Journal of Alzheimer's Disease - Volume Pre-press, issue Pre-press

Authors: Schmidt, Sergio L. | Boechat, Yolanda Eliza Moreira | Schmidt, Guilherme J. | Nicaretta, Denise | van Duinkerken, Eelco | Schmidt, Juliana J.

Article Type: Research Article

Abstract: Background: The Clinical Dementia Rating (CDR) scale is commonly used to stage cognitive impairment, despite having educational limitations. In elderly with low education, a previous study has shown that intraindividual variability of reaction time (CV) and commission errors (CE), measured using a culture-free Go/No-Go task, can reliably distinguish early Alzheimer’s disease (AD) from mild cognitive impairment (MCI) and healthy controls. Objective: We aimed to extend the clinical utility of this culture-free Go/No-Go task in a sample with high educational disparity. Methods: One hundred and ten participants with a wide range of years of formal education (0–14 …years) were randomly selected from a geriatric unit and divided based on their CDR scores into cognitively unimpaired (CDR = 0), MCI (CDR = 0.5), and early AD (CDR = 1). All underwent a 90-s reaction-time test that measured the variables previously found to predict CDR in low educated elderly. Here we added years of formal education (educational level) to the model. Multivariate analyses compared differences in group means using educational level as confounding factor. A confirmatory discriminant analyses was performed, to assess if CDR scores could be predicted by the two Go/No-Go variables in a sample with high educational disparity. Results: Over all three groups, differences in both CE and CV reached statistical significance (p  <  0.05). The discriminant analysis demonstrated that CV and CE discriminated cognitively impaired from cognitively normal elderly. These results remained similar when discriminating MCI from cognitively unimpaired elderly. Conclusion: The Go/No-Go task reliably discriminates elderly with MCI from elderly without cognitive impairment independent of educational disparity. Show more

Keywords: Attention, cognitive dysfunction, dementia, neuropsychology, reaction time

DOI: 10.3233/JAD-210151

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-7, 2021

Authors: Aitken, William W. | Lombard, Joanna | Wang, Kefeng | Toro, Matthew | Byrne, Margaret | Nardi, Maria I. | Kardys, Jack | Parrish, Abraham | Dong, Chuanhui | Szapocznik, José | Rundek, Tatjana | Brown, Scott C.

Article Type: Research Article

Abstract: Background: Neighborhood greenness (vegetative presence) has been linked to multiple health outcomes, but its relationship to Alzheimer’s disease (AD) and non-Alzheimer’s (non-AD) dementia has been less studied. Objective: This study examines the relationship of greenness to both AD and non-AD dementia in a population-based sample of Medicare beneficiaries. Methods: Participants were 249,405 US Medicare beneficiaries aged >  65 living in Miami-Dade County, FL, from 2010 to 2011. Multi-level analyses examined the relationship of greenness, assessed by mean Census block level Normalized Difference Vegetation Index (NDVI), to odds of each of AD, Alzheimer’s disease and related dementias …(ADRD), and non-AD dementia, respectively. Covariates included age, gender, race/ethnicity, number of comorbid health conditions, and neighborhood income. Results: Higher greenness was associated with reduced risk of AD, ADRD, and non-AD dementia, respectively, adjusting for individual and neighborhood sociodemographics. Compared to the lowest greenness tertile, the highest greenness tertile was associated with reduced odds of AD by 20%(odds ratio, 0.80; 95%CI, 0.75–0.85), ADRD by 18%(odds ratio, 0.82; 95%CI, 0.77–0.86), and non-AD dementia by 11%(odds ratio, 0.89; 95%CI, 0.82–0.96). After further adjusting for number of comorbidities, compared to the lowest greenness tertile, the highest greenness tertile was associated with reduced odds of AD (OR, 0.94; 95%CI, 0.88–1.00) and ADRD (OR, 0.93; 95%CI, 0.88–0.99), but not non-AD dementia (OR, 1.01; 95%CI, 0.93–1.08). Conclusion: High neighborhood greenness may be associated with lower odds of AD and ADRD. Environmental improvements, such as increasing neighborhood vegetation, may be a strategy to reduce risk for AD and possibly other dementias. Show more

Keywords: Alzheimer’s disease, built environment, dementia, health disparities, medicare beneficiaries, natural environment, neighborhood greenness, older adults

DOI: 10.3233/JAD-201179

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-10, 2021

Authors: Zheng, Yi-Ming | Zhao, Yang-Yang | Zhang, Ting | Hou, Xiao-He | Bi, Yan-Lin | Ma, Ya-Hui | Xu, Wei | Shen, Xue-Ning | Dong, Qiang | Tan, Lan | Yu, Jin-Tai

Article Type: Research Article

Abstract: Background: Heart failure has been considered as a potential modifiable risk factor for cognitive impairment and dementia. Left ventricular ejection fraction (LVEF), an indicator of cardiac dysfunction, has also been associated with cognitive aging. However, the effect of LVEF on Alzheimer’s disease (AD) pathology is still less known. Objective: We aimed to investigate the associations of LVEF with cerebrospinal fluid (CSF) biomarkers for AD in cognitively normal elders. Methods: A total of 423 cognitively normal individuals without heart failure were included from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) study. Participants were divided …into low LVEF group (50%≤LVEF <  60%) and high LVEF group (LVEF≥60%). The associations of LVEF with CSF AD biomarkers including CSF amyloid-β 42 (Aβ 42 ), total-tau (t-tau), and phosphorylated tau (p-tau) were analyzed using multivariate linear regression models. Results: Participants with low LVEF had higher levels of CSF t-tau (β= –0.009, p  = 0.006) and t-tau/Aβ 42 ratios (β= –0.108, p  = 0.026). Subgroup analyses showed that the associations only existed in female and middle-aged groups (<  65 years old). Besides, participants with low LVEF had higher levels of CSF p-tau (β= –0.002, p  = 0.043) in middle-aged group. Conclusion: In conclusion, our findings revealed the associations between LVEF and AD pathology, which may provide new insights into AD prevention through maintaining cardiac function. Show more

Keywords: Alzheimer’s disease, biomarker, cerebrospinal fluid, left ventricular ejection fraction

DOI: 10.3233/JAD-201222

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-8, 2021

Authors: Wang, Xuewei | Bui, Hai | Vemuri, Prashanthi | Graff-Radford, Jonathan | Jack Jr, Clifford R. | Petersen, Ronald C. | Mielke, Michelle M.

Article Type: Research Article

Abstract: Background: Lipid alterations contribute to Alzheimer’s disease (AD) pathogenesis. Lipidomics studies could help systematically characterize such alterations and identify potential biomarkers. Objective: To identify lipids associated with mild cognitive impairment and amyloid-β deposition, and to examine lipid correlation patterns within phenotype groups Methods: Eighty plasma lipids were measured using mass spectrometry for 1,255 non-demented participants enrolled in the Mayo Clinic Study of Aging. Individual lipids associated with mild cognitive impairment (MCI) were first identified. Correlation network analysis was then performed to identify lipid species with stable correlations across conditions. Finally, differential correlation network analysis was used …to determine lipids with altered correlations between phenotype groups, specifically cognitively unimpaired versus MCI, and with elevated brain amyloid versus without. Results: Seven lipids were associated with MCI after adjustment for age, sex, and APOE4 . Lipid correlation network analysis revealed that lipids from a few species correlated well with each other, demonstrated by subnetworks of these lipids. 177 lipid pairs differently correlated between cognitively unimpaired and MCI patients, whereas 337 pairs of lipids exhibited altered correlation between patients with and without elevated brain amyloid. In particular, 51 lipid pairs showed correlation alterations by both cognitive status and brain amyloid. Interestingly, the lipids central to the network of these 51 lipid pairs were not significantly associated with either MCI or amyloid, suggesting network-based approaches could provide biological insights complementary to traditional association analyses. Conclusion: Our attempt to characterize the alterations of lipids at network-level provides additional insights beyond individual lipids, as shown by differential correlations in our study. Show more

Keywords: Aging, Alzheimer’s disease, amyloid, lipid, lipidomics, mild cognitive impairment, network analysis, systems biology

DOI: 10.3233/JAD-201347

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2021

Authors: Rodríguez, Danelly | Ayers, Emmeline | Weiss, Erica F. | Verghese, Joe

Article Type: Research Article

Abstract: Background: Very few studies have explored the utility of subjective cognitive complaints (SCCs) in primary care settings. Objective: We aim to investigate associations between SCCs (item-level), objective cognitive function (across domains and global), and mood in a diverse primary care population, including subjects with mild cognitive impairment. Methods: We studied 199 (75.9%females; 57.8%Hispanics; 42.2%African Americans) older adults (mean age 72.5 years) with memory concerns at a primary care clinic. A five-item SCC questionnaire, and objective cognitive assessments, including the Montreal Cognitive Assessment (MoCA) and the Geriatric Depression Scale, were administered. Results: …Logistic regression analyses showed associations between SCC score and depressive symptoms. A memory-specific (“memory worsening”) SCC predicted scores on the MoCA (p  = 0.005) in Hispanics. Conclusion: SCCs are strongly linked to depressive symptoms in African Americans and Hispanics in a primary care setting; a specific type of SCC is related to global cognitive function in Hispanics. Show more

Keywords: Cognitive function, cross-sectional, depressive symptoms, primary care, subjective health complaint, underserved populations

DOI: 10.3233/JAD-201399

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2021

Authors: Manera, Valeria | Galperti, Guenda | Rovini, Erika | Zeghari, Radia | Mancioppi, Gianmaria | Fiorini, Laura | Gros, Auriane | Mouton, Aurélie | Robert, Philippe | Cavallo, Filippo

Article Type: Research Article

Abstract: Background: Social apathy, a reduction in initiative in proposing or engaging in social activities or interactions, is common in mild neurocognitive disorders (MND). Current apathy assessment relies on self-reports or clinical scales, but growing attention is devoted to defining more objective, measurable and non-invasive apathy proxies. Objective: In the present study we investigated the interest of recording action kinematics in a social reach-to-grasp task for the assessment of social apathy. Methods: Thirty participants took part in the study: 11 healthy controls (HC; 6 females, mean age = 68.3±10.5 years) and 19 subjects with MND (13 females, mean age = 75.7±6.3 …years). Based on the Diagnostic Criteria for Apathy, MND subjects were classified as socially apathetic (A-MND, N  = 9) versus non-apathetic (NA-MND, N  = 10). SensRing, a ring-shaped wearable sensor, was placed on their index finger, and subjects were asked to reach and grasp a can to place it into a cup (individual condition) and pass it to a partner (social condition). Results: In the reach-to-grasp phase of the action, HC and NA-MND showed different acceleration and velocity profiles in the social versus individual condition. No differences were found for A-MND. Conclusion: Previous studies showed the interest of recording patients’ level of weekly motor activity for apathy assessment. Here we showed that a 10-min reach-to-grasp task may provide information to differentiate socially apathetic and non-apathetic subjects with MND, thus providing a tool easily usable in the clinical practice. Future studies with a bigger sample are needed to better characterize these findings. Show more

Keywords: Apathy, diagnosis, intention, motivation, motor activity, neurocognitive disorders, social behavior, social isolation

DOI: 10.3233/JAD-200966

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2021

Authors: Martínez-Florez, Juan F. | Osorio, Juan D. | Cediel, Judith C. | Rivas, Juan C. | Granados-Sánchez, Ana M. | López-Peláez, Jéssica | Jaramillo, Tania | Cardona, Juan F.

Article Type: Research Article

Abstract: Background: Amnestic mild cognitive impairment (aMCI) is the most common preclinical stage of Alzheimer’s disease (AD). A strategy to reduce the impact of AD is the early aMCI diagnosis and clinical intervention. Neuroimaging, neurobiological, and genetic markers have proved to be sensitive and specific for the early diagnosis of AD. However, the high cost of these procedures is prohibitive in low-income and middle-income countries (LIMCs). The neuropsychological assessments currently aim to identify cognitive markers that could contribute to the early diagnosis of dementia. Objective: Compare machine learning (ML) architectures classifying and predicting aMCI and asset the contribution of …cognitive measures including binding function in distinction and prediction of aMCI. Methods: We conducted a two-year follow-up assessment of a sample of 154 subjects with a comprehensive multidomain neuropsychological battery. Statistical analysis was proposed using complete ML architectures to compare subjects’ performance to classify and predict aMCI. Additionally, permutation importance and Shapley additive explanations (SHAP) routines were implemented for feature importance selection. Results: AdaBoost, gradient boosting, and XGBoost had the highest performance with over 80%success classifying aMCI, and decision tree and random forest had the highest performance with over 70%success predictive routines. Feature importance points, the auditory verbal learning test, short-term memory binding tasks, and verbal and category fluency tasks were used as variables with the first grade of importance to distinguish healthy cognition and aMCI. Conclusion: Although neuropsychological measures do not replace biomarkers’ utility, it is a relatively sensitive and specific diagnostic tool for aMCI. Further studies with ML must identify cognitive performance that differentiates conversion from average MCI to the pathological MCI observed in AD. Show more

Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, cognitive markers, healthy aging, machine learning

DOI: 10.3233/JAD-201447

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2021

Authors: Zhang, Yun | Natale, Ginny | Clouston, Sean

Article Type: Research Article

Abstract: Background: Larger, or more active social networks are estimated to be associated with lower risks of cognitive decline. However, roles of various social relationships in a broad social network in protecting against cognitive decline remain to be elucidated. Objective: We aimed to investigate how social roles within a social network and number of social network members are associated with cognitive decline. Methods: Six waves of National Health and Aging Trends Study (2011-2016, NHATS) were utilized to examine the development of mild cognitive impairment (MCI) and probable dementia determined using validated criteria. Multivariable-adjusted multi-state survival models were …used to model incidences and transitions, jointly with misclassification errors. Results: A total of 6,078 eligible NHATS participants were included (average age: 77.49±7.79 years; female: 58.42%; non-Hispanic white: 68.99%). Multivariable-adjusted analyses revealed that having more social network members was associated with lower hazards of conversion from MCI to probable dementia (adjusted Hazard Ratio; aHR = 0.82; 95%confidence intervals; 95%CI = [0.67–0.99]), meanwhile having at least one college-educated family member within a social network was associated with lower incidence of probable dementia (aHR = 0.37 [0.26–0.51]). Having at least one friend within a social network was associated with a lower hazard of incidence of probable dementia (aHR = 0.48 [0.33–0.71]), but a higher risk of mortality in the MCI group (aHR = 2.58 [1.47–4.51 ]). Conclusion: Having more social network members, having at least one friend, and having at least one college-educated family member within a social network, were associated with lower risks of incidence of dementia or conversion from MCI to dementia. Show more

Keywords: Cognition, dementia, multistate modeling, social networking

DOI: 10.3233/JAD-201196

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Boström, Gustaf | Freyhult, Eva | Virhammar, Johan | Alcolea, Daniel | Tumani, Hayrettin | Otto, Markus | Brundin, Rose-Marie | Kilander, Lena | Löwenmark, Malin | Giedraitis, Vilmantas | Lleó, Alberto | von Arnim, Christine A.F. | Kultima, Kim | Ingelsson, Martin

Article Type: Research Article

Abstract: Background: Neuroinflammatory processes are common in neurodegenerative diseases such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD), but current knowledge is limited as to whether cerebrospinal fluid (CSF) levels of neuroinflammatory proteins are altered in these diseases. Objective: To identify and characterize neuroinflammatory signatures in CSF from patients with AD, mild cognitive impairment (MCI), and FTD. Methods: We used proximity extension assay and ANOVA to measure and compare levels of 92 inflammatory proteins in CSF from 42 patients with AD, 29 with MCI due to AD (MCI/AD), 22 with stable MCI, 42 with FTD, and 49 …control subjects, correcting for age, gender, collection unit, and multiple testing. Results: Levels of matrix metalloproteinase-10 (MMP-10) were increased in AD, MCI/AD, and FTD compared with controls (AD: fold change [FC] = 1.32, 95%confidence interval [CI] 1.14–1.53, q  = 0.018; MCI/AD: FC = 1.53, 95%CI 1.20–1.94, q  = 0.045; and FTD: FC = 1.42, 95%CI 1.10–1.83, q  = 0.020). MMP-10 and eleven additional proteins were increased in MCI/AD, compared with MCI (q  <  0.05). In FTD, 36 proteins were decreased, while none was decreased in AD or MCI/AD, compared with controls (q  <  0.05). Conclusion: In this cross-sectional multi-center study, we found distinct patterns of CSF inflammatory marker levels in FTD and in both early and established AD, suggesting differing neuroinflammatory processes in the two disorders. Show more

Keywords: Alzheimer’s disease, frontotemporal dementia, mild cognitive impairment, neuroinflammation, proteomics

DOI: 10.3233/JAD-201565

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Kanatome, Ayana | Ano, Yasuhisa | Shinagawa, Kazushi | Ide, Yumiko | Shibata, Midori | Umeda, Satoshi

Article Type: Research Article

Abstract: Background: Epidemiological studies have shown that dairy product consumption is beneficial for cognitive function in elderly individuals. β-lactolin is a lacto-tetrapeptide Gly–Thr–Trp–Tyr rich in fermented dairy products that improves memory retrieval, attention, and executive function in older adults with subjective cognitive decline and prevents the pathology of Alzheimer’s disease in rodents. There has been no study on the effects of β-lactolin on neural activity in humans. Objective: We investigated the effects of β-lactolin on neural activity and cognitive function in healthy adults. Methods: In this randomized, double-blind, placebo-controlled study, 30 participants (45–64 years old) consumed β-lactolin …or placebo for 6 weeks. Neural activity during auditory and language tasks was measured through 64-channel electroencephalography. Moreover, verbal fluency tests were performed at baseline and after 6 weeks. Results: The β-lactolin group had a significantly higher P300 amplitude at the Cp2 site (a part of the parietal lobe near the center of brain, p  = 0.008), and C4 site (the area between the frontal and parietal lobe, p  = 0.021) during the auditory tasks after 6 weeks than the placebo group. Thus, β-lactolin supplementation promoted neural activity in the parietal area, which increases attention during auditory cognitive tasks. Compared with the placebo group, the β-lactolin group also showed significant changes in the scores of verbal fluency test after 6 weeks (p  = 0.03). Conclusion: Our findings provide insight into the mechanisms underlying the effects of β-lactolin on attention in healthy adults. Show more

Keywords: Attention, clinical trial, cognitive function, EEG, β-lactoglobulin, β-lactolin, β-lactopeptide, memory, P300, whey

DOI: 10.3233/JAD-201413

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-10, 2021