Authors: Shi, Xiaolei | Zhou, Nan | Sun, Bin | Wu, Yongshun | Hu, Yachun | Ning, Yuping
Article Type: Research Article
Abstract: Background: Reduced signal on fluorodeoxyglucose-positron emission tomography (FDG-PET) is a valid proxy for neurodegeneration in Alzheimer’s disease (AD). Perivascular space (PVS) is believed to be associated with AD pathology and cognitive decline. Objective: This study aimed to investigate the associations of PVS with FDG-PET and cognitive performance based on the burden of amyloid pathology. Methods: We used magnetic resonance imaging (MRI) data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). MRI-visible PVS in basal ganglia (BG) and centrum semi-oval (CSO) were visually classified as: none/mild, moderate or frequent/severe. The association of PVS with brain FDG-PET was explored based on the burden …of amyloid pathology, where a cerebrospinal fluid (CSF) t-tau/Aβ42 with the ratio≥0.27 was defined as high amyloid pathology. Moreover, the relationships between PVS and cognitive performance variables (ADNI-MEM and ADNI-EF) were studied. Results: For participants with higher tau/Aβ42 ratio, CSO-PVS severity was independently associated with lower FDG-PET. There were significant interaction effects between moderate or frequent/severe CSO-PVS and time on FDG decline in people with high amyloid pathology. The interaction between CSO-PVS and time (follow-up) was consistently associated with ADNI-MEM and ADNI-EF decline in individuals with high amyloid pathology. Conclusion: The study established the differential utility of PVS in BG and CSO for predicting brain metabolism. These findings suggest that CSO-PVS serves as a contributing factor to brain metabolism and cognitive decline associated with amyloid pathology. Show more
Keywords: Amyloid, basal ganglia, centrum semi-oval, metabolism, perivascular space
DOI: 10.3233/JAD-220426
Citation: Journal of Alzheimer's Disease, vol. 90, no. 3, pp. 1329-1337, 2022
Authors: Chen, Ben | Zhong, Xiaomei | Mai, Naikeng | Peng, Qi | Zhang, Min | Chen, Xinru | Wu, Zhangying | Zou, Laiquan | Liang, Wanyuan | Ouyang, Cong | Wu, Yujie | Ning, Yuping
Article Type: Research Article
Abstract: Olfactory identification (OI) deficits have been regarded as an indicator of cognitive impairment in the elderly, but few studies have analyzed the mixed effect of depression on OI. Since depression is common in the elderly and strongly associated with OI, we aimed to explore whether the comorbidity of depression and cognitive impairment may be associated with worse outcomes. In total, 153 elderly patients with depression and 154 normal elderly were recruited. Subjects underwent assessments of depression, cognitive function, and OI. Information on the factors that may affect OI performance was collected (age, sex, smoking history, diabetes, etc.). Correlation analysis showed …that several factors had a significant influence on OI performance in the elderly, including severity of depression, cognitive scores, age, sex, and years of education (p < 0.05). Among the different cognitive domains, OI was positively associated with global cognition, memory, language, executive function, and attention performance (p < 0.05). The multiple linear regression analysis indicated that memory scores, age, HAMD scores, and sex were the most relevant factors to OI scores across all elderly participants. The factorial analysis suggested that elderly with comorbidity of depression and cognitive impairment (memory deficits or language deficits) had worse OI impairment, and there was an interactive effect of depression and memory deficits on OI in elderly people. The present study suggested that the coexistence of depressive symptoms and cognitive impairment was associated with worse OI in the elderly. Studies exploring the association between OI and cognitive function should include an assessment of depression and adjust the interactive effects of depression. Show more
Keywords: Cognition, depression, geriatric, neuropsychology, olfactory
DOI: 10.3233/JAD-180760
Citation: Journal of Alzheimer's Disease, vol. 66, no. 4, pp. 1645-1655, 2018
Authors: Jia, Jianping | Ji, Yong | Feng, Tao | Ye, Qinyong | Peng, Dantao | Kuang, Weihong | Ning, Yuping | Liang, Zhihou | Fan, Dongsheng | Wei, Wenshi | Li, Yansheng | Xiao, Shifu
Article Type: Research Article
Abstract: Background: Rivastigmine is a cholinesterase inhibitor, approved for the treatment of mild-to-moderate dementia of Alzheimer’s type. Objective: To explore the efficacy and safety of the maximal tolerated dose of rivastigmine capsules in Chinese patients with mild-to-moderate Alzheimer’s disease (AD). Methods: The study was a multicenter, open-label, single-arm, phase IV clinical study in mild-to-moderate drug-naïve AD patients treated with rivastigmine capsules. The primary endpoint was the changes in the total scores of Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) from baseline to week 16. Secondary endpoints included changes in the scores of the following assessment scales and safety: Alzheimer’s Disease Cooperative Study; …Activities of Daily Living; Mini-Mental Status Examination (MMSE); Neuropsychiatry Index (NPI), and Caregiver Burden Inventory. Results: 222 patients were enrolled. Of these, 136 (75.1%) patients received and maintained the effective dose (≥6 mg/d) of rivastigmine for at least 4 weeks. The ADAS-Cog scale score improved in rivastigmine-treated patients at week 16 compared with baseline (p < 0.001) by 2.0 (95% CI: –3.0 to –1.1) points, which met the pre-defined superiority criteria. NPI-10 and NPI-12 scores improved by 3.6 and 4.0 points at week 16 (p = 0.001, p < 0.001), respectively. A total of 107 patients (59.1%) experienced adverse effects (AEs) during the study; common AEs included nausea (20.5%), vomiting (16.6%), anorexia (7.8%), dizziness (7.7%), and diarrhea (7.2%). Conclusion: This was the first phase IV study on rivastigmine in mainland China. The study preliminarily demonstrated that rivastigmine capsules showed good tolerability and efficacy in mild-to-moderate AD patients with the maximal tolerated dose. Show more
Keywords: Alzheimer’s disease, capsule, Chinese population, rivastigmine
DOI: 10.3233/JAD-190791
Citation: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1313-1322, 2019
Authors: Zhong, Xiaomei | Shi, Haishan | Shen, Zhiwei | Hou, Le | Luo, Xinni | Chen, Xinru | Liu, Sha | Zhang, Yuefeng | Zheng, Dong | Tan, Yan | Huang, Guimao | Fang, Yaxiu | Zhang, Hui | Mu, Nan | Chen, Jianping | Wu, Renhua | Ning, Yuping
Article Type: Research Article
Abstract: FDG-PET and SPECT studies suggest that hypometabolism and hypoperfusion in occipital lobe and posterior cingulate gyrus (PCG) are prominent features of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), respectively. Cerebral blood flow and glucose metabolism are tightly linked to brain energy metabolism. 1 H-MRS is a useful tool to directly detect energy metabolism. We aimed to use 1 H-MRS to characterize metabolite concentrations in the occipital lobe and PCG in DLB and AD patients, and estimate their usefulness in the diagnosis of DLB. Nineteen DLB, 21 AD, and 18 normal control (NC) subjects underwent 1 H-MRS with the …voxels placed in bilateral occipital lobes and left PCG. The N-acetylaspartate (NAA) and glutamate (Glu) concentrations in occipital lobe in DLB were lower than those in AD and NC. Concentrations of these two metabolites in PCG in DLB were lower than those in NC, and were the same as those in AD. These results remained robust after correcting for relative gray matter volume in the region of interest. The NAA and Glu concentrations in occipital lobe in DLB were found correlated with global cognitive function. From the ROC curves with Glu concentrations in occipital lobe, the mean areas under the curve were 0.845 for the DLB/control (with sensitivity 83.3% and specificity 84.2%) and 0.773 for the DLB/AD (with sensitivity 66.7% and specificity 84.2%). Our study suggests that 1 H-MRS investigation is valuable to detect the characteristic patterns of metabolite concentrations and is helpful in the diagnostic process and assessing dementia severity in DLB. Show more
Keywords: Dementia with Lewy bodies, Alzheimer's disease, diagnosis, differential diagnosis, hydrogen proton magnetic resonance spectroscopy, occipital lobe, posterior cingulate gyrus
DOI: 10.3233/JAD-131517
Citation: Journal of Alzheimer's Disease, vol. 40, no. 4, pp. 953-966, 2014
Authors: Wang, Qiang | Chen, Ben | Zhong, Xiaomei | Zhou, Huarong | Zhang, Min | Mai, Naikeng | Wu, Zhangying | Huang, Xingxiao | Haehner, Antje | Chen, Xinru | Auber, Lavinia Alberi | Peng, Qi | Hummel, Thomas | Ning, Yuping
Article Type: Research Article
Abstract: Background: Odor identification dysfunction occurs early in Alzheimer’s disease (AD) and is considered a preclinical symptom along with subjective cognitive decline (SCD). Nevertheless, whether subjects with SCD are co-symptomatic with odor identification dysfunction remains unclear. Objective: To compare the degree of odor identification dysfunction and assess the relation between odor identification and cognitive performance in the AD spectrum (including SCD, mild cognitive impairment (MCI), and AD). Methods: Patients (84 SCD, 129 MCI, 52 AD) and 35 controls underwent the Sniffin’ Sticks Screen 16 test and comprehensive neuropsychological examination. Results: Odor identification scores were progressively lower moving from normal older adult …to SCD, MCI, and AD. Additionally,the proportion of odor identification dysfunction were increasingly higher in the AD spectrum (p for trend <0.001), but no significant difference was found in the proportion of subjective olfactory dysfunction. No significant correlation was found between odor identification and cognition in the normal older adults and SCD subjects, but odor identification correlated with global cognition in the MCI (r = 0.199, p = 0.033) and in the AD (r = 0.300, p = 0.036) patients. Multiple linear regression showed that odor identification dysfunction was most strongly associated with memory among different cognitive subdomains and was most strongly associated with immediate verbal recall among different memory subdomains. Conclusion: Odor identification dysfunction is already present with SCD and deepens with disease severity in the AD spectrum, and it may contribute to predicting cognitive decline and identifying SCD subjects who are at risk of developing AD. Show more
Keywords: Alzheimer’s disease, mild cognitive impairment, neuropsychology, olfactory dysfunction, subjective cognitive decline
DOI: 10.3233/JAD-201168
Citation: Journal of Alzheimer's Disease, vol. 79, no. 2, pp. 585-595, 2021
Authors: Zhang, Min | Zhong, Xiaomei | Shi, Haishan | Vanmechelen, Eugeen | De Vos, Ann | Liu, Sen | Chen, Ben | Mai, Naikeng | Peng, Qi | Chen, Xinru | Wu, Zhangying | Hou, Le | Zhou, Huarong | Ouyang, Cong | Zhang, Weiru | Liang, Wanyuan | Dai, Chunying | Ning, Yuping
Article Type: Research Article
Abstract: Background: Patients with spirochetal infection, which causes neurosyphilis (NS) and at a later stage general paresis of the insane (GPI), present with brain pathology features of Alzheimer’s disease (AD). However, the relationships among these illnesses regarding biomarker levels are still unclear. Objective: To explore biomarker levels in NS and GPI compared with those in AD and the relationship between biomarker levels and cognitive function in NS and GPI. Methods: Levels of neurogranin (NGRN) and β-amyloid precursor protein cleaving enzyme (BACE1) in cerebrospinal fluid (CSF)/plasma, together with amyloid-β 1–40 (Aβ40 ), Aβ42 , and total tau in the CSF of 23 …AD patients, 55 GPI patients, and 13 NS patients were measured. Patients were classified into none-to-mild, moderate, and severe stages of cognitive impairment. Results: Levels of CSF NGRN, BACE1, and tau as well as plasma BACE1 levels were significantly different among groups. In the none-to-mild stage, plasma BACE1 levels correlated with the protein levels in CSF and were significantly increased in AD patients versus GPI patients. The CSF tau levels in AD patients were significantly increased versus GPI patients in the moderate and severe stages. Pooling data from GPI and NS patients, both CSF tau and plasma NGRN levels correlated with cognitive scale scores. Conclusion: GPI and NS patients might have different biomarker level patterns compared to AD patients. While plasma BACE1 could be a promising early biomarker for distinguishing AD from GPI, CSF tau and plasma NGRN levels might be valuable in indications of cognitive function in pooled NS populations. Show more
Keywords: Alzheimer’s disease, BACE1, general paresis of insane, neurogranin, neurosyphilis
DOI: 10.3233/JAD-200362
Citation: Journal of Alzheimer's Disease, vol. 77, no. 1, pp. 313-322, 2020
Authors: Yang, Mingfeng | Chen, Ben | Zhou, Huarong | Mai, Naikeng | Zhang, Min | Wu, Zhangying | Peng, Qi | Wang, Qiang | Liu, Meiling | Zhang, Si | Lin, Gaohong | Lao, Jingyi | Zeng, Yijie | Zhong, Xiaomei | Ning, Yuping
Article Type: Research Article
Abstract: Background: Both late-life depression (LLD) and short sleep duration increase the risk of cognitive impairment. Increased insular resting-state functional connectivity (FC) has been reported in individuals with short sleep duration and dementia. Objective: This study aimed to investigate whether short sleep duration is associated with impaired cognition and higher insular FC in patients with LLD. Methods: This case– control study recruited 186 patients with LLD and 83 normal controls (NC), and comprehensive psychometric assessments, sleep duration reports and resting-state functional MRI scans (81 LLD patients and 54 NC) were conducted. Results: Patients with LLD and short sleep duration (LLD-SS patients) …exhibited more severe depressive symptoms and worse cognitive function than those with normal sleep duration (LLD-NS patients) and NC. LLD-SS patients exhibited higher FC between the bilateral insula and inferior frontal gyrus (IFG) pars triangularis than LLD-NS patients and NC, while LLD-NS patients exhibited lower FC than NC. Increased insular FC was correlated with short sleep duration, severe depressive symptoms, and slower information processing speeds. Furthermore, an additive effect was found between sleep duration and LLD on global cognition and insular FC. Conclusion: LLD-SS patients exhibited impaired cognition and increased insular FC. Abnormal FC in LLD-SS patients may be a therapeutic target for neuromodulation to improve sleep and cognitive performance and thus decrease the risk of dementia. Show more
Keywords: Alzheimer’s disease, cognitive impairment, functional connectivity, late-life depression, MRI, sleep duration
DOI: 10.3233/JAD-220968
Citation: Journal of Alzheimer's Disease, vol. 93, no. 4, pp. 1317-1327, 2023