METHODS: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models.

RESULTS: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs.

METHODS: We used individual participant data (N = 39271, Mage  = 70.67 (40-102), 58.86% female, Meducation  = 8.43 years, Mfollow-up  = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes.

RESULTS: We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality.

DISCUSSION: Different aspects of social connections - structure, function, and quality - are associated with benefits for healthy aging internationally.

METHODS: Data were from population-based studies of aging and their Harmonized Cognitive Assessment Protocols (HCAPs) in the US, South Africa, India, and Mexico (N = 10,037; Age range: 50 to 105 years; 2016 to 2020). Main lifetime occupational skill was classified according to the International Standard Classification of Occupations. Weighted, adjusted regression models estimated pooled and country-specific associations between main lifetime occupational skill and later-life general cognitive function in men and women.

RESULTS: We observed positive gradients between occupational skill and later-life cognitive function for men and women in the US and Mexico, a positive gradient for women but not men in India, and no association for men or women in South Africa.

DISCUSSION: Main lifetime occupations may be a source of later-life cognitive reserve, with cross-national heterogeneity in this association.

METHODS: Plasma and CSF NfL levels were measured and compared between groups, adjusting for age, sex, and weight.

METHODS: We harmonized longitudinal data of 11,988 participants from 10 cohorts in eight countries to examine the dose-response relationship between late-life physical activity and incident dementia among older adults.

RESULTS: Using no physical activity as a reference, dementia risk decreased with duration of physical activity up to 3.1 to 6.0 hours/week (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.67 to 1.15 for 0.1 to 3.0 hours/week; HR 0.68, 95% CI 0.52 to 0.89 for 3.1 to 6.0 hours/week), but plateaued with higher duration. For the amount of physical activity, a similar pattern of dose-response curve was observed, with an inflection point of 9.1 to 18.0 metabolic equivalent value (MET)-hours/week (HR 0.92, 95% CI 0.70 to 1.22 for 0.1 to 9.0 MET-hours/week; HR 0.70, 95% CI 0.53 to 0.93 for 9.1 to 18.0 MET-hours/week).

METHOD: Male Sprague Dawley rats were used for the induction of diabetes by intraperitoneal injection of nicotinamide (50 mg/kg and streptozotocin 50 mg/kg), and SD was induced by intracisternal administration of GOD (50 U/5 µl at 1 µL/minute). The BC (50 and 100 mg/kg; p.o.) and donepezil (1 mg/kg; p.o.) were administered for 15 consecutive days. The cognitive function was assessed by the Morris water maze test and biomarkers i.e., blood glucose & insulin; serum nitric oxide (NO); tissue acetylcholinesterase (AChE), galectin-1 (G1), NADPH oxidase (NOX4) activity & glucose transporter 1 (GLUT1) levels were evaluated.

RESULT: GOD potentially changes the neurovascular unit in the brain which leads to a rise the insulin resistance (IR), NO, G1, & GLUT1 levels; and decreases the NOX4 activity. The GOD causes the potential cognitive dysfunctions. However, the treatment of BC attenuated the GOD-associated cognitive dysfunction and biomarker changes.

METHOD: A total of 137 fecal samples of the elderly were collected, and subjected to DNA analysis, and enzyme-linked immunosorbent assays (ELISA). Plasma samples were subjected to mass spectrometry proteomic analysis. The parameters of the subjects measured include functional reach test (FRT), handgrip strength (HGS), Visual Cognitive Assessment Test (VCAT), Montreal Cognitive Assessment (MoCA), timed up and go (TUG) and UCLA three-item loneliness scale (UCLA-3).

RESULT: At the genus level, Alistipes which are potential drivers of dysbiosis, are significantly increased in CF subjects. Proteobacteria are also negatively linked to FRT, HGS, VCAT, and MoCA, but positively correlated to TUG and UCLA-3. Lactoferrin was upregulated in pre-frail subjects. The plasma apolipoprotein AI (Apo-AI) was upregulated 5 times in the CF subjects.

METHOD: This study was approved by the institutional Ethics Committees. Postmortem nasal mucosa and brain tissues from patients with AD (n = 10) and normal subjects (n = 10) were collected with patient consent at the Fukushimura Brain Bank. Nasal and brain tissue homogenates were added to HEK293 cells expressing tau 3-repeat domain with the L266V and V337M mutations (3RD∗VM) or 4-repeat domain with the P301L and V337M mutations (4RD∗LM), which was fused with GFP at the C-terminus.

RESULT: GFP fluorescence was detected uniformly within the cell bodies of HEK293T cells expressing 3RD∗VM-EGFP and 4RD∗LM-EGFP. There were no changes in the fluorescence after the additions of the brain homogenates from normal subjects. In contrast, a large number of fluorescent puncta was detected both in HEK293T cells expressing 3RD∗VM-EGFP and 4RD∗LM-EGFP at 4 days after the additions of the brain homogenates from patients with AD. Furthermore, the nasal tissue homogenates from patients with AD also induce the formation of fluorescent aggregates in HEK293T cells expressing 3RD∗VM-EGFP and 4RD∗LM-EGFP. Quantitative analysis revealed that the nasal tissue homogenates from AD patients significantly induced the aggregate formation, compared with normal subjects.

METHOD: Data were obtained from 36 members of COSMIC, representing 28 countries across 6 continents (HICs: Australia, Canada, Faroe Islands, France, Germany, Greece, Italy, Japan, Netherlands, South Korea, Spain, Sweden, & USA; LMICs: Brazil, China, Cuba, Dominican Republic, Ecuador, Indonesia, Malaysia, Mexico, Nigeria, Peru, Philippines, Republic of Congo, & Tanzania). For each member study, we calculated incidence rates for all-cause dementia. Findings from 14 studies, with a consensus diagnosis are presented in the results. Using an Item Response Theory approach, we are currently calculating a comparable incidence rate for those studies without a consensus diagnosis.

RESULT: Consistent with previous trends, incidence rates (per 100 person-years) increased with age, from 65-70 years-old to 85-90 years-old, for both males (i.e., Republic of Congo, 4.41 to 19.57; France, 0.46 to 3.89; USA, 0.17 to 3.22; Spain, 0.31 to 4.22; 65-70 & 85-90 cohorts respectively) and females (i.e., Republic of Congo, 3.57 to 15.31; France, 0.45 to 3.72; USA, 0.22 to 4.25; Spain, 0.36 to 4.96; 65-70 & 85-90 cohorts respectively). There were no sex differences in incidence rates in younger age groups (60-65). Among older age groups, however, women tended to have higher incidence rates than men, in some countries (Faroe Islands, Germany, Sweden, and USA).

METHOD: A scoping review was conducted utilizing the Joanna Briggs Institute guidance. Four databases (OvidMedline, Scopus, PsycINFO, and CINAHL) were searched for eligible studies reporting dementia research priorities in LMICs in Southeast Asian. Comparisons were made to a stakeholders' consultation during a two-day workshop from the 9th to 10th February 2023 in Kuala Lumpur, Malaysia. Participants included the Southeast Asia-Dementia (SEA-Dem) Research Network members key stakeholders from Malaysia, Indonesia, Vietnam, Philippines, Singapore, and Hong Kong (n = 20). Research priorities from each participating country were generated and ranked, harmonized with those from the nominal group technique into tiers of priorities.

RESULT: Only two studies from Malaysia and Vietnam were eligible, reporting unranked research priorities. Nominal group technique ranked outcomes from Malaysia, Vietnam, Indonesia, and the Philippines were included. Top dementia research priorities were (1) local research and data collection capacity, (2) community awareness and engagement, and (3) health policy. Second-tier research priorities included harmonizing guidelines and tools standardization, health inequalities, and availability of carer support. The third tier comprised multisectoral collaboration, integration of care, telemedicine, digital approaches, dementia risk reduction, health economics, and sustainable interventions.

METHOD: We synthesised the evidence from our three previous systematic reviews (covering all literature from inception to 2023 from PubMed, Embase, and PsychInfo) on dementia risk prediction modelling. The aim was to identify models that have been specifically developed and tested specifically in LMICs. There were no language or time restrictions applied.

RESULT: To date, over 50 different dementia risk prediction models have been developed and tested with only 7 models reported from two LMICs including five studies from China and two studies from Mexico. The models incorporated variables typically linked to dementia including demographics (e.g., age, sex, education), health (e.g., diabetes, hypertension, heart disease) and lifestyle (e.g., smoking and alcohol) variables. The 7 models also have varying degrees of predictive accuracy (c-statistic range 0.65 [95%CI: 0.64-0.67] to 0.92 [95%CI: 0.88-0.95]) and none has undergone external validation. These models have been developed using traditional statistical approaches including Cox and Logistic Regression. Further, model development has not considered factors such as socioeconomic status, literacy, access to healthcare, diet, stress, pollution, and workplace hazards that may be crucial in predicting dementia risk in LMICs.

CONCLUSION: There is an urgent need to create context-specific dementia prediction models to inform the development of risk reduction and preventative interventions in LMICs where dementia case numbers are greatest. Dementia risk model development and testing need to be extended to LMICs across different regions (e.g., Asia, Middle East, Global South, Africa) and income levels (e.g., low, lower-middle, and upper-middle income).

METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis.

RESULTS: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed.

DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups.