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Journal of Alzheimer's Disease - Volume 52, issue 1
ISSN 1387-2877 (P)
ISSN 1875-8908 (E)
The Journal of Alzheimer's Disease is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer's disease.
The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. The journal is dedicated to providing an open forum for original research that will expedite our fundamental understanding of Alzheimer's disease.
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Shared Genetic Risk Factors for Late-Life Depression and Alzheimer's Disease
Authors: Ye, Qing | Bai, Feng | Zhang, Zhijun
Article Type: Review Article
Abstract: Background: Considerable evidence has been reported for the comorbidity between late-life depression (LLD) and Alzheimer's disease (AD), both of which are very common in the general elderly population and represent a large burden on the health of the elderly. The pathophysiological mechanisms underlying the link between LLD and AD are poorly understood. Because both LLD and AD can be heritable and are influenced by multiple risk genes, shared genetic risk factors between LLD and AD may exist. Objective: The objective is to review the existing evidence for genetic risk factors that are common to LLD and AD …and to outline the biological substrates proposed to mediate this association. Methods: A literature review was performed. Results: Genetic polymorphisms of brain-derived neurotrophic factor, apolipoprotein E, interleukin 1-beta, and methylenetetrahydrofolate reductase have been demonstrated to confer increased risk to both LLD and AD by studies examining either LLD or AD patients. These results contribute to the understanding of pathophysiological mechanisms that are common to both of these disorders, including deficits in nerve growth factors, inflammatory changes, and dysregulation mechanisms involving lipoprotein and folate. Other conflicting results have also been reviewed, and few studies have investigated the effects of the described polymorphisms on both LLD and AD. Conclusion: The findings suggest that common genetic pathways may underlie LLD and AD comorbidity. Studies to evaluate the genetic relationship between LLD and AD may provide insights into the molecular mechanisms that trigger disease progression as the population ages. Show more
Keywords: Alzheimer's disease, apolipoprotein E, brain-derived neurotrophic factor, interleukin 1-beta, late-life depression, methylenetetrahydrofolate reductase, single nucleotide polymorphism
Citation: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 1-15, 2016
Development of a Standardized Approach to Disclosing Amyloid Imaging Research Results in Mild Cognitive Impairment
Authors: Lingler, Jennifer H. | Butters, Meryl A. | Gentry, Amanda L. | Hu, Lu | Hunsaker, Amanda E. | Klunk, William E. | Mattos, Meghan K. | Parker, Lisa A. | Roberts, J. Scott | Schulz, Richard
Abstract: The increased use of PET amyloid imaging in clinical research has sparked numerous concerns about whether and how to return such research test results to study participants. Chief among these is the question of how best to disclose amyloid imaging research results to individuals who have cognitive symptoms that could impede comprehension of the information conveyed. We systematically developed and evaluated informational materials for use in pre-test counseling and post-test disclosures of amyloid imaging research results in mild cognitive impairment (MCI). Using simulated sessions, persons with MCI and their family care partners (N = 10 dyads) received fictitious but realistic information …regarding brain amyloid status, followed by an explanation of how results impact Alzheimer's disease risk. Satisfaction surveys, comprehension assessments, and focus group data were analyzed to evaluate the materials developed. The majority of persons with MCI and their care partners comprehended and were highly satisfied with the information presented. Focus group data reinforced findings of high satisfaction and included 6 recommendations for practice: 1) offer pre-test counseling, 2) use clear graphics, 3) review participants' own brain images during disclosures, 4) offer take-home materials, 5) call participants post-disclosure to address emerging questions, and 6) communicate seamlessly with primary care providers. Further analysis of focus group data revealed that participants understood the limitations of amyloid imaging, but nevertheless viewed the prospect of learning one's amyloid status as valuable and empowering. Show more
Keywords: Communication, counseling, mild cognitive impairment, positron emission tomography, research ethics
Citation: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 17-24, 2016
Diversity of Cognitive Phenotypes Associated with C9ORF72 Hexanucleotide Expansion
Authors: Gómez-Tortosa, Estrella | Prieto-Jurczynska, Cristina | Serrano, Soledad | Franco-Macías, Emilio | Olivié, Laura | Gallego, Jesús | Guerrero-López, Rosa | Trujillo-Tiebas, María José | Ayuso, Carmen | García Ruiz, Pedro | Pérez-Pérez, Julián | Sainz, María José
Article Type: Short Communication
Abstract: For diagnostic purposes, we screened for the C9ORF72 mutation in a) 162 FTLD cases, and b) 145 cases with other diagnoses but with some frontotemporal features or manifestations previously reported in C9 carriers. Ten cases (onset 50 to 75 years) harbored the expansion: seven had FTLD syndromes (4.3% of total, 11% of familial cases), and three (2%) had a different diagnosis. All positive cases had family history of dementia, psychiatric disease, or ALS, but only 20% of families with mixed FTLD/ALS phenotypes carried the expansion. Language impairment was the most common symptom, followed by behavioral changes, memory deficits, and …parkinsonism. C9ORF72 mutation has a low frequency in our dementia series and very diverse clinical manifestations. Show more
Keywords: C9ORF72 gene, frontotemporal dementia, hexanucleotide expansion
Nutritional Status is Associated with Faster Cognitive Decline and Worse Functional Impairment in the Progression of Dementia: The Cache County Dementia Progression Study
Authors: Sanders, Chelsea | Behrens, Stephanie | Schwartz, Sarah | Wengreen, Heidi | Corcoran, Chris D. | Lyketsos, Constantine G. | Tschanz, JoAnn T.
Abstract: Nutritional status may be a modifiable factor in the progression of dementia. We examined the association of nutritional status and rate of cognitive and functional decline in a U.S. population-based sample. Study design was an observational longitudinal study with annual follow-ups up to 6 years of 292 persons with dementia (72% Alzheimer's disease, 56% female) in Cache County, UT using the Mini-Mental State Exam (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-sb), and modified Mini Nutritional Assessment (mMNA). mMNA scores declined by approximately 0.50 points/year, suggesting increasing risk for malnutrition. Lower mMNA score predicted faster rate of decline on the …MMSE at earlier follow-up times, but slower decline at later follow-up times, whereas higher mMNA scores had the opposite pattern (mMNA by time β= 0.22, p = 0.017; mMNA by time2 β= –0.04, p = 0.04). Lower mMNA score was associated with greater impairment on the CDR-sb over the course of dementia (β= 0.35, p < 0.001). Assessment of malnutrition may be useful in predicting rates of progression in dementia and may provide a target for clinical intervention. Show more
Keywords: Cognitive symptoms, dementia, disease progression, malnutrition, nutrition assessment
Association of Frontotemporal Dementia GWAS Loci with Late-Onset Alzheimer's Disease in a Northern Han Chinese Population
Authors: Tan, Chen-Chen | Wan, Yu | Tan, Meng-Shan | Zhang, Wei | Wang, Zi-Xuan | Sun, Fu-Rong | Miao, Dan | Tan, Lan | Yu, Jin-Tai
Abstract: Background: Both Alzheimer's disease (AD) and frontotemporal dementia (FTD) are a class of neurodegenerative diseases. Strong similarities in cerebrospinal fluid biomarker, imaging markers, and disease progression profiles suggest that some or most of the pathophysiology is shared between AD and FTD. A recent large genome-wide association study reported several single nucleotide polymorphisms (SNPs) at the RAB38, RAB38/CTSC, HLA-DRA/HLA-DRB5 , and BTNL2 in association with FTD. Objective: To explore whether these SNPs are associated with AD risk. Methods: We conducted a case-control study to investigate the association of FTD-associated loci in 2338 Han Chinese subjects. …Results: We observed significant differences in genotype distributions of rs302668 (pc = 0.025), rs9268877 (pc = 0.025), rs9268856 (p < 0.001), and rs1980493 (pc = 0.045) between cases and controls. The SNPs rs16913634 for RAB38/CTSC was unrelated to LOAD risk (p = 0.088). Conclusion: The SNPs rs302668 in RAB38, rs9268877 and rs9268856 polymorphism in HLA-DRA/HLA-DRB5, and rs1980493 polymorphism in BTNL2 might play a role in the susceptibility to late-onset AD in the Han Chinese population. Show more
Keywords: Alzheimer's disease, association study, frontotemporal dementia, polymorphism
Comparison of Different Matrices as Potential Quality Control Samples for Neurochemical Dementia Diagnostics
Authors: Lelental, Natalia | Brandner, Sebastian | Kofanova, Olga | Blennow, Kaj | Zetterberg, Henrik | Andreasson, Ulf | Engelborghs, Sebastiaan | Mroczko, Barbara | Gabryelewicz, Tomasz | Teunissen, Charlotte | Mollenhauer, Brit | Parnetti, Lucilla | Chiasserini, Davide | Molinuevo, Jose Luis | Perret-Liaudet, Armand | Verbeek, Marcel M. | Andreasen, Niels | Brosseron, Frederic | Bahl, Justyna M.C. | Herukka, Sanna-Kaisa | Hausner, Lucrezia | Frölich, Lutz | Labonte, Anne | Poirier, Judes | Miller, Anne-Marie | Zilka, Norbert | Kovacech, Branislav | Urbani, Andrea | Suardi, Silvia | Oliveira, Catarina | Baldeiras, Ines | Dubois, Bruno | Rot, Uros | Lehmann, Sylvain | Skinningsrud, Anders | Betsou, Fay | Wiltfang, Jens | Gkatzima, Olymbia | Winblad, Bengt | Buchfelder, Michael | Kornhuber, Johannes | Lewczuk, Piotr
Abstract: Background: Assay-vendor independent quality control (QC) samples for neurochemical dementia diagnostics (NDD) biomarkers are so far commercially unavailable. This requires that NDD laboratories prepare their own QC samples, for example by pooling leftover cerebrospinal fluid (CSF) samples. Objective: To prepare and test alternative matrices for QC samples that could facilitate intra- and inter-laboratory QC of the NDD biomarkers. Methods: Three matrices were validated in this study: (A) human pooled CSF, (B) Aβ peptides spiked into human prediluted plasma, and (C) Aβ peptides spiked into solution of bovine serum albumin in phosphate-buffered saline. All matrices were …tested also after supplementation with an antibacterial agent (sodium azide). We analyzed short- and long-term stability of the biomarkers with ELISA and chemiluminescence (Fujirebio Europe, MSD, IBL International), and performed an inter-laboratory variability study. Results: NDD biomarkers turned out to be stable in almost all samples stored at the tested conditions for up to 14 days as well as in samples stored deep-frozen (at – 80°C) for up to one year. Sodium azide did not influence biomarker stability. Inter-center variability of the samples sent at room temperature (pooled CSF, freeze-dried CSF, and four artificial matrices) was comparable to the results obtained on deep-frozen samples in other large-scale projects. Conclusion: Our results suggest that it is possible to replace self-made, CSF-based QC samples with large-scale volumes of QC materials prepared with artificial peptides and matrices. This would greatly facilitate intra- and inter-laboratory QC schedules for NDD measurements. Show more
Keywords: Alzheimer's disease, amyloid-β, biomarkers, cerebrospinal fluid, laboratory diagnostics, quality control, tau
Salidroside, a Bioactive Compound of Rhodiola Rosea, Ameliorates Memory and Emotional Behavior in Adult Mice
Authors: Palmeri, Agostino | Mammana, Leonardo | Tropea, Maria Rosaria | Gulisano, Walter | Puzzo, Daniela
Abstract: Rhodiola Rosea (R. Rosea ) is a plant used in traditional popular medicine to enhance cognition and physical performance. R. Rosea medicinal properties have been related to its capability to act as an adaptogen, i.e., a substance able to increase the organism's resistance to a variety of chemical, biological, and physical stressors in a non-specific way. These adaptogen properties have been mainly attributed to the glycoside salidroside, one of the bioactive compounds present in the standardized extracts of R. Rosea . Here, we aimed to investigate whether a single dose of salidroside is able to affect memory and emotional …behavior in wild type adult mice. We performed fear conditioning to assess cued and contextual memory, elevated plus maze and open field to evaluate anxiety, and tail suspension test to evaluate depression. Our results showed that a single i.p. administration of salidroside was able to enhance fear memory and exerted an anxiolytic and antidepressant effect. These data confirmed the adaptogenic effect of R. Rosea bioactive compounds in animal models and suggest that salidroside might represent an interesting pharmacological tool to ameliorate cognition and counteract mood disorders. Show more
Keywords: Adaptogen, anxiety, depression, memory, Rhodiola rosea, salidroside
Spatial Navigation in Preclinical Alzheimer's Disease
Authors: Allison, Samantha L. | Fagan, Anne M. | Morris, John C. | Head, Denise
Abstract: Although several previous studies have demonstrated navigational deficits in early-stage symptomatic Alzheimer's disease (AD), navigational abilities in preclinical AD have not been examined. The present investigation examined the effects of preclinical AD and early-stage symptomatic AD on spatial navigation performance. Performance on tasks of wayfinding and route learning in a virtual reality environment were examined. Comparisons were made across the following three groups: Clinically normal without preclinical AD (n = 42), clinically normal with preclinical AD (n = 13), and early-stage symptomatic AD (n = 16) groups. Preclinical AD was defined based on cerebrospinal fluid Aβ42 levels below 500 pg/ml. Preclinical AD …was associated with deficits in the use of a wayfinding strategy, but not a route learning strategy. Moreover, post-hoc analyses indicated that wayfinding performance had moderate sensitivity and specificity. Results also confirmed early-stage symptomatic AD-related deficits in the use of both wayfinding and route learning strategies. The results of this study suggest that aspects of spatial navigation may be particularly sensitive at detecting the earliest cognitive deficits of AD. Show more
Keywords: Aging, allocentric, amyloid, caudate nucleus, egocentric, hippocampus
Differences in Depressive Patterns According to Disease Severityin Early-Onset Alzheimer's Disease
Authors: Yoon, Bora | Yang, Dong Won | Hong, Yun Jeong | Choi, Seong Hye | Park, Sun Ah | Park, Hee Kyung | Kim, Yong Duk | Shim, Yong S.
Abstract: Background & Objective: Depression frequently combines with dementia, including early-onset Alzheimer's disease (EOAD). We investigated differences in prevalence and characteristics of depressive symptoms according to dementia severity in EOAD patients. Methods: The 15-item Korean version of the Geriatric Depression Scale (GDS-15) was administered to 412 EOAD patients. Factor analysis was used to assess GDS-15 factor structure. We subdivided participants into three groups by disease severity, then compared the frequencies and scores of individual GDS-15 items and performed logistic regression analysis to assess associations between depressive symptoms and EOAD stage. Results: Factor analysis yielded three factor …categories: 1) "hopelessness and ominousness" (symptoms no. 6, 8, 12, 14, 15); 2) "unhappiness and dissatisfaction" (no. 1, 3, 5, 7, 11); and 3) "monotony and lack of energy" (no. 2, 4, 9, 10, 13). Factor 2 depressive symptoms (no. 1, 5, 11) were less common in moderate EOAD. The risk of Factor 1 symptoms: no. 12 (OR, 2.04; 95% CI, 1.19–3.50; p = 0.010) and 14 (OR, 1.84; 95% CI, 1.07–3.16; p = 0.028) was higher in mild than very mild EOAD. The risk of Factor 2 symptoms: no. 9 (OR, 2.69; 95% CI, 1.08–6.71; p = 0.033) and 13 (OR, 2.12; 95% CI, 1.02–4.40; p = 0.043) was higher in moderate than mild EOAD. Conclusion: We confirmed that depressive symptoms differ according to EOAD severity. When assessing depressive symptoms related to dementia progression, we recommend focusing on "hopelessness and ominousness" in very mild EOAD and "unhappiness and dissatisfaction" in mild EOAD. Show more
Keywords: Alzheimer's disease, depression, disease progression, early-onset, geriatric depression scale, prediction
Chronic Obstructive Pulmonary Disease as a Risk Factor for Cognitive Dysfunction: A Meta-Analysis of Current Studies
Authors: Zhang, Ximeng | Cai, Xiaoying | Shi, Xiaolei | Zheng, Zhenyang | Zhang, Aiwu | Guo, Junliang | Fang, Yannan
Abstract: Cognitive dysfunction has been shown to be associated with many risk factors, such as smoking, diabetes, and body mass index. Chronic obstructive pulmonary disease (COPD), a common disease within the elderly population, has also been found to be related to cognitive decline. However, whether COPD is a risk factor of cognitive dysfunction is not well established. The purpose of this meta-analysis is to investigate the role COPD plays in cognitive dysfunction. PubMed, Cochrane library and Web of Science databases were searched. Three cohort studies and eleven cross-sectional studies were found to be eligible. According to our results, COPD patients had …a higher risk of cognitive dysfunction than controls (OR [odds ratio]: 1.72; 95% CI, 1.12–2.65; p = 0.01). The exacerbation of COPD was strongly correlated with cognitive decline. COPD patients performed worse than controls on the Mini– Mental State Examination test, but the results were not statistically significant (OR: –0.79; 95% CI, [–1.78, 0.19]; p = 0.11). Thus, more attention should be given to the occurrence of cognitive decline in COPD patients. The prevention and control of COPD exacerbation are critical. Show more
Keywords: Chronic obstructive pulmonary disease, cognition, dementia, meta-analysis
Citation: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 101-111, 2016
Strong Impact of Chronic Cerebral Hypoperfusion on Neurovascular Unit, Cerebrovascular Remodeling, and Neurovascular Trophic Coupling in Alzheimer's Disease Model Mouse
Authors: Shang, Jingwei | Yamashita, Toru | Zhai, Yun | Nakano, Yumiko | Morihara, Ryuta | Fukui, Yusuke | Hishikawa, Nozomi | Ohta, Yasuyuki | Abe, Koji
Abstract: Although chronic cerebral hypoperfusion (CCH) may affect Alzheimer's disease (AD) pathogenesis, the mechanism remains elusive. In the present study, we investigated the role of CCH on an AD mouse model in neurovascular unit, cerebrovascular remodeling, and neurovascular trophic coupling. Moreover, examined protective effect of galantamine. Alzheimer's disease transgenic mice (APP23) were subjected to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive cerebral hypoperfusion. CCH exacerbated neuronal loss and decrease of α 7 subunit of nicotinic acetylcholine receptors (α 7-nAChRs) expression in hippocampus and thalamus at 12 months. Meanwhile, CCH greatly induced advanced glycation end products expression, and …blood-brain barrier leakage through observing IgG and MMP9 expressions. Furthermore, a significant number of dramatic enlarged cerebral vessels with remodeling, BDNF/TrkB decreased in neurovascular trophic coupling. The present study demonstrated that CCH strongly enhanced primary AD pathology including neurodegeneration, neurovascular unit disruption, cerebrovascular remodeling and neurovascular trophic coupling damage in AD mice, and that galantamine treatment greatly ameliorated such neuropathologic abnormalities. Show more
Keywords: Alzheimer's disease, APP23 mice, cerebrovascular remodeling, chronic cerebral hypoperfusion, galantamine, neurovascular unit, neurovascular trophic coupling
Incidence and Duration of Cumulative Bisphosphonate Use among Community-Dwelling Persons with or without Alzheimer's Disease
Authors: Tiihonen, Miia | Taipale, Heidi | Tanskanen, Antti | Tiihonen, Jari | Hartikainen, Sirpa
Abstract: We studied the incidence and duration of cumulative bisphosphonate use among older Finnish women and men with or without Alzheimer's disease (AD). The MEDALZ-2005 cohort is a nationwide sample of all persons with clinically diagnosed AD on 31 December 2005 and their age-, gender-, and region of residence-matched control persons without AD. Information on bisphosphonate use by persons with an AD diagnosis and their controls without AD during 2002–2009 was obtained from the prescription register database containing reimbursed medications. A total of 6,041 (11.8%) persons used bisphosphonates during the 8-year follow-up. Bisphosphonates were more commonly used among persons without AD …(n = 3121, 12.3%) than among persons with AD (n = 2,920, 11.2%) (p = 0.001). The median duration of bisphosphonate use was 743 days (IQR). Among persons with AD, the median duration of use was 777 days (IQR) and among persons without AD, 701 days (IQR) (p = 0.011). People without AD more often used bisphosphonate combination preparations including vitamin D than did people with AD (p < 0.0001). Bisphosphonate use was more common among people without AD who had comorbidities, asthma/COPD, or rheumatoid arthritis compared with users with AD. Short-term users were more likely to be male, at least 80 years old, and not having AD. Although the incidence of bisphosphonate use was slightly higher among persons without AD, the cumulative duration of bisphosphonate use was longer in persons with AD. Short-term use was associated with male gender, older age, and not having AD. Show more
Keywords: Alzheimer's disease, bisphosphonates, community dwelling, osteoporosis
Searching for Primary Predictors of Conversion from Mild Cognitive Impairment to Alzheimer's Disease: A Multivariate Follow-Up Study
Authors: López, María Eugenia | Turrero, Agustín | Cuesta, Pablo | López-Sanz, David | Bruña, Ricardo | Marcos, Alberto | Gil, Pedro | Yus, Miguel | Barabash, Ana | Cabranes, José Antonio | Maestú, Fernando | Fernández, Alberto
Abstract: Recent proposals of diagnostic criteria within the healthy aging-Alzheimer's disease (AD) continuum stressed the role of biomarker information. More importantly, such information might be critical to predict those mild cognitive impairment (MCI) patients at a higher risk of conversion to AD. Usually, follow-up studies utilize a reduced number of potential markers although the conversion phenomenon may be deemed as multifactorial in essence. In addition, not only biological but also cognitive markers may play an important role. Considering this background, we investigated the role of cognitive reserve, cognitive performance in neuropsychological testing, hippocampal volumes, APOE genotype, and magnetoencephalography power sources to …predict the conversion to AD in a sample of 33 MCI patients. MCIs were followed up during a 2-year period and divided into two subgroups according to their outcome: The "stable" MCI group (sMCI, 21 subjects) and the "progressive" MCI group (pMCI, 12 subjects). Baseline multifactorial information was submitted to a hierarchical logistic regression analysis to build a predictive model of conversion to AD. Results indicated that the combination of left hippocampal volume, occipital cortex theta power, and clock drawing copy subtest scores predicted conversion to AD with a 100% of sensitivity and 94.7% of specificity. According to these results it might be suggested that anatomical, cognitive, and neurophysiological markers may be considered as "first order" predictors of progression to AD, while APOE or cognitive reserve proxies might play a more secondary role. Show more
Keywords: Alzheimer's disease, APOE, cognitive reserve, hippocampal volume, magnetoencephalography; mild cognitive impairment, neuropsychological tests, predictive model
Glutamine and Glutamate Complex, as Measured by Functional Magnetic Resonance Spectroscopy, Alters During Face-Name Association Task in Patients with Mild Cognitive Impairment and Alzheimer's Disease
Authors: Jahng, Geon-Ho | Oh, Janghoon | Lee, Do-Wan | Kim, Hyug-Gi | Rhee, Hak Young | Shin, Wonchul | Paik, Jong-Woo | Lee, Kyung Mi | Park, Soonchan | Choe, Bo-Young | Ryu, Chang-Woo
Abstract: Background: The metabolite response during a memory task in Alzheimer's disease (AD) patients is unknown. Objective: To investigate the metabolite changes in subjects with AD, amnestic mild cognitive impairment (aMCI), and cognitively normal (CN) elderly during a memory task using functional magnetic resonance spectroscopy (fMRS). Methods: This study involved 23 young normal controls (YC), 24 CN elderly, 24 aMCI, and 24 mild and probable AD individuals. fMRS data were acquired at the precuneus and posterior cingulate brain regions during a face-name association task. Statistical analyses of quantified metabolites were performed to evaluate differences of the …metabolite values between the stimulation conditions and among the four subject groups. Receiver operating curve analysis was performed to evaluate whether the metabolic changes after functional activations can differentiate the subject groups. Result: Glutamine and glutamate complex (Glx) was statistically significantly different between the fixation and repeat conditions in aMCI (p = 0.0492) as well as between the fixation and the novel conditions in the AD (p = 0.0412) group. The total N-acetylaspartate (tNAA) was statistically significantly different among the four subject groups in the fixation condition (DF = 3, F = 7.673, p < 0.001), the novel condition (DF = 3, F = 6.945, p < 0.001), and the repeat condition (DF = 3, F = 7.127, p < 0.001). tNAA, tCr, and mIns could be used to differentiate CN from aMCI. Furthermore, tNAA, tCr, Glx, and Glu could also differentiate CN from AD, and aMCI from AD. Conclusion: Glx was altered during a stimulation that may be used to evaluate neuronal dysfunction in a demented patient. tNAA and tCr were reduced in patients with AD. Show more
Keywords: Alzheimer–s disease, functional magnetic resonance spectroscopy, glutamine and glutamate complex (Glx), mild cognitive impairment, total N-acetylaspartate (tNAA)
Association of Plasma Aβ 40 Peptides, But Not Aβ 42, with Coronary Artery Disease and Diabetes Mellitus
Authors: Roeben, Benjamin | Maetzler, Walter | Vanmechelen, Eugeen | Schulte, Claudia | Heinzel, Sebastian | Stellos, Konstantinos | Godau, Jana | Huber, Heiko | Brockmann, Kathrin | Wurster, Isabel | Gaenslen, Alexandra | Grüner, Eva | Niebler, Raphael | Eschweiler, Gerhard W. | Berg, Daniela | the TREND study team
Abstract: Background/Objective: Plasma levels of amyloid-beta (Aβ) 1-40 peptide have been proposed to be associated with cardiovascular mortality in patients with coronary artery disease (CAD). Therefore, we aimed to investigate the association of plasma Aβ levels with CAD, cardiovascular risk factors (CVRF), and APOE genotype in non-demented elderly individuals. Methods: Plasma Aβ1 - 40 and Aβ1 - 42 levels of 526 individuals (mean age of 63.0±7.3 years) were quantified with the INNO-BIA plasma Aβ forms assay based on multiplextrademark technique. APOE genotype was determined with an established protocol. Presence of CAD and CVRFs were ascertained using a questionnaire …and/or medical records. Results: Plasma Aβ1 - 40 levels were significantly higher in individuals with CAD (p = 0.043) and, independently, in individuals with diabetes mellitus (DM) type 2 (p = 0.001) while accounting for age- and gender-effects. Plasma Aβ1 - 42 levels were higher in APOE ɛ 4 carriers (p = 0.004), but were neither relevantly associated with CAD nor with any CVRF. Plasma Aβ1 - 40 showed no association with APOE genotype. Discussion: Our findings argue for an association of circulating plasma Aβ1 - 40 peptides with incident CAD and DM. Further investigations are needed to entangle the role of Aβ1 - 40 role in the pathophysiology of cardiovascular disease independent of its known role in Alzheimer's disease. Show more
Keywords: Alzheimer's disease, amyloid-beta, APOE genotype, coronary artery disease, diabetes mellitus, vascular
Cognitive Profile and its Association with Neuroimaging Markers of Non-Demented Cerebral Amyloid Angiopathy Patients in a Stroke Unit
Authors: Xiong, Li | Davidsdottir, Sigurros | Reijmer, Yael D. | Shoamanesh, Ashkan | Roongpiboonsopit, Duangnapa | Thanprasertsuk, Sekh | Martinez-Ramirez, Sergi | Charidimou, Andreas | Ayres, Alison M. | Fotiadis, Panagiotis | Gurol, Edip | Blacker, Deborah L. | Greenberg, Steven M. | Viswanathan, Anand
Abstract: Background: Cerebral amyloid angiopathy (CAA) is increasingly recognized as a cause of cognitive impairment in the elderly, but the cognitive profile in patients with the disease has not been well characterized. Objective: To characterize the neuropsychological profile of CAA patients without dementia and to determine the association between cognitive performance in different domains and neuroimaging lesions characteristic of CAA. Methods: Fifty-eight non-demented CAA patients were compared to 138 cognitively normal subjects using a standard neuropsychological test battery. Total brain volume (TBV), white matter hyperintensities, number of lobar cerebral microbleeds, hippocampal volume, and cortical superficial siderosis …in all CAA patients were assessed. The association between these neuroimaging markers and neuropsychological performance in different cognitive domains in the CAA group were analyzed. Results: Patients with CAA had significantly worse performance on all individual neuropsychological domains tested, when compared to the cognitive normal group. The cognitive decline of CAA patients was most noticeable in tests for processing speed with a Z score of –1.92±1.56 (mean±SD), then followed by executive function (–0.93±1.01), episodic memory (–0.87±1.29), semantic fluency (–0.73±1.06), and attention (–0.42±0.98). TBV of the CAA patients was correlated with processing speed (β= 0.335, p = 0.03) and executive function (β= 0.394, p = 0.01). Conclusions: Non-demented patients with CAA had cognitive deficits in multiple areas. Lower TBV was related to slower processing speed and worse executive function. Show more
Keywords: Brain atrophy, cerebral amyloid angiopathy, cerebral microbleeds, clinical neuropsychology, cognitive impairment, hippocampal atrophy, intracranial hemorrhage, white matter hyperintensities
Bridging Integrator 1 ( BIN1) Genotypes Mediate Alzheimer's Disease Risk by Altering Neuronal Degeneration
Authors: Wang, Hui-Fu | Wan, Yu | Hao, Xiao-Ke | Cao, Lei | Zhu, Xi-Chen | Jiang, Teng | Tan, Meng-Shan | Tan, Lin | Zhang, Dao-Qiang | Tan, Lan | Yu, Jin-Tai | Disease Neuroimaging Initiative Alzheimer's
Abstract: Background: Bridging integrator 1 (BIN1 ) has been identified as one of the most associated loci for Alzheimer's disease (AD), and recently was reported to modulate tau pathology to mediate AD in vitro . However, the effects of BIN1 on the AD related biomarkers in AD continuum were not specifically assessed. Objective: We explored the effects of BIN1 loci on AD specific biomarkers (CSF proteins, brain structures, glucose and amyloid-β (Aβ) metabolisms) to investigate the role BIN1 in AD pathogenesis. Methods: We calculated the associations of BIN1 loci with these markers …at baseline and follow-up in multiple linear models in 812 ADNI subjects. Results: BIN1 loci were significantly associated with the levels of T-tau (rs744373: pc = 0.047, rs13031703: pc = 0.042) and P-tau (rs744373: pc = 0.044, rs13031703: pc = 0.019), but not with Aβ in CSF test. BIN1 genotypes were strongly related to atrophy of hippocampus (rs7561528: pc = 0.011), CA1 (rs1469980: pc = 0.029) and parahippocampus (rs72838284, pc = 0.017) on MRI, and to glucose metabolism on FDG-PET, but not to Aβ deposition on AV45-PET imaging. Furthermore, haplotype and subgroup analysis confirmed these significant findings. In addition, the loci associated with these markers were also identified to influence the risk for AD in the meta-analysis of 74 046 European individuals. Conclusion: This study supported that BIN1 contributes to the risk of AD by altering neural degeneration (abnormal tau, brain atrophy and glucose metabolism) but not Aβ pathology. Show more
Keywords: Aβ deposition, Alzheimer's disease, BIN1, brain structure, cerebrospinal fluid, glucose metabolism
A Late Life Risk Index for Severe Cognitive Impairment in Mexico
Authors: Downer, Brian | Veeranki, Sreenivas P. | Wong, Rebeca
Abstract: Background: Several dementia risk indices have been developed for older adults in high-income countries. However, no index has been developed for populations in low- or middle-income countries. Objective: To create a risk index for predicting severe cognitive impairment among adults aged ≥60 in Mexico and to compare the accuracy of this index to the Dementia Screening Indicator (DSI). Methods: This study included 3,002 participants from the Mexican Health and Aging Study (MHAS) interviewed in 2001 and 2012. The MHAS risk index included sociodemographic, health, and functional characteristics collected in 2001. A point value based on …the beta coefficients from a multivariable logistic regression model was assigned to each risk factor and the total score was calculated. Results: The MHAS risk index (AUC = 0.74 95% CI = 0.70–0.77) and DSI (AUC = 0.72 95% CI = 0.69–0.77) had similar accuracy for discriminating between participants who developed severe cognitive impairment from those who did not. A score of ≥16 on the MHAS risk index had a sensitivity of 0.69 (95% CI = 0.64–0.70) and specificity of 0.67 (95% CI = 0.66–0.69). A score of ≥23 on the DSI had a sensitivity of 0.56 (95% CI = 0.50–0.63) and specificity of 0.78 (95% CI = 0.76–0.79). Discussion: The MHAS risk index and DSI have moderate accuracy for predicting severe cognitive impairment among older adults in Mexico. This provides evidence that existing dementia risk indices may be applicable in low- and middle-income countries such as Mexico. Future research should seek to identify additional risk factors that can improve the accuracy of the MHAS risk index. Show more
Keywords: Aging, dementia, diagnosis, Mexico
Different Clinical and Neuroimaging Characteristics in Early Stage Parkinson's Disease with Dementia and Dementia with Lewy Bodies
Authors: Takemoto, Mami | Sato, Kota | Hatanaka, Noriko | Yamashita, Toru | Ohta, Yasuyuki | Hishikawa, Nozomi | Abe, Koji
Abstract: Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) both commonly exhibit brain Lewy body pathology and similar end-stage symptoms, but early symptoms differ. To clarify these differences, we compared the demographic characteristics, symptoms, cognitive and affective functioning, activities of daily life, and neuroimaging results between PDD (n = 52) and DLB (n = 46) patients. In measures of cognitive functioning, PDD patients had worse Hasegawa dementia scale-revised (HDS-R) scores (11.2±4.8) and better frontal assessment battery (FAB) scores (11.3±4.1) compared with DLB (17.0±6.4, p = 0.013 and 8.6±4.7, p = 0.039, respectively). DLB patients performed worse than PDD patients in "orientation to …place" tasks. In affective functions, DLB patients had worse GDS (7.6±3.4) and ABS (9.9±5.3) scores than PDD patients (5.1±4.1 and 4.8±3.0, respectively). 99m Tc-ECD images showed greater CBF in the whole cingulate gyrus and a lower CBF in the precuneus area in DLB than in PDD. These results suggest that PDD patients' lower average scores for "repetition" (MMSE), "recent memory" (HDS-R), and "lexical fluency" (FAB) were related to lower CBF in the cingulate gyrus than in DLB. Furthermore, DLB patients' poorer average subscale scores of "orientation to place" (MMSE) and "similarities", "conflicting instructions", and "go-no go" (FAB) tasks may be related to the lower CBF in the precuneus area in DLB than PDD. Show more
Keywords: Affective function, cognitive function, dementia with Lewybodies, Parkinson's disease with dementia, 99mTc-ECD images
Influence of Incipient Dementia on Hospitalization for Primary Care Sensitive Conditions: A Population-Based Cohort Study
Authors: Pimouguet, Clément | Rizzuto, Debora | Fastbom, Johan | Lagergren, Mårten | Fratiglioni, Laura | Xu, Weili
Abstract: Background: Studies have reported that moderate/severe stages of dementia are linked to increased hospitalization rates, but little is known about the influence of incipient dementia on hospitalizations for primary care sensitive conditions (PCSCs). Objective: To examine the associations between incipient dementia and hospitalization outcomes, including all-cause and PCSC hospitalization. Methods: A total of 2,268 dementia-free participants in the Swedish National study on Aging and Care-Kungsholmen were interviewed and clinically examined at baseline. Participants aged ≥78 years were followed for 3 years, and those aged 60–72 years, for 6 years. Number of hospitalizations was retrieved from …the National Patient Register. Dementia was diagnosed in accordance with Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Hospitalization outcomes were compared in participants who did and did not develop dementia. Zero-inflated Poisson regressions and logistic regressions were used in data analysis. Results: During the follow-up, 175 participants developed dementia. The unadjusted PCSC admission rate was 88.2 per 1000 person-years in those who developed dementia and 25.6 per 1000 person-years in those who did not. In the fully adjusted logistic regression model, incipient dementia was associated with an increased risk of hospitalization for PCSCs (OR = 2.3, 95% CI 1.3–3.9) but not with the number of hospitalizations or with all-cause hospitalization. Risks for hospitalization for diabetes, congestive heart failure, and pyelonephritis were higher in those who developed dementia than in those who did not. About 10% participants had a PCSC hospitalization attributable to incipient dementia. Conclusion: People with incipient dementia are more prone to hospitalization for PCSCs but not to all-cause hospitalization. Show more
Keywords: Dementia, hospitalization longitudinal follow-up, population based study
Netrin-1 Interrupts Amyloid-β Amplification, Increases sAβPPα in vitro and in vivo, and Improves Cognition in a Mouse Model of Alzheimer's Disease
Authors: Spilman, Patricia R. | Corset, Veronique | Gorostiza, Olivia | Poksay, Karen S. | Galvan, Veronica | Zhang, Junli | Rao, Rammohan | Peters-Libeu, Clare | Vincelette, Jon | McGeehan, Andrew | Dvorak-Ewell, Melita | Beyer, Janine | Campagna, Jesus | Bankiewicz, Krystof | Mehlen, Patrick | John, Varghese | Bredesen, Dale E.
Abstract: Recent studies have shown that inoculation of susceptible mice with amyloid-β (Aβ) peptides accelerates Aβ deposition in the brain, supporting the idea that Aβ may be self-amplifying; however, the exact mechanism is not understood. Here we provide evidence that Aβ may self-amplify, in part, by inhibiting α-secretase ADAM10 (a disintegrin and metalloprotease) cleavage of full-length Aβ precursor protein (FL AβPP) and therefore allow greater β-secretase processing, and that Aβ itself is a substrate for ADAM10. Exposure of primary neuronal cultures from PDAβPP mice to exogenous rat Aβ1- 40 resulted in increased de novo human Aβ1-42 production and exposure …of cells to Aβ decreased production of ADAM10 cleavage product soluble AβPPα (sAβPPα). In a cell-free assay, Aβ decreased ADAM10 cleavage of the chimeric substrate MBP-AβPPC125 and Aβ itself was apparently cleaved by the enzyme. The axonal guidance and trophic factor netrin-1, however, reduced the Aβ1- 40 -induced Aβ1-42 increase, increased sAβPPα, and reversed the Aβ-induced sAβPPα decrease in vitro . In vivo , induction of netrin-1 expression in PDAβPPSwe/Ind transgenic mice resulted in reductions in both Aβ1-42 and Aβ1- 40 , and ICV delivery of netrin-1 to PDAβPPSwe/Ind mice increased sAβPPα, decreased Aβ, and improved working memory. Finally, to support further study of netrin-1's potential as a therapeutic for Alzheimer's disease, pilot gene therapy studies were performed and a netrin mimetic peptide synthesized and tested that, like netrin, can increase sAβPPα and decrease Aβ1-42 in vitro . Taken together, these data provide mechanistic insights into Aβ self-amplification and the ability of netrin-1 to disrupt it. Show more
Keywords: Aβ1-42, AβPP, amplification, CED, inducible, mimetic, netrin-1, sAβPPα
Fibrillar Amyloid-β Accumulation Triggers an Inflammatory Mechanism Leading to Hyperphosphorylation of the Carboxyl-Terminal End of Tau Polypeptide in the Hippocampal Formation of the 3×Tg-AD Transgen…
Authors: Ontiveros-Torres, Miguel Ángel | Labra-Barrios, María Luisa | Díaz-Cintra, Sofía | Aguilar-Vázquez, Azucena Ruth | Moreno-Campuzano, Samadhi | Flores-Rodríguez, Paola | Luna-Herrera, Claudia | Mena, Raúl | Perry, George | Florán-Garduño, Benjamín | Luna-Muñoz, José | Luna-Arias, Juan Pedro
Abstract: Alzheimer's disease (AD) is a degenerative and irreversible disorder whose progressiveness is dependent on age. It is histopathologically characterized by the massive accumulation of insoluble forms of tau and amyloid-β (Aβ) asneurofibrillary tangles and neuritic plaques, respectively. Many studies have documented that these two polypeptides suffer several posttranslational modifications employing postmortem tissue sections from brains of patients with AD. In order to elucidate the molecular mechanisms underlying the posttranslational modifications of key players in this disease, including Aβ and tau, several transgenic mouse models have been developed. One of these models is the 3×Tg-AD transgenic mouse, carrying three transgenes encoding …APPSWE, S1M146V, and TauP301L proteins. To further characterize this transgenicmouse, we determined the accumulation of fibrillar Aβ as a function of age in relation to the hyperphosphorylation patterns of TauP301L at both its N- and C-terminus in the hippocampal formation by immunofluorescence and confocal microscopy. Moreover, we searched for the expression of activated protein kinases and mediators of inflammation by western blot of wholeprotein extracts from hippocampal tissue sections since 3 to 28 months as well. Our results indicate that the presence of fibrillar Aβ deposits correlates with a significant activation of astrocytes and microglia in subiculum and CA1 regions of hippocampus. Accordingly, we also observed a significant increase in the expression of TNF-α associated to neuritic plaques and glial cells. Importantly, there is an overexpression of the stress activated protein kinases SAPK/JNK and Cdk-5 in pyramidal neurons, which might phosphorylate several residues at the C-terminus of TauP301L. Therefore, the accumulation of Aβ oligomers results in an inflammatory environment that upregulates kinases involved in hyperphosphorylation of TauP301L polypeptide. Show more
Keywords: Amyloid-β, hippocampus, inflammation, TauP301L, 3×Tg-AD transgenic mouse
Specific Features of Subjective Cognitive Decline Predict Faster Conversion to Mild Cognitive Impairment
Authors: Fernández-Blázquez, Miguel A. | Ávila-Villanueva, Marina | Maestú, Fernando | Medina, Miguel
Abstract: Background: Alzheimer's disease (AD) is a silent disorder that needs the earliest possible intervention in order to reduce its high economic and social impact. It has been recently suggested that subjective cognitive decline (SCD) appears at preclinical stages many years before the onset of AD. Therefore, SCD could become an ideal target for early therapeutic intervention. Objective: The goal of this study was to evaluate the clinical significance of SCD on the conversion from a cognitively healthy stage to a mild cognitive impairment (MCI) in one-year follow-up. Methods: A total of 608 cognitively intact individuals …from the Vallecas Project's cohort, a community-based prospective study to identify early markers of AD, were enrolled in this study. Participants were classified in three groups: i) No Complaints (NCg), ii) Subjects with complaints in one or more cognitive domains (SCDg), and iii) Subjects who, besides complaints, fulfilled the features of SCD Plus proposed by the International Working Group of SCD (SCD-Pg). Results: Individuals were followed up for a mean of 13.1 months (range 10.7–22.4). During this time, 41 volunteers developed MCI (6.7% of total sample). The conversion rate for SCD-Pg (18.9%) was significantly higher than SCDg (5.6%) and NCg (4.9%). Conclusion: Specific features associated with SCD may help to identify individuals at high risk of fast conversion to MCI. These results highlight the importance of a close follow-up of subjects with SCD-P and include them in early intervention programs because of their increased risk for the development of MCI. Show more
Keywords: Aging, Alzheimer's disease, cognitive symptoms, dementia, mild cognitive impairment, subjective cognitive decline
The Memory Binding Test: Development of Two Alternate Forms into Spanish and Catalan
Authors: Gramunt, Nina | Sánchez-Benavides, Gonzalo | Buschke, Herman | Diéguez-Vide, Faustino | Peña-Casanova, Jordi | Masramon, Xavier | Fauria, Karine | Gispert, Juan D. | Molinuevo, José L.
Abstract: Background: The Memory Binding Test (MBT) is emerging as a promising tool for the detection of subtle memory impairment suggestive of Alzheimer's disease (AD). For such a test to be widely accessed and used, the availability of both alternate forms and language adaptations is required. Objectives: To develop a thorough methodology for obtaining alternate forms (A and B) of the MBT in Spanish and Catalan and to assess their equivalence. Method: According to the original development of the test, frequency was taken as the lexical variable of reference for the Spanish and Catalan adaptations. A …crossed design protocol by form and language was used to compare the MBT results in a sample of 290 cognitively normal middle-aged participants. Pairwise Intraclass Correlation Coefficients (ICCs) were calculated among the six possible combinations. Results: The Spanish and Catalan lists of words for the MBT A and B resulting from the adaptation process as well as the original lists in English are presented. ICC indices for the comparisons between forms and languages ranged from 0.56 to 0.82. Conclusion: The MBT A and B in Spanish and Catalan showed similar outcomes and can be considered equivalent. Moreover, the thorough methodology presented here for the transcultural adaptation and equivalence study, could serve as a model for future adaptations of the MBT and other verbal tests. Show more
Keywords: Alzheimer–s disease, cognition, episodic memory, neuropsychological assessment, preclinical, psycholinguistics
PDE5 Exists in Human Neurons and is a Viable Therapeutic Target for Neurologic Disease
Authors: Teich, Andrew F. | Sakurai, Mikako | Patel, Mitesh | Holman, Cameron | Saeed, Faisal | Fiorito, Jole | Arancio, Ottavio
Abstract: Phosphodiesterase 5 (PDE5) is a critical component of the cGMP-PKG axis of cellular signaling in neurons, and inhibition of PDE5 has been shown to be therapeutic in a wide range of neurologic conditions in animal models. However, enthusiasm for PDE5 inhibitors in humans is limited by data suggesting that PDE5 may not exist in human neurons. Here, we first show that past attempts to quantify PDE5 mRNA were flawed due to the use of incorrect primers, and that when correct primers are used, PDE5 mRNA is detectable in human brain tissue. We then show that PDE5 protein exists in human …brain by western blot and ELISA. Most importantly, we performed immunohistochemistry and demonstrate that PDE5 is present in human neurons. We hope that this work will trigger a renewed interest in the development of PDE5 inhibitors for neurologic disease. Show more
Keywords: Alzheimer's disease, memory, PDE5 inhibitors, phosphodiesterase 5
Comparing the Effects of Multisensory Stimulation and Individualized Music Sessions on Elderly People with Severe Dementia: A Randomized Controlled Trial
Authors: Sánchez, Alba | Maseda, Ana | Marante-Moar, M. Pilar | de Labra, Carmen | Lorenzo-López, Laura | Millán-Calenti, José Carlos
Abstract: The objective of this study was to compare the effects of a multisensory stimulation environment (MSSE) and individualized music sessions on agitation, emotional and cognitive status, and dementia severity in a sample of institutionalized patients with severe dementia. Twenty-two participants with a diagnosis of severe or very severe dementia were randomly assigned to two groups: MSSE and individualized music sessions. Both groups participated in two 30-min weekly sessions over 16 weeks. Outcomes were agitation (Cohen-Mansfield Agitation Inventory, CMAI), mood (Cornell Scale for Depression in Dementia, CSDD), anxiety (Rating Anxiety in Dementia, RAID), cognitive function (Severe Mini-Mental State Examination, SMMSE), and …the overall severity of dementia (Bedford Alzheimer Nursing Severity Scale, BANS-S). They were assessed at baseline (pre-trial), in the middle (mid-trial), at the end of the intervention (post-trial), and 8 weeks after the intervention (follow-up). Patients in the MSSE group showed significant improvement in their RAID and BANS-S scores compared with the individualized music group post- versus pre-trial. With regard to agitation, there was improvement during the intervention in both the MSSE and individualized music groups in the CMAI total score after 16 weeks of intervention, with no significant differences between the groups. The results suggest that MSSE could have better effects on anxiety symptoms and dementia severity in comparison with individualized music sessions in elderly patients with severe dementia. Show more
Keywords: Dementia, elderly, individualized music, multisensory environments, multisensory stimulation, randomized controlled trial, Snoezelen
Age-Related Effects of the Apolipoprotein E Gene on Brain Function
Authors: Matura, Silke | Prvulovic, David | Hartmann, Daniel | Scheibe, Monika | Sepanski, Beate | Butz, Marius | Oertel-Knöchel, Viola | Knöchel, Christian | Karakaya, Tarik | Fußer, Fabian | Hattingen, Elke | Pantel, Johannes
Abstract: The apolipoprotein E (ApoE) ɛ 4 allele is a well-established genetic risk factor for sporadic Alzheimer's disease. Some evidence suggests a negative role of the ApoE ɛ 4 allele for cognitive performance in late life, while beneficial effects on cognition have been shown in young age. We investigated age-related effects of the ApoE gene on brain function by assessing cognitive performance, as well as functional activation patterns during retrieval of Face-Name pairs in a group of young (n = 50; age 26.4±4.6 years, 25 ɛ 4 carriers) and old (n = 40; age 66.1±7.0 years, 20 ɛ 4 carriers) participants. A cross-sectional …factorial design was used to examine the effects of age, ApoE genotype, and their interaction on both cognitive performance and the blood oxygenation level dependent (BOLD) brain response during retrieval of Face-Name pairs. While there were no genotype-related differences in cognitive performance, we found a significant interaction of age and ApoE genotype on task-related activation bilaterally in anterior cingulate gyrus and superior frontal gyrus, as well as left and right insula. Old age was associated with increased activity in ɛ 4 carriers. The increased BOLD response in old ɛ 4 carriers during retrieval could indicate a neurocognitive disadvantage associated with the ɛ 4 allele with increasing age. Furthermore, recruitment of neuronal resources resulted in enhanced memory performance in young ɛ 4 carriers, pointing to a better neurofunctional capacity associated with the ApoE4 genotype in young age. Show more
Keywords: Apolipoprotein 4, brain, functional MRI, memory
Exercise Prevents Amyloid-β-Induced Hippocampal Network Disruption by Inhibiting GSK3β Activation
Authors: Isla, Arturo G. | Vázquez-Cuevas, Francisco Gabriel | Peña-Ortega, Fernando
Abstract: Exercise is becoming a promising therapeutic approach to prevent alterations both in Alzheimer's disease (AD) patients and in transgenic models of AD. This neuroprotection has been associated with changes in hippocampal structure and function, as well as with the reduction of amyloid-β (Aβ) production and accumulation. However, whether exercise produces lasting changes in hippocampal population activity and renders it resistant to Aβ-induced network dysfunction is still unknown. Thus, we tested whether voluntary exercise changes hippocampal population activity and prevents its alteration in the presence of Aβ, which has been associated to glycogen synthase kinase-3β (GSK3β) activation. We found that the …hippocampal population activity recorded in slices obtained from mice that exercised voluntarily (with free access to a running wheel for 21 days) exhibits higher power and faster frequency composition than slices obtained from sedentary animals. Moreover, the hippocampal network of mice that exercised becomes insensitive to Aβ-induced inhibition of spontaneous population activity. This protective effect correlates with the inability of Aβ to activate GSK3β, is mimicked by GSK3β inhibition with SB126763 (in slices obtained from sedentary mice), and is abolished by the inhibition of PI3K with LY294002 (in slices obtained from mice that exercised). We conclude that voluntary exercise produces a lasting protective state in the hippocampus, maintained in hippocampal slices by a PI3K-dependent mechanism that precludes its functional disruption in the presence of Aβ by avoiding GSK3β activation. Show more
Keywords: Amyloid-β, GSK3β, hippocampus, PI3K, spontaneous population activity, voluntary-exercise
Efficacy and Safety of Sustained Release Donepezil High Dose versus Immediate Release Donepezil Standard Dose in Japanese Patients with Severe Alzheimer's Disease: A Randomized, Double-Blind Trial
Authors: Homma, Akira | Atarashi, Hirotsugu | Kubota, Naoki | Nakai, Kenya | Takase, Takao
Abstract: Background: Donepezil is an established treatment for mild, moderate, and severe Alzheimer's disease (AD). An international study demonstrated superior efficacy of sustained release (SR) 23 mg/day donepezil over immediate release (IR) 10 mg/day donepezil for cognitive function, but not global function in moderate-to-severe AD. Objective: To demonstrate the superiority of SR 23 mg/day donepezil over IR 10 mg/day donepezil in Japanese patients with severe AD (SAD). Methods: In this multicenter, randomized, double-blind, parallel-group study, Japanese outpatients with SAD were randomly assigned to continue IR 10 mg/day or switch to SR 23 mg/day for 24 weeks. Endpoints included the Severe Impairment Battery …(SIB), Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus), and safety. Results: Overall, 166 and 185 patients were randomized to receive IR 10 mg/day and SR 23 mg/day, respectively. SR 23 mg/day was not statistically superior to IR 10 mg/day by SIB (least squares mean difference [LSMD]: 0.0; 95% confidence interval [CI]: –1.7, 1.8; p = 0.981) or CIBIC-plus (LSMD: 0.2; 95% CI: 0.0, 0.4; p = 0.080). Common adverse events in the SR 23 mg group were decreased appetite, vomiting, diarrhea, and contusion. Safety findings were consistent with known safety profiles of donepezil. Conclusion: SR 23 mg/day donepezil was not superior to IR 10 mg/day donepezil regarding the efficacy endpoints for Japanese SAD. Considering that a 10 mg/day dose is approved for SAD in Japan, the present findings suggest that IR 10 mg/day donepezil is the optimal dosage for Japanese patients with SAD. Show more
Keywords: Alzheimer's disease, cholinesterase inhibitors, donepezil, double-blind study, Japan
Activation of p53 in Down Syndrome and in the Ts65Dn Mouse Brain is Associated with a Pro-Apoptotic Phenotype
Authors: Tramutola, Antonella | Pupo, Gilda | Di Domenico, Fabio | Barone, Eugenio | Arena, Andrea | Lanzillotta, Chiara | Broekaart, Diede | Blarzino, Carla | Head, Elizabeth | Butterfield, D. Allan | Perluigi, Marzia
Abstract: Down syndrome (DS) is the most common genetic cause of intellectual disability, resulting from trisomy of chromosome 21. The main feature of DS neuropathology includes early onset of Alzheimer's disease (AD), with deposition of senile plaques and tangles. We hypothesized that apoptosis may be activated in the presence of AD neuropathology in DS, thus we measured proteins associated with upstream and downstream pathways of p53 in the frontal cortex from DS cases with and without AD pathology and from Ts65Dn mice, at different ages. We observed increased acetylation and phosphorylation of p53, coupled to reduced MDM2/p53 complex level and lower …levels of SIRT1. Activation of p53 was associated with a number of targets (BAX, PARP1, caspase-3, p21, heat shock proteins, and PGC1α ) that were modulated in both DS and DS/AD compared with age-matched controls. In particular, the most relevant changes (increased p-p53 and acetyl-p53 and reduced formation of MDM2/p53 complex) were found to be modified only in the presence of AD pathology in DS. In addition, a similar pattern of alterations in the p53 pathway was found in Ts65Dn mice. These results suggest that p53 may integrate different signals, which can result in a pro-apoptotic-phenotype contributing to AD neuropathology in people with DS. Show more
Keywords: Apoptosis, caspase, p53, sirtuins, Ts65Dn mouse model, trisomy 21
Hippocampal Sclerosis of Aging, a Common Alzheimer's Disease 'Mimic': Risk Genotypes are Associated with Brain Atrophy Outside the Temporal Lobe
Authors: Nho, Kwangsik | Saykin, Andrew J. | Alzheimer's Disease Neuroimaging Initiative | Nelson, Peter T.
Abstract: Hippocampal sclerosis of aging (HS-Aging) is a common brain disease in older adults with a clinical course that is similar to Alzheimer's disease. Four single-nucleotide polymorphisms (SNPs) have previously shown association with HS-Aging. The present study investigated structural brain changes associated with these SNPs using surface-based analysis. Participants from the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n = 1,239), with both MRI scans and genotype data, were used to assess the association between brain atrophy and previously identified HS-Aging risk SNPs in the following genes: GRN , TMEM106B , ABCC9 , and KCNMB2 (minor allele frequency for each is >30%). …A fifth SNP (near the ABCC9 gene) was evaluated in post-hoc analysis. The GRN risk SNP (rs5848_T) was associated with a pattern of atrophy in the dorsomedial frontal lobes bilaterally, remarkable since GRN is a risk factor for frontotemporal dementia. The ABCC9 risk SNP (rs704180_A) was associated with multifocal atrophy whereas a SNP (rs7488080_A) nearby (∼50 kb upstream) ABCC9 was associated with atrophy in the right entorhinal cortex. Neither TMEM106B (rs1990622_T), KCNMB2 (rs9637454_A), nor any of the non-risk alleles were associated with brain atrophy. When all four previously identified HS-Aging risk SNPs were summed into a polygenic risk score, there was a pattern of associated multifocal brain atrophy in a predominately frontal pattern. We conclude that common SNPs previously linked to HS-Aging pathology were associated with a distinct pattern of anterior cortical atrophy. Genetic variation associated with HS-Aging pathology may represent a non-Alzheimer's disease contribution to atrophy outside of the hippocampus in older adults. Show more
Keywords: Arteriolosclerosis, dementia, KATP, progranulin, rs5848, rs704180, rs1990622, rs9637454, SUR2, TDP-43
Upcoming Meetings Related to Alzheimer's Disease


We can create balloon flowers for almost any event or delivery. Balloon flowers bring immense color and fun to any party or special delivery.
Here are some great ideas for balloon bouquets with mylars in them. The T Mobile mylars were custom printed. Contact us with a special event in mind!


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U.S. presidential election, 1984
Presidential Candidate
Running Mate
(Electoral Votes)
Ronald Reagan of California (W) 525 54,455,000 58.8% Republican George H. W. Bush of Texas (525)
Walter F. Mondale of Minnesota 13 37,577,000 40.5% Democrat Geraldine A. Ferraro of New York (13)
David Bergland 0 228,705 0.3% Libertarian Jim Lewis (0)
Lyndon LaRouche 0 78,807 0.1% Democrat Billy Davis (0)
Other 303,000 0.3%
Total 92,652,842 100.0%
Other elections: 1972, 1976, 1980, 1984, 1988, 1992, 1996
Source: U.S. Office of the Federal Register
Geraldine A. Ferraro was the first woman to be nominated for either Vice President or President by a major party.
See also: President of the United States, U.S. presidential election, 1984, History of the United States (1980-present)
zh-cn:1984年美国总统选举

redpajama_set_name: RedPajamaCommonCrawl


IROKO has spent many years working within the community, both locally and nationally bringing a unique taste of African arts and culture to the public. We offer a number of options suitable for all occasions, from Family Fun Days to Festivals.
Live drumming, dance, chants, songs, and sometimes masquerades are used to create an unforgettable experience filled with excitement and fun for everyone.
Our Family Fun Day encourages family bonding and community cohesion as people from varied cultural backgrounds participate in fun and inclusive cultural activities in a relaxed and non-judgemental environment.
"The horns cannot be too heavy for the head of the cow that must carry them."


Great training week for me. There has been an unusual amount of sun here in Port Angeles the last few days. Perfect chance to get into the mountains, coast and on the trail. That now has came to an end, since it is now raining as I write this.
Living 3 miles from the Elwha River Valley. I often frequent the Olympic National Park by just heading upriver. It has been my backpacking training grounds all winter. Wouldn't have it any other way.
This week I walked on the bottom of old Lake Mills for the first time. Amazing the destructive power of water and man. Would've liked to seen it in its original state.
Let me share a few favorite photos from the second half of the week.
Old Driftwood. Held behind the dams for 100 years.
Moon, N. Olympic Mountains & the Elwha.
A beautiful coffee table book on the dam removal of this area - The Undammed Elwha River.


JACKSONVILLE, Fla., July 18, 2017 (GLOBE NEWSWIRE) -- CSX Corporation (Nasdaq:CSX) today announced second quarter 2017 net earnings of $510 million, or $0.55 per share, up from $445 million, or $0.47 per share, in the same period of last year. Excluding a $122 million restructuring charge in this year's second quarter results, adjusted earnings per share was $0.64 as shown in the table below.
Revenue for the second quarter increased 8 percent when compared to the previous year, with growth across nearly all markets. This growth was primarily driven by coal-related gains, strength in core pricing and volume across the other markets, and increased fuel recovery.
In the second quarter, CSX delivered improved asset utilization, cost control and fuel optimization. These operational improvements, coupled with the benefits from the management restructuring that was completed early in the second quarter, drove $90 million in efficiency gains. These gains more than offset the cost of inflation in the quarter.
CSX is intensely focused on implementing Precision Scheduled Railroading throughout the system. The company is on track to achieve record efficiency gains and a step-function improvement in its key financial measures for the year given continued economic growth and stable coal markets.
Adjusting for restructuring charges, CSX continues to expect to drive a full-year operating ratio in the mid-60s, earnings per share growth of around 25 percent off the 2016 reported base of $1.81, and free cash flow before dividends of around $1.5 billion (please see the company's non-GAAP statements below).
As a result, the Board authorized an additional $500 million for the current share repurchase program, which now totals $1.5 billion. As part of this program, nearly $500 million of company shares were repurchased in the second quarter. At the same time, the company is currently evaluating its cash deployment strategy with respect to capital structure and shareholder distributions, and is committed to an investment grade rating.
CSX executives will conduct a quarterly earnings conference call with the investment community on July 19, 2017, at 8:30 a.m. Eastern time. Investors, media and the public may listen to the conference call by dialing 1-888-EARN-CSX (888-327-6279) and asking for the CSX earnings call. Callers outside the U.S., dial 1-773-756-0199. Participants should dial in 10 minutes prior to the call. In conjunction with the call, a live webcast will be accessible and presentation materials will be posted on the company's website at http://investors.csx.com. Following the earnings call, an internet replay of the presentation will be archived on the company website.


text:
animationstudies 2.0
Previous Themes
"Alternative/Forgotten Histories"
20 Years of Pixar Features
30 Years of Blue Sky Studios
Acting and Performance in Animation
Adaptation in Animation II
Adult Animation
Animals and Animation
Animating Industry
Animation & Movement
Animation and Documentary
Animation and Invisibility
Animation and Paratextuality
Animation and Philosophy
Animation and Robots
Animation and Science Fiction
Animation and Seriality
Animation and Stardom
Animation and the Comic Book
Animation Auteurs
Animation Franchises and the Studio System
Asian Animation
Cats in Animation
Children's Animation
Collaboration & Animation
Education and Animation
Education in/and Animation
European Animation
Experimental Animation
Gender and Animation
Genre and Animation
Health Issues and Animation
Jim Henson's Animated Universes
National Animation
New and forthcoming texts (reviews)
New Theoretical Approaches in Animation
Norman McLaren Centenary: McLaren and Movement
Politics in and of Animation
Queer/ing Animation
Sound and Music in Animation
Technological developments in animation I (pre-digital)
Technological developments in animation II (the post digital)
The Persistence of Walt Disney's Snow White and the Seven Dwarfs
The Sound of Animation
Early, Silent and Pre-cinematic Animation
Special Edition- Multi themed month
CFP Watching Animation
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The Fleischer Studio's 'Setback' Camera vs. Disney realism
by Luke Jaeger • May 7, 2013 • 13 Comments
Ask an American "who invented animation" and the most likely response will be "Walt Disney." Students of animation history know better, of course — but while Disney contributed significantly to the development of the form, his most permanent legacy may be the tireless self-promotion with which he stamped his own name on animated cinema. Foremost among Walt Disney's gifts was his facility with storytelling, so it's no surprise that to this day, millions accept as historical fact the studio's own carefully constructed narrative about its role as engine of technological progress in animation.
But in the silent era and well into the 1930's, animation's technology leader was the Fleischer Studio; other studios, including Disney, struggled to keep up with Fleischer's visual and mechanical inventiveness. And while Disney, obsessed with realism, strove to create an environment in which rigidly contained characters behave according to strict visual, narrative, and social rules, the principles at work in Fleischer-space are the exact opposite. Betty Boop and Popeye inhabit a profoundly rubbery world, in which the fourth wall is full of holes, distinctions between human, animal, vegetable and inanimate taxonomies are unstable, and the boundary between cartoonal and real space is up for grabs.
Fleischer deployed a number of techniques in the service of this anarchic cinematic vision, among them rotoscoping (patented by Max Fleischer in 1917); integrating live action shots; and using still photographs as animation backgrounds to create the illusion of cartoon characters inhabiting a real-world space, as in the opening scene of the astounding Betty Boop short Ha! Ha! Ha! (1934). The most technologically ornate item in Fleischer's toolbox was the setback camera (sometimes erroneously called the 'stereoptical process'), used in a number of shorts and in the feature film Hoppity Goes To Town (1941).
The setback is often confused with Disney's multiplane camera. Both systems evolved somewhat contemporaneously, and both create the illusion of dimensional depth, but functionally they have little in common. The setback rig consists of a forced-perspective, miniature set mounted on a turntable, serving as background to the cel art held in a vertical glass platen, and a horizontal animation camera. The turntable is rotated incrementally behind the cels, creating the effect of a "tracking shot" — the 2D animated character, in a side-view walk cycle, traverses a realistically proportioned (but still recognizably Fleischeresque) 3D environment which moves perspectivally across the background.
Getting the setback rig to work at all must have been a major technical feat — the lighting challenges alone seem headache-inducing — and it's easy to imagine that 1930's audiences, unaccustomed to full 3D motion in cartoons, were amazed by the onscreen results. Yet the scenes in which the studio deployed setback shots seem chosen at random. Setback made its public debut during a fast and comical chase scene in the Popeye short For Better Or Worser (1935), but in Li'l Swee' Pea (1936) the setback shots accompany such humdrum, utilitarian scenes (Popeye walking; Popeye pushing stroller) that the overall effect is underwhelming.
Setback shots in the color two-reeler Popeye the Sailor Meets Sindbad the Sailor (1936) are more sophisticated; some feature an additional foreground layer of sliding 3D scenery between camera and platen, with the nearer objects convincingly off-focus. The animators found new ways to make the drawn characters interact spatially with the backgrounds: Popeye climbs a staircase (walking 'between' two balustrades built into the turntable) and Bluto convincingly enters a 3D cave. Some shots vary the turntable velocity, with the animation timed accordingly. In one of the better-executed gags, 2D Bluto plunges his hands into a 3D treasure chest and scoops out handfuls of 2D gems. The lighting crew evidently struggled to eliminate shadows and glare from these more complex shots, sometimes without success.
Setback also makes a few appearances in Popeye the Sailor Meets Ali Baba's Forty Thieves (1937), including the film's impressive final shot: Popeye and Olive Oyl ride a 3D wagon (its wheels spinning in stop-motion); a pan within the setback shot reveals 2D Bluto and his vanquished team of badguys towing the wagon. In the big-budget Hoppity, Fleischer's failed bid for legitimacy in the animated feature arena (and the point of no return in the studio's decline), the setback camera slowly descends on its y-axis during the visually gorgeous but narratively superfluous opening 'crane shot.'
Disney's multiplane camera, though technically complex, only shot 2D artwork. Fleischer attempted something more ambitious — in-camera compositing of 2D and 3D animation — decades before it became possible to do so optically or digitally. Perhaps setback was born too soon; despite its heady promise of merging the 2D and 3D worlds, the system was a one-trick pony. The technical limitations became narrative ones: since the forced-perspective effect depended on a fixed distance between the camera and turntable, setback was constrained to panning along the x-axis — an efficient but not very engaging way of moving a character from here to there. If Fleischer ever attempted moving one of the setback elements in z-space, the results must have been judged unfit for presentation. The more flexible multiplane system allowed z-axis camera moves which drew the audience into the pictorial space.
But Disney didn't overtake Fleischer just by stumbling upon superior filmmaking machinery — history is full of bad technologies that prevail over better ones — but by harnessing all of the studio's resources, including multiplane, to build a triumphant narrative about technological progress. Disney leveraged its story-structure chops both on and off the screen: not only did the multiplane camera highlight important moments in a given film's narrative with its swooping spatial moves (announcing its presence in Pinocchio, for example, with soaring flocks of birds and tolling church bells), it also played a key role in Disney's meta-narrative about how technically challenging the films were to make.
Over the following decades, the studio unspooled this story over and over, in countless promotional 'making-of' films shown during Disney's TV program, and in every other known communication medium except possibly Morse Code and smoke signals. With every new feature Disney unleashed increasingly baroque publicity storms, always emphasizing how hard everyone worked to make the picture: to what distant locales the artists traveled; what species of exotic fauna the studio installed in its in-house zoo for visual reference; how many trainloads of paper and ink were consumed during production, and so on.
That any of this was necessary underscores the lasting irony of Disney's achievement: in the service of realism, Disney drove his artists and technicians to previously unattained levels of craft, with the result that audiences forgot they were watching animation and had to be constantly reminded, through channels external to the films themselves, how hard it was to create the illusion.
Unlike Fleischer's animators, who couldn't stay out of the picture, Disney's crew did their jobs so well that they made themselves disappear.
Luke Jaeger grew up in Brooklyn and attended Yale University, the School of the Museum of Fine Arts, and Massachusetts College of Art. He and his family now live in Western Massachusetts. His animated films have been shown in festivals and theaters worldwide. More at http://www.trickfilm.org
Tags: Animation History Betty Boop Disney Fleischer multiplane Popeye setback
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13 comments for "The Fleischer Studio's 'Setback' Camera vs. Disney realism"
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Brett Knoss
If the sets on each row were tilted back, would they appear to be closer?
Luke Jaeger
hi Brett — no, probably not — it would just create a distorted-looking environment. Think of a forced-perspective or anamorphic miniature set, like you might find in a puppet show. By exaggerating the scale of objects (bigger in foreground, smaller in background) you create the illusion of greater depth than really exists in the scene. It all converges down to a single vanishing point at the phony 'horizon'. The setback rig does this on a turntable that spins during shooting, with the pivot point of the turntable serving as the vanishing point. When you look out the window of a train travelling through a flat landscape you see exactly this effect.
Claire Chidgey
I need confermation on the difference between the rotograph, setbacks and the stereoptical process. Every site has different info. Do you have any ideas?
You can find patent drawings online for the setback system (described above) and for the rotoscope, a system for tracing live action film onto animation paper (there are lots of ways to do this digitally too, though obviously these didn't exist in 1917).
I don't know why the setback system was sometimes called the "stereoptical process" … there's nothing stereoptical about it, but I guess that was shorthand for "3D effect"
Ray Pointer
I can explain the use of the term "Stereoptical Process." It is credited on the original openings of the cartoons, displaying the Patent Number for the device. The term is a play on the old Stereopticon slides of the Victorian era.
In the studio, according to the production manual and production records, the in house reference to the type of background to be used was "Setback," a shorthand for background set. These, as you know were models.
The advantages that this system had over Disney's Multiplane was that its use of forced perspective on the model sets allowed for everything to move together in correct parallax. The Disney Multiplane had to have each level calculated and moved at separate increments, employing a Camera assistant for each level, and each level requiring lighting. Also the Multiplane took up more space, being a vertical device. Also, the Multiplane was limited moving in with levels moving on vertical Pans.
Fleischer's Steroptical device was more versatile. Not only could the camera could move in along with the rotating Pan effect, it could tilt up or down as if going up in the air from a plane or a construction elevator. It could also change from day to night using the same model set simply by changing the lighting.
Yes, the term "Stereopcial Process" is correct. All of this and more is explained in my book, THE ART AND INVENTIONS OF MAX FLEISCHER: AMERICAN ANIMATION PIONEER, coming this fall from McFarland & Company books.
The Rotogarph was a pioneering form of Aerial Image Photography where live action film footage was rephotographed to composite with animation. This is a separate device from the Rotoscope, which was a motion study and tracing device used to copy live action movements and also provide reference lines for composting animation with live action. "Setback"s were the in house reference to the model set backgrounds used for the "Stereoptical" Camera. The "Stereoptical "Process" was the name credited on the original openings of those cartoons using it, referencing the effect and the device that made it possible. What is interesting about each of these Fleischer Patents is that these names do not appear in the original patent applications. They are mere referred to as a "device for producing motion pictures."
Richard J. Kennedy
My first exposure to what I believe is the "setback" camera process is in the opening sequence of the Betty Boop cartoon "Judge for a Day".
When Betty leaves her house and walks down the street, everything in the background, especially the rosebushes she walks past, are in 3D. The first time I saw it, it blew me away. I couldn't believe they could do that in the early 1930s. That cartoon is available to see online whereas the Popeye cartoons referenced above have all been pulled, I assume for copyright reasons.
I do remember the Popeye cartoon scene, referenced above also, where Bluto plunges his hands into a 3D treasure chest. That was pretty impressive too.
Finally, as stated above too, it is interesting that these setback camera shots are seemingly placed randomly in the cartoons mentioned and the 3D effect is only a brief sequence in each cartoon.
As impressive as the effect was, it was time consuming and complicated to shoot.
The animation was usually planned for one level, meaning one cel level change for each exposure. There were also more drawings made for these scenes. They were snot on "ones," which means that a new cel had to be made for each incremental move of the background to maintain the impress of contact without the impression of "slipping." Rare did the shoot animation on "twos" using the Setback camera. The slow skipping along seen in SOMEWHERE IN DREAMLAND is a rare example where the animation was on 'twos," however.
The Color Classic, MUSICAL MEMORIES has the most extensive use of The Stereoptical Process, one in every scene. This fit the film since it was built around the old couple looking at the old fashioned Stereopticon 3D slides. There are something like 18 of these scenes and in color.
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Jeff Whelan
There are many reasons for the success of Disney films over other studios, but it certainly did not boil down to hype. How about story telling structure and convincing motives and actions of characters just to name a few distinctives that are emulated right up to the latest installment of "The Incredibles."
Ramiro Pych
Hi there! It's hard to find anything interesting on this subject (I mean something that is not overly simplistic), because everything related to 3D seems very difficult. You however sound like you know what you're talking about 🙂 Thank you for spending your time writing some good content for us!
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text:
The Impact of Covid-19 on Pensions
Advocacy Talking Points 19 January 2021
Sivananth Ramachandran CFA Janet Li CFA David Knox David Dong Renuka Sane PhD
Industry experts discuss the changes to the 2020 Mercer CFA Institute Global Pensions Index and the diverse efforts by governments across the world to support their communities' health and finances.
Webinar Presentation
Financial security in retirement can never be taken for granted. In a CFA Institute survey of over 400 defined-benefit pension plans conducted prior to the pandemic, 48% of respondents said it is likely or very likely (greater than a 60% chance) that their fund will not be able to pay 100% of benefits in the next 10 years.
Pension systems around the world faced additional pressures in 2020. Governments, pension regulators, plan fiduciaries, and millions of workers responded in a variety of ways to COVID-19. The unusual events of 2020 had several immediate effects but will also have a long term impact on future retirement income. This effect will be caused by lower pension contributions or early withdrawals, low interest rates driving down expected returns across asset classes, high government debt potentially reducing future government support, and members switching to defensive portfolios at the wrong time, crystallizing losses.
In this webinar, we discuss the changes to the 2020 Mercer CFA Institute Global Pensions Index. We also discuss the diverse responses by governments across the world to support their communities' health and finances. Lastly, our panel of experts debates how individuals, industry, and pension systems will need to adapt in a post-pandemic world.
Janet Li, Partner, Asia Wealth Business Leader, Mercer
David Knox, PhD., Senior Partner, Mercer
David Dong, Deputy CEO, China Universal Asset Management (Hong Kong) Co., Ltd
Renuka Sane, PhD., Associate Professor, National Institute of Public Finance and Policy, India
Sivananth Ramachandran, CFA, Director, Capital Markets Policy, India, CFA Institute
Duration: 1 hr 7 min.
Recorded: 19 January 2021.
Sivananth Ramachandran CFA
Sivananth Ramachandran (Siva) is the Director of Capital Markets Policy, India at the CFA Institute. In his role, he is responsible for advocating policy positions on issues that impact Indian capital markets, including corporate governance, ESG, and financial reporting, to name a few. Siva recently contributed as part of a SEBI working group that reviewed the related party transaction regulations. He is frequently quoted in media. Siva has nearly thirteen years of experience in financial services. Prior to joining the CFA Institute, Siva spent five years at Morningstar, and led their global index product development team. He also served as a spokesperson for sustainability at Morningstar India. Prior to his time at Morningstar, Siva spent nearly five years at MSCI where he co-authored research papers on small cap investing, portfolio construction, and economic exposure. Siva has an MBA from the Indian Institute of Management, Lucknow. He also holds the Chartered Financial Analyst (CFA) and Professional Risk Management (PRM) designations, and the Fundamentals of Sustainability Accounting (FSA) credential provided by Sustainability Accounting Standards Board (SASB).
Janet Li CFA
Janet Li, CFA, MAoF, is a Partner and the Asia Wealth Business Leader at Mercer. She oversees and is responsible for Mercer's Wealth (Investment and Retirement) Business in Asia. In her role, she leads and drives strategic growth to the business as well as its operations and implementations. Janet has vast experience working with institutional clients (sovereigns, pension, insurance, corporate and wealth management). Her experience also spans across a wide range of retirement and investment services (asset liability review and strategy, portfolio construction, manager review, selection and monitoring, investment governance and transformation, discretionary management, member communication and education and related tools' developments) and a diverse range of asset classes (public equities and fixed income, private equities, illiquid credit, real estate and infrastructure).
David is a Senior Partner at Mercer and Senior Actuary for Australia. He is the National Leader for Research and the actuary to the Tasmanian and Western Australian public sector superannuation plans. Before joining Mercer in 2005, David was at PricewaterhouseCoopers and prior to that was the Foundation Professor of Actuarial Studies at The University of Melbourne. In his two decades in academia, he acted as a consultant to a range of financial organisations, in both the private and public sectors, specialising in the superannuation and retirement incomes area. David has a Bachelor of Arts and Doctorate (which focused on pensions) from Macquarie University and is a Fellow of the Actuaries Institute.
David Dong
Mr. David Dong joined China Universal Asset Management (Hong Kong) Company Limited in 2010 and currently acts as the Deputy Chief Executive Officer, who is in charge of the overall business development, product development, and oversight of sales and marketing activities. David has more than 15 years of experience in finance and investment markets, and he is also responsible for overall business development of international business of parent company, China Universal Asset Management Co. Ltd. Prior to joining CUAM HK, David acted as the Senior Manager in the International Business Department of China Universal Asset Management Co. Ltd since 2008.
David holds a Master's degree, and he is the International Business Committee member of Asset Management Association of China (AMAC), and Pacific Policy Council Member of ICI Global.
Renuka Sane PhD
Renuka Sane is an Associate Professor at the National Institute of Public Finance and Policy (NIPFP). Her research interests are in household finance, especially on household choice in financial instruments such as credit, pensions, insurance and equity markets, as well as consumer protection in finance. She is also interested in research and policy on the criminal justice system in India.
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