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

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

Article Type: Research Article

Abstract: Background: Scales for cognitive deterioration usually depend on education level. Objective: We aimed to study the clinical utility of a culture-free Go/No-Go task in a multi-ethnic cohort with low education level. Methods: Sixty-four participants with less than 4 years of formal education were included and divided on the basis of their Clinical-Dementia-Rate scores (CDR) into cognitively unimpaired (CDR = 0), mild cognitive impairment (MCI; CDR = 0.5), and early Alzheimer’s disease (AD, CDR = 1). All underwent a 90-s Continuous Visual Attention Test. This test consisted of a 90-s Go/No-go task with 72 (80%) targets and 18 (20%) non-targets. For each participant, …reaction times and intraindividual variability of reaction times of all correct target responses, as well as the number of omission and commission errors were evaluated. Coefficient of variability was calculated for each participant by dividing the standard deviation of the reaction times by the mean reaction time. A MANCOVA was performed to examine between-group differences using age and sex as covariates. Discriminate analysis was performed to find the most reliable test-variable to discriminate the three groups. Results: Commission error, intraindividual variability of reaction time, and coefficient of variability progressively worsened with increasing CDR level. Discriminant analysis demonstrated that coefficient of variability was the best discriminant factor, followed by intraindividual variability of reaction time and commission error. Conclusion: The Go/No-Go task was able to discriminate people with MCI or early AD from controls in the setting of illiteracy. Show more

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

DOI: 10.3233/JAD-200881

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2020

Authors: Shams, Mana | Martola, Juha | Charidimou, Andreas | Granberg, Tobias | Ferreira, Daniel | Westman, Eric | Wintermark, Max | Iv, Michael | Larvie, Mykol | Kristoffersen Wiberg, Maria | Kaijser, Magnus | Forsgard, Niklas | Zetterberg, Henrik | Wahlund, Lars-Olof | Shams, Sara

Article Type: Research Article

Abstract: Background: Brain metal homeostasis is essential for brain health, and deregulation can result in oxidative stress on the brain parenchyma. Objective: Our objective in this study was to focus on two hemorrhagic MRI manifestations of small vessel disease [cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS)] and associations with cerebrospinal fluid (CSF) iron levels. In addition, we aimed to analyze CSF biomarkers for dementia and associations with CSF metal levels. Methods: This is a cross-sectional study of 196 patients who underwent memory clinic investigation, including brain MRI. CSF was collected and analyzed for metals, amyloid-β (Aβ) …42, total tau (T-tau), and phosphorylated tau (P-tau), and CSF/serum albumin ratios. Statistical analyses were performed using generalized linear models. Results: No significant difference was found between CSF metal levels across diagnostic groups. Higher iron and copper levels were associated with higher CSF levels of Aβ42 , T-tau, P-tau, and CSF/serum albumin ratios (p  < 0.05). Zinc was associated with higher CSF/serum albumin ratios. There was no significant association between CMBs or cSS and CSF iron levels. An increase in CSF iron with the number of CMBs was seen in APOE ɛ 4 carriers. Conclusion: CSF iron levels are elevated with cerebral microbleeds in APOE ɛ 4 carriers, with no other association seen with hemorrhagic markers of small vessel disease. The association of elevated CSF iron and copper with tau could represent findings of increased neurodegeneration in these patients. Show more

Keywords: Alzheimer’s disease, cerebrospinal fluid, cognitive aging, dementia, magnetic resonance imaging

DOI: 10.3233/JAD-200656

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-8, 2020

Authors: Clare, Linda | Martyr, Anthony | Henderson, Catherine | Gamble, Laura | Matthews, Fiona E. | Quinn, Catherine | Nelis, Sharon M. | Rusted, Jennifer | Thom, Jeanette | Knapp, Martin | Hart, Nicola | Victor, Christina

Article Type: Research Article

Abstract: Background: A significant proportion of people with dementia live alone, but little is known about their specific needs. Objective: To understand the profile of people living alone with mild-to-moderate dementia in the UK and identify any systematic differences associated with living situation. Methods: We analyzed cross-sectional data from 1,541 people with mild-to-moderate dementia and 1,277 caregivers participating in the IDEAL cohort at the first wave of assessment. Results: There were 1,256 (81.5%) people with dementia living with others and 285 (18.5%) living alone, of whom 51 (3% of whole sample) reported little or no …informal support. There were relatively few differences associated with living situation and odds ratios were generally small. People living alone were older on average, and more likely to be female, than those living with others. Those living alone were more likely to have higher cognitive ability and self-reported functional ability, and more social contact with those from other households. They were also lonelier, expressed less satisfaction with life, and used home care services and equipment more. There were no differences in symptoms, mood, quality of life, or well-being. Conclusion: The findings support the view that it is possible to ‘live well’ with mild-to-moderate dementia while living alone, given appropriate support, including home care and equipment. Nevertheless, it is important to consider how those living alone may be supported to have a more satisfactory experience, and how health and social care services can best respond to their needs. Show more

Keywords: Aids and adaptations, Alzheimer’s disease, service use, social capitals, assets and resources, vascular dementia

DOI: 10.3233/JAD-200638

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-10, 2020

Authors: Bartels, Claudia | Kögel, Anna | Schweda, Mark | Wiltfang, Jens | Pentzek, Michael | Schicktanz, Silke | Schneider, Anja

Article Type: Research Article

Abstract: Background: The National Institute of Aging and Alzheimer’s Association’s diagnostic recommendations for preclinical Alzheimer’s disease (AD) and mild cognitive impairment (MCI) define AD by pathological processes which can be detected by biomarkers. These criteria were established as part of a research framework intended for research purposes but progressively enter the clinical practice. Objective: We investigated the availability, frequency of use, interpretation, and therapeutic implications of biomarkers for the etiologic diagnosis and prognosis in MCI and subjective cognitive decline (SCD) in routine clinical care. Methods: We conducted a cross-sectional questionnaire survey among 215 expert dementia centers (hospitals …and memory clinics) in Germany. Results: From the 98 centers (45.6% of contacted centers) included, two-thirds reported use of the cerebrospinal fluid (CSF) biomarkers Aβ42 , tau, and phospho-tau in the diagnostic workup of MCI and one third in SCD. CSF biomarker analysis was more often employed by neurological (MCI 84%; SCD 42%) compared to psychiatric institutions (MCI 61%; SCD 33%; p ≤0.001). Although dementia experts disagreed on the risk of progression associated with different CSF biomarker constellations, CSF biomarker results guided therapeutic decisions: ∼40% of responders reported to initiate cholinesterase inhibitor therapy in MCI and 18% in SCD (p  = 0.006), given that all CSF biomarkers were in the pathological range. Conclusion: Considering the vast heterogeneity among dementia expert centers in use of CSF biomarker analysis, interpretation of results, and therapeutic consequences, a standardization of biomarker-based diagnosis practice in pre-dementia stages is needed. Show more

Keywords: Alzheimer’s disease, biomarker, mild cognitive impairment, prediction, questionnaires, subjective cognitive decline, surveys

DOI: 10.3233/JAD-200794

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2020

Authors: Tan, Meng-Shan | Yang, Yu-Xiang | Wang, Hui-Fu | Xu, Wei | Tan, Chen-Chen | Zuo, Chuan-Tao | Dong, Qiang | Tan, Lan | Yu, Jin-Tai | Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Amyloid-β (Aβ) plaques and tau neurofibrillary tangles are two neuropathological hallmarks of Alzheimer’s disease (AD), which both can be visualized in vivo using PET radiotracers, opening new opportunities to study disease mechanisms. Objective: Our study investigated 11 non-PET factors in 5 categories (including demographic, clinical, genetic, MRI, and cerebrospinal fluid (CSF) features) possibly affecting PET amyloid and tau status to explore the relationships between amyloid and tau pathology, and whether these features had a different association with amyloid and tau status. Methods: We included 372 nondemented elderly from the Alzheimer’s Disease Neuroimaging Initiative cohort. …All underwent PET amyloid and tau analysis simultaneously, and were grouped into amyloid/tau quadrants based on previously established abnormality cut points. We examined the associations of above selected features with PET amyloid and tau status using a multivariable logistic regression model, then explored whether there was an obvious correlation between the significant features and PET amyloid or tau levels. Results: Our results demonstrated that PET amyloid and tau status were differently affected by patient features, and CSF biomarker features provided most significant values associating PET findings. CSF Aβ42/40 was the most important factor affecting amyloid PET status, and negatively correlated with amyloid PET levels. CSF pTau could significantly influence both amyloid and tau PET status. Besides CSF pTau and Aβ42 , APOE ɛ 4 allele status and Mini-Mental State Examination scores also could influence tau PET status, and significantly correlated with tau PET levels. Conclusion: Our results support that tau pathology possibly affected by Aβ-independent factors, implicating the importance of tau pathology in AD pathogenesis. Show more

Keywords: Alzheimer’s disease, amyloid-β, APOE, biomarker, cerebrospinal fluid, Mini-Mental State Examination, PET, tau

DOI: 10.3233/JAD-200124

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-8, 2020

Authors: Zhang, Zhihua | Sheng, Hongxia | Liao, Li | Xu, Chen | Zhang, Ang | Yang, Yang | Zhao, Long | Duan, Lian | Chen, Hu | Zhang, Bin

Article Type: Research Article

Abstract: Background: Mesenchymal stem cells-conditioned medium (MSC-CM) provides a promising cell-free therapy for Alzheimer’s disease (AD) mainly due to the paracrine of MSCs, but the precise mechanisms remain unclear. Studies suggests that mitochondrial dysfunction precedes the accumulation of amyloid-β plaques and neurofibrillary tangles, and involves in the onset and development of AD. Objective: In the present study, we evaluated the protective effects and explored the related-mitochondrial mechanisms of human umbilical cord derived MSC-CM (hucMSC-CM) in an AD model in vitro . Methods: To this end, an AD cellular model was firstly established by okadaic acid (OA)-treated SH-SY5Y …cells, and then treated by hucMSC-CM to assess the oxidative stress, mitochondrial function, apoptosis, AD-related genes, and signaling pathways. Results: hucMSC-CM significantly deceased tau phosphorylated at Thr181 (p181 -tau) level, which was increased in AD. hucMSC-CM also alleviated intracellular and mitochondrial oxidative stress in OA-treated SH-SY5Y cells. In addition, hucMSC-CM suppressed apoptosis and improved mitochondrial function in OA-treated SH-SY5Y cells. Flow cytometric analysis indicated that hucMSC-CM exerted the protective effects relying on or partly extracellular vesicle (EV) mitochondrial transfer from hucMSCs to OA-treated SH-SY5Y cells. Moreover, RNA sequencing data further demonstrated that hucMSC-CM regulated many AD-related genes, signaling pathways and mitochondrial function. Conclusion: These results indicated that MSC-CM or MSC-EVs containing abundant mitochondria may provide a novel potential therapeutic approach for AD. Show more

Keywords: Alzheimer’s disease, apoptosis, mesenchymal stem cell-conditioned medium, mitochondrial dysfunction, mitochondrial transfer

DOI: 10.3233/JAD-200686

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-16, 2020

Authors: Ghilain, Matthieu | Hobeika, Lise | Lesaffre, Micheline | Schiaratura, Loris | Singh, Ashmita | Six, Joren | Huvent-Grelle, Dominique | Puisieux, François | Samson, Séverine

Article Type: Research Article

Abstract: Background: Music-based interventions appear to be efficient approaches to improve emotional, social, and cognitive functioning of patients with neurodegenerative diseases. Objective: Because benefits seem to increase with patient’s motor involvement, we studied sensorimotor synchronization (SMS) abilities of patients with cognitive impairments (Alzheimer’s disease, vascular and mixed dementia) and of patients with no evidence of cognitive impairments. More specifically, we compared the impact of a live performance by a musician to a video recording on SMS. Methods: SMS to a metronomic or a musical stimulus was assessed while patients watched a live musician or his pre-recorded video. …Results: SMS to a metronome was better than to music but this effect was modulated by the social context. While SMS to a metronome was better when facing a video than a live performance, there was no impact of social context on SMS to music. No group differences of SMS were found. Conclusion: The decrease in SMS to a metronome in a live performance may be due to social pressure. Such a pressure might be removed in pleasant social activities, like moving with music in a group, explaining the lack of effect on SMS to music. We found no performance differences in groups, suggesting relatively spared SMS in cognitively impaired patients. By showing that it is possible to encourage patients to synchronize with others, even when facing a video, our results indicate that SMS can be used as a relevant predictor in clinical trials and open up promising therapeutic options for isolated patients. Show more

Keywords: Aging, Alzheimer’s disease, cognitive impairment, dementia, motor activity, music therapy, social interaction

DOI: 10.3233/JAD-200521

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2020

Authors: Gkioka, Mara | Schneider, Julia | Kruse, Andreas | Tsolaki, Magda | Moraitou, Despina | Teichmann, Birgit

Article Type: Research Article

Abstract: Background: People with dementia (PwD) are frequently admitted to hospital settings. The lack of proper dementia knowledge, poor communication skills, negative attitudes toward dementia, and lack of confidence affects the quality of care, thus development of dementia trainings has increased. Nevertheless, literature regarding the effectiveness of training implementation is limited. Objective: The aim of this narrative synthesis is to 1) identify the characteristics of training programs and 2) explore the effectiveness of these training programs in everyday clinical practice. Methods: A systematic search in PubMed, PsycINFO, CINAHL, and Cochrane was conducted, including qualitative and quantitative peer-reviewed …studies. Holton’s evaluation model with its three outcome levels (learning, individual performance, and organizational results) was adopted. 14 studies were included. Results: The synthesis of the results was divided into two parts: 1) to describe the characteristics and content of trainings 2) to evaluate the effectiveness of training programs according to the three outcome levels of Holton’s model, taking into consideration its construct domains: ability, motivation, and environment. Learning outcomes were assessed in all selected studies: 13 studies observed changes in individual performance, four studies reported changes within the organizational level, and only five showed sustainable changes over time. Conclusion: Person-centered care (PCC) approaches, interactive and varied teaching methods, supporting conditions like champions, action plans, and setting care policies, are all characteristics of effective trainings. Successful programs should be sustainable over time, demonstrating positive outcomes across the organization. Based on current findings, there is a lack of adequate evaluation with regard to training programs on the organizational level. Show more

Keywords: Alzheimer’s disease, education, health facilities, literature synthesis, personnel, workforce development

DOI: 10.3233/JAD-200741

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-20, 2020

Authors: Liu, Kathy Y. | Costello, Harry | Reeves, Suzanne | Howard, Robert | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Agitation in Alzheimer’s disease (AD) has been hypothesized to be an expression of anxiety, but whether anxiety early in the course of dementia could be a risk factor for developing later agitation is unknown. Objective: We used the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to examine the longitudinal relationship between anxiety and incident agitation in individuals with a diagnosis of AD at baseline or during follow-up. Methods: Longitudinal neuropsychiatric symptom data from AD individuals who were agitation-free at study baseline (N  = 272) were analyzed using mixed effects regression models to test the longitudinal relationship between …baseline and incident anxiety with incident agitation. Results: Anxiety at baseline was not associated with subsequent agitation, but there was a positive linear relationship between incident anxiety and agitation over the study duration. Baseline apathy and delusions were consistently associated with subsequent agitation and greater disease severity and illness duration also appeared to be risk factors for agitation. Conclusion: Our findings support the concept that anxiety and agitation are likely to be distinct rather than equivalent constructs in mild-moderate AD. Future longitudinal cohort studies are needed to replicate these findings and further characterize potential risk factors for agitation, such as apathy and delusions. Show more

Keywords: Agitation, Alzheimer’s disease, Alzheimer’s Disease Neuroimaging Initiative, anxiety, apathy, delusions

DOI: 10.3233/JAD-200516

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2020

Authors: Hallab, Asma | Lange, Catharina | Apostolova, Ivayla | Özden, Cansu | Gonzalez-Escamilla, Gabriel | Klutmann, Susanne | Brenner, Winfried | Grothe, Michel J. | Buchert, Ralph | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Research in rodents identified specific neuron populations encoding information for spatial navigation with particularly high density in the medial part of the entorhinal cortex (ERC), which may be homologous with Brodmann area 34 (BA34) in the human brain. Objective: The aim of this study was to test whether impaired spatial navigation frequently occurring in mild cognitive impairment (MCI) is specifically associated with neurodegeneration in BA34. Methods: The study included baseline data of MCI patients enrolled in the Alzheimer’s Disease Neuroimaging Initiative with high-resolution structural MRI, brain FDG PET, and complete visuospatial ability scores of the …Everyday Cognition test (VS-ECog) within 30 days of PET. A standard mask of BA34 predefined in MNI space was mapped to individual native space to determine grey matter volume and metabolic activity in BA34 on MRI and on (partial volume corrected) FDG PET, respectively. The association of the VS-ECog sum score with grey matter volume and metabolic activity in BA34, APOE4 carrier status, age, education, and global cognition (ADAS-cog-13 score) was tested by linear regression. BA28, which constitutes the lateral part of the ERC, was used as control region. Results: The eligibility criteria led to inclusion of 379 MCI subjects. The VS-ECog sum score was negatively correlated with grey matter volume in BA34 (β= –0.229, p  = 0.022) and age (β= –0.124, p  = 0.036), and was positively correlated with ADAS-cog-13 (β= 0.175, p  = 0.003). None of the other predictor variables contributed significantly. Conclusion: Impairment of spatial navigation in MCI is weakly associated with BA34 atrophy. Show more

Keywords: Entorhinal cortex, 18F-fluorodeoxyglucose, grid cells, magnetic resonance imaging, mild cognitive impairment, positron emission tomography, spatial navigation, volumetry

DOI: 10.3233/JAD-200520

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2020