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Journal of Prevention of Alzheimer's Disease

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https://read.qxmd.com/read/30756122/report-from-the-first-clinical-trials-on-alzheimer-s-disease-ctad-asia-china-2018-bringing-together-global-leaders
#1
J K Chhetri, P Chan, B Vellas, J Touchon, S Gauthier
Population of older adults in Asia, and particularly in China is increasing rapidly. Older population are at increased risk of Alzheimer's disease (AD) and other dementias. Soon, the Chinese population with AD will represent almost half of the world's AD population. There is a desperate need of disease modifying therapies to delay or slow the progression of AD, to tackle this emerging healthcare emergency. In this context, the first CTAD Asia-China conference was held in China to bring together Western and Asian leaders in AD...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30756121/cross-sectional-characterization-of-albumin-glycation-state-in-cerebrospinal-fluid-and-plasma-from-alzheimer-s-disease-patients
#2
M Costa, A Mestre, R Horrillo, A M Ortiz, A Pérez, A Ruiz, M Boada, S Grancha
We determined albumin post-translational modifications (PTMs) by mass spectrometry (MS) in plasma and cerebrospinal fluid (CSF) from 31 Alzheimer's disease (AD) patients (with 27 samples of paired plasma-CSF from the same patients). Results were cross-sectionally compared with healthy controls. For percentage of relative intensity of glycated isoforms, plasma albumin was globally more glycated in AD patients than in healthy controls (P<0.01). MS results in plasma were confirmed by a quantitative enzymatic assay (Lucica GA-L) for albumin early-glycation detection...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30756120/implementing-a-memory-clinic-model-to-facilitate-recruitment-into-early-phase-clinical-trials-for-mild-cognitive-impairment-and-alzheimer-s-disease
#3
L Park, C Kouhanim, S Lee, Z Mendoza, K Patrick, L Gertsik, C Aguilar, D Gullaba, S Semenova, S Jhee
BACKGROUND: The recruitment challenges for MCI and AD subjects into clinical trials are well known, and this is particularly true for early phase studies. Currently, only 10-20% of all patients who are referred for research from the community are trial eligible (Grill and Karlawish, 2011). Due to the limited and specific study objectives in early phase study designs, these rates drop to approximately one patient every two months. Barriers to research recruitment are multi-factorial, involving patient centered factors, issues related to caregiver/study partner participation, and aspects related to the involvement of their treating physicians...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30756119/factors-associated-with-alzheimer-s-disease-an-overview-of-reviews
#4
M Rochoy, V Rivas, E Chazard, E Decarpentry, G Saudemont, P-A Hazard, F Puisieux, S Gautier, R Bordet
Alzheimer's disease (AD) is a frequent pathology, with a poor prognosis, for which no curative treatment is available in 2018. AD prevention is an important issue, and is an important research topic. In this manuscript, we have synthesized the literature reviews and meta-analyses relating to modifiable risk factors associated with AD. Smoking, diabetes, high blood pressure, obesity, hypercholesterolemia, physical inactivity, depression, head trauma, heart failure, bleeding and ischemic strokes, sleep apnea syndrome appeared to be associated with an increased risk of AD...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30756118/biological-and-cognitive-markers-of-presenilin1-e280a-autosomal-dominant-alzheimer-s-disease-a-comprehensive-review-of-the-colombian-kindred
#5
J T Fuller, A Cronin-Golomb, J R Gatchel, D J Norton, E Guzmán-Vélez, H I L Jacobs, B Hanseeuw, E Pardilla-Delgado, A Artola, A Baena, Y Bocanegra, K S Kosik, K Chen, P N Tariot, K Johnson, R A Sperling, E M Reiman, F Lopera, Y T Quiroz
The study of individuals with autosomal dominant Alzheimer's disease affords one of the best opportunities to characterize the biological and cognitive changes of Alzheimer's disease that occur over the course of the preclinical and symptomatic stages. Unifying the knowledge gained from the past three decades of research in the world's largest single-mutation autosomal dominant Alzheimer's disease kindred - a family in Antioquia, Colombia with the E280A mutation in the Presenilin1 gene - will provide new directions for Alzheimer's research and a framework for generalizing the findings from this cohort to the more common sporadic form of Alzheimer's disease...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30756117/shift-in-hospitalizations-for-alzheimer-s-disease-to-related-dementias-in-france-between-2007-and-2017
#6
M Rochoy, E Chazard, S Gautier, R Bordet
INTRODUCTION: Alzheimer's disease (AD) is the first cause of dementia. Diagnostic criteria have evolved: proposals to revise the NINCDS-ADRDA criteria were published in 2007. Our aim was to analyze the evolution in the coding of AD in the French nationwide exhaustive hospital discharge database (PMSI) between 2007 and 2017. METHODS: We analyzed evolution of International Classification of Diseases and Related Health Problems, 10th edition (ICD-10) coding for AD and AD dementia in the PMSI database from 2008 to 2017 (285,748,938 inpatient stays)...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30756116/mri-clinical-ratings-and-cognitive-function-in-a-cross-sectional-population-study-of-dementia-the-cache-county-memory-study
#7
Y H W Tsui-Caldwell, T J Farrer, Z McDonnell, Z Christensen, C Finuf, E D Bigler, J T Tschanz, M C Norton, K A Welsh-Bohmer
BACKGROUND: White matter integrity in aging populations is associated with increased risk of cognitive decline, dementia diagnosis, and mortality. Population-based data can elucidate this association. OBJECTIVES: To examine the association between white matter integrity, as measured by a clinical rating scale of hyperintensities, and mental status in older adults including advanced aging. DESIGN: Scheltens Ratings Scale was used to qualitatively assess white matter (WM) hyperintensities in participants of the Cache County Memory Study (CCMS), an epidemiological study of Alzheimer's disease in an exceptionally long-lived population...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30756115/utilization-of-observational-data-as-a-proxy-cohort-for-comparison-purposes-with-open-label-study-results-an-example-from-alzheimer-s-disease
#8
C Reed, M Happich, J Raskin, A Tockhorn-Heidenreich, M Belger
BACKGROUND: Randomized placebo-controlled trials in the development of disease-modifying treatments for Alzheimer's disease are typically of short duration (12-18 months), and health economic modeling requires extrapolation of treatment effects beyond the trial period. OBJECTIVES: To investigate whether observational data can be used to extrapolate data from open-label trials, we compared outcomes (cognition, function, behavior) over 36 months for patients with mild Alzheimer's disease dementia in the GERAS observational study (proxy for placebo control) with those of the mild Alzheimer's disease population on active treatment (solanezumab) in two 18-month randomized placebo-controlled trials (EXPEDITION and EXPEDITION2) and the additional 18-month open-label extension study (EXPEDITION-EXT)...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30756114/assessment-of-clinical-meaningfulness-of-endpoints-in-the-generation-program-by-the-insights-to-model-alzheimer-s-progression-in-real-life-imap-study
#9
A Graf, V Risson, A Gustavsson, V Bezlyak, A Caputo, P N Tariot, J B Langbaum, C Lopez Lopez, V Viglietta
We are launching the Insights to Model Alzheimer's Progression in Real Life study in parallel with the Alzheimer Prevention Initiative Generation Program. This is a 5-year, multinational, prospective, longitudinal, non-interventional cohort study that will collect data across the spectrum of Alzheimer's disease. The primary objective is to assess the ability of the Alzheimer's Prevention Initiative Cognitive Composite Test Score and Repeatable Battery for the Assessment of Neuropsychological Status to predict clinically meaningful outcomes such as diagnosis of mild cognitive impairment or dementia due to Alzheimer's disease, and change in Clinical Dementia Rating - Global Score...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30756113/editorial-implications-for-bace1-inhibitor-clinical-trials-adult-conditional-bace1-knockout-mice-exhibit-axonal-organization-defects-in-the-hippocampus
#10
R Vassar
BACE1 is the rate-limiting enzyme for the production of the Aβ peptide that forms amyloid plaques in Alzheimer's disease (AD). Small molecule inhibitors of BACE1 are being tested in clinical trials for AD, but the safety and efficacy of BACE1 inhibition has yet to be fully explored. Knockout of the Bace1 gene in the germline of mice causes multiple neurological phenotypes, suggesting that BACE1 inhibition could be toxic. However, these phenotypes could be the result of BACE1 deficiency during development rather than due to the lack of BACE1 function in the adult...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30569089/bifidobacterium-breve-a1-supplementation-improved-cognitive-decline-in-older-adults-with-mild-cognitive-impairment-an-open-label-single-arm-study
#11
Y Kobayashi, T Kinoshita, A Matsumoto, K Yoshino, I Saito, J-Z Xiao
OBJECTIVES: We previously reported the therapeutic potential of Bifidobacterium breve A1 (B. breve A1) for preventing cognitive impairment in Alzheimer's disease model mice, which suggested that supplementation of the probiotics could be an effective therapeutic strategy for managing cognitive function in mild cognitive impairment (MCI). DESIGN AND SETTINGS: We conducted an open-label, single-arm study to examine the effects of 24-week supplementation of B. breve A1 on elderly with MCI in Aki Orthopedics Rehabilitation Clinic in Japan...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30569088/aadvac1-an-active-immunotherapy-for-alzheimer-s-disease-and-non-alzheimer-tauopathies-an-overview-of-preclinical-and-clinical-development
#12
P Novak, N Zilka, M Zilkova, B Kovacech, R Skrabana, M Ondrus, L Fialova, E Kontsekova, M Otto, M Novak
Neurofibrillary tau protein pathology is closely associated with the progression and phenotype of cognitive decline in Alzheimer's disease and other tauopathies, and a high-priority target for disease-modifying therapies. Herein, we provide an overview of the development of AADvac1, an active immunotherapy against tau pathology, and tau epitopes that are potential targets for immunotherapy. The vaccine leads to the production of antibodies that target conformational epitopes in the microtubule-binding region of tau, with the aim to prevent tau aggregation and spreading of pathology, and promote tau clearance...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30569087/increased-functional-connectivity-after-listening-to-favored-music-in-adults-with-alzheimer-dementia
#13
J B King, K G Jones, E Goldberg, M Rollins, K MacNamee, C Moffit, S R Naidu, M A Ferguson, E Garcia-Leavitt, J Amaro, K R Breitenbach, J M Watson, R K Gurgel, J S Anderson, N L Foster
BACKGROUND: Personalized music programs have been proposed as an adjunct therapy for patients with Alzheimer disease related dementia, and multicenter trials have now demonstrated improvements in agitation, anxiety, and behavioral symptoms. Underlying neurophysiological mechanisms for these effects remain unclear. METHODS: We examined 17 individuals with a clinical diagnosis of Alzheimer disease related dementia using functional MRI following a training period in a personalized music listening program...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30569086/diet-as-a-risk-factor-for-cognitive-decline-in-african-americans-and-caucasians-with-a-parental-history-of-alzheimer-s-disease-a-cross-sectional-pilot-study-dietary-patterns
#14
A C Nutaitis, S D Tharwani, M C Serra, F C Goldstein, L Zhao, S S Sher, D D Verble, W Wharton
BACKGROUND: African Americans (AA) are more likely to develop Alzheimer's disease (AD) than Caucasians (CC). Dietary modification may have the potential to reduce the risk of developing AD. OBJECTIVE: The objective of this study is to investigate the relationship between Southern and Prudent diet patterns and cognitive performance in individuals at risk for developing AD. DESIGN: Cross-sectional observational study. PARTICIPANTS: Sixty-six cognitively normal AA and CC individuals aged 46-77 years with a parental history of AD were enrolled...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30569085/treatable-vascular-risk-and-cognitive-performance-in-persons-aged-35-years-or-older-longitudinal-study-of-six-years
#15
M E A van Eersel, H Joosten, R T Gansevoort, J P J Slaets, G J Izaks
BACKGROUND: Poor cognitive performance is associated with high vascular risk. However, this association is only investigated in elderly. As neuropathological changes precede clinical symptoms of cognitive impairment by several decades, it is likely that cognitive performance is already associated with vascular risk at middle-age. OBJECTIVES: To investigate the association of cognitive performance with treatable vascular risk in middle-aged and old persons. DESIGN: Longitudinal study with three measurements during follow-up period of 5...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30569084/plasma-a%C3%AE-42-40-ratio-detects-early-stages-of-alzheimer-s-disease-and-correlates-with-csf-and-neuroimaging-biomarkers-in-the-ab255-study
#16
V Pérez-Grijalba, J Romero, P Pesini, L Sarasa, I Monleón, I San-José, J Arbizu, P Martínez-Lage, J Munuera, A Ruiz, L Tárraga, M Boada, M Sarasa
BACKGROUND: Easily accessible biomarkers are needed for the early identification of individuals at risk of developing Alzheimer's disease (AD) in large population screening strategies. OBJECTIVES: This study evaluated the potential of plasma β-amyloid (Aβ) biomarkers in identifying early stages of AD and predicting cognitive decline over the following two years. DESIGN: Total plasma Aβ42/40 ratio (TP42/40) was determined in 83 cognitively normal individuals (CN) and 145 subjects with amnestic mild cognitive impairment (a-MCI) stratified by an FDG-PET AD-risk pattern...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30569083/pimavanserin-in-alzheimer-s-disease-psychosis-efficacy-in-patients-with-more-pronounced-psychotic-symptoms
#17
C Ballard, J M Youakim, B Coate, S Stankovic
BACKGROUND: Pimavanserin is a 5-HT2A receptor inverse agonist/antagonist and is approved in the United States for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. OBJECTIVE: Evaluate the efficacy of pimavanserin on symptoms of psychosis in patients with Alzheimer's disease (AD). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Nursing home residents. PARTICIPANTS: Patients with AD psychosis...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30569082/designing-trials-of-disease-modifying-agents-for-early-and-preclinical-alzheimer-s-disease-intervention-what-evidence-is-meaningful-to-patients-providers-and-payers
#18
D A Messner, P Rabins, A C Downing, M Irizarry, N L Foster, J Al Naber, O Dabbous, H Fillit, S Gabler, R Krakauer, D Lotz, E Payzant, L Schneider, J Tyrone, D Van Amerongen, D Wuest
BACKGROUND: Drug development for disease modifying agents in Alzheimer's disease (AD) is focused increasingly on targeting underlying pathology in very early stages of AD or in cognitively normal patients at elevated risk of developing dementia due to Alzheimer's. Very early interventional studies of this type have many uncertainties, including whether they can provide the clinical results that payers, providers, and patients will wish to see for decisions. This paper describes an initiative to create greater transparency for researchers to anticipate these decision needs...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30569081/polygenic-risk-score-analysis-of-alzheimer-s-disease-in-cases-without-apoe4-or-apoe2-alleles
#19
V Escott-Price, A Myers, M Huentelman, M Shoai, J Hardy
The We and others have previously shown that polygenic risk score analysis (PRS) has considerable predictive utility for identifying those at high risk of developing Alzheimer's disease (AD) with an area under the curve (AUC) of >0.8. However, by far the greatest determinant of this risk is the apolipoprotein E locus with the E4 allele alone giving an AUC of ~0.68 and the inclusion of the protective E2 allele increasing this to ~0.69 in a clinical cohort. An important question is to determine how good PRS is at predicting risk in those who do not carry the E4 allele (E3 homozygotes, E3E2 and E2E2) and in those who carry neither the E4 or E2 allele (i...
2019: Journal of Prevention of Alzheimer's Disease
https://read.qxmd.com/read/30569080/revisiting-the-cholinergic-hypothesis-in-alzheimer-s-disease-emerging-evidence-from-translational-and-clinical-research
#20
H Hampel, M-M Mesulam, A C Cuello, A S Khachaturian, A Vergallo, M R Farlow, P J Snyder, E Giacobini, Z S Khachaturian
Scientific evidence collected over the past 4 decades suggests that a loss of cholinergic innervation in the cerebral cortex of patients with Alzheimer's disease is an early pathogenic event correlated with cognitive impairment. This evidence led to the formulation of the "Cholinergic Hypothesis of AD" and the development of cholinesterase inhibitor therapies. Although approved only as symptomatic therapies, recent studies suggest that long-term use of these drugs may also have disease-modifying benefits...
2019: Journal of Prevention of Alzheimer's Disease
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