Authors: Cao, Qiao-Ling | Sun, Yan | Hu, Hao | Wang, Zuo-teng | Tan, Lan | Yu, Jin-Tai
Article Type: Research Article
Abstract: Background: The links between cerebral small vessel disease (CSVD) burden and neuropsychiatric symptoms (NPS) have not been fully studied. Objective: We aimed to explore the associations of the CSVD burden with Neuropsychiatric Inventory (NPI) total scores and its subsyndromes in the elderly without dementia. Methods: We investigated 630 non-demented participants from the Alzheimer’s Disease Neuroimaging Initiative. All of them had NPI assessments and 3 Tesla MRI scans at baseline and 616 had longitudinal NPI assessments during the follow-up. Linear mixed-effects models were used to investigate the cross-sectional and longitudinal associations of CSVD burden with NPI total scores and its subsyndromes. …Results: Higher CSVD burden longitudinally predicted more serious neuropsychiatric symptoms, including NPS (p < 0.0001), hyperactivity (p = 0.0006), affective symptoms (p = 0.0091), and apathy (p < 0.0001) in the total participants. Lacunar infarcts (LIs), white matter hyperactivities (WMHs), and cerebral microbleeds (CMBs) might play important roles in the occurrence of NPS, since they were longitudinally associated with specific neuropsychiatric subsyndromes. LIs contributed to hyperactivity (p = 0.0092), psychosis (p = 0.0402), affective symptoms (p = 0.0156), and apathy (p < 0.0001). WMHs were associated with hyperactivity (p = 0.0377) and apathy (p = 0.0343). However, CMBs were only related to apathy (p = 0.0141). Conclusion: CSVD burden was associated with multiple neuropsychiatric symptoms, suggesting the importance of monitoring and controlling vascular risk factors. Different markers of CSVD were associated with specific subsyndromes of NPS, suggesting that different markers tended to occur in different encephalic regions. Show more
Keywords: Alzheimer’s Disease Neuroimaging Initiative, cerebral small vessel disease burden, neuropsychiatric subsyndrome, non-demented elders
DOI: 10.3233/JAD-220128
Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 583-592, 2022
Authors: Huang, Liang-Yu | Hu, He-Ying | Wang, Zuo-Teng | Ma, Ya-Hui | Dong, Qiang | Tan, Lan | Yu, Jin-Tai
Article Type: Research Article
Abstract: 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 < 0.01) for MCI. In terms of work complexity, higher work complexity conferred a 5% reduced risk (95% CI = 0.91–1.00, I² = 57.00%, p < 0.01) for dementia. In terms of occupational exposure, high strain and passive job in the longest-held job conferred a 1.21- and 1.15-fold excess risk (95% CI = 1.05–1.39 I² = 62.00%, p < 0.05; 95% CI = 1.05–1.26 I² = 31.00%, p = 0.23; respectively) of cognitive decline. Besides, magnetic field exposure conferred a 1.26-fold excess risk (95% CI = 1.01–1.57, I² = 69.00%, p < 0.01) for dementia. Conclusion: Novel prevention strategies based on occupational factors may hold promise against dementia and MCI. Show more
Keywords: Dementia, job strain, meta-analysis, occupation, occupational exposure, work complexity
DOI: 10.3233/JAD-200605
Citation: Journal of Alzheimer's Disease, vol. 78, no. 1, pp. 217-227, 2020
Authors: Wang, Yan-Li | Chen, Wei | Cai, Wen-Jie | Hu, Hao | Xu, Wei | Wang, Zuo-Teng | Cao, Xi-Peng | Tan, Lan | Yu, Jin-Tai | Alzheimer’s Disease Neuroimaging Initiative
Article Type: Research Article
Abstract: White matter hyperintensities (WMHs), mainly caused by cerebrovascular injury, may lead to cognitive impairment. In order to identify whether the volume of WMHs is associated with cognitive decline over years, this longitudinal study involved 818 individuals from the ADNI-2 dataset from August 2010 to May 2017. Cross-sectional and longitudinal associations of WMHs with 8 cognitive domains were explored, using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating Sum of Boxes (CDRSB), Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog13), Rey Auditory Verbal Learning Test (RAVLT), Functional Assessment Questionnaire (FAQ), executive function (ADNI-EF), and memory function (ADNI-Mem). The association analyses were …performed using multiple linear regression models, linear mixed models, Spearman rank correlation, and Kaplan-Meier survival curves. The volumes of WMHs were greater in patients with Alzheimer’s disease (AD) dementia compared with controls (p < 0.001) and mild cognitive impairment (p = 0.006) patients at baseline. The bigger volumes of WMHs correlated with worse performances on ADAS-Cog13 and ADNI-EF (p = 0.029; p = 0.003) at baseline and MMSE, MoCA, CDRSB, ADAS-Cog13, FAQ, and ADNI-Mem (overall p < 0.05) longitudinally, after adjusting for age, sex, educational level, apolipoprotein E ɛ 4 genotype, hypertension, hyperlipidemia, diabetes, smoking, infarction, and diagnosis. Additionally, the correlations between the change rate of WMHs and change rates of MMSE, MoCA, CDRSB, FAQ, ADNI-EF, and ADNI-Mem were statistically significant. Furthermore, patients with high WMH volumes showed an increased likelihood of dementia. The results of the study suggest that WMH volume is associated with cognitive decline, and it contributes to the conversion to AD. Show more
Keywords: Alzheimer’s disease, Alzheimer’s Disease Neuroimaging Initiative, cognition, white matter hyperintensities
DOI: 10.3233/JAD-191005
Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 759-768, 2020
Authors: Sun, Yan | Tan, Lin | Xu, Wei | Wang, Zuo-Teng | Hu, Hao | Li, Jie-Qiong | Dong, Qiang | Tan, Lan | Yu, Jin-Tai | on behalf of Alzheimer’s Disease Neuroimaging Initiative
Article Type: Research Article
Abstract: White matter hyperintensities (WMH) is mainly caused by cerebrovascular injury and may also increase the possibilities of progression to Alzheimer’s disease. The present study aims to determine whether plasma neurofilament light (NFL) protein levels could predict the progression of WMH volume in elderly persons without dementia. The present study enrolled 1029 non-dementia participants from the Alzheimer’s Disease Neuroimaging Initiative in which all had measurements of plasma NFL and WMH at baseline and 589 had longitudinal measurements during follow-up. Spearman correlation analyses and regression models were used to assess cross-sectional and longitudinal associations between plasma NFL and WMH. Plasma NFL concentration …had a moderately strong correlation with WMH at baseline (r = 0.17, p < 0.001). Longitudinal analyses showed that higher baseline plasma NFL concentration was associated with accelerated progression of WMH (β=0.015, p = 0.007). Furthermore, higher change rates of plasma NFL could predict faster progression of WMH in the future (β=0.581, p = 0.002). The results of the study suggest that plasma NFL level might be used as a noninvasive biomarker to track variation trend in WMH in elderly persons without dementia. Show more
Keywords: Alzheimer’s disease neuroimaging initiative, cognitively decline, non-dementia elders, noninvasive biomarker, plasma neurofilament light protein, white matter hyperintensity
DOI: 10.3233/JAD-200022
Citation: Journal of Alzheimer's Disease, vol. 75, no. 3, pp. 729-737, 2020
Authors: Fu, Yan | Wang, Zuo-Teng | Qu, Yi | Wang, Xiao-Tong | Ma, Ya-Hui | Bi, Yan-Lin | Dong, Qiang | Tan, Lan | Yu, Jin-Tai
Article Type: Research Article
Abstract: Background: The associations between sleep characteristics and cognition are complicated. Alzheimer’s disease (AD) pathologies have been proven to be associated with sleep characteristics. Objective: We aimed to investigate the associations between sleep characteristics and cognitive function and examine the roles of AD pathologies in modulating the association of sleep duration with cognition. Methods: A total of 974 participants who had measurements of cerebrospinal fluid (CSF) amyloid-β (Aβ), phosphorylated tau (P-tau), total tau proteins (T-tau), cognitive function, and sleep characteristics were included from the Chinese Alzheimer’s Biomarker and Lifestyle (CABLE) study. Linear regression analyses were utilized to explore the associations of …sleep characteristics with cognition. Non-linear regression analyses were utilized to explore the associations of sleep habits with cognition. Causal mediation analyses were conducted to explore the mediation effects of AD pathologies on cognition. Results: The Pittsburgh Sleep Quality Index (PSQI) total score was significantly negatively correlated with Montreal Cognitive Assessment (MoCA) score (p = 0.0176). Long latency (p = 0.0054) and low efficiency (p = 0.0273) were associated with cognitive impairment. Habitual nap behavior was associated with lower MoCA scores (p = 0.0045). U-shaped associations were observed between sleep habits (bedtime and nocturnal sleep duration) and cognition. A causal mediation analysis indicated that P-tau/Aβ42 mediated the association of sleep duration with cognition. Conclusion: These findings showed sleep characteristics were associated with cognitive functions. Sleep habits (duration, bedtime) had U-shaped associations with cognition. AD core pathologies might partially mediate the influence of sleep duration on cognitive impairments. Show more
Keywords: Alzheimer’s disease, cerebrospinal fluid, cognition, montreal cognitive assessment, sleep
DOI: 10.3233/JAD-215017
Citation: Journal of Alzheimer's Disease, vol. 84, no. 3, pp. 1029-1038, 2021
Authors: Zhang, Peng-Fei | Wang, Zuo-Teng | Liu, Ying | Hu, Hao | Sun, Yan | Hu, He-Ying | Ma, Ya-Hui | Tan, Lan | Yu, Jin-Tai
Article Type: Research Article
Abstract: Background: Inflammation plays a role in occurrence and progression of Alzheimer’s disease (AD). Whether peripheral immune cells are involved in major pathological processes including amyloid-β plaques and tau tangles is still controversial. Objective: We aimed to examine whether peripheral immune cells counts were associated with early changes in cerebrospinal fluid (CSF) biomarkers of AD pathology in cognitively intact older adults. Methods: This study included 738 objective cognitive normal participants from the Chinese Alzheimer’s Biomarker and Lifestyle (CABLE) database. Group comparisons of peripheral immune cells counts were tested by analysis of covariance. Multiple linear regression models were used to examine the …associations of peripheral immune cells counts with CSF AD biomarkers. Results: In preclinical AD, peripheral lymphocytes and eosinophils changed dynamically along with disease progression. Consistently, regression analysis showed that lymphocytes and eosinophils were associated with Aβ pathology. There were no interaction effects of peripheral immune cells counts with APOE ɛ4, gender, age, and educate. Eosinophil to lymphocyte ratio were also significantly associated with Aβ-related biomarkers. Conclusion: Our findings showed the relationship between peripheral immune cells and Aβ pathological biomarkers, which indicated that peripheral immune might play a role in progression of AD pathology. Show more
Keywords: Alzheimer’s disease, cerebrospinal fluid, inflammation, pathology, peripheral immune cells
DOI: 10.3233/JAD-220057
Citation: Journal of Alzheimer's Disease, vol. 87, no. 2, pp. 721-730, 2022
Authors: Liu, Ying | Han, Pei-Ran | Hu, Hao | Wang, Zuo-Teng | Guo, Yu | Ou, Ya-Nan | Cao, Xi-Peng | Tan, Lan | Yu, Jin-Tai | Alzheimer’s Disease Neuroimaging Initiative
Article Type: Research Article
Abstract: Background: In the 2018 AT(N) framework, neurodegenerative (N) biomarkers plays an essential role in the research and staging of Alzheimer’s disease (AD); however, the different choice of N may result in discordances. Objective: We aimed to compare different potential N biomarkers. Methods: We examined these N biomarkers among 1,238 participants from Alzheimer’s Disease Neuroimaging Initiative (ADNI) in their 1) diagnostic utility, 2) cross-sectional and longitudinal correlations between different N biomarkers and clinical variables, and 3) the conversion risk of different N profiles. Results: Six neurodegenerative biomarkers changed significantly from preclinical AD, through prodromal AD to AD dementia stage, thus they …were chosen as the candidate N biomarkers: hippocampal volume (HV), 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET), cerebrospinal fluid (CSF), total tau (T-tau), plasma neurofilament light chain (NFL), CSF NFL, and CSF neurogranin (Ng). Results indicated that FDG-PET not only had the greatest diagnostic utility in differentiating AD from controls (area under the curve: FDG-PET, 0.922), but also had the strongest association with cognitive scores. Furthermore, FDG-PET positive group showed the fastest memory decline (hazard ratio: FDG-PET, 3.45), which was also true even in the presence of amyloid-β pathology. Moreover, we observed great discordances between three valuable N biomarkers (FDG-PET, HV, and T-tau). Conclusion: These results underline the importance of using FDG-PET as N in terms of cognitive decline and AD conversion, followed by HV, and could be a great complement to the AT(N) framework. Show more
Keywords: Alzheimer’s disease, Alzheimer’s disease neuroimaging initiative, AT(N), biomarker, FDG, neurodegeneration
DOI: 10.3233/JAD-215724
Citation: Journal of Alzheimer's Disease, vol. 87, no. 1, pp. 197-209, 2022
Authors: Huang, Yu-Yuan | Chen, Shi-Dong | Leng, Xin-Yi | Kuo, Kevin | Wang, Zuo-Teng | Cui, Mei | Tan, Lan | Wang, Kai | Dong, Qiang | Yu, Jin-Tai
Article Type: Review Article
Abstract: Stroke, characterized as a neurological deficit of cerebrovascular cause, is very common in older adults. Increasing evidence suggests stroke contributes to the risk and severity of cognitive impairment. People with cognitive impairment following stroke often face with quality-of-life issues and require ongoing support, which have a profound effect on caregivers and society. The high morbidity of post-stroke cognitive impairment (PSCI) demands effective management strategies, in which preventive strategies are more appealing, especially those targeting towards modifiable risk factors. In this review article, we attempt to summarize existing evidence and knowledge gaps on PSCI: elaborating on the heterogeneity in current definitions, …reporting the inconsistent findings in PSCI prevalence in the literature, exploring established or less established predictors, outlining prevention and treatment strategies potentially effective or currently being tested, and proposing promising directions for future research. Show more
Keywords: Cognitive dysfunction, epidemiology, prevention, screening, stroke, treatment
DOI: 10.3233/JAD-215644
Citation: Journal of Alzheimer's Disease, vol. 86, no. 3, pp. 983-999, 2022
Authors: Yu, Guang-Xiang | Zhang, Ting | Hou, Xiao-He | Ou, Ya-Nan | Hu, Hao | Wang, Zuo-Teng | Guo, Yu | Xu, Wei | Tan, Lin | Yu, Jin-Tai | Tan, Lan | Alzheimer’s Disease Neuroimaging Initiative
Article Type: Research Article
Abstract: Background: Increasing evidence supports an important role of vascular risk in cognitive decline and dementia. Objective: This study aimed to examine whether vascular risk was associated with cognitive decline, cerebral hypometabolism, and clinical progression in cognitively intact elders. Methods: Vascular risk was assessed by the Framingham Heart Study general Cardiovascular disease (FHS-CVD) risk score. The cross-sectional and longitudinal associations of FHS-CVD risk score with cognition and brain glucose metabolism were explored using multivariate linear regression and linear mixed effects models, respectively. The risk of clinical progression conversion was assessed using Kaplan-Meier survival curves and multivariate Cox proportional hazard models. Results: …A total of 491 cognitively intact elders were included from Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Participants with high FHS-CVD risk scores had lower baseline Mini-Mental State Examination (MMSE) (p = 0.009), executive function (EF) (p < 0.001), memory function (MEM) (p < 0.001) scores, and F18-fluorodeoxyglucose positron emission tomography (FDG-PET) uptake (p < 0.001) than those with low FHS-CVD risk scores. In longitudinal analyses, individuals with higher FHS-CVD risk scores had greater longitudinal declines in MMSE (p = 0.043), EF (p = 0.029) scores, and FDG-PET uptake (p = 0.035). Besides, individuals with a higher vascular risk had an increased risk of clinical progression (p = 0.004). Conclusion: These findings indicated effects of vascular risk on cognitive decline, cerebral hypometabolism, and clinical progression. Early detection and management of vascular risk factors might be useful in the prevention of dementia. Show more
Keywords: Clinical progression, cognition, dementia, FDG-PET, vascular risk
DOI: 10.3233/JAD-201117
Citation: Journal of Alzheimer's Disease, vol. 80, no. 1, pp. 321-330, 2021
Authors: Wang, Zuo-Teng | Li, Kun-Yan | Tan, Chen-Chen | Xu, Wei | Shen, Xue-Ning | Cao, Xi-Peng | Wang, Ping | Bi, Yan-Lin | Dong, Qiang | Tan, Lan | Yu, Jin-Tai
Article Type: Research Article
Abstract: Background: The relationship between alcohol consumption and Alzheimer’s disease (AD) pathology is unclear. Amyloid-β (Aβ) and tau biomarkers in cerebrospinal fluid (CSF) have been proven valuable in establishing prognosis in pre-clinical AD. Objective: We sought to examine the associations between alcohol consumption and CSF AD biomarkers in cognitive intact subjects. Methods: A total of 806 cognitively intact participants who had measurements of CSF Aβ, pTau, and total Tau proteins and drinking characteristics were included from the Chinese Alzheimer’s Biomarker and Lifestyle (CABLE) study. Linear and logistic regression analyses were utilized to explore the associations of alcohol consumption with CSF AD …biomarkers. We examined the interaction effects of age, gender, and apolipoprotein epsilon (APOE ) ɛ4 status on the relationships between the frequency of drinking and CSF biomarkers. Results: The multiple linear regression analyses revealed significant differences in CSF AD biomarkers between infrequent drinking (< 1 times/week) and frequent drinking groups (≥1 times/week). Participants in frequent drinking group had higher CSF p-tau/Aβ42 and tTau/Aβ42 . Frequent drinking was significantly associated with greater pTau and tTau abnormalities compared to the infrequent drinking group in older (> 65 years) participants. Conclusion: The present study showed significant associations between drinking frequency and CSF AD biomarkers in cognitively intact older adults. Alcohol consumption may have an influence on AD by modulating amyloid deposition and tau phosphorylation in the preclinical stage. Show more
Keywords: Alcohol consumption, Alzheimer’s disease, amyloid, cerebrospinal fluid, magnetic resonance imaging, tau proteins
DOI: 10.3233/JAD-210140
Citation: Journal of Alzheimer's Disease, vol. 82, no. 3, pp. 1045-1054, 2021