The Effect of Polyphenols on Working and Episodic Memory in Non-pathological and Pathological Aging: A Systematic Review and Meta-Analysis

Life expectancy steadily increases, and so do age-associated diseases, leading to a growing population suffering from cognitive decline and dementia. Impairments in working memory (WM) and episodic memory (EM) are associated with an increased risk of developing dementia. While there are no effective pharmacological therapies to preserve or enhance cognition and to slow down the progression from mild memory complaints to dementia so far, plant-based nutrients including polyphenols have been suggested to exert beneficial effects on brain aging. This review studies whether supplementary polyphenols are effective in preserving or enhancing memory in both non-pathological and pathological aging, and whether there are polyphenol efficiency differences between WM and EM. A systematic literature search was conducted and 66 out of 294 randomized clinical trials with 20 participants or more per group, aged 40 years or older were included. These covered a daily intake of 35–1,600 mg polyphenols, e.g., flavonols, flavonoids, isoflovones, anthocyanins, and/or stilbenes, over the course of 2 weeks to 6.5 years duration. In total, around half of the studies reported a significantly improved performance after polyphenol administration compared to control, while three studies reported a worsening of performance, and the remainder did not observe any effects. According to pooled WM and EM meta-analysis of all memory outcomes reported in 49 studies, overall effect size for WM and EM indicated a significant small positive effect on EM and WM with similar estimates (b ~ 0.24, p < 0.001), with large study heterogeneity and significant Funnel asymmetry tests suggesting a positivity bias. These results remained similar when excluding studies reporting extremely large positive effect sizes from the meta-analyses. While Ginkgo biloba and isoflavones did not show benefits in subgroup meta-analyses, those suggested some effects in extracts containing anthocyanins, other flavonoids and resveratrol, again potentially resulting from publication bias. To conclude, a systematic review and meta-analysis indicate that short- to moderate-term polyphenol interventions might improve WM and EM in middle-to older aged adults, however, publication bias in favor of positive results seems likely, rendering definite conclusions difficult. Future studies with larger, more diverse samples and sensitive monitoring of cardiovascular, metabolic and beginning brain pathologies as well as longer follow-up are needed to better understand the impact of age, (beginning) pathologies, gender, and long-term use on polyphenol action.Peer Reviewe

Synapse Plasticity in Motor, Sensory, and Limbo-Prefrontal Cortex Areas as Measured by Degrading Axon Terminals in an Environment Model of Gerbils (Meriones unguiculatus)

Still little is known about naturally occurring synaptogenesis in the adult neocortex and related impacts of epigenetic influences. We therefore investigated (pre)synaptic plasticity in various cortices of adult rodents, visualized by secondary lysosome accumulations (LA) in remodeling axon terminals. Twenty-two male gerbils from either enriched (ER) or impoverished rearing (IR) were used for quantification of silver-stained LA. ER-animals showed rather low LA densities in most primary fields, whereas barrel and secondary/associative cortices exhibited higher densities and layer-specific differences. In IR-animals, these differences were evened out or even inverted. Basic plastic capacities might be linked with remodeling of local intrinsic circuits in the context of cortical map adaptation in both IR- and ER-animals. Frequently described disturbances due to IR in multiple corticocortical and extracortical afferent systems, including the mesocortical dopamine projection, might have led to maladaptations in the plastic capacities of prefronto-limbic areas, as indicated by different LA densities in IR- compared with ER-animals

Feasibility and first results of a group program to increase the frequency of cognitively stimulating leisure activities in people with mild cognitive impairment (AKTIVA–MCI)

AKTIVA-MCI is a program for patients with mild cognitive impairment (MCI) that aims to enhance participation in cognitively stimulating leisure activities. Participation in cognitively stimulating activities seems to be a potential strategy for people with MCI delaying cognitive decline for a while. In total, 35 MCI patients were enrolled in the pilot study of whom 29 completed the whole program (16 female, 71.1±7.5 years; Mini Mental Status Examination score: 28±2.2). Daily activity protocols were used to measure the frequency of participation in cognitively stimulating activities during the program (12 sessions). Additional standardized psychometric tests and questionnaires were used to assess cognition, mood, and subjective memory decline. Analyses of the daily activity protocols showed that during the intervention participants increased the frequency of several cognitively stimulating leisure activities. Comparison of pre-post data indicates no changes in cognitive status, mood, and subjective memory decline. These findings indicate that the program is suitable for patients with MCI

Less Animal-Based Food, Better Weight Status: Associations of the Restriction of Animal-Based Product Intake with Body-Mass-Index, Depressive Symptoms and Personality in the General Population

Restricting animal-based products from diet may exert beneficial effects on weight status; however, less is known about such a diet and emotional health. Moreover, personality traits, for example high neuroticism, may contribute to restrictive eating habits and potentially confound diet-health associations. We aim to systematically assess if restrictive dietary intake of animal-based products relates to lower weight and higher depressive symptoms, and if differences in personality traits play a significant role. Cross-sectional data from the baseline LIFE-Adult study were collected from 2011–2014 in Leipzig, Germany (n = 8943). Main outcomes of interest were dietary frequency of animal-derived products in the last year measured using a Food Frequency Questionnaire (FFQ), body-mass-index (BMI) (kg/m2), and the Center of Epidemiological Studies Depression Scale (CES-D). Personality traits were assessed in a subsample of n = 7906 using the Five Factor Inventory (NEO-FFI). Higher restriction of animal-based product intake was associated with a lower BMI, but not with depression scores. Personality, i.e., lower extraversion, was related to higher frequency of animal product intake. Moreover, personality traits were significantly associated with depressive symptoms, i.e., higher neuroticism, lower extraversion, lower agreeableness, lower conscientiousness, and with higher BMI. These findings encourage future longitudinal studies to test the efficacy of restricting animal-based products as a preventive and therapeutic strategy for overweight and obesity

Impact of Resveratrol on Glucose Control, Hippocampal Structure and Connectivity, and Memory Performance in Patients with Mild Cognitive Impairment

In healthy older adults, resveratrol supplementation has been shown to improve long-term glucose control, resting-state functional connectivity (RSFC) of the hippocampus, and memory function. Here, we aimed to investigate if these beneficial effects extend to individuals at high-risk for dementia, i.e., patients with mild cognitive impairment (MCI). In a randomized, double-blind interventional study, 40 well-characterized patients with MCI (21 females; 50–80 years) completed 26 weeks of resveratrol (200 mg/d; n = 18) or placebo (1,015 mg/d olive oil; n = 22) intake. Serum levels of glucose, glycated hemoglobin A1c and insulin were determined before and after intervention. Moreover, cerebral magnetic resonance imaging (MRI) (3T) (n = 14 vs. 16) was conducted to analyze hippocampus volume, microstructure and RSFC, and neuropsychological testing was conducted to assess learning and memory (primary endpoint) at both time points. In comparison to the control group, resveratrol supplementation resulted in lower glycated hemoglobin A1c concentration with a moderate effect size (ANOVARM p = 0.059, Cohen's d = 0.66), higher RSFC between right anterior hippocampus and right angular cortex (p < 0.001), and led to a moderate preservation of left anterior hippocampus volume (ANOVARM p = 0.061, Cohen's d = 0.68). No significant differences in memory performance emerged between groups. This proof-of-concept study indicates for the first-time that resveratrol intake may reduce glycated hemoglobin A1c, preserves hippocampus volume, and improves hippocampus RSFC in at-risk patients for dementia. Larger trials with longer intervention time should now determine if these benefits can be validated and extended to cognitive function

Early volumetric changes of hippocampus and medial prefrontal cortex following medial temporal lobe resection

Previous studies have shown that cognitive demands and physical exercise stimulate adult neurogenesis in the dentate gyrus and hippocampus. Recent observations in healthy humans and patients with mild cognitive impairment moreover suggest that training-induced increases in hippocampal volume may be associated with improved memory performance. The corresponding plasticity processes in hippocampal volume may occur on timescales of months to years. For patients with focal lesions in this region, previous functional imaging studies suggest that increased recruitment of the contralateral hippocampus and extratemporal regions may be an important part of the reorganization of episodic memory. However, it is currently unclear whether focal damage to the medial temporal lobe (MTL) induces gray matter (GM) volume changes in the intact contralateral hippocampus and in connected network regions on a shorter timescale. We therefore investigated whether unilateral resection of the MTL, including the hippocampus, induces measurable volumetric changes in the contralateral hippocampus and in the default mode network (DMN). We recruited 31 patients with unilateral left (N = 19) or right (N = 12) hippocampal sclerosis undergoing MTL resection for treatment of drug-resistant epilepsy. Structural MRI was acquired immediately before and 3 months after surgery. Longitudinal voxel-based morphometry (VBM) analysis revealed a significant increase of right hippocampal volume following resection of the left anterior MTL. Furthermore, this patient group showed GM volume increases in the DMN. These results demonstrate significant structural plasticity of the contralateral hippocampus, even in patients with a long-standing unilateral hippocampal dysfunction and structural reorganization processes extending to distant, but functionally connected brain regions

Mindreading From the Eyes Declines With Aging - Evidence From 1,603 Subjects.

Social cognition, in particular mindreading, enables the understanding of another individual's feelings, intentions, desires, and mental states. The Reading the Mind in the Eyes Test (RMET) captures the ability to identify mental states from gaze. We investigated RMET accuracy in the context of age and cognition across the whole adult age-range (19-79 years) in a very large population-based sample (N = 1,603) with linear regression models accounting for cognitive abilities, neurological diseases, and psychiatric disorders. Higher age predicted lower RMET performance in women and men, suggesting difficulties to infer mental states from gaze at older age. Effects remained stable when taking other cognitive abilities and psychiatric disorders or neurological diseases into account. Our results show that RMET performance as a measure of social cognition declines with increasing age

Age-Related Changes of Peak Width Skeletonized Mean Diffusivity (PSMD) Across the Adult Lifespan: A Multi-Cohort Study

Parameters of water diffusion in white matter derived from diffusion-weighted imaging (DWI), such as fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, and RD), and more recently, peak width of skeletonized mean diffusivity (PSMD), have been proposed as potential markers of normal and pathological brain ageing. However, their relative evolution over the entire adult lifespan in healthy individuals remains partly unknown during early and late adulthood, and particularly for the PSMD index. Here, we gathered and analyzed cross-sectional diffusion tensor imaging (DTI) data from 10 population-based cohort studies in order to establish the time course of white matter water diffusion phenotypes from post-adolescence to late adulthood. DTI data were obtained from a total of 20,005 individuals aged 18.1 to 92.6 years and analyzed with the same pipeline for computing skeletonized DTI metrics from DTI maps. For each individual, MD, AD, RD, and FA mean values were computed over their FA volume skeleton, PSMD being calculated as the 90% peak width of the MD values distribution across the FA skeleton. Mean values of each DTI metric were found to strongly vary across cohorts, most likely due to major differences in DWI acquisition protocols as well as pre-processing and DTI model fitting. However, age effects on each DTI metric were found to be highly consistent across cohorts. RD, MD, and AD variations with age exhibited the same U-shape pattern, first slowly decreasing during post-adolescence until the age of 30, 40, and 50 years, respectively, then progressively increasing until late life. FA showed a reverse profile, initially increasing then continuously decreasing, slowly until the 70s, then sharply declining thereafter. By contrast, PSMD constantly increased, first slowly until the 60s, then more sharply. These results demonstrate that, in the general population, age affects PSMD in a manner different from that of other DTI metrics. The constant increase in PSMD throughout the entire adult life, including during post-adolescence, indicates that PSMD could be an early marker of the ageing process