Aging brain最新文献

This study evaluated the effect of dietary inclusions of aspartame and sucrose on some selected behavioral and biochemical indices linked with Alzheimer's disease in a transgenic fruit fly (Drosophila melanogaster) model expressing human amyloid precursor protein and secretase. Flies were raised on a diet supplemented with sucrose and aspartame for 14 days. Thereafter, the flies were assessed for their survival rate, learning and memory, as well as locomotor performance, 14 days post-treatment. This was followed by homogenising the fly heads, and the homogenates were assayed for acetylcholinesterase and monoamine oxidase activities, as well as levels of lipid peroxidation, reactive oxygen species, and total thiol. The results showed aspartame at all levels of dietary intake and a high proportion of sucrose significantly aggravated the mortality rate, locomotor deficiency, and impaired biomarkers of oxidative stress and antioxidant status in the transgenic flies, while no significant effect was found on acetylcholinesterase activity or memory function. These findings therefore suggest that while low dietary inclusions of sucrose are tolerable under AD-like phenotypes in the flies, high inclusions of sucrose and all proportions of aspartame tested aggravated mortality rate, locomotion and oxidative stress in the flies.

Amyloid-beta (Aβ) is produced from amyloid precursor protein (APP) primarily after APP is internalised by endocytosis and clathrin-mediated endocytic processes are altered in Alzheimer’s disease (AD). There is also evidence that cholesterol and flotillin affect APP endocytosis. We hypothesised that endocytic protein expression would be altered in the brains of people with AD compared to non-diseased subjects which could be linked to increased Aβ generation. We compared protein expression in frontal cortex samples from men with AD compared to age-matched, non-diseased controls. Soluble and insoluble Aβ40 and Aβ42, the soluble Aβ42/Aβ40 ratio, βCTF, BACE1, presenilin-1 and the ratio of phosphorylated:total GSK3β were significantly increased while the insoluble Aβ42:Aβ40 ratio was significantly decreased in AD brains. Total and phosphorylated tau were markedly increased in AD brains. Significant increases in clathrin, AP2, PICALM isoform 4, Rab-5 and caveolin-1 and 2 were seen in AD brains but BIN1 was decreased. However, using immunohistochemistry, caveolin-1 and 2 were decreased. The results obtained here suggest an overall increase in endocytosis in the AD brain, explaining, at least in part, the increased production of Aβ during AD.

Cognitive resilience in Alzheimer’s disease (AD) can be defined as retention of high cognition despite presence of considerable cerebral AD lesions. We sought to identify factors associated with this phenomenon.

Data were obtained from National Alzheimer’s Coordinating Centre (NACC) dataset. Subjects with severe AD neuropathology, based on National Institute on Aging–Reagan (NIA-Reagan) criteria, no other primary neuropathology, and a ≤ 2-year interval between last follow-up and death were included. Mini-mental status examination score ≥ 24 was used as a proxy for normal cognition.

In total, 654 cases were included; 59 (9%) were cognitively resilient. Multivariable logistic regression model showed that resilient participants were more educated, had a lower body mass index (BMI), were more likely to be lifetime/recent smoker or use an anticoagulant/antiplatelet agent, compared with cognitively impaired subjects.

In addition to expected protective factors such as higher education and lower BMI, our results showed that smoking (especially recent smoking) and anticoagulant/antiplatelet consumption are associated with resilience to clinical cognitive expression of severe AD pathology. Pharmacological approaches using this information might be explored for clinical AD amelioration.

Age-related changes in sleep appear to contribute to cognitive aging and dementia. However, most of the current understanding of sleep across the lifespan is based on cross-sectional evidence. Using data from the Sleep Heart Health Study, we investigated longitudinal changes in sleep micro-architecture, focusing on whether such age-related changes are experienced uniformly across individuals. Participants were 2,202 adults (age_Baseline = 62.40 ± 10.38, 55.36 % female, 87.92 % White) who completed home polysomnography assessment at two study visits, which were 5.23 years apart (range: 4–7 years). We analyzed NREM and REM spectral power density for each 0.5 Hz frequency bin, including slow oscillation (0.5–1 Hz), delta (1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), sigma (12–15 Hz), and beta-1 (15–20 Hz) bands. Longitudinal comparisons showed a 5-year decline in NREM delta (p <.001) and NREM sigma power density (p <.001) as well as a 5-year increase in theta power density during NREM (p =.001) and power density for all frequency bands during REM sleep (ps < 0.05). In contrast to the notion that sleep declines linearly with advancing age, longitudinal trajectories varied considerably across individuals. Within individuals, the 5-year changes in NREM and REM power density were strongly correlated (slow oscillation: r = 0.46; delta: r = 0.67; theta r = 0.78; alpha r = 0.66; sigma: r = 0.71; beta-1: r = 0.73; ps < 0.001). The convergence in the longitudinal trajectories of NREM and REM activity may reflect age-related neural de-differentiation and/or compensation processes. Future research should investigate the neurocognitive implications of longitudinal changes in sleep micro-architecture and test whether interventions for improving key sleep micro-architecture features (such as NREM delta and sigma activity) also benefit cognition over time.

The ability to sleep declines with age. The National Sleep Foundation, USA has recommended a minimum sleep amount for all ages. Individuals who experience sleep lesser than the recommended amount could be sleep-deprived. Several factors like stress, altered circadian cycle, medical conditions, etc. cause sleep deficiency. Almost 50–60 % of elderly population suffer from sleep disorders such as sleep apnea, restless legs syndrome, REM sleep behavior disorder, etc. Chronic sleep deprivation may further lead to the development of diseases such as Alzheimer's and Parkinson's. This paper reviews the prevalence of sleep disorders and consequences of sleep loss in young and old adults.

Working Memory (WM) training has shown promise in supporting cognitive functioning in older adult populations, but effects that generalize beyond the trained task have been inconsistent. Targeting cognitive processes in isolation might be a limiting factor given that metacognitive and motivational factors have been shown to impact older adults’ engagement with challenging cognitive activities, such as WM training. The current feasibility study implemented a novel metacognitive intervention in conjunction with WM training in older adults and examined its potential amplifying short- and long-term effects on cognitive and self-report outcomes as compared to WM or active control training alone. One-hundred and nineteen older adults completed a cognitive training over the course of 20 sessions at home. The cognitive training targeted either WM or general knowledge. In addition, one of the WM training groups completed a metacognitive program via group seminars. We tested for group differences in WM, inhibitory control, and episodic memory, and we assessed participants’ perceived self-efficacy and everyday memory failures. At post-test, we replicated earlier work by demonstrating that participants who completed the WM intervention outperformed the active control group in non-trained WM measures, and to some extent, in inhibitory control. However, we found no evidence that the supplemental metacognitive program led to benefits over and above the WM intervention. Nonetheless, we conclude that our metacognitive program is a step in the right direction given the tentative long-term effects and participants’ positive feedback, but more longitudinal data with larger sample sizes are needed to confirm these early findings.

The precision of temporal multisensory integration is associated with specific aspects of physical functioning in ageing, including gait speed and incidents of falling. However, it is unknown if such an association exists between multisensory integration and grip strength, an important index of frailty and brain health and predictor of disease and mortality in older adults. Here, we investigated whether temporal multisensory integration is associated with longitudinal (eight-year) grip strength trajectories in a large sample of 2,061 older adults (mean age = 64.42 years, SD = 7.20; 52% female) drawn from The Irish Longitudinal Study on Ageing (TILDA). Grip strength (kg) for the dominant hand was assessed with a hand-held dynamometer across four testing waves. Longitudinal k-means clustering was applied to these data separately for sex (male, female) and age group (50–64, 65–74, 75+ years). At wave 3, older adults participated in the Sound Induced Flash Illusion (SIFI), a measure of the precision of temporal audio-visual integration, which included three audio-visual stimulus onset asynchronies (SOAs): 70, 150 and 230 ms. Results showed that older adults with a relatively lower (i.e., weaker) grip strength were more susceptible to the SIFI at the longer SOAs compared to those with a relatively higher (i.e., stronger) grip strength (p <.001). These novel findings suggest that older adults with relatively weaker grip strength exhibit an expanded temporal binding window for audio-visual events, possibly reflecting a reduction in the integrity of the central nervous system.