopausal with retrospective data collection, with only one study contemporaneously collecting data from participants during the period of hormonal contraceptive use. Studies reported associations between hormonal contraceptive use and a lower risk of ADRD, particularly Alzheimer's disease (AD), better cognition and larger grey matter volume. Some studies reported stronger associations with longer duration of hormonal contraceptive use, however, results were inconsistent. Four studies reported no significant associations between hormonal contraceptive use and measures of brain health, including brain age on MRI scans and risk of AD diagnosis. Discussion: Further research is needed on young adults taking hormonal contraceptives, on different types of hormonal contraceptives (other than oral) and to explore intersections between sex, gender, race and ethnicity. Systematic Review Registration: https://doi.org/10.17605/OSF.IO/MVX63, identifier: OSF.io: 10.17605/OSF.IO/MVX63.

Reducing fear and avoidance of memory loss improves mood and social engagement in community-based older adults: a randomized trial.

BACKGROUND: Alzheimer's disease and related dementias (ADRD) are among the most feared age-related conditions. The aim of this study was to evaluate a brief psychological intervention to promote adaptive coping in older adults experiencing heightened fear of ADRD and investigate positive downstream effects on health-related secondary outcomes, including frequency of reported memory failures, psychosocial functioning, and quality of life. METHODS: Eighty-one older adults were recruited and randomized into REFRAME or active control intervention arms. Both groups received psycho-education and training in mindful monitoring of fears related to ADRD. The REFRAME group received an additional behavioral activation component intended to disrupt maladaptive avoidant coping (i.e., avoidance) strategies. Both groups completed 3-weeks of intervention exercises with accompanying questionnaires (baseline, mid- and post-intervention and 4-week follow-up). RESULTS: Adherence was strong (> 75%). We observed a significant reduction in ADRD-related fear and avoidance in both groups. Significant reductions were also observed for frequency of self-reported memory failures, anxiety, and depression. Depression was significantly reduced in the REFRAME group compared to the control group. Significant increases in participants' ability to participate in social activities and well-being were also observed. CONCLUSIONS: Findings suggest that a brief psychological intervention can mitigate ADRD-related fears and avoidant coping in older adults, and that benefits extend to broader health-related outcomes including anxiety, depression, social functioning, and well-being. Addressing ADRD-related fear has implications for healthy aging and risk reduction, as individuals may be more likely to engage in activities that are protective against ADRD but were previously avoided. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04821960 .

Young Adult Brain Capital: A New Opportunity for Dementia Prevention.

The potential for future prevention of Alzheimer's disease and related dementias (ADRD) through healthy lifestyle change is spurring a positive brain health movement. However, most ADRD research continues to focus on mid- and later life. We lack evidence regarding risk exposure and protective factors in young adulthood, i.e., 18-39 years. Brain capital is an emerging framework that represents the combination of education, knowledge, skills, and optimal brain health that people accumulate over their lives. Building on this framework, we present a new model that focuses on optimizing brain health in young adulthood; namely, young adult brain capital. Increasing focus on younger populations is critical for developing citizens who are emotionally intelligent, resilient and can anticipate and cope with rapid changes in the world. By understanding the values that are key drivers and motivators for young adults, we can empower the next generation to become active agents in optimizing their brain health and reducing their risk for future ADRD.

Validation of the Fear and Avoidance of Memory Loss scale in community-based older adults.

Introduction: Alzheimer's disease and related dementias (ADRD) are among the most feared conditions. However, research around ADRD-specific fear and avoidance behaviors is lacking. Here, we validated a novel measure of fear and avoidance specific to memory loss, the Fear and Avoidance of Memory Loss (FAM) scale, and examined associations between fear avoidance and psychosocial functioning in older adults. Methods: We assessed FAM Scale internal reliability and concurrent validity, and candidate subscales across two samples (total N = 813). We then examined associations between fear avoidance and memory performance, anxiety, depressive symptoms, sleep, social functioning, and quality of life. Results: We identified two subscales: fear and avoidance, which yielded strong psychometric validity. Higher fear was associated with memory failures and sleep disturbance. Higher avoidance was associated with memory failures, poorer verbal memory, reduced social functioning, and quality of life. Discussion: We present the first measure of fear avoidance specific to memory loss. We propose that targeting fear avoidance can promote ADRD risk reduction and resiliency.

Neuroscience from the comfort of your home: Repeated, self-administered wireless dry EEG measures brain function with high fidelity.

Recent advances have enabled the creation of wireless, "dry" electroencephalography (EEG) recording systems, and easy-to-use engaging tasks, that can be operated repeatedly by naïve users, unsupervised in the home. Here, we evaluated the validity of dry-EEG, cognitive task gamification, and unsupervised home-based recordings used in combination. Two separate cohorts of participants-older and younger adults-collected data at home over several weeks using a wireless dry EEG system interfaced with a tablet for task presentation. Older adults (n = 50; 25 females; mean age = 67.8 years) collected data over a 6-week period. Younger male adults (n = 30; mean age = 25.6 years) collected data over a 4-week period. All participants were asked to complete gamified versions of a visual Oddball task and Flanker task 5-7 days per week. Usability of the EEG system was evaluated via participant adherence, percentage of sessions successfully completed, and quantitative feedback using the System Usability Scale. In total, 1,449 EEG sessions from older adults (mean = 28.9; SD = 6.64) and 684 sessions from younger adults (mean = 22.87; SD = 1.92) were collected. Older adults successfully completed 93% of sessions requested and reported a mean usability score of 84.5. Younger adults successfully completed 96% of sessions and reported a mean usability score of 88.3. Characteristic event-related potential (ERP) components-the P300 and error-related negativity-were observed in the Oddball and Flanker tasks, respectively. Using a conservative threshold for inclusion of artifact-free data, 50% of trials were rejected per at-home session. Aggregation of ERPs across sessions (2-4, depending on task) resulted in grand average signal quality with similar Standard Measurement Error values to those of single-session wet EEG data collected by experts in a laboratory setting from a young adult sample. Our results indicate that easy-to-use task-driven EEG can enable large-scale investigations in cognitive neuroscience. In future, this approach may be useful in clinical applications such as screening and tracking of treatment response.

Hippocampal and prefrontal contributions to memory retrieval: Examination of immediate early gene, NMDA receptor and environmental interactions.

Animals can use a range of strategies to recall important locations. These include simple stimulus-response strategies and more complex spatial (place) strategies, which are thought to have distinct neural substrates. The hippocampus-and NMDA receptor activation therein-is considered to be crucial for spatial, but not response strategies. The medial prefrontal cortex has also been implicated in memory retrieval; however, evidence concerning its specific role is equivocal. Both hippocampal and prefrontal regions have been associated with flexible behavioural responding (e.g. when task demands change). Here, we investigated the use of spatial and non-spatial strategies in the Morris water maze and their associated brain areas in rats using immediate early gene (IEG) imaging of Zif268 and c-Fos. Specifically, we charted the involvement of hippocampal and prefrontal subregions during retrieval of spatial and non-spatial memories. Behavioural flexibility was also examined using intact and partial cue configurations during recall. Results indicated that regions of both the hippocampus (area CA3) and prefrontal cortex (anterior cingulate cortex) were preferentially engaged in spatial memory recall compared to response learning. In addition, both spatial and non-spatial memories were dependent on NMDA receptor activation. MK801 impaired recall performance across all groups and reduced IEG activation across hippocampal and prefrontal regions. Finally, IEG results revealed divergent patterns of Zif268 and c-Fos activity and support the suggestion that Zif268 plays a functional role in the recall of long-term memories.

Contralateral delay activity is not a robust marker of cognitive function in older adults at risk of mild cognitive impairment.

Contralateral delay activity (CDA) has been proposed as a pre-clinical neural marker for mild cognitive impairment (MCI). However, existing evidence is limited to one study with a small sample size (n = 24). Our aim was to extend previous work by investigating the relationship between the CDA and MCI risk in a large sample of older adults (n = 76). We used a regression approach to determine whether (and when) CDA amplitude predicted MCI risk, as indexed by the Montreal Cognitive Assessment (MoCA). CDA amplitude from ~300-500 and ~800-900 ms predicted MoCA performance. However, significant effects were only observed for specific electrodes (P5/P6 and CP3/CP4, but not PO7/PO8) and the nature of the relationship between the CDA and MoCA scores differed across time and according to set size. Bayesian regression analysis indicated partial evidence in favour of the null hypothesis (BF10 values = 4-1.18). Contrary to previous results, our findings suggest that the CDA may not a robust marker of MCI risk. More broadly, our results highlight the difficulty in identifying at-risk individuals, particularly as MCI is a heterogeneous, unstable condition. Future research should prioritise longitudinal approaches in order to track the progression of the CDA and its association with cognitive decline in later life.

EEG spectral power, but not theta/beta ratio, is a neuromarker for adult ADHD.

Adults with attention-deficit/hyperactivity disorder (ADHD) have been described as having altered resting-state electroencephalographic (EEG) spectral power and theta/beta ratio (TBR). However, a recent review (Pulini et al. 2018) identified methodological errors in neuroimaging, including EEG, ADHD classification studies. Therefore, the specific EEG neuromarkers of adult ADHD remain to be identified, as do the EEG characteristics that mediate between genes and behaviour (mediational endophenotypes). Resting-state eyes-open and eyes-closed EEG was measured from 38 adults with ADHD, 45 first-degree relatives of people with ADHD and 51 unrelated controls. A machine learning classification analysis using penalized logistic regression (Elastic Net) examined if EEG spectral power (1-45 Hz) and TBR could classify participants into ADHD, first-degree relatives and/or control groups. Random-label permutation was used to quantify any bias in the analysis. Eyes-open absolute and relative EEG power distinguished ADHD from control participants (area under receiver operating characteristic = 0.71-0.77). The best predictors of ADHD status were increased power in delta, theta and low-alpha over centro-parietal regions, and in frontal low-beta and parietal mid-beta. TBR did not successfully classify ADHD status. Elevated eyes-open power in delta, theta, low-alpha and low-beta distinguished first-degree relatives from controls (area under receiver operating characteristic = 0.68-0.72), suggesting that these features may be a mediational endophenotype for adult ADHD. Resting-state EEG spectral power may be a neuromarker and mediational endophenotype of adult ADHD. These results did not support TBR as a diagnostic neuromarker for ADHD. It is possible that TBR is a characteristic of childhood ADHD.

Depression diagnoses, but not individual differences in depression symptoms, are associated with reduced autobiographical memory specificity.

OBJECTIVES: Difficulties recalling specific events from one's autobiographical past have been associated with a range of emotional disorders. We present the first examination of whether diagnoses of depression or individual differences in depression severity explain the most variance in autobiographical memory specificity. We also examine the contribution of other key cognitive factors associated with reduced memory specificity - rumination and verbal fluency - to these effects. METHODS: Participants with (n = 21) and without (n = 25) major depressive disorder completed self-report measures of depression severity (Beck Depression Inventory version II; BDI-II) and ruminative tendency (Ruminative Response Scale), a measure of verbal fluency, and the Autobiographical Memory Test (AMT) to assess memory specificity. RESULTS: People diagnosed with depression recalled significantly fewer specific memories in the AMT relative to healthy controls. In a linear regression, diagnostic status explained a significant amount of unique variance in specificity whereas BDI-II scores did not. Diagnostic group differences in verbal fluency also explained a significant amount of variance in specificity. CONCLUSIONS: Our findings extend our understanding of the mechanisms involved in reduced memory specificity but future research must explore the causal contribution of weak executive functioning to reduced memory specificity. PRACTITIONERS POINTS: Diagnoses of depression were associated with problems recalling specific events from one's past. Problems with memory specificity amongst depressed people were associated with executive functioning difficulties. Problems with specificity were not associated with individual differences in depression severity or ruminative tendencies.

Synaesthesia lost and found: two cases of person- and music-colour synaesthesia.

Synaesthesia is a developmental condition involving cross-communication between sensory modalities or substreams whereby an inducer (e.g. a sound) automatically evokes a concurrent percept in another modality (e.g. a colour). Whether this condition arises due to atypical structural connectivity (e.g., between normally unconnected cortical areas) or altered neurochemistry remains a central question. We report the exceptional cases of two synaesthetes - subjects AB and CD - both of whom experience coloured auras around individuals, as well as coloured perceptions in response to music. Both subjects have, in recent years, suffered a complete loss or reduction of their synaesthetic experiences, one (AB) through successive head traumas, including a lightning strike, followed by a number of medications, and the other (CD) while taking anxiolytic medications. Using semi-structured interviews and data from the Synaesthesia Battery and a colourpicker task, we characterize the phenomenological characteristics of their pre-loss synaesthesia, as well as the subsequent restoration of each subject's synaesthetic experiences (in the months post-trauma for AB, and after cessation of medication for CD). Even after years of suppression, the patterns of associations were highly consistent with those experienced pre-injury. The phenomenological experience of synaesthesia can, thus, like most conscious experiences, be modulated by pharmacologically diverse medications or head injury. However, the underlying neural substrates mediating specific synaesthetic pairings appear remarkably 'hard-wired' and can persist over very long periods even under conditions that alter or completely suppress the conscious synaesthetic experience itself.

Differential expression of immediate early genes Zif268 and c-Fos in the hippocampus and prefrontal cortex following spatial learning and glutamate receptor antagonism.

The objective of this study was to examine the effects of NMDAR and AMPAR antagonism on the expression of Zif268 and c-Fos in the hippocampus and medial prefrontal cortex during spatial memory encoding in rats trained in the Morris water maze. NMDAR inhibition impaired navigation and significantly attenuated expression of Zif268, but not c-Fos, in area CA1. AMPAR channel blockade had little effect on learning or IEG expression. Overall, Zif268 and c-Fos displayed markedly different patterns of hippocampal and prefrontal expression, with Zif268 being more closely linked to spatial learning.

Learning efficiency: The influence of cue salience during spatial navigation.

In three experiments, male Wistar rats were trained to find a hidden platform in the Morris water maze using two cues for five or ten days. Experiments 1 and 2 investigated two factors of cue salience; proximity to the goal and brightness. Results from Experiment 1 showed that rats tested with a bright distal cue were significantly better at locating the platform than rats tested with the proximal cue after five- and ten-day training with both cues. In Experiment 2, the position of the cues was reversed. Rats tested with a brighter proximal cue outperformed those tested with a distal cue. Findings from Experiments 1 and 2 suggest that brightness acquired more control over rats' behaviour than proximity to the goal. Animals in Experiment 3 were trained with equally bright proximal and distal cues. Unexpectedly, probe tests revealed that rats tested with the farther cue were more accurate than those tested with the proximal cue, but only after extended training. Possible explanations for this result are discussed with reference to errors in directional information estimation and cue assignment, cue elevation and the use of the pool wall as a navigational aid. Taken together, findings point towards the use of an elemental learning strategy involving the more salient of the two cues which emerged earlier when the relative saliences of the cues differed considerably.