Exergame and cognitive training for preventing falls in community-dwelling older people: a randomized controlled trial.

Exergame training, in which video games are used to promote exercise, can be tailored to address cognitive and physical risk factors for falls and is a promising method for fall prevention in older people. Here, we performed a randomized clinical trial using the smart±step gaming system to examine the effectiveness of two home-based computer game interventions, seated cognitive training and step exergame training, for fall prevention in community-dwelling older people, as compared with a minimal-intervention control group. Participants aged 65 years or older (n = 769, 71% female) living independently in the community were randomized to one of three arms: (1) cognitive training using a computerized touchpad while seated, (2) exergame step training on a computerized mat or (3) control (provided with an education booklet on healthy ageing and fall prevention). The rate of falls reported monthly over 12 months-the primary outcome of the trial-was significantly reduced in the exergame training group compared with the control group (incidence rate ratio = 0.74, 95% confidence interval = 0.56-0.98), but was not statistically different between the cognitive training and control groups (incidence rate ratio = 0.86, 95% confidence interval = 0.65-1.12). No beneficial effects of the interventions were found for secondary outcomes of physical and cognitive function, and no serious intervention-related adverse events were reported. The results of this trial support the use of exergame step training for preventing falls in community-dwelling older people. As this intervention can be conducted at home and requires only minimal equipment, it has the potential for scalability as a public health intervention to address the increasing problem of falls and fall-related injuries. Australian and New Zealand Clinical Trial Registry identifier: ACTRN12616001325493 .

The effects of computerised cognitive training on post-CABG delirium and cognitive change: A prospective randomised controlled trial.

Background: Cognitive impairments, including delirium, are common after coronary artery bypass grafting (CABG). Improving cognition pre- and post-operatively using computerised cognitive training (CCT) may be an effective approach to improve cognitive outcomes in CABG patients. Objectives: Investigate the effect of remotely supervised CCT on cognitive outcomes, including delirium, in older adults undergoing CABG surgery. Methods: Thirty-six participants, were analysed in a single-blinded randomised controlled trial (CCT Intervention: n = 18, Control: n = 18). CCT was completed by the intervention group pre-operatively (every other day, 45-60-minute sessions until surgery) and post-operatively, beginning 1-month post-CABG (3 x 45-60-minute sessions/week for 12-weeks), while the control group maintained usual care plus weekly phone calls. Cognitive assessments were conducted pre- and post-operatively at multiple follow-ups (discharge, 4-months and 6-months). Post-operative delirium incidence was assessed daily until discharge. Cognitive change data were calculated at each follow-up for each cognitive test (Addenbrooke's Cognitive Examination III and CANTAB; z-scored). Results: Adherence to the CCT intervention (completion of three pre-operative or 66% of post-operative sessions) was achieved in 68% of pre-CABG and 59% of post-CABG participants. There were no statistically significant effects of CCT on any cognitive outcome, including delirium incidence. Conclusion: Adherence to the CCT program was comparatively higher than previous feasibility studies, possibly due to the level of supervision and support provided (blend of face-to-face and home-based training, with support phone calls). Implementing CCT interventions both pre- and post-operatively is feasible in those undergoing CABG. No statistically significant benefits from the CCT interventions were identified for delirium or cognitive function post-CABG, likely due to the sample size available (study recruitment greatly impacted by COVID-19). It also may be the case that multimodal intervention would be more effective.

Harmonisation and Between-Country Differences of the Lifetime of Experiences Questionnaire in Older Adults.

Background: The Lifetime of Experiences Questionnaire (LEQ) assesses complex mental activity across the life-course and has been associated with brain and cognitive health. The different education systems and occupation classifications across countries represent a challenge for international comparisons. The objectives of this study were four-fold: to adapt and harmonise the LEQ across four European countries, assess its validity across countries, explore its association with brain and cognition and begin to investigate between-country differences in life-course mental activities. Method: The LEQ was administered to 359 cognitively unimpaired older adults (mean age and education: 71.2, 13.2 years) from IMAP and EU-funded Medit-Ageing projects. Education systems, classification of occupations and scoring guidelines were adapted to allow comparisons between France, Germany, Spain and United Kingdom. We assessed the LEQ's (i) concurrent validity with a similar instrument (cognitive activities questionnaire - CAQ) and its structural validity by testing the factors' structure across countries, (ii) we investigated its association with cognition and neuroimaging, and (iii) compared its scores between countries. Results: The LEQ showed moderate to strong positive associations with the CAQ and revealed a stable multidimensional structure across countries that was similar to the original LEQ. The LEQ was positively associated with global cognition. Between-country differences were observed in leisure activities across the life-course. Conclusions: The LEQ is a promising tool for assessing the multidimensional construct of cognitive reserve and can be used to measure socio-behavioural determinants of cognitive reserve in older adults across countries. Longitudinal studies are warranted to test further its clinical utility.

Computerised cognitive training to improve cognition including delirium following coronary artery bypass grafting surgery: protocol for a blinded randomised controlled trial.

INTRODUCTION: Coronary artery bypass grafting (CABG) surgery is known to improve vascular function and cardiac-related mortality rates; however, it is associated with high rates of postoperative cognitive decline and delirium. Previous attempts to prevent post-CABG cognitive decline using pharmacological and surgical approaches have been largely unsuccessful. Cognitive prehabilitation and rehabilitation are a viable yet untested option for CABG patients. We aim to investigate the effects of preoperative cognitive training on delirium incidence, and preoperative and postoperative cognitive training on cognitive decline at 4 months post-CABG. METHODS AND ANALYSIS: This study is a randomised, single-blinded, controlled trial investigating the use of computerised cognitive training (CCT) both pre-CABG and post-CABG (intervention group) compared with usual care (control group) in older adults undergoing CABG in Adelaide, South Australia. Those in the intervention group will complete 1-2 weeks of CCT preoperatively (45-60 min sessions, 3.5 sessions/week) and 12 weeks of CCT postoperatively (commencing 1 month following surgery, 45-60 min sessions, 3 sessions/week). All participants will undergo cognitive testing preoperatively, over their hospital stay including delirium, and postoperatively for up to 1 year. The primary delirium outcome variable will be delirium incidence (presence vs absence); the primary cognitive decline variable will be at 4 months (significant decline vs no significant decline/improvement from baseline). Logistic regression modelling will be used, with age and gender as covariates. Secondary outcomes include cognitive decline from baseline to discharge, and at 6 months and 1 year post-CABG. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Central Adelaide Local Health Network Human Research Ethics Committee (South Australia, Australia) and the University of South Australia Human Ethics Committee, with original approval obtained on 13 December 2017. It is anticipated that approximately two to four publications and multiple conference presentations (national and international) will result from this research. TRIAL REGISTRATION NUMBER: This clinical trial is registered with the Australian New Zealand Clinical Trials Registry and relates to the pre-results stage. Registration number: ACTRN12618000799257.

Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI.

Dementia affects 47 million individuals worldwide, and assuming the status quo is projected to rise to 150 million by 2050. Prevention of age-related cognitive impairment in older persons with lifestyle interventions continues to garner evidence but whether this can combat underlying neurodegeneration is unknown. The Study of Mental Activity and Resistance Training (SMART) trial has previously reported within-training findings; the aim of this study was to investigate the long-term neurostructural and cognitive impact of resistance exercise in Mild Cognitive Impairment (MCI). For the first time we show that hippocampal subareas particularly susceptible to volume loss in Alzheimer's disease (AD) are protected by resistance exercise for up to one year after training. One hundred MCI participants were randomised to one of four training groups: (1) Combined high intensity progressive resistance and computerised cognitive training (PRT+CCT), (2) PRT+Sham CCT, (3) CCT+Sham PRT, (4) Sham physical+sham cognitive training (SHAM+SHAM). Physical, neuropsychological and MRI assessments were carried out at baseline, 6 months (directly after training) and 18 months from baseline (12 months after intervention cessation). Here we report neuro-structural and functional changes over the 18-month trial period and the association with global cognitive and executive function measures. PRT but not CCT or PRT+CCT led to global long-term cognitive improvements above SHAM intervention at 18-month follow-up. Furthermore, hippocampal subfields susceptible to atrophy in AD were protected by PRT revealing an elimination of long-term atrophy in the left subiculum, and attenuation of atrophy in left CA1 and dentate gyrus when compared to SHAM+SHAM (p = 0.023, p = 0.020 and p = 0.027). These neuroprotective effects mediated a significant portion of long-term cognitive benefits. By contrast, within-training posterior cingulate plasticity decayed after training cessation and was unrelated to long term cognitive benefits. Neither general physical activity levels nor fitness change over the 18-month period mediated hippocampal trajectory, demonstrating that enduring hippocampal subfield plasticity is not a simple reflection of post-training changes in fitness or physical activity participation. Notably, resting-state fMRI analysis revealed that both the hippocampus and posterior cingulate participate in a functional network that continued to be upregulated following intervention cessation. Multiple structural mechanisms may contribute to the long-term global cognitive benefit of resistance exercise, developing along different time courses but functionally linked. For the first time we show that 6 months of high intensity resistance exercise is capable of not only promoting better cognition in those with MCI, but also protecting AD-vulnerable hippocampal subfields from degeneration for at least 12 months post-intervention. These findings emphasise the therapeutic potential of resistance exercise; however, future work will need to establish just how long-lived these outcomes are and whether they are sufficient to delay dementia.

Memory Performance Correlates of Hippocampal Subfield Volume in Mild Cognitive Impairment Subtype.

The increased understanding that neuropathology begins decades before symptom onset, has led to the conceptualization and widespread utilization of Mild Cognitive Impairment (MCI) as an important transitional state between healthy aging and dementia. Further subcategorization to MCI subtype has led to more distinct prognoses and it is widely considered that amnestic and non-amnestic MCI (aMCI, naMCI) likely have distinct pathophysiologies. Yet, accurately classification remains contentious. Here, we differentiate hippocampal subfield volume between subtypes, diagnosed according to stringent clinical consensus criteria, where aMCI is characterized based on deficits in delayed recall (rather than encoding). We then identify memory performance correlates to subfield volume and associations with long-term cognitive performance and outcome. 3D T1-weighted structural MRI was acquired in 142 participants recruited from the Healthy Brain Aging (HBA) Clinic and diagnosed with aMCI (n = 38), naMCI (n = 84) or subjective memory complaints (SMC; n = 20). T1-weighted datasets were processed with the cortical and hippocampal subfield processing streams in FreeSurfer (v6.0). Subfield volumes, and associations with baseline and longitudinal objective memory scores were then examined. Subfield volumes were found to differentiate clinical profiles: subiculum, CA1, CA4 and dentate gyrus volumes were significantly reduced in aMCI compared to both naMCI and SMC. CA1 subfield volume was shown to predict concurrent memory performance in aMCI, while dentate gyrus volume significantly predicted longitudinal verbal learning and memory decline in the entire cohort. Our findings demonstrate that using a more stringent diagnostic approach to characterizing aMCI is well justified, as delayed recall deficits are strongly linked to underlying volumetric subfield reductions in CA1, CA4 and the dentate gyrus, subfields known to be associated with mnemonic processes. Further research is now warranted to replicate these findings in other MCI samples.

Cognitive dysfunction in naturally occurring canine idiopathic epilepsy.

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments.

Age is no barrier: predictors of academic success in older learners.

Although predictors of academic success have been identified in young adults, such predictors are unlikely to translate directly to an older student population, where such information is scarce. The current study aimed to examine cognitive, psychosocial, lifetime, and genetic predictors of university-level academic performance in older adults (50-79 years old). Participants were mostly female (71%) and had a greater than high school education level (M = 14.06 years, SD = 2.76), on average. Two multiple linear regression analyses were conducted. The first examined all potential predictors of grade point average (GPA) in the subset of participants who had volunteered samples for genetic analysis (N = 181). Significant predictors of GPA were then re-examined in a second multiple linear regression using the full sample (N = 329). Our data show that the cognitive domains of episodic memory and language processing, in conjunction with midlife engagement in cognitively stimulating activities, have a role in predicting academic performance as measured by GPA in the first year of study. In contrast, it was determined that age, IQ, gender, working memory, psychosocial factors, and common brain gene polymorphisms linked to brain function, plasticity and degeneration (APOE, BDNF, COMT, KIBRA, SERT) did not influence academic performance. These findings demonstrate that ageing does not impede academic achievement, and that discrete cognitive skills as well as lifetime engagement in cognitively stimulating activities can promote academic success in older adults.

Midlife managerial experience is linked to late life hippocampal morphology and function.

An active cognitive lifestyle has been suggested to have a protective role in the long-term maintenance of cognition. Amongst healthy older adults, more managerial or supervisory experiences in midlife are linked to a slower hippocampal atrophy rate in late life. Yet whether similar links exist in individuals with Mild Cognitive Impairment (MCI) is not known, nor whether these differences have any functional implications. 68 volunteers from the Sydney SMART Trial, diagnosed with non-amnestic MCI, were divided into high and low managerial experience (HME/LME) during their working life. All participants underwent neuropsychological testing, structural and resting-state functional MRI. Group comparisons were performed on hippocampal volume, morphology, hippocampal seed-based functional connectivity, memory and executive function and self-ratings of memory proficiency. HME was linked to better memory function (p = 0.024), mediated by larger hippocampal volume (p = 0.025). More specifically, deformation analysis found HME had relatively more volume in the CA1 sub-region of the hippocampus (p < 0.05). Paradoxically, this group rated their memory proficiency worse (p = 0.004), a result correlated with diminished functional connectivity between the right hippocampus and right prefrontal cortex (p < 0.001). Finally, hierarchical regression modelling substantiated this double dissociation.

Social cognition is not associated with cognitive reserve in older adults.

Social and general cognitive abilities decline in late life. Those with high cognitive reserve display better general cognitive performance in old age; however, it is unknown whether this is also the case for social cognition. A total of 115 healthy older adults, aged 60-85 years (m = 44, f = 71) were assessed using The Awareness of Social Inference Test (TASIT-R; social cognition), the Lifetime of Experiences Questionnaire (LEQ; cognitive reserve), and the Wechsler Abbreviated Scale of Intelligence (WASI-II; general cognitive ability). The LEQ did not predict performance on any TASIT-R subtest: Emotion Evaluation Test (ß = -.097, p = .325), Social Inference - Minimal (ß = -.004, p = .972), or Social Inference - Enriched (ß = -.016, p = .878). Sensitivity analyses using two alternative cognitive reserve measures, years of education and the National Adult Reading Test, supported these effects. Cognitive reserve was strongly related to WASI-II performance. Unlike general cognitive ability, social cognition appears unaffected by cognitive reserve. Findings contribute to the emerging understanding that cognitive reserve differentially affects individual cognitive domains, which has implications for the theoretical understanding of cognitive reserve and its brain correlates. Cognitive measures unbiased by cognitive reserve may serve as best indicators of brain health, free of compensatory mechanisms.

Posterior compensatory network in cognitively intact elders with hippocampal atrophy.

Functional compensation in late life is poorly understood but may be vital to understanding long-term cognitive trajectories. To study this we first established an empirically derived threshold to distinguish hippocampal atrophy in those with Mild Cognitive Impairment (MCI n = 34) from those with proficient cognition (PRO n = 22), using data from a population-based cohort. Next, to identify compensatory networks we compared cortical activity patterns during a graded spatial working memory (SWM) task in only cognitively proficient individuals, either with (PROATR ) or without hippocampal atrophy (PRONIL ). Multivariate Partial Least Squares analyses revealed that these groups engaged spatially distinct SWM-related networks. In those with hippocampal atrophy and under conditions of basic-SWM demand, expression of a posterior compensatory network (PCN) comprised calcarine and posterior parietal cortex strongly correlated with superior SWM performance (r = -0.96). In these individuals, basic level SWM response times were faster and no less accurate than in those with no hippocampal atrophy. Cognitively proficient older individuals with hippocampal atrophy may, therefore, uniquely engage posterior brain areas when performing simple spatial working memory tasks.

BDNF and COMT polymorphisms have a limited association with episodic memory performance or engagement in complex cognitive activity in healthy older adults.

Cognitive decline is a major factor in lowering the quality of life in older populations, and contributes substantially to social, economic, and health costs. As humans age, cognitive function decreases differentially, and individual differences in cognitive ageing are likely attributed to a range of causes, including environmental and genetic influences. The current study included 360 participants (240 females and 120 males) aged between 50 and 79years from the Tasmanian Healthy Brain Project. The brain-derived neurotrophic factor (BDNF) Val66Met and Catechol-O-Methyltransferase (COMT) Val158Met polymorphisms were examined for their association with visual and auditory episodic memory performance. The polymorphisms were also investigated for their association with reported life-long engagement in complex cognitive activity using a retrospective questionnaire. Relative to the demographic variables, the gene variations were found to have no association with episodic memory performance, with the exception of the COMT polymorphism on a single measure of auditory memory (RAVLT). Several other studies also demonstrated that these polymorphisms have no, small, or inconsistent effects on memory function. The BDNF Val66Met and COMT Val158Met polymorphisms were also found to be of little significance to active engagement in complex cognitive activity throughout most of the lifespan. An association was detected between BDNF Val66Met and engagement in cognitive activity in early life (p=.04, d=.23), however this did not reach significance when adjusted for multiple comparisons. The biological mechanisms that underlie engagement in cognitive activity are elusive, thus the potential relationship between BDNF Val66Met genotype and early life cognitive engagement warrants further investigation.

Cognitive and social lifestyle: links with neuropathology and cognition in late life.

Many studies report an association of cognitive and social experiential factors and related traits with dementia risk. Further, many clinical-pathologic studies find a poor correspondence between levels of neuropathology and the presence of dementia and level of cognitive impairment. The poor correspondence suggests that other factors contribute to the maintenance or loss of cognitive function, with factors associated with the maintenance of function referred to as neural or cognitive reserve. This has led investigators to examine the associations of cognitive and social experiential factors with neuropathology as a first step in disentangling the complex associations between these experiential risk factors, neuropathology, and cognitive impairment. Despite the consistent associations of a range of cognitive and social lifestyle factors with cognitive decline and dementia risk, the extant clinical-pathologic data find only a single factor from one cohort, linguistic ability, related to AD pathology. Other factors, including education, harm avoidance, and emotional neglect, are associated with cerebrovascular disease. Overall, the associations are weak. Some factors, such as education, social networks, and purpose in life, modify the relation of neuropathology to cognition. Finally, some factors such as cognitive activity appear to bypass known pathologies altogether suggesting a more direct association with biologic indices that promote person-specific differences in reserve and resilience. Future work will first need to replicate findings across more studies to ensure the veracity of the existing data. Second, effort is needed to identify the molecular substrates of neural reserve as potential mediators of the association of lifestyle factors with cognition.

Cognitive lifestyle in older persons: the population-based Sydney Memory and Ageing Study.

BACKGROUND: Cognitive lifestyle may be an important modifiable risk factor for dementia but has not yet been comprehensively studied in healthy elderly. OBJECTIVE: To examine gender- and lifespan-related differences in cognitive lifestyle in a population-based cohort. METHODS: 872 individuals from the second wave of the Sydney Memory and Ageing Study (MAS) cohort were invited to complete the Lifetime of Experiences Questionnaire (LEQ), a validated measure of cognitive lifestyle. Of 555 questionnaires returned (64%), 253 were excluded due to prior diagnosis of mild cognitive impairment, leaving n = 302 cognitively-intact elders (mean age 80.1 years, ±SD 4.7, 40.1% men). RESULTS: Total LEQ was significantly higher in men (97.9 ± 20.0) than women (90.0 ± 24.5), resulting mainly from midlife LEQ differences. Men were more likely to have worked in managerial or professional jobs (73.8% versus 39.5% women), and twice as likely to have supervised large groups of workers. In late life, women were significantly more likely to be living alone (68.1% versus 25.4% men), but otherwise significantly more engaged in specific cognitive activities, including reading novels (72.3% versus 52.0% men) and incorporating volunteer work (31.9% versus 19.7% men) and socializing (59.0% versus 37.0% men) into their typical day. Over the adult lifespan, it was more common for men and women to transition between LEQ tertiles than remain the same. CONCLUSIONS: Cognitive lifestyle changes over the adult lifespan and exhibits a range of gender-based differences. While older women are more likely to be living alone they generally lead a more active current cognitive lifestyle.

The Tasmanian Healthy Brain Project (THBP): a prospective longitudinal examination of the effect of university-level education in older adults in preventing age-related cognitive decline and reducing the risk of dementia.

BACKGROUND: Differences in the level of cognitive compromise between individuals following brain injury are thought to arise from underlying differences in cognitive reserve. The level of cognitive reserve attained by an individual is influenced by both genetic and life experience factors such as educational attainment and occupational history. The Tasmanian Healthy Brain Project (THBP) is a world-first prospective study examining the capacity of university-level education to enhance cognitive reserve in older adults and subsequently reduce age-related cognitive decline and risk for neurodegenerative disease. METHODS: Up to 1,000 adults aged 50-79 years at the time of entry into the study will be recruited to participate in the THBP. All participants will be healthy and free of significant medical, psychological, or psychiatric illness. Of the participant sample, 90% will undertake a minimum of 12 months part-time university-level study as an intervention. The remaining 10% will act as a control reference group. Participants will complete an annual comprehensive assessment of neuropsychological function, medical health, socialization, and personal well-being. Premorbid estimates of past cognitive, education, occupational, and physical function will be used to account for the mediating influence of prior life experience on outcomes. Potential contributing genetic factors will also be explored. RESULTS: Participant results will be assessed annually. Participants displaying evidence of dementia on the comprehensive neuropsychological assessment will be referred to an independent psycho-geriatrician for screening and diagnosis. CONCLUSIONS: The THBP commenced in 2011 and is expected to run for 10-20 years duration. To date, a total of 383 participants have been recruited into the THBP.

Age-specific effects of voluntary exercise on memory and the older brain.

BACKGROUND: Physical exercise in early adulthood and mid-life improves cognitive function and enhances brain plasticity, but the effects of commencing exercise in late adulthood are not well-understood. METHOD: We investigated the effects of voluntary exercise in the restoration of place recognition memory in aged rats and examined hippocampal changes of synaptic density and neurogenesis. RESULTS: We found a highly selective age-related deficit in place recognition memory that is stable across retest sessions and correlates strongly with loss of hippocampal synapses. Additionally, 12 weeks of voluntary running at 20 months of age removed the deficit in the hippocampally dependent place recognition memory. Voluntary running restored presynaptic density in the dentate gyrus and CA3 hippocampal subregions in aged rats to levels beyond those observed in younger animals, in which exercise had no functional or synaptic effects. By contrast, hippocampal neurogenesis, a possible memory-related mechanism, increased in both young and aged rats after physical exercise but was not linked with performance in the place recognition task. We used graph-based network analysis based on synaptic covariance patterns to characterize efficient intrahippocampal connectivity. This analysis revealed that voluntary running completely reverses the profound degradation of hippocampal network efficiency that accompanies sedentary aging. Furthermore, at an individual animal level, both overall hippocampal presynaptic density and subregional connectivity independently contribute to prediction of successful place recognition memory performance. CONCLUSIONS: Our findings emphasize the unique synaptic effects of exercise on the aged brain and their specific relevance to a hippocampally based memory system for place recognition.

Active cognitive lifestyle is associated with positive cognitive health transitions and compression of morbidity from age sixty-five.

BACKGROUND: Three factors commonly used as measures of cognitive lifestyle are education, occupation, and social engagement. This study determined the relative importance of each variable to long term cognitive health in those with and without severe cognitive impairment. METHODS: Data came from 12,470 participants from a multi-centre population-based cohort (Medical Research Council Cognitive Function and Ageing Study). Respondents were aged 65 years and over and were followed-up over 16 years. Cognitive states of no impairment, slight impairment, and moderate/severe impairment were defined, based on scores from the Mini-Mental State Examination. Multi-state modelling was used to investigate links between component cognitive lifestyle variables, cognitive state transitions over time, and death. RESULTS: Higher educational attainment and a more complex mid-life occupation were associated with a lower risk of moving from a non-impaired to a slightly impaired state (hazard ratios 0.5 and 0.8), but with increased mortality from a severely impaired state (1.3 and 1.1). More socially engaged individuals had a decreased risk of moving from a slightly impaired state to a moderately/severely impaired state (0.7). All three cognitive lifestyle variables were linked to an increased chance of cognitive recovery back to the non-impaired state. CONCLUSIONS: In those without severe cognitive impairment, different aspects of cognitive lifestyle predict positive cognitive transitions over time, and in those with severe cognitive impairment, a reduced life-expectancy. An active cognitive lifestyle is therefore linked to compression of cognitive morbidity in late life.

Supervisory experience at work is linked to low rate of hippocampal atrophy in late life.

Cultivation of an active cognitive lifestyle, including diverse and challenging educational, occupational and cognitively-loaded leisure activities may be protective against development of dementia but the mechanisms underlying this link are not clear. We used the Lifetime Experiences Questionnaire (LEQ) to assess the structural brain correlates of cognitive lifestyle in the Sydney Memory and Aging Study, a large population-based cohort of originally 1037 non-demented elderly aged over 70 years of age. After excluding those without structural Magnetic Resonance Image data or Mild Cognitive Impairment at their most recent assessment, 151 cognitively intact subjects were studied. Whole-brain voxel based morphometric analysis found that higher total Lifetime Experiences Questionnaire scores are linked with increased grey matter volume in the medial temporal lobe, especially in the hippocampus. Through a series of more specific analyses, we found that supervisory and managerial experience in midlife was the dominant contributor to this effect. Furthermore, in those with longitudinal neuroimaging data (N=91), we measured hippocampal structural changes over a 2-3 year period by gold-standard manual tracing. The rate of hippocampal atrophy in late-life in those with high level supervisory experience in midlife was five-times slower than those with no midlife supervisory experience (p<0.001). Individual differences in intracranial volume, age, gender, physical activity, depressive symptoms, or apolipoprotein ε4 genetic status could not explain these findings, nor could specific lifestyle patterns in late life. For the first time, we reveal that managerial and supervisory experience during our working life is connected to hippocampal integrity after retirement, some 20-30 years later. Our results stimulate several questions about the nature of work-related effects on longterm behaviour, structural neuroplasticity and neuroprotection, and may help explain differences in dementia-risk based on cognitive lifestyle.

Active cognitive lifestyle associates with cognitive recovery and a reduced risk of cognitive decline.

Education and lifestyle factors linked with complex mental activity are thought to affect the progression of cognitive decline. Collectively, these factors can be combined to create a cognitive reserve or cognitive lifestyle score. This study tested the association between cognitive lifestyle score and cognitive change in a population-based cohort of older persons from five sites across England and Wales. Data came from 13,004 participants of the Medical Research Council Cognitive Function and Ageing Study who were aged 65 years and over. Cognition was assessed at multiple waves over 16 years using the Mini-Mental State Examination. Subjects were grouped into four cognitive states (no impairment, slight impairment, moderate impairment, severe impairment) and cognitive lifestyle score was assessed as a composite measure of education, mid-life occupation, and current social engagement. A multi-state model was used to test the effect of cognitive lifestyle score on cognitive transitions. Hazard ratios for cognitive lifestyle score showed significant differences between those in the upper compared to the lower tertile with a more active cognitive lifestyle associating with: a decreased risk of moving from no to slight impairment (0.58, 95% CI (0.45, 0.74)); recovery from a slightly impaired state back to a non-impaired state (2.93 (1.35, 6.38)); but an increased mortality risk from a severely impaired state (1.28 (1.12, 1.45)). An active cognitive lifestyle is associated with a more favorable cognitive trajectory in older persons. Future studies would ideally incorporate neuroradiological and neuropathological data to determine if there is causal evidence for these associations.