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Objective: The social cognitive abilities of emotion perception, cognitive theory of mind (ToM), affective ToM, and emotional empathy change across adulthood. Few existing studies have examined the performance of a single social cognitive domain in later life, with no known studies having examined all four abilities together. Although it is well understood how non-social cognitive performance changes with age, and this has helped inform diagnostic methods for age-related disorders, relatively little is known about typical age-related social cognitive performance in later life. The current study aimed to investigate the association between age and social cognitive performance within a sample of healthy midlife to older adults., Method: This cross-sectional study examined emotion perception using the Mini-SEA Facial Emotion Recognition Test, cognitive and affective ToM using The Shortened Awareness of Social Inference Test-Short Form, and emotional empathy using the Interpersonal Reactivity Index in 236 healthy adults aged 43-80 years (M = 60.30, SD = 6.88, 76% female)., Results: Multiple linear regression analyses revealed that age only had a significant, medium, negative association with cognitive (B = -.08, p < .001) and affective (B = -.05, p < .001) ToM and was not significantly associated with emotion perception or emotional empathy., Conclusions: These findings enhance our understanding of normal social cognitive aging in later life, which can inform decisions around adding social cognitive measures into existing neuropsychological diagnostic tools for psychiatric, neurological, and developmental disorders., (© The Author(s) 2025. Published by Oxford University Press.)

Background: Healthy dietary patterns can support the maintenance of cognition and brain health in older age and are negatively associated with cardiometabolic risk. Cardiometabolic risk factors are similarly important for cognition and may play an important role in linking diet to cognition., Aim: This study aimed to explore the relationship between dietary patterns and cognition and to determine whether cardiometabolic health markers moderate these relationships in older adulthood., Design: A cross-sectional analysis of observational data from the baseline of the ACTIVate study., Participants: The cohort included 426 cognitively normal adults aged 60-70 years., Methods: The Australian Eating Survey (AES) Food Frequency Questionnaire was used to collect data on usual dietary intake, along with additional questions assessing intake of dietary oils. Principal component analysis (PCA) was applied to reduce the dimensionality of dietary data. Cardiometabolic risk was quantified using the metabolic syndrome severity score (MetSSS). Tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were used to derive composite scores on four cognitive domains: processing speed, executive function, short-term memory, and long-term memory., Results: Three dietary patterns were identified using PCA: a plant-dominant diet, a Western-style diet, and a meat-dominant diet. After controlling for age, sex, total years of education, energy intake, and moderate-to-vigorous physical activity (MVPA), there was a small, negative association between the meat-dominant diets and long-term memory. Subsequent moderation analysis indicated that MetSSS significantly moderated this relationship., Conclusions: Findings highlight the link between diet, cardiometabolic health, and cognitive function in older, cognitively healthy adults. However, longitudinal studies are needed to confirm observations and evaluate the dynamics of diet, cardiometabolic health, and cognitive function over time.

Delirium is a common and acute neurocognitive disorder in older adults associated with increased risk of dementia and death. Understanding the interaction between brain vulnerability and acute stressors is key to delirium pathophysiology, but the neurophysiology of delirium vulnerability is not well defined. This study aimed to identify pre-operative resting-state EEG and event-related potential markers of incident delirium and its subtypes in older adults undergoing elective cardiac procedures. This prospective observational study included 58 older participants (mean age = 75.6 years, SD = 7.1; 46 male/12 female); COVID-19 restrictions limited recruitment. Baseline assessments were conducted in the weeks before elective cardiac procedures and included a 4-min resting-state EEG recording (2-min eyes open and 2-min eyes closed), a 5-min frequency auditory oddball paradigm recording, and cognitive and depression examinations. Periodic peak power, peak frequency and bandwidth measures, and aperiodic offsets and exponents were derived from resting-state EEG data. Event-related potentials were measured as mean component amplitudes (first positive component, first negative component, early third positive component, and mismatch negativity) following standard and deviant auditory stimuli. Incident delirium occurred in 21 participants: 10 hypoactive, 6 mixed, and 5 hyperactive. Incident hyperactive delirium was associated with higher pre-operative eyes open ( P = 0.045, d = 1.0) and closed ( P = 0.036, d = 1.0) aperiodic offsets. Incident mixed delirium was associated with significantly larger pre-operative first positive component amplitudes to deviants ( P = 0.037, d = 1.0) and larger third positive component amplitudes to standards ( P = 0.025, d = 1.0) and deviants ( P = 0.041, d = 0.9). Other statistically non-significant but moderate-to-large effects were observed in relation to all subtypes. We report evidence of neurophysiological markers of delirium risk weeks prior to elective cardiac procedures in older adults. Despite being underpowered due to COVID-19-related recruitment impacts, these findings indicate pre-operative dysfunction in neural excitation/inhibition balance associated with different delirium subtypes and warrant further investigation on a larger scale., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Theory of mind (ToM) has been argued to be a multidimensional construct, with ToM inferences depending on distinct processes across affective and cognitive ToM tasks and across first-order cognitive and second-order cognitive ToM tasks. Behavioural evidence for a multidimensional account has primarily depended on dissociations identified via analysis of variance, a statistical approach insufficient for assessing dimensionality. Instead, state-trace analysis (STA) is a more appropriate statistical technique to uncover dimensionality. The current study first applied STA to two summary datasets that had previously identified key dissociations between cognitive and affective ToM; these reanalyses did not support a multidimensional account of ToM. Next, STA was applied to a more detailed dataset to reveal whether ToM is based on multiple processes in a sample of 115 older adults aged 60-85 years (M = 68.5, SD = 5.92, 61.7% female) with higher or lower emotion perception ability. Participants made ToM judgements about different social exchanges (e.g., sarcasm or lying). STA results supported a multidimensional account of ToM across first-order cognitive, second-order cognitive, and affective ToM subdomains. These results lay a more rigorous foundation for subsequent studies to further examine the dimensionality of ToM and to apply formal modelling, progressing the field's understanding and measurement of the cognitive processes driving ToM judgements., (© 2023. The Author(s).)

Emotional empathy is a congruent emotional response stemming from another's emotional state and has mixed evidence for its association with age. We sought to synthesize existing data to investigate cross-sectional changes in emotional empathy across adulthood using random-effects meta-analyses. Embase, APA PsycInfo, Medline, and Scopus databases were systematically searched until October 2022. Thirty-three studies assessed age categorically by comparing older ( M = 68.42, SD = 4.95) with younger ( M = 27.55, SD = 6.82) adults and demonstrated higher emotional empathy in older adults ( g = 0.10, p = .039). Seven studies examined age continuously (18-100 years), resulting in a positive correlation with age ( z r = .08, p = .033). Subgroup analyses identified age effects differed based on the emotional empathy measure but not on measure type (state vs. trait) or gender ratio (73% women and 27% men). Cross-sectional results indicate emotional empathy may increase across adulthood. These results clarify the previously mixed reports of typical emotional empathy functioning in later life. Age effects varying due to the emotional empathy measure examined indicate that these measures' convergent validity should be reexamined. Further research should employ older, population-based, non-western, educated, industrialized, rich, and democratic samples and longitudinal designs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

SpecParam (formally known as FOOOF) allows for the refined measurements of electroencephalography periodic and aperiodic activity, and potentially provides a non-invasive measurement of excitation: inhibition balance. However, little is known about the psychometric properties of this technique. This is integral for understanding the usefulness of SpecParam as a tool to determine differences in measurements of cognitive function, and electroencephalography activity. We used intraclass correlation coefficients to examine the test-retest reliability of parameterized activity across three sessions (90 minutes apart and 30 days later) in 49 healthy young adults at rest with eyes open, eyes closed, and during three eyes closed cognitive tasks including subtraction (Math), music recall (Music), and episodic memory (Memory). Intraclass correlation coefficients were good for the aperiodic exponent and offset (intraclass correlation coefficients > 0.70) and parameterized periodic activity (intraclass correlation coefficients > 0.66 for alpha and beta power, central frequency, and bandwidth) across conditions. Across all three sessions, SpecParam performed poorly in eyes open (40% of participants had poor fits over non-central sites) and had poor test-retest reliability for parameterized periodic activity. SpecParam mostly provides reliable metrics of individual differences in parameterized neural activity. More work is needed to understand the suitability of eyes open resting data for parameterization using SpecParam., (© The Author(s) 2023. Published by Oxford University Press.)

We investigated how resting electroencephalography (EEG) measures are associated with risk factors for late-life cognitive impairment and dementia, including age, apolipoprotein E ɛ4 (APOE-ɛ4) carriage, and cardiometabolic burden. Resting EEG was recorded from 86 adults (50-80 years of age). Participants additionally completed the Addenbrooke's Cognitive Examination (ACE) III and had blood drawn to assess APOE-ɛ4 carriage status and cardiometabolic burden. EEG power spectra were decomposed into sources of periodic and aperiodic activity to derive measures of aperiodic component slope and alpha (7-14 Hz) and beta (15-30 Hz) peak power and peak frequency. Alpha and beta peak power measures were corrected for aperiodic activity. The aperiodic component slope was correlated with ACE-III scores but not age. Alpha peak frequency decreased with age. Individuals with higher cardiometabolic burden had lower alpha peak frequencies and lower beta peak power. APOE-ɛ4 carriers had lower beta peak frequencies. Our findings suggest that the slope of the aperiodic component of resting EEG power spectra is more closely associated with measures of cognitive performance rather than chronological age in older adults., Competing Interests: Disclosure statement The authors report no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Expert adult readers process fluent and disfluent fonts differently, at both early perceptual and late higher-order processing stages. This finding has been interpreted as reflecting the more difficult to read disfluent fonts requiring greater neural resources. We aimed to investigate whether neural activity is affected by font disfluency in pre-adolescent readers, and to determine if neural responses are related to reading performance. Thirty-three participants between 8 and 12 years old completed two one-back tasks using letter and word stimuli, where font was manipulated (fluent versus disfluent stimuli), during which electroencephalography was recorded. Event related potentials (ERPs) were calculated relative to non-target stimuli for both tasks. The Woodcock Johnson III Tests of Achievement reading specific tests, and the Castles and Coltheart Test 2 were also collected. Font (fluent versus disfluent stimuli) did not consistently affect neural activity during both the letter and word tasks. Fluent stimuli elicited greater late activity (450-600 ms) than disfluent stimuli during the word task, suggesting easy-to-read fonts may enhance the maintenance of words in visual working memory and facilitate the retrieval of semantic information. However, reading performance was not associated with neural disfluency effects, suggesting that pre-adolescents are still at an early developmental reading period. Font manipulation may be a useful way to track developmental reading trajectories in the brain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: Implantable cardioverter defibrillators (ICDs) prevent sudden cardiac death. Anxiety, depression, and post-traumatic stress disorder (PTSD) are underappreciated symptoms. We aimed to systematically synthesize prevalence estimates of mood disorders and symptom severities, pre- and post-ICD insertions. Comparisons were made with control groups, as well as within ICD patients by indication (primary vs. secondary), sex, shock status, and over time., Methods: Databases (Medline, PsycINFO, PubMed, and Embase) were searched without limits from inception to 31 August 2022; 4661 articles were identified, 109 (39 954 patients) of which met criteria., Results: Random-effects meta-analyses revealed clinically relevant anxiety in 22.58% (95%CI 18.26-26.91%) of ICD patients across all timepoints following insertion and depression in 15.42% (95%CI 11.90-18.94%). Post-traumatic stress disorder was seen in 12.43% (95%CI 6.90-17.96%). Rates did not vary relative to indication group. Clinically relevant anxiety and depression were more likely in ICD patients who experienced shocks [anxiety odds ratio (OR) = 3.92 (95%CI 1.67-9.19); depression OR = 1.87 (95%CI 1.34-2.59)]. Higher symptoms of anxiety were seen in females than males post-insertion [Hedges' g = 0.39 (95%CI 0.15-0.62)]. Depression symptoms decreased in the first 5 months post-insertion [Hedges' g = 0.13 (95%CI 0.03-0.23)] and anxiety symptoms after 6 months [Hedges' g = 0.07 (95%CI 0-0.14)]., Conclusion: Depression and anxiety are highly prevalent in ICD patients, especially in those who experience shocks. Of particular concern is the prevalence of PTSD following ICD implantation. Psychological assessment, monitoring, and therapy should be offered to ICD patients and their partners as part of routine care., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Population-based autopsy studies provide valuable insights into the causes of dementia but are limited by sample size and restriction to specific populations. Harmonisation across studies increases statistical power and allows meaningful comparisons between studies. We aimed to harmonise neuropathology measures across studies and assess the prevalence, correlation, and co-occurrence of neuropathologies in the ageing population., Methods: We combined data from six community-based autopsy cohorts in the US and the UK in a coordinated cross-sectional analysis. Among all decedents aged 80 years or older, we assessed 12 neuropathologies known to be associated with dementia: arteriolosclerosis, atherosclerosis, macroinfarcts, microinfarcts, lacunes, cerebral amyloid angiopathy, Braak neurofibrillary tangle stage, Consortium to Establish a Registry for Alzheimer's disease (CERAD) diffuse plaque score, CERAD neuritic plaque score, hippocampal sclerosis, limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and Lewy body pathology. We divided measures into three groups describing level of confidence (low, moderate, and high) in harmonisation. We described the prevalence, correlations, and co-occurrence of neuropathologies., Findings: The cohorts included 4354 decedents aged 80 years or older with autopsy data. All cohorts included more women than men, with the exception of one study that only included men, and all cohorts included decedents at older ages (range of mean age at death across cohorts 88·0-91·6 years). Measures of Alzheimer's disease neuropathological change, Braak stage and CERAD scores, were in the high confidence category, whereas measures of vascular neuropathologies were in the low (arterioloscerosis, atherosclerosis, cerebral amyloid angiopathy, and lacunes) or moderate (macroinfarcts and microinfarcts) categories. Neuropathology prevalence and co-occurrence was high (2443 [91%] of 2695 participants had more than one of six key neuropathologies and 1106 [41%] of 2695 had three or more). Co-occurrence was strongly but not deterministically associated with dementia status. Vascular and Alzheimer's disease features clustered separately in correlation analyses, and LATE-NC had moderate associations with Alzheimer's disease measures (eg, Braak stage ρ=0·31 [95% CI 0·20-0·42])., Interpretation: Higher variability and more inconsistency in the measurement of vascular neuropathologies compared with the measurement of Alzheimer's disease neuropathological change suggests the development of new frameworks for the measurement of vascular neuropathologies might be helpful. Results highlight the complexity and multi-morbidity of the brain pathologies that underlie dementia in older adults and suggest that prevention efforts and treatments should be multifaceted., Funding: Gates Ventures., Competing Interests: Declaration of interests SS reports consulting fees from Biogen and Eisai. JS reports consulting fees from AVID, Alnylam Pharmaceuticals, and Cerveau Technologies. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Physical activity, sedentary behaviour and sleep are associated with cognitive function in older adults. However, these behaviours are not independent, but instead make up exclusive and exhaustive components of the 24-h day. Few studies have investigated associations between 24-h time-use composition and cognitive function in older adults. Of these, none have considered how the quality of sleep, or the context of physical activity and sedentary behaviour may impact these relationships. This study aims to understand how 24-h time-use composition is associated with cognitive function across a range of domains in healthy older adults, and whether the level of recreational physical activity, amount of television (TV) watching, or the quality of sleep impact these potential associations., Methods: 384 healthy older adults (age 65.5 ± 3.0 years, 68% female, 63% non-smokers, mean education = 16.5 ± 3.2 years) participated in this study across two Australian sites (Adelaide, n = 207; Newcastle, n = 177). Twenty-four-hour time-use composition was captured using triaxial accelerometry, measured continuously across 7 days. Total time spent watching TV per day was used to capture the context of sedentary behaviours, whilst total time spent in recreational physical activity was used to capture the context of physical activity (i.e., recreational accumulation of physical activity vs. other contexts). Sleep quality was measured using a single item extracted from the Pittsburgh Sleep Quality Index. Cognitive function was measured using a global cognition index (Addenbrooke's Cognitive Examination III) and four cognitive domain composite scores (derived from five tests of the Cambridge Neuropsychological Test Automated Battery: Paired Associates Learning; One Touch Stockings of Cambridge; Multitasking; Reaction Time; Verbal Recognition Memory). Pairwise correlations were used to describe independent relationships between time use variables and cognitive outcomes. Then, compositional data analysis regression methods were used to quantify associations between cognition and 24-h time-use composition., Results: After adjusting for covariates and false discovery rate there were no significant associations between time-use composition and global cognition, long-term memory, short-term memory, executive function, or processing speed outcomes, and no significant interactions between TV watching time, recreational physical activity engagement or sleep quality and time-use composition for any cognitive outcomes., Discussion: The findings highlight the importance of considering all activities across the 24-h day against cognitive function in older adults. Future studies should consider investigating these relationships longitudinally to uncover temporal effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mellow, Dumuid, Wade, Stanford, Olds, Karayanidis, Hunter, Keage, Dorrian, Goldsworthy and Smith.)

People's perceptions of the mental effort required for everyday activities may drive variation in the relationships between lifestyles and cognitive ability. We asked n = 259 healthy older adults aged 60 to 70 years (90 males, 169 females) to provide a rating of the Perceived Mental Effort (PME) for each activity instance they recalled over a 48-h period as part of a time-use recall. PME was rated on a 9-point scale from "very, very low" (score of 1) to "very, very high" (score of 9). Across the entire sample, participants rated a total of 196 different activities and 17,433 activity instances. The mean PME for individual activities was 3.50 ± 1.58. PMEs varied significantly by activity domain, with highest ratings being for Work (5.48 ± 1.72) and the lowest for Self-Care (2.89 ± 0.98). In multivariate analyses, PME ratings were higher in males than females (+0.30), PMEs were higher later in the day, increased with task duration, and decreased with age (all p < 0.0001). Time-weighted average individual PMEs across the two days of recall ranged from 1.86 to 6.50, and were 0.3 units higher for males, but unrelated to age. Repeated intra-individual PME ratings for the same activity were very reliable (ICC = 0.995, mean absolute difference = 0.03 ± 0.17). PMEs show promise as a reliable measure of mental effort., Competing Interests: Declaration of competing interest None., (Copyright © 2022. Published by Elsevier Inc.)

Background: Delirium is a common neurocognitive disorder in hospitalised older adults with vast negative consequences. The predominant method of subtyping delirium is by motor activity profile into hypoactive, hyperactive and mixed groups., Objective: This systematic review and meta-analysis investigated how predisposing factors differ between delirium motor subtypes., Methods: Databases (Medline, PsycINFO, Embase) were systematically searched for studies reporting predisposing factors (prior to delirium) for delirium motor subtypes. A total of 61 studies met inclusion criteria (N = 14,407, mean age 73.63 years). Random-effects meta-analyses synthesised differences between delirium motor subtypes relative to 22 factors., Results: Hypoactive cases were older, had poorer cognition and higher physical risk scores than hyperactive cases and were more likely to be women, living in care homes, taking more medications, with worse functional performance and history of cerebrovascular disease than all remaining subtypes. Hyperactive cases were younger than hypoactive and mixed subtypes and were more likely to be men, with better cognition and lower physical risk scores than all other subtypes. Those with no motor subtype (unable to be classified) were more likely to be women and have better functional performance. Effect sizes were small., Conclusions: Important differences in those who develop motor subtypes of delirium were shown prior to delirium occurrence. We provide robust quantitative evidence for a common clinical assumption that indices of frailty (institutional living, cognitive and functional impairment) are seen more in hypoactive patients. Motor subtypes should be measured across delirium research. Motor subtyping has great potential to improve the clinical risk assessment and management of delirium., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer's disease neuropathologic change (ADNC) are each associated with substantial cognitive impairment in aging populations. However, the prevalence of LATE-NC across the full range of ADNC remains uncertain. To address this knowledge gap, neuropathologic, genetic, and clinical data were compiled from 13 high-quality community- and population-based longitudinal studies. Participants were recruited from United States (8 cohorts, including one focusing on Japanese-American men), United Kingdom (2 cohorts), Brazil, Austria, and Finland. The total number of participants included was 6196, and the average age of death was 88.1 years. Not all data were available on each individual and there were differences between the cohorts in study designs and the amount of missing data. Among those with known cognitive status before death (n = 5665), 43.0% were cognitively normal, 14.9% had MCI, and 42.4% had dementia-broadly consistent with epidemiologic data in this age group. Approximately 99% of participants (n = 6125) had available CERAD neuritic amyloid plaque score data. In this subsample, 39.4% had autopsy-confirmed LATE-NC of any stage. Among brains with "frequent" neuritic amyloid plaques, 54.9% had comorbid LATE-NC, whereas in brains with no detected neuritic amyloid plaques, 27.0% had LATE-NC. Data on LATE-NC stages were available for 3803 participants, of which 25% had LATE-NC stage > 1 (associated with cognitive impairment). In the subset of individuals with Thal Aβ phase = 0 (lacking detectable Aβ plaques), the brains with LATE-NC had relatively more severe primary age-related tauopathy (PART). A total of 3267 participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of definite FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In the 10 cohorts with detailed neurocognitive assessments proximal to death, cognition tended to be worse with LATE-NC across the full spectrum of ADNC severity. This study provided a credible estimate of the current prevalence of LATE-NC in advanced age. LATE-NC was seen in almost 40% of participants and often, but not always, coexisted with Alzheimer's disease neuropathology., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Blood pressure variability (BPV) has been linked with cognitive impairment and dementia. However, the pathophysiological mechanisms by which BPV affects cognition are unclear. This systematic review aims to assess the links between different BPV measures and white and grey matter structures., Methods and Results: The following databases were searched from inception through to January 2021; EMBASE, MEDLINE, EMCARE and SCOPUS. Studies that reported on the relationship between within-individual BPV (short, medium or long-term variability) or a circadian blood pressure (BP) measurement and MRI assessed brain structures were included. Overall, 20 studies met the criteria and were included, of which 11 studies looked at short-term BPV, eight articles investigated visit-to-visit BPV and one study looked at a compositional BPV measurement. Due to heterogeneity in study samples, meta-analysis was not possible. Across the included studies, associations between MRI indices and BP dipping patterns were mixed; higher long-term BPV and higher sleep systolic BPV was found to be associated with lower whole brain volume and hippocampal volume., Conclusion: Increased BPV, in particular systolic long-term and systolic night-time BPV, appears to be associated with lower brain volume and hippocampal volume. This highlights the adverse effect that increased BPV has upon the brain, potentially contributing to cognitive decline, including dementia, in late-life., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The aim of this study was to assess the long-term risk for mortality and incident dementia associated with exposure to intimate partner violence (IPV) at any time over the life course. Data were taken from the Australian Longitudinal Study of Women's Health, a population-based cohort study initiated in 1996. Analysis is based on 12,085 community-dwelling women aged 70 to 75 years at baseline from all states and territories. Self-reported exposure to violence was separated into historical (any time before baseline), current (past 12 months), or both. Date of death was obtained from the National Death Index, and dementia status was self-reported or obtained from administrative data. We modeled mortality risk using Cox regression, and risk for incident dementia using Fine-Gray proportional hazards modeling with death as a competing risk. Follow up continued to December 2017. At baseline, 728 women (6.0%) reported historical IPV, 121 (1.0%) reported current violence, and 38 reported both (0.3%). Historical IPV increased 20-year mortality risk after controlling for demographic, socioeconomic, and lifestyle variables (hazard ratio 1.10, 95% confidence interval = [1.00, 1.20]). There was no relationship between current violence and mortality (hazard ratio 1.04, 95% confidence interval = [0.85, 1.29]). There was also no association between IPV and risk for incident dementia (hazard ratio 1.02, 95% confidence interval = [0.89, 1.17]). Older women who self-report exposure to IPV over the lifespan die significantly earlier than women who do not. Further research that considers the mediating role of psychological trauma is needed to examine the relationship between IPV and dementia.

Delirium is a common neurocognitive disorder in hospitalised older adults with substantial negative consequences. Impaired global cognition is a well-established delirium risk factor. However, poor performance on attention tests and higher intra-subject variability may be more sensitive delirium risk factors, given the disorder is characterised by a fluctuating course and attentional deficits. We systematically searched databases (Embase, PsycINFO, MEDLINE) and 44 studies satisfied inclusion criteria. Random-effects meta-analysis models showed poor performance in all cognitive domains except perception was significantly associated with incident delirium. Largest effects were for orientation (g=-1.20) and construction and motor performance (g=-0.60). These effects were no longer significant in the subgroup without pre-existing cognitive impairment, where executive functions and verbal functions and language skills were associated with incident delirium. A small, non-significant association between intra-subject variability and incident delirium was found (g=0.42). Cognitive domain specific tests may be quicker and more sensitive predictors of incident delirium. This pattern of neuropsychological findings supports the proposition that vulnerability for delirium manifests as a dysfunction of whole-brain information integration., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Delirium is a neurocognitive disorder common in older adults in acute care settings. Those who develop delirium are at an increased risk of dementia, cognitive decline and death. Electroencephalography (EEG) during delirium in older adults is characterised by slowing and reduced functional connectivity, but markers of vulnerability are poorly described. We aim to identify EEG spectral power and event-related potential (ERP) markers of incident delirium in older adults to understand neural mechanisms of delirium vulnerability. Characterising delirium vulnerability will provide substantial theoretical advances and outcomes have the potential to be translated into delirium risk assessment tools., Methods and Analysis: We will record EEG in 90 participants over 65 years of age prior to elective coronary artery bypass grafting (CABG) or transcatheter aortic valve implantation (TAVI). We will record 4-minutes of resting state (eyes open and eyes closed) and a 5-minute frequency auditory oddball paradigm. Outcome measures will include frequency band power, 1/f offset and slope, and ERP amplitude measures. Participants will undergo cognitive and EEG testing before their elective procedures and daily postoperative delirium assessments. Group allocation will be done retrospectively by linking preoperative EEG data according to postoperative delirium status (presence, severity, duration and subtype)., Ethics and Dissemination: This study is approved by the Human Research Ethics Committee of the Royal Adelaide Hospital, Central Adelaide Local Health Network and the University of South Australia Human Ethics Committee. Findings will be disseminated through peer-reviewed journal articles and presentations at national and international conferences., Trial Registration Number: ACTRN12618001114235 and ACTRN12618000799257., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: There are well established modifiable risk factors for late-life dementia. These risk factors account for over 30% of population attributable dementia risk and accrue over the lifespan. Young adults have the greatest potential to reduce their own risk for dementia. This study aimed to investigate what young Australian adults know about dementia and its risk factors, and further, how they estimated these risks., Methods: An online survey promoted through various social media platforms was completed by 604 young Australian adults aged 18-44 years of age., Results: Seventy percent of participants had a limited understanding of dementia (identifying cognitive or functional impairment), 25% had a good understanding, with 5% having no understanding. Twenty percent of respondents thought there were no modifiable risk factors for dementia. Less the half of participants agreed with two of the nine established dementia risk factors (hearing loss in midlife and education in early life), with over half of participants agreeing to the remaining seven risk factors. Females consistently judged the risks conferred by the nine established dementia risk factors to be higher than males. Those who were lonely judged the dementia risk conferred by loneliness to be higher than those who were not lonely; and smokers judged the dementia risk conferred by smoking to be less than non-smokers., Conclusion: Young adults have the greatest potential to change their dementia risk, and these findings show that there are important gaps in knowledge of dementia and its risk factors in this group., (© 2021. The Author(s).)

Objective: To assess the psychological impacts and risk for elder abuse associated with historical intimate partner violence (IPV) in older women., Design: Prospective cohort study SETTING: All Australian states and territories., Participants: A total of 12,259 women aged 70-75 years at baseline participating in the Australian Longitudinal Study of Women's Health., Measurements: Women were asked at baseline whether they had ever been in a violent relationship with a partner, and completed a comprehensive survey about their physical and psychological health every 3 years (15 years follow-up) including the Short Form-36 Mental Health subscale (SF-MH) and Vulnerability to Abuse Screening Scale (VASS). Linear mixed effects modelling with maximum likelihood estimation assessed the impact of IPV over time on the SF-MH and VASS. Risk for incident depression and experiencing physical or sexual violence over follow-up was examined using logistic regression models., Results: The 782 (6.4%) women who reported historical IPV recorded significantly poorer psychological wellbeing at all timepoints compared to those who did not report historical IPV, and were at higher risk for incident depression over follow up (adjusted odds ratio [aOR] = 1.36, 95% confidence interval [CI]:1.11-1.67). There was no significant relationship between historical IPV and self-reported exposure to physical or sexual violence in late life (aOR = 0.87, 95%CI: 0.53-1.43), but women who reported historical IPV recorded higher rates of vulnerability to abuse on the VASS., Discussion: Women who have experienced a violent relationship continue to experience negative effects into older age, highlighting the importance of clinical monitoring and ongoing support for survivors as they age., (Copyright © 2021 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Transcatheter aortic valve implantation (TAVI) has become the standard-of-care for treatment of severe symptomatic aortic stenosis and is also being increasingly recommended for low-risk patients. While TAVI boasts positive post-procedural outcomes, it is also associated with cognitive complications, namely delirium and cognitive decline. There is a pressing need for accurate risk tools which can identify TAVI patients at risk of delirium and cognitive decline, as risk scores designed for general cardiovascular surgery fall short. The present effect-finding exploratory study will assess the utility of various measures in the context of aging and frailty in predicting who will and who will not develop delirium or cognitive impairment following TAVI. The measures we propose include gait, visual symptoms, voice, swallowing, mood and sleep. Methods: This is an observational prospective cohort study focused on identifying pre-procedural risk factors for the development of delirium and cognitive decline following TAVI. Potential risk factors will be measured prior to TAVI. Primary outcomes will be post-procedure cognitive decline and delirium. Secondary outcomes include activities of daily living, quality of life, and mortality. Delirium presence will be measured on each of the first 2 days following TAVI. All other outcomes will be assessed at 3-, 6-, and 12-months post-operatively. A series of logistic regressions will be run to investigate the relationship between potential predictors and outcomes (presence vs. absence of either delirium or cognitive decline). Discussion: This study will assess the strengths of associations between a range of measures drawn from frailty and aging literature in terms of association with cognitive decline and delirium following TAVI. Identified measures can be used in future development of TAVI risk prediction models, which are essential for the accurate identification of cognitive at-risk patients and successful application of pre-procedural interventions. Clinical Trial Registration: This trial is registered with the Australian New Zealand Clinical Trials Registry. [https://bit.ly/2PAotP5], [ACTRN12618001114235]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ghezzi, Psaltis, Loetscher, Davis, Montarello, Lau, Delacroix, Bourke, McLoughlin, Keage and Keage.)

Current evidence suggests that the ability to detect and react to information under lowered alertness conditions might be more impaired on the left than the right side of space. This evidence derives mainly from right-handers being assessed in computer and paper-and-pencil spatial attention tasks. However, there are suggestions that left-handers might show impairments on the opposite (right) side compared to right-handers with lowered alertness, and it is unclear whether the impairments observed in the computer tasks have any real-world implications for activities such as driving. The current study investigated the alertness and spatial attention relationship under simulated monotonous driving in left- and right-handers. Twenty left-handed and 22 right-handed participants (15 males, mean age = 23.6 years, SD = 5.0 years) were assessed on a simulated driving task (lasting approximately 60 min) to induce a time-on-task effect. The driving task involved responding to stimuli appearing at six different horizontal locations on the screen, whilst driving in a 50 km/h zone. Decreases in alertness and driving performance were evident with time-on-task in both handedness groups. We found handedness impacts reacting to lateral stimuli differently with time-on-task: right-handers reacted slower to the leftmost stimuli, while left-handers showed the opposite pattern (although not statistically significant) in the second compared to first half of the drive. Our findings support suggestions that handedness modulates the spatial attention and alertness interactions. The interactions were observed in a simulated driving task which calls for further research to understand the safety implications of these interactions for activities such as driving.

Introduction: Apathy is a prevalent neuropsychiatric symptom for older adults residing in aged care. Left untreated, apathy has been associated with accelerated cognitive decline and increased risk of mortality. Reminiscence therapy is commonly used in aged care and has demonstrated to reduce apathy. Traditional methods of reminiscence use physical objects and more recently technology including tablets and laptop computers have demonstrated potential. Virtual reality (VR) has successfully been used to treat psychological disorders; however, there is little evidence on using VR for behavioural symptoms such as apathy in older adults. Using VR to deliver reminiscence therapy provides an immersive experience, and readily available applications provide access to a large range of content allowing easier delivery of therapy over traditional forms of therapy. This study aims to identify changes in apathy after a reminiscence therapy intervention using head-mounted displays (HMDs)., Methods and Analysis: Participants will be allocated to one of three groups; reminiscence therapy using VR; an active control using a laptop computer or physical items and a passive control. A total of 45 participants will be recruited from residential aged care (15 in each group). The three groups will be compared at baseline and follow-up. The primary outcome is apathy, and secondary outcomes include cognition and depression. Side effects from using HMDs will also be examined in the VR group. Primary and secondary outcomes at baseline and follow-up will be analysed using linear mixed modelling., Ethics and Dissemination: Ethics approval was obtained from the University of South Australia Human Research Ethics Committee. The results from this study will be disseminated through manuscript publications and national/international conferences., Trial Registration Number: ACTRN12619001510134., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cognitive side effects of anticholinergic medications in older adults are well documented. Whether these poor cognitive outcomes are observed in children has not been systematically investigated. We aimed to conduct a systematic review and meta-analysis on the associations between anticholinergic medication use and cognitive performance in children. Systematic review was conducted using Medline, PsychInfo, and Embase, identifying studies testing cognitive performance relative to the presence versus absence of anticholinergic medication(s) in children. We assessed effects overall, as well as relative to drug class, potency (low and high), cognitive domain, and duration of administration. The systematic search identified 46 articles suitable for meta-analysis. For the most part, random effects meta-analyses did not identify statistically significant associations between anticholinergic exposure and cognitive performance in children; the one exception was a small effect of anticholinergic anti-depressants being associated with better cognitive function (Hedges' g = 0.24, 95% CI 0.06-0.42, p = 0.01). Anticholinergic medications do not appear to be associated with poor cognitive outcomes in children, as they do in older adults. The discrepancy in findings with older adults may be due to shorter durations of exposure in children, differences in study design (predominantly experimental studies in children rather than predominantly epidemiological in older adults), biological ageing (e.g. blood brain barrier integrity), along with less residual confounding due to minimal polypharmacy and comorbidity in children.

Delirium is a common neurocognitive disorder in hospital settings, characterised by fluctuating impairments in attention and arousal following an acute precipitant. Electroencephalography (EEG) is a useful method to understand delirium pathophysiology. We performed a systematic review to investigate associations between delirium and EEG measures recorded prior, during, and after delirium. A total of 1,655 articles were identified using PsycINFO, Embase and MEDLINE, 31 of which satisfied inclusion criteria. Methodological quality assessment was undertaken, resulting in a mean quality score of 4 out of a maximum of 5. Qualitative synthesis revealed EEG slowing and reduced functional connectivity discriminated between those with and without delirium (i.e. EEG during delirium); the opposite pattern was apparent in children, with cortical hyperexcitability. EEG appears to have utility in differentiating those with and without delirium, but delirium vulnerability and the long-term effects on brain function require further investigation. Findings provide empirical support for the theory that delirium is a disorder of reduced functional brain integration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background Coronary artery bypass grafting (CABG) is known to improve heart function and quality of life, while rates of surgery-related mortality are low. However, delirium and cognitive decline are common complications. We sought to identify preoperative, intraoperative, and postoperative risk or protective factors associated with delirium and cognitive decline (across time) in patients undergoing CABG. Methods and Results We conducted a systematic search of Medline, PsycINFO, EMBASE, and Cochrane (March 26, 2019) for peer-reviewed, English publications reporting post-CABG delirium or cognitive decline data, for at least one risk factor. Random-effects meta-analyses estimated pooled odds ratio for categorical data and mean difference or standardized mean difference for continuous data. Ninety-seven studies, comprising data from 60 479 patients who underwent CABG, were included. Moderate to large and statistically significant risk factors for delirium were as follows: (1) preoperative cognitive impairment, depression, stroke history, and higher European System for Cardiac Operative Risk Evaluation (EuroSCORE) score, (2) intraoperative increase in intubation time, and (3) postoperative presence of arrythmia and increased days in the intensive care unit; higher preoperative cognitive performance was protective for delirium. Moderate to large and statistically significant risk factors for acute cognitive decline were as follows: (1) preoperative depression and older age, (2) intraoperative increase in intubation time, and (3) postoperative presence of delirium and increased days in the intensive care unit. Presence of depression preoperatively was a moderate risk factor for midterm (1-6 months) post-CABG cognitive decline. Conclusions This meta-analysis identified several key risk factors for delirium and cognitive decline following CABG, most of which are nonmodifiable. Future research should target preoperative risk factors, such as depression or cognitive impairment, which are potentially modifiable. Registration URL: https://www.crd.york.ac.uk/prosp​ero/; Unique identifier: CRD42020149276.

Higher and lower levels of alertness typically lead to a leftward and rightward bias in attention, respectively. This relationship between alertness and spatial attention potentially has major implications for health and safety. The current study examined alertness and spatial attention under simulated shiftworking conditions. Nineteen healthy right-handed participants (M = 24.6 ± 5.3 years, 11 males) completed a seven-day laboratory based simulated shiftwork study. Measures of alertness (Stanford Sleepiness Scale and Psychomotor Vigilance Task) and spatial attention (Landmark Task and Detection Task) were assessed across the protocol. Detection Task performance revealed slower reaction times and higher omissions of peripheral (compared to central) stimuli, with lowered alertness; suggesting narrowed visuospatial attention and a slight left-sided neglect. There were no associations between alertness and spatial bias on the Landmark Task. Our findings provide tentative evidence for a slight neglect of the left side and a narrowing of attention with lowered alertness. The possibility that one's ability to sufficiently react to information in the periphery and the left-side may be compromised under conditions of lowered alertness highlights the need for future research to better understand the relationship between spatial attention and alertness under shiftworking conditions.

Background The Mediterranean diet has been linked to improved cognitive function and reduced risk of dementia. However, a traditional Mediterranean diet may not meet calcium requirements for older non-Mediterranean populations, which could limit long-term sustainability in Western countries. The current study therefore aimed to determine the cognitive and psychological effects of a Mediterranean diet with adequate calcium for an ageing Australian population. Method: A randomized controlled cross-over design trial compared a Mediterranean diet with 3-4 daily serves of dairy food (MedDairy) with a low-fat (LF) control diet. Forty-one participants aged ≥45 years with systolic blood pressure ≥120 mm Hg and at least two other risk factors for cardiovascular disease completed each dietary intervention for 8 weeks, with an 8-week washout period separating interventions. Attention, processing speed, memory and planning were assessed at the start and end of each intervention using the Cambridge Automated Neuropsychological Test Battery. Mood and health-related quality of life were evaluated using the Profile of Mood States (POMS) and Short-Form Health Survey (SF-36). Dementia risk was also measured using the Framingham Vascular Risk and CAIDE scores. Results Significant improvements were observed for processing speed ( P  = .04), Total Mood Disturbance ( P  = .01), Tension ( P  = .03), Depression ( P  = .03), Anger ( P  = .02), and Confusion ( P  = .004) following the MedDairy intervention. No significant effects were found for attention, memory and planning, or measures of dementia risk. Conclusion Our study provides evidence that a Mediterranean diet supplemented with dairy foods may benefit cognitive function and psychological well-being in an ageing population at risk of dementia.

Cardiometabolic diseases and risk factors increase the risk of late-life cognitive impairment and dementia and have also been associated with detrimental gray and white matter changes. However, the functional brain changes associated with cardiometabolic health in late-life are unclear. We sought to characterize these functional changes by recording event-related potentials (ERPs) during an n-back working memory task (0, 1, and 2 back) in 85 adults (60% female) between 50 and 80 years of age. Due to a stratified recruitment approach, participants varied widely in relation to cognitive function and cardiometabolic health. Standard and objective cut-offs for high blood glucose, waist to hip ratio (i.e., obesity), high blood cholesterol, and hypertension were employed to generate a summative score for cardiometabolic burden (none, one, or two or more above cut-off). Mixed effects modeling (covarying for age and gender) revealed no statistically significant associations between cardiometabolic burden and visual P1 and N1 component amplitudes. There was a significant effect for the P3b component: as cardiometabolic burden increased, P3b amplitude decreased. We show that cardiometabolic factors related to the development of cognitive impairment and dementia in late-life associate with brain activity, as recorded via ERPs. Findings have relevance for the monitoring of lifestyle interventions (typically targeting cardiometabolic factors) in aging, as ERPs may provide a more sensitive measure of change than cognitive performance. Further, our results raise questions related to the findings of a broad range of ERP studies where the groups compared may differ in their cardiometabolic health status (not only in psychological symptomatology)., (Copyright © 2020 Keage, Feuerriegel, Greaves, Tregoweth, Coussens and Smith.)

Changes to cognition, both decline and improvement, are commonly reported after transcatheter aortic valve implantation (TAVI). However, previous systematic reviews and meta-analyses have missed these subgroups by assessing whole-group-averages for cognitive outcomes. We sought to pool estimates to identify the prevalence of cognitive decline and improvement after TAVI, as well as associated factors for these outcomes. A systematic review identified 15 articles appropriate for meta-analysis. When robust cognitive change definitions were employed, the pooled prevalence of incident cognitive impairment up to 1-, 1 to 6-, and ≥6-months post-TAVI was 7%, 14%, and 12%, respectively. For cognitive improvement, the prevalence from 1 to 6 months and ≥6 months after TAVI was estimated to be 19% and 11%, respectively. Two factors were associated with these cognitive outcomes: (1) using a cerebral embolic protection device was associated with decreased prevalence of cognitive decline up to 1-week post-TAVI; (2) baseline cognitive impairment had a large association with post-TAVI cognitive improvement. In conclusion, cognitive decline and cognitive improvement are experienced by approximately 7% to 19% of patients after TAVI, respectively. Those with the lowest cognitive performance pre-TAVI appear to have the most to gain in terms of cognitive improvement post-TAVI. Identifying further predictive factors for cognitive decline and improvement post-TAVI will facilitate a personalized-medicine approach for cognitive care and prognosis., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Children often have a lack of dementia understanding and poor attitudes toward people with dementia. Intergenerational programs are increasingly common, but the effects on knowledge and attitudes related to dementia are mixed, especially in the long-term (6 months). Using a RE-AIM framework, we quantitatively evaluated the effects of an educational dementia program (with and without an intergenerational program) on dementia attitudes in the short and long-term, and qualitatively, which elements of the program facilitated this change. Methods: Eighty-one children (9.63 ± 0.52 years, 35 males) from three classes participated in an 8-week dementia education program and 52 also interacted with older adults through an intergenerational experience. Program reach was measured as the percentage of children who participated in the study. The Kids Insight into Dementia Survey (KIDS) was implemented to measure dementia knowledge and attitudes: efficacy and maintenance. Qualitative interviews with all participant groups informed both adoption and implementation. Cost-benefit analysis was used as a secondary outcome measure for efficacy. Results: The program demonstrated strong levels of impact reaching 93% of school children across the three included classes. Efficacy was demonstrated by a positive change in children's dementia knowledge and attitudes immediately post program, which remained increased (as compared to baseline) 6- months post intervention; there were no differences between groups (those who interacted with older adults and those who did not). Interviews identified positive changes in children's empathy and improved community awareness. Barriers to adoption included the project scope, time constraints incurred by school terms and the management of children-to-adult ratios. Conclusions: These findings provide the first evidence that school-based dementia education improves knowledge of and attitudes toward people with dementia long-term. We demonstrated programs such as this can be successful in both primary school and wider community settings, with support from school and community partners key to the success., (Copyright © 2020 Smith, Kamm, Lai, Hull, Baker, Milte, Ratcliffe, Loetscher and Keage.)

The use of head-mounted displays (HMD) for virtual reality (VR) application-based purposes including therapy, rehabilitation, and training is increasing. Despite advancements in VR technologies, many users still experience sickness symptoms. VR sickness may be influenced by technological differences within HMDs such as resolution and refresh rate, however, VR content also plays a significant role. The primary objective of this systematic review and meta-analysis was to examine the literature on HMDs that report Simulator Sickness Questionnaire (SSQ) scores to determine the impact of content. User factors associated with VR sickness were also examined. A systematic search was conducted according to PRISMA guidelines. Fifty-five articles met inclusion criteria, representing 3,016 participants (mean age range 19.5-80; 41% female). Findings show gaming content recorded the highest total SSQ mean 34.26 (95%CI 29.57-38.95). VR sickness profiles were also influenced by visual stimulation, locomotion and exposure times. Older samples (mean age ≥35 years) scored significantly lower total SSQ means than younger samples, however, these findings are based on a small evidence base as a limited number of studies included older users. No sex differences were found. Across all types of content, the pooled total SSQ mean was relatively high 28.00 (95%CI 24.66-31.35) compared with recommended SSQ cut-off scores. These findings are of relevance for informing future research and the application of VR in different contexts., (Copyright © 2020 Saredakis, Szpak, Birckhead, Keage, Rizzo and Loetscher.)

Limbic-predominant age-related TAR-DNA-binding protein-43 (TDP-43) encephalopathy with hippocampal sclerosis pathology (LATE-NC + HS) is a neurodegenerative disorder characterized by severe hippocampal CA1 neuron loss and TDP-43-pathology, leading to cognitive dysfunction and dementia. Polymorphisms in GRN, TMEM106B and ABCC9 are proposed as LATE-NC + HS risk factors in brain bank collections. To replicate these results in independent population-representative cohorts, hippocampal sections from brains donated to three such studies (Cambridge City over 75-Cohort [CC75C], Cognitive Function and Ageing Study [CFAS], and Vantaa 85+ Study) were stained with hematoxylin-eosin (n = 744) and anti-pTDP-43 (n = 713), and evaluated for LATE-NC + HS and TDP-43 pathology. Single nucleotide polymorphism genotypes in GRN rs5848, TMEM106B rs1990622 and ABCC9 rs704178 were determined. LATE-NC + HS (n = 58) was significantly associated with the GRN rs5848 genotype (χ 2 (2) = 20.61, P < 0.001) and T-allele (χ 2 (1) = 21.04, P < 0.001), and TMEM106B rs1990622 genotype (Fisher's exact test, P < 0.001) and A-allele (χ 2 (1) = 25.75, P < 0.001). No differences in ABCC9 rs704178 genotype or allele frequency were found between LATE-NC + HS and non-LATE-NC + HS neuropathology cases. Dentate gyrus TDP-43 pathology associated with GRN and TMEM106B variations, but the association with TMEM106B nullified when LATE-NC + HS cases were excluded. Our results indicate that GRN and TMEM106B are associated with severe loss of CA1 neurons in the aging brain, while ABCC9 was not confirmed as a genetic risk factor for LATE-NC + HS. The association between TMEM106B and LATE-NC + HS may be independent of dentate TDP-43 pathology., (© 2019 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)

Introduction: Coronary artery bypass grafting (CABG) surgery is known to improve vascular function and cardiac-related mortality rates; however, it is associated with high rates of postoperative cognitive decline and delirium. Previous attempts to prevent post-CABG cognitive decline using pharmacological and surgical approaches have been largely unsuccessful. Cognitive prehabilitation and rehabilitation are a viable yet untested option for CABG patients. We aim to investigate the effects of preoperative cognitive training on delirium incidence, and preoperative and postoperative cognitive training on cognitive decline at 4 months post-CABG., Methods and Analysis: This study is a randomised, single-blinded, controlled trial investigating the use of computerised cognitive training (CCT) both pre-CABG and post-CABG (intervention group) compared with usual care (control group) in older adults undergoing CABG in Adelaide, South Australia. Those in the intervention group will complete 1-2 weeks of CCT preoperatively (45-60 min sessions, 3.5 sessions/week) and 12 weeks of CCT postoperatively (commencing 1 month following surgery, 45-60 min sessions, 3 sessions/week). All participants will undergo cognitive testing preoperatively, over their hospital stay including delirium, and postoperatively for up to 1 year. The primary delirium outcome variable will be delirium incidence (presence vs absence); the primary cognitive decline variable will be at 4 months (significant decline vs no significant decline/improvement from baseline). Logistic regression modelling will be used, with age and gender as covariates. Secondary outcomes include cognitive decline from baseline to discharge, and at 6 months and 1 year post-CABG., Ethics and Dissemination: Ethics approval was obtained from the Central Adelaide Local Health Network Human Research Ethics Committee (South Australia, Australia) and the University of South Australia Human Ethics Committee, with original approval obtained on 13 December 2017. It is anticipated that approximately two to four publications and multiple conference presentations (national and international) will result from this research., Trial Registration Number: This clinical trial is registered with the Australian New Zealand Clinical Trials Registry and relates to the pre-results stage. Registration number: ACTRN12618000799257., Competing Interests: Competing interests: The computerised intervention is provided for the study by HappyNeuron Pro at no cost to the research team. However, HappyNeuron Pro has no input as to the dissemination of the results of this study. AL codeveloped systems for remote delivery of computerised cognitive training as part of industry collaborations with Synaptikon funded by the Australian National Health and Medical Research Council (NHMRC GNT1095097) and the German Federal Ministry of Education and Research (BMBF grant 13GW0212A), but has no financial interests in these or any other computerised cognitive training program. MJV is scientific founder of the University of Sydney spin-out company Skin2Neuron, where he has a financial interest unrelated to this work. He receives inkind research support from NeuroNation (Synaptikon) and COGSTATE towards the National Health and Medical Research Council of Australia-funded Maintain Your Brain Dementia Prevention Trial., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Recent evidence has linked cerebrovascular abnormalities with Parkinson's Disease (PD), which may provide a new neurophysiological understanding of cognitive impairment in PD. The current study aimed to compare cerebrovascular functioning, during a cognitive task and at rest, in those with and without PD., Methods: Idiopathic PD patients (n = 30) and age- and gender-matched healthy controls (n = 30) undertook cognitive testing and completed a word generation task while blood flow velocity was monitored bilaterally with functional transcranial Doppler sonography (fTCD) of the middle cerebral arteries. The lateralisation index and its standard deviation and timing, along with the maximum peak velocity for the left and right hemispheres and their latencies and standard deviations, were calculated for each participant., Results: The PD patients showed significantly more variability of the lateralisation index compared to the control group; but there were no differences in the lateralisation index itself nor in the peak velocities. In the PD group, the variability in the peak velocities showed significant positive correlations with performance on executive function tests., Conclusion: Normal ageing has been associated with a reduction in the lateralisation index, but no alterations in the standard deviation, suggesting that cerebrovascular functional changes associated with PD differ from those of typical ageing. The within-subject variability observed in the PD group indicate abnormalities within the neurovascular coupling response. Further, the association between the within-subject variability and executive functioning in the PD group, suggests that cerebrovascular dysfunction plays an important role in cognitive impairment in PD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Pathologies associated with the Tar-DNA binding protein 43 KDa (TDP-43) are associated with neurodegenerative diseases and aging. Phosphorylation of cellular proteins is a well-accepted mechanism of biological control and can be associated with disease pathways. Phosphorylation state associated with TDP-43 associated pathology has not been investigated with respect to dementia status in a population representative sample. TDP-43 immunohistochemistry directed toward phosphorylated (TDP-43P) and unphosphorylated (TDP-43U) was assessed in sections of hippocampus and temporal cortex from 222 brains donated to the population representative Cambridge City over-75s Cohort. Relationships between dementia status and age at death for TDP-43 immunoreactive pathologies by phosphorylation state were investigated. TDP-43 pathologies are common in the oldest old in the population and often do not conform to MacKenzie classification. Increasing age is associated with glial (TDP-43P) and neuronal inclusions (TDP-43P and TDP-43U), neurites, and granulovacuolar degeneration (GVD). Dementia status is associated with GVD and glial (TDP-43 P) and neural inclusions (TDP-43 P and U). Dementia severity was associated with glial (TDP-43P) and neuronal inclusions (TDP-43U and TDP-43P), GVD, and neurites. The associations between dementia severity and both glial cytoplasmic inclusions and GVD were independent from other pathologies and TDP-43 neuronal cytoplasmic inclusions. TDP-43 pathology contributes to dementia status and progression in a variety of ways in different phosphorylation states involving both neurons and glia, independently from age and from classic Alzheimer-related pathologies. TDP-43 pathologies as cytoplasmic inclusions in neurons or glia or as GVD contribute independently to dementia.

Background: Long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA) are essential nutrients and may be capable of delaying age-related cognitive decline. However, previous studies indicate that Australians are not meeting recommendations for LCn-3 PUFA intake. The current study therefore examined LCn-3 PUFA intake in an older Australia sample, as well as associations between LCn-3 PUFA intake and cognitive function., Methods: Cross-sectional data were collected from 90 adults aged 50 to 80 years. LCn-3 PUFA intake was assessed using a food frequency questionnaire and red blood cell fatty acid profiles were used to calculate the Omega-3 Index (RBC n-3 index). Cognitive function was measured using Addenbrooke's Cognitive Examination-III., Results: Positive associations were observed between age and RBC n-3 index (b=0.06, 95% CI: 0.01 - 0.10, P=0.01), and age and LCn-3 PUFA intake from fish oil capsules (b=17.5, 95% CI: 2.4 - 32.5 mg/day, P=0.02). When adjusting for LCn-3 PUFA from fish oil capsules, the association between age and RBC n-3 index was no longer significant. No associations were observed between LCn-3 PUFA intake and cognitive function., Conclusion: LCn-3 PUFA and fish oil consumption increased with age in this sample of older Australians, particularly due to supplement intake. However, LCn-3 PUFA intake was not associated with cognitive function., Competing Interests: The authors declare no conflict of interest.

Brain connectivity studies have reported that functional networks change with older age. We aim to (1) investigate whether electroencephalography (EEG) data can be used to distinguish between individual functional networks of young and old adults; and (2) identify the functional connections that contribute to this classification. Two eyes-open resting-state EEG recording sessions with 64 electrodes for each of 22 younger adults (19-37 years) and 22 older adults (63-85 years) were conducted. For each session, imaginary coherence matrices in delta, theta, alpha, beta and gamma bands were computed. A range of machine learning classification methods were utilized to distinguish younger and older adult brains. A support vector machine (SVM) classifier was 93% accurate in classifying the brains by age group. We report decreased functional connectivity with older age in delta, theta, alpha and gamma bands, and increased connectivity with older age in beta band. Most connections involving frontal, temporal, and parietal electrodes, and more than half of connections involving occipital electrodes, showed decreased connectivity with older age. Slightly less than half of the connections involving central electrodes showed increased connectivity with older age. Functional connections showing decreased strength with older age were not significantly different in electrode-to-electrode distance than those that increased with older age. Most of the connections used by the classifier to distinguish participants by age group belonged to the alpha band. Findings suggest a decrease in connectivity in key networks and frequency bands associated with attention and awareness, and an increase in connectivity of the sensorimotor functional networks with aging during a resting state., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

Risk perception has recently been shown to reveal a mental spatial representation, with people responding faster to low-risk items on the left side, and high-risk items on the right side. Subjective risk perception has a stronger spatial representation than objective risk perception; however, both reveal small effect sizes. With risk magnitude being a new domain within spatial mapping literature, we sought to explore its nuances. Following discussion surrounding the relationship between spatial mapping and level of expertise, this study investigated the effect of training an objective risk magnitude sequence on mental spatial representations. Participants (n = 34) used their left and right hands to indicate whether eight risk stimuli were lower or higher risk than a referent activity, both before and after training. Training involved repetitively learning the objectively correct order of the same eight risk stimuli for approximately 15 min. Pre-training results demonstrated the expected spatial representations. Contrary to our predictions, the spatial representation did not get stronger post-training, but instead disappeared. Previous research has demonstrated a loss of spatial-numerical mappings with increased task load. An increase in post-training reaction times could reflect an increase in task load due to a lack of adequate knowledge of risk stimulus order; thus revealing no mental spatial representation. However, failure to find training effects highlights the flexibility of weaker spatial representations, and supports research demonstrating spatial representation flexibility.

Attending to the visuospatial field is paramount for safety. The inability to sufficiently allocate attention in the environment could lead to unfavourable consequences. One's ability to attend quickly to left- and right-sided stimuli can vary depending on the person's level of alertness. A dominant model of this relationship proposes that low alertness is associated with a rightward bias in attention, with increases in alertness shifting attention leftward. The current study sought to synthesise the literature on spatial attention and alertness and identify modulators of this relationship in healthy adults. Nineteen articles meeting inclusion criteria were identified for meta-analysis. A small effect of alertness on spatial bias (d = .302) with no evidence for a systematic publication bias was found. Of the five investigated modulators, namely, the experimental design relative to alertness, direction of alertness manipulation, measurement of alertness, the nature of the spatial task, and handedness, only the latter was identified as a significant modulator of the relationship between alertness and spatial attention. The review's findings tie in with the influential framework by Corbetta and Shulman (2011) and support the idea to increase alertness as a rehabilitation approach to reduce inattention to the left side in neglect patients. Findings also suggest a need for future research to investigate neurological processes that underlie the alertness and spatial attention relationship, and a need to examine the transfer effects of laboratory-based experiments for real-world implications., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Cognitive impairments, including delirium, are common after coronary artery bypass grafting (CABG) surgery, as described in over three decades of research. Our aim was to pool estimates across the literature for the first-time, relative to time (from pre- to post-CABG) and diagnosis (cognitive impairment, delirium and dementia)., Methods: A systematic search of four databases was undertaken. 215 studies incorporating data from 91,829 patients were used to estimate the prevalence of cognitive impairments pre- and post-CABG, including delirium and dementia post-CABG, using random effects meta-analyses., Results: Pre-surgical cognitive impairment was seen in 19% of patients. Post-operatively, cognitive impairment was seen in around 43% of patients acutely; this resolved to 19% at 4-6 months and then increased to 25% of patients between 6-months to 1-year post-operatively. In the long term, between 1 and 5-years post-operatively, cognitive impairment increased and was seen in nearly 40% of patients. Post-operative delirium was apparent in 18% of CABG patients which increased to 24% when a diagnostic instrument was utilized alongside clinical criteria. Dementia was present in 7% of patients 5-7 years post-surgery., Conclusion: The results of this meta-analysis demonstrate that cognitive impairment and delirium are major issues in CABG patients which require specific attention. It is imperative that appropriate methods for investigating cognitive impairment, and screening for delirium using a diagnostic instrument, occur in both pre-and post-CABG settings., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To systematically review and meta-analyse conversion rates from normal cognition to Mild Cognitive Impairment (MCI) and dementia in Parkinson's disease (PD) patients. Reversion rates in patients with MCI (i.e. PD-MCI) were also investigated., Methods: Electronic searches of PsycINFO, Medline and EBSCOhost were conducted in January 2018, with 1833 articles identified after duplicate removal. Articles were included if they assessed conversion/reversion in PD patients between normal cognition, PD-MCI and PD dementia (PD-D)., Results: In total, 39 articles met the inclusion criteria, representing 4011 patients (mean age range 58-75; 61% male). Within three years, in those with PD and normal cognition, 25% (95%CI 20-30%) converted to PD-MCI and 2% (95%CI 1-7%) converted to dementia. Of those with PD-MCI, 20% (95%CI 13-30%) converted to dementia while 28% (95%CI 20-37%) reverted back to a state of normal cognitive function. The conversion rates to MCI and dementia were higher, and reversion rates lower, when follow-up was ≥3 years. When International Parkinson and Movement Disorder Society (MDS) criteria were used to diagnose MCI, Level I criteria were associated with a greater reversion estimate from PD-MCI to normal cognitive function., Conclusions: These findings summarise the trajectory of cognitive impairment in PD and highlight that MCI is common in this patient group. Understanding cognitive trajectories in PD patients is important for patient care in terms of prognosis, as well as for identifying windows for intervention for cognitive symptoms. As the number of PD patients increases with an ageing population, this information can inform future policy and planning., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The Mediterranean diet may be capable of improving cognitive function. However, the red meat restrictions of the diet could impact long-term adherence in Western populations. The current study therefore examined the cognitive effects of a Mediterranean diet with additional red meat., Methods: A 24-week parallel crossover design compared a Mediterranean diet with 2-3 weekly servings of fresh, lean pork (MedPork) and a low-fat (LF) control diet. Thirty-five participants aged between 45 and 80 years and at risk of cardiovascular disease followed each intervention for 8 weeks, separated by an 8-week washout period. Cognitive function was assessed using the Cambridge Neuropsychological Test Automated Battery. Psychological well-being was measured through the SF-36 Health Survey and mood was measured using the Profile of Mood States (POMS)., Results: During the MedPork intervention, participants consumed an average of 3 weekly servings of fresh pork. Compared to LF, the MedPork intervention led to higher processing speed performance ( p = 0.01) and emotional role functioning ( p = 0.03). No other significant differences were observed between diets., Conclusion: Our findings indicate that a Mediterranean diet inclusive of fresh, lean pork can be adhered to by an older non-Mediterranean population while leading to positive cognitive outcomes.

This review aimed to systematically evaluate associations between the Metabolic Syndrome and domain specific cognitive performance from cross-sectional studies. PsycINFO and Medline were searched on 12 January 2017 with the terms "Metabolic Syndrome" and "cogni*." A total of 973 articles were identified, with 26 meeting inclusion criteria. Individuals with Metabolic Syndrome were consistently reported to have poorer performance on executive function tasks that were not adaptations of the verbal fluency task, including the Stockings of Cambridge test, Color-Word Inference Test and Frontal Assessment Battery; findings from adaptations of the verbal fluency test showed less consistent results. Associations with performance in attention/working memory/information processing, memory, language, and construction/motor performance domains were mixed. All studies reporting on perception showed nonsignificant results. Non-language based executive function tasks appear to be the most sensitive tests of Metabolic Syndrome, and hold promise as a cognitive screen and for the tracking of interventions in this group.