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

Authors: Kim, Jieun | Lee, Yujeong | Lee, Seulah | Kim, Kipom | Song, Minjung | Lee, Jaewon

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease worldwide, but its cause remains unclear. Although a few drugs can provide temporary and partial relief of symptoms in some patients, no curative treatment is available. Therefore, attention has been focused on research using stem cells to treat AD. Among stem cells, mesenchymal stem cells (MSCs) have been used to treat the related pathologies in animal models of AD, and other neurodegenerative disease. This review describes latest research trends on the use of MSC-based therapies in AD and its action of mechanism. MSCs have several beneficial effects. They would be …specified as the reduction of neuroinflammation, the elimination of amyloid-β, neurofibrillary tangles, and abnormal protein degradation, the promotion of autophagy-associated and blood-brain barrier recoveries, the upregulation of acetylcholine levels, improved cognition, and the recovery of mitochondrial transport. Therefore, this review describes the latest research trends in MSC-based therapy for AD by demonstrating the importance of MSC-based therapy and understanding of its mechanisms in AD and discusses the limitations and perspectives of stem cell therapy in AD. Show more

Keywords: Alzheimer’s disease, mesenchymal stem cells, stem cell therapy

DOI: 10.3233/JAD-200219

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2020

Authors: Xu, Anping | Tang, Yinshan | Zeng, Qingtao | Wang, Xin | Tian, Huiling | Zhou, You | Li, Zhigang

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is a neurodegenerative disease, yet there is no effective treatment. Electroacupuncture (EA) is a complementary alternative medicine approach. In clinical and animal studies, EA promotes cognition in AD and vascular dementia. It has been previously reported that cognitive decline in AD might be closely related to reduced glucose intake in the brain. It is worth mentioning that the regions of glucose hypometabolism are usually found to be associated with neuroinflammation. Objective: This study is to explore whether the protective mechanism of EA on cognition is related to the regulation of glucose metabolism and neuroinflammation. …Methods: APP/PS1 mice were randomly divided into AD group and the treatment (AD + EA) group. In the AD + EA group, EA was applied on Baihui (GV20) and Yintang (GV29) for 20 min and then pricked at Shuigou (GV26), once every alternate day for 4 weeks. Morris water maze (MWM) tests were performed to evaluate the effects of EA treatment on cognitive functions. 18 F-FDG PET, immunofluorescence, and western blot were used to examine the mechanisms underlying EA effects. Results: From MWM tests, EA treatment significantly improved cognition of APP/PS1 mice. From the 18 F-FDG PET, the levels of uptake rate of glucose in frontal lobe were higher than the AD group after EA. From immunofluorescence and western blot, amyloid-β (Aβ) and neuroinflammation were reduced after EA. Conclusion: These results suggest that EA may prevent cognitive decline in AD mouse models by enhancing glucose metabolism and inhibiting inflammation-mediated Aβ deposition in the frontal lobe. Show more

Keywords: Alzheimer’s disease, cognition, electroacupuncture, 18F-FDG PET, frontal lobe, glucose metabolism, neuroinflammation

DOI: 10.3233/JAD-200242

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2020

Authors: Schneider, Julia | Schönstein, Anton | Teschauer, Winfried | Kruse, Andreas | Teichmann, Birgit

Article Type: Research Article

Abstract: Background: The outcomes of hospitalized People with Dementia (PwD) are likely to be negative due to, among other key causes, negative staff attitudes and limited staff knowledge regarding dementia. Targeted interventions have been shown to positively change the attitudes of the hospital staff while also increasing their overall knowledge of dementia. However, training effects are often short-lived and frequently long-term effects are not examined in studies. Objective: To examine whether attending a dementia training program changes the attitudes of hospital staff toward PwD and/or increases their knowledge levels about dementia, and whether or not these changes are stable. …Methods: The training program lasted two days and N  = 60 attending hospital staff members agreed to participate in the study. Data were assessed with questionnaires prior to the training, 3 months, and 6 months after the training. German versions of the Dementia Attitude Scale (DAS-D) and the Knowledge in Dementia (KIDE) scale were used. Additionally, data about perception of PwD and confidence in dealing with challenging behavior were collected and analyzed. Results: After the training program, participants showed a significantly better attitude toward PwD as measured by DAS-D. These time-effects occurred in both DAS-D subscales (“dementia knowledge” and “social comfort”). Although a positive trend could be seen in the KIDE scale, no statistically significant increase occurred over time. Conclusion: Specialist training programs seem to be promising in positively changing attitudes toward and increasing knowledge about PwD with long-term effects. Further research should address the effects of attitude change in patient care. Show more

Keywords: Education, health facilities, health personnel, neurocognitive disorders, staff development

DOI: 10.3233/JAD-200268

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

Authors: Lepper, Simon | Rädke, Anika | Wehrmann, Hannah | Michalowsky, Bernhard | Hoffmann, Wolfgang

Article Type: Research Article

Abstract: Background: Treatment decisions based on guidelines rather than patients’ preferences determine adherence to and compliance with treatment, which, in turn, could improve health-related outcomes. Objectives: To summarize the stated treatment and care preferences of people with dementia (PwD). Methods: A systematic review was conducted to assess the stated preferences of PwD. The inclusion criterion was the use of quantitative methods to elicit stated preferences, enabling a ranking of preferences. Results: Eleven studies revealed preferences for diagnostics, treatment decisions, patient-related outcomes, care services, end-of-life care, leisure activities, and digital life story work. PwDs prefer accurate, …pain-free, and comfortable diagnostic procedures without radioactive markers as well as being accompanied by a caregiver. PwD’s quality of life (QoL), self-efficacy, and depression were equally most important for PwD and caregivers. However, PwD memory was only important for caregivers but not for PwD, and caregiver QoL was moderately important for PwD but least important for caregivers. Additionally, comfort and family involvement were most important for patients’ end-of-life care, whereas caregivers most preferred good communication and pain management. Also, preferences depend on the living situation: Patients living not alone prefer a regular care provider most, whereas those living alone only want to live nearby the caregiver. Preferences for leisure activities did not differ between past and present ratings, indicating that PwD prefer activities that have always been carried out. Conclusion: Only a few studies have applied quantitative methods to elicit the preferences of PwD. More research is needed to capture the stated preferences for the treatment, care, and support of PwD to improve health-related outcomes and the allocation of healthcare resources. Show more

Keywords: Dementia, decision making, patient outcome assessment, patient preference

DOI: 10.3233/JAD-191299

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-17, 2020

Authors: Hu, Li | Zhu, Shaoping | Peng, Xiaoping | Li, Kanglan | Peng, Wanjuan | Zhong, Yu | Kang, Chenyao | Cao, Xingxing | Liu, Zhou | Zhao, Bin

Article Type: Research Article

Abstract: Background: Excessive salt intake is considered an important risk factor for cognitive impairment, which might be the consequence of imbalanced intestinal homeostasis. Objective: To investigate the effects of dietary salt on the gut microbiota and cognitive performance and the underlying mechanisms. Methods: Adult female C57BL6 mice were maintained on either normal chow (control group, CON) or sodium-rich chow containing 8% NaCl (high-salt diet, HSD) for 8 weeks. Spatial learning and memory ability, short-chain fatty acids (SCFAs) concentrations, gut bacterial flora composition, blood-brain barrier permeability, and proinflammatory cytokine levels and apoptosis in the brain were evaluated. …Results: The mice fed an HSD for 8 weeks displayed impaired learning and memory abilities. HSD significantly reduced the proportions of Bacteroidetes (S24-7 and Alloprevotella) and Proteobacteria and increased that of Firmicutes (Lachnospiraceae and Ruminococcaceae). SCFA concentrations decreased in the absolute concentrations of acetate, propionate, and butyrate in the fecal samples from the HSD-fed mice. The HSD induced both BBB dysfunction and microglial activation in the mouse brain, and increased the IL-1β , IL-6, and TNF-α expression levels in the cortex. More importantly, the degree of apoptosis was higher in the cortex and hippocampus region of mice fed the HSD, and this effect was accompanied by significantly higher expression of cleaved caspase-3, caspase-3, and caspase-1. Conclusion: The HSD directly causes cognitive dysfunction in mice by eliciting an inflammatory environment and triggering apoptosis in the brain, and these effects are accompanied by gut dysbiosis, particularly reduced SCFA production. Show more

Keywords: Blood-brain barrier, cognition, gut microbiota, high-salt diet, microglia, short-chain fatty acids

DOI: 10.3233/JAD-200035

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

Authors: Sheng, Can | Yang, Kun | Wang, Xiaoni | Li, Hongyan | Li, Taoran | Lin, Li | Liu, Yi | Yang, Qin | Wang, Xiaoqi | Wang, Xue | Sun, Yu | Han, Ying

Article Type: Research Article

Abstract: Background: Subjective cognitive decline (SCD) is considered the earliest symptomatic manifestation of preclinical Alzheimer’s disease (AD). Currently, given the lack of effective and curable pharmacological treatments for AD, non-pharmacological interventions (NPIs) for individuals with SCD may provide a valuable opportunity for the secondary prevention of AD. Objective: This systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, aimed to investigate the benefits of current NPIs in the population with SCD. Methods: The online electronic databases, including MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, PsycInfo, and CINAHL, were searched to identify randomized controlled trials …of NPIs for SCD. Intervention strategies were psychological and health-related education interventions, mind-body therapy, lifestyle modification, cognitive training, and multidomain interventions. Outcomes included subjective memory, objective memory, global cognitive function, psychological well-being, and mood. Study quality was determined using the criteria of the Cochrane collaboration’s tool. The Hedges’ g of change was analyzed. Results: Eighteen studies were included in this review and meta-analysis. Overall, psychological and health-related education interventions exhibited a medium effect on objective memory function (Hedges’ g  = 0.53, p  = 0.01). Cognitive training led to a small effect on objective memory, which was marginal statistically (Hedges’ g  = 0.19, p  = 0.05). In addition, cognitive training also significantly improved subjective memory performance (Hedges’ g  = 0.49, p  = 0.0003) and psychological well-being (Hedges’ g  = 0.27, p  = 0.03). Conclusion: Overall, the psychological intervention and cognitive training may be beneficial to cognitive function and psychological well-being. NPIs may be effectively implemented in older adults with SCD. Show more

Keywords: Alzheimer’s disease, cognitive training, intervention, lifestyle, non-pharmacological, psychological, subjective cognitive decline

DOI: 10.3233/JAD-191295

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-18, 2020

Authors: de Leeuw, Francisca A. | Honer, William G. | Schneider, Julie A. | Morris, Martha Clare

Article Type: Research Article

Abstract: Background: Higher vitamin E intake has been widely related to lower risks of cognitive decline and dementia. Animal models suggest that this relationship might be (partially) explained by the protection of vitamin E against presynaptic protein oxidation. Objective: In this cross-sectional study, we aimed to examine the associations between brain tocopherols and presynaptic protein levels in elderly humans. Methods: We examined associations of α - and γ -tocopherol brain levels with presynaptic protein levels in 113 deceased participants (age 88.5±6.0 years, 45 (40%) female) from the prospective Memory and Aging project. Three distinct presynaptic proteins, a …SNARE protein composite, a synaptotagmin synaptophysin composite and the protein-protein interaction between synaptosomal-associated protein 25 (SNAP-25), and syntaxin were measured in two cortical brain regions. Linear regression models assessed associations of brain tocopherols with presynaptic protein levels. Results: Higher brain γ -tocopherol levels were associated with higher levels of the SNARE protein composite, complexin-I, complexin-II, the synaptotagmin synaptophysin composite, and septin-5 in the midfrontal cortex (B(SE) = 0.272 to 0.412 (0.084 to 0.091), p  < 0.001 to 0.003). When additionally adjusted for global Alzheimer’s disease pathology, cerebral infarcts, and Lewy body disease pathology, these associations remained largely similar. No associations were found between α -tocopherol and presynaptic protein levels. Conclusion: In this cross-sectional study, we found higher brain γ -tocopherol levels were associated with presynaptic protein levels in the midfrontal cortex. These results are consistent with a proposed role of vitamin E to maintain presynaptic protein levels. Show more

Keywords: Antioxidants, SNARE protein, tocopherols, vitamin E

DOI: 10.3233/JAD-200166

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

Authors: Trammell, Antoine R. | McDaniel, Darius J. | Obideen, Malik | Okafor, Maureen | Thomas, Tiffany L. | Goldstein, Felicia C. | Shaw, Leslie M. | Hajjar, Ihab M.

Article Type: Research Article

Abstract: Background: African Americans (AA) have a higher Alzheimer’s disease (AD) prevalence and report more perceived stress than White Americans. The biological basis of the stress-AD link is unclear. This study investigates the connection between stress and AD biomarkers in a biracial cohort. Objective: Establish biomarker evidence for the observed association between stress and AD, especially in AA. Methods: A cross-sectional study (n  = 364, 41.8% AA) administering cognitive tests and the perceived stress scale (PSS) questionnaire. A subset (n  = 309) provided cerebrospinal fluid for measurement of Aβ 42 , Tau, Ptau, Tau/Aβ 42 (TAR), and Ptau/Aβ …42 (PTAR). Multivariate linear regression, including factors that confound racial differences in AD, was performed. Results: Higher PSS scores were associated with higher Ptau (β = 0.43, p  = 0.01) and PTAR (β = 0.005, p  = 0.03) in AA with impaired cognition (mild cognitive impairment). Conclusion: Higher PSS scores were associated with Tau-related AD biomarker indices in AA/MCI, suggesting a potential biological connection for stress with AD and its racial disparity. Show more

Keywords: African Americans, Alzheimer’s disease, tauopathy, amyloid-β peptides, cognitive function, mild cognitive impairment, neurocognitive tests, psychological stress

DOI: 10.3233/JAD-200089

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

Authors: Tan, Ji-Ping | Wang, Xiaoxiao | Lan, Xiaoyang | Li, Nan | Zhang, Shimin | Zhao, Yiming | Wang, Lu-Ning

Article Type: Research Article

Abstract: Background: Over time, improved cognitive abilities in elderly individuals lead to an overall increase in performance on widely used cognitive screening tests (e.g., Mini-Mental State Examination, MMSE) and impact screening efficacy. Objective: We aimed to examine the epoch effect on cognitive function measured using MMSE, in addition to the influence of demographic characteristics on MMSE. We also evaluated the ability of the MMSE in detecting dementia and examined the discrimination ability and measurement precision of the MMSE. Methods: In a cross-sectional survey, Chinese veterans aged ≥60 years were interviewed. Multiple linear regression analysis was applied to …explore the factors affecting the MMSE. The expected MMSE score was calculated to examine the epoch effect. The diagnostic accuracy of the MMSE was determined via receiver operating characteristic curve analyses. Item response theory methods were implemented using Stata 16.0. Results: The MMSE score increased with higher education and decreased with advancing age. The observed MMSE score in this study (26.9) was higher than the expected MMSE score (24.9). It demonstrated 78.3% /84.1% /89.9% sensitivity and 85.8% /79.5% /66.8% specificity in detecting dementia using the cut-off score 25/26/27. The MMSE showed reduced discrimination and provided little information for ability level of −1 and above. Conclusion: Improved cognitive ability over time may increase the performance on cognitive screening tests (e.g., MMSE). This impact of epoch in cognitive function emphasizes the importance of regularly updating cognitive screening tests. Show more

Keywords: Dementia, epoch effect, item response theory, Mini-Mental State Examination

DOI: 10.3233/JAD-200112

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

Authors: Lamballais, Sander | Zijlmans, Jendé L. | Vernooij, Meike W. | Ikram, M. Kamran | Luik, Annemarie I. | Ikram, M. Arfan

Article Type: Research Article

Abstract: Background: Individual differences in the risk to develop dementia remain poorly understood. These differences may partly be explained through reserve, which is the ability to buffer cognitive decline due to neuropathology and age. Objective: To determine how much early and late–life cognitive reserve (CR) and brain reserve (BR) contribute to the risk of dementia. Methods: 4,112 dementia-free participants (mean age = 66.3 years) from the Rotterdam Study were followed up for on average 6.0 years. Early-life CR and BR were defined as attained education and intracranial volume, respectively. Late-life CR was derived through variance decomposition based on cognition. …Late-life BR was set as the total non-lesioned brain volume divided by intracranial volume. Results: Higher early-life CR (hazard ratio = 0.48, 95% CI = [0.21; 1.06]) but not early-life BR associated with a lower risk of incident dementia. Higher late-life CR (hazard ratio = 0.57, 95% CI = [0.48; 0.68]) and late-life BR (hazard ratio = 0.54, 95% CI = [0.43; 0.68]) also showed lower levels of dementia. Combining all proxies into one model attenuated the association between early-life CR and dementia (hazard ratio = 0.56, 95% CI = [0.25; 1.25]) whereas the other associations were unaffected. These findings were stable upon stratification for sex, age, and APOE ɛ 4. Finally, high levels of late-life CR and BR provided additive protection against dementia. Conclusion: The findings illustrate the importance of late-life over early-life reserve in understanding the risk of dementia, and show the need to study CR and BR conjointly. Show more

Keywords: Cognition, cognitive reserve, dementia, education, neuroimaging

DOI: 10.3233/JAD-200264

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