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BACKGROUND: Studies suggested that vascular dysfunction might increase the risk of developing Alzheimer’s disease (AD), but the underlying mechanisms still remain obscure. Objective: To evaluate the associations of vascular risk burden with AD core pathologies and investigate the effects of AD core pathologies on relationships between vascular risk burden and cognitive impairments. Design: The Chinese Alzheimer’s Biomarker and LifestyLE (CABLE) study was principally focusing on aging, as well as the risk factors and biomarkers of AD initiated in 2017. Setting: The CABLE study was a large cohort study established in Qingdao, China. Participants: A total of 618 non-demented elders were obtained from CABLE study. Measurements: The general vascular risk burden was assessed by the Framingham General Cardiovascular Risk Score (FGCRS). Multivariate linear regression analyses were performed to evaluate the associations of FGCRS with cerebrospinal fluid (CSF) AD biomarkers and cognition. Casual mediation analyses were performed to investigate the mediating effects of AD biomarkers on cognition. Results: Increased FGCRS was related to higher levels of CSF total tau (t-tau, p < 0.001), phosphorylated tau (p-tau, p < 0.001) as well as the ratio of t-tau and amyloid-β 42 (t-tau/Aβ42, p = 0.010), and lower Chinese-Modified Mini-Mental State Examination (CM-MMSE, p = 0.010) score. Stratified analysis indicated that age modified the associations, with FGCRS being significantly associated with tau pathology (p < 0.001 for t-tau and p-tau) in middle-aged group (

Background White matter hyperintensities of presumed vascular origin (WMH) are one of the imaging features of cerebral small vessel disease. Controversies persist about the effects of WMH on cognitive dysfunction. This meta-analysis aimed to identify the associations of WMH with risks of cognitive impairment and dementia. Methods We searched PubMed, EMBASE and Cochrane Library for prospective studies. Primary analyses of cognitive dysfunction and sub-analyses of specific outcomes and study characteristics were conducted using random-effect models. Results Thirty-six prospective studies with 19,040 participants were included. WMH at baseline conferred a 14 % elevated risk of cognitive impairment and all-cause dementia (ACD). WMH also conferred 25 % elevated risk of Alzheimer’s disease and 73 % elevated risk of vascular dementia. Risk effects of high-grade WMH and continually increasing WMH (in volume or severity) on ACD were revealed. Periventricular WMH conferred a 1.51-fold excess risk for dementia. Conclusions WMH were associated with increased risk of cognitive dysfunction and could become a neuroimaging indicator of dementia.

Background: Several existing studies have reported that occupational factors might play an important part in cognitive function with aging. Objective: We aim to explore the associations between modifiable occupational factors and risk of dementia or mild cognitive impairment (MCI). Methods: Adopting random-effect models, this study conducted primary analyses for all occupational factors and subgroup analyses for the effect of occupation type based on prospective cohort and case-control studies searched from PubMed and EMBASE databases up to March 2020. Results: Among the 38,111 identified literatures, 9 studies on occupation type, 4 studies on work complexity, and 30 studies on occupational exposure were included. In terms of occupation type, mental work conferred a 44% reduced risk (95% CI = 0.34–0.94, I² = 85.00%, p

Controversies persist about the associations of body mass index (BMI) with risk of cognitive impairment and dementia. This study aimed to evaluate these associations from various aspects, in which Embase, PubMed and Cochrane databases were searched to identify prospective studies up to May 2019. Random-effects meta-analyses and dose-response meta-analysis were conducted, involving twenty-nine of 20,083 identified literatures. Meta-analysis showed that midlife underweight, obesity and late-life underweight conferred 1.39-, 1.31- and 1.64-fold excess risk for cognitive impairment and dementia, while late-life overweight and obesity conferred 21% and 25% reduced risk. In dose-response meta-analysis, all cause dementia (ACD), Alzheimer's disease (AD) and vascular dementia (VaD) risk in midlife was significantly elevated when BMI surpassed 29, 30 and 32 kg/m2. AD risk in late-life was decreased when BMI was under 27 kg/m2, while this protection for VaD was absent when BMI surpassed 39 kg/m2. Higher BMI produced opposite exerted opposite effects on dementia in mid- and late-age population. Firstly reported, a dose-response relationship further supports the guideline from the standpoint of dementia prevention.

It is unclear how blood glucose levels mediate the pathology of Alzheimer's disease (AD). This study aimed to investigate whether fasting blood glucose (FBG) levels are associated with cerebrospinal fluid (CSF) biomarkers preferentially affected by AD in non-diabetic cognitively normal elders. A total of 499 non-diabetic cognitively normal elders were from the Chinese Alzheimer’s Biomarker and LifestyLE (CABLE) study. We detected the associations of FBG with individual CSF measures using multiple linear regression models controlling for age, sex, educational level, and apolipoprotein E (APOE) ε4 genotype. Fasting blood glucose level was positively correlated with CSF Aβ42 level (β = 0.045, p = 0.010), CSF Aβ42/Aβ40 ratio (β = 0.005, p < 0.001), Aβ42/P-tau ratio (β = 0.282, p = 0.013), and Aβ42/T-tau ratio (β = 0.050, p = 0.040). Interaction analysis indicated that gender affected the correlations of FBG level with CSF Aβ40 (p < 0.001) and Aβ42/Aβ40 ratio (p < 0.001). This study raises additional questions about the role of blood glucose in the predisposition to AD and supports the possibility of targeting these processes in pre-symptomatic AD trials in non-diabetic elders.

Background: Subjective cognitive decline (SCD) as an early pathological manifestation of brain aging has become more prevalent among older adults. Objectives: We aimed to investigate the associations of subjective cognitive decline (SCD) with the combined risk of cognitive impairment and dementia. Design: We performed a systematic review and meta-analysis via searching Embase, PubMed and Cochrane electronic databases from January 1 st 1970 to June 4th, 2020. Setting: Prospective cohort studies Participants: Healthy individuals were recruited from community, clinics and population. Measurements: Healthy individuals with SCD were classified into exposure groups, while those without were considered as the reference group. Adjusted relative risks (RR) were estimated in a random-effects model. Both primary and subgroup analyses were conducted. Results: Of 28,895 identified studies, 21 studies containing 22 cohorts were eligible for inclusion in the meta-analysis. SCD increased the risk of subsequent cognitive disorders (RR=2.12, 95% confidence intervals [CI] =1.75-2.58, I2=87%, P15 years) subgroup and subgroup of clinics showed a higher risk of developing objective cognitive disorders. Conclusions: SCD is associated with an increased combined risk of cognitive impairment and incident dementia and should be considered a risk factor for objective cognitive disorders.

Background Cognitive impairment and dementia is a universal phenomenon in the older. And as a feature of cerebral small vessel disease (CSVD), cerebral microbleed (CMB) plays a role in the process of cognitive decline. Aims We aim to identify the association of CMBs with risks of cognitive impairment and dementia prospectively. Methods From database inception to Sept. 12, 2020, we systematically searched PubMed, Embase and Ovid databases to obtain relative articles which have exact values in the relationship between CMB and dementia. In primary analysis, we divided the cognitive normal subjects at baseline into dementia and mild cognitive impairment (MCI) groups as outcomes. In the dementia group, we conducted subgroup analysis according to the number and locations of CMBs. Results A total of 32641 articles were identified and 14 articles with 11407 participants were included. The presence of CMBs increased the risk of dementia (relative risk (RR) =1.32, 95% confidence interval (CI) =1.00-1.72, I2=21.2%, P=0.268), as well as the risk of VaD (vascular dementia) (RR=2.41, 95%CI=1.28-4.54, I2=0%, P=0.381). Subgroup analyses showed that ≥2 CMBs (RR=2.27, 95%CI=1.71-3.01, I2=0%, P=0.627) and deep and/or mixed CMBs (RR=1.75, 95%CI=1.09-2.80, I2=23.3%, P=0.012) were associated with the risk of dementia. Conclusion Results indicated that as CMB numbers increased, the associations with dementia were more significant. The present of CMBs in specific cerebral areas helps in understanding the pathogenesis of dementia. Future work will focus on finding treatments to improve long-term prognosis of patients with CMBs.

As brain insults, sleep disorders could enhance microglial activation and aggravate neuroinflammation. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) serves as a readout for TREM2-associated microglial responses. We aimed to study the association of sleep characteristics with CSF sTREM2 in cognitively normal (CN) older adults. Linear and non-linear regression analyses were conducted in 830 participants with measurements of sleep characteristics and CSF sTREM2, after adjusting for age, sex, education, the Chinese-Modified Mini-Mental State Examination (CM-MMSE) scores, and APOE4 status. These analyses were also performed in amyloid-negative (A −) and amyloid-positive (A +) individuals. Linear relationships between sleep characteristics and CSF sTREM2 were found. In all the participants, sleep efficiency score in Pittsburgh Sleep Quality Index (PSQI) (p = 0.037) showed a positive linear association with CSF sTREM2. In A + individuals, the grade of PSQI total score (p = 0.011) as well as subjective sleep quality score (p = 0.048) and sleep efficiency score (p