Journal of Alzheimer's Disease - Volume 74, issue 2

Authors: Koch, Manja | Costanzo, Simona | Fitzpatrick, Annette L. | Lopez, Oscar L. | DeKosky, Steven | Kuller, Lewis H. | Price, Julie | Mackey, Rachel H. | Jensen, Majken K. | Mukamal, Kenneth J.

Article Type: Research Article

Abstract: Background: Light to moderate alcohol consumption has been variably associated with lower or higher risk of dementia, but effects on Alzheimer’s disease pathology are less clear. Objective: We determined whether late-life alcohol consumption was associated with Alzheimer’s disease pathology among older adults. Methods: We assessed the associations of alcohol consumption self-reported in 2000–2002 with brain amyloid-β deposition on PET scans, and white matter lesion and hippocampal volume on MRIs measured 7–9 years later in 189 participants of the Ginkgo Evaluation of Memory Study (age 75–87 years at baseline) who were free of clinical dementia, using multivariable-adjusted …and inverse probability-weighted robust linear regression models. Results: Alcohol consumption was not statistically significantly associated with amyloid-β deposition (standardized uptake value ratio difference per drink: –0.013 [95% CI: –0.027, 0.002]). Both non-drinkers and participants consuming ≥1 drink(s)/week had higher white matter lesion volume (% intracranial volume) than did the reference group of those consuming <1 drink/week (differences: 0.25 % [95% CI: 0.01, 0.50]; 0.26 % [95% CI: 0.02, 0.50]). The association of alcohol consumption and hippocampal volume was modified by age (p  = 0.02). Among participants younger than 77 years, participants consuming 1–7 drinks/week had larger hippocampal volume compared with participants consuming <1 drink/week. Conclusions: Alcohol consumption was not statistically significantly associated with amyloid-β deposition 7–9 years later. Non-drinking and greater alcohol consumption were associated with higher white matter lesion volume compared with drinking <1 drink/week. Moderate drinking was associated with higher hippocampal volume in younger individuals. Given the selective nature of this population and adverse health effects of excessive alcohol consumption, these findings warrant further investigation, but cannot be translated into clinical recommendations. Show more

Keywords: Alcohol, brain amyloid-β , epidemiology, hippocampal volume, white matter lesions

DOI: 10.3233/JAD-190834

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 509-519, 2020

Authors: Hou, Ting-ting | Han, Yun-Dan | Cong, Lin | Liu, Cui-cui | Liang, Xiao-Yan | Xue, Fu-zhong | Du, Yi-feng

Article Type: Research Article

Abstract: Hyperphosphorylated tau is one of the key characteristics of Alzheimer’s disease (AD), and tau pathology correlates with cognitive impairment in AD better than amyloid-β (Aβ) pathology. Thus, a complete understanding of the relevant factors involved in tau phosphorylation is important for AD treatment. APOE ɛ 4 , the strongest genetic risk factor for AD, was found to be involved in tau pathology in frontotemporal dementia. This result indicated that apolipoprotein E (ApoE) may also participate in tau phosphorylation in AD. In the present study, we injected Aβ oligomer (AβO) into the lateral ventricles of wild-type (WT) mice and apoE-/- …mice to test the process of tau phosphorylation in the acute phase. We found that the phosphorylated tau and phosphokinase levels were higher in WT mice than in apoE-/- mice. These phenomena were also confirmed in vitro . ApoE ɛ 4-treated apoE-/- neurons exhibited more phosphorylated tau than ApoE ɛ 2- and ApoE ɛ 3-treated neurons. We also found that AβO induced more serious inflammation in WT mice and in ApoE-positive cultured neurons. Anti-inflammatory treatment reduced the phosphorylated tau level induced by AβOs in ApoE-positive neurons. These results suggest that ApoE may facilitate the phosphorylation of tau induced by AβO via inflammation. Show more

Keywords: Alzheimer’s disease, amyloid-β oligomer, apolipoprotein E, inflammation, phosphorylated tau

DOI: 10.3233/JAD-190711

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 521-534, 2020

Authors: Sun, Lin | Cheng, Baoying | Zhou, Yuxun | Fan, Yating | Li, Wei | Qiu, Qi | Fang, Yuan | Xiao, Shifu | Zheng, Honghua | Li, Xia

Article Type: Research Article

Abstract: Background: Amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) includes a large spectrum of neurodegenerative disorders. Objective: To identify the relationship of ErbB4 mutation and ALS/FTD. Methods: Here, we report an atypical case of frontal variant behavioral abnormalities at the initial stage, a stable plateau stage of 5 years, and paralysis involving both upper and lower motor neurons followed by progressive cognitive dysfunction at the advanced stage. The clinical findings suggested a diagnosis of ALS/FTD, and genetic testing revealed erb-b2 receptor tyrosine kinase 4 (ErbB4 ) heterozygous mutation (c.2136 T>G, p.I712M), identified in an ALS pedigree previously. …We modeled mutant ErbB4 protein through the SWISS-MODEL Server, and speculated on the structural change caused by the mutation. We also identified that ErbB4 (I712M) mutation led to reduced auto-phosphorylation of ErbB4 upon neuregulin-1 (NRG1) stimulation. Results: A functional analysis of ErbB4 mutation demonstrated an obviously decreased auto-phosphorylation of ErbB4 involving in the pathogenesis of ALS/FTD. Conclusion: We firstly found ErbB4 mutation to be identified in ALS/FTD. Show more

Keywords: Amyotrophic lateral sclerosis, ErbB4, frontotemporal dementia, I712M, neuregulin-1

DOI: 10.3233/JAD-191230

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 535-544, 2020

Authors: Patel, Hamel | Iniesta, Raquel | Stahl, Daniel | Dobson, Richard J.B. | Newhouse, Stephen J.

Article Type: Research Article

Abstract: Background: The typical approach to identify blood-derived gene expression signatures as a biomarker for Alzheimer’s disease (AD) have relied on training classification models using AD and healthy controls only. This may inadvertently result in the identification of markers for general illness rather than being disease-specific. Objective: Investigate whether incorporating additional related disorders in the classification model development process can lead to the discovery of an AD-specific gene expression signature. Methods: Two types of XGBoost classification models were developed. The first used 160 AD and 127 healthy controls and the second used the same 160 AD with …6,318 upsampled mixed controls consisting of Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, bipolar disorder, schizophrenia, coronary artery disease, rheumatoid arthritis, chronic obstructive pulmonary disease, and cognitively healthy subjects. Both classification models were evaluated in an independent cohort consisting of 127 AD and 687 mixed controls. Results: The AD versus healthy control models resulted in an average 48.7% sensitivity (95% CI = 34.7–64.6), 41.9% specificity (95% CI = 26.8–54.3), 13.6% PPV (95% CI = 9.9–18.5), and 81.1% NPV (95% CI = 73.3–87.7). In contrast, the mixed control models resulted in an average of 40.8% sensitivity (95% CI = 27.5–52.0), 95.3% specificity (95% CI = 93.3–97.1), 61.4% PPV (95% CI = 53.8–69.6), and 89.7% NPV (95% CI = 87.8–91.4). Conclusions: This early work demonstrates the value of incorporating additional related disorders into the classification model developmental process, which can result in models with improved ability to distinguish AD from a heterogeneous aging population. However, further improvement to the sensitivity of the test is still required. Show more

Keywords: Age-related memory disorders, Alzheimer’s disease, biomarkers, dementia, gene expression, human, machine learning, microarray analysis, neurodegenerative disorders

DOI: 10.3233/JAD-191163

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 545-561, 2020

Authors: Cipollari, Eleonora | Szapary, Hannah J. | Picataggi, Antonino | Billheimer, Jeffrey T. | Lyssenko, Catherine A. | Ying, Gui-Shuang | Shaw, Leslie M. | Kling, Mitchel A. | Kaddurah-Daouk, Rima | Rader, Daniel J. | Praticò, Domenico | Lyssenko, Nicholas N. | for the Alzheimer’s Disease Metabolomics Consortium

Article Type: Research Article

Abstract: Background: Basic research has implicated intracellular cholesterol in neurons, microglia, and astrocytes in the pathogenesis of Alzheimer’s disease (AD), but there is presently no assay to access intracellular cholesterol in neural cells in living people in the context of AD. Objective: To devise and characterize an assay that can access intracellular cholesterol and cholesterol efflux in neural cells in living subjects. Methods: We modified the protocol for high-density lipoprotein cholesterol efflux capacity (CEC) from macrophages, a biomarker that accesses cholesterol in macrophages in atherosclerosis. To measure cerebrospinal fluid (CSF) CECs from neurons, microglia, and astrocytes, CSF …was exposed to, correspondingly, neuronal, microglial, and astrocytic cholesterol source cells. Human neuroblastoma SH-SY5Y, mouse microglial N9, and human astroglial A172 cells were used as the cholesterol source cells. CSF samples were screened for contamination with blood. CSF CECs were measured in a small cohort of 22 individuals. Results: CSF CECs from neurons, microglia, and astrocytes were moderately to moderately strongly correlated with CSF concentrations of cholesterol, apolipoprotein A-I, apolipoprotein E, and clusterin (Pearson’s r  = 0.53–0.86), were in poor agreement with one another regarding CEC of the CSF samples (Lin’s concordance coefficient r c  = 0.71–0.76), and were best predicted by models consisting of, correspondingly, CSF phospholipid (R2  = 0.87, p  < 0.0001), CSF apolipoprotein A-I and clusterin (R2  = 0.90, p  < 0.0001), and CSF clusterin (R2  = 0.62, p  = 0.0005). Conclusion: Characteristics of the CSF CEC metrics suggest a potential for independent association with AD and provision of fresh insight into the role of cholesterol in AD pathogenesis. Show more

Keywords: ABCA1, ABCG1, Alzheimer’s disease biomarkers, apolipoprotein A-I, apolipoprotein E, cell cholesterol efflux, clusterin (apolipoprotein J), SR-BI

DOI: 10.3233/JAD-191246

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 563-578, 2020

Authors: Zhang, Wei | Luo, Peng

Article Type: Research Article

Abstract: Cardiovascular disorders, e.g., atherosclerosis and hypertension, increase susceptibility to neurodegenerative diseases, like dementia and Alzheimer’s disease (AD), with undetermined mechanisms. Moreover, whether myocardial infarction (MI) may similarly increases occurrence of AD is unknown. In the current study, we performed a MI model in wild-type and AD-prone APP/PS1 mice and assessed the development of AD in these mice. We found that MI-treated mice of both wild-type and APP/PS1 behaved poorer in a social recognition test, the Morris water maze, and the plus-maze discriminative avoidance task, compared to sham-treated controls. Mechanistically, MI significantly increased the levels of reactive oxygen species, as well …as increased deposition of amyloid-β peptide aggregates and phosphorylation of tau protein in mouse brain, two signature pathological features for AD. Moreover, the microglia in the MI-mice appeared to alter polarization to a more proinflammatory phenotype. Together, our data suggest that MI may be a predisposing factor for AD development. Show more

Keywords: Alzheimer’s disease, amyloid-β peptide aggregates, microglia, myocardial infarction, reactive oxygen species, tau

DOI: 10.3233/JAD-191225

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 579-587, 2020

Authors: Okafor, Maureen | Nye, Jonathon A. | Shokouhi, Mahsa | Shaw, Leslie M. | Goldstein, Felicia | Hajjar, Ihab

Article Type: Research Article

Abstract: Background: Tau positron emission tomography (PET) imaging is used in research, but its relation to cerebrospinal fluid (CSF) tau and other Alzheimer’s disease (AD)-related clinical measures is unclear in mild cognitive impairment with AD biomarkers (MCI-AD). Objective: To determine associations between 18 F-flortaucipir PET and CSF AD biomarkers, cognitive functioning, and neuroimaging measures in MCI-AD. Methods: In 29 participants 50 years or older with MCI-AD, 18 F-flortaucipir PET, CSF total tau (T-tau), phosphorylated tau181p (P-tau), amyloid-β (Aβ), structural MRI, and neuropsychological testing were collected as baseline assessments of an ongoing clinical trial. 11 C-Pittsburgh compound …B PET was simultaneously conducted in 20 participants. Associations between 18 F-flortaucipir PET and these measures were assessed by multiple linear regression adjusted for potential confounders and using global, lobar, and voxel-wise standardized uptake value ratio (SUVr). Results: Whole brain 18 F-flortaucipir SUVr was significantly associated with CSF T-tau (r  = 0.68, p  < 0.001) and P-tau (r  = 0.42, p  = 0.04) after adjusting for age, sex, race, and education, with strongest associations in the temporal region (T-tau: r  = 0.69, p  < 0.001; P-tau: r  = 0.49, p  = 0.02). Voxel-wise analysis confirmed these regional associations. 18 F-flortaucipir PET was also associated with CSF Aβ (r  = –0.45, p  = 0.03), episodic memory (r  = –0.61, p  = 0.001), visuospatial working memory (r  = –0.46, p  = 0.02), and brain cortical thickness (r  = –0.44, p  = 0.03) but not hippocampal volume. In the amyloid PET subset, although 11 C-PiB PET associated strongly with 18 F-flortaucipir (r  = 0.79, p ≤0.001), associations were stronger between 11 C-PiB and key outcomes, compared to 18 F-flortaucipir. Conclusion: 18 F-flortaucipir PET is moderately associated with CSF AD biomarkers and other AD-related phenotypes. The associations in this MCI-AD sample are stronger than previously described in other populations. Show more

Keywords: Alzheimer’s disease, cerebrospinal fluid biomarkers, cognitive function, cortical thickness, flortaucipir, mild cognitive impairment, positron emission tomography, tau PET

DOI: 10.3233/JAD-191330

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 589-601, 2020

Authors: Xia, Wenqing | Luo, Yong | Chen, Yu-Chen | Chen, Huiyou | Ma, Jianhua | Yin, Xindao

Article Type: Research Article

Abstract: Background: Type 2 diabetes mellitus (T2DM) accelerates cognitive decline, which is believed to be triggered by aberrant neural activity. Objective: To explore how glucose fluctuations impact brain functional architecture and cognition in T2DM patients. Methods: T2DM patients were divided according to glycemic variability, forming two categories: patients with fluctuating glucose levels and patients with stable glucose levels. Degree centrality (DC) was calculated within the cerebral gray matter of each participant and was compared among the two patient groups and a healthy control group. The relationships between glucose fluctuations and aberrant DC and cognitive performance, as well …as the relationship between aberrant DC and cognitive performance, were further explored. Results: Compared with T2DM patients with stable glucose levels, T2DM patients with fluctuating glucose levels exhibited significantly worse performance on the Montreal Cognitive Assessment, Trail Making Test-B (TMT-B), and verbal fluency test (VFT), as well as significant decreases in DC in certain regions, most of which were within the default mode network. In the combined T2DM group, the mean amplitude of glycemic excursions (MAGE) was positively correlated with TMT-B scores and negatively correlated with VFT scores. Moreover, the MAGE was negatively correlated with DC in the left medial prefrontal cortex (mPFC). In addition, TMT-B scores were negatively correlated with reduced DC in the left mPFC. Conclusion: These findings further contribute to the mounting evidence of the effects of glycemic variability on the diabetic brain. Tightened control of glucose fluctuations might prevent cognitive decline and changes in brain functional architecture in T2DM individuals. Show more

Keywords: Brain, cognitive impairments, functional magnetic resonance imaging, type 2 diabetes mellitus

DOI: 10.3233/JAD-191217

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 603-613, 2020

Authors: Toniolo, Sofia | Serra, Laura | Olivito, Giusy | Caltagirone, Carlo | Mercuri, Nicola Biagio | Marra, Camillo | Cercignani, Mara | Bozzali, Marco

Article Type: Research Article

Abstract: The cognitive role of the cerebellum has recently gained much attention, and its pivotal role in Alzheimer’s disease (AD) has now been widely recognized. Diffusion tensor imaging (DTI) has been used to evaluate the disruption of the microstructural milieu in AD, and though several white matter (WM) tracts such as corpus callosum, inferior and superior longitudinal fasciculus, cingulum, fornix, and uncinate fasciculus have been evaluated in AD, data on cerebellar WM tracts are currently lacking. We performed a tractography-based DTI reconstruction of the middle cerebellar peduncle (MCP), and the left and right superior cerebellar peduncles separately (SCPL and SCPR) and …addressed the differences in fractional anisotropy (FA), axial diffusivity (Dax), radial diffusivity (RD), and mean diffusivity (MD) in the three tracts between 50 patients with AD and 25 healthy subjects. We found that AD patients showed a lower FA and a higher RD compared to healthy subjects in MCP, SCPL, and SCPR. Moreover, higher MD was found in SCPR and SCPL and higher Dax in SCPL. This result is important as it challenges the traditional view that WM bundles in the cerebellum are unaffected in AD and might identify new targets for therapeutic interventions. Show more

Keywords: Alzheimer’s disease, cerebellum, diffusion tensor imaging, probabilistic tractography, white matter

DOI: 10.3233/JAD-191125

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 615-624, 2020

Authors: James, Hailey J. | Van Houtven, Courtney Harold | Lippmann, Steven | Burke, James R. | Shepherd-Banigan, Megan | Belanger, Emmanuelle | Wetle, Terrie Fox | Plassman, Brenda L.

Article Type: Research Article

Abstract: Background: Amyloid-β PET scans will likely become an integral part of the diagnostic evaluation for Alzheimer’s disease if Medicare approves reimbursement for the scans. However, little is known about patients’ and their care partners’ interpretation of scan results. Objective: This study seeks to understand how accurately patients with mild cognitive impairment (MCI) or dementia and their care partners report results of amyloid-β PET scans and factors related to correct reporting. Methods: A mixed-methods approach was used to analyze survey data from 1,845 patient-care partner dyads and responses to open-ended questions about interpretation of scan results from …a sub-sample of 200 dyads. Results: Eighty-three percent of patients and 85% of care partners correctly reported amyloid-β PET scan results. Patients’ higher cognitive function was associated with a small but significant decrease in the predicted probability of not only patients accurately reporting scan results (ME: –0.004, 95% CI: –0.007, –0.000), but also care partners accurately reporting scan results (ME: –0.006, 95% CI: –0.007, –0.001), as well as decreased concordance between patient and care partner reports (ME: –0.004, 95% CI: –0.007, –0.001). Content analysis of open-ended responses found that participants who reported the scan results incorrectly exhibited more confusion about diagnostic terminology than those who correctly reported the scan results. Conclusion: Overall, patients with MCI or dementia showed high rates of accurate reporting of amyloid-β PET scan results. However, responses to questions about the meaning of the scan results highlight the need for improved provider communication, including providing written explanations and better prognostic information. Show more

Keywords: Alzheimer’s disease, amyloid PET, caregivers, dementia, mild cognitive impairment

DOI: 10.3233/JAD-190922

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 625-636, 2020

Authors: Miguel, Laetitia | Frebourg, Thierry | Campion, Dominique | Lecourtois, Magalie

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is neuropathologically defined by two key hallmarks: extracellular senile plaques composed primarily of amyloid-β (Aβ) peptide and intraneuronal neurofibrillary tangles, containing abnormally hyperphosphorylated tau protein. The tau protein is encoded by the MAPT gene. Recently, the H1 and H2 haplotypes of the MAPT gene were associated with AD risk. The minor MAPT H2 haplotype has been linked with a decreased risk of developing late-onset AD (LOAD). MAPT haplotypes show different levels of MAPT/Tau expression with H1 being ∼1.5-fold more expressed than H2, suggesting that MAPT expression level could be related to …LOAD risk. In this study, we investigated whether this moderate difference in MAPT/Tau expression could influence Aβ-induced toxicity in vivo. We show that modest overexpression of tau protein in Drosophila exacerbates neuronal phenotypes in AβPP/BACE1 flies. The exacerbation of neuronal defects correlates with the accumulation of insoluble dTau oligomers, suggesting that the moderate difference in level of tau expression observed between H1 and H2 haplotypes could influence Aβ toxicity through the production of oligomeric tau insoluble species. Show more

Keywords: Alzheimer’s disease, amyloid-β peptide, Drosophila , oligomers, tau

DOI: 10.3233/JAD-190906

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 637-647, 2020

Authors: Livny, Abigail | Schnaider Beeri, Michal | Heymann, Anthony | Moshier, Erin | Berman, Yuval | Mamistalov, Mary | Shahar, Danit-Rivka | Tsarfaty, Galia | Leroith, Derek | Preiss, Rachel | Soleimani, Laili | Silverman, Jeremy M. | Bendlin, Barbara B. | Levy, Andrew | Ravona-Springer, Ramit

Article Type: Research Article

Abstract: Backgrounds: The efficacy of vitamin E in prevention of diabetes-related complications differs by Haptoglobin (Hp) genotype. Objective: To examine the role of Hp genotype in the relationship of vitamin E intake with brain volume in cognitively normal elderly patients with type 2 diabetes. Methods: Brain volumes for the superior, middle, and inferior frontal gyri and for the middle temporal gyrus were generated from structural T1 MRI in 181 study participants (Hp 1-1: n  = 24, Hp 2-1: n  = 77, Hp 2-2: n  = 80). Daily vitamin E intake was assessed using the Food Frequency Questionnaire. Analyses of covariance, …controlling for demographic and cardiovascular variables was used to evaluate whether the association of daily vitamin E intake with brain volume was modified by Hp genotype. Results: Average age was 70.8 (SD = 4.2) with 40% females, and mean Mini-Mental State Examination score of 28.17 (SD = 1.90). A significant interaction was found between vitamin E intake and Hp genotype in inferior frontal gyrus’ volume; p  = 0.0108. For every 1 microgram increase in vitamin E intake, the volume of the inferior frontal gyrus decreased by 0.955% for Hp 1-1 (p  = 0.0348), increased by 0.429% for Hp 2-1 (p  = 0.0457), and by 0.077% for Hp 2-2 (p  = 0.6318). There were no significant interactions between vitamin E intake and Hp genotype for the middle (p  = 0.6011) and superior (p  = 0.2025) frontal gyri or for the middle temporal gyrus (p  = 0.503). Conclusions: The effect of dietary vitamin E on the brain may differ by Hp genotype. Studies examining the impact of vitamin E on brain-related outcomes should consider Hp genotype. Show more

Keywords: Brain volume, diabetes, haptoglobin genotype, vitamin E

DOI: 10.3233/JAD-191294

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 649-658, 2020

Authors: Moazzami, Kasra | Wittbrodt, Matthew T. | Lima, Bruno B. | Kim, Jeong Hwan | Hammadah, Muhammad | Ko, Yi-An | Obideen, Malik | Abdelhadi, Naser | Kaseer, Belal | Gafeer, M. Mazen | Nye, Jonathon A. | Shah, Amit J. | Ward, Laura | Raggi, Paolo | Waller, Edmund K. | Bremner, J. Douglas | Quyyumi, Arshed A. | Vaccarino, Viola

Article Type: Research Article

Abstract: Background: Circulating progenitor cells (CPC) have been associated with memory function and cognitive impairment in healthy adults. However, it is unclear whether such associations also exist in patients with coronary artery disease (CAD). Objective: To assess the association between CPCs and memory performance among individuals with CAD. Methods: We assessed cognitive function in 509 patients with CAD using the verbal and visual Memory subtests of the Wechsler memory scale-IV and the Trail Making Test parts A and B. CPCs were enumerated with flow cytometry as CD45med /CD34+ blood mononuclear cells, those co-expressing other epitopes representing populations …enriched for hematopoietic and endothelial progenitors. Results: After adjusting for demographic and cardiovascular risk factors, lower number of endothelial progenitor cell counts were independently associated with lower visual and verbal memory scores (p for all < 0.05). There was a significant interaction in the magnitude of this association with race (p  < 0.01), such that the association of verbal memory scores with endothelial progenitor subsets was present in Black but not in non-Black participants. No associations were present with the hematopoietic progenitor-enriched cells or with the Trail Making Tests. Conclusion: Lower numbers of circulating endothelial progenitor cells are associated with cognitive impairment in patients with CAD, suggesting a protective effect of repair/regeneration processes in the maintenance of cognitive status. Impairment of verbal memory function was more strongly associated with lower CPC counts in Black compared to non-Black participants with CAD. Whether strategies designed to improve regenerative capacity will improve cognition needs further study. Show more

Keywords: Circulating progenitor cells, cognitive impairment, coronary artery disease, dementia, memory, trail making tests, Wechsler Memory Scale

DOI: 10.3233/JAD-191063

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 659-668, 2020

Authors: Zeghari, Radia | Manera, Valeria | Fabre, Roxane | Guerchouche, Rachid | König, Alexandra | Phan Tran, Minh Khue | Robert, Philippe

Article Type: Research Article

Abstract: Background: Apathy, a highly prevalent behavioral disorder in Alzheimer’s disease and other related disorders, is currently assessed using clinical scales as it is for all neuropsychiatric disorders. Objective: The aim of this study is to propose a new type of assessment using new technologies designed to assess loss of interest by a more implicit and indirect method. Methods: The Interest Game is a form of interactive self-report, where categories of interests are presented in order to quantify them and identify the activities that constitute them. Two indices can be extracted, the number of categories and the …number of activities selected. We compared the scores between three groups: Apathetic (A) and Non-Apathetic (NA) subjects (according to the Apathy Diagnostic Criteria) and controls with no objective cognitive impairment. Results: 95 subjects were included. Results showed that subjects from the A group had significantly less interests (both categories and images selected) than the NA group. As expected, the control group selected a higher number of categories than the other groups. The diagnosis (minor or major neurocognitive disorder) and level of education had also a significant effect on the number of categories selected. Furthermore, subjects with major neurocognitive disorder (NCD) had significantly less interests than minor NCD group. The number of categories measure was more sensitive than the number of images selected. Conclusion: The Interest Game is a promising tool to quantify and identify subject interests and differentiate between apathetic and non-apathetic subjects. Future studies should focus on including more apathetic subjects in the minor NCD group and validating this tool with the general population. Show more

Keywords: Apathy, interest, leisure activities, neurocognitive disorders, serious games

DOI: 10.3233/JAD-191282

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 669-677, 2020

Authors: Zhu, Yi | Zhong, Qian | Ji, Jie | Ma, Jinhui | Wu, Han | Gao, Yaxin | Ali, Nawab | Wang, Tong

Article Type: Research Article

Abstract: Background: Regular aerobic exercises could improve global cognition in older adults with mild cognitive impairment (MCI), such as aerobic dance a type of commonly practiced aerobic exercises. However, its effects remain debatable in improving the cognitive function in patients with MCI. Objective: The aim of this systematic review and meta-analysis is to evaluate the effects of aerobic dance on cognitive function among older adults with MCI. Methods: We searched articles in the MEDLINE, PubMed, Embase, and The Cochrane Library databases from inception to 28 February 2019, with the following criteria: 1) randomized controlled trials; 2) older …adults with MCI; 3) aerobic dance intervention. Results: Five studies of 842 participants were identified. This meta-analysis showed that aerobic dance can significantly improve global cognition (Mini-Mental State Examination: MD = 1.43; 95% CI:[0.59, 2.27]; p  = 0.0009; Alzheimer’s Disease Assessment Scale-Cognitive Subscale: MD=–2.30; 95% CI:[–3.60, –1.00]; p  = 0.0005), and delayed recall ability (SMD = 0.46;95% CI: [0.30, 0.62]; p  < 0.00001) in older adults with MCI. In addition, have positive effects on improving executive function (Trial-Making Test A: MD = –2.37;95% CI:[–4.16, –0.58]; p  = 0.010; Trial-Making Test B: MD = –16.0; 95% CI: [–30.03, –2.11]; p  = 0.020) and immediate recall ability (SMD = 0.24;95% CI: [0.01, 0.46]; p  = 0.04). Conclusion: Aerobic dance significantly improves global cognitive function and memory in older adults with MCI. In addition, it also benefits executive function. However, due to the limitations as the review states, more randomized controlled trials with better study design and larger sample sizes should be conducted in the future research to make it much clearer. Show more

Keywords: Aerobic dance, cognition, executive function, memory, meta-analysis, mild cognitive function, randomized controlled trials

DOI: 10.3233/JAD-190681

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 679-690, 2020

Authors: Maasakkers, Carlijn M. | de Heus, Rianne A.A. | Thijssen, Dick H.J. | Melis, René J.F. | Gardiner, Paul A. | Claassen, Jurgen A.H.R.

Article Type: Research Article

Abstract: Background: Physicians are cautious to prescribe antihypertensive drugs in frail older adults because of the potential adverse effects, especially in those with cognitive complaints. Lifestyle aspects might provide safe targets to lower blood pressure in older adults. Objective: Our goal was to evaluate the associations between activity patterns and blood pressure in memory clinic patients. Methods: We used an observational cross-sectional study to measure activity patterns with the ActivPAL accelerometer, and simultaneous home blood pressure levels in memory clinic patients (age range 51–87 years old). Office blood pressure was assessed during routine clinical practice. …Results: 41 patients (mean age of 74.3 (7.7) years of age, 46% female) were included. Sedentary parameters were associated with higher mean home blood pressure, with the strongest correlation between more prolonged sitting bouts and higher SBP (r  = 0.58, p  < .0001). Physical activity parameters were negatively associated with mean home blood pressure. Adjusted regression estimates remained significant, showing, e.g., a 4.5 (95% CI = 1.6;7.4) mmHg increase in SBP for every hour of sitting per day and a –1.0 (95% CI = –1.8;–0.2) mmHg decrease in DBP for every additional 1000 steps per day. No strong correlations were found between any of the activity pattern variables and office blood pressure. Conclusion: Associations between activity pattern variables and blood pressure were only found with home blood pressure measurements, not with office measurements. Longitudinal evaluations of these associations are now needed to explore if reducing prolonged sedentary bouts and increasing step count indeed serve as safe targets to lower blood pressure. Show more

Keywords: Blood pressure, cognitive decline, dementia, hypertension, physical activity, sedentary behavior

DOI: 10.3233/JAD-191310

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 691-697, 2020

Authors: Gardner, Raquel C. | Rivera, Ernesto | O’Grady, Megan | Doherty, Colin | Yaffe, Kristine | Corrigan, John D. | Bogner, Jennifer | Kramer, Joel | Wilson, Fiona

Article Type: Research Article

Abstract: Background: Traumatic brain injury (TBI) is an established risk factor for dementia but mechanisms are uncertain. Accurate TBI exposure classification is critical for cognitive aging research studies seeking to discover mechanisms and treatments of post-TBI dementia. Brief TBI screens, commonly used in epidemiological studies of cognitive aging, are insensitive, leading to exposure mis-classification. Comprehensive TBI interviews, while more sensitive, may be impractical. Objective: We aimed to develop and validate a scalable, self-administered, comprehensive, web-based, TBI exposure survey for use in international cognitive aging research. Methods: We adapted a gold-standard comprehensive TBI interview (the Ohio State University …TBI Identification Method; OSU TBI-ID) into a self-administered web-based survey for older adults (Older Adult modification of the OSU TBI-ID; OA OSU TBI-ID). We assessed reliability of our web-based survey versus the gold-standard interview among 97 older adults with normal cognition and mild cognitive impairment (MCI). In addition, we assessed sensitivity of the National Alzheimer’s Coordinating Center Uniform Data Set (NACC UDS) brief TBI screen versus the interview among 70 older adults with normal cognition. Results: Our OA OSU TBI-ID web-based survey had good to excellent reliability versus the interview (κ 0.66–0.73; ICCs 0.68–0.81) even among the sub-set with MCI (κ 0.74–0.88; ICCs 0.76–0.85), except for several age-at-injury variables. The NACC UDS brief TBI screen missed 50% of TBI exposures identified using the OSU TBI-ID interview. Conclusion: The OSU TBI-ID interview and web-based survey may facilitate more accurate TBI exposure classification in cognitive aging research thereby accelerating discovery of targetable mechanisms of post-TBI dementia. Show more

Keywords: Clinical research, cognitive aging, reliability, screening, traumatic brain injury, validation

DOI: 10.3233/JAD-191138

Citation: Journal of Alzheimer's Disease, vol. 74, no. 2, pp. 699-711, 2020