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Background: Evidence has emerged that altered ventricular electrocardiogram profiles are associated with dementia, but the neuropathological mechanisms underlying their associations are poorly understood. Objective: To investigate the interrelationships of ventricular electrocardiogram profiles with dementia and plasma Alzheimer's disease (AD) biomarkers among older adults. Methods: This population-based cross-sectional study included 5,153 participants (age ≥65 years; 57.3% women) living in rural communities in China; of these, 1,281 had data on plasma amyloid-β (Aβ)40, Aβ42, total-tau, and neurofilament light chain (NfL) protein. The QT, QTc, JT, JTc, QRS intervals, and QRS axis were derived from the 10-second electrocardiogram recording. The DSM-IV criteria were followed for clinical diagnosis of dementia, the NIA-AA criteria for AD, and the NINDS-AIREN criteria for vascular dementia (VaD). Data were analyzed using general linear models, multinomial logistic models, and restricted cubic splines. Results: Of the 5,153 participants, 299 (5.8%) were diagnosed with dementia, including 194 with AD and 94 with VaD. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with all-cause dementia, AD, and VaD (p < 0.05). Left QRS axis deviation was significantly associated with all-cause dementia and VaD (p < 0.01). In the subsample of plasma biomarkers (n = 1,281), prolonged QT, JT, and JTc intervals were significantly associated with a lower Aβ42/Aβ40 ratio and higher plasma NfL concentrations (p < 0.05). Conclusion: Alterations in ventricular repolarization and depolarization are independently associated with all-cause dementia, AD, VaD, and AD plasma biomarkers in older adults (age ≥65 years). Ventricular electrocardiogram parameters may be valuable clinical markers for dementia and the underlying AD pathologies and neurodegeneration. [ABSTRACT FROM AUTHOR]

Background: Few studies have examined occurrence and progression of cognitive impairment, no dementia (CIND) in rural China.Objective: To determine the prevalence and incidence of CIND in rural-dwelling Chinese older adults, and to examine risk and protective factors associated with progression to CIND and dementia.Methods: This population-based study included 2,781 dementia-free participants (age≥65 years) who were examined at baseline (2014) and followed in 2018. Demographic, epidemiological, clinical, and neuropsychological data were collected following a structured questionnaire. We defined CIND according to subjective cognitive complaints and the age- and education-specific Mini-Mental State Examination (MMSE) score. Data were analyzed with the multinomial logistic regression models.Results: The overall prevalence of CIND was 10.54% and the incidence was 28.26 per 1,000 person-years. CIND at baseline was associated with the multi-adjusted odds ratio (OR) of 2.06 (95% confidence interval = 1.23-3.47) for incident dementia. Multinomial logistic regression analysis suggested that compared with no CIND, the multi-adjusted OR of incident CIND was 2.21 (1.51-3.23) for women and 0.62 (0.38-0.99) for high social support, whereas the multi-adjusted OR of incident dementia was 1.14 (1.09-1.18) for older age, 0.29 (0.16-0.53) for high education, and 2.91 (1.47-5.74) for having a stroke history.Conclusion: CIND affects over one-tenth of older adults living in rural communities of western Shandong province. People with CIND are twice as likely to progress to dementia as people without CIND. Female sex, low education, stroke history, and low social support are associated with an increased risk of progression from normal cognition to CIND or dementia. [ABSTRACT FROM AUTHOR]

Background: Structural brain magnetic resonance imaging (MRI) scans may provide reliable neuroimaging markers for defining amnestic mild cognitive impairment (aMCI).Objective: We sought to characterize global and regional brain structures of aMCI among rural-dwelling older adults with limited education in China.Methods: This population-based study included 180 participants (aged≥65 years, 42 with aMCI and 138 normal controls) in the Shandong Yanggu Study of Aging and Dementia during 2014-2016. We defined aMCI following the Petersen's criteria. Global and regional brain volumes were automatically segmented on MRI scans and compared using a region-of-interest approach. Data were analyzed using general linear regression models.Results: Multi-adjusted β-coefficient (95% confidence interval) of brain volumes (cm3) associated with aMCI was -12.07 (-21.49, -2.64) for global grey matter (GM), -18.31 (-28.45, -8.17) for global white matter (WM), 28.17 (12.83, 44.07) for cerebrospinal fluid (CSF), and 2.20 (0.24, 4.16) for white matter hyperintensities (WMH). Furthermore, aMCI was significantly associated with lower GM volumes in bilateral superior temporal gyri, thalamus and right cuneus, and lower WM volumes in lateral areas extending from the frontal to the parietal, temporal, and occipital lobes, as well as right hippocampus (p < 0.05).Conclusion: Brain structure of older adults with aMCI is characterized by reduced global GM and WM volumes, enlarged CSF volume, increased WMH burden, reduced GM volumes in bilateral superior temporal gyri, thalamus, and right cuneus, and widespread reductions of lateral WM volumes. [ABSTRACT FROM AUTHOR]

Background: Sedentary behavior is associated with cognitive impairment, but the neuropathological mechanisms underlying their associations are poorly understood. Objective: To investigate the associations of accelerometer-measured sedentary behavior patterns with brain structure and cognition, and further to explore the potential mechanisms. Methods: This community-based study included 2,019 older adults (age≥60 years, 59% women) without dementia derived from participants in the baseline examination of MIND-China (2018–2020). We assessed sedentary parameters using an accelerometer and cognitive function using a neuropsychological test battery. Structural brain markers were assessed on the structural brain MRI scans in a subsample (n = 1,009). Data were analyzed using the general linear, isotemporal substitution, and mediation models. Results: In the total sample (n = 2,019), adjusting for multiple covariates and moderate-to-vigorous-intensity physical activity, longer mean sedentary bout duration was linearly related with lower z-scores of global cognition, verbal fluency, and memory (ptrend < 0.05), whereas greater total sedentary time was linearly associated with lower z-scores of global cognition, verbal fluency, and memory only among individuals with long sedentary time (>10 h/day) (ptrend < 0.05); Breaking up sedentary time with same amount of light-intensity physical activity was significantly associated with higher verbal fluency and memory z-scores (p < 0.05). In the MRI subsample (n = 1,009), separately entering structural brain MRI markers into the mediation models substantially attenuated the associations of mean sedentary bout duration with global cognition, verbal fluency, and memory z-scores. Conclusion: Prolonged uninterrupted sedentary time is associated with poor global cognition, memory, and verbal fluency among rural older adults, and structural brain markers could partially mediate the association. [ABSTRACT FROM AUTHOR]

Background: Evidence has linked self-reported sedentary behavior (SB) and physical activity (PA) with cognitive impairment; however, the underlying mechanisms are poorly understood. We examined the associations of the accelerometer-measured movement behaviors with plasma neurofilament light chain (NfL) among older adults and the role of systemic low-grade inflammation in the associations. Results: This population-based study included 1,029 dementia-free older adults (age ≥ 60 years, range 60–88 years; 59.48% women) who undertook the ActiGraph substudy (March 2018-December 2020) in MIND-China. There were nonlinear relationships of daily SB and PA time with plasma NfL concentration, such that more daily SB time or less time spent in daily light-intensity physical activity (LPA) and moderate-to-vigorous-intensity physical activity (MVPA) was significantly associated with increased plasma NfL only when SB time ≥ 8.00 h/day or LPA time < 5.00 h/day or MVPA time < 2.00 h/day. Furthermore, more daily SB time or less daily LPA and MVPA time was significantly associated with higher serum low-grade inflammation score, a composite measure generated from serum IL-6, IL-8, TNF-α, and ICAM-1 (P < 0.05). Finally, low-grade inflammation score accounted for 14.5% to 17.8% of the associations between movement behaviors and plasma NfL. Conclusions: More daily SB and less PA time are associated with neurodegeneration and systemic low-grade inflammation in older adults. The association of movement behaviors with neurodegeneration is partially mediated by low-grade inflammation. [ABSTRACT FROM AUTHOR]

Background: Few community-based studies have examined occurrence and progression of subjective cognitive decline (SCD). Objective: To investigate prevalence and progression of SCD among rural-dwelling Chinese elderly people. Methods: This cohort study included 2,488 cognitively unimpaired adults (age≥65 years) who were examined at baseline (2014-2015) and followed in 2018. Demographic, epidemiological, clinical, and neuropsychological data were collected via in-person interviews and clinical examinations following a structured questionnaire. At baseline, SCD was assessed using the self-rated Ascertain Dementia 8-item Questionnaire. At follow-up, Alzheimer's disease (AD) and vascular dementia (VaD) were clinically diagnosed following the international criteria. Data were analyzed using logistic regression models. Results: The prevalence of SCD was 40.07%. SCD at baseline was associated with the multivariable-adjusted odds ratio (OR) of 1.51 (95% confidence interval 1.10–2.07) for incident cognitive impairment, no dementia (CIND) and 3.11 (1.64–5.93) for incident AD. Among people with SCD at baseline, the multivariable-adjusted OR of incident CIND was 0.55(0.32–0.96) for hyperlipidemia; the multivariable-adjusted OR of incident AD was 1.21 (1.14–1.30) for older age, 0.32 (0.12–0.88) for high education, 2.60 (1.11–6.08) for carrying APOEɛ4 allele, and 0.34 (0.13–0.86) for high social support, whereas the multivariable-adjusted OR of incident VaD was 6.30 (1.71–23.18) for obesity. Conclusion: SCD affects over 40% of rural-dwelling cognitively unimpaired older adults in China. SCD is associated with accelerated progression to CIND and AD. Older age, lack of school education, APOEɛ4 allele, and low social support are associated with an increased risk of progression from SCD to AD, whereas obesity is related to accelerated progression to VaD. [ABSTRACT FROM AUTHOR]

• WWC1 rs17070145 was marginally associated with AD and VaD in older adults. • WWC1 exonic SNPs rs3822660 and rs3822659 are in strong LD with rs17070145. • The strong LD may explain the association of WWC1 rs17070145 C allele with AD. • Stroke may partly explain the association of rs17070145 CC genotype with VaD. We sought to examine the associations of common WWC1 variants with Alzheimer's disease (AD) and vascular dementia (VaD) among rural-dwelling older adults in China. This population-based study used data from the baseline assessments (March –September 2018) of MIND-China. AD and VaD were diagnosed following the international criteria. Of the 5455 participants (age≥60 years, 57.27% women), 182 were diagnosed with AD and 88 with VaD. Logistic regression analysis suggested that WWC1 rs17070145 C allele (vs. T) was associated with multivariable-adjusted odds ratio of 1.23 (95% confidence interval 0.96–1.58) for AD, and that CC genotype (vs. TT) was associated with multivariable-adjusted odds ratio of 2.19(1.10–4.39) for VaD, but the association with VaD became non-significant when further adjusting for stroke history. Furthermore, exonic SNPs rs3822660 and rs3822659 were in strong linkage disequilibrium (LD) with rs17070145 (D' = 0.88). These results suggest that the strong LD between rs17070145 and 2 exonic SNPs may explain the association of WWC1 rs17070145 C allele with AD and that stroke may partly explain the association of WWC1 rs17070145 CC genotype with VaD. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence has linked electrocardiographic parameters with serum adhesion molecules and cognition; however, their interrelationship has not been explored. Objective: We sought to investigate the associations of ventricular depolarization and repolarization intervals with serum adhesion molecules and cognitive function among rural-dwelling older adults. Methods: This population-based study engaged 4,886 dementia-free participants (age ≥60 years, 56.2% women) in the baseline examination (March-September 2018) of MIND-China. Of these, serum intercellular and vascular adhesion molecules (ICAM-1 and VCAM-1) were measured in 1591 persons. We used a neuropsychological test battery to assess cognitive function. Resting heart rate, QT, JT intervals, and QRS duration were assessed with electrocardiogram. Data were analyzed using general linear models adjusting for multiple confounders. Results: Longer JT interval was significantly associated with lower z-scores of global cognition (multivariable-adjusted β= –0.035; 95% confidence interval = –0.055, –0.015), verbal fluency (–0.035; –0.063, –0.007), attention (–0.037; –0.065, –0.010), and executive function (–0.044; –0.072, –0.015), but not with memory function (–0.023; –0.054, 0.009). There were similar association patterns of QT interval with cognitive functions. In the serum biomarker subsample, longer JT and QT intervals remained significantly associated with poorer executive function and higher serum adhesion molecules. We detected statistical interactions of JT interval with adhesion molecules (pinteraction <0.05), such that longer JT interval was significantly associated with a lower executive function z-score only among individuals with higher serum ICAM-1 and VCAM-1. Conclusion: Longer ventricular depolarization and repolarization intervals are associated with worse cognitive function in older adults and vascular endothelial dysfunction may play a part in the associations. [ABSTRACT FROM AUTHOR]

Background: Cognitive reserve (CR) partly explains cognitive variability in the presence of pathological brain aging. Objective: We investigated the interplay of lifelong CR with age, sex, and brain aging markers in cognitive phenotypes among older adults with very limited education. Methods: This population-based cross-sectional study included 179 dementia-free participants (age ≥65 years; 39.7% women; 67.0% had no or elementary education) examined in 2014–2016. We assessed lacunes and volumes of hippocampus, ventricles, grey matter, white matter (WM), and white matter hyperintensities. Lifelong CR score was generated from six lifespan intellectual factors (e.g., education and social support). We used Mini-Mental State Examination (MMSE) score to assess cognition and Petersen's criteria to define mild cognitive impairment (MCI). Data were analyzed using general linear and logistic models. Results: The association of higher lifelong CR score (range: –4.0–5.0) with higher MMSE score was stronger in women (multivariable-adjusted β-coefficient and 95% CI: 1.75;0.99–2.51) than in men (0.68;0.33–1.03) (pinteraction = 0.006). The association of higher CR with MCI (multivariable-adjusted odds ratio and 95% CI: 0.77;0.60–0.99) did not vary by age or sex. Among participants with low CR (<1.4[median]), greater hippocampal and WM volumes were related to higher MMSE scores with multivariable-adjusted β-coefficients being 1.77(0.41–3.13) and 0.44(0.15–0.74); the corresponding figures in those with high CR were 0.15(–0.76–1.07) and –0.17(–0.41–0.07) (pinteraction <0.01). There was no statistical interaction of CR with MRI markers on MCI. Conclusion: Greater lifelong CR capacity is associated with better late-life cognition among people with limited education, possibly by compensating for impact of neurodegeneration. [ABSTRACT FROM AUTHOR]

Background and purpose: Little is known about whether nonalcoholic fatty liver disease (NAFLD) is associated with dementia or the role of serum proinflammatory cytokines in the association. We aimed to investigate the interrelationships of NAFLD, serum cytokines, and dementia among rural‐dwelling older adults. Methods: This population‐based cross‐sectional study included 5129 participants (aged ≥60 years; 61.79% women) who were living in rural communities and examined in March 2018–September 2018. NAFLD was defined through transabdominal ultrasound examination in the absence of hepatitis B or excessive alcohol consumption. Serum cytokines were measured in a subsample (n = 1686). Dementia, Alzheimer disease (AD), and vascular dementia (VaD) were diagnosed following international criteria. Data were analyzed with logistic regression and mediation models. Results: Of the 5129 participants, 455 (8.87%) were detected with moderate‐to‐severe NAFLD, and 292 (5.69%) were diagnosed with dementia (188 with AD and 96 with VaD). The multivariable adjusted odds ratios associated with moderate‐to‐severe (vs. no‐to‐mild) NAFLD were 2.22 (95% confidence interval [CI] = 1.41–3.49) for all‐cause dementia, 1.88 (95% CI = 1.01–3.50) for AD, and 2.62 (95% CI = 1.33–5.17) for VaD. In the cytokine subsample, controlling for multiple potential confounders, moderate‐to‐severe NAFLD was significantly associated with higher levels of serum monocyte chemotactic protein‐1, interleukin‐17A, interleukin‐6 (IL‐6), interleukin‐8, and tumor necrosis factor‐α (P < 0.05). The mediation analysis showed that IL‐6 mediated 12.56% of the association between NAFLD and VaD. Conclusions: Moderate‐to‐severe nonalcoholic fatty liver disease is associated with dementia and AD, especially with VaD, among rural‐dwelling Chinese older adults, in which the association with VaD is partly mediated by serum inflammatory cytokines. [ABSTRACT FROM AUTHOR]

• TOMM40 genotype but not PVRL2 gene was associated with Alzheimer's disease in Chinese older adults, depending on APOE genotype. • TOMM40 could interact with PVRL2 to substantially increase the likelihood of Alzheimer's disease. • The TOMM40 GG genotype was associated with low plasma Aβ42 concentration and the Aβ42-to-Aβ40 ratio. Genetic studies have identified Alzheimer's disease (AD)-associated SNPs in TOMM40 and PVRL2 genes, but the underlying mechanisms remain unknown. We examined their associations and interactions with AD risk and plasma biomarkers among Chinese older adults. This population-based study included 4876 participants. TOMM40 (rs2075650) and PVRL2 (rs6859) polymorphisms were detected using multiple-polymerase chain reaction amplification. Plasma Aβ40, Aβ42, and t-tau concentrations were measured using SIMOA in a subsample (n = 1257). AD was diagnosed following the international criteria. Data were analyzed using multiple logistic and general linear models. AD was diagnosed in 182 participants. The multiadjusted odds ratio of AD was 6.24 (95% CI 1.73–22.48) for TOMM40 GG, 1.47 (0.89–2.42) for PVRL2 AA, and 12.87 (3.97–41.73) for having both risk alleles (P interaction = 0.0003). Among APOE ε3/ε3 carriers, the multiadjusted odds ratio of AD associated with TOMM40 AG was 2.90(1.15–7.31). In biomarker subsample, TOMM40 GG was significantly associated with lower plasma Aβ42 and the Aβ42-to-Aβ40 ratio (p < 0.05). TOMM40 genotype is differentially associated with AD risk depending on APOE genotype. TOMM40 and PVRL2 genes could interact to substantially increase AD risk, possibly through influencing Aβ metabolism. [ABSTRACT FROM AUTHOR]

Background: Sleep characteristics associated with dementia are poorly defined and whether their associations vary by demographics and APOE genotype among older adults are unclear.Methods: This population-based cross-sectional study included 4742 participants (age ≥ 65 years, 57.1% women) living in rural China. Sleep parameters were measured using the self-rated questionnaires of the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria, and the National Institute on Aging-Alzheimer's Association criteria for Alzheimer's disease (AD). Data were analysed using multiple logistic and general linear regression models.Results: Dementia was diagnosed in 173 participants (115 with AD). Multivariable-adjusted odds ratio (OR) of dementia was 1.71 (95%CI, 1.07-2.72) for sleep duration ≤4 h/night (vs. > 6-8 h/night), 0.76 (0.49-1.18) for > 4-6 h/night, 1.63 (1.05-2.55) for > 8 h/night, 1.11 (1.03-1.20) for lower sleep efficiency (per 10% decrease), and 1.85 (1.19-2.89) for excessive daytime sleepiness. Very short sleep duration (≤4 h/night), lower sleep efficiency, and excessive daytime sleepiness were significantly associated with being diagnosed with AD (multivariable-adjusted OR range = 1.12-2.07; p < 0.05). The associations of sleep problems with dementia and AD were evident mainly among young-old adults (65-74 years) or APOE ε4 carriers. Among dementia-free participants, these sleep characteristics were significantly associated with a lower MMSE score.Conclusions: Self-reported sleep problems in dementia are characterized by very short or long sleep duration, low sleep efficiency, and excessive daytime sleepiness, especially among young-old people and APOE ε4 carriers.Trial Registration: ChiCTR1800017758 (Aug 13, 2018). [ABSTRACT FROM AUTHOR]

Background: Evidence has emerged that anemia is associated with dementia, but data on the relationships of red blood cell distribution width (RDW) with dementia and cognitive function in older adults are sparse.Objective: We sought to investigate the associations of RDW with dementia and global cognitive performance among rural-dwelling Chinese older adults and further to examine their associations by anemia status.Methods: This population-based cross-sectional study included 5,115 participants (age≥65 years, 57.0%women) in the baseline examination (March-September 2018) of the Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-CHINA). We collected data through face-to-face interviews, clinical examinations, and laboratory tests. Global cognitive function was evaluated using the Mini-Mental State Examination (MMSE). We defined dementia, Alzheimer's disease (AD), and vascular dementia (VaD) following the respective international criteria. Data were analyzed using multinomial logistic and general linear regression models.Results: Of all participants, 300 were diagnosed with dementia, including 195 with AD and 95 VaD. The multiple-adjusted odds ratio of dementia associated with quartiles of RDW were 1.45 (95%CI: 0.87-2.44), 1.00 (reference), 1.77 (1.07-2.93), and 2.28 (1.40-3.72). Similar J-shaped patterns existed for the association of RDW with odds ratio of AD and VaD. Anemia was not significantly associated with dementia. The J-shaped associations of RDW with dementia and subtypes were statistically evident only among participants without anemia. There was an inverted J-shaped relationship between RDW quartiles and β-coefficients of MMSE score.Conclusion: There is a J-shaped association between RDW level and likelihood of dementias among rural-dwelling Chinese older adults, especially among people without anemia. [ABSTRACT FROM AUTHOR]

Background and purpose: Current evidence supports the involvement of lipids in brain aging. A range of serum lipids is explored in association with brain structure and cognitive function amongst rural‐dwelling older adults. Methods: This population‐based cross‐sectional study included 184 rural‐dwelling adults (age ≥ 65 years, 39.1% women) in Shandong, China. In 2014–2016, data on demographics, lifestyle, health conditions and serum lipids were collected. Volumes of gray matter, white matter, ventricles, hippocampus and white matter hyperintensity were automatically estimated on brain magnetic resonance imaging. Global cognitive function was assessed with the Mini‐Mental State Examination (MMSE), and mild cognitive impairment (MCI) was defined according to Petersen's criteria. Data were analyzed using the general linear regression, logistic regression and mediation models. Results: Of the 184 participants, 47 were defined with MCI. Low high‐density lipoprotein cholesterol (HDL‐C; <1.55 vs. ≥1.55 mmol/l) was significantly associated with reduced volumes of total white matter (multi‐adjusted β = −9.77, 95% confidence interval −19.48–0.06) and hippocampus (−0.23, −0.46–0.01), a lower MMSE score (−1.49, −2.67–0.31) and a higher likelihood of MCI (multi‐adjusted odds ratio 3.21, 95% confidence interval 1.42–7.29). The mediation effects of structural brain measures on the associations between a low level of HDL‐C and MMSE score or MCI were not statistically significant (p > 0.05). Conclusions: This study suggests that low HDL‐C may be involved in structural brain aging and cognitive dysfunction amongst rural‐dwelling older adults in China, but the association of low HDL‐C with cognitive aging phenotypes appears not to be mediated by brain structure. [ABSTRACT FROM AUTHOR]