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Cognitive epidemiology investigates cognitive predictors of health and disease outcomes. Post-operative cognitive impairment is a common complication of surgery but has been neglected as a health outcome in cognitive epidemiology research. This is despite the fact that knowledge of cognitive predictors of post-operative cognitive impairment can be utilized for risk stratification, informed decision-making (in elective surgery), and personalized care of patients during the postoperative period. In this narrative review, the current literature on cognitive predictors of post-operative cognitive impairment and gaps therein are summarized. [ABSTRACT FROM AUTHOR]

SUMMARY: As we age, there are characteristic changes in our thinking, reasoning and memory skills (referred to as cognitive ageing). However, variation between people in the timing and degree of change experienced suggests that a range of factors determine individual cognitive ageing trajectories. This narrative review considers some of the lifestyle factors that might promote (or harm) cognitive health. The focus on lifestyle factors is because these are potentially modifiable by individuals or may be the targets of behavioural or societal interventions. To support that, the review briefly considers people's beliefs and attitudes about cognitive ageing; the nature and timing of cognitive changes across the lifespan; and the genetic contributions to cognitive ability level and change. In introducing potentially modifiable determinants, a framing that draws evidence derived from epidemiological studies of dementia is provided, before an overview of lifestyle and behavioural predictors of cognitive health, including education and occupation, diet and activity. [ABSTRACT FROM AUTHOR]

Objective: Cognitive impairment is a key element in most mental disorders. Its objective assessment at initial patient contact in primary care can lead to better adjusted and timely care with personalised treatment and recovery. To enable this, we designed the Mindmore self-administrative cognitive screening battery. What is presented here is normative data for the Mindmore battery for the Swedish population. Method: A total of 720 healthy adults (17 to 93 years) completed the Mindmore screening battery, which consists of 14 individual tests across five cognitive domains: attention and processing speed, memory, language, visuospatial functions and executive functions. Regression-based normative data were established for 42 test result measures, investigating linear, non-linear and interaction effects between age, education and sex. Results: The test results were most affected by age and to a lesser extent by education and sex. All but one test displayed either linear or accelerated age-related decline, or a U-shaped association with age. All but two tests showed beneficial effects of education, either linear or subsiding after 12 years of educational attainment. Sex affected tests in the memory and executive domains. In three tests, an interaction between age and education revealed an increased benefit of education later in life. Conclusion: This study provides normative models for 14 traditional cognitive tests adapted for self-administration through a digital platform. The models will enable more accurate interpretation of test results, hopefully leading to improved clinical decision making and better care for patients with cognitive impairment. [ABSTRACT FROM AUTHOR]

Recent studies suggest that knowledge representations and control processes are the two key components underpinning semantic cognition, and are also crucial indicators of the shifting cognitive architecture of semantics in later life. Although there are many standardized assessments that provide measures of the quantity of semantic knowledge participants possess, normative data for tasks that probe semantic control processes are not yet available. Here, we present normative data from more than 200 young and older participants on a large set of stimuli in two semantic tasks, which probe controlled semantic processing (feature-matching task) and semantic knowledge (synonym judgement task). We verify the validity of our norms by replicating established age- and psycholinguistic-property-related effects on semantic cognition. Specifically, we find that older people have more detailed semantic knowledge than young people but have less effective semantic control processes. We also obtain expected effects of word frequency and inter-item competition on performance. Parametrically varied difficulty levels are defined for half of the stimuli based on participants' behavioural performance, allowing future studies to produce customized sets of experimental stimuli based on our norms. We provide all stimuli, data and code used for analysis, in the hope that they are useful to other researchers.

The current study investigated whether preference for positive affect would be observed in the context of a higher order control process with increasing age given the premise of affective prioritization with ageing. The study examined how affect interacted with cognitive control mechanisms across young, middle-aged and older adults. Conflict monitoring and adaptation for affective stimuli was examined with a face-word Stroop task using happy and fearful facial expressions. The participants' task was to detect the emotional expression (Happy or Fear) of the face shown with a distractor word (Happy or Fear) written across the face. Reaction time and accuracy data was analysed to compare adaptation effect and Stroop interference as a function of age, valence and previous trial congruence. The results demonstrated a stronger adaptation effect for negative affect in young adults and for positive affect in middle-aged adults and older adults. These results can be explained in terms of the socio-emotional selectivity theory of affective bias in the elderly and the involvement of attentional control mechanisms. This study empirically demonstrates shifts in affective bias towards positive affect with ageing through the implicit recruitment of cognitive control. [ABSTRACT FROM AUTHOR]

Abstract Objective Studies of postoperative cognitive dysfunction (POCD) rely on repeat neuropsychological testing. The stability of the applied instruments, which are affected by natural variability in performance and measurement imprecision, is often unclear. We determined the stability of a neuropsychological test battery using a sample of older adults from the general population. Forty-five participants aged 65 to 89 years performed six computerized and non-computerized neuropsychological tests at baseline and again at 7 day and 3 months follow-up sessions. Mean scores on each test were compared across time points using repeated measures analyses of variance (ANOVA) with pairwise comparison. Two-way mixed effects, absolute agreement analyses of variance intra-class correlation coefficients (ICC) determined test–retest reliability. Results All tests had moderate to excellent test–retest reliability during 7-day (ICC range 0.63 to 0.94; all p

Objectives: Lifestyle behaviours have been linked to dementia incidence, but their cumulative impact on dementia and the underlying mechanisms remain poorly understood. This study investigated the association of co-occurring lifestyle behaviours with dementia incidence and the mediating role of systemic inflammation in this association., Methods: The sample comprised 3131 participants (55.2% female) from the English Longitudinal Study of Ageing aged 52-92 years at baseline (2008/09). Self-reported baseline lifestyle behaviours (alcohol intake, fruit and vegetable consumption, smoking, physical activity, sleep duration, social engagement, and cognitive activity) were summed to derive an index of lifestyle behaviours, ranging from 0 to 7, with higher scores denoting a higher number of health-risk behaviours. Incident dementia cases (n = 130, 4.2%) were identified through doctor-diagnosed dementia, informant interviews, and health records between 2014/15 and 2018/19. Systemic inflammation was measured through fasting plasma concentrations of C-reactive protein in 2012/13., Results: Binary logistic regression models indicated that the odds of subsequent dementia increased by 1.19 for each additional health-risk behaviour (95% confidence intervals: 1.04, 1.37, p  = 0.014) after adjusting for age, sex, ethnicity, wealth, education, marital status, body mass index, coronary heart disease, hypertension, stroke, and depression. However, this association was not mediated by C-reactive protein., Conclusions: Co-occurring health-risk behaviours were associated with higher dementia incidence up to 10 years later, underscoring the importance of modifying health-risk behaviours for the prevention of dementia. Systemic inflammation did not explain the association between behaviours and dementia., Competing Interests: There is no conflict of interest among all authors., (© 2024 The Authors. Published by Elsevier Inc.)

Background: Grip strength is an indicator of physical function with potential predictive value for health in ageing populations. We assessed whether trends in grip strength from midlife predicted later-life brain health and cognition. Methods: 446 participants in an ongoing British birth cohort study, the National Survey of Health and Development (NSHD), had their maximum grip strength measured at ages 53, 60–64, and 69, and subsequently underwent neuroimaging as part of a neuroscience sub-study, referred to as "Insight 46", at age 69–71. A group-based trajectory model identified latent groups of individuals in the whole NSHD cohort with below- or above-average grip strength over time, plus a reference group. Group assignment, plus standardised grip strength levels and change from midlife were each related to measures of whole-brain volume (WBV) and white matter hyperintensity volume (WMHV), plus several cognitive tests. Models were adjusted for sex, body size, head size (where appropriate), sociodemographics, and behavioural and vascular risk factors. Results: Lower grip strength from midlife was associated with smaller WBV and lower matrix reasoning scores at age 69–71, with findings consistent between analysis of individual time points and analysis of trajectory groups. There was little evidence of an association between grip strength and other cognitive test scores. Although greater declines in grip strength showed a weak association with higher WMHV at age 69–71, trends in the opposite direction were seen at individual time points with higher grip strength at ages 60–64, and 69 associated with higher WMHV. Conclusions: This study provides preliminary evidence that maximum grip strength may have value in predicting brain health. Future work should assess to what extent age-related declines in grip strength from midlife reflect concurrent changes in brain structure. [ABSTRACT FROM AUTHOR]

Objectives frail older adults may be more vulnerable to stressors, resulting in steeper declines in cognitive function. Whether the frailty–cognition link differs by cognitive domain remains unclear; however, it could lend insight into underlying mechanisms. Methods we tested whether domain-specific cognitive trajectories (clock-drawing test, (CDT), immediate and delayed recall, orientation to date, time, president and vice-president naming) measured annually (2011–2016) differ by baseline frailty (physical frailty phenotype) in the National Health and Aging Trends Study (n  = 7,439), a nationally representative sample of older adult U.S. Medicare beneficiaries, using mixed effects models to describe repeated measures of each cognitive outcome. To determine if the association between frailty and subsequent cognitive change differed by education, we tested for interaction using the Wald test. Results we observed steeper declines for frail compared to non-frail participants in each domain-specific outcome, except for immediate recall. Largest differences in slope were observed for CDT (difference = −0.12 (standard deviations) SD/year, 95%CI: −0.15, −0.08). By 2016, mean CDT scores for frail participants were 1.8 SD below the mean (95%CI: −1.99, −1.67); for non-frail participants, scores were 0.8 SD below the mean (95%CI: −0.89, −0.69). Associations differed by education for global cognitive function (P interaction < 0.001) and for each domain-specific outcome: CDT (P interaction < 0.001), orientation (P interaction < 0.001), immediate (P interaction < 0.001) and delayed (P interaction < 0.001) word recalls. Conclusion frailty is associated with lower levels and steeper declines in cognitive function, with strongest associations for executive function. These findings suggest that aetiologies are multifactorial, though primarily vascular related; further research into its association with dementia sub-types and related pathologies is critical. [ABSTRACT FROM AUTHOR]

Background chronic pain, a common complaint among older adults, affects physical and mental well-being. While opioid use for pain management has increased over the years, pain management in older adults remains challenging, due to potential severe adverse effects of opioids in this population. Objective we examined the association between opioid use, and changes in cognitive function of older adults. Design prospective study. Setting community dwelling older adults. Subjects study population consisted of 2,222 individuals aged 65–69 years at baseline from the Personality and Total Health Through Life Study in Australia. Methods medication data were obtained from the Pharmaceutical Benefits Scheme. Cognitive measures were obtained from neuropsychological battery assessment. Opioid exposure was quantified as Total Morphine Equivalent Dose (MED). The association between change in cognitive function between Wave 2 and Wave 3, and cumulative opioid use was assessed through generalized linear models. Results cumulative opioid exposure exceeding total MED of 2,940 was significantly associated with poorer performance in the Mini Mental State Examination (MMSE). Compared with those not on opioids, individuals exposed to opioids resulting in cumulative total MED of greater than 2,940 had significantly lower scores in the MMSE (Model 1: β = −0.34, Model 2: β = −0.35 and Model 3: β = −0.39, P  < 0.01). Performance in other cognitive assessments was not associated with opioid use. Conclusion prolonged opioid use in older adults can affect cognitive function, further encouraging the need for alternative pain management strategies in this population. Pain management options should not adversely affect healthy ageing trajectories and cognitive health. [ABSTRACT FROM AUTHOR]

Background: Although the pathophysiology of cognitive decline is multifactorial, and modifiable by lifestyle, the evidence for the role of diet on cognitive function is still accumulating, particularly the potentially preventive role of constituents of plant-based foods.Methods: We aimed to determine whether higher habitual intake of dietary flavonoids, key components of plant-based diets, were associated with improved cognition and medial temporal lobe volumes using three complementary approaches (longitudinal, cross-sectional and co-twin analyses). In 1126 female twins (n=224 with a 10-year follow-up of diet and cognition data) aged 18-89 years, habitual intakes of total flavonoids and seven subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, polymeric flavonoids (and proanthocyanidins separately)) were calculated using validated food frequency questionnaires. Cognition was assessed using the Cambridge Neuropsychological Test Automated Battery test. Hippocampal volumes were measured in a subset using magnetic resonance imaging (16 monozygotic-twin pairs). Statistical models were adjusted for a range of diet and lifestyle factors.Results: Higher intakes of flavanones (tertile (T)3-T1=0.45, 95%CI 0.13,0.77; p=0.01) and anthocyanins (T3-T1=0.45, 95%CI 0.08,0.81; p=0.02) were associated with improvements in age-related cognition score over 10 years. In cross-sectional analysis higher intake of flavanones (T3-T1= 0.12, 95% CI 0.02, 0.21; p=0.02) and proanthocyanidins (T3-T1= 0.13, 95% CI 0.02, 0.24; p=0.02) were associated with improved paired-associates learning. Higher intake of anthocyanins was significantly associated with improved executive function (T3-T1= -0.52, 95% CI 0.19, 0.84; p=0.001) and with faster simple reaction times (T3-T1= -18.1, 95% CI -35.4, -0.7; p=0.04). In co-twin analysis, those with higher anthocyanin (2.0%, p=0.01) and proanthocyanidin (2.0%, p=0.02) intakes at baseline had the largest left hippocampal volumes after 12 years.Conclusion: Small increases in habitual intake of flavonoid-rich foods (containing anthocyanins, flavanones and proanthocyanidins; equivalent to approximately two servings of oranges and blueberries per day) over long time periods have the potential to attenuate cognitive ageing. [ABSTRACT FROM AUTHOR]

Background: Cognitive reserve is most commonly measured using socio-behavioural proxy variables. These variables are easy to collect, have a straightforward interpretation, and are widely associated with reduced risk of dementia and cognitive decline in epidemiological studies. However, the specific proxies vary across studies and have rarely been assessed in complete models of cognitive reserve (i.e. alongside both a measure of cognitive outcome and a measure of brain structure). Complete models can test independent associations between proxies and cognitive function in addition to the moderation effect of proxies on the brain-cognition relationship. Consequently, there is insufficient empirical evidence guiding the choice of proxy measures of cognitive reserve and poor comparability across studies. Method: In a cross-sectional study, we assessed the validity of 5 common proxies (education, occupational complexity, verbal intelligence, leisure activities, and exercise) and all possible combinations of these proxies in 2 separate community-dwelling older adult cohorts: The Irish Longitudinal Study on Ageing (TILDA; N = 313, mean age = 68.9 years, range = 54–88) and the Cognitive Reserve/Reference Ability Neural Network Study (CR/RANN; N = 234, mean age = 64.49 years, range = 50–80). Fifteen models were created with 3 brain structure variables (grey matter volume, hippocampal volume, and mean cortical thickness) and 5 cognitive variables (verbal fluency, processing speed, executive function, episodic memory, and global cognition). Results: No moderation effects were observed. There were robust positive associations with cognitive function, independent of brain structure, for 2 individual proxies (verbal intelligence and education) and 16 composites (i.e. combinations of proxies). Verbal intelligence was statistically significant in all models. Education was significant only in models with executive function as the cognitive outcome variable. Three robust composites were observed in more than two-thirds of brain-cognition models: the composites of (1) occupational complexity and verbal intelligence, (2) education and verbal intelligence, and (3) education, occupational complexity, and verbal intelligence. However, no composite had larger average effects nor was more robust than verbal intelligence alone. Conclusion: These results support the use of verbal intelligence as a proxy measure of CR in cross-sectional studies of cognitively healthy older adults. [ABSTRACT FROM AUTHOR]

The ageing brain is vulnerable to a wide array of neuropathologies. Prior work estimated that the three most studied of these, Alzheimer's disease, infarcts, and Lewy bodies, account for ∼40% of the variation in late life cognitive decline. However, that estimate did not incorporate many other diseases that are now recognized as potent drivers of cognitive decline [e.g. limbic predominant age-related TDP-43 encephalopathy (LATE-NC), hippocampal sclerosis, other cerebrovascular conditions]. We examined the degree to which person-specific cognitive decline in old age is driven by a wide array of neuropathologies. Deceased participants (n = 1164) from two longitudinal clinical-pathological studies, the Rush Memory and Aging Project and Religious Orders Study, completed up to 24 annual evaluations including 17 cognitive performance tests and underwent brain autopsy. Neuropathological examinations provided 11 pathological indices, including markers of Alzheimer's disease, non- Alzheimer's disease neurodegenerative diseases (i.e. LATE-NC, hippocampal sclerosis, Lewy bodies), and cerebrovascular conditions (i.e. macroscopic infarcts, microinfarcts, cerebral amyloid angiopathy, atherosclerosis, and arteriolosclerosis). Mixed effects models examined the linear relation of pathological indices with global cognitive decline, and random change point models examined the relation of the pathological indices with the onset of terminal decline and rates of preterminal and terminal decline. Cognition declined an average of about 0.10 unit per year (estimate = -0.101, SE = 0.003, P < 0.001) with considerable heterogeneity in rates of decline (variance estimate for the person-specific slope of decline was 0.0094, P < 0.001). When considered separately, 10 of 11 pathological indices were associated with faster decline and accounted for between 2% and 34% of the variation in decline, respectively. When considered simultaneously, the 11 pathological indices together accounted for 43% of the variation in decline; Alzheimer's disease-related indices accounted for 30-36% of the variation, non-Alzheimer's disease neurodegenerative indices 4-10%, and cerebrovascular indices 3-8%. Finally, the 11 pathological indices combined accounted for less than a third of the variation in the onset of terminal decline (28%) and rates of preterminal (32%) and terminal decline (19%). Although age-related neuropathologies account for a large proportion of the variation in late life cognitive decline, considerable variation remains unexplained even after considering a wide array of neuropathologies. These findings highlight the complexity of cognitive ageing and have important implications for the ongoing effort to develop effective therapeutics and identify novel treatment targets. [ABSTRACT FROM AUTHOR]

In a large multicentre sample of cognitively normal subjects, as a function of age, gender and APOE genotype, we studied the frequency of abnormal cerebrospinal fluid levels of Alzheimer's disease biomarkers including: total tau, phosphorylated tau and amyloid-β1-42. Fifteen cohorts from 12 different centres with either enzyme-linked immunosorbent assays or Luminex® measurements were selected for this study. Each centre sent nine new cerebrospinal fluid aliquots that were used to measure total tau, phosphorylated tau and amyloid-β1-42 in the Gothenburg laboratory. Seven centres showed a high correlation with the new Gothenburg measurements; therefore, 10 cohorts from these centres are included in the analyses here (1233 healthy control subjects, 40-84 years old). Amyloid-β amyloid status (negative or positive) and neurodegeneration status (negative or positive) was established based on the pathological cerebrospinal fluid Alzheimer's disease cut-off values for cerebrospinal fluid amyloid-β1-42 and total tau, respectively. While gender did not affect these biomarker values, APOE genotype modified the age-associated changes in cerebrospinal fluid biomarkers such that APOE ε4 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-β1-42 values and APOE ε2 carriers showed the opposite effect. At 40 years of age, 76% of the subjects were classified as amyloid negative, neurodegeneration negative and their frequency decreased to 32% at 85 years. The amyloid-positive neurodegeneration-negative group remained stable. The amyloid-negative neurodegeneration-positive group frequency increased slowly from 1% at 44 years to 16% at 85 years, but its frequency was not affected by APOE genotype. The amyloid-positive neurodegeneration-positive frequency increased from 1% at 53 years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-β1-42 levels were already frequent in midlife and APOE genotype strongly affects the levels of cerebrospinal fluid amyloid-β1-42, phosphorylated tau and total tau across the lifespan without influencing the frequency of subjects with suspected non-amyloid pathology.

Background: Studies suggest that a higher education and occupation are each associated with a higher late-life cognitive ability, but their inter-relationships in their association with cognitive ability and the contribution of peak IQ in young adulthood ('pre-morbid IQ') often remain unclear.Methods: Cross-sectional analysis of 623 participants aged ≥65 years of the BioCog study. Education was coded according to the International Standard Classification of Education (ISCED; range 1 to 6). Occupation was coded as 'semi/unskilled', 'skilled manual', 'skilled non-manual', 'managerial', 'professional'. A summary score of global ability ('g') was constructed from six cognitive tests. Pre-morbid IQ was estimated from vocabulary. The Geriatric Depression Scale assessed symptoms of depression. Age- and sex-adjusted analyses of covariance were performed.Results: Education (partial eta2 0.076; p < 0.001) and occupation (partial eta2 = 0.037; p < 0.001) were each significantly associated with g. For education, the association was attenuated but remained statistically significant when pre-morbid IQ was controlled for (partial eta2 0.036; p < 0.001) and was unchanged with additional adjustment for depression (partial eta2 0.037; p < 0.001). For occupation, the association with g was no longer significant when pre-morbid IQ (partial eta2 = 0.015; p = 0.06) and depression (partial eta2 = 0.011; p = 0.18) were entered as covariates in separate steps. When education and occupation were entered concurrently into the fully adjusted model, only education was independently associated with g (partial eta2 0.030; p < 0.001; occupation, p = 0.93).Conclusion: While a higher education and a higher occupation were each associated with a higher late-life cognitive ability, only for education some unique contribution to cognitive ability remained over and above its relationship with pre-morbid IQ, depression, and occupation. Further research is needed to address whether a longer time spent in education may promote late-life cognitive ability. [ABSTRACT FROM AUTHOR]

Background: Affective symptoms are associated with cognition in mid-life and later life. However, the role of cardiometabolic risk in this association has not been previously examined.Aims: To investigate how cardiometabolic risk contributes to associations between affective symptoms and mid-life cognition.Method: Data were used from the National Child Development Study (NCDS), a sample of people born in Britain during one week in 1958. Measures of immediate and delayed memory, verbal fluency and information processing speed and accuracy were available at age 50. Affective symptoms were assessed at ages 23, 33 and 42 years and a measure of accumulation was derived. A cardiometabolic risk score was calculated from nine cardiometabolic biomarkers at age 44. Path models were run to test these associations, adjusting for sex, education, socioeconomic position and affective symptoms at age 50.Results: After accounting for missing data using multiple imputation, path models indicated significant indirect associations between affective symptoms and mid-life immediate memory (β = -0.002, s.e. = 0.001, P = 0.009), delayed memory (β = -0.002, s.e. = 0.001, P = 0.02) and verbal fluency (β = -0.002, s.e. = 0.001, P = 0.045) through cardiometabolic risk.Conclusions: These findings suggest that cardiometabolic risk may play an important role in the association between affective symptoms and cognitive function (memory and verbal fluency). Results contribute to understanding of biological mechanisms underlying associations between affective symptoms and cognitive ageing, which can have implications for early detection of, and intervention for, those at risk of poorer cognitive outcomes. [ABSTRACT FROM AUTHOR]

Background/Aims: To detect cognitive decline in older adults, measures of verbal fluency and verbal memory are widely used. Less is known about performance in these measures in younger persons or according to education level and gender. We investigated cognitive performance according to age, education and gender among cognitively healthy adults aged 30–100 years. Methods: The study population comprised 4,174 cognitively healthy persons participating in the nationally representative Finnish Health 2011 survey. Cognitive assessment included verbal fluency, word list memory, word list recall and word list savings from the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery. Results: Total variance in the cognitive test performance explained by age, education and gender varied from 12.3 to 31.2%. A decreasing trend in cognitive performance existed in all subtests by advancing age, with differences appearing between 50 and 55 years. Persons with the highest-education level performed best for all measures. For the participants < 55 years, education explained part of the variance, while age and gender did not. Conclusions: When assessing cognition, age and education should be accounted for in more detail in research and clinical practice. Additionally, the cohort effect and its potential impact on the renewal cycle of future normative values for cognitive tests should be considered.

Objectives: Evidence of premature cognitive ageing amongst people living with HIV (PLHIV) remains controversial due to previous research limitations including underpowered studies, samples with suboptimal antiretroviral access, varying rate of virological control, high rate of AIDS, over‐representation of non‐community samples, and inclusion of inappropriate controls. The current study addresses these limitations, while also considering mental health and non‐HIV comorbidity burden to determine whether PLHIV showed premature cognitive ageing compared with closely comparable HIV‐negative controls. Methods: This study enrolled 254 PLHIV [92% on antiretroviral therapy; 84% with HIV RNA < 50 copies/mL; 15% with AIDS) and 72 HIV‐negative gay and bisexual men [mean (SD) age = 49 (10.2) years] from a single primary care clinic in Sydney, Australia. Neurocognitive function was evaluated with the Cogstate Computerized Battery (CCB) at baseline and 6 months after. Linear mixed‐effects (LME) models examined main and interaction effects of HIV status and chronological age on the CCB demographically uncorrected global neurocognitive z‐score (GZS), adjusting for repeated testing, and then adjusting sequentially for HIV disease markers, mental health and comorbidities. Results: HIV status and age interacted with a lower GZS (β = −0.43, P < 0.05). Higher level of anxiety symptoms (β = −0.11, P < 0.01), historical AIDS (β = −0.12, P < 0.05) and historical HIV brain involvement (β = −0.12, P < 0.05) were associated with lower GZS. Conclusions: We found a robust medium‐sized premature ageing effect on cognition in a community sample with optimal HIV care. Our study supports routine screening of cognitive and mental health among PLHIV aged ≥ 50 years. [ABSTRACT FROM AUTHOR]

Causal inference with observational longitudinal data and time‐varying exposures is often complicated by time‐dependent confounding and attrition. The G‐computation formula is one approach for estimating a causal effect in this setting. The parametric modelling approach typically used in practice relies on strong modelling assumptions for valid inference and moreover depends on an assumption of missing at random, which is not appropriate when the missingness is missing not at random (MNAR) or due to death. In this work we develop a flexible Bayesian semi‐parametric G‐computation approach for assessing the causal effect on the subpopulation that would survive irrespective of exposure, in a setting with MNAR dropout. The approach is to specify models for the observed data using Bayesian additive regression trees, and then, use assumptions with embedded sensitivity parameters to identify and estimate the causal effect. The proposed approach is motivated by a longitudinal cohort study on cognition, health and ageing and we apply our approach to study the effect of becoming a widow on memory. We also compare our approach to several standard methods. [ABSTRACT FROM AUTHOR]

Objectives: The criteria for objective memory impairment in mild cognitive impairment (MCI) are vaguely defined. Aggregating the number of abnormal memory scores (NAMS) is one way to operationalise memory impairment, which we hypothesised would predict progression to Alzheimer's disease (AD) dementia. Methods: As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 896 older adults who did not have dementia were administered a psychometric battery including three neuropsychological tests of memory, yielding 10 indices of memory. We calculated the number of memory scores corresponding to z ≤ −1.5 (i.e., NAMS) for each participant. Incident diagnosis of AD dementia was established by consensus of an expert panel after 3 years. Results: Of the 722 (80.6%) participants who were followed up, 54 (7.5%) developed AD dementia. There was a strong correlation between NAMS and probability of developing AD dementia (r =.91, p =.0003). Each abnormal memory score conferred an additional 9.8% risk of progressing to AD dementia. The area under the receiver operating characteristic curve for NAMS was 0.87 [95% confidence interval (CI).81–.93, p <.01]. The odds ratio for NAMS was 1.67 (95% CI 1.40–2.01, p <.01) after correcting for age, sex, education, estimated intelligence quotient, subjective memory complaint, Mini-Mental State Exam (MMSE) score and apolipoprotein E ϵ4 status. Conclusions: Aggregation of abnormal memory scores may be a useful way of operationalising objective memory impairment, predicting incident AD dementia and providing prognostic stratification for individuals with MCI. [ABSTRACT FROM AUTHOR]

Visual working memory for features and bindings is susceptible to age-related decline. Two experiments were used to examine whether older adults are able to strategically prioritise more valuable information in working memory and whether this could reduce age-related impairments. Younger (18–33 years) and older (60–90 years) adults were presented with coloured shapes and, following a brief delay, asked to recall the feature that had accompanied the probe item. In Experiment 1, participants were either asked to prioritise a more valuable object in the array (serial position 1, 2, or 3) or to treat them all equally. Older adults exhibited worse overall memory performance but were as able as younger adults to prioritise objects. In both groups, this ability was particularly apparent at the middle serial position. Experiment 2 then explored whether younger and older adults' prioritisation is affected by presentation time. Replicating Experiment 1, older adults were able to prioritise the more valuable object in working memory, showing equivalent benefits and costs as younger adults. However, processing speed, as indexed by presentation time, was shown not to limit strategic prioritisation in either age group. Taken together, these findings demonstrate that, although older adults have poorer visual working memory overall, the ability to strategically direct attention to more valuable items in working memory is preserved across ageing. [ABSTRACT FROM AUTHOR]

Brain-predicted age difference scores are calculated by subtracting chronological age from 'brain' age, which is estimated using neuroimaging data. Positive scores reflect accelerated ageing and are associated with increased mortality risk and poorer physical function. To date, however, the relationship between brain-predicted age difference scores and specific cognitive functions has not been systematically examined using appropriate statistical methods. First, applying machine learning to 1359 T1-weighted MRI scans, we predicted the relationship between chronological age and voxel-wise grey matter data. This model was then applied to MRI data from three independent datasets, significantly predicting chronological age in each dataset: Dokuz Eylül University (n = 175), the Cognitive Reserve/Reference Ability Neural Network study (n = 380), and The Irish Longitudinal Study on Ageing (n = 487). Each independent dataset had rich neuropsychological data. Brain-predicted age difference scores were significantly negatively correlated with performance on measures of general cognitive status (two datasets); processing speed, visual attention, and cognitive flexibility (three datasets); visual attention and cognitive flexibility (two datasets); and semantic verbal fluency (two datasets). As such, there is firm evidence of correlations between increased brain-predicted age differences and reduced cognitive function in some domains that are implicated in cognitive ageing. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of later-life formal education or learning on quality of life (QOL), wellbeing, mood, and cognition. Methods: A systematic literature review of interventional clinical trials and observational studies was conducted for adults aged ≥55 years who had undertaken formal education or learning programs. Outcome measures included physical activity, happiness, affective and behavioral symptoms, cognitive function, and QOL. Bias was assessed using funnel plots, Egger's test, and leave1out analysis. Results: From 32 studies identified, we showed qualitative increases in cognitive function, life satisfaction, and self-confidence associated with learning. A meta-analysis revealed a significant pooled mean difference in MMSE scores (0.40, 95% confidence intervals = [0.12, 0.67]). Although there was a low risk of publication bias there was a high risk of sampling bias. Conclusion: Participation in formal education or learning contributed to increased wellbeing, QOL, healthy cognitive function, self-dependency, and a sense of belonging in older adults. [ABSTRACT FROM AUTHOR]

Older adults are thought to compensate for slower lexical processing by making greater use of contextual knowledge, relative to young adults, to predict words in sentences. Accordingly, compared to young adults, older adults should produce larger contextual predictability effects in reading times and skipping rates for words. Empirical support for this account is nevertheless scarce. Perhaps the clearest evidence to date comes from a recent Chinese study showing larger word predictability effects for older adults in reading times but not skipping rates for two-character words. However, one possibility is that the absence of a word-skipping effect in this experiment was due to the older readers skipping words infrequently because of difficulty processing two-character words parafoveally. We therefore took a further look at this issue, using one-character target words to boost word-skipping. Young (18–30 years) and older (65+ years) adults read sentences containing a target word that was either highly predictable or less predictable from the prior sentence context. Our results replicate the finding that older adults produce larger word predictability effects in reading times but not word-skipping, despite high skipping rates. We discuss these findings in relation to ageing effects on reading in different writing systems. [ABSTRACT FROM AUTHOR]

Cognitive epidemiology investigates cognitive predictors of health and disease outcomes. Post-operative cognitive impairment is a common complication of surgery but has been neglected as a health outcome in cognitive epidemiology research. This is despite the fact that knowledge of cognitive predictors of post-operative cognitive impairment can be utilized for risk stratification, informed decision-making (in elective surgery), and personalized care of patients during the postoperative period. In this narrative review, the current literature on cognitive predictors of post-operative cognitive impairment and gaps therein are summarized.

To investigate whether blood–brain barrier (BBB) disruption is a potential mechanism of usual age-related cognitive decline, we conducted dynamic contrast–enhanced (DCE) MRI to measure BBB leakage in a healthy sample, and investigated the association with longitudinal cognitive decline. In a sample of neurologically and cognitively healthy, older individuals, BBB leakage rate in the white and grey matter and hippocampus was measured using DCE MRI with pharmacokinetic modelling. Regression analysis was performed to investigate whether the leakage rate was associated with decline in cognitive performance (memory encoding, memory retrieval, executive functioning and processing speed) over 12 years. White and grey matter BBB leakages were significantly associated with decline in memory retrieval. No significant relations were found between hippocampal BBB leakage and cognitive performance. BBB disruption already being associated with usual cognitive ageing, supports that this neurovascular alteration is a possible explanation for the cognitive decline inherent to the ageing process. More insight into BBB leakage during the normal ageing process could improve estimation and interpretation of leakage rate in pathological conditions. The current results might also stimulate the search for strategies to maintain BBB integrity and help increase the proportion people experiencing successful ageing. Netherlands Trial Register number: NL6358, date of registration: 2017-03-24. [ABSTRACT FROM AUTHOR]

People are living longer and functioning better than at the same age in prior decades, and those aged 60 years and older are often assumed to have similar levels of health and functioning to each other. This study analyzed health and social data from the 2016 Survey of Population Change and Well-being in the Context of Aging Society using the characteristics approach. This method determines variation in the speed of cognitive ageing - assessed through a measurement integrating memory and numeracy, in relation to education levels. A higher education was found to be statistically significantly associated with better cognitive ageing. Great disparities existed in cognitive functioning between those with a below-primary level of education and those with higher education levels. Men tended to have higher scores than women in cognitive function at 60 years of age, but women had a much slower trajectory of cognitive decline associated with ageing. The characteristics approach provides a quantitative perspective on how social gradients can affect people at older ages. [ABSTRACT FROM AUTHOR]

BackgroundThe apolipoprotein E ε4 allele (APOE*ε4) is indicated as a risk for Alzheimer's disease and other age-related diseases. The risk attributable to APOE*ε4 for depression is less clear and may be because of confounding of the relationship between dementia and depression.AimsWe examined the risk of APOE* ε4 for incident depression and depressive symptomology over a 12-year period across the adult lifespan.MethodParticipants were from the Personality and Total Health Through Life study, aged 20 to 24 (n = 1420), 40 to 44 (n = 1592) or 60–64 (n = 1768) at baseline, and interviewed every 4 years since 1999. Ethnicities other than White, those without genotyping and those with depression at baseline, or who reported strokes and scores on the Mini-Mental State Examination

Episodic memory performance declines with increasing age. It has sometimes been reported that this decline is more marked when episodic recollection is estimated by "objective" measures such as source memory performance than when it is estimated by "subjective" measures such as the "Remember/Know" procedure. Here, our main goal was to directly contrast recollection estimates derived from these procedures in the same samples of young and older participants (24 adults per age group, within-subjects manipulation of test procedure). Following identical study phases in which words were paired with either faces or scenes, participants' memories were assessed in separate test blocks using either Remember/Know or source memory procedures. Contrary to several prior reports, the deleterious effects of age on recollection estimates did not differ according to test type. Thus, we found no evidence that age differentially impacts subjective and objective recollection estimates. Additionally, and consistent with prior findings, effects of age on estimates of familiarity-driven recognition were small and non-significant. [ABSTRACT FROM AUTHOR]

Cognitive ageing in developing societies is marked with psychosocial issues such as education, occupation, lifestyle, social support, social interaction and exclusion that may affect cognitive–affective–behavioural changes with ageing. We also present a study based on cognitive profiling of young (N = 79), middle-aged (N = 54) and older adults (N = 43) in India, which examined learning and memory for verbal and visuospatial information, overall cognitive functions, subjective complaints about cognitive difficulties, neuropsychiatric problems, anxiety and emotion regulation. The study shows cognitive changes compared to young and comparable rate of learning and retrieval among middle-aged and older adults for verbal and visuospatial material, correlated with general cognitive ability. The subjective complaints were not correlated with the objective measures of cognitive functions, highlighting the importance of both to show early cognitive changes. The relationship between cognitive functions and emotion regulation or behavioural/emotional changes was observed for young and middle-aged adults but not for older adults. Findings are discussed in the context of the lifespan perspective of cognitive ageing, cognitive reserve, psychosocial environment and social–emotional selectivity theory. [ABSTRACT FROM AUTHOR]

Working memory (WM) training with the N-Back task has been argued to improve cognitive capacity and general cognitive abilities (the Capacity Hypothesis of training), although several studies have shown little or no evidence for such improvements beyond tasks that are very similar to the trained task. Laine et al. demonstrated that instructing young adult participants to use a specific visualisation strategy for N-back training resulted in clear, generalised benefits from only 30 min of training (Strategy Mediation Hypothesis of training). Here, we report a systematic replication and extension of the Laine et al. study, by administering 60 younger and 60 older participants a set of WM tasks before and after a 30-min N-back training session. Half the participants were instructed to use a visualisation strategy, the others received no instruction. The pre-post test battery encompassed a criterion task (digit N-back), two untrained tasks N-back tasks (letters and colours), and three structurally different WM tasks. The instructed visualisation strategy significantly boosted at least some measures of N-back performance in participants of both age groups, although the strategy generally appeared more difficult to implement and less beneficial for older adults. However, the strategy did not improve performance on structurally different WM tasks. We also found significant associations between N-back performance and the type and level of detail of self-generated strategies in the uninstructed participants, as well as age group differences in reported strategy types. WM performance appeared to partly reflect the application of strategies, and Strategy Mediation should be considered to understand the mechanisms of WM training. Claims of efficient training should demonstrate useful improvement beyond task-specific strategies. [ABSTRACT FROM AUTHOR]

During the visual search, cognitive control mechanisms activate to inhibit distracting information and efficiently orient attention towards contextually relevant regions likely to contain the search target. Cognitive ageing is known to hinder cognitive control mechanisms, however little is known about their interplay with contextual expectations, and their role in visual search. In two eye-tracking experiments, we compared the performance of a younger and an older group of participants searching for a target object varying in semantic consistency with the search scene (e.g., a basket of bread vs. a clothes iron in a restaurant scene) after being primed with contextual information either congruent or incongruent with it (e.g., a restaurant vs. a bathroom). Primes were administered either as scenes (Experiment 1) or words (Experiment 2, which included scrambled words as neutral primes). Participants also completed two inhibition tasks (Stroop and Flanker) to assess their cognitive control. Older adults had greater difficulty than younger adults when searching for inconsistent objects, especially when primed with congruent information (Experiment 1), or a scrambled word (neutral condition, Experiment 2). When the target object violates the semantics of the search context, congruent expectations or perceptual distractors, have to be suppressed through cognitive control, as they are irrelevant to the search. In fact, higher cognitive control, especially in older participants, was associated with better target detection in these more challenging conditions, although it did not influence eye-movement responses. These results shed new light on the links between cognitive control, contextual expectations and visual attention in healthy ageing. [ABSTRACT FROM AUTHOR]

Objective: Studies of postoperative cognitive dysfunction (POCD) rely on repeat neuropsychological testing. The stability of the applied instruments, which are affected by natural variability in performance and measurement imprecision, is often unclear. We determined the stability of a neuropsychological test battery using a sample of older adults from the general population. Forty-five participants aged 65 to 89 years performed six computerized and non-computerized neuropsychological tests at baseline and again at 7 day and 3 months follow-up sessions. Mean scores on each test were compared across time points using repeated measures analyses of variance (ANOVA) with pairwise comparison. Two-way mixed effects, absolute agreement analyses of variance intra-class correlation coefficients (ICC) determined test–retest reliability. Results: All tests had moderate to excellent test–retest reliability during 7-day (ICC range 0.63 to 0.94; all p < 0.01) and 3-month intervals (ICC range 0.60 to 0.92; all p < 0.01) though confidence intervals of ICC estimates were large throughout. Practice effects apparent at 7 days eased off by 3 months. No substantial differences between computerized and non-computerized tests were observed. We conclude that the present six-test neuropsychological test battery is appropriate for use in POCD research though small sample size of our study needs to be recognized as a limitation. Trial registration ClinicalTrials.gov Identifier NCT02265263 (15th October 2014) [ABSTRACT FROM AUTHOR]

Background: Work has been associated with cognitive health. We examined whether retirement from work is associated with a decrease in episodic memory and whether this effect differs when considering workers' occupational class.Methods: In this prospective study using the English Longitudinal Study of Ageing (ELSA), we examined 1629 persons aged 50-75 years who were in paid work at baseline. A two-slope random effects linear regression centred at retirement was used to study the effect of retirement on episodic memory. The potential effect modification by occupational class was examined.Results: While memory trajectories show slightly decreasing memory scores before and afterretirement, the decreasing rates for both periods were similar [episodic memory β2b-β2a= -0.03, 95% confidence interval (CI) -0.08, 0.02]. When stratifying by occupational class, there was also no substantial difference in episodic memory trajectories before and after retirement. However, the lower occupational class showed a clear decline in episodic memory with time (pre-retirement β2a = -0.11, 95% CI -0.19, -0.03; post-retirement β2b = -0.13, 95% CI -0.19, -0.07) which was not evident for the higher occupational classes.Conclusions: Our results show no observable difference in trajectories of change in episodic memory before and after retirement. However, the steeper memory decline in workers belonging to the lower occupational class may limit their prospect of prolonging their working lives. Hence enrichment programmes for the prevention of memory decline for these workers should be considered. [ABSTRACT FROM AUTHOR]

Background: Little is known about the link between affective symptoms and cognitive function across the life course. This study aims to investigate whether affective symptoms in adolescence and adulthood predict trajectories of cognitive function from middle to late-adulthood.Methods: Data from the MRC National Survey of Health and Development (NSHD), a cohort of 5362 individuals born in mainland UK in 1946, were utilised. Linear mixed models were used to model cognitive trajectories (memory and processing speed) over a three-decade period (from 43 to 69) and to test effects of affective symptoms in adolescence (ages 13-15) and adulthood (ages 36 and 43) on cognitive function at first testing (age 43) and decline in cognitive function (from 43 to 69). Models were adjusted for sex, childhood cognition, childhood socioeconomic position, and education.Results: A quadratic model best fitted memory and processing speed data. Models revealed that adolescent affective symptoms were associated with lower memory (b = -1.11, SE = 0.53, p = .04) and processing speed (b = -18.17, SE = 7.53, p = .02) at first cognitive testing, but not with rates of decline from 43 to 69. There were no significant associations between adult affective symptoms and cognitive trajectories.Limitations: Missing data is a potential limitation of this study. This was dealt with using maximum likelihood estimation and multiple imputation.Conclusions: Findings suggest that adolescent, but not adult, affective symptoms are important predictors of cognitive function in midlife, but not rate of cognitive decline. This highlights the importance of early intervention to manage mental health in adolescence to protect later cognitive function. [ABSTRACT FROM AUTHOR]

Research into strategies that can combat episodic memory decline in healthy older adults has gained widespread attention over the years. Evidence suggests that a short period of rest immediately after learning can enhance memory consolidation, as compared to engaging in cognitive tasks. However, a recent study in younger adults has shown that post-encoding engagement in a working memory task leads to the same degree of memory consolidation as from post-encoding rest. Here, we tested whether this finding can be extended to older adults. Using a delayed recognition test, we compared the memory consolidation of word–picture pairs learned prior to 9 min of rest or a 2-Back working memory task, and examined its relationship with executive functioning and mindwandering propensity. Our results show that (1) similar to younger adults, memory for the word–picture associations did not differ when encoding was followed by post-encoding rest or 2-Back task and (2) older adults with higher mindwandering propensity retained more word–picture associations encoded prior to rest relative to those encoded prior to the 2-Back task, whereas participants with lower mindwandering propensity had better memory performance for the pairs encoded prior to the 2-Back task. Overall, our results indicate that the degree of episodic memory consolidation during both active and passive post-encoding periods depends on individual mindwandering tendency. [ABSTRACT FROM AUTHOR]

Purpose: Amyloid (Aβ) brain deposition can occur in cognitively normal individuals and is associated with cortical volume abnormalities. Aβ-related volume changes are inconsistent across studies. Since volume is composed of surface area and thickness, the relative contribution of Aβ deposition on each of these metrics remains to be understood in cognitively normal individuals. Methods: A group of 104 cognitively normal individuals underwent neuropsychological assessment, PiB-PET scan, and MRI acquisition. Surface-based cortical analyses were performed to investigate the effects of cortical and subcortical Aβ burden on cortical volume, thickness, and surface area. Mediation analyses were used to study the effect of thickness and surface area on Aβ-associated volume changes. We also investigated the relationships between structural metrics in clusters with abnormal morphology and regions underlying resting-state functional networks and cognitive performance. Results: Cortical Aβ was not associated with cortical morphology. Subcortical Aβ burden was associated with changes in cortical volume, thickness, and surface area. Aβ-associated volume changes were driven by cortical surface area with or without thickness but never by thickness alone. Aβ-associated changes overlapped greatly with regions from the default mode network and were associated with lower performance in visuospatial abilities, episodic memory, and working memory. Conclusions: In cognitively normal individuals, subcortical Aβ is associated with cortical volume, and this effect was driven by surface area with or without thickness. Aβ-associated cortical changes were found in the default mode network and affected cognitive performance. Our findings demonstrate the importance of studying subcortical Aβ and cortical surface area in normal ageing. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Type 2 diabetes, hyperglycaemia and insulin resistance are associated with cognitive impairment and dementia, but causal inference studies using Mendelian randomisation do not confirm this. We hypothesised that early-life cognition and social/educational advantage may confound the relationship. Methods: From the population-based British 1946 birth cohort, a maximum number of 1780 participants had metabolic variables (type 2 diabetes, insulin resistance [HOMA2-IR] and HbA1c) assessed at age 60–64 years, and cognitive state (Addenbrooke's Cognitive Examination III [ACE-III]) and verbal memory assessed at age 69 years. Earlier-life measures included socioeconomic position (SEP), cognition at age 8 years and educational attainment. Polygenic risk scores (PRSs) for type 2 diabetes were calculated. We first used a PRS approach with multivariable linear regression to estimate associations between PRSs and metabolic traits and later-life cognitive state. Second, using a path model approach, we estimated the interrelationships between earlier-life measures, features of mid-life type 2 diabetes and cognitive state at age 69 years. All models were adjusted for sex. Results: The externally weighted PRS for type 2 diabetes was associated with mid-life metabolic traits (e.g. HOMA2-IR β = 0.08 [95% CI 0.02, 0.16]), but not with ACE-III (β = 0.04 [−0.02, 0.90]) or other cognitive outcomes. While there was an association between HOMA2-IR and subsequent ACE-III (β = −0.09 [−0.15, −0.03]), path modelling showed no direct effect (β = −0.01 [−0.06, 0.03]) after accounting for the association between childhood SEP and education with HOMA2-IR. The same pattern was observed for later-life verbal memory. Conclusions/interpretation: Associations between type 2 diabetes and mid-life metabolic traits with subsequent cognitive state do not appear causal, and instead they may be explained by SEP in early life, childhood cognition and educational attainment. Therefore, glucose-lowering medication may be unlikely to combat cognitive impairment in older age. [ABSTRACT FROM AUTHOR]