Sex-Specific Protective Effects of Cognitive Reserve on Age-Related Cognitive Decline: A 5-Year Prospective Cohort Study.

BACKGROUND AND OBJECTIVES: Females have a higher age-adjusted incidence of Alzheimer disease than males but the reasons for this remain unclear. One proposed contributing factor is that, historically, females had less access to education and, therefore, may accumulate less cognitive reserve. However, educational attainment is confounded by IQ, which in itself is a component of cognitive reserve and does not differ between sexes. Steeper age-related cognitive declines are associated with increased risk of dementia. We, therefore, evaluated the moderating effects of 2 proxies for cognitive reserve, education and IQ, on the steepness of age-related declining cognitive trajectories in unimpaired older males and females. METHODS: The Tasmanian Healthy Brain Project, a long-term cohort study, recruited healthy Australians aged 50-80 years without cognitive impairment. Baseline cognitive reserve was measured using educational history and IQ, measured by the Wechsler Test of Adult Reading, Full Scale Predicted IQ (WTAR-FSIQ). Cognitive trajectories for language, executive function, and episodic and working memory over 5 years were extracted from neuropsychological assessments. The adjusted effects of education, estimated IQ, and APOE allelic variant on cognitive trajectories were compared between males and females. RESULTS: Five hundred sixty-two individuals (mean [SD] age 60 [6.7] years; 68% male; 33% APOE ε4+) were followed up over 5 years with 1,924 assessments and 24,946 cognitive test scores (annualized attrition rate 6.6% per year). Estimated IQ correlated with years of education (p < 0.001). Estimated IQ interacted with sex to moderate age-related cognitive trajectories (p = 0.03; adjusted for education); lower IQ males experienced steeper declining trajectories than higher IQ males, but lower IQ females had similar steepness of declining trajectories to higher IQ females. Education was not associated with rate of cognitive decline (p = 0.67; adjusted for WTAR-FSIQ). There were no significant differences in age-related cognitive trajectories between APOE genotypes in either sex. DISCUSSION: IQ, a measure of cognitive reserve, predicted the steepness of declining cognitive trajectories in males only. Education did not explain as much variation in cognitive trajectories as IQ. Our findings do not support the hypothesis that historical sex disparities in access to education contribute to the higher female incidence of Alzheimer disease.

Path analysis of biomarkers for cognitive decline in early Parkinson's disease.

Clinical and biochemical diversity of Parkinson's disease (PD) and numerous demographic, clinical, and pathological measures influencing cognitive function and its decline in PD create problems with the determination of effects of individual measures on cognition in PD. This is particularly the case where these measures significantly interrelate with each other producing intricate networks of direct and indirect effects on cognition. Here, we use generalized structural equation modelling (GSEM) to identify and characterize significant paths for direct and indirect effects of 14 baseline measures on global cognition in PD at baseline and at 4 years later. We consider 269 drug-naïve participants from the Parkinson's Progression Marker Initiative database, diagnosed with idiopathic PD and observed for at least 4 years after baseline. Two GSEM networks are derived, highlighting the possibility of at least two different molecular pathways or two different PD sub-types, with either CSF p-tau181 or amyloid beta (1-42) being the primary protein variables potentially driving progression of cognitive decline. The models provide insights into the interrelations between the 14 baseline variables, and determined their total effects on cognition in early PD. High CSF amyloid concentrations (> 500 pg/ml) are associated with nearly full protection against cognitive decline in early PD in the whole range of baseline age between 40 and 80 years, and irrespectively of whether p-tau181 or amyloid beta (1-42) are considered as the primary protein variables. The total effect of depression on cognition is shown to be strongly amplified by PD, but not at the time of diagnosis or at prodromal stages. CSF p-tau181 protein could not be a reliable indicator of cognitive decline because of its significantly heterogeneous effects on cognition. The outcomes will enable better understanding of the roles of the clinical and pathological measures and their mutual effects on cognition in early PD.

Fronto-temporal functional disconnection precedes hippocampal atrophy in clinically confirmed multi-domain amnestic Mild Cognitive Impairment.

Mild Cognitive Impairment (MCI) is fraught with high false positive diagnostic errors. The high rate of false positive diagnosis hampers attempts to identify reliable and valid biomarkers for MCI. Recent research suggests that aberrant functional neurocircuitries emerge prior to significant cognitive deficits. The aim of the present study was to examine this in clinically confirmed multi-domain amnestic-MCI (mdaMCI) using an established, multi-time point, methodology for minimizing false positive diagnosis. Structural and resting-state functional MRI data were acquired in healthy controls (HC, n=24), clinically-confirmed multi-domain amnestic-MCI (mdaMCI, n=14) and mild Alzheimer's Dementia (mAD, n=6). Group differences in cortical thickness, hippocampal volume and functional connectivity were investigated. Hippocampal subvolumes differentiated mAD from HC and mdaMCI. Functional decoupling of fronto-temporal networks implicated in memory and executive function differentiated HC and mdaMCI. Decreased functional connectivity in these networks was associated with poorer cognitive performance scores. Preliminary findings suggest the large-scale decoupling of fronto-temporal networks associated with cognitive decline precedes measurable structural neurodegeneration in clinically confirmed MCI and may represent a potential biomarker for disease progression.

Studying at university in later life slows cognitive decline: A long-term prospective study.

INTRODUCTION: Declining cognition in later life is associated with loss of independence and quality of life. This decline in cognition may potentially be reduced or reversed through engaging in cognitively stimulating activities. This study examined the potential for university attendance in later life to enhance cognitive function in older adults. METHODS: Cognitively unimpaired adults (n = 485, 69% female, median age 60 years) were given the opportunity to undertake free university study. Repeated neurocognitive assessment was performed over 7 years. RESULTS: Participants in the university education group (n = 383) improved z = .02 SD (.01, .03) per year of the study compared to controls (P = .001; averaged across a battery of cognitive tests). The largest improvements were observed on tests of language and verbal learning, memory, and episodic memory. DISCUSSION: Later-life university study was associated with improved cognitive trajectories. Later-life education may preserve cognitive function, specifically for functions associated with communication, social interaction, and maintaining independence.

Association Between Components of Cognitive Reserve and Serum BDNF in Healthy Older Adults.

Background: The brain-derived neurotrophic factor (BDNF) protein has been shown to have a prominent role in neuron survival, growth, and function in experimental models, and the BDNF Val66Met polymorphism which regulates its expression has been linked to resilience toward the effects of aging on cognition. Cognitively stimulating activity is linked to both increased levels of BDNF in the brain, and protection against age-related cognitive decline. The aim of this study was to investigate the associations between serum BDNF levels, the BDNF Val66Met genotype, and components of cognitive reserve in early and mid-life, measured with the Lifetime of Experiences Questionnaire (LEQ). Methods: Serum BDNF levels were measured cross-sectionally in 156 participants from the Tasmanian Healthy Brain Project (THBP) cohort, a study examining the potential benefits of older adults engaging in a university-level education intervention. Multiple linear regression was used to estimate serum BDNF's association with age, education, gender, BDNF Val66Met genotype, later-life university-level study, and cognitively stimulating activities measured by the LEQ. Results: Serum BDNF in older adults was associated with early life education and training, increasing 0.007 log(pg/ml) [95%CI 0.001, 0.012] per unit on the LEQ subscale. Conversely, education and training in mid-life were associated with a -0.007 log(pg/ml) [-0.012, -0.001] decrease per unit on the LEQ subscale. Serum BDNF decreased with age (-0.008 log(pg/ml) [-0.015, -0.001] per year), and male gender (-0.109 log(pg/ml) [-0.203, -0.015]), but mean differences between the BDNF Val66Met polymorphisms were not significant (p = 0.066). All effect sizes were small, with mid-life education and training having the largest effect size ( η p 2 = 0.044). Conclusion: Education in both early and mid-life explained small but significant amounts of variance in serum BDNF levels, more than age or gender. These effects were opposed and independent, suggesting that education at different stages of life may be associated with different cognitive and neural demands. Education at different stages of life may be important covariates when estimating associations between other exposures and serum BDNF.

The My Active and Healthy Aging ICT platform prevents quality of life decline in older adults: a randomised controlled study.

INTRODUCTION: Prevention of frailty is paramount in older adults. We evaluated the efficacy of a tailored multidomain intervention, monitored with the My Active and Healthy Aging platform, in reducing conversion from a prefrail status to overt frailty and preventing decline in quality of life. METHODS: We performed a multicentre, multicultural, randomised control study. The effects of multidomain interventions on frailty parameters, quality of life, physical, cognitive, psychosocial function, nutrition and sleep were evaluated in a group of 101 prefrail older subjects and compared with 100 prefrail controls, receiving general health advice. RESULTS: At the 12-month assessment, controls showed a decline in quality of life that was absent in the active group. In addition, active participants showed an increase in mood and nutrition function. No effect on remaining parameter was observed. DISCUSSION: Our study supports the use of personalised multidomain intervention, monitored with an information and communication technology platform, in preventing quality of life decline in older adults.

Assessing mindfulness: Experimental support for the discriminant validity of breath counting as a measure of mindfulness but not self-report questionnaires.

The current study sought to examine the discriminant validity of 3 commonly used measures of mindfulness. The discriminative ability of the Mindful Attention Awareness Scale (MAAS), the Five Factor Mindfulness Questionnaire (FFMQ), and a breath counting task (BCT) was assessed in a randomized control trial involving an 8-week mindfulness training (MT) condition (n = 53) and an active control computerized attention training (CT) program (n = 33). No evidence to support the discriminant validity of MAAS or FFMQ scores was found, as these self-report measures responded to both the MT and CT conditions. Breath counting scores however demonstrated unique responsiveness to the MT program, suggesting this behavioral task may be useful in measuring changes in mindfulness as it closely resembles core cognitive processes trained during this practice. Implications of these findings for the construct validity of both self-report and behavioral measures of mindfulness are discussed, along with the suitability of current mindfulness-based interventions in studies aiming to assess mindfulness outcomes. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Neural changes in early visual processing after 6 months of mindfulness training in older adults.

Mindfulness has been shown to improve attentional performance, which is known to decline in aging. Long-latency electroencephalographic (EEG) event-related potential (ERP) changes have been reported immediately after mindfulness training, however the enduring stability of these effects is unknown. Furthermore, the ability of mindfulness to impact earlier stages of information processing is unclear. We examined neural activation using high density EEG in older adults engaged in mindfulness training to examine the long-term stability of training effects. After 6 months of training, mindfulness practitioners displayed enhanced neural activation during sensory encoding and perceptual processing of a visual cue. Enhanced perceptual processing of a visual cue was associated with increased neural activation during post-perceptual processing of a subsequent target. Similar changes were not observed in a control group engaged in computer-based attention training over the same period. Neural changes following mindfulness training were accompanied by behavioural improvements in attentional performance. Our results are suggestive of increased efficiency of the neural pathways subserving bottom-up visual processing together with an enhanced ability to mobilise top-down attentional processes during perceptual and post-perceptual processing following mindfulness training. These results indicate that mindfulness may enhance neural processes known to deteriorate in normal aging and age-related neurodegenerative diseases.

Reduced cerebral pressure-flow responses are associated with electrophysiological markers of attention in healthy older adults.

The aim of this study was to determine the effect of age on the relationship between cerebrovascular function and the neural bases of sustained attention. Twenty-seven healthy young adults (aged 18-30 years) and 24 older adults (60-75 years) underwent assessments of cerebrovascular function and sustained attention. Blood flow velocity of the middle cerebral artery was assessed via Transcranial Doppler Ultrasound, during seated rest, in response to hypocapnic breathing (cerebrovascular reactivity) and during a repeated sit-to-stand procedure (pressure-flow response). Attentional processing was assessed using the N2 and P3 components of the event-related potential during a two-tone auditory oddball task. Poorer pressure-flow responses were significantly associated with reductions in N2 and P3 amplitude in the old group (b = -0.50, p = .029 and b = -0.46, p = .045), but not the young group. These results suggest that alterations in the brain's capacity to combat reductions in perfusion pressure are associated with age-related differences in attentional processing, supporting the hypothesis that cerebrovascular hemodynamic disturbances play a role in age-related cognitive decline.

Auditory event-related potentials in individuals with subjective and mild cognitive impairment.

OBJECTIVE: The analysis of event-related potentials (ERPs) is a useful tool to differentiate between healthy older adults, and individuals with mild cognitive impairment (MCI). Less is known about the ERPs' sensitivity of differentiating between individuals with subjective cognitive impairment (SCI) and MCI, as early evidence indicates similar brain alterations between these two groups. In order, to establish tests that are sensitive to subclinical impairment, this study compared auditory evoked ERPs between individuals with SCI and MCI. METHODS: Besides assessing cognitive performance in four neuropsychological tests (Trail Making Test A + B, verbal fluency letter and category task), latency and amplitude of ERP components evoked by an auditory oddball paradigm were compared between two groups of either individuals with SCI (n = 13) or MCI (n = 13). RESULTS: While individuals with MCI performed significantly worse in all neuropsychological tests (TMT A: p = 0.001, Cohen's d = 1.5; TMT B: p = 0.030, Cohen's d = 0.94; verbal fluency letter: p = 0.0011, Cohen's d = 1.08; verbal fluency category: p = 0.038; Cohen's d = 0.86), no significant differences (p > 0.05) were found in ERP components with small to moderate effect sizes (Cohen's d ranged between 0.11 - 0.59). CONCLUSION: ERPs evoked by an auditory oddball paradigm lack sensitivity to differentiate between individuals with SCI and MCI, although significant differences in cognitive performance were detected by neuropsychological tests. Similar pathophysiological brain alterations may limit utility of ERPs as indicated by previous research and results of this study. Cognitively more challenging tasks than the auditory oddball paradigm may be considered by future investigations.

Cerebrovascular Correlates of Subclinical Attentional Disturbances in Non-stroke Cardiovascular Disease.

Evidence suggests that cerebrovascular hemodynamic disturbances underlie cognitive deterioration secondary to cardiovascular disease (CVD), including manifestations other than stroke, but the mechanisms remain unclear. To date, the majority of studies have used neuropsychological measures validated for the detection of clinically significant cognitive decline but lack the sensitivity to accurately detect subclinical or subtle cognitive changes. The N2 and P3 components of the event-related potential are sensitive markers of attention and cognitive processing, and are valuable in the assessment of age-related cognitive changes and neurodegenerative disease. The aims of this study were to test (a) the sensitivity of N2 and P3 components in differentiating older adults with CVD from healthy controls, and (b) whether cerebrovascular hemodynamics are associated with alterations in attention in persons with non-stroke CVD. Older adults with CVD (n = 20) and healthy older adults (n = 20) without cognitive impairment or history of stroke and matched for age, were recruited. Cerebral blood flow velocity of the middle cerebral artery (MCAv) and Gosling's Pulsatility Index (PI) were assessed using Transcranial Doppler ultrasound (TCD). ERPs were elicited using a two-tone auditory oddball task. N2 amplitude was significantly reduced in the CVD group at midline frontal, central and parietal sites (p < .05, d > 0.6). No significant group differences were observed in N2 latency, P3 amplitude, or P3 latency. Further, MCAv and PI were strongly associated with N2 amplitude in the CVD group, such that greater MCAv was associated with reductions in N2 amplitude (b = -0.58, p = .018), whilst PI was associated with increases in N2 amplitude (b = 0.66, p = .006). No relationships between MCAv or PI with N2 or P3 ERP components were observed in the healthy control group. The data reported here suggest that a reduction in N2 amplitude may be an important objective indicator of subclinical cognitive and attentional alterations in non-stroke CVD, and support the notion that cerebrovascular hemodynamic disturbances play a role in the pathogenesis of cognitive deterioration secondary to non-stroke CVD.

Healthy aging affects cerebrovascular reactivity and pressure-flow responses, but not neurovascular coupling: A cross-sectional study.

BACKGROUND AND PURPOSE: Aging leads to alterations in cerebrovascular function, and these are thought to contribute to cognitive decline/dementia. Disturbances to cerebral blood flow regulation have been reported, but the findings are inconsistent and to date no study has comprehensively tested the collective and independent contribution of these parameters in the same age range. Such lines of enquiry are vital since aging is a heterogeneous and complex process, with cerebrovascular parameters being differentially affected depending on the individual. A multicomponent comprehensive measure of cerebrovascular function, which accounts for such diversity, is needed to differentiate between healthy young and old adults. METHODS: We tested the effect of aging on cerebrovascular function by comparing healthy young adults aged 18-30 and older adults aged 60-75, without cognitive impairments. Cerebrovascular blood flow velocity was assessed using transcranial Doppler ultrasound. Parameters included resting middle cerebral artery velocity (MCAv), neurovascular coupling, cerebrovascular reactivity to CO2 (hypercapnia and hypocapnia), and the pressure-flow response during a sit-to-stand procedure. RESULTS: MANOVA revealed that collectively, the parameters discriminated the groups (p < .001). MCAv and pressure-flow responses were lower in the older group (p < .001). While there were no differences in hypercapnic responses (p = .908) and neurovascular coupling (p = .517), hypocapnic responses were elevated in the old (p = .002). CONCLUSIONS: Collectively, cerebrovascular parameters can distinguish between healthy young and older adults, with aging leading to reductions in MCAv, and altering cerebrovascular reactivity and pressure-flow responses under hypotensive conditions.

Mental training affects electrophysiological markers of attention resource allocation in healthy older adults.

Aging is associated with a decline in performance and speed of attentional processing. Mindfulness has been shown to enhance attentional performance, however evidence of this is lacking in aging cohorts. A longitudinal RCT was conducted to examine the effect of mindfulness training on attentional performance in healthy older adults (n = 49) together with an active control computer-based attention training group (n = 30). While both groups displayed decreased N2 amplitudes at frontal and central regions during an auditory oddball task after training, only the mindfulness group showed reductions in frontal N2 and P3 latency. These results suggest that programs targeting sustained attention may result in efficient allocation of attentional resources in older adults. In particular, mindfulness may enhance the speed of attentional processes which are known to decline in aging, thereby providing benefits against age-related cognitive decline.

Validation of a Dynamic Measure of Current Cognitive Reserve in a Longitudinally Assessed Sample of Healthy Older Adults: The Tasmanian Healthy Brain Project.

Cognitive reserve (CR) is a theoretical construct describing the underlying cognitive capacity of an individual that confers differential levels of resistance to, and recovery from, brain injuries of various types. To date, estimates of an individual's level of CR have been based on single proxy measures that are retrospective and static in nature. To develop a measure of dynamic change in CR across a lifetime, we previously identified a latent factor, derived from an exploratory factor analysis of a large sample of healthy older adults, as current CR (cCR). In the present study, we examined the longitudinal results of a sample of 272 older adults enrolled in the Tasmanian Healthy Brain Project. Using results from 12-month and 24-month reassessments, we examined the longitudinal validity of the cCR factor using confirmatory factor analyses. The results of these analyses indicate that the cCR factor structure is longitudinally stable. These results, in conjunction with recent results from our group demonstrating dynamic increases in cCR over time in older adults undertaking further education, lend weight to this cCR measure being a valid estimate of dynamic change in CR over time.

The My Active and Healthy Aging (My-AHA) ICT platform to detect and prevent frailty in older adults: Randomized control trial design and protocol.

INTRODUCTION: Frailty increases the risk of poor health outcomes, disability, hospitalization, and death in older adults and affects 7%-12% of the aging population. Secondary impacts of frailty on psychological health and socialization are significant negative contributors to poor outcomes for frail older adults. METHOD: The My Active and Healthy Aging (My-AHA) consortium has developed an information and communications technology-based platform to support active and healthy aging through early detection of prefrailty and provision of individually tailored interventions, targeting multidomain risks for frailty across physical activity, cognitive activity, diet and nutrition, sleep, and psychosocial activities. Six hundred adults aged 60 years and older will be recruited to participate in a multinational, multisite 18-month randomized controlled trial to test the efficacy of the My-AHA platform to detect prefrailty and the efficacy of individually tailored interventions to prevent development of clinical frailty in this cohort. A total of 10 centers from Italy, Germany, Austria, Spain, United Kingdom, Belgium, Sweden, Japan, South Korea, and Australia will participate in the randomized controlled trial. RESULTS: Pilot testing (Alpha Wave) of the My-AHA platform and all ancillary systems has been completed with a small group of older adults in Europe with the full randomized controlled trial scheduled to commence in 2018. DISCUSSION: The My-AHA study will expand the understanding of antecedent risk factors for clinical frailty so as to deliver targeted interventions to adults with prefrailty. Through the use of an information and communications technology platform that can connect with multiple devices within the older adult's own home, the My-AHA platform is designed to measure an individual's risk factors for frailty across multiple domains and then deliver personalized domain-specific interventions to the individual. The My-AHA platform is technology-agnostic, enabling the integration of new devices and sensor platforms as they emerge.

The Effect of Non-Stroke Cardiovascular Disease States on Risk for Cognitive Decline and Dementia: A Systematic and Meta-Analytic Review.

Cardiovascular disease is associated with increased risk for cognitive decline and dementia, but it is unclear whether this risk varies across disease states or occurs in the absence of symptomatic stroke. To examine the evidence of increased risk for cognitive decline and dementia following non-stroke cardiovascular disease we conducted two independent meta-analyses in accordance with PRISMA guidelines. The first review examined cardiovascular diagnoses (atrial fibrillation, congestive heart failure, periphery artery disease and myocardial infarction) while the second review assessed the impact of atherosclerotic burden (as indicated by degree of stenosis, calcification score, plaque morphology or number of plaques). Studies eligible for review longitudinally assessed risk for clinically significant cognitive decline and/or dementia and excluded stroke and cognitive impairment at baseline. Summary statistics were computed via the inverse variance weighted method, utilising Cox Proportional Hazards data (Hazard Ratios, HR). Both atrial fibrillation (n = 5, HR = 1.26, 95% CI [1.12, 1.43]) and severe atherosclerosis (n = 4, HR = 1.59, 95% CI [1.12, 2.26]) emerged as significant risk factors for cognitive decline and/or dementia. A small set of studies reviewed, insufficient for meta-analysis, examining congestive heart failure, peripheral artery disease and myocardial infarction suggested that these conditions may also be associated with an increased risk of cognitive decline/dementia. In the absence of stroke, patients with atrial fibrillation or generalised atherosclerosis are at heightened risk for cognitive deterioration. Nonetheless, this paper highlights the need for methodologically rigorous and prospective investigation of the relationship between CVD and dementia.

Further education improves cognitive reserve and triggers improvement in selective cognitive functions in older adults: The Tasmanian Healthy Brain Project.

INTRODUCTION: The strong link between early-life education and subsequent reduced risk of dementia suggests that education in later life could enhance cognitive function and may reduce age-related cognitive decline and protect against dementia. METHODS: Episodic memory, working memory, executive function, and language processing performances were assessed annually over 4 years in 359 healthy older adults who attended university for a minimum of 12 months (intervention) and were compared against 100 healthy adult controls. RESULTS: Multiple group latent growth curve modeling revealed a significant improvement in language processing capacity over time in the intervention group. No changes were detected for episodic memory, working memory, or executive function. DISCUSSION: These results suggest that complex mental stimulation resulting from late-life further education results in improved crystallized knowledge but no changes to fluid cognitive functions.

Diagnostic Accuracy of Memory Measures in Alzheimer's Dementia and Mild Cognitive Impairment: a Systematic Review and Meta-Analysis.

With an increasing focus on biomarkers in dementia research, illustrating the role of neuropsychological assessment in detecting mild cognitive impairment (MCI) and Alzheimer's dementia (AD) is important. This systematic review and meta-analysis, conducted in accordance with PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) standards, summarizes the sensitivity and specificity of memory measures in individuals with MCI and AD. Both meta-analytic and qualitative examination of AD versus healthy control (HC) studies (n = 47) revealed generally high sensitivity and specificity (≥ 80% for AD comparisons) for measures of immediate (sensitivity = 87%, specificity = 88%) and delayed memory (sensitivity = 89%, specificity = 89%), especially those involving word-list recall. Examination of MCI versus HC studies (n = 38) revealed generally lower diagnostic accuracy for both immediate (sensitivity = 72%, specificity = 81%) and delayed memory (sensitivity = 75%, specificity = 81%). Measures that differentiated AD from other conditions (n = 10 studies) yielded mixed results, with generally high sensitivity in the context of low or variable specificity. Results confirm that memory measures have high diagnostic accuracy for identification of AD, are promising but require further refinement for identification of MCI, and provide support for ongoing investigation of neuropsychological assessment as a cognitive biomarker of preclinical AD. Emphasizing diagnostic test accuracy statistics over null hypothesis testing in future studies will promote the ongoing use of neuropsychological tests as Alzheimer's disease research and clinical criteria increasingly rely upon cerebrospinal fluid (CSF) and neuroimaging biomarkers.

Environmental novelty exacerbates stress hormones and Aß pathology in an Alzheimer's model.

Cognitive stimulation has been proposed as a non-pharmacological intervention to be used in primary, secondary and tertiary prevention approaches for Alzheimer's disease. A common familial Alzheimer's disease transgenic model showed heightened levels of the stress hormone, corticosterone. When exposed to periodic enhanced cognitive stimulation, these animals demonstrated further heightened levels of corticosterone as well as increased Aß pathology. Hence, Alzheimer's disease may be associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction, causing stimulatory environments to become stress-inducing, leading to a glucocorticoid-pathology cycle contributing to further Aß release and plaque formation. This finding suggests that stimulation-based interventions and local environments for people with Alzheimer's disease need to be designed to minimise a stress response that may exacerbate brain pathology.