METHODS: CJ57BL/6 breeder F0 mice were fed with EBN (10 mg/kg) from different sources. After 6 weeks of diet supplementations, the F0 animals were bred to produce F1 and F2 animals. At 6 weeks of age, the F1 and F2 animals were tested for spatial recognition memory using a Y-maze test. The sialic acid content from EBN and brain gene expression were analyzed using HPLC and PCR, respectively.

RESULTS: All EBN samples contained glycoprotein with high level of sialic acid. Dietary EBN supplementation also showed an upregulation of GNE, ST8SiaIV, SLC17A5, and BDNF mRNA associated with an improvement in Y-maze cognitive performance in both generations of animal. Qualitatively, the densities of synaptic vesicles in the presynaptic terminal were higher in the F1 and F2 animals which might derive from maternal EBN supplementation.

DESIGN: This study was a two-arm within-participants trial with 4- and 12-wk follow-ups. Allocation ratio was 1:1, and pretraining and posttraining measurements were included. A total number of 25 healthy older adults were enrolled (mean = 63.32, SD = 4.44). Participants were randomly allocated into two conditions: (a) prospective memory training: participants underwent a multicomponent prospective memory training, and (b) control: participants were not contacted during the training phase. After the training phase was finished, participants crossed over to undergo the condition they did not experience before. The differences between pretraining and posttraining measures of prospective memory, activities of daily living, negative mood (depression), and anxiety were assessed. All changes in the measurements were analyzed using general linear method. This trial is registered at https://www.isrctn.com (#ISRCTN57600070).

RESULTS: Multicomponent prospective memory training program was significantly effective on both subjective and objective prospective memory performances among healthy older adults. Moreover, the training had significant positive effects on activities of daily living (independence) among participants. In addition, negative mood and anxiety levels were reduced after the training was finished.

METHODS: Memory deficiency was produced by AlCl3 (100 mg/kg; p.o.) in experimental animals. Learning and memory activity was measured using Morris water maze (MWM) test model. Central cholinergic activity was evaluated through the measurement of brain acetylcholinesterase (AChE) activity. In addition to the above, oxidative stress was determined through assessment of brain thiobarbituric acid-reactive species (TBARS) and glutathione (GSH) levels.

RESULTS: AlCl3 administration prompted significant deficiency of learning and memory in rats, as specified by a noticeable reduction in MWM presentation. AlCl3 administration also produced a significant deterioration in brain AChE action and brain oxidative stress (increase in TBARS and decrease in GSH) levels. Treatment with morusin (5.0 and 10.0 mg/kg, dose orally) significantly overturned AlCl3- induced learning and memory shortages along with diminution of AlCl3-induced rise in brain AChE activity and brain oxidative stress levels.

METHODS: We harmonised data from 13 longitudinal cohort studies of ageing in North America, South America, Europe, Africa, Asia, and Australia. Studies were eligible for inclusion if they had baseline data for social connection markers and at least two waves of cognitive scores. Follow-up periods ranged from 0 years to 15 years across cohorts. We included participants with cognitive data for at least two waves and social connection data for at least one wave. We then identified and excluded people with dementia at baseline. Primary outcomes were annual rates of change in global cognition and cognitive domain scores over time until final follow-up within each cohort study analysed by use of an individual participant data meta-analysis. Linear mixed models within cohorts used baseline social connection markers as predictors of the primary outcomes. Effects were pooled in two stages using random-effects meta-analyses. We assessed the primary outcomes in the main (partially adjusted) and fully adjusted models. Partially adjusted models controlled for age, sex, and education; fully adjusted models additionally controlled for diabetes, hypertension, smoking, cardiovascular risk, and depression.

FINDINGS: Of the 40 006 participants in the 13 cohort studies, we excluded 1392 people with dementia at baseline. 38 614 individual participants were included in our analyses. For the main models, being in a relationship or married predicted slower global cognitive decline (b=0·010, 95% CI 0·000-0·019) than did being single or never married; living with others predicted slower global cognitive (b=0·007, 0·002-0·012), memory (b=0·017, 0·006-0·028), and language (b=0·008, 0·000-0·015) decline than did living alone; and weekly interactions with family and friends (b=0·016, 0·006-0·026) and weekly community group engagement (b=0·030, 0·007-0·052) predicted slower memory decline than did no interactions and no engagement. Never feeling lonely predicted slower global cognitive (b=0·047, 95% CI 0·018-0·075) and executive function (b=0·047, 0·017-0·077) decline than did often feeling lonely. Degree of social support, having a confidante, and relationship satisfaction did not predict cognitive decline across global cognition or cognitive domains. Heterogeneity was low (I2=0·00-15·11%) for all but two of the significant findings (association between slower memory decline and living with others [I2=58·33%] and community group engagement, I2=37·54-72·19%), suggesting robust results across studies.

INTERPRETATION: Good social connections (ie, living with others, weekly community group engagement, interacting weekly with family and friends, and never feeling lonely) are associated with slower cognitive decline.