Journal of Alzheimer's Disease - Volume 90, issue 2

Authors: Souza, Melyssa Alves | Peres Bomfim, Larissa Gomes | de Barros, Vinicius Lúcio | Medeiros Jr , Reinaldo Coelho | Ginsicke, Danielle Cristine | Colovati, Mileny Esbravatti Stephano | Daly, Timothy | Zanesco, Angelina

Article Type: Research Article

Abstract: Background: Modifiable risk factors exert crucial impact on dementia. Objective: We sought to answer the question: do two modifiable risk factors, schooling level and physical activity (PA), affect cognitive function similarly in each sex? Methods: This cross-sectional study was conducted in 2019 and 2021, and the survey was applied to the residents of the metropolitan area of Santos, a seashore of Sao Paulo State. Four hundred and twenty-two participants (women = 254 and men = 168) were eligible. Baecke questionnaire for the elderly was applied for the classification as physically inactive (PI) or active (PA). Cognitive function was assessed by …the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR). Participants were also stratified by schooling status for both sexes. Results: Higher education had a sex-independent positive influence on MMSE and CDR (p  < 0.001). PA influences positively MMSE in older women (PI: 25±5 and PA: 27±3, p  < 0.03), but has no effect in older men (26±5 and 25±5, p  > 0.05). Concordantly, older women who were PA (1.7 and 0 %) showed a lower prevalence of dementia compared with PI (6.2 and 2.1%), for mild and moderate respectively. Active older women had higher odds of improving the MMSE score (OR: 1.093; 95% CI: 1.008–1.186) than men (OR: 0.97 (95% CI: 0.896–1.051). Conclusion: Education affects cognitive function equally in Brazilian elderly whereas older women are more responsive to the beneficial effects of PA for dementia than men. Show more

Keywords: Cognitive function, physical activity, schooling status, sex difference

DOI: 10.3233/JAD-220517

Citation: Journal of Alzheimer's Disease, vol. 90, no. 2, pp. 859-867, 2022

Authors: Rabi, Rahel | Chow, Ricky | Paracha, Shahier | Hasher, Lynn | Gardner, Sandra | Anderson, Nicole D. | Alain, Claude

Article Type: Research Article

Abstract: Background: Amnestic mild cognitive impairment (aMCI), a prodromal phase of Alzheimer’s disease (AD), is characterized by episodic memory dysfunction, but inhibitory deficits have also been commonly reported. Time of day (TOD) effects have been confirmed in 1) healthy aging on cognitive processes such as inhibitory control, and 2) on behavior in AD (termed the sundowning effect), but no such research has addressed aMCI. Objective: The present study examined the impact of TOD on the behavioral and electrophysiological correlates of inhibition in 54 individuals with aMCI and 52 healthy controls (HCs), all of morning chronotype. Methods: Participants …were randomly assigned to complete two inhibition tasks (Go-NoGo and Flanker) during their optimal (morning) or non-optimal (evening) TOD, while electroencephalography was recorded. Results: Both tasks elicited changes in N2 and P3 event-related potential (ERP) components, which commonly index inhibitory functioning. Analyses showed that the Go-NoGo difference in P3 amplitude was reduced in individuals with aMCI relative to HCs. Compared to HCs, the Flanker difference in P3 amplitude was also reduced and coincided with more errors in the aMCI group. Notably, these behavioral and ERP differences were exaggerated in the non-optimal TOD relative to the optimal TOD. Conclusion: Findings confirm the presence of inhibition deficits in aMCI and provide novel evidence of sundowning effects on inhibitory control in aMCI. Results reinforce the need to consider the influences of TOD in clinical assessments involving individuals with aMCI. Show more

Keywords: Amnestic mild cognitive impairment, circadian rhythms, chronotype, executive functions, Flanker task, Go-NoGo task

DOI: 10.3233/JAD-220580

Citation: Journal of Alzheimer's Disease, vol. 90, no. 2, pp. 869-890, 2022

Authors: Wu, Xinxing | Peng, Chong | Nelson, Peter T. | Cheng, Qiang

Article Type: Research Article

Abstract: Background: The progression of Alzheimer’s disease (AD) varies in different patients at different stages, which makes predicting the time of disease conversions challenging. Objective: We established an algorithm by leveraging machine learning techniques to predict the probability of the conversion time to next stage for different subjects during a given period. Methods: Firstly, we used Kaplan-Meier (KM) estimation to get the transition curves of different AD stages, and calculated Log-rank statistics to test whether the progression rate between different stages was identical. This quantitatively confirmed the progression rates known in the literature. Then, we developed an …approach based on deep learning model, DeepSurv, to predict the probabilities of time-to-conversion. Finally, to help interpret the deep learning model in our approach, we identified important variables contributing the most to the DeepSurv prediction, whose significance were validated with the analysis of variance (ANOVA). Results: Our machine learning approach predicted the time to conversion with a high accuracy. For each of the different stages, the concordance index (CI) of our approach was at least 86%, and the integrated Brier score (IBS) was less than 0.1. To facilitate interpretability of the prediction results, our approach identified the top 10 variables for each disease conversion scenario, which were clinicopathologically meaningful, and most of them were also statistically significant. Conclusion: Our study has the potential to provide individualized prediction for future time course of AD conversions years before their actual occurrence, thus facilitating personalized prevention and intervention strategies to slow down the progression of AD. Show more

Keywords: Analysis of variance, dementia, machine learning, survival analysis

DOI: 10.3233/JAD-220590

Citation: Journal of Alzheimer's Disease, vol. 90, no. 2, pp. 891-903, 2022

Authors: O’Bryant, Sid E. | Petersen, Melissa | Hall, James | Johnson, Leigh A. | Barber, Robert | Phillips, Nicole | Braskie, Meredith N. | Yaffe, Kristine | Rissman, Robert | Toga, Arthur

Article Type: Research Article

Abstract: Background: Despite tremendous advancements in the field, our understanding of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) among Mexican Americans remains limited. Objective: The aim of this study was to characterize MCI and dementia among Mexican Americans and non-Hispanic whites. Methods: Baseline data were analyzed from n  = 1,705 (n  = 890 Mexican American; n  = 815 non-Hispanic white) participants enrolled in the Health and Aging Brain Study-Health Disparities (HABS-HD). Results: Among Mexican Americans, age (OR = 1.07), depression (OR = 1.09), and MRI-based neurodegeneration (OR = 0.01) were associated with dementia, but none of these factors were associated with MCI. Among …non-Hispanic whites, male gender (OR = 0.33), neighborhood deprivation (OR = 1.34), depression (OR = 1.09), and MRI-based neurodegeneration (OR = 0.03) were associated with MCI, while depression (OR = 1.09) and APOE ɛ 4 genotype (OR = 4.38) were associated with dementia. Conclusion: Findings from this study revealed that the demographic, clinical, sociocultural and biomarker characteristics of MCI and dementia are different among Mexican Americans as compared to non-Hispanic whites. Show more

Keywords: Alzheimer’s disease, health disparities, Hispanic, mild cognitive impairment

DOI: 10.3233/JAD-220300

Citation: Journal of Alzheimer's Disease, vol. 90, no. 2, pp. 905-915, 2022

Authors: Yang, Yuan-Han | Hsieh, Sun-Wung | Chang, Hsi-Wen | Sung, Jia-Li | Chuu, Chih-Pin | Yen, Chen-Wen | Hour, Tzyh-Chyuan

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) was the main cause of dementia in an aging society; unfortunately, there is no effective treatment for AD now. Meditation has been reported to thicken the cerebral cortex, and gamma wave at a frequency of 40 hertz (Hz) was recorded during the meditation process from the brain. Previous study showed that non-invasive scintillation gamma frequency oscillation increased the space in recognition and memory of auditory cortex hippocampal gyrus in AD mice model. However, the AD-related molecular change by exposure of 40 Hz gamma frequency in brain cells was still unclear. Objective: We investigated the AD-related …molecular change by exposure of 40 Hz gamma frequency in SH-SY5Y cells. Methods: We designed the light and sound generators at 40 Hz gamma frequency for this study. SH-SY5Y cells were exposed to sound or light of 40 Hz gamma frequency, respectively. The concentrations of amyloid-β40 (Aβ40 ) and amyloid-β42 (Aβ42 ) were quantified by enzyme-linked immunosorbent assay. The protein levels were examined by Western blotting. The aggregation of Aβ42 was examined by thioflavin T assay. Results: Our results showed that the secretion of Aβ, phosphorylation of AKT, mTOR, and tau, and aggregation of Aβ42 were significantly inhibited by 40 Hz gamma frequency in SH-SY5Y cells. The phosphorylation of 4E-BP1, downstream of mTOR, was induced by 40 Hz gamma frequency in SH-SY5Y cells. Conclusion: Our study showed 40 Hz gamma frequency involved in the inhibition of secretion and aggregation of Aβ and inhibition of p-Tau protein expression through the mTOR/4E-BP1/Tau signaling pathway. Show more

Keywords: Alzheimer disease, amyloid-β, gamma frequency, mTOR, tau

DOI: 10.3233/JAD-220307

Citation: Journal of Alzheimer's Disease, vol. 90, no. 2, pp. 917-928, 2022

Authors: Schaffert, Jeff | Bue, Christian Lo | Hynan, Linda S. | Hart Jr., John | Rossetti, Heidi | Carlew, Anne R. | Lacritz, Laura | White III, Charles L. | Cullum, C. Munro

Article Type: Correction

DOI: 10.3233/JAD-229015

Citation: Journal of Alzheimer's Disease, vol. 90, no. 2, pp. 929-929, 2022

Article Type: Correction

DOI: 10.3233/JAD-229016

Citation: Journal of Alzheimer's Disease, vol. 90, no. 2, pp. 931-931, 2022