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Background: Although social networks are deemed as moderators of incident Alzheimer’s disease (AD), few data are available on the mechanism relevant to AD pathology. Objective: We aimed to investigate whether social networks affect metabolism of cerebrospinal fluid (CSF) AD biomarkers during early stage and identify modification effects of genetic factor and subjective cognitive decline (SCD). Methods: We studied participants from the Chinese Alzheimer’s disease Biomarker and Lifestyle (CABLE) database who received cognition assessments and CSF amyloid-β (Aβ1–42 and Aβ1–40) and tau proteins (total-tau [T-tau] and phosphorylated-tau [P-tau]) measurements. The social networks were measured using self-reported questionnaires about social ties. Linear regression models were used. Results: Data were analyzed from 886 cognitively intact individuals aged 61.91 years (SD = 10.51), including 295 preclinical AD participants and 591 healthy controls. Social networks were mostly associated with CSF indicators of AD multi-pathologies (low P-tau/Aβ1–42 and T-tau/Aβ1–42 and high Aβ1–42/Aβ1–40). Significant differences of genetic and cognitive status were observed for CSF indicators, in which associations of social network scores with CSF P-tau and indicators of multi-pathologies appeared stronger in APOE 4 carriers (versus non-carriers) and participants with SCD (versus controls), respectively. Alternatively, more pronounced associations for CSF T-tau (β= –0.005, p

Background: Green tea has been widely recognized in ameliorating cognitive impairment and Alzheimer’s disease (AD), especially the progression of cognitive dysfunction. But the underlying mechanism is still unclear. Objective: This study was designed to determine the role of green tea consumption in the association with cerebrospinal fluid (CSF) biomarkers of AD pathology and to ascertain whether specific population backgrounds showed the differences toward these relationships. Methods: Multivariate linear models analyzed the available data on CSF biomarkers and frequency of green tea consumption of 722 cognitively intact participants from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database, and we additionally detected the interaction effects of tea consumption with APOE ɛ4 status and gender using a two-way analysis of covariance. Results: Frequent green tea consumption was associated with a decreased level of CSF total-tau protein (t-tau) (p = 0.041) but not with the levels of CSF amyloid-β 42 (Aβ42) and CSF phosphorylated tau. The more pronounced associations of green tea consumption with CSF t-tau (p = 0.007) and CSF t-tau/Aβ42 (p = 0.039) were observed in individuals aged 65 years or younger. Additionally, males with frequent green tea consumption had a significantly low level of CSF t-tau/Aβ42 and a modest trend toward decreased CSF t-tau. There were no interaction effects of green tea consumption with APOE ɛ4 and gender. Conclusion: Collectively, our findings consolidated the favorable effects of green tea on the mitigation of AD risk. The constituents of green tea may improve abnormal tau metabolism and are promising targets in interventions and drug therapies.

The ATP-binding cassette transporter A7 (ABCA7) was identified as a known risk factor for Alzheimer's disease (AD). However, the relation between ABCA7 and AD was still inconsistent across these studies. Here, our meta-analysis aimed at confirming the association of ABCA7 with AD. Finally, 16 case-control studies (63747 versus 85833) were retrieved from PubMed and other databases. Three common loci were confirmed to increase the risk of AD (rs3764650: OR = 1.20, 95% CI = 1.16-1.24; rs3752246: OR = 1.13,95% CI = 1.08-1.19; rs4147929: OR = 1.17, 95% CI = 1.10-1.24), but the associations varied among the different races. Furthermore, ABCA7 loss-of-function (LOF) mutations conferred a higher risk for AD than did the above variants (LOF: OR = 1.78, 95% = 1.43-2.22). In conclusion, ABCA7 genetic variants, especially the LOF mutations, were significantly associated with the risk of AD.

BACKGROUND Vascular dementia (VaD) is the second most common type of dementia. So far, little is known about the contribution of genetic polymorphisms to the risk of VaD. Many candidate genetic polymorphisms have been examined in a large number of studies. However, due to the conflicting results, the genetics of VaD is still behind the shadow. OBJECTIVE We conducted a comprehensive meta-analysis on associations between genetic polymorphisms of any gene and VaD to investigate the genetics of VaD. METHOD We sought the published studies of associations between any genetic polymorphism and VaD and critically appraised them. We assessed the effects of genetic models by calculating pooled odds ratios (ORs), investigating the origin of heterogeneity by subgroup analysis, and testing the robustness by random effect model and sensitivity analysis. RESULTS 69 studies with 4,462 cases and 11,583 controls were included. We identified APOE ɛ2/ɛ3/ɛ4 and additional four genetic polymorphisms including MTHFR C677T, PON1 L55M, TGF-β1 +29C/T, and TNF-α -850C/T associated with VaD. Tested by random effect model and sensitivity analysis, the pooled results show nice robustness. CONCLUSIONS Our comprehensive meta-analysis highlighted the genetic contribution to sporadic VaD. Because of the small amount of data on associations between genetic polymorphisms, except for APOE, and VaD, more studies are needed to test the existing genetic polymorphisms and detect other related genetic variants.

Background: In the past 20 years, substantial evidence from laboratory and epidemiologic studies have suggested that anti-inflammatory medications could defer or prevent the occurrence of Alzheimer's disease (AD). However, several studies do not corroborate these findings. Objective: To evaluate the association of anti-inflammatory drug use on the incidence of AD. Methods: Pubmed, Embase, and Cochrane Library databases were searched up to March 2014. Studies evaluating the association between use of anti-inflammatory drugs and AD risk were included. Relative risks (RRs) with 95% confidence intervals (CIs) were meta-analyzed using random effects models and were grouped by anti-inflammatory type and duration of drug use. Results: In observational studies, use of non-steroidal anti-inflammatory drugs (NSAIDs) was significantly associated with a reduced risk of AD (RR, 0.72; 95%CI, 0.62-0.84) compared to no use of NSAIDs, especially in long term users (RR, 0.36; 95%CI, 0.17-0.74); the risks of AD were also lower in both aspirin (RR, 0.77; 95%CI, 0.63-0.95) and non-aspirin NSAID users (RR, 0.65; 95%CI, 0.47-0.88) compared with nonusers; whereas the use of corticosteroids showed no significant association (RR, 0.62; 95%CI, 0.26-1.46). In the single randomized controlled trial (RCT), NSAID use showed no significant effect on AD risk among dementia-free individuals (p > 0.05). Conclusion: Observational studies support the use of NSAIDs for prevention of AD, but RCT do not. Well-designed studies and innovative approaches are required to illuminate the exact relationship between NSAID use and AD risk. The appropriate dosage and duration of use to benefit and the safety are also needed to determine.

Background/objective We examine whether midlife vascular risk factors (VRFs) are associated with increased risk of incident Alzheimer's disease (AD) in a systematic review and meta-analysis of published cohort studies. Methods Original cohort studies were included if they reported adjusted combined odds ratio (COR) and corresponding 95% confidence intervals (CIs) or enough information to quantify the association between risk for AD in late-life and baseline VRFs of midlife. Results There were positive and significant associations between high blood pressure (COR 1.31; 95% CI: 1.01-1.70), hypercholesterolemia (COR 1.72; 95% CI: 1.32-2.24), obesity (COR 1.88; 95% CI: 1.32-2.69), and diabetes mellitus in midlife (COR 1.4; 95% CI: 1.25-1.57). Smoking and hyperhomocysteinemia (although only one high-quality paper) were also associated with an increased risk of AD generally. Conclusions These results strengthen the epidemiological evidence that VRFs of midlife significantly increase risk for AD.

BACKGROUND Non-pharmacological interventions, including cognition-based intervention and physical exercise, are available for mild cognitive impairment (MCI), but their efficacy remains uncertain. OBJECTIVE To evaluate efficacy of cognition-based intervention and physical exercise on cognitive domains in patients with MCI. METHODS We searched MEDLINE, EMBASE, the Cochrane library, and BIOSIS previews to identify randomized controlled trials (RCTs) that involved cognition-based intervention and physical exercise for persons who were diagnosed with MCI. The pooled weight mean difference or standard mean difference (SMD) were calculated using a random-effect model. RESULTS We found significant effects of cognition-based intervention on global cognitive function (SMD 0.37 [0.07, 0.68] p = 0.02). Besides, cognition-based intervention produced significant effects on executive function reported with TMT-B (SMD 0.8 [0.09, 1.5] p = 0.03) and delayed memory (SMD 0.31 [0.01, 0.61] p = 0.05). A beneficial improvement in global cognitive function was also seen in the exercise group compared to the control group (SMD 0.25 [0.08, 0.41] p = 0.003). CONCLUSIONS Both of cognition-based intervention and physical exercise had the potential to improve global cognitive function. Weak evidence of improvements was also observed for the domains of executive function and delayed memory following cognition-based intervention. Nevertheless, future standard RCTs are still needed to identify the clinical value of our results.

Background The role of currently available drugs for Alzheimer's disease (AD) has been controversial, with some national formularies restricting their use, and health economists questioning whether the small clinical effects are economically worthwhile. Objective To estimate the efficacy and safety of donepezil, galantamine, rivastigmine, and memantine for the treatment of AD. Methods Double-blind, placebo-controlled, with random assignment to a cholinesterase inhibitor or memantine trials were included into the pooled studies. Results Cognitive effects were significant for all drugs, ranging from a -1.29 points mean difference (95% CI -2.30 to -0.28) in the 20 mg daily memantine trials to -3.20 points (95% CI -3.28 to -3.12) in the 32 mg daily galantamine group. Only memantine had no effect on the Clinicians' Global Impression of Change scale. No behavioral benefits were observed, except for -2.72 (95% CI -4.92 to -0.52) in the 10 mg daily donepezil group and -1.72 (95% CI -3.12 to -0.33) for 24 mg daily galantamine trial. Only 5 mg daily donepezil had no effect on the function outcome. Compared with placebo, more dropouts and adverse events occurred with the cholinesterase inhibitors, but not with memantine. Conclusions Cholinesterase inhibitors and memantine are able to stabilize or slow decline in cognition, function, behavior, and global change.

Recent findings that human serum contains stably expressed microRNAs (miRNAs) have revealed a great potential of serum miRNA signature as disease fingerprints to diagnosis. Here we used genome-wide serum miRNA expression analysis to investigate the value of serum miRNAs as biomarkers for the diagnosis of Alzheimer's disease (AD). Illumina HiSeq 2000 sequencing followed by individual quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays was used to test the difference in levels of serum miRNAs between 50 AD patients and 50 controls in the screening stages. The detected serum miRNAs then were validated by qRT-PCR in 158 patients and 155 controls. MiR-98-5p, miR-885-5p, miR-483-3p, miR-342-3p, miR-191-5p, and miR-let-7d-5p displayed significantly different expression levels in AD patients compared with controls. Among the 6 miRNAs, miR-342-3p has the best sensitivity (81.5%) and specificity (70.1%) and was correlated to Mini-Mental State Examination score. This study identified six serum miRNAs that distinguish AD patients from healthy controls with high sensitivity and specificity. Serum miRNA panel (or miR-342-3p alone) may serve as a novel, noninvasive biomarker for AD.

We conducted a replication study of the 2 genetic variants, rs11754661 and rs2073067, in MTHFD1L that have been recently reported to be associated with late-onset Alzheimer's disease (LOAD) in a genome-wide study in Caucasians. The associations were evaluated in a case-control sample comprising 1,189 Northern Han-Chinese individuals. The rs11754661 polymorphism is associated with LOAD (OR = 1.727; p = 0.016). For rs2073067, LOAD association was found only in APOEe4 carriers (OR = 0.400; p < 0.001). Haplotype analysis revealed the "AC" haplotype increased the risk of developing LOAD (OR = 1.730; p = 0.015). Our findings support a role of MTHFD1L gene in LOAD.