Journal of Alzheimer's Disease - Volume 67, issue 3

Authors: van der Hoek, Marjanne D. | Nieuwenhuizen, Arie | Keijer, Jaap | Ashford, J. Wesson

Article Type: Research Article

Abstract: Cognitive impairment is a leading cause of dysfunction in the elderly. When mild cognitive impairment (MCI) occurs in elderly, it is frequently a prodromal condition to dementia. The Montreal Cognitive Assessment (MoCA) is a commonly used tool to screen for MCI. However, this test requires a face-to-face administration and is composed of an assortment of questions whose responses are added together by the rater to provide a score whose precise meaning has been controversial. This study was designed to evaluate the performance of a computerized memory test (MemTrax), which is an adaptation of a continuous recognition task, with respect to …the MoCA. Two outcome measures are generated from the MemTrax test: MemTraxspeed and MemTraxcorrect . Subjects were administered the MoCA and the MemTrax test. Based on the results of the MoCA, subjects were divided in two groups of cognitive status: normal cognition (n = 45) and MCI (n = 37). Mean MemTrax scores were significantly lower in the MCI than in the normal cognition group. All MemTrax outcome variables were positively associated with the MoCA. Two methods, computing the average MTX score and linear regression were used to estimate the cutoff values of the MemTrax test to detect MCI. These methods showed that for the outcome MemTraxspeed a score below the range of 0.87 – 91 s-1 is an indication of MCI, and for the outcome MemTraxcorrect a score below the range of 85 – 90% is an indication for MCI. Show more

Keywords: Alzheimer’s disease, continuous performance task, dementia, elderly, memory, mild cognitive impairment, screening

DOI: 10.3233/JAD-181003

Citation: Journal of Alzheimer's Disease, vol. 67, no. 3, pp. 1045-1054, 2019

Authors: Möllers, Tobias | Perna, Laura | Ihle, Peter | Schubert, Ingrid | Bauer, Jürgen | Brenner, Hermann

Article Type: Research Article

Abstract: BACKGROUND: Hospital care of older adults, especially of those with dementia, is associated with a high risk of complications and increased mortality. Adverse events are often triggered by hospital-related factors, hence the time spent in hospitals should be limited. There is little knowledge of the specific factors influencing hospitalizations of older persons. OBJECTIVES: To assess the duration of length of stay (LOS) and risk factors of increased LOS, and, specifically, the role of delirium and neuropsychiatric symptoms (NPS) among a large sample of older adults with and without dementia in Germany. METHODS: A claims data based …dynamic retrospective cohort study from 2004 to 2015 was conducted. People with dementia (PWD) were identified using ICD-10 codes and the application of diagnostic measures. A control group without diagnosis of dementia (CG) were matched in a 3: 1 ratio. Multivariate methods were used to investigate the factors associated with LOS. RESULTS: 7,139 PWD and 21,417 controls were included. PWD had longer hospitalizations (first LOS: +4.3 days; second LOS: +0.2 days) than the CG. Diagnosis of delirium was associated with LOS, both for PWD (first LOS: +9.6 days; second LOS: +5.3 days) and CG (first LOS: +13.7 days; second LOS: +7.2 days). CONCLUSION: Major determinants of LOS were similar in PWD and the CG. The strongest association was found for the presence of delirium and NPS. Future research should focus on prevention and intervention strategies that may reduce the impact of delirium as well as NPS on the length of stay especially for PWD. Show more

Keywords: Claims data, dementia, hospitalization, neuropsychiatric symptoms, observational study

DOI: 10.3233/JAD-180593

Citation: Journal of Alzheimer's Disease, vol. 67, no. 3, pp. 1055-1065, 2019

Authors: Deng, Jing-Huan | Huang, Kai-Yong | Hu, Xiao-Xiao | Huang, Xiao-Wei | Tang, Xian-Yan | Wei, Xiao | Feng, Lei | Lu, Guo-Dong

Article Type: Research Article

Abstract: Mild cognitive impairment (MCI), as a transitional stage between normal aging and dementia, causes cognitive decline among one-fifth of elders aged 65 years and older. Health-related lifestyles (HRL) are generally regarded as modifiable influencing factors of cognitive decline. The present study investigated how HRLs at two different life stages (one at midlife and the other at later life) affect MCI occurrence among community-dwelling elders, as part of the Diet and Healthy Aging (DaHA) study in Singapore. The frequencies of major HRL activities were compared between 119 clinical diagnosed MCI cases and 632 normal aging controls with functional cognition. The associations …of HRLs with MCI were determined by multivariate logistic regression analysis and adjusted according to known factors including age, childhood education, and major chronic diseases (hypertension, stroke, diabetes, and cataracts or glaucoma). Long-hour working in midlife (adjusted OR = 0.418 with 95% CI 0.215–0.812) and social engagement in later-life (adjusted OR = 0.532 with 95% CI 0.329–0.859) were associated with reduced risks of MCI, respectively. It is important to note that those elders who had both midlife long-hour working and later-life social engagement were related to the lowest risk of MCI (adjusted OR = 0.285 with 95% CI 0.143-0.565), when compared to the least active subgroup who neither had worked long hours in midlife nor participate in social activities in later-life. Therefore, the present study demonstrated that midlife long-hour working and later-life social engagement were modifiable factors for the maintenance of cognitive functions. Show more

Keywords: Health-related lifestyle, later-life, midlife, mild cognitive impairment, social engagement, work

DOI: 10.3233/JAD-180605

Citation: Journal of Alzheimer's Disease, vol. 67, no. 3, pp. 1067-1077, 2019

Authors: Manabe, Tatsuo | Matsumura, Akihiro | Yokokawa, Kazuki | Saito, Taro | Fujikura, Mai | Iwahara, Naotoshi | Matsushita, Takashi | Suzuki, Syuuichirou | Hisahara, Shin | Kawamata, Jun | Suzuki, Hiromi | Emoto, Miho C. | Fujii, Hirotada G. | Shimohama, Shun

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases responsible for progressive dementia. Deposition of amyloid-β (Aβ) in the brain is the most important pathophysiological hallmark of AD. In addition, recent evidence indicates that reactive oxygen species (ROS) derived from mitochondria contribute to progression of AD pathology. We thus hypothesized that Aβ accumulates and oxidative stress increases in the brain mitochondria of a transgenic mouse model of AD (APdE9). We measured the quantity of Aβ and the activity of the antioxidant enzyme superoxide dismutase (SOD) in brain mitochondrial fractions prepared from APdE9 and wild-type (WT) mice aged 6, …9, 15, and 18 months. We also quantified the age-related changes in redox status in the mitochondrial fractions obtained from both APdE9 and WT mouse brains by electron paramagnetic resonance (EPR) spectrometry using a paramagnetic nitroxide “Mito-Tempo” [(2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride monohydrate] as a mitochondria-targeted redox-sensitive probe. In APdE9 mice, Aβ accumulated in brain mitochondria earlier than in the non-mitochondrial fraction of the brain. Furthermore, increased oxidative stress was demonstrated in brain mitochondria of APdE9 mice by in vitro SOD assay as well as EPR spectroscopy. EPR combined with a mitochondria-targeted redox-sensitive nitroxide probe is a potentially powerful tool to elucidate the etiology of AD and facilitate the development of new therapeutic strategies for AD. Show more

Keywords: Alzheimer’s disease, amyloid-β, electron paramagnetic resonance, mitochondria, reactive oxygen special, redox status, oxidative stress

DOI: 10.3233/JAD-180985

Citation: Journal of Alzheimer's Disease, vol. 67, no. 3, pp. 1079-1087, 2019

Authors: Chen, Ci-Di | Zeldich, Ella | Khodr, Christina | Camara, Kaddy | Tung, Tze Yu | Lauder, Emma C. | Mullen, Patrick | Polanco, Taryn J. | Liu, Yen-Yu | Zeldich, Dean | Xia, Weiming | Van Nostrand, William E. | Brown, Lauren E. | Porco Jr., John A. | Abraham, Carmela R.

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is characterized by the accumulation of neurotoxic amyloid-β (Aβ) peptides consisting of 39-43 amino acids, proteolytically derived fragments of the amyloid-β protein precursor (AβPP), and the accumulation of the hyperphosphorylated microtubule-associated protein tau. Inhibiting Aβ production may reduce neurodegeneration and cognitive dysfunction associated with AD. We have previously used an AβPP-firefly luciferase enzyme complementation assay to conduct a high throughput screen of a compound library for inhibitors of AβPP dimerization, and identified a compound that reduces Aβ levels. In the present study, we have identified an analog, compound Y10, which also reduced Aβ. Initial kinase profiling assays …identified the receptor tyrosine kinase cKit as a putative Y10 target. To elucidate the precise mechanism involved, AβPP phosphorylation was examined by IP-western blotting. We found that Y10 inhibits cKit phosphorylation and increases AβPP phosphorylation mainly on tyrosine residue Y743, according to AβPP751 numbering. A known cKit inhibitor and siRNA specific to cKit were also found to increase AβPP phosphorylation and lower Aβ levels. We also investigated a cKit downstream signaling molecule, the Shp2 phosphatase, and found that known Shp2 inhibitors and siRNA specific to Shp2 also increase AβPP phosphorylation, suggesting that the cKit signaling pathway is also involved in AβPP phosphorylation and Aβ production. We further found that inhibitors of both cKit and Shp2 enhance AβPP surface localization. Thus, regulation of AβPP phosphorylation by small molecules should be considered as a novel therapeutic intervention for AD. Show more

Keywords: High throughput screening, kinase, neurodegeneration, phosphatase, phosphorylation

DOI: 10.3233/JAD-180923

Citation: Journal of Alzheimer's Disease, vol. 67, no. 3, pp. 1089-1106, 2019

Article Type: Correction

DOI: 10.3233/JAD-189014

Citation: Journal of Alzheimer's Disease, vol. 67, no. 3, pp. 1107-1107, 2019