Triggering receptor expressed on myeloid cells 2 (TREM2) is a single-pass transmembrane immune receptor that is mainly expressed on microglia in the brain and macrophages in the periphery. Recent studies have identified TREM2 as a risk factor for Alzheimer’s disease (AD). Increasing evidence has shown that TREM2 can affect lipid metabolism both in the central nervous system (CNS) and in the periphery. In the CNS, TREM2 affects the metabolism of cholesterol, myelin, and phospholipids and promotes the transition of microglia into a disease-associated phenotype. In the periphery, TREM2 influences lipid metabolism by regulating the onset and progression of obesity and its complications, such as hypercholesterolemia, atherosclerosis, and nonalcoholic fatty liver disease. All these altered lipid metabolism processes could influence the pathogenesis of AD through several means, including affecting inflammation, insulin resistance, and AD pathologies. Herein, we will discuss a potential pathway that TREM2 mediates lipid metabolism to influence the pathogenesis of AD in both the CNS and periphery. Moreover, we discuss the possibility that TREM2 may be a key factor that links central and peripheral lipid metabolism under disease conditions, including AD. This link may be due to impacts on the integrity of the blood–brain barrier, and we introduce potential pathways by which TREM2 affects the blood–brain barrier. Moreover, we discuss the role of lipids in TREM2-associated treatments for AD. We propose some potential therapies targeting TREM2 and discuss the prospect and limitations of these therapies.

Context: Elevation of homocysteine (Hcy) levels is well-established as a risk factor for dementia, yet controversy exists regarding whether B-vitamin-mediated reduction of homocysteine levels can benefit cognitive function.Objective: To investigate whether B vitamin supplementation can reduce the risk of cognitive decline and incident dementia.Data sources: The PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched for articles published from the inception dates to March 1, 2020. Randomized controlled trials (RCT) were included if B vitamins were supplied to investigate their effect on the rate of cognitive decline. Cohort studies investigating dietary intake of B vitamins and the risk of incident dementia were eligible. Cross-sectional studies comparing differences in levels of B vitamins and Hcy were included.Data extraction: Two reviewers independently performed data extraction and assessed the study quality.Data analysis: Random-effect or fixed-effect models, depending on the degree of heterogeneity, were performed to calculate mean differences (MDs), hazard ratios (HRs), and odds ratios (ORs).Results: A total of 95 studies with 46175 participants (25 RCTs, 20 cohort studies, and 50 cross-sectional studies) were included in this meta-analysis. This meta-analysis supports that B vitamins can benefit cognitive function as measured by Mini-Mental State Examination score changes (6155 participants; MD, 0.14, 95%CI 0.04 to 0.23), and this result was also significant in studies where placebo groups developed cognitive decline (4211 participants; MD, 0.16, 95%CI 0.05 to 0.26), suggesting that B vitamins slow cognitive decline. For the > 12 months interventional period stratum, B vitamin supplementation decreased cognitive decline (3814 participants; MD, 0.15, 95%CI 0.05 to 0.26) compared to placebo; no such outcome was detected for the shorter interventional stratum (806 participants; MD, 0.18, 95%CI -0.25 to 0.61). In the non-dementia population, B vitamin supplementation slowed cognitive decline (3431 participants; MD, 0.15, 95%CI 0.04 to 0.25) compared to placebo; this outcome was not found for the dementia population (642 participants; MD, 0.20, 95%CI -0.35 to 0.75). Lower folate levels (but not B12 or B6 deficiency) and higher Hcy levels were significantly associated with higher risks of dementia (folate: 6654 participants; OR, 1.76, 95%CI 1.24 to 2.50; Hcy: 12665 participants; OR, 2.09, 95%CI 1.60 to 2.74) and cognitive decline (folate: 4336 participants; OR, 1.26, 95%CI 1.02 to 1.55; Hcy: 6149 participants; OR, 1.19, 95%CI 1.05 to 1.34). Among the population without dementia aged 50 years and above, the risk of incident dementia was significantly decreased among individuals with higher intake of folate (13529 participants; HR, 0.61, 95%CI 0.47 to 0.78), whereas higher intake of B12 or B6 was not associated with lower dementia risk.Conclusions: This meta-analysis suggests that B vitamin supplementation is associated with slowing of cognitive decline, especially in populations who received early intervention and intervention of long duration; the study also indicates that higher intake of dietary folate, but not B12 or B6, is associated with a reduced risk of incident dementia in non-dementia aged population. Given the prevalence of dementia cases in many countries with aging populations, public health policies should be introduced to ensure that subgroups of the population at risk have an adequate B vitamin status.

INTRODUCTION: We examined the burden of Alzheimer's disease and other dementias (ADOD) and attributable factors at the national and provincial levels in China.METHODS: Using the Global Burden of Diseases Study 2021, we estimated incidence, prevalence, mortality rate, disability‐adjusted life years (DALYs), and the ratio of years lived with disability (YLD) to DALYs for ADOD in China. Estimated annual percentage changes (EAPCs) were used to quantify the temporal trends from 1990 to 2021.RESULTS: In 2021, China experienced the highest ADOD burden among Group of 20 member nations. The EAPCs for age‐standardized rates for incidence, age‐standardized rates for prevalence, and age‐standardized mortality rate were 0.41 (uncertainty intervals [UIs] 0.34–0.49); 0.44 (UI: 0.36–0.52); and –0.19 (UI: ‐0.23 to ‐0.15), respectively. Between 1990 and 2021, the number of people with ADOD increased by 322.18% and DALYs associated with ADOD increased by 272.71%; most of these increases were explained by population aging.DISCUSSION: Considering the aging Chinese population, targeted strategies to prevent dementia are urgently needed.Highlights: China experienced the highest dementia burden among Group of 20 member nations. High body mass index, high fasting plasma glucose, and smoking were major risk factors for Alzheimer's disease and other dementias (ADOD) burden. Since 1990, the incidence and prevalence of ADOD increased substantially in China. The mortality rate related to ADOD decreased consistently. Considering the aging Chinese population, targeted strategies are urgently needed.

Background: To evaluate the relationship between atherosclerosis and Alzheimer's disease (AD), we conducted a systematic review and meta‐analysis to study the difference of carotid intima–media thickness (CIMT) and the prevalence of atherosclerosis between AD patients and non‐AD controls.Methods: The studies on the association between atherosclerosis and AD were manually searched in PubMed, Embase, Cochrane Library, and CNKI (China National Knowledge Infrastructure) spanned to September 2018 according to PRISMA (the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) guidelines.Results: Thirteen studies were included in the final analysis, seven studies with data on the mean CIMT (610 cases and 417 controls) and ten studies reporting on the prevalence of atherosclerosis (1,698 cases and 6,452 controls). Compared with controls, AD group showed a significantly higher CIMT (overall standard mean difference = 0.94; 95% CI, 0.48–1.40; p < .0001) and an increased prevalence of atherosclerosis (OR = 1.46; 95% CI, 1.26–1.68; p < .0001).Conclusions: Atherosclerosis is significantly associated with AD. CIMT might be a useful marker to predict the risk of AD and assess the vascular burden. The finding is also important for possible prevention and treatment of AD in the future.