Lifelong environmental enrichment in the absence of exercise protects the brain from age-related cognitive decline

2019 ◽  
Vol 145 ◽  
pp. 59-74 ◽  
Author(s):  
Amy M. Birch ◽  
Áine M. Kelly
2021 ◽  
Author(s):  
Tyler S Saunders ◽  
Amanda Heslegrave ◽  
Declan King ◽  
Sarah Harris ◽  
Craig W Ritchie ◽  
...  

INTRODUCTION: Plasma phospho-tau 181 (p-tau181) is a promising blood biomarker for Alzheimer's disease. However, its predictive validity for age-related cognitive decline without dementia remains unclear. Several forms of p-tau have been shown to contribute to synapse degeneration, but it is unknown whether p-tau181 is present in synapses. Here, we tested whether plasma p-tau181predicts cognitive decline and whether it is present in synapses in human brain. METHODS: General cognitive ability and plasma p-tau181 concentration were measured in 195 participants at ages 72 and 82. Levels of p-tau181 in total homogenate and synaptic fractions were compared with western blot (n=10-12 per group), and synaptic localisation was examined using array tomography. RESULTS: Elevated baseline plasma p-tau181 and increasing p-tau181 over time predicted steeper general cognitive decline. We observe p-tau181 in neurites, presynapses, and post-synapses in the brain. DISCUSSION: Baseline and subsequent change in plasma p-tau181 may represent rare biomarkers of differences in cognitive ageing across the 8th decade of life and may play a role in synaptic function in the brain.


2020 ◽  
Vol 61 (10) ◽  
pp. 1308-1319
Author(s):  
Eileen E. Parks ◽  
Sreemathi Logan ◽  
Alexander Yeganeh ◽  
Julie A. Farley ◽  
Daniel B. Owen ◽  
...  

Cognitive decline with age is a harmful process that can reduce quality of life. Multiple factors have been established to contribute to cognitive decline, but the overall etiology remains unknown. Here, we hypothesized that cognitive dysfunction is mediated, in part, by increased levels of inflammatory cytokines that alter allopregnanolone (AlloP) levels, an important neurosteroid in the brain. We assessed the levels and regulation of AlloP and the effects of AlloP supplementation on cognitive function in 4-month-old and 24-month-old male C57BL/6 mice. With age, the expression of enzymes involved in the AlloP synthetic pathway was decreased and corticosterone (CORT) synthesis increased. Supplementation of AlloP improved cognitive function. Interestingly, interleukin 6 (IL-6) infusion in young animals significantly reduced the production of AlloP compared with controls. It is notable that inhibition of IL-6 with its natural inhibitor, soluble membrane glycoprotein 130, significantly improved spatial memory in aged mice. These findings were supported by in vitro experiments in primary murine astrocyte cultures, indicating that IL-6 decreases production of AlloP and increases CORT levels. Our results indicate that age-related increases in IL-6 levels reduce progesterone substrate availability, resulting in a decline in AlloP levels and an increase in CORT. Furthermore, our results indicate that AlloP is a critical link between inflammatory cytokines and the age-related decline in cognitive function.


2017 ◽  
Vol 41 (S1) ◽  
pp. S372-S372 ◽  
Author(s):  
D. Wincewicz ◽  
T. Tolmunen ◽  
A.K. Brem ◽  
J. Kauhanen ◽  
S. Lehto

IntroductionModulators of the brain renin-angiotensin system (RAS) have been shown to improve cognitive functioning in several animal models of neuropsychiatric disorders. Moreover, the brain RAS has been considered a new target for the treatment of Alzheimer's disease (AD). However, there are no population-based follow-up studies supporting this hypothesis.ObjectivesCross-sectional and prospective relationships between cognitive decline and ARB treatment were examined in the population-based Kuopio Ischemic Heart Disease Risk Factor Study.AimsTo evaluate procognitive/antidementia capacity of orally delivered angiotensin II receptor blockers (ARB).MethodsThe study was conducted on a sample of 1774 subjects (920 females, 854 males; age range at baseline: 42–61 years) from Eastern Finland. An established cutoff score of at least 2-point decrease in the Mini Mental State Examination over a 9-year follow-up was used to detect age-related cognitive decline in the cross-sectional setting. In the prospective setting, a hospital discharge diagnosis of dementia/AD was used as outcome variable. Cross-sectional relationships were determined with logistic regression and prospective analyses were conducted with the Cox proportional hazards model (both adjusted for relevant background variables).ResultsCross-sectional analysis displayed a decrease of the odds of cognitive decline (n = 87; 4.9% of participants) in those with ARB treatment; OR = 0.445, 95% CI: 0.22–0.90, P = 0.024. Furthermore, in the prospective setting, the risk of dementia/AD diagnosis (n = 149; 8.4% of participants) was significantly reduced in ARB treated participants; HR = 0.621, 95% CI: 0.40–0.98, P = 0.038.ConclusionsARB treatment is associated with a decreased risk for age-related cognitive decline and dementia/AD manifestation.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2019 ◽  
Author(s):  
Gregory D. Clemenson ◽  
Shauna M. Stark ◽  
Samantha M. Rutledge ◽  
Craig E.L. Stark

AbstractHealthy aging is accompanied by a steady cognitive decline with clear losses in memory. Animal studies have consistently demonstrated that simply modifying an animal’s living environment (known as environmental enrichment) can have a positive influence on age-related cognitive decline in the hippocampus. Previously, we showed that playing immersive 3D video games can improve hippocampal-based memory in young healthy adults, suggesting that the exploration of the large open worlds of modern-day video games may act as proxy for environmental enrichment in humans. Here, we replicated our previous video game study in older adults and showing that playing video games for 4 weeks can improve hippocampal-based memory in a population that is already experiencing age-related decline in this memory. Furthermore, we showed that the improvements last for up to 4 weeks past the intervention, highlighting the potential of video games as intervention for age-related cognitive decline.


Author(s):  
Yvonne Rogalski ◽  
Muriel Quintana

The population of older adults is rapidly increasing, as is the number and type of products and interventions proposed to prevent or reduce the risk of age-related cognitive decline. Advocacy and prevention are part of the American Speech-Language-Hearing Association’s (ASHA’s) scope of practice documents, and speech-language pathologists must have basic awareness of the evidence contributing to healthy cognitive aging. In this article, we provide a brief overview outlining the evidence on activity engagement and its effects on cognition in older adults. We explore the current evidence around the activities of eating and drinking with a discussion on the potential benefits of omega-3 fatty acids, polyphenols, alcohol, and coffee. We investigate the evidence on the hypothesized neuroprotective effects of social activity, the evidence on computerized cognitive training, and the emerging behavioral and neuroimaging evidence on physical activity. We conclude that actively aging using a combination of several strategies may be our best line of defense against cognitive decline.


2021 ◽  
Vol 67 ◽  
pp. 101302
Author(s):  
Benjamin Kioussis ◽  
Camilla S.L. Tuttle ◽  
Daniel S. Heard ◽  
Brian K. Kennedy ◽  
Nicola T. Lautenschlager ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1611
Author(s):  
Nur Fathiah Abdul Abdul Sani ◽  
Ahmad Imran Zaydi Amir Amir Hamzah ◽  
Zulzikry Hafiz Abu Abu Bakar ◽  
Yasmin Anum Mohd Mohd Yusof ◽  
Suzana Makpol ◽  
...  

The mechanism of cognitive aging at the molecular level is complex and not well understood. Growing evidence suggests that cognitive differences might also be caused by ethnicity. Thus, this study aims to determine the gene expression changes associated with age-related cognitive decline among Malay adults in Malaysia. A cross-sectional study was conducted on 160 healthy Malay subjects, aged between 28 and 79, and recruited around Selangor and Klang Valley, Malaysia. Gene expression analysis was performed using a HumanHT-12v4.0 Expression BeadChip microarray kit. The top 20 differentially expressed genes at p < 0.05 and fold change (FC) = 1.2 showed that PAFAH1B3, HIST1H1E, KCNA3, TM7SF2, RGS1, and TGFBRAP1 were regulated with increased age. The gene set analysis suggests that the Malay adult’s susceptibility to developing age-related cognitive decline might be due to the changes in gene expression patterns associated with inflammation, signal transduction, and metabolic pathway in the genetic network. It may, perhaps, have important implications for finding a biomarker for cognitive decline and offer molecular targets to achieve successful aging, mainly in the Malay population in Malaysia.


BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e046879
Author(s):  
Bernhard Grässler ◽  
Fabian Herold ◽  
Milos Dordevic ◽  
Tariq Ali Gujar ◽  
Sabine Darius ◽  
...  

IntroductionThe diagnosis of mild cognitive impairment (MCI), that is, the transitory phase between normal age-related cognitive decline and dementia, remains a challenging task. It was observed that a multimodal approach (simultaneous analysis of several complementary modalities) can improve the classification accuracy. We will combine three noninvasive measurement modalities: functional near-infrared spectroscopy (fNIRS), electroencephalography and heart rate variability via ECG. Our aim is to explore neurophysiological correlates of cognitive performance and whether our multimodal approach can aid in early identification of individuals with MCI.Methods and analysisThis study will be a cross-sectional with patients with MCI and healthy controls (HC). The neurophysiological signals will be measured during rest and while performing cognitive tasks: (1) Stroop, (2) N-back and (3) verbal fluency test (VFT). Main aims of statistical analysis are to (1) determine the differences in neurophysiological responses of HC and MCI, (2) investigate relationships between measures of cognitive performance and neurophysiological responses and (3) investigate whether the classification accuracy can be improved by using our multimodal approach. To meet these targets, statistical analysis will include machine learning approaches.This is, to the best of our knowledge, the first study that applies simultaneously these three modalities in MCI and HC. We hypothesise that the multimodal approach improves the classification accuracy between HC and MCI as compared with a unimodal approach. If our hypothesis is verified, this study paves the way for additional research on multimodal approaches for dementia research and fosters the exploration of new biomarkers for an early detection of nonphysiological age-related cognitive decline.Ethics and disseminationEthics approval was obtained from the local Ethics Committee (reference: 83/19). Data will be shared with the scientific community no more than 1 year following completion of study and data assembly.Trial registration numberClinicalTrials.gov, NCT04427436, registered on 10 June 2020, https://clinicaltrials.gov/ct2/show/study/NCT04427436.


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