Authors: Zhao, Qianhua | Xiong, Yunyun | Ding, Ding | Guo, Qihao | Hong, Zhen
Article Type: Research Article
Abstract: Diabetes is thought to contribute to cognitive impairment in the elderly. The risk may be modified by genetic factors such as apolipoprotein E (APOE). We aim to determine the prevalence of dementia in Chinese diabetics and non-diabetic individuals, and assess the effect of the APOE genotype. A cross-sectional study was conducted among participants aged 50 and over in an urban community. Subjects were 1 : 1 matched for age and gender (diabetes group (n = 497) versus non-diabetes group (n = 497)). Each subject was interviewed for dementia and related risk factors. Fasting blood samples were drawn for glucose and …APOE. Subjects were screened using the Mini Mental State Examination (MMSE) and were examined by a series of neuropsychological tests if screened positive (indicated by an MMSE score below 19, 21, and 24, respectively according to different educational attainment). A diagnosis of dementia was defined according to DSM-IV criteria. The prevalence of all-cause dementia, Alzheimer's disease, and vascular dementia in diabetics (4.8%, 2.7%, 1.4%) was higher than that of non-diabetics (2.2%, 1.2%, 0.4%) (all-cause dementia, diabetics versus non-diabetics, p < 0.05). APOE ε4 carriers had higher prevalence of dementia and AD (diabetics: 9.2%, 7.55%, non-diabetics: 3.3%, 3.3%) than APOE ε4 non-carriers (diabetics: 6.3%, 2.3%, non-diabetics: 2.35%, 0.7%) (p < 0.05). Diabetics carrying the APOE ε4 allele had a 3.982-fold [95%CI, 1.418–11.184] likelihood of having dementia compared with those without these two factors. This study showed that the prevalence of dementia was significantly higher in diabetics than non-diabetics. APOE ε4 further enhanced the risk. Show more
Keywords: Alzheimer's disease, apolipoprotein E, dementia, diabetes
DOI: 10.3233/JAD-2012-120442
Citation: Journal of Alzheimer's Disease, vol. 32, no. 4, pp. 1019-1027, 2012
Authors: Wang, Zan | Dai, Zhengjia | Shu, Hao | Liu, Duan | Guo, Qihao | He, Yong | Zhang, Zhijun
Article Type: Research Article
Abstract: Both the apolipoprotein E (APOE) ɛ 4 allele and amnestic mild cognitive impairment (aMCI) are considered to be risk factors for Alzheimer’s disease (AD). The primary aim of this study was to determine whether the aMCI-related abnormality in gray matter (GM) cortical thickness and white matter (WM) tracts integrity would be modified by the APOE genotype. A total of 146 older adults, including 64 aMCI patients (28 ɛ 4 carriers and 36 non-carriers) and 82 healthy controls (39 ɛ 4 carriers and 43 non-carriers), underwent a standardized clinical interview, neuropsychological battery assessment, and multi-modal brain magnetic resonance imaging scans. Compared …with control subjects, the patients with aMCI showed significantly reduced cortical thickness bilaterally in the parahippocampal gyrus and disrupted WM integrity in the limbic tracts (e.g., increased mean diffusivity in the right parahippocampal cingulum and bilateral uncinate fasciculus). However, no significant main effects of the APOE genotype and diagnosis-by-genotype interaction on GM thickness and WM integrity were observed. Further, diffusivity measures of the limbic WM tracts were significantly correlated with the parahippocampal atrophy in aMCI. Importantly, the parahippocampal thickness and diffusivity measures of the limbic WM tracts were significantly correlated with the cognitive performance (i.e., episodic memory Z score) in patients with aMCI. These results demonstrate that WM microstructural disruptions in the limbic tracts are present at the early stage of AD in an APOE-independent manner; and this degeneration may occur progressively, in parallel with parahippocampal atrophy, and may specifically contribute to early initial impairment in episodic memory. Show more
Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, apolipoprotein E, cortical thickness, white matter integrity
DOI: 10.3233/JAD-160724
Citation: Journal of Alzheimer's Disease, vol. 56, no. 1, pp. 415-428, 2017
Authors: Zhou, Bin | Zhao, Qianhua | Teramukai, Satoshi | Ding, Ding | Guo, Qihao | Fukushima, Masanori | Hong, Zhen
Article Type: Research Article
Abstract: We aimed to investigate the natural history of Alzheimer's disease (AD) and the risk factors associated with survival. We performed a 5-year retrospective cohort study on 467 consecutive outpatients clinically diagnosed with AD and treated between January 1, 2003, and December 31, 2006, at Huashan Hospital, Shanghai, China. The primary endpoint in this study was survival. At baseline, we evaluated the patients' demographic characteristics and neuropsychological characteristics, comorbid conditions, neuroimaging findings, complications, and neurological signs. Among the 467 patients, 398 survived. Male gender, age, and disease severity were associated with mortality. Survival analysis using the proportional hazard model with adjustments …for gender, age, and disease stage revealed that the cognition factors that predicted longer survival included high total score [hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.76–0.96] and sub-scores in the verbal fluency test (animals, vegetables, and fruits). The presence of at least 1 complication was an independent factor predictive of a decreased lifespan (HR, 5.55; 95% CI, 1.91–16.13). In AD patients, presence of complications was an indicator of poor survival, while good performance in assessments of executive function, such as the verbal fluency test and Stroop test, at baseline was associated with longer survival. Show more
Keywords: Alzheimer's disease, complications, executive function, prognosis, retrospective longitudinal
DOI: 10.3233/JAD-2010-100318
Citation: Journal of Alzheimer's Disease, vol. 22, no. 2, pp. 673-682, 2010
Authors: Lin, Yijia | Hu, Tingjun | Cheng, Lizhen | Chen, Yixin | Li, Wei | Guo, Qihao | Miao, Ya
Article Type: Research Article
Abstract: Background: A connection between plasma levels of haptoglobin (Hp) and Alzheimer’s disease (AD) has been shown in several observational studies. It is debatable, nonetheless, how the two are related causally. Objective: To establish the causal relationship between Hp and AD using a two-sample Mendelian randomization (MR) study. Methods: From the extensive genome-wide association studies and FinnGen dataset, summaries and statistics pertaining to AD were gathered. We investigated the possibility of a causal link between Hp and AD using a two-sample MR study. Inverse variance weighting was used as the primary analytical technique, and it was supported by the joint application …of complementary analyses and fixed effects meta-analysis to combine results from various sources. Results: Genetically determined Hp was causally associated with AD [odds ratio (OR), 1.05; 95% confidence interval (CI), 1.02 to 1.09; p = 8.96×10–4 ]; Inverse variance-weighted estimates coming from different data sources were combined in a meta-analysis with consistent findings (OR, 1.03; 95% CI, 1.01 to 1.05; p = 2.00×10–3 ). The outcomes of the inverse MR analysis showed that AD had no appreciable causal impact on Hp. Conclusion: The present MR analysis shows that higher plasma Hp leads to an increased risk of AD. Strategies for plasma Hp testing may open up new doors for the early diagnosis and prevention of AD. Show more
Keywords: Alzheimer’s disease, causality, haptoglobins, Mendelian randomization analysis
DOI: 10.3233/JAD-230159
Citation: Journal of Alzheimer's Disease, vol. 95, no. 1, pp. 339-348, 2023
Authors: Huang, Lin | Li, Yatian | Wu, Jingnan | Chen, Nan | Xia, Huanhuan | Guo, Qihao
Article Type: Research Article
Abstract: Background: A rapid digital instrument is needed to facilitate community-based screening of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) in China. Objective: We developed a voice recognition-based cognitive assessment (Shanghai Cognitive Screening, SCS) on mobile devices and evaluated its diagnostic performance. Methods: Participants (N = 251) including healthy controls (N = 98), subjective cognitive decline (SCD, N = 42), MCI (N = 80), and mild AD (N = 31) were recruited from the memory clinic at Shanghai Sixth People’s Hospital. The SCS is fully self-administered, takes about six minutes and measures the function of visual memory, language, and executive function. Participants were instructed to complete SCS tests, gold-standard neuropsychological …tests and standardized structural 3T brain MRI. Results: The Cronbach’s alpha was 0.910 of the overall scale, indicating high internal consistency. The SCS total score had an AUC of 0.921 to detect AD (sensitivity = 0.903, specificity = 0.945, positive predictive value = 0.700, negative predictive value = 0.986, likelihood ratio = 16.42, number needed for screening utility = 0.639), and an AUC of 0.838 to detect MCI (sensitivity = 0.793, specificity = 0.671, positive predictive value = 0.657, negative predictive value = 0.803, likelihood ratio = 2.41, number needed for screening utility = 0.944). The subtests demonstrated moderate to high correlations with the gold-standard tests from their respective cognitive domains. The SCS total score and its memory scores all correlated positively with relative volumes of the whole hippocampus and almost all subregions, after controlling for age, sex, and education. Conclusion: The SCS has good diagnostic accuracy for detecting MCI and AD dementia and has the potential to facilitate large-scale screening in the general community. Show more
Keywords: Alzheimer’s disease, cognitive dysfunction, episodic memory, neuropsychology
DOI: 10.3233/JAD-230277
Citation: Journal of Alzheimer's Disease, vol. 95, no. 1, pp. 227-236, 2023
Authors: Miao, Ya | Cui, Liang | Li, Junpeng | Chen, Yixin | Xie, Xiangqing | Guo, Qihao
Article Type: Review Article
Abstract: Alzheimer’s disease (AD) is a degenerative disease of the central nervous system with insidious onset and chronic progression. The pathogenesis of AD is complex, which is currently considered to be the result of the interaction between genetic and environmental factors. The APOE ɛ4 is the strongest genetic risk factor for sporadic AD and a risk factor for progression from mild cognitive impairment (MCI) to AD. So far, no effective drugs have been found for the progression of MCI. However, the effects of nonpharmacological interventions such as nutrition, cognitive, and physical exercises on early AD have received increasing attention. We followed …up cognitive assessment scales, Aβ-PET and MRI examination of a patient with MCI for 4 years, who carried APOE ɛ4 homozygous with a clear family history. After 4 years of multi-domain lifestyle interventions including nutrition, socialization, and physical exercises, the patient’s cognitive function, especially memory function, improved significantly. Intracerebral amyloid deposition was decreased, and hippocampal atrophy improved. Based on this case, this study reviewed and discussed the interaction of APOE ɛ4 with the environment in AD research in recent years, as well as the impact and mechanisms of non-pharmaceutical multi-domain lifestyle interventions on MCI or early AD. Both the literature review and this case showed that multi-domain lifestyle interventions may reduce the risk of disease progression by reducing Aβ deposition in the brain and other different pathologic mechanisms, which offers promise in brain amyloid-positivity or APOE ɛ4 carriers. Show more
Keywords: Alzheimer’s disease, APOE, diet, genetic risk effect, mild cognitive impairment, nutrition, physical activities, social contacts
DOI: 10.3233/JAD-220374
Citation: Journal of Alzheimer's Disease, vol. 89, no. 4, pp. 1131-1142, 2022
Authors: Wang, Fei | Luo, Jianfeng | Ding, Ding | Zhao, Qianhua | Guo, Qihao | Liang, Xiaoniu | Zhou, Fen | Deng, Wei | Hong, Zhen
Article Type: Research Article
Abstract: Background: Several studies have demonstrated that the elevated fasting blood glucose (FBG) may increase the risk of incident dementia in older adults with or without diabetes mellitus (DM). However, similar results are rarely reported in Chinese population. Objective: This study aimed to demonstrate the association between FBG and risk of incident cognitive decline in older Chinese adults. Methods: We prospectively followed up 1,555 dementia-free participants with baseline FBG measurement in the Shanghai Aging Study. Results: We identified 126 incident dementia cases across a mean of 5.2 years. Cumulative dementia incidence in type II DM participants with higher FBG (>6.1 mmol/L) increased …most dramatically, second with that of non-DM participants with higher FBG, than that of participants with lower FBG (≤6.1 mmol/L). DM participants had a significant higher risk of incident dementia (adjusted HR 1.51, 95% CI 1.25–1.82) by every 1 mmol/L increment of FBG. Among DM participants, baseline FBG was positively related to the rate of annual decline of MMSE (β= 0.10, p = 0.0018). Conclusions: Our results suggest that especially in people with type II DM, effective blood glucose control may help to prevent cognitive impairment in later life. Show more
Keywords: Cognitive function, cohort study, dementia, diabetes mellitus, fasting glucose, incidence
DOI: 10.3233/JAD-180662
Citation: Journal of Alzheimer's Disease, vol. 67, no. 4, pp. 1255-1265, 2019
Authors: Wu, Wanqing | Ding, Ding | Zhao, Qianhua | Wang, Ruru | Liang, Xiaoniu | Xiao, Zhenxu | Luo, Jianfeng | Guo, Qihao | Hong, Zhen
Article Type: Research Article
Abstract: Background: There is significant evidence that physical activity has profound effects on the neurochemistry and plasticity of the brain and may prevent cognitive decline. Objective: This study aimed to determine the association between physical activity and incident dementia among older Chinese adults. Methods: In the prospective phase of the Shanghai Aging Study, 1,648 community-dwellers aged 60 years or older were followed for an average of 5 years. Their physical activity was assessed based on questionnaires. The physical activities were further transformed into metabolic equivalent values. A consensus diagnosis of incident dementia was ascertained based on medical, neurological, and neuropsychological data …and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Results: We identified 166 incident dementia cases; the incidence rate was 19.4 per 1000 person-years. A multivariate Cox regression model indicated that compared to low levels of physical activity, medium-to-high levels of physical activity were associated with a reduced risk of dementia (hazard ratio, 95% confidence interval = 0.62, 0.44–0.89) after adjusting for age, sex, years of education, apolipoprotein E ɛ 4, and other confounders. Conclusion: Our findings demonstrate that medium-to-high level of physical activity is protective against dementia in older adults. Show more
Keywords: Chinese, cognition, cohort studies, dementia, incidence, physical activity
DOI: 10.3233/JAD-190937
Citation: Journal of Alzheimer's Disease, vol. 73, no. 2, pp. 751-758, 2020
Authors: Mortimer, James A. | Ding, Ding | Borenstein, Amy R. | DeCarli, Charles | Guo, Qihao | Wu, Yougui | Zhao, Qianhua | Chu, Shugang
Article Type: Research Article
Abstract: Physical exercise has been shown to increase brain volume and improve cognition in randomized trials of non-demented elderly. Although greater social engagement was found to reduce dementia risk in observational studies, randomized trials of social interventions have not been reported. A representative sample of 120 elderly from Shanghai, China was randomized to four groups (Tai Chi, Walking, Social Interaction, No Intervention) for 40 weeks. Two MRIs were obtained, one before the intervention period, the other after. A neuropsychological battery was administered at baseline, 20 weeks, and 40 weeks. Comparison of changes in brain volumes in intervention groups with the No …Intervention group were assessed by t-tests. Time-intervention group interactions for neuropsychological measures were evaluated with repeated-measures mixed models. Compared to the No Intervention group, significant increases in brain volume were seen in the Tai Chi and Social Intervention groups (p < 0.05). Improvements also were observed in several neuropsychological measures in the Tai Chi group, including the Mattis Dementia Rating Scale score (p = 0.004), the Trailmaking Test A (p = 0.002) and B (p = 0.0002), the Auditory Verbal Learning Test (p = 0.009), and verbal fluency for animals (p = 0.01). The Social Interaction group showed improvement on some, but fewer neuropsychological indices. No differences were observed between the Walking and No Intervention groups. The findings differ from previous clinical trials in showing increases in brain volume and improvements in cognition with a largely non-aerobic exercise (Tai Chi). In addition, intellectual stimulation through social interaction was associated with increases in brain volume as well as with some cognitive improvements. Show more
Keywords: Cognition, exercise, intervention studies, magnetic resonance imaging, pilot study, Tai Chi
DOI: 10.3233/JAD-2012-120079
Citation: Journal of Alzheimer's Disease, vol. 30, no. 4, pp. 757-766, 2012
Authors: Schwab, Simon | Afyouni, Soroosh | Chen, Yan | Han, Zaizhu | Guo, Qihao | Dierks, Thomas | Wahlund, Lars-Olof | Grieder, Matthias
Article Type: Research Article
Abstract: Background: Semantic memory impairments in semantic dementia are attributed to atrophy and functional disruption of the anterior temporal lobes. In contrast, the posterior medial temporal neurodegeneration found in Alzheimer’s disease is associated with episodic memory disturbance. The two dementia subtypes share hippocampal deterioration, despite a relatively spared episodic memory in semantic dementia. Objective: To unravel mutual and divergent functional alterations in Alzheimer’s disease and semantic dementia, we assessed functional connectivity between temporal lobe regions in Alzheimer’s disease (n = 16), semantic dementia (n = 23), and healthy controls (n = 17). Methods: In an exploratory study, we used a functional parcellation of the …temporal cortex to extract time series from 66 regions for correlation analysis. Results: Apart from differing connections between Alzheimer’s disease and semantic dementia that yielded reduced functional connectivity, we identified a common pathway between the right anterior temporal lobe and the right orbitofrontal cortex in both dementia subtypes. This disconnectivity might be related to social knowledge deficits as part of semantic memory decline. However, such interpretations are preferably made in a holistic context of disease-specific semantic impairments and functional connectivity changes. Conclusion: Despite a major limitation owed to unbalanced databases between study groups, this study provides a preliminary picture of the brain’s functional disconnectivity in Alzheimer’s disease and semantic dementia. Future studies are needed to replicate findings of a common pathway with consistent diagnostic criteria and neuropsychological evaluation, balanced designs, and matched data MRI acquisition procedures. Show more
Keywords: Alzheimer’s disease, functional connectivity, semantic dementia, temporal lobe
DOI: 10.3233/JAD-191113
Citation: Journal of Alzheimer's Disease, vol. 76, no. 4, pp. 1461-1475, 2020