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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We aimed to investigate individual differences that associate with peoples’ acute risk perception for activities such as walking and giving birth, including objective risk and the mapping of numerical magnitudes. The Amazon Mechanical Turk platform was used, with 284 participants recruited (40% female) ranging between 19 and 68 years. Participants had to indicate the positions of (1) the relative death risk of activities on a horizontal-line with ‘very low risk of death’ and ‘very high risk of death’ as left and right anchors respectively and (2), numerical magnitudes on a horizontal-line ranging 0–1000. The MicroMort framework was used to index acute risk of death (one/million chance of dying from an accident). Previous experience with the activities, handedness, along with risk propensity and unrealistic optimism were also measured. Linear mixed-effects modelling was used to investigate predictors of subjective MicroMort judgments. Individuals subjectively judged activities to be riskier if the activity was objectively riskier, if they over-estimated on the numerical task (more so for low-risk activities as compared to high-risk), or if they had not experienced the activity previously. The observed relationship between the number line task and everyday risk judgments is in keeping with the idea of a common magnitude representation system. In conclusion, individuals are able to discriminate between activities varying in risk in an absolute sense, however intuition for judging the relative differences in risk is poor. The relationship between the misjudging of both risks and numerical magnitudes warrants further investigation, as may inform the development of risk communication strategies. [ABSTRACT FROM AUTHOR]

The spatial numerical association of response code (SNARC) effect is characterized by low numbers mapped to the left side of space and high numbers mapped to the right side of space. In addition to numbers, SNARC-like effects have been found in non-numerical magnitude domains such as time, size, letters, luminance, and more, whereby the smaller/earlier and larger/later magnitudes are typically mapped to the left and right of space, respectively. The purpose of this systematic and meta-analytic review was to identify and summarise all empirical papers that have investigated horizontal (left-right) SNARC-like mappings using non-numerical stimuli. A systematic search was conducted using EMBASE, Medline, and PsycINFO, where 2216 publications were identified, with 57 papers meeting the inclusion criteria (representing 112 experiments). Ninety-five of these experiments were included in a meta-analysis, resulting in an overall effect size of d = .488 for a SNARC-like effect. Additional analyses revealed a significant effect size advantage for explicit instruction tasks compared with implicit instructions, yet yielded no difference for the role of expertise on SNARC-like effects. There was clear evidence for a publication bias in the field, but the impact of this bias is likely to be modest, and it is unlikely that the SNARC-like effect is a pure artefact of this bias. The similarities in the response properties for the spatial mappings of numerical and non-numerical domains support the concept of a general higher order magnitude system. Yet, further research will need to be conducted to identify all the factors modulating the strength of the spatial associations. [ABSTRACT FROM AUTHOR]

The brain is dependent on the cerebrovascular system, particularly microvasculature, for a consistent blood supply; however, age-related changes in this system affect neuronal and therefore cognitive function. Structural vascular markers and vascular disease appear to preferentially affect fluid cognitive abilities, sparing crystallized abilities. We sought to investigate the relationships between cerebrovascular function and cognitive domains. Fifty individuals between 60 and 75 years of age (31 women, 19 men) underwent cognitive testing: Wechsler Vocabulary and Matrix Reasoning subtests (crystallized and fluid ability measures, respectively Wechsler, 2011), and the Addenbrooke's Cognitive Examination-Revised (ACE-R; general cognitive ability; Mioshi, Dawson, Mitchell, Arnold, & Hodges, 2006). Transcranial Doppler (TCD) measures were also collected at rest and during a cognitive word-generation task, from which a lateralization index was calculated. Lower pulsatility index at rest, and greater left lateralization during the TCD cognitive task were associated with better performance on the Matrix Reasoning but not the Vocabulary test; these effects were independent from each other and from any vascular comorbidity burden. These functional findings confirm previous structural studies, which revealed that fluid abilities are more vulnerable to cerebrovascular dysfunction than crystallized abilities, and identify two (likely related) mechanisms: degraded cerebrovascular integrity (indexed by pulsatility index) and a delateralization of function. Cerebrovascular dysfunction is a key contributor to cognitive aging that deserves further attention, particularly in relation to early diagnostic markers of impairment and monitoring of vascular (e.g., physical activity) interventions. [ABSTRACT FROM AUTHOR]

Background: The significance of TDP-43 pathology in relation to aging and dementia in the population is unclear.Objective: We aimed to determine the prevalence of transactive response DNA-binding protein of 43 kDA (TDP-43) neuronal inclusions in a population-based sample, and associations with age group at death (≤90 and >90 years) and clinical dementia status prior to death. Further, we investigate associations between TDP-43 inclusions and other key dementia-related neuropathologies (plaques, tangles, and neuronal loss) within the hippocampus and entorhinal and temporal cortices.Methods: All brain donors within the Cambridge City over-75 s Cohort (CC75C), which is population-based and longitudinally tracked (n = 228), were included. Age at death ranged from 78 to 106 years. TDP-43 neuronal inclusions were assessed in the hippocampus, entorhinal cortex, and temporal cortex. These data were combined with existing clinical and neuropathological data.Results: TDP-43 neuronal inclusions were present in 27% of the sample, 36% of those with clinical dementia and 18% without dementia. Individuals who died later (>90 years) or with clinical dementia were more likely to show TDP-43 inclusions. Hippocampal and entorhinal TDP-43 inclusions were significantly associated with dementia severity and increasing age, taking into account other neuropathologies. TDP-43 neuronal inclusions appeared to be co-localize with severe neuronal loss.Conclusion: Findings indicate that hippocampal and entorhinal TDP-43 inclusions are important substrates of late onset dementia which appear to co-localize with severe neuronal loss, but not with Alzheimer's disease markers of amyloid and tau. This broadens the accepted view of TDP-43 pathology in dementias. [ABSTRACT FROM AUTHOR]

Background: Deposition of amyloid-β (Aβ) in vessel walls of the brain as cerebral amyloid angiopathy (CAA) could be a major factor in the pathogenesis of dementia. Here we investigate the relationship between dementia and the prevalence of CAA in older populations. We searched the literature for prospective population-based epidemiological clinicopathological studies, free of the biases of other sampling techniques, which were used as a comparison. Methods: To identify population-based studies assessing CAA and dementia, a previous systematic review of population-based clinicopathological studies of ageing and dementia was employed. To identify selected-sample studies, PsychInfo (1806-April Week 3 2008), OVID MEDLINE (1950-April Week 2 2008) and Pubmed (searched 21 April 2008) databases were searched using the term "amyloid angiopathy". These databases were also employed to search for any population-based studies not included in the previous systematic review. Studies were included if they reported the prevalence of CAA relative to a dementia classification (clinical or neuropathological). Results: Four population-based studies were identified. They showed that on average 55-59% of those with dementia displayed CAA (of any severity) compared to 28-38% of the non-demented. 37-43% of the demented displayed severe CAA in contrast to 7-24% of the non-demented. There was no overlap in the range of these averages and they were less variable and lower than those reported in 38 selected sample studies (demented v non-demented: 32-100 v 0-77% regardless of severity; 0-50 v 0-11% for severe only). Conclusion: CAA prevalence in populations is consistently higher in the demented as compared to the non-demented. This supports a significant role for CAA in the pathogenesis of dementia. [ABSTRACT FROM AUTHOR]

The current study aimed to investigate whether children and adolescents diagnosed with Attention Deficit/Hyperactivity Disorder Predominantly Inattentive (AD/HD-in; Child n = 24, Adolescent n = 33) and Combined (AD/HD-com; Child n = 30, Adolescent n = 42) subtypes were more distractible than controls (Child n = 54; Adolescents n = 75), by assessing event-related potential (ERP), performance and peripheral arousal measures. All AD/HD groups displayed smaller amplitudes and/or shorter latencies of the P3a ERP component — thought to reflect involuntary attention switching — following task-deviant novel stimuli (checkerboard patterns) embedded in a Working Memory (WM) task. The P3a results suggested that both AD/HD-in and AD/HD-com subtypes ineffectively evaluate deviant stimuli and are hence more "distractible". These abnormalities were most pronounced over the central areas. AD/HD groups did not display any abnormalities in averaged heart rate over the WM task, a measure of peripheral arousal. They did display abnormalities in performance measures from the task, but these were unrelated to P3a abnormalities. AD/HD groups also displayed a number of deficits on Switching of Attention and Verbal Memory tasks, however, the pattern of abnormality mostly reflected general cognitive deficits rather than resulting from distraction. [ABSTRACT FROM AUTHOR]

When thinking about quantifiable domains such as numbers, pitch, and size, they are implicitly mapped on to representational space with small/low/less and large/high/more of the respective domain represented on the left and right sides of representational space, respectively. Recent research has also demonstrated that more abstract domains (colours, language, political party names) are also mapped in the same way. This study investigated a new abstract domain, risk, to examine if this same pattern of effects is apparent (left = low risk/right = high risk) to get a better understanding of how risk magnitudes are processed. Experiment 1 (n = 26) presented objective, statistically calculated risk stimuli (micromorts) to participants, who indicated if the stimuli had lower or higher risks than a referent, with their left and right hands. Experiment 2 (n = 25) utilised the same task, but the risk stimuli were generated by the participants themselves. Both experiments found the expected association of risk with space—indicated by faster left-hand responses to low-risk stimuli and faster right-hand responses to high-risk stimuli. Risks appear to fit onto a standard left-right spatial association; however, the effect sizes for all analyses were small. The results of this study are not only in line with the idea of a generalised magnitude processing system, but might also inform best practices in effective communications of risks. [ABSTRACT FROM AUTHOR]

Cognitive reserve beneficially affects cognitive performance, even into advanced age. However, the benefits afforded by high cognitive reserve may not extend to all cognitive domains. This study investigated whether cognitive reserve differentially affects performance on cognitive tasks, in 521 cognitively healthy individuals aged 60 to 98 years (Mage = 68, SD = 6.22, 287 female); years of education was used to index cognitive reserve. Cognitive performance variables assessed attention, executive functions, verbal memory, motor performance, orientation, perception of emotion, processing speed, and working memory. Bootstrapped regression analyses revealed that cognitive reserve was associated with attention, executive functions, verbal and working memory, and orientation; and not significantly related to emotion perception, processing speed, or motor performance. Cognitive reserve appears to differentially affect individual cognitive domains, which extends current theory that purports benefits for all domains. This finding highlights the possibility of using tests not (or minimally) associated with cognitive reserve, to screen for cognitive impairment and dementia in late life; these tests will likely best track brain health, free of compensatory neural mechanisms. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which is concerned with dementia.

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. [ABSTRACT FROM AUTHOR]

The potential protective role of education for dementia is an area of major interest. Almost all older people have some pathology in their brain at death but have not necessarily died with dementia. We have explored these two observations in large population-based cohort studies (Epidemiological Clinicopathological Studies in Europe; EClipSE) in an investigation of the relationships of brain pathology at death, clinical dementia and time in education, testing the hypothesis that greater exposure to education reduces the risk of dementia. EClipSE has harmonized longitudinal clinical data and neuropathology from three longstanding population-based studies that included post-mortem brain donation. These three studies started between 1985 and 1991. Number of years of education during earlier life was recorded at baseline. Incident dementia was detected through follow-up interviews, complemented by retrospective informant interviews, death certificate data and linked health/social records (dependent on study) after death. Dementia-related neuropathologies were assessed in each study in a comparable manner based on the Consortium to Establish a Registry for Alzheimer's Disease protocol. Eight hundred and seventy-two brain donors were included, of whom 56% were demented at death. Longer years in education were associated with decreased dementia risk and greater brain weight but had no relationship to neurodegenerative or vascular pathologies. The associations between neuropathological variables and clinical dementia differed according to the ‘dose’ of education such that more education reduced dementia risk largely independently of severity of pathology. More education did not protect individuals from developing neurodegenerative and vascular neuropathology by the time they died but it did appear to mitigate the impact of pathology on the clinical expression of dementia before death. The findings suggest that an understanding of the mechanisms leading to functional protection in the presence of pathology may be of considerable value to society. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (χ2(2) = 20.61, P < 0.001) and T‐allele (χ2(1) = 21.04, P < 0.001), and TMEM106B rs1990622 genotype (Fisher's exact test, P < 0.001) and A‐allele (χ2(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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Hippocampal neuron loss is a common neuropathological feature in old age with various underlying etiologies. Hippocampal sclerosis of aging (HS‐Aging) is neuropathologically characterized by severe CA1 neuronal loss and frequent presence of transactive response DNA‐binding protein of 43 kDa (TDP‐43) aggregations. Its etiology is unclear and currently no standardized approaches to measure HS‐Aging exist. We developed a semi‐quantitative protocol, which captures various hippocampal neuron loss patterns, and compared their occurrence in the context of HS‐Aging, TDP‐43, vascular and tau pathology in 672 brains (TDP‐43 staining n = 642/672, 96%) donated for the population‐based Cambridge City over‐75s Cohort and the Cognitive Function and Ageing Study. HS‐Aging was first evaluated independently from the protocol using the most common criteria defined in literature, and then described in detail through examination of neuron loss patterns and associated pathologies. 34 (5%) cases were identified, with a maximum of five pyramidal neurons in each of over half CA1 fields‐of‐view (x200 magnification), no vascular damage, no neuron loss in CA2‐CA4, but consistent TDP‐43 neuronal solid inclusions and neurites. We also report focal CA1 neuron loss with vascular pathology to affect predominantly CA1 bordering CA2 (Fisher's exact, P = 0.009), whereas neuron loss in the subicular end of CA1 was associated with TDP‐43 inclusions (Fisher's exact, P < 0.001) and high Braak stage (Fisher's exact, P = 0.001). Hippocampal neuron loss in CA4‐CA2 was not associated with TDP‐43. We conclude that hippocampal neuron loss patterns are associated with different etiologies within CA1, and propose that these patterns can be used to form objective criteria for HS‐Aging diagnosis. Finally, based on our results we hypothesize that neuron loss leading to HS‐Aging starts from the subicular end of CA1 when it is associated with TDP‐43 pathology, and that this neurodegenerative process is likely to be significantly more common than “end‐stage” HS‐Aging only. [ABSTRACT FROM AUTHOR]

There is a need for short, reliable, sensitive assessment tools to measure social cognition. The Awareness of Social Inference Test (TASIT) is an ecologically valid instrument that uses videos of actors engaged in everyday conversations to assess emotion perception, the ability to detect lies, sarcasm and sincerity, and the ability to judge what others are thinking, intending, feeling, and saying. A recently developed short version of TASIT retains the structure of the original test and its clinical sensitivity. In this paper, we compare TASIT-S performance in healthy adolescents, adults, and older adults as well as the effects of country (U.S.A. and Australia), English familiarity and gender. In this study 616 Australians including 226 adolescents (13-19) and 390 adults aged 20-75 + along with 180 U.S. residents (aged 20-74) completed one, two, or three parts of TASIT-S either face to face (Australians) or on-line (US residents). Results indicated that there were minor differences in TASIT-S performance (Part 3 only) based on country of residence and no significant effects for English familiarity in adolescents (not examined in adults). There were no gender effects. Young and middle aged adults (20-59) tended to perform better than adolescents and older adults on most parts of TASIT-S. In general, TASIT-S scores decreased moderately with advancing age. In conclusion, TASIT-S is a useful screen for social cognitive impairment in English speakers that is appropriate for use from adolescence through to older age. It produces comparable scores in the U.S.A. and Australia. [ABSTRACT FROM AUTHOR]

Background: The oldest-old (aged ≥85 years) are the fastest growing age group, with the highest risk of cognitive impairment and dementia. This study investigated whether cognitive reserve applies to the oldest-old. This has implications for cognitive interventions in this age group.Methods: Baseline and 5-year follow-up data from the Newcastle 85+ Study were used (N = 845, mean age = 85.5, 38% male). A Cognitive Reserve Index (CRI) was created, including: education, social class, marital status, engagement in mental activities, social participation, and physical activity. Global (Mini-Mental State Examination) and domain specific (Cognitive Drug Research Battery subtests assessing memory, attention, and speed) cognitive functions were assessed. Dementia diagnosis was determined by health records. Logistic regression analysis examined the association between CRI scores and incident dementia. Mixed effects models investigated baseline and longitudinal associations between the CRI scores and cognitive function. Analyses controlled for sex, age, depression, and cardiovascular disease history.Results: Higher reserve associated with better cognitive performance on all baseline measures, but not 5-year rate of change. The CRI associated with prevalent, but not incident dementia.Conclusions: In the oldest-old, higher reserve associated with better baseline global and domain-specific cognitive function and reduced risk of prevalent dementia; but not cognitive decline or incident dementia. Increasing reserve could promote cognitive function in the oldest-old. The results suggest there would be little impact on trajectories, but replication is needed. Development of preventative strategies would benefit from identifying the role of each factor in building reserve and why rate of change is not affected. [ABSTRACT FROM AUTHOR]

Background: The Mediterranean diet is characterised by the high consumption of extra virgin olive oil, fruits, vegetables, grains, legumes and nuts; moderate consumption of fish, poultry, eggs and dairy; and low consumption of red meat and sweets. Cross sectional, longitudinal and intervention studies indicate that a Mediterranean diet may be effective for the prevention of cardiovascular disease and dementia. However, previous research suggests that an Australian population may find red meat restrictions difficult, which could affect long term sustainability of the diet.Methods: This paper outlines the protocol for a randomised controlled trial that will assess the cardiovascular and cognitive benefits of a Mediterranean diet modified to include 2-3 weekly serves of fresh, lean pork. A 24-week cross-over design trial will compare a modified Mediterranean diet with a low-fat control diet in at-risk men and women. Participants will follow each of the two diets for 8 weeks, with an 8-week washout period separating interventions. Home measured systolic blood pressure will be the primary outcome measure. Secondary outcomes will include body mass index, body composition, fasting blood lipids, C-reactive protein, fasting plasma glucose, fasting serum insulin, erythrocyte fatty acids, cognitive function, psychological health and well-being, and dementia risk.Discussion: To our knowledge this research is the first to investigate whether an alternate source of protein can be included in the Mediterranean diet to increase sustainability and feasibility for a non-Mediterranean population. Findings will be significant for the prevention of cardiovascular disease and age-related decline, and may inform individuals, clinicians and public health policy.Trial Registration: ACTRN12616001046493 . Registered 5 August 2016. [ABSTRACT FROM AUTHOR]

Objective Dementia with Lewy bodies is an α-synucleinopathy characterized by neocortical Lewy-related pathology ( LRP). We carried out a genome-wide association study ( GWAS) on neocortical LRP in a population-based sample of subjects aged 85 or over. Methods LRP was analyzed in 304 subjects in the Vantaa 85+ sample from Southern Finland. The GWAS included 41 cases with midbrain, hippocampal, and neocortical LRP and 177 controls without midbrain and hippocampal LRP. The Medical Research Council Cognitive Function and Ageing Study ( CFAS) material was used for replication (51 cases and 131 controls). Results By analyzing 327,010 markers the top signal was obtained at the HLA- DPA1/ DPB1 locus ( P = 1.29 × 10−7); five other loci on chromosomes 15q14, 2p21, 2q31, 18p11, and 5q23 were associated with neocortical LRP at P < 10−5. Two loci were marked by multiple markers, 2p21 ( P = 3.9 × 10−6, upstream of the SPTBN1 gene), and HLA- DPA1/ DPB1; these were tested in the CFAS material. Single marker ( P = 0.0035) and haplotype ( P = 0.04) associations on 2p21 were replicated in CFAS, whereas HLA- DPA1/ DPB1 association was not. Bioinformatic analyses suggest functional effects for the HLA- DPA1/ DPB1 markers as well as the 15q14 marker rs8037309. Interpretation We identified suggestive novel risk factors for neocortical LRP. SPTBN1 is the candidate on 2p21, it encodes beta-spectrin, an α-synuclein binding protein and a component of Lewy bodies. The HLA- DPA1/ DPB1 association suggests a role for antigen presentation or alternatively, cis-regulatory effects, one of the regulated neighboring genes identified here (vacuolar protein sorting 52) plays a role in vesicular trafficking and has been shown to interact with α-synuclein in a yeast model. [ABSTRACT FROM AUTHOR]

Background The contribution of cerebrovascular function to cognitive performance is gaining increased attention. Transcranial doppler (TCD) is portable, reliable, inexpensive and extremely well tolerated by young and clinical samples. It enables measurement of blood flow velocity in major cerebral arteries at rest and during cognitive tasks. Methods We systematically reviewed evidence for associations between cognitive performance and cerebrovascular function in children (0-18 years), as measured using TCD. A total of 2778 articles were retrieved from PsychInfo, Pubmed, and EMBASE searches and 25 relevant articles were identified. Results Most studies investigated clinical groups, where decreased blood flow velocities in infants were associated with poor neurological functioning, and increased blood flow velocities in children with Sickle cell disease were typically associated with cognitive impairment and lower intelligence. Studies were also identified assessing autistic behaviour, mental retardation and sleep disordered breathing. In healthy children, the majority of studies reported cognitive processing produced lateralised changes in blood flow velocities however these physiological responses did not appear to correlate with behavioural cognitive performance. Conclusion Poor cognitive performance appears to be associated with decreased blood flow velocities in premature infants, and increased velocities in Sickle cell disease children using TCD methods. However knowledge in healthy samples is relatively limited. The technique is well tolerated by children, is portable and inexpensive. It therefore stands to make a valuable contribution to knowledge regarding the underlying functional biology of cognitive performance in childhood. [ABSTRACT FROM AUTHOR]

Epidemiological studies investigating the pathological bases of late onset dementia focus on classical markers such as plaques and tangles. The significance of pathologies characteristically associated with rare dementia syndromes such as Pick bodies and severe neuronal loss are considered to be well defined. The significance of other pathologies, often accepted as a feature of neurodegenerative syndromes, such as Hirano bodies and gliosis is not clear. This study investigated the significance of these rarer and 'disregarded' pathologies to dementia in the population. A total of 627 individuals aged 71-103 from the Epidemiological CLInicoPathologial Studies in Europe (EClipSE) project with clinical dementia status at death determined were assessed. Pathologies assessed included Pick bodies, severe neuronal loss, gliosis, and granulovacuolar degeneration (GVD) in the cortex and/or hippocampus, along with brainstem plaques, tangles, neuronal loss, gliosis, pigmentary incontinence, and Lewy bodies. All pathologies were associated with dementia when controlling for plaques and tangles except Hirano bodies, GVD, and brainstem plaques. These included hippocampal and entorhinal gliosis; cortical, hippocampal, and entorhinal neuronal loss; along with brainstem neuronal loss, gliosis, pigmentary incontinence, Lewy bodies, and tangles. Pick bodies were present in five individuals, all with clinical dementia. These epidemiological data indicate that dementia in old age is associated with a broad range of pathological and anatomical substrates pointing to potential areas for future research, particularly the brainstem. [ABSTRACT FROM AUTHOR]

Background: The contribution of cerebrovascular function to cognitive performance is gaining increased attention. Transcranial doppler (TCD) is portable, reliable, inexpensive and extremely well tolerated by young and clinical samples. It enables measurement of blood flow velocity in major cerebral arteries at rest and during cognitive tasks.Methods: We systematically reviewed evidence for associations between cognitive performance and cerebrovascular function in children (0-18 years), as measured using TCD. A total of 2778 articles were retrieved from PsychInfo, Pubmed, and EMBASE searches and 25 relevant articles were identified.Results: Most studies investigated clinical groups, where decreased blood flow velocities in infants were associated with poor neurological functioning, and increased blood flow velocities in children with Sickle cell disease were typically associated with cognitive impairment and lower intelligence. Studies were also identified assessing autistic behaviour, mental retardation and sleep disordered breathing. In healthy children, the majority of studies reported cognitive processing produced lateralised changes in blood flow velocities however these physiological responses did not appear to correlate with behavioural cognitive performance.Conclusion: Poor cognitive performance appears to be associated with decreased blood flow velocities in premature infants, and increased velocities in Sickle cell disease children using TCD methods. However knowledge in healthy samples is relatively limited. The technique is well tolerated by children, is portable and inexpensive. It therefore stands to make a valuable contribution to knowledge regarding the underlying functional biology of cognitive performance in childhood. [ABSTRACT FROM AUTHOR]